Anatomy & Physiology for Midwives 3: Third Edition

Chapter 11. Physiological adaptation to pregnancy

Learning objectives

• To outline the roles of hormones mediating the physiological adaptation to pregnancy.

• To describe cardiovascular adaptations to pregnancy.

• To describe the respiratory changes in pregnancy.

• To describe the gastrointestinal adaptations in pregnancy.

• To discuss alterations in maternal carbohydrate metabolism in pregnancy.

• To discuss the need for iron supplementation in pregnancy.

• To relate physiological changes with signs, symptoms and discomforts of pregnancy.

Introduction

During the 279 days (40 weeks) of an average pregnancy (measured from the first day of the last menstrual period), maternal physiology changes remarkably to support the development of the fetus and to prepare the mother for labour and lactation. The changes begin in the luteal phase of the menstrual cycle, before fertilization and implantation, as progesterone secretion from the corpus luteum is initiated. If fertilization is successful, levels of progesterone and oestrogen progressively increase. Together, they orchestrate many of the changes to the maternal physiology in pregnancy.

Chapter case study

Zara is now in the third trimester of her pregnancy. She informs her midwife that she is not sleeping well, and James prefers to sleep in the spare room as Zara's loud snoring and frequent waking disturbs him. When Zara does sleep, she experiences vivid dreams that cause her to wake suddenly. Her sleeping is not helped by the fact she often wakes up feeling hungry and thirsty and is having to make increasingly frequent visits to the toilet. Zara has now stopped working and finds that the only way she can cope is to a have a rest in the afternoon. She often falls asleep sitting in front of the television for 3–4h and says this afternoon sleep is less disturbed than the night time.

• What physiological changes could account for these changes in Zara's sleep pattern and what reasons would you give to reassure Zara that this is normal?

• Why do you think Zara is able to sleep more peacefully in the afternoon?

• Are there any advantages in these behavioural changes and might they be preparing Zara to care for her newborn baby?

Endocrine changes in pregnancy

The physiological changes of pregnancy are controlled by an alteration in hormone secretion. The trophoblastic cells produce human chorionic gonadotrophin (hCG), which stimulates secretion from the corpus luteum, increasing ovarian steroid hormone production. As the placenta develops, it also produces oestrogen and progesterone. However, placental endocrine function is much broader as the placenta synthesizes a range of hormones and releasing factors that are similar to those originating from the hypothalamus and other maternal endocrine organs (see Chapter 8). Placental products may reach both the maternal and fetal circulation, thus regulating maternal physiology and fetal development.

Steroid hormones

Steroidogenesis depends on interaction and cooperation between the mother, placenta and fetus. The mother is the source of precursors for placental progesterone production and the fetus is the source of precursors for placental oestrogen production. Placental progesterone is used for fetal synthesis of testosterone, corticosteroids and mineralocorticoids. Progesterone is known as the hormone of pregnancy; it stimulates respiration, relaxes smooth muscle (of blood vessels, uterus and gut), increases body temperature, increases sodium and chloride excretion, and may act as an immunosuppressant in the placenta (Picciano, 2003). It is suggested that the repeated miscarriages might be associated with decreased progesterone levels due to stress (Arck et al., 2007). Stress affects the hypothalamic–pituitary–adrenal (HPA) axis and increases levels of the classical stress mediators, corticotrophin-releasing hormone (CRH) and glucocorticoids. CRH can inhibit GnRH and glucocorticoids can suppress pituitary luteinizing hormone (LH) secretion and thus affect steroid hormone production.

Progesterone levels increase gradually at first (Fig. 11.1). There is little change in progesterone concentration between the 5th and 10th week, but after the 10th week the levels increase more markedly as the placenta becomes the main site of steroid hormone synthesis. By the end of the first trimester, levels of progesterone are 50% higher than luteal levels and by term the levels have increased threefold. The syncytiotrophoblast uses maternal cholesterol as a substrate for progesterone synthesis. Placental production of progesterone is adequate by 5–6 weeks. A primate pregnancy can survive ovariectomy (oophorectomy, removal of ovaries), although the corpus luteum is essential in other mammalian pregnancies (Johnson and Everitt, 2000). Human corpus luteal production of 17α-hydroxyprogesterone decreases from 6 to 9 weeks as placental production increases. Measurement of the different progesterone metabolites was commonly used to assess placental function.

Fig. 11.1 Increasing concentrations of oestrogen and progesterone during pregnancy.

The primary oestrogen of pregnancy is oestriol. Early in pregnancy, oestrone and oestradiol levels increase but oestriol levels do not begin to rise until the 9th week when the fetal adrenal glands begin to synthesize the precursor dehydroepiandrosterone sulphate (DHEAS) from placental pregnenolone; DHEAS is the substrate for placental production of oestriol (see Chapter 3). Maternal and placental steroids are conjugated in the fetal liver and adrenal glands into water soluble, and thus biologically inactive, forms (so the fetus is protected from the effect of the steroids' precursors). As the 16-hydroxyl precursor originates only from the fetal liver, production of oestriol indicates fetal well-being. In ‘at risk’ pregnancies, decreased oestriol may indicate fetal distress and the need to induce premature delivery, although as an index of placental function and fetal well-being it has largely been replaced by Doppler investigation and biophysical profiling. Oestriol measurement is part of the Bart's (triple) test for Down's syndrome (see Chapter 7). Oestrone and oestriol levels increase about 100 times and oestradiol levels about 1000 times during the course of the pregnancy (Blackburn, 2007). The oestrogens promote the growth of the endometrium and breasts, enhance myometrial activity, increase sensitivity to carbon dioxide, increase pituitary prolactin secretion, promote myometrial vasodilation, stimulate fluid retention, alter the composition of connective tissue and increase the sensitivity of the uterus to progesterone in late pregnancy.

Human chorionic gonadotrophin

The main function of hCG is to maintain production of steroid hormones from the corpus luteum in early pregnancy until the placenta can take over. hCG has a very similar structure to that of LH – as well as follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) – and acts on the LH receptors, prolonging the life of the corpus luteum. hCG is produced initially by the outer cells of the blastocyst which are the cells that differentiate into trophoblast cells and subsequently into the placenta. The syncytiotrophoblast, which evolves from the trophoblast (see Chapter 8), continues to produce hCG. It is secreted, and can be detected before implantation, in vaginal secretions and in the maternal circulation (see Fig. 11.1). As the lacunae begin to be formed by the invading syncytiotrophoblast, the hCG diffuses into the maternal blood and significant levels can be detected. Measurable urine values are present 2 weeks after fertilization; home pregnancy tests are very sensitive and specific. The presence of hCG confirms successful fertilization as, apart from very rare production by certain gut tumours, it is not produced by other tissues (Iles and Chard, 1991). hCG is produced in large amounts by hydatidiform moles (see Chapter 8); following evacuation of a molar pregnancy, urinalysis for the presence of hCG is continued for 2 years to exclude the development of choriocarcinoma.

Production of hCG is maximal at 8–10 weeks and then falls to a low plateau level that is maintained throughout the pregnancy. hCG levels, therefore, reflect the placental transformation from an organ of invasion to one of transfer. Persistently low levels of hCG are associated with abnormal placental development or ectopic pregnancy. If hCG is given to non-pregnant women, the corpus luteum is maintained and progesterone secretion rises. Alternatively, antibodies to hCG given to a pregnant woman cause the corpus luteum to regress. hCG, rather than LH, is used to induce ovulation in fertility treatment. By 4–5 weeks, the placenta and fetus are synthesizing significant amounts of steroid hormones and can assume endocrine control of the pregnancy. hCG has thyroid-hormone-stimulating properties, affecting appetite and fat deposition, and also affects thirst, release of antidiuretic hormone (ADH) and other osmoregulatory changes (Davison et al., 1990). It also promotes myometrial growth and inhibits myometrial contractility (Kornyei, Lei and Rao, 1993). The effects of hCG are summarized in Box 11.1.

Box 11.1

Effects of human chorionic gonadotrophin (hCG)

• Luteotrophic effect on corpus luteum that maintains synthesis and secretion of oestrogen and progesterone

• Simulates placental progesterone production

• Possesses thyrotrophic activity

• May be responsible for nausea and vomiting

• Stimulates maternal thyroid gland; increases appetite and fat deposition

• Increases sensitivity to glucose

• Decreases osmotic threshold for thirst and release of ADH

• Suppresses maternal lymphocyte response thus preventing rejection of the placenta

• Promotes myometrial growth

• Inhibits myometrial contractility

• Modulates trophoblastic invasion

• Affects fetal nervous tissue development

• Affects male sexual differentiation and stimulates fetal testes to produce testosterone

• Stimulates fetal adrenal glands to increase production of corticosteroids

Human placental lactogen

As hCG levels fall, there is increased secretion of human placental lactogen (hPL). The levels of hPL increase in parallel with the size of the placenta and correlate well with fetal and placental weight. hPL has a similar structure and properties to growth hormone and prolactin; it is a single polypeptide chain and is lactogenic and stimulates growth of both maternal and fetal tissues. hPL appears to protect the fetus from rejection, and low levels of hPL are associated with pregnancy failure and spontaneous abortion. hPL is antagonistic to insulin, resulting in increased maternal metabolism and utilization of fat as an energy substrate. This diabetogenic effect of pregnancy reduces glucose uptake by maternal cells, thus making more available for fetal use (see below). hPL is also called human chorionic somatomammatrophin.

Relaxin

Relaxin is produced by the corpus luteum, and to a lesser extent by the myometrium and placenta. Levels of relaxin are highest in the first trimester. Relaxin has a role in the softening of elastic ligaments of pelvic bones and has been used clinically to enhance cervical ripening during induction of labour (see Chapter 13). Relaxin acts with progesterone to maintain uterine quiescence; it may also suppress oxytocin release and affect gap junction permeability. The softening and relaxation of the pelvic ligaments allow mobilization and growth of the uterus into the abdomen. Sometimes women experience low-back pain in pregnancy, which is associated with the stretching of these ligaments. For some women, this results in the pelvic joints becoming unstable and in severe cases results in symphysis pubis dysfunction (SPD), with severe pain on walking. Relaxin is also thought to be involved in endometrial differentiation during embryo implantation, wound healing and, possibly, tumour growth and progression (Ivell and Einspanier, 2002).

Adrenal and pituitary hormones

The adrenal gland increases in both size and activity during pregnancy. Oestrogen stimulates adrenal cortisol production by inhibiting the metabolism of cortisol and increasing the synthesis of cortisol-binding protein (transcortin). Progesterone increases tissue resistance to cortisol by competing at the receptor level and binding to the cortisol-binding protein; this also results in an increase in cortisol production. CRH from the hypothalamus affects the release of adrenocorticotrophin (ACTH), melanocyte-stimulating hormone (MSH) and β-endorphin from the anterior pituitary gland. ACTH stimulates the adrenal gland production of cortisol. Cortisol levels increase in response to stress, including increased cardiac output and decreased fasting glucose levels in the second trimester of pregnancy. Both CRH and ACTH are also produced by the placenta as well as by the maternal hypothalamic–pituitary axis; the placental hormones are subject to different feedback control mechanisms and may be important in initiating labour (see Chapter 13).

The increase in circulating levels of cortisol has a positive effect on certain conditions, such as rheumatoid arthritis and eczema. This observation led to the clinical use of exogenous cortisol as a treatment for these conditions. Both progesterone and oestrogen act synergistically to increase aldosterone production. Adrenal synthesis of androgens, oestrogen, progesterone and cholesterol increases in pregnancy.

The pituitary gland enlarges markedly during pregnancy. Much of the increase is due to increased number and activity of cells of the anterior pituitary gland. The gonadotrophs decrease in number as the raised oestrogen concentration inhibits release of FSH and LH, which are barely detectable for most of the pregnancy. However, under the influence of progesterone and oestrogen, the prolactin-secreting cells increase from 10% of the cell population to 50%. Prolactin levels increase progressively through the pregnancy to values 20 times higher than the prepregnant level. Production of ACTH increases, resulting in increased adrenal activity. MSH synthesis also increases so hyperpigmentation may occur (Elling and Powell, 1997). Pregnant women frequently observe that they tan more deeply or develop irregular pigmented patches. Towards the second half of pregnancy, oxytocin production from the posterior pituitary increases.

Thyroid hormones

The hypothalamic–pituitary–thyroid axis undergoes marked changes in pregnancy. Oestrogen, hCG and altered hepatic and renal function together act to change the levels of tri-iodothyronine (T₃), thyroxine (T₄) and thyroid-binding globulin (TBG); these changes are important to support the altered metabolism of pregnancy. Oestrogen stimulates hepatic synthesis of TBG by 50–100 times resulting in increased total amounts of T₃ and T₄, although free concentrations remain within normal physiological limits. hCG has mild TSH activity so it stimulates both the production of T₄ and the deiodination of T₄ to T₃ in the peripheral tissues. The high concentrations of hCG in the first trimester and the consequent increased secretion of thyroid hormones results in TSH release from the pituitary gland being inhibited. This means that maternal circulating concentrations of free T₃ and free T₄ peak at the end of the first trimester (de Escobar et al., 2008) requiring an increased availability of iodine. If iodine is limiting, the maternal thyroid exhibits an autoregulatory response, increasing synthesis of T₃ (which requires 3 iodine atoms per molecule) at the expense of T₄ production. Thus there is no change in TSH but there will be less T₄transported across the placenta to the fetus which could compromise neurodevelopment. Thyroid hormone receptors can be demonstrated in the fetal brain early in development (Bernal and Pekonen, 1984) suggesting early brain development requires maternal thyroid hormone input (later in gestation, both the maternal and fetal thyroid glands provide T₄). It should be noted that production of sufficient thyroid hormone requires a doubling of iodine intake compared to pregnancy requirement (which may mean potassium iodide supplements should be recommended – see Chapter 12).

Pregnancy mimics hyperthyroidism in a number of respects, for instance by increasing body temperature, and stimulating appetite and feelings of fatigue. In most pregnant women, the thyroid gland enlarges because thyroid activity increases and renal iodine loss is increased. Ancient Egyptians used the observation of pregnancy-induced goitre (thyroid gland hypertrophy) as confirmation of pregnancy (Glinoer and Lemone, 1992). The thyroid gland hypertrophies as it attempts to increase uptake of iodine for hormone synthesis. Nowadays, maternal goitre is rare in pregnancy partly because of better diets and iodine supplementation of table salt, but subclinical iodine deficiency can compromise fetal brain and central nervous system development resulting in neurological anomalies, reduced cephalic size (microcephaly) and reduced intelligence quotient (IQ). Many women are at the threshold of iodine deficiency and the demands of pregnancy can compromise them further, adding support for routine iodine supplementation in pregnancy (Perez-Lopez, 2007). Basal metabolic rate increases by 20–25% from the 4th month of pregnancy but much of the increase is related to the increased surface area of the mother and the increased work she has to do maintaining maternal and fetal tissue requirements. Nausea and vomiting have been linked not only to the changes in hCG (see above) but also directly to the rise in free T₄.

Hypothyroidism is common in women of reproductive age and in pregnancy can be associated with adverse maternal and neonatal outcomes including increased risk of pregnancy-induced hypertension, miscarriage, still-birth, postpartum haemorrhage, congenital malformation and fetal distress (Idris et al., 2005). Women with pre-existing thyroid deficiencies require close monitoring of thyroid function during pregnancy and often require increased doses of thyroxine due the altered metabolic demands of pregnancy.

The reproductive system

The blood vessels

The vasculature of the uterus undergoes a number of remarkable and unique changes during pregnancy. Uterine blood flow increases: the vessel diameter of the spiral arteries increases and vascular resistance falls (see Chapter 8). These essential changes accommodate the increased blood flow to the placenta, which is maintained under conditions of low blood pressure. The coursing of blood through the enlarged tortuous arteries produces a uterine ‘souffle’, which may be heard through a stethoscope or with a sonicaid. The enhanced blood supply to the uterus and the concomitant establishment of the maternal circulation to the placenta effectively diverts blood away from the legs (Burton et al., 2009).

The uterus

The uterus increases in all dimensions and also changes shape (see Chapters 2 and 13) during pregnancy. Uterine hyperplasia begins after implantation and is driven by oestrogen and growth factors (it occurs if the embryo is implanted in an extrauterine site; Blackburn, 2007). Early growth results in thickening of the uterine wall. The endometrium thickens into the decidua. The three layers of the myometrium become clearly defined as the uterine muscle undergoes initial hyperplasia (development of new fibres) and subsequent hypertrophy (increase in length and thickness of existing muscle fibres). Later uterine growth is mostly hypertrophy and hyperplasia of the myocytes and remodelling of connective tissue which is driven by distension as the fetus enlarges. The muscle fibres increase in length and width as the timing and speed of the myometrial action potentials change and the muscle cells increase their content of actin and myosin, gap junctions, sarcoplasmic reticulum and mitochondria.

In early pregnancy, the uterine isthmus increases from about 7 to 25 mm (Fig. 11.2). From 32 to 34 weeks, the isthmus forms the lower uterine segment (LUS). As effacement commences (at approximately 36 weeks), the external os is incorporated into the LUS (see Chapter 13). The blastocyst usually implants in the fundus (upper part) of the uterus. By 12 weeks, the fetus fills the uterine cavity and the fundus can just be palpated (felt) at the pelvic brim. By 20 weeks the fundus reaches the maternal umbilicus and by 8 months it reaches the sternum. As the uterus expands during pregnancy, it loses its anteverted and anteflexed configuration and becomes erect, tilting and then rotating to the right under the pressure of the descending colon. The uterus changes from its non-pregnant pear-shape and becomes spherical and then cylindrical. Abdominal measurement using the symphysis pubis as a reference point is often used to assess uterine size and fetal growth as pregnancy progresses.

Fig. 11.2 The uterine isthmus increases from about 7 to 25 mm in the early part of pregnancy. (Reproduced with permission from Miller and Hanretty, 1998.)

Uterine quiescence is mediated by progesterone, relaxin, nitric oxide (NO) and prostacyclin (also known as prostaglandin PGI₂). The uterus is never completely quiescent and exhibits low-frequency activity throughout the pregnancy (as it does in the non-pregnant state). Braxton Hicks contractions are painless contractions that are measurable from the first trimester of the pregnancy. These contractions do not dilate the cervix but assist in the circulation of blood to the placenta. The contractions are usually irregular and weak, unsynchronized and multifocal in origin. The contractions of the circular muscles are less than those of the longitudinal ones (Blackburn, 2007). The uterine ligaments soften and thicken under the influence of oestrogen, resulting in increased mobility and capacity of the pelvis.

The cervix

The cervix increases in mass and width during the pregnancy. Oestrogen increases the blood supply to the cervix resulting in a lilac coloration and softer tissue texture; the water content of the cervix also changes. The collagen fibre bundles become less tightly bound (see Chapter 13). The cervical mucosa proliferates and the glands become more complex and secrete thickened mucus, which forms a plug or operculum protecting the cervix from ascending infection. The plug is held laterally by projections of thickened mucus in the mouths of the mucus-secreting glands. It is this plug that is released as ‘the show’ at the onset of labour when the cervix starts to be drawn up to form the LUS.

The vagina

Blood flow to the vagina increases likewise, resulting in softer vaginal tissue which is more distensible. The lilac coloration of the vagina and cervix was traditionally recognized as being an indicator of pregnancy (described as Jacquemier's sign). The increased blood flow means that the pulsating of the uterine arteries can be felt through the lateral fornices (Osiander's sign). The increased vascularization of the vagina can result in increased sensitivity and sexual arousal. Venous engorgement results in increased vascular transudation, which together with the increased cervical mucus production results in an increased vaginal discharge. The vaginal discharge (leucorrhoea) has a low pH (because of the effect of raised oestrogen levels on the vaginal flora) and is thick and white with an inoffensive odour. Oestrogen also stimulates the vaginal epithelial cell division so the cells acquire a distinctly boat-shaped appearance (which should not be mistaken for carcinoma cells). Early in pregnancy, the hypertrophied corpus luteum, which is about 3–5 cm long, distends from the ovarian surface; this may be palpated in some women or visualized during endoscopic examination in women undergoing egg retrieval for IVF (in vitrofertilization).

The breasts

In early pregnancy, vascularization of the breasts increases. This tends to result in a marbled appearance of the skin owing to the marked dilation of the superficial veins. The breasts, specially the nipple areas, may feel sensitive and tingle because of the engorgement of blood. (Changes to the breast in pregnancy are described in more detail in Chapter 16.) Pregnancy following diagnosis and treatment for breast cancer is becoming more common with earlier diagnosis and delayed childbirth. Although concerns have been raised about the possible promotional effects of raised oestrogen levels during pregnancy on residual metastatic disease, the majority of studies indicate no adverse effect on the outcome of pregnancy or on survival (de Bree et al., 2010).

The signs of pregnancy are summarized in Box 11.2.

Box 11.2

Signs of pregnancy

• Amenorrhoea

• Softening of vagina and cervix

• Increased blood flow to vagina and cervix causing lilac coloration (Jacquemier's sign)

• Pulsating of uterine arteries (Osiander's sign)

• Tingling and sensitive breasts with dilated superficial veins marbling surface

• Nausea and vomiting, possible changes in taste

• Increased frequency of urination as uterus compresses bladder

• Increased pigmentation of skin

• Bleeding gums

• Tiredness

• Increased appetite and thirst

The cardiovascular system

The most notable physiological changes occur in the cardiovascular system in preparation for the increased demands of maternal and fetal tissues (Fig. 11.3). These changes are caused both indirectly by hormones (oestrogen, progesterone, prostaglandins and other vasoactive substances) and directly by mechanical effects and as a result of the increased load on the system. Marked haemodynamic adjustments take place in pregnancy; maternal blood volume and cardiac output quickly increase but paradoxically blood pressure falls because of the marked reduction in systemic vascular resistance and reduced blood viscosity due to haemodilution. Heart disease affects less than 1% of pregnancies and causes 10 deaths per million in England and Wales, but symptoms of heart disease (such as breathlessness, palpitations, fainting and oedema) are present in over 90% of pregnant women (de Swiet, 1998a). Superimposed on a pre-existing cardiac disease state, pregnancy may be dangerous and even potentially fatal. Measurement of cardiovascular system parameters is technically difficult and notoriously variable. Measurements obviously have to be indirect and are very sensitive to changes such as emotion, exertion and posture. In the research literature, there are many inconsistencies, some of which reflect differences in standardization of conditions (de Swiet, 1998a). In the last couple of decades there has been an increased incidence of myocardial infarction (MI) in pregnancy which reflects the increasing proposition of older women having babies (the risk of MI is 30-times higher in women over 40 years compared to women under 20 years; Curry et al., 2009) and increased obesity and pre-existing diabetes (Ward et al., 2007).

Fig. 11.3 The changed distribution of blood flow in pregnancy.

Blood volume

Total blood volume increases by 30–50%, more in multiple pregnancies (Brown and Gallery, 1994), resulting in a fall in plasma osmolality. The rise in blood volume correlates well with birth weight and, as it begins early in pregnancy, the mechanism of these early changes in the cardiovascular system is thought to be hormonally driven. It has been disputed whether the increase in volume (sodium and fluid retention) precedes the increased vascular space (‘overfill’ hypothesis) or whether the changes are stimulated by relative hypovolaemia (increased vascular capacity), known as the ‘underfill’ hypothesis (Schrier, 1992). The arguments for the ‘underfill’ hypothesis are supported by the observation that blood pressure falls before plasma volume expands (Duvekot et al., 1993). The consensus is that both mechanisms are important but the initial change is probably the decreased systemic resistance (Ward et al., 2007). Often in early pregnancy women feel faint, suggesting that the physiological compensation of the underfill has yet to occur.

Oestrogen stimulates angiogenesis (formation of new blood vessels and vascular beds) and increases the blood flow to the tissues. Oestrogen affects the distribution of collagen in the tunica media of the large vessel walls, increasing venous distensibility. Oestrogen also stimulates endothelium-dependent vasodilatation, by increasing synthesis of NO (a potent vasodilator) and vasodilatory prostaglandins and inhibiting the release of endothelin-I (a vasoconstrictor). Production of both prostacyclin and NO increases in pregnancy (Morris et al., 1996). These signals affect placental blood flow, particularly remodelling of the spiral arteries (see Chapter 8).

Progesterone relaxes vascular smooth muscle causing systemic vasodilatation and decreased peripheral resistance, probably via vasoactive prostaglandins and enhanced nitric oxide (NO) production. The syncytiotrophoblast is an essential site of NO production which is important in maintaining vasodilation of the uterine blood vessels and ensuring a high flow and low resistance blood supply to the uteroplacental bed and fetus. The effect of the vasodilation is that the circulatory system increases its capacity and is relatively underfilled. One of the early effects of this is decreased glomerular arteriolar resistance which results in increased glomerular filtration rate (GFR) and renal blood flow (Ward et al., 2007). Relaxin production is stimulated by hCG and is also involved in renal vasodilation (Conrad et al., 2005). The decreased vascular tone in the blood supply to the kidneys causes renal compensatory mechanisms to increase plasma volume and cardiac output. In addition, both progesterone and oestrogen increase water retention by affecting the renin–angiotensin system (RAS) and oestrogen increases hepatic angiotensinogen production. This results in a rise in angiotensin II, which increases renal fluid resorption and stimulates the production of aldosterone. All components of the RAS increase in pregnancy but there is decreased sensitivity to vasoconstrictors such as angiotensin II and noradrenaline during pregnancy (so blood pressure does not rise). Renin is produced by the uterus, placenta and fetus, as well as the kidney. Levels of renin are two- to threefold higher than before pregnancy. These changes in the RAS may mediate the oestrogen-stimulated angiogenesis and increased cell growth and division. Relaxin increases production of ADH and oxytocin and modulates responses to angiotensin II. The increased ADH promotes water retention and thirst; the raised oxytocin promotes vasodilation and sodium excretion partly by increasing cardiac atrial natriuretic peptide production (Brunton et al., 2008).

Progesterone stimulates a 10-fold increase in the amount of circulating aldosterone. Progesterone is antagonistic to aldosterone but some progesterone is converted to deoxycorticosterone, which has mild aldosterone-like properties. Progesterone augments its effects on the circulatory volume by resetting the thirst centres in the hypothalamus and increasing thirst. Progesterone also lowers the sodium threshold for the RAS and blocks the vasopressive activity of angiotensin II in pregnancy (Blackburn, 2007). The net result of the changes in oestrogen and progesterone is an increase in vascular resistance followed by increased sodium and water retention and expansion of the circulating volume (Fig. 11.4).

Fig. 11.4 The likely pathways for blood volume increase in pregnancy.

Cardiac output

Blood volume and cardiac output increase in parallel (Fig. 11.5). Cardiac output increases by 30–50%, an average increase of 1.5 L/min from 4.5 to 6 L/min. Cardiac output rises quickly in the first trimester and is maintained throughout the pregnancy. The increase in cardiac output is greater in multiple pregnancies. Cardiac output is affected by posture: when the pregnant woman lies supine, her uterus impedes venous return from the inferior vena cava resulting in an apparent decrease in cardiac output. The measured drop in cardiac output in the third trimester, observed by a number of researchers, was most probably the result of measurements being made with the woman lying supine (Mabie et al., 1994). In labour, cardiac output increases by about 2.0 L/min.

Fig. 11.5 The parallel increase in (A) blood volume and (B) cardiac output during pregnancy. Blood volume is increased up to 40%, thus increasing the load on the heart. (Reproduced with permission from Chamberlain et al., 1991. (B) After Whitfield, 1986.)

Cardiac output is the result of two variables: heart rate and stroke volume (see Chapter 1). In pregnancy, both heart rate and stroke volume increase. Heart rate increases soon after implantation, by about 20% (an average of 15 beats more per minute) from about 70 to 85 beats/min. Stroke volume typically increases by about 10% from 64 to 71 mL. Steroid hormones and prolactin may affect the myocardium directly. Oestrogen stimulates an increased accumulation of components of the myocardial cells and increases contractility (Duvekot and Peeters, 1998). Heart rate is usually measured by the palpation of peripheral pulses and the increase in stroke volume means the pulse is easy to palpate in a pregnant woman. Heart rate is affected by many things; tachycardia (fast pulse) may be caused by excitement, stress, fear, medication, illegal use of drugs, etc. and so, in isolation, can be a poor indicator of physical problems such as sepsis and haemorrhage so needs to be considered in conjunction with other abnormal observations such as raised blood pressure, temperature, or respiratory rate.

Bradycardia is an abnormally slow heartbeat and is rare in pregnant women but can indicate heart block, raised intracranial pressure, medication and use of illegal drugs.

Heart

The early changes relating to the heart occur early in the pregnancy and are caused by hormonal changes. Later, the heart is displaced upwards by elevation of the diaphragm and is rotated forward so the electrocardiogram (ECG) changes and the location of the apex beat is directed forward to the anterior chest wall. The heart increases in size by an average of 70–80 mL (about 12%). This increase is due to increased filling and oestrogen-stimulated cardiac muscle hypertrophy (an increase in the size of pre-existing cardiomyocytes). The remodelling of the heart that occurs in pregnancy in response to increased blood volume and workload is an adaptive response analogous to the ventricular hypertrophy of an athlete's heart in continuous training. However, heart hypertrophy can lead to cardiac disturbances such as cardiac arrhythmias (Eghbali et al., 2006). The pregnant woman's heart is thus dilated and has increased contractility. Increased blood volume results in an increase in venous return and therefore increased atrial size. The heart sounds change because the mitral valve closes marginally before the closure of the tricuspid valve; thus the first heart sound is louder with an exaggerated split. Many pregnant women (92–95%) develop innocent (non-significant) systolic murmurs in pregnancy. The increased blood flow through the mammary blood vessels may be perceived as a possible heart murmur; this is more common in lactation. The net result of increased contractility, increased venous return, cardiac hypertrophy, decreased peripheral resistance and increased heart rate is increased cardiac output. Women with known pre-existing cardiac disease must be carefully monitored during pregnancy as they may not have the physiological reserve to cope with this increased demand on the heart (see Case Study 11.1). Other conditions may also pose serious risk in pregnancy relating to increased cardiac output such as Marfan syndrome (see Box 11.3).

Case study 11.1

Moira is a 23-year-old primigravida who, at the age of 19 underwent a heart and lung transplant as a result of cystic fibrosis. Moira and her partner had been well informed of the risks associated with a pregnancy, had planned not to have any children and so this pregnancy was unexpected.

• How should Moira's care be managed in relation to her transplant status and her pregnancy and what is the role of the midwife in this complex case?

• What are the possible complications and risks in this case and what would the midwife need to know and do to ensure early recognition, referral and intervention is optimized?

Box 11.3

Marfan Syndrome

Marfan syndrome is a disorder of connective tissue and as a result has a high incidence of aortic aneurism due to the inherent weakness of the artery wall. Incidence of the disease is about 2 per 10000 births and affects both men and women equally. As cardiac output is increased in pregnancy, the risk of aortic aneurism occurring is greatly increased and so the pregnant woman should have regular cardiac ultrasounds to optimize early detection of this potentially life threatening situation. If aortic aneurism occurs, emergency surgical intervention is required which involves the weakness of the aortic wall being strengthened by synthetic graft material.

Arteriovenous (AV) difference

Increased cardiac output exceeds increased oxygen consumption (especially early in pregnancy when cardiac output increases considerably and oxygen consumption is relatively low) so more oxygen is returned to the heart from venous circulation compared with prepregnant values and the AV difference is smaller. The AV difference is 34 mL in mid-pregnancy rising towards term but is always less than the non-pregnant values of about 45 mL (de Swiet, 1998a). The higher return of oxygen to the heart suggests that the commonly measured decrease in haemoglobin concentration is not physiologically inadequate and the relatively small increase in total haemoglobin (oxygen-carrying capacity) is more than sufficient to compensate for increased oxygen requirements. This supports the argument that the term ‘physiological anaemia’ is inappropriate (see p. 269). The increased AV difference, especially early in the pregnancy before increased oxygen consumption, means that early fetal development and organogenesis occur in an environment which is adequately oxygenated despite the maternal spiral arteries not connecting with the intervillous spaces in the early part of pregnancy (see Chapter 8).

Blood pressure

Normal pregnancy has relatively little effect on arterial blood pressure. Despite increased cardiac output and increased vascular capacitance, there is relatively little change in systolic pressure in pregnancy. However, diastolic blood pressure is lower in the first two trimesters and returns to prepregnant values in the third trimester. Both the development of new vascular beds and the relaxation of peripheral tone by progesterone result in decreased resistance to flow. This is augmented by a change in the profile of prostaglandins produced. The levels of the prostaglandin PGE₂ and prostacyclin, which stimulate vasodilation, rise early in pregnancy. NO (nitric oxide; formerly known as endothelium-derived relaxing factor, EDRF) also appears to play an important vasodilatory role (Palmer et al., 1987). The most important stimulator for NO production is shear stress such as that generated from a pulsatile blood flow (Maul et al., 2003). The increased difference between diastolic and systolic blood pressure means that for much of the pregnancy the pulse pressure is increased. Hypotension, particularly in early pregnancy, has been associated with fatigue, headaches and dizziness, which many women experience.

In pregnancy, changes in posture can cause acute haemodynamic changes (Blackburn, 2007). Blood pressure in normotensive women is higher when sitting and falls on lying, especially in the supine position (Box 11.4). Effects on venous pressure are relatively dramatic compared with the effects on arterial pressure. As there are no valves between the return from the femoral veins to the vena cava and heart, venous pressure in the legs is similar to the pressure in the heart so, if a pregnant woman lies in a supine position, the uterus can compress the aorta and, particularly, the thin-walled vena cava and iliac veins. (The aorta is compressed as well but to a lesser degree because it has a much thicker vessel wall.) Return of blood to the heart can also be impeded by the pressure of the fetal head on the iliac veins and by hydrodynamic obstruction due to outflow of blood from the uterine vessels. Most women experience a drop in blood pressure greater than 10% when they lie down; for some of these women this fall is extreme, reaching up to 50%. The effect of assuming the lithotomy position in labour is to decrease cardiac output significantly (Carbonne et al., 1996).

Box 11.4

Blood pressure monitoring

As high blood pressure in pregnancy is a risk factor for serious maternal and fetal complications, it is important that blood pressure is measured accurately (NICE, 2008). Oscillometric (automated) blood pressure equipment is usually used however this is best used when serial monitoring is required such as in fulminating pre-eclampsia or eclampsia. Routine blood pressure monitoring should be undertaken with manual equipment (NICE, 2008). Important factors that affect the blood pressure reading include correct cuff size and the woman's position and posture, avoiding recent intake of caffeine or nicotine, taking the average of two readings, etc. The usual clinical definition of hypertension is:

(1) a single diastolic reading of 110 mmHg or above

(2) or a diastolic of 90 mmHg or above (but below 110) on 2 consecutive occasions at least 4h apart

(3) and/or a systolic reading of 160 mmHg or above on 2 consecutive occasions at least 4h apart.

Some women may not show the expected reduction in blood pressure in early pregnancy. This may be due to a degree of pre-existing renal disease or condition causing chronic hypertension but may also be an early indicator of hypertensive disease in pregnancy. Note that pre-eclampsia can be superimposed on chronic hypertension. A rise in blood pressure is often associated but not always present in pre-eclampsia. Other reasons for high blood pressure may be stress and anxiety, acute renal disease such as infection, raised inter-cranial pressure (the significance of this is increased with a slowing pulse). The blood pressure reading needs to be considered in the context of other risk factors. A drop in blood pressure may be caused by haemorrhage (significance is increased with the presence of tachycardia), advanced sepsis (septic shock), and drug induced.

In late pregnancy, most women experience oedema of the lower extremities (see Case study 11.2) owing to the combined effects of progesterone relaxing the vascular tone, the impeding of the venous return by the gravid uterus and gravitational forces. The peripheral circulatory volume is increased by 500–600 mL/limb (de Swiet, 1998a). Oedema is further increased in hypertensive women and tends to increase with increased maternal age. Fluid drunk by the pregnant woman appears as increased leg volume and the expected diuresis is delayed until, she lies down, resulting in increased nocturia. Blood pressure is higher on the side of placental implantation and oedema may also be more marked in the leg on the side of placental implantation (de Swiet, 1998a). The effect of increased venous pressure is to increase the incidence and severity of varicose veins of the legs, vulva and haemorrhoids (Fig. 11.6).

Case study 11.2

It is the height of summer and Kathy, 38 weeks' pregnant, informs her midwife she feels fat and sluggish and cannot cope with the hot weather. Kathy's ankles are visibly swollen.

• Is the midwife right to assume that this is normal?

• What indicators would the midwife be able to use in an assessment to reassure Kathy that all is well?

• What factors may alert the midwife to suspect that all is not well?

Three days later Kathy presents to the midwives' clinic complaining of breathlessness and chest pain.

• What should the midwife do in response to Cathy's worsening symptoms?

• What are the possible causes of these symptoms?

Fig. 11.6 The effect of increased venous pressure leading to increased incidence of varicose veins of the legs, vulva and haemorrhoids. (A) Normal vein with normal vascular tone; (B) varicose vein: the effects of progesterone on muscle tone cause incomplete valve closure, allowing the back-flow of blood.

The tendency to develop oedema is a also affected by the concentration of plasma proteins (see Box 11.5). The increment in plasma volume is not matched by an increase in plasma protein synthesis so there is decreased plasma colloidal pressure. This, together with the increased venous pressure, means there is an increase in fluid loss from the capillaries. There may also be an increase in capillary permeability (Blackburn, 2007).

Box 11.5

Oedema and hypertension

The pressures in the right ventricle, pulmonary arteries and pulmonary capillaries do not change but cardiac output increases. The higher pulmonary blood flow therefore has to be absorbed by decreased pulmonary resistance and dilatation of the pulmonary vascular bed so the volume of pulmonary circulation increases to match the increased cardiac output. Conditions where pulmonary resistance is increased or fixed have a poor maternal prognosis such as Eisenmenger's syndrome, which has a 30–50% mortality rate. Exercise presents an increased demand on the cardiovascular system (see Box 11.6).

The effects of exercise on the cardiovascular system are summarized in Box 11.6.

Box 11.6

Exercise in pregnancy

Exercise affects maternal physiology because there is a hormonal response, weight is redistributed and heat is generated. Many women experience very good physical health especially early in pregnancy. However, the question is whether the adaptive response to exercise compromises fetal oxygenation and well-being. The ability to increase cardiac output in response to exercise progressively declines throughout pregnancy. Theoretically, redistribution of weight could affect the venous return and blood could be preferentially circulated to the skeletal muscles and to the skin for heat dissipation. Studies on animals suggest that uterine blood flow can be decreased substantially before fetal oxygen uptake or temperature regulation is compromised. It has been reported that over a third of the female medal winners in the 1956 Russian Olympic team were pregnant and the cardiovascular changes enhanced for their performance (de Swiet, 1998a). In practice, moderate exercise in normal healthy pregnancy is encouraged as maternal and fetal health seem to benefit. However, pregnant women are advised to avoid jumping and jerky movements because of joint instability. Vigorous exercise is not recommended during hot humid weather or if the mother has a fever. It is suggested that heart rate should not exceed 140 beats per minute, strenuous exercise should be done for less than 15 min at a time and a pregnant woman should not allow herself to become breathless. A pregnant woman should stop physical exercise if pain, vaginal bleeding or dizziness is experienced or there are known risk factors.

Distribution of blood flow

Oestrogen increases blood flow to all tissues but the distribution of flow is affected by posture. Venous tone is affected by progesterone. The increased venous distensibility results in an increased incidence of varicose veins, venous thrombosis and thromboembolism. The uterus is the central target of the increased circulatory flow during pregnancy but distribution of flow to other organ systems, including kidneys, skin, lungs and breasts, increases as well. It is difficult to distinguish between blood flow to the increasing uterine tissue mass and that going specifically to supply the placenta because the uterine vessels are complex and inaccessible. AV shunts in the uterine vasculature have been identified; these allow a short circuit of the placental site after delivery of the placenta, rather than being important in increased flow during pregnancy. The increased flow to the uterus is about 500 mL/min more than that to the non-pregnant uterus but changes in uterine flow occur relatively late in pregnancy (de Swiet, 1998a). In rare situations of maternal cardiac arrest in late pregnancy, the altered blood flow will affect the ability of external cardiac massage to provide vital organ oxygenation. In such situations, immediate delivery of the infant must be considered either by perimortum caesarean section or an instrumental delivery if in the second stage of labour. Once delivered, the empty uterus will contract down enabling more blood to enter the central circulation improving oxygenation to the vital organs (Lewis, 2007).

Blood flow to the kidneys increases by about 400 mL/min from early pregnancy, facilitating elimination of waste products. Vasodilatory prostaglandins are implicated in the peripheral vasodilation, which is particularly evident in the vessels of the breasts, hands and face. Oestrogen and progesterone depress the normal response to angiotensin II and oestrogen abrogates the vasoconstriction mediated by the sympathetic nervous system. Blood flow to the lungs increases, reflecting the increased circulating blood volume and cardiac output. Distribution of blood to the skin is greatly increased (by about 500 mL/min) expediting heat loss. It is common for pregnant women to complain of being hot. Pregnant women usually have warm hands and feet and often complain that midwives' hands are cold. This vasodilatory effect is enhanced in smokers. Blood flow to the hands increases about sevenfold giving a very marked increase in skin temperature. The resulting peripheral vasodilation causes the capillaries to dilate and stimulates angiogenesis, and may give rise to the development of vascular spiders and palmar erythema, which is often associated with burning sensations (Henry et al., 2006). The increased blood flow means there is a decreased tendency to arteriolar spasm, and therefore conditions such as Raynaud's syndrome are abolished.

The increased blood flow to the skin stimulates the growth of nails and hair. The ratio of actively growing hair to resting (prior to falling out) hair is altered from 85:15 to 95:5 (de Swiet, 1998a). When this ratio returns to normal in the puerperium, vast amounts of hair can be lost. Mammary blood flow also increases (see Chapter 16). Coronary blood flow probably increases, reflecting the increased workload of the left ventricle, but it is thought that hepatic and cerebral blood flow do not significantly increase (de Swiet, 1998a).

In evolutionary terms, heat dissipation from the mucous membranes had been very important in mammals (this is best illustrated by dogs panting to lose heat). The increased flow to the mucous membranes in pregnancy can result in an increased congestion of the mucosa, which is demonstrated by an increased incidence of sinusitis, nosebleeds and snoring in pregnancy. It is suggested that elimination of waste products by the kidneys and heat by the skin is best fulfilled by an increased plasma volume rather than an increase in whole blood, which demonstrates the importance of the apparent physiological anaemia.

Haematological changes

The changes in maternal blood volume and composition increase the efficiency of the transplacental circulation and exchange mechanisms, thus benefiting fetal development. The haematological changes are also part of a maternal adaptive response that protects maternal homeostasis, including the ability to tolerate a sudden blood loss and to cope with placental separation. Thus, even women who have a degree of iron deficiency prior to pregnancy are protected from some decrease in haemoglobin levels at delivery. However, the adaptive responses to pregnancy potentiate the risks of iron-deficiency anaemia, thromboembolism and other clotting problems.

Plasma volume and blood cell mass/number

Pregnancy is a state of hypervolaemia. Blood volume increases in healthy pregnant women by about 1.5 L (30–50%, with a range of individual variation). Plasma volume increases initially rapidly from about 6 weeks' gestation and then the rate of increase becomes slower (Blackburn, 2007). The 40–50% increase in plasma volume is not matched by increased red blood cell mass and plasma protein production so there is a haemodilution (an apparent decrease) in haemoglobin and plasma protein concentration. Red blood cell mass increases by about 15–18% in women who do not take iron supplements and by about 25–33% in women supplemented with iron (Blackburn, 2007). The differences in plasma volume and red blood cell mass are accentuated by differential timing of the increases. Red blood cell mass begins to expand in the second trimester and the rate peaks in the third trimester. The maternal RAS may be involved; angiotensinogen competes for the erythropoietin receptors and may be a precursor of erythropoietin.

The increase in blood volume is higher in multigravidae and women who are obese, have multiple pregnancies or where the pregnancy is prolonged. The increment in plasma volume is positively correlated with birth weight and placental weight; pregnancies resulting in recurrent abortions, stillborn and low-birth-weight babies are associated with an abnormally low increase in plasma volume and an apparent increase (or no normal decrease) in haemoglobin concentration.

There is no reason for the relationship between plasma volume and blood cell mass, which are controlled by different mechanisms, to be retained throughout the pregnancy. The role of plasma is to fill the vascular space, maintaining the blood pressure, and to dissipate heat. Calculations suggest that the hypervolaemia is adequate to fill the increased vascular space of the pregnant uterus and the enlarged vascular beds of the breasts, muscles, kidneys and skin and to provide a reservoir against the pooling of blood in the lower extremities. It will also decrease the effect of the haemoglobin lost in bleeding at delivery. The decreased viscosity of the blood lessens the resistance to flow and therefore the cardiac effort required to propel the blood. Observation of a ‘normal’ (prepregnant) or increased haemoglobin level (rather than a lower level seen in healthy pregnancies) may therefore represent an unsatisfactory increase in plasma volume rather than a true increase in haemoglobin concentration. Levels of haemoglobin are at their lowest between 16 and 22 weeks. The assertion that a degree of haemodilution is normal and a requisite adaptation to pregnancy, rather than indicating pathological anaemia, is supported by the increased AV difference (see above).

Most of the increase in blood cell mass is in the form of red blood cells. An initial depression of erythropoietin levels occurs, but progesterone, prolactin and hPL all stimulate erythropoietin synthesis and so promote red blood cell production; however, red blood cell mass correlates best with hPL levels. These influences result in mild hyperplasia of the bone marrow and an increased reticulocyte count. The function of red blood cells is oxygen transport; therefore red blood cell mass will increase physiologically at high altitude and decrease with prolonged bed rest. In pregnancy, the increment in red blood cells should reflect the need for more oxygen; the estimated increased requirement to supply the increased maternal tissues and conceptus is 15.0–16.5%, which is slightly lower than the measured rise of 18%.

Levels of 2,3-DPG (2,3-diphosphoglycerate) increase from early pregnancy so the oxygen–haemoglobin dissociation curve shifts to the right (see Chapter 1) thus facilitating oxygen unloading at the peripheral tissues. Red blood cells become more spherical, with an increased diameter and thickness, because plasma colloid pressure falls and thus more water crosses the erythrocyte membrane by osmosis.

Iron status

As plasma volume increases, haemoglobin concentration and haematocrit fall, reaching a lowest point at 16–22 weeks (Blackburn, 2007). The World Health Organization recommends that haemoglobin concentration should not fall below 11 g/dL at any point in pregnancy; others suggest it should not fall below 10 g/dL. If iron stores can be demonstrated not to be depleted, it would suggest that the decreased haemoglobin concentration is not attributable to iron deficiency. In pregnancy, the most accurate and appropriate method of determining iron status and anaemia is measurement of serum ferritin levels. Serum ferritin, the major iron-storage protein, becomes depleted before clinical indicators reveal anaemia. Serum ferritin is stable, is not affected by recent ingestion of iron and quantitatively reflects iron stores, particularly in the lower range. Serum ferritin levels of less than 50 g/L in early pregnancy indicate a need for iron supplementation and levels above 80 g/L are probably adequate to protect the woman from iron depletion. However, routine iron supplementation in pregnancy, of apparently healthy women with no apparent iron deficiency, results in red blood cells increasing by 30% rather than by 18% in unsupplemented women (Letsky, 1998). One method of assessing anaemia in non-pregnant subjects is by observing an increased red blood cell mass in response to increased iron supplementation (Yip and Dallman, 1996).

The need for routine iron supplementation in pregnancy is a controversial area (Haram et al., 2001). Letsky (1998) argues strongly that clinical indicators of anaemia are not sensitive enough to demonstrate iron deficiency in practice. Iron depletion causes a reduction in mean blood cell volume (MCV). However, increased erythropoiesis results in a higher proportion of young larger red blood cells, which tends to mask the effect of iron deficiency on cell volume even with established anaemia.

Although the amenorrhoea of pregnancy helps to conserve iron stores and absorption of dietary iron increases, the theoretical requirement of iron in pregnancy can probably be met only if the woman has good iron stores prior to conception. Letsky argues that, although pregnancy is a physiological state, many women enter pregnancy with insufficient iron stores to supply the high requirements particularly of the third trimester. However, maternal iron absorption increases by about fivefold in the second trimester of pregnancy and by about ninefold in the third trimester (Barrett et al., 1994) suggesting that absorption of iron increases in parallel with the increased requirement. Active transport of iron across the placenta is maximal in the last 4 weeks of pregnancy. The inadequacy of dietary iron may be related to the move away from the Palaeolithic iron-rich diet that was normal for most of human evolution to a cereal-based one with less meat and fish (Cordain et al., 2002). Although most of the body's iron is associated with haemoglobin, iron is also a component of the electron transport chain. Tissue enzyme malfunction occurs in the first stages of iron deficiency before significant anaemia is apparent and supplements can increase perceptions of well-being. Subclinical degrees of iron deficiency may adversely affect maternal exercise tolerance, cerebral function and well-being (Letsky, 1998). Offspring of iron-deficient mothers may have reduced iron stores and are at risk of infantile anaemia, which may affect their mental and motor development and have long-term consequences. Maternal iron-deficiency anaemia correlates with high placental fetal weight, suggesting fetal growth is impaired (see Chapter 9). Low birth weight and high placental fetal weight have been associated with hypertension in adult life (Godfrey et al., 1991), so iron-deficiency anaemia in pregnancy may have long-lasting and far-reaching effects. Concerns have been expressed about iron supplementation in early pregnancy (Weinberg, 2010) when iron demands are low because the embryo is so small and the increase in red blood cell mass can be met by iron ‘savings’ from menstrual loss having ceased. The placental circulation during the embryonic period creates an environment which is relatively hypoxic (see Chapter 8) so excess iron which can induce oxidative stress could potentially pose a teratogenic risk to the embryo at a period of maximum susceptibility. In addition, it is argued that iron loading could increase the risk of maternal gestational diabetes and pre-eclampsia (Weinberg, 2009).

Haemostasis

Pregnancy is a hypercoagulable state. Bleeding time in pregnancy decreases by about 30% because the ratio of clotting and fibrinolytic factors alters. There is an increase in fibrinogen and other clotting factors leading to an increased generation of thrombin and a decrease in fibrinolytic or anticoagulant substances (for instance protein S activity decreases and resistance develops to activated protein C). The number of platelets decreases slightly towards term but generally remains within the non-pregnant range. This response is variable; there may be increased platelet turnover and low-grade platelet activation (an increased number of aggregated platelets) as the pregnancy progresses, resulting in a larger proportion of younger platelets with increased volume. Low-grade chronic intravascular coagulation in the uteroplacental circulation may be part of the normal physiological response to pregnancy. Platelet count is further decreased in pregnancies with fetal growth retardation, and even in mild pre-eclampsia the lifespan of platelets is reduced.

Synthesis of antithrombin III (the main physiological inhibitor of thrombin and factor Xa) increases in pregnancy in parallel with the increased plasma volume. Levels decrease at delivery (thus increasing the tendency to thrombosis) and increase 1 week postpartum. There is a general increase in clotting factors, particularly in late pregnancy, as demonstrated in Von Willebrand's syndrome (an inherited clotting disorder), which improves with pregnancy. The change in amount of clotting factors seems to be compensatory in preparation for labour. The overall effect is hypercoagulability which is augmented by venous stasis of the lower limbs (Holmes and Wallace, 2005). The hypercoagulability is optimal in labour, meeting the demands of placental separation but can increase the risks of thrombosis and disseminated intravascular coagulation. At delivery, total blood loss can be as much as 500 mL. The normal blood flow of 500–800 mL/min is staunched within seconds (aided by myometrial contraction, which decreases blood flow and rapidly closes spiral arteries). A fibrin mesh then rapidly covers the placental site as 5–10% of the total circulating fibrinogen is deposited. Fibrinolytic activity decreases in pregnancy and remains low in labour. It returns to normal within an hour of delivery; the placenta produces inhibitors that block fibrinolysis. Most of the physiological changes in pregnancy are reversed quickly in the puerperium; however, the hypercoagulable state may exist for much longer (possibly over 6 weeks). This puts the woman in the early postnatal period at a higher risk of developing deep vein thrombosis and pulmonary embolism from changes that occur in the antenatal period.

Table 11.1 summarizes the haematological changes in pregnancy.

Table 11.1 Summary of haematological changes in pregnancy
	Change in Pregnancy	Notes
Plasma volume correlates	Increases by about 50% from 2600 to 3900 mL	More in second and subsequent pregnancies; with birth weight
Red blood cell mass	Increases by about 18%	Increase is greater with iron supplementation (to 30%)
Neutrophil count	Both cell number and metabolic activity increase	Initial increase occurs early in pregnancy and is similar to the response to other physiological stresses
Plasma proteins	Decrease	Decreased osmotic pressure predisposes to oedema
Clotting factors	Increase	Fibrinolytic factors decrease
Platelet count	Slight fall	Coagulability increases

The respiratory system

Maternal respiratory effort has to be increased in pregnancy to meet the increased metabolic demands of the maternal and fetal tissues. By the end of the pregnancy, 16–20% more oxygen is consumed. The respiratory system is also affected by the expanding uterine volume. In terms of physiological reserve, the stress put on the respiratory system by pregnancy is small compared with the increases that can be measured on exercise (Table 11.2). This contrasts with the much larger proportion of the cardiovascular physiological reserve required in pregnancy. The clinical implication of this is that patients with respiratory disease are much less likely to deteriorate in pregnancy than are those with cardiac disease.

Table 11.2 Pregnancy and physiological reserve
Parameter	Normal	Pregnancy	% Increase	Exercise	% Increase
Minute volume	7.5 L/min	10.5 L/min	40	80 L/min	1000
Oxygen consumption	220 mL/min	255 mL/min	16
Cardiac output	4.5 L/min	6 L/min	30	12 L/min

Anatomy

Early in pregnancy, and therefore not secondary to pressure from the uterus, the diaphragm is displaced upwards by 4 cm (de Swiet, 1998b; Fig. 11.7). The respiratory excursion of the diaphragm increases and there is an increased flaring of the lower ribs (increasing the substernal angle from 68° to 103° by late pregnancy; Blackburn, 2007). This compensatory increase in the diameter of the thorax by about 2 cm (the circumference of the chest increases by about 15 cm) means that the volume of the thoracic cavity is about the same as that before pregnancy. The diaphragm performs the major work of respiration; the breathing is thoracic rather than abdominal. Hormonal influences cause the muscles and cartilage in the thoracic region to relax so the chest broadens. The subsequent decrease in chest wall compliance means the thoracic wall can move further inwards so there is less trapped air and the residual volume decreases. These anatomical changes probably do not completely reverse after the pregnancy (indeed it is said that the increased flaring of the rib cage is beneficial to opera singers after pregnancy).

Fig. 11.7 Displacement of the diaphragm in pregnancy: the ribcage in pregnancy (light) and the non-pregnancy state (dark), showing the increased subcostal angle, the increased transverse diameter and the raised diaphragm in pregnancy.

Progesterone is a respiratory stimulant; it lowers the sensitivity of the peripheral and central chemoreceptors for carbon dioxide (Prabhakar and Peng, 2004). This means that respiratory drive is stimulated at lower carbon dioxide levels so pregnant women breathe more deeply. As progesterone increases during the pregnancy, the increased responsiveness to PCO₂ results in an increased tidal volume and therefore minute volume (Table 11.3). So hyperventilation (increased tidal volume) is normal in pregnancy. Oxygen consumption increases but arterial oxygen pressure does not change.

Table 11.3 Lung volumes and capacities
Parameter	Definition	Normal Range	Change in Pregnancy
Tidal volume (TV)	Volume of a normal breath at rest	500 mL	Increases by 150–200 mL (25–40%) 75% increase occurs within first trimester
Respiratory rate (RR)	Number of breaths per minute	12 breaths/min	Unchanged/slightly increased to 15 breaths/min
Minute volume (MV)	Total air taken in 1 min of respiration (= TV × RR)	6000 mL/min	Increased by about 40%
		6.5 L/min	10 L/min
Inspiratory reserve volume (IRV)	Volume of air that can be inspired above the resting tidal volume	3100 mL	Unchanged
Expiratory reserve volume (ERV)	Volume of gas that can be expired in addition to the tidal volume	1200 mL	Reduces progressively from early pregnancy to about 1100 mL
Residual volume (RV)	Volume of gas remaining in the lungs after a maximal expiration	1200 mL	Decreases progressively
Total lung capacity (TLC)	Maximum volume of the lungs (= TV + IRV + ERV + dead space)	6000 mL	Unchanged
Vital capacity (VC)	Total volume of gas that can be moved in and out of the lungs (= TLC − residual volume)	4800 mL	Increased 100–200 mL in late pregnancy? (not apparent in obese women)
Inspiratory capacity	Total inspiratory ability of the lungs (= IRC + TV)	2200 mL	Increased about 2500 mL at term
Functional residual capacity (FRC)	Volume of gas remaining in the lungs after a resting breath (= ERV + RV)	2800 mL	Decreases progressively to 2300 mL – increases mixing efficiency
Residual volume (RV)	Volume of gas remaining after a maximal expiration (= FRC − ERV)	2400 mL
Physiological dead space			Increases by ~60 mL
Alveolar ventilation	Difference between TV and volume of physiological dead space		Increased

In pregnancy, the respiratory rate is unchanged but minute ventilation increases by 40% because tidal volume increases; this is apparent as early as 7 weeks. This hyperventilation exceeds the increased oxygen consumption. Efficiency of alveolar gas exchange is much more efficient when tidal volume is increased rather than respiratory rate (Fig. 11.8). Alveolar ventilation is further enhanced by the decrease in residual volume. About 150 mL of an inspired breath remains in the upper airways where no gas exchange takes place (this is known as the anatomical dead space). Although the dead space increases by about 60 mL in pregnancy because of dilatation of the smaller bronchioles, the net alveolar ventilation is increased. The increased tidal volume means that the functional residual capacity is reduced, thus an increased volume of fresh air mixes with a much smaller residual volume of air remaining in the lungs. Alveolar ventilation in pregnancy is thus increased by about 70% resulting in increased efficiency of mixing of gases, which facilitates gas exchange because the diffusion gradient is bigger. The increased gradient of carbon dioxide concentrations between maternal and fetal blood aids transfer of carbon dioxide across the placenta and may be particularly important in adverse circumstances. Progesterone increases carbonic anhydrase levels in red blood cells (see Chapter 1) thus further increasing the efficiency of carbon dioxide transfer.

Fig. 11.8 (A) Alteration in alveolar gas exchange during pregnancy, and (B) its mechanisms.

Maternal partial pressures of oxygen increase slightly (from 95–100 to 101–106 mmHg) and levels of carbon dioxide decrease (from 35–40 to 26–34 mmHg). The small increase in PO₂ has little effect on haemoglobin saturation. Posture, however, affects alveolar oxygen levels: a supine position in late pregnancy results in a lower alveolar oxygen pressure than when in a sitting position. This change in alveolar oxygenation is probably not significant for the fetus although it may be compensatory at high altitude. Air travel is associated with increased dyspnoea and respiratory rate. The decreased level of carbon dioxide in pregnancy results in a mild respiratory alkalosis. The change in pH affects levels of circulatory cations such as sodium, potassium and calcium, aiding transfer across the placenta and increasing provision for fetal growth. Metabolic compensation to the relative alkalosis occurs by increasing renal excretion of bicarbonate ions. The resulting fall in serum bicarbonate, which limits the buffering capacity in pregnant women, causes maternal pH levels to increase to the upper end of the normal physiological range, from 7.40 to 7.45. Maternal ability to compensate further for metabolic acidosis is therefore limited, which may create problems in prolonged labour or where there is inadequate tissue perfusion (see Chapter 13).

Progesterone has a local effect on the smooth muscle tone of the airways and the pulmonary blood vessels and decreases airway resistance. Diffusion capacity is the ease with which gases can cross the pulmonary membranes. In early pregnancy, diffusion capacity decreases probably because of the effects of oestrogen on the composition of the mucopolysaccharides of the capillary walls, which increases diffusion distance (de Swiet, 1998b). This effect may last for months after delivery. Increased water retention in the pulmonary tissues also results in a decrease in diffusion capacity. There is an increased closing volume suggesting that the calibre of the small airways is decreased; this may be due to increased lung fluid. The decreased efficiency of pulmonary gas transfer is partially compensated for by progesterone-induced relaxation of bronchiole smooth muscle, which decreases airway resistance. The decreased airway resistance means that air flow is increased. Prostaglandins also affect bronchiole smooth muscle. PGF_2α, which increases throughout the pregnancy, is a smooth muscle constrictor; PGE₁ and PGE₂, which increase in the third trimester, are smooth muscle dilators. The work of breathing is probably unchanged as the decreased airway resistance compensates for the congestion in the bronchial wall capillaries.

Many pregnant women experience dyspnoea, causing discomfort and anxiety, often early in pregnancy before there are changes in intra-abdominal pressure. This correlates well with PCO₂ and may be due to hyperventilation (de Swiet, 1998b). Capillaries in the upper respiratory tract become engorged, which can create difficulties in breathing via the nose and aggravate respiratory infections. Laryngeal changes and oedema of the vocal cords caused by vascular dilation can promote hoarseness and deepening of the voice, and a persistent cough. In severe cases, these changes in laryngeal thickening may cause complications should endotracheal intubation be necessary, for instance in anaesthesia. Forced expiratory volume over 1s and peak flow rate are not usually affected in pregnancy.

In labour, pain causes an increase in tidal volume and respiratory rate (these effects are abolished by effective epidural anaesthesia). In the second stage, muscle demands result in metabolic acidosis (increased lactate and pyruvate production); this is countered to a degree by the respiratory alkalosis from hyperventilation (Blackburn, 2007). Pregnant and recently delivered women with identified respiratory risk factors or complications should have their respiratory rates monitored because increased respiratory rate can be an early indicator of physical deterioration. Oxygen saturation monitoring should not be used in place of observing respiratory rate because a drop in SaO₂ is usually a late sign of physical deterioration. SaO₂ will often be normal in the presence of a raised respiratory rate as this initial compensatory effect maintains adequate oxygenation. If the respiratory rate is raised, SaO₂ monitoring should be used so that interventions such as oxygen therapy are observed to be effective in preventing further deterioration (Lewis, 2007).

The renal system

Increased urinary frequency, leakage and nocturia are so common that they are considered a ‘normal’ part of physiological adaptation to pregnancy; urinary tract infections (UTIs) are also relatively common. The marked haemodynamic and hormonal changes in pregnancy cause renal function to be altered. During pregnancy, the kidneys increase excretion of waste products in response to the increase in maternal and fetal metabolism, and retention of fluid and electrolytes is altered in response to cardiovascular changes. It is generally accepted that the increased circulating blood volume and haemodilution in pregnancy are achieved by the kidneys increasing their tubular reabsorption rate of sodium. The retention of sodium is stimulated by deoxycorticosterone derived from progesterone. Fluid retention is facilitated by the action of angiotensin II (see above for description of the RAS). Oestrogen increases both angiotensinogen production and renin production. ADH secretion tends to be triggered at lower plasma osmolality during pregnancy, possibly affected by hCG levels (Blackburn, 2007). Likewise, the osmotic threshold for thirst decreases from early pregnancy.

The gross anatomy of the renal system is altered in pregnancy. The kidneys enlarge, by about 1 cm in length and by about 30% in volume, owing to an increase in renal blood flow and vascular volume (Jeyabalan and Lain, 2007). Alterations in both prolactin, prostaglandin and relaxin levels have effects on renal blood flow (Baylis and Davison, 1998). The increased renal blood flow, due to haemodilution and hormonal changes, results in an increased GFR from early pregnancy. The increased GFR results in more sodium, glucose and amino acids in the filtrate; however, tubular reabsorption also increases so most of the increased sodium load is reabsorbed. The sodium retention results in water accumulation. The increase in GFR also results in a fall in serum creatine and urea levels so a ‘normal’ non-pregnant level of serum creatinine (of 1 mg/dL) may indicate renal impairment in pregnancy (Maynard and Thadhani, 2009) or other conditions associated with a lack of plasma volume expansion such as pre-eclampsia (Jeyabalan and Lain, 2007). Assessment of proteinuria is also important in indicating pre-eclampsia and in the care of pregnant women with pre-existing kidney disease. Pregnancy is more becoming more common in kidney transplant recipients as fertility increases markedly after transplantation. The outcome of pregnancy in women with chronic kidney disease (CKD), who have mild renal impairment, little proteinuria and normal blood pressure, is good, though more severe CKD is a risk for preterm delivery and pre-eclampsia. Routine antenatal care includes dipstick protein testing of a random urine sample to monitor proteinuria. Although this screening method has a high incidence of false-negative and false-positive results, it is much less cumbersome than a 24-h urine collection which can be inaccurate if there is undercollection (Maynard and Thadhani, 2009).

The tendency for pregnant women to become insulin-resistant in the latter part of pregnancy results in increased blood glucose. This, together with the increased GFR, results in increased glucose concentration of the filtrate, which together with an increased tubular flow rate, can mean that the maximum capacity for glucose reabsorption in the tubules is exceeded causing some glucose to be present in the urine (glucosuria). This does not necessarily indicate diabetes. Likewise mild proteinuria is common and benign in pregnancy, although with coexisting hypertension it can indicate complications of pre-eclampsia.

There is a cumulative retention of sodium and potassium especially in the last trimester when fetal demands for sodium are high. Urinary excretion of calcium increases but free calcium levels remain stable as dietary absorption of calcium increases. Acid–base balance is also altered in pregnancy (Baylis and Davison, 1998). Hydrogen ions fall slightly primarily because of respiratory alkalaemia associated with hyperventilation. Although systemic blood pressure may be reduced, autoregulation (local control of glomerular blood pressure) maintains optimal renal function.

The calyces of the kidneys and the ureters become dilated and lose some of their peristaltic activity in pregnancy. The ureters elongate and become tortuous so they accommodate an increased volume of urine, which is associated with an increased risk of infection. It was generally accepted that this dilation of the ureters was primarily due to the action of progesterone on smooth muscle. However, the ovarian arteries and veins increase in size and compress the ureters, particularly on the right side where the vessels cross over the ureter almost at right-angles, whereas on the left they run approximately parallel to the ureter. This, together with the stress imposed on the ureters by the expanding uterus upon the pelvic brim, explains the extent of these morphological changes.

Bladder function is also affected in pregnancy. Urinary frequency and urgency increase early in pregnancy as the enlarging uterus in the pelvic cavity puts pressure on the bladder; fluid intake is also higher. At term, when engagement occurs, the presenting part of the fetus increases stress on the bladder. In the second trimester, the bladder is displaced upwards so urinary frequency is closer to prepregnant levels. Urinary incontinence is also relatively common in pregnancy (FitzGerald and Graziano, 2007) and may negatively affect quality of life. Under the effect of progesterone, bladder tone decreases during pregnancy so its capacity increases and may be up to a litre by term. The decreased bladder tone and displacement of the ureters by the enlarging uterus can affect competence of the vesicoureteral sphincters (valves created by the normal oblique angle of entry of the ureters into the bladder wall become compromised as the entry of the ureters tends to be perpendicular). The result is possible reflux of urine from the bladder into the ureters, which increases the chance of ascending urinary infection, which if severe, can cause infection of the kidney (pyelonephritis). Urinary retention is not common in pregnancy but classically it occurs at the end of the first trimester; there are several predisposing factors for urinary retention including a retroverted uterus, uterine fibroids, uterine anomalies and a contracted pelvis (FitzGerald and Graziano, 2007).

The walls of the bladder become more oedematous and hyperaemic, which increases the vulnerability to infection and trauma. The relatively lax walls of the bladder may also result in incomplete emptying of urine. This urinary stasis increases the risk of a UTI as the urine, which is richer in glucose and amino acids in pregnancy, remains in the bladder allowing the usually harmless number of bacteria in the urine to reach pathological levels. Women with UTI are thought to be at increased risk of premature labour. As the pregnancy progresses the effect of posture on renal function becomes exacerbated. The structural changes of the renal system persist into the puerperium (see Chapter 14) and women who have experienced a UTI during pregnancy are at increased risk of recurrent infection in the puerperium. Women who have a positive result for Group B Streptococcal B infection (colloquially known as ‘strep B’) during antenatal screening do not normally need antibiotic therapy in the antenatal period unless a UTI develops. A UTI in these circumstances indicates an exceptionally high bacterial load which increases the risk of transmission to the fetus during birth so should be treated (RCOG, 2003).

Case study 11.3 details an example of a urogenital tract infection.

Case study 11.3

Penny is expecting her second child at 24 weeks' gestation and presents herself at the maternity day assessment unit. Two days previously, Penny noticed her frequency of micturition had dramatically increased. Since then she has felt lower central abdominal pain radiating from the groin round to the right side of her back. The midwife suspects that Penny may have a UTI. A provisional diagnosis is made on ward-based urinalysis that indicates the presence of leukocytes and nitrites.

• What is the significance of these findings and why do they indicate the presence of an infection?

The midwife instructs Penny on how to provide a midstream specimen of urine (MSU) and requests that the duty doctor examine Penny. Penny is prescribed a course of antibiotics with the proviso that this may be changed if the laboratory tests indicate that the antibiotic is inappropriate.

• How could the midwife describe to Penny the reasons why the UTI has occurred?

• What else besides taking the antibiotics could the midwife advise Penny to do to (a) help resolve the infection now and (b) avoid further infection in the future?

• What are the risks and possible consequences if the infection is not treated?

The gastrointestinal system

Maternal nutrition is very important in the outcome of pregnancy but disturbances of gastrointestinal function are the most common cause of complaints in pregnancy (Fig. 11.9). Over 50% of women experience an increased appetite (and consequent increased consumption of food) and even more an increased thirst. hCG affects the hypothalamus decreasing the osmotic threshold for thirst. The changes are most marked in the first half of pregnancy; subsequently they may decline although some persist, albeit to a lesser extent. Surveys have measured an increased intake of food and drink in pregnant women although not all of them are conscious of these changes (Hytten, 1991). Changes in maternal appetite do not directly reflect changes in fetal growth or maternal metabolism. Appetite tends to be increased in early pregnancy and may be promoted by several hormones including leptin. Leptin usually suppresses food intake but in pregnancy, leptin levels increase because hormonally induced central leptin resistance develops (Grattan et al., 2007). This means that despite the raised levels of leptin, food intake and thus fat deposition are increased. In advanced pregnancy, both appetite and the capacity for food intake decline owing to upward gastric displacement and pressure from the gravid uterus. A pregnant woman can compensate for her limited capacity by increasing the frequency of consumption of small meals and snacks. Oestrogen suppresses appetite but progesterone stimulates it, causing a shift in the central control of energy balance. Decreased plasma glucose and amino acid levels, which are secondary to increased responsiveness to insulin, also stimulate appetite. Cyclical patterns of appetite are also observed during the menstrual cycle. Thirst is increased; progesterone resets the thirst threshold by 10mOsm so plasma osmolarity falls. Increased angiotensin, prolactin and relaxin levels are also dipsogenic.

Fig. 11.9 Gastrointestinal function in pregnancy.

Food cravings and aversions

Changes in food habits can be deliberate, for instance avoiding fried or fatty foods that are considered less healthy. Two-thirds of pregnant women express marked food preferences as cravings or aversions. The commonest cravings are for fruit and highly flavoured foods such as pickles, kippers and cheese. It is suggested that the sensitivity of the taste buds is dulled in pregnancy (Bowen, 1992) so highly seasoned foods are more appreciated. Unsatisfied cravings are often thought to explain food-shaped birthmarks (King, 2000). Common aversions are to tea and coffee, meat, fried foods and eggs and to caffeinated drinks, alcohol and smoking. Food cravings and aversions need to be assessed as part of a full dietary assessment; they do not necessarily have an adverse effect on dietary quality. Usually cravings cause an increase in energy and calcium intakes and aversions frequently result in decreased intake of alcohol, coffee and animal protein.

Pica, an extreme craving usually for a non-nutritious substance, has been identified for coal, soap, disinfectant, toothpaste, mothballs and ice. Usually pica does not affect either maternal or fetal health. In the southern states of America, there seems to be a social tradition of Black women eating laundry starch, chalk and clay. Sense of smell may be enhanced; pregnant women are especially sensitive to noxious smells such as nicotine and coffee. The timing of the changes in taste and smell appears to reflect secretion of hCG.

Nausea and vomiting in pregnancy

Between 50% and 90% of pregnant women experience nausea and vomiting in pregnancy (NVP), usually in the first trimester although 20% of women experience NVP throughout gestation. It may be the first physical manifestation of pregnancy. NVP is more common in Westernized urban populations and is affected by ethnicity, occupational status and maternal age (Coad et al., 2000). The peak of NVP is usually at about 8–12 weeks; symptoms usually resolve by mid-pregnancy. Although about 50% of women suffering from NVP are affected to a greater extent in the morning, some women experience nausea and vomiting in the evening, in a biphasic pattern or throughout the day. It is thought that women who are underweight experience less severe symptoms of NVP compared to women with normal preconceptual weight (Huxley, 2000). NVP does not necessarily mean that nutrient intake is decreased. Some women eat more as continual snacking alleviates symptoms and others alter their diet in a way that usually improves dietary quality (Coad et al., 2002).

There are several theories about the causes of NVP. Serum hCG peaks in the first trimester but the relationship between NVP and hCG secretion is not clearly established. The effects of progesterone on gastric smooth muscle tone, particularly those on upper gastrointestinal tract motility, the patency of the lower oesophageal sphincter and delayed gastric emptying, suggest a possible role for steroid hormones. NVP is usually conservatively treated with rest and reassurance and advice to consume frequent small meals rich in easily digested carbohydrate and low in fat (King and Murphy, 2009). Meat and strong smells may aggravate NVP. It has been suggested that NVP is an evolutionary mechanism that protects the embryo by causing pregnant women to physically expel and subsequently avoid foods that might contain teratogenic and abortifacient chemicals (Flaxman and Sherman, 2000). An alternative explanation is that NVP has a functional role in stimulating early placental growth by reducing maternal energy intake and suppressing maternal tissue synthesis in early pregnancy so nutrient partitioning favours the developing placenta (Huxley, 2000). Although NVP may have a socioeconomic impact and create much misery, it is considered to be favourable prognostic sign and is associated with a positive outcome of pregnancy (Coad et al., 2002). Intractable and persistent nausea and vomiting causing dehydration, electrolyte imbalance (hypokalaemia), metabolic disturbances (ketonuria) and nutritional deficiencies is known as hyperemesis gravidarum (HG). This may require hospitalization to correct the electrolyte and fluid imbalances. Risk factors for HG include previous HG, hyperthyroid disorders, pre-existing psychiatric diagnosis, molar pregnancy, gastrointestinal disorders, and multiple gestation with a female and male twin (King and Murphy, 2009).

Mouth

Gums often become hyperaemic, oedematous and spongy. This is because of the effects of oestrogen on blood flow and connective tissue consistency. Gums therefore bleed more easily and are vulnerable to abrasive food and vigorous tooth brushing. Gingivitis and periodontal disease occur in a large proportion of pregnant women and are more extreme with increased maternal age and parity and where there are pre-existing dental problems. Contrary to folklore belief that a tooth is lost for every baby, there is no evidence of demineralization of dentine resulting from pregnancy as fetal calcium stores are drawn from maternal body stores (skeleton) and not from maternal teeth (Blackburn, 2007). However, there is an increase in the number of caries treated during pregnancy. This may be because gum changes result in an increased awareness of dental problems and many women receive free dental care in pregnancy. Saliva becomes more acidic in pregnancy, but the volume produced does not usually change. In rare instances, excessive production of saliva, termed ptyalism or ptyalorrhoea, may occur. It can occur in isolation or in association with HG, where swallowing of saliva induces extreme nausea and vomiting in an affected woman.

Oesophagus

Heartburn, a painful retrosternal burning sensation, is common in pregnancy, affecting 30–70% women. The effects of progesterone on the tone of the lower oesophageal sphincter mean its competence is impaired and regurgitation of gastric acid is more likely. Similar changes occur during the menstrual cycle and in women taking combined oral contraceptive pills. These changes are associated with increased progesterone levels. The risk of a hiatus hernia is increased; the sphincter is displaced and becomes intrathoracic instead of straddling the diaphragm. This usually begins in the second trimester and worsens as the pregnancy progresses. It is due to progesterone-induced relaxation of the lower oesophageal sphincter and a change in pressure gradients across the stomach. The enlarging uterus causes distortion of the stomach and changes the angle of entry of the oesophagus. Because the patency of the pyloric sphincter may also be impaired, both alkaline and acidic secretions may reflux into the oesophagus.

Heartburn is increased with multiple pregnancies, polyhydramnios, obesity and excessive bending over. Alcohol, chocolate and coffee all act directly on the lower oesophageal sphincter, reducing the muscle tone and exacerbating heartburn. Gastric reflux can be limited by advising more frequent intake of smaller meals, the avoidance of seasoned food, and of postural influences such as lying horizontally or bending forwards. Antacid preparations are associated with a number of undesirable side-effects: aluminium salts may cause diarrhoea, magnesium salts are associated with constipation, phosphorus may affect the calcium/phosphorus balance and exacerbate cramp, sodium may affect water balance and long-term use of antacids is associated with malabsorption, particularly of drugs and dietary minerals.

Stomach

Studies on gastric secretion in pregnancy are not conclusive but suggest acid secretion tends to decrease, which may explain why remission of symptoms of a peptic ulcer is not an uncommon event. Secretion of pepsin also falls; this is probably secondary to the decreased acid secretion. Studies have shown that stomach gastric tone and motility markedly decrease in pregnancy. Thus in advanced pregnancy the stomach drapes loosely over the uterine fundus. This tends to delay gastric emptying especially following ingestion of solid foods. The delay of chyme released from the stomach may increase the likelihood of heartburn and nausea and can result in delayed absorption of glucose.

Intestine and colon

Progesterone-induced relaxation of smooth muscle decreases gut tone and motility and thus transit time in the gut increases which may enhance absorption (Blackburn, 2007). However, pregnant women may experience bloating and abdominal distension. Duodenal villi hypertrophy and increase in height, which expands absorption capacity. Absorption of several nutrients, such as iron, calcium, glucose, amino acids, water, sodium and chloride is increased (Blackburn, 2007); the increased absorption of iron in late pregnancy coincides with raised placental uptake and decreased maternal stores. However, progesterone may inhibit transport mechanisms for other nutrients such as the B group of vitamins.

The relaxation of the smooth muscle in the colon leads to increased water absorption and increases the incidence of constipation (Case study 11.4). The raised levels of angiotensin and aldosterone also increase sodium and water absorption from the colon in pregnancy. As the enlarging uterus compresses the colon, many women experience increased flatulence.

Case study 11.4

Josie is 14 weeks pregnant and is suffering from constipation. She is a vegetarian and normally consumes a high-fibre diet.

• What physiological changes may account for her constipation?

• What advice could the midwife give to help alleviate this problem?

Liver and gall bladder

Progesterone affects the smooth muscle tone of the gall bladder resulting in flaccidity, increased bile volume storage and decreased emptying rate. Water resorption by the epithelium cells of the gall bladder is decreased so the bile is more dilute and contains less cholesterol. There is a tendency to retain bile salts resulting in the formation of cholesterol-based gallstones in pregnancy. Cholestasis is a condition often observed in late pregnancy where women complain of itchy and irritable skin (though no rash is present) because bile salts are deposited in the skin.

In many species, pregnancy-induced liver enlargement results from increased circulation. In humans, however, morphological changes appear to result from hepatic displacement by the gravid uterus rather than an actual growth increase. Increased glycogen and triacylglyceride storage occurs in the hepatic cells. The raised level of oestrogen affects hepatic synthesis of plasma proteins, enzymes and lipids. The most marked changes are the fall in albumin (which is exaggerated by haemodilution), increase in fibrinogen (see above) and increased cholesterol synthesis. Synthesis of many binding proteins involved with placental transport of nutrients increases. Although epigastric pain is common in pregnancy due to reflux of gastric contents through the lower oesophageal sphincter, it may be a symptom of severe complications such as fulminating pre-eclampsia caused by hepatic oedema.

Changes in the liver and other physiological systems can affect drug kinetics. Changes in gastric secretion and gut motility can affect absorption and bioavailability of drugs. Changes in the cardiovascular system such as plasma volume and protein binding changes can affect the apparent volume of distribution and changes in the renal system can affect drug elimination particularly increased renal excretion of drugs unchanged. Hepatic metabolism of drugs catalysed by certain isoenzymes are increased during pregnancy. Therefore pregnant women may require different dosing regimes (changes in dose and timing of the dose) of various drugs (Pavek et al., 2009).

The skin and appearance

A number of changes can be observed in the appearance of a pregnant woman (Box 11.7). The increase in MSH means that there is a progressive increase in skin pigmentation, especially in women with dark hair and complexions. The nipple and the areola darken early in pregnancy. A dark line develops from the navel to pubis; this is the linea nigra showing the embryonic folding and fusion line of the abdomen. Facial chloasma (melasma) – irregular blotchy pigmentation usually in the shape of a butterfly mask (‘mask of pregnancy’) around the eyes and forehead – is common. Freckles and recent scars may darken and many women tan more deeply in pregnancy. Pigmentation changes may remain after pregnancy in women with darker hair and skin, and chloasma may be exacerbated by exposure to the sun. Endocrine changes of pregnancy result in changes in the structure and function of the blood and lymph vessel structure of the skin and mucous membranes (Henry et al., 2006).

Box 11.7

Top-to-toe observation of a pregnant woman

• Hair: thicker and glossier

• Face: may have chloasma and/or oedema

• Hands: warm, may develop vascular spiders and palmar erythema

• Skin: warm, well-vascularized, hyperpigmentation (related to MSH production)

• Skin conditions, such as eczema, may improve

• Abdominal wall: pigmentation of linea nigra, lax abdominal muscles, striae gravidarum may be seen (related to cortisol production)

• Pruritus (localized itching usually of abdomen): occurs in about 20% of pregnant women in the third trimester, but earlier in pregnancy it may be a sign of pruritus gravidarum (intrahepatic cholestasis of pregnancy due to raised bile acids), which is associated with premature delivery, fetal distress and perinatal mortality

• Breasts: dilation of superficial veins, pigmentation of nipples and areola

• Legs: oedema may be evident around ankles; varicose veins may develop

• Posture and gait: lordosis, changed centre of gravity (related to effects of hormones on cartilage and connective tissue)

The skeleton and joints

Posture and gait change in pregnancy. The weight of the gravid uterus changes the woman's centre of gravity altering the angle of inclination of the pelvic brim to the horizontal plane. The lumbar spine is naturally anteriorly convex, but the combined effects of progesterone, relaxin and the weight of the uterus on the intravertebral discs exaggerate this curve. The resulting lordosis of the spine compensates for the shift in the centre of gravity but may result in muscle and ligament strain. By the end of pregnancy, many women adopt a typical posture where they stand and walk with their backs arched and the shoulders held backwards. Lordosis is increased by poor posture generally, obesity, skeletal disorders, tuberculosis and by wearing high-heeled shoes. Oestrogen and relaxin affect the composition of the cartilage and connective tissue of pelvic joints, which soften in preparation for labour. The large diameter collagen fibres are remodelled via the action of elastin and collagenolysis to smaller diameter fibres (Ward et al., 2007) The symphysis pubis and sacroiliac joints become more mobile and flexible so the pelvis becomes wider resulting in a rolling unstable movement and waddling gait when walking. Pregnant women may, therefore, experience muscle and ligament strain and discomfort or pain. The incidence of backache increases particularly after the 5th month. Some women experience severe back pain, often with peak intensity at night.

Occasionally in late pregnancy the symphysis pubis may separate. This condition, described as diastasis or SPD, can cause the pregnant woman great discomfort when walking or when her legs are abducted. In severe cases, women are often observed to walk sideways as this tends to be less painfully when walking in a normal forward motion. The lower back is also affected by breast changes, stretching of the round ligament and decreased tone of abdominal muscles. In the third trimester, pressure of the uterus stretching or compressing nerves and blood vessels can result in numbness and tingling of extremities. Leg cramps, especially of the calf and thigh muscles, are common in the second half of pregnancy. They may be related to calcium/phosphorus metabolism and increased neuromuscular irritability. Raised phosphate levels are implicated and reducing dietary intake of milk is often beneficial. About 10% of pregnant women experience restless legs syndrome 10–20min after getting into bed; the cause is unknown (Manconi et al., 2004). Calf pain is also associated with deep vein thrombosis which is not so common but there is an increase risk of this in pregnancy and so all calf pain needs careful investigation and monitoring.

Calcium metabolism

There is increased turnover of calcium early in pregnancy. Maternal calcium metabolism changes to facilitate calcium transport to the fetus. The placenta actively transports calcium from the maternal blood during the third trimester. Placental calcium concentrations are higher than maternal levels so the fetus is protected if maternal concentrations fall. Placental efficiency is much greater than the absorptive capability of a fetus's gastrointestinal tract; thus a baby born prematurely with immature gut function cannot absorb calcium efficiently and the skeleton is slower to mineralize. In the last 10 weeks of gestation, the fetus obtains 18 g of calcium and 10 g of phosphorus from the maternal circulation, which is equivalent to 80% of the mother's normal dietary calcium in that period. However, the 28–30 g of calcium accumulated by the fetus represents a very small fraction of the total maternal calcium.

hPL and prolactin stimulate vitamin D synthesis, which increases absorption of calcium. Gastrointestinal absorption of calcium increases throughout the pregnancy even in vitamin D deficiency (Fudge and Kovacs, 2010). hPL increases bone reabsorption of calcium. Oestrogen stimulates parathyroid hormone secretion, which increases calcium absorption, decreases urinary losses and increases release of calcium from bone. Calcitonin secretion is also increased; calcitonin inhibits mineral release from the maternal skeleton but allows the actions of parathyroid hormone on the gut and kidney. Maternal serum calcium levels fall progressively in pregnancy. Levels are related to haemodilution of albumin and increased urinary losses and transport across the placenta. Urinary excretion of calcium decreases after 36 weeks, which augments dietary sources of calcium.

Homeostasis, mediated by maternal hormones, means that the maternal skeleton is conserved. If dietary calcium is adequate, there is no marked change in maternal skeletal mass or bone density. There is no evidence that high parity is associated with increased fractures in later life. Calcium supplements tend to reduce blood pressure by a small amount and may be useful in the treatment of pre-eclampsia (see Chapter 12). Calcium requirements in pregnancy are probably overestimated; clinical deficiency is rarely observed. However, a low vitamin D intake in pregnancy and little exposure to sunlight is associated with osteomalacia, as demonstrated by Asian women in the UK who have lower plasma calcium and an increased incidence of maternal osteomalacia and neonatal rickets.

Vision

The changed hormonal profile of pregnancy influences the maternal nervous system. In the third trimester, mild corneal oedema is common; fluid is retained and the cornea becomes slightly thicker, which affects refraction. Tear composition changes; levels of lysozyme alter and tears often become greasy. This, together with altered corneal sensitivity, may cause blurring or intolerance to contact lenses. Progesterone, relaxin and hCG affect intraocular pressure, which can fall (which will improve glaucoma). Unless they experience problems, it is wise for pregnant women to delay new prescriptions for spectacles. Women with pre-eclampsia and retinal oedema, and those with diabetes, are particularly prone to visual complications which may also be associated with headaches at the back of the upper neck.

The nose and larynx

The nasal mucosa becomes hyperaemic and congested in pregnancy, causing nasal stuffiness and obstruction. This seems to be oestrogen-related and may interfere with sleep and sense of smell. It is associated with congestion of the Eustachian tubes (often described as blocked ears unrelieved by swallowing), which may cause a transient mild hearing loss. Many women will develop snoring during pregnancy (see above). Erythema and oedema of the vocal cords can lead to hoarseness, coughing and vocal changes. Softening of the cartilage within the larynx is not usually a problem but it may make tracheal intubation harder if required. Difficult intubation in pregnant women is further complicated by obesity and so it is good practice to ensure that intubation guidelines are present in all maternity units providing both routine and emergency surgical intervention.

Sleep

Sleep patterns change in pregnancy. An increased desire for sleep and napping in the first trimester has been observed (Brunner et al., 1994). It is suggested that progesterone affects neuronal activity in the brain reducing the level of excitatory neurotransmitters (Smith, 1991). Oestrogen enhances this effect by increasing the number of receptors for progesterone. The amount of rapid eye movement (REM) sleep increases from 25 weeks, peaking at 33–36 weeks. Stage 4 non-REM sleep (deep sleep) decreases. It is this state that appears important for tissue repair and recovery from fatigue. In the second half of pregnancy, women tend to sleep less as they frequently are disturbed by nocturia, dyspnoea, heartburn, nasal congestion, muscle aches, stress and anxiety and fetal activity.

Carbohydrate metabolism

Maternal metabolism changes in pregnancy to meet increased maternal needs, including the accumulation of maternal energy stores in readiness for labour and lactation, and to facilitate fetal growth and development (Fig. 11.10). Metabolism in pregnancy must also facilitate both the accumulation of fetal energy stores for the transition to extrauterine life (see Chapter 15) and maternal accumulation of fat stores in preparation for labour and lactation. Pregnancy is primarily anabolic: food intake and appetite increase and activity decreases. Pregnancy has been described as a ‘state of accelerated starvation’ (Frienkel et al., 1972) because there is an increased tendency to become ketotic. Pregnancy is a diabetogenic state; women acquire insulin resistance in later pregnancy which appears to represent a temporary excursion into metabolic syndrome.

Fig. 11.10 Changes in maternal carbohydrate handling during pregnancy.

Early pregnancy

Metabolism in the first trimester is predominantly anabolic with synthesis of new maternal tissues including deposition of maternal fat. It can be considered as a time of preparation for the subsequent high demands of rapid fetal growth; over 90% of fetal growth occurs in the second half of pregnancy (King, 2000). Early in the pregnancy, there is an increased response to insulin so fasting blood glucose levels are lower than normal. The tissues exhibit increased sensitivity to insulin so there is increased uptake of nutrients and synthesis of macromolecules by cells which promotes maternal tissue growth. As the pregnancy progresses, most women develop insulin resistance so levels of glucose and amino acids in the blood rise, thus increasing the availability of substrates required by the fetus and placental uptake.

In the first trimester, increased insulin is produced in response to glucose. Early in pregnancy, the raised levels of oestrogen and progesterone orchestrate the changes in metabolism. Oestrogen stimulates pancreatic β-cell growth (hyperplasia and hypertrophy) and therefore insulin secretion. It also enhances glucose utilization in peripheral tissues and increases plasma cortisol. So the net effect is to decrease fasting glucose levels, improve glucose tolerance and increase glycogen storage. Hepatic metabolism of insulin may also be altered. Lowered glucose levels between meals increase the tendency to become ketotic. Placental transfer of amino acids, increased hepatic gluconeogenesis (conversion of amino acids, particularly alanine, to glucose) and raised insulin levels, which stimulate cellular uptake, together result in lowered maternal levels of amino acids. During the first half of pregnancy, the progressive increment in insulin levels, augmented by progesterone and cortisol, stimulates hepatic lipogenesis (triacylglyceride synthesis and storage) and suppresses lipolysis (fat breakdown). An increase in the numbers of insulin receptors on the adipocytes means there is enhanced removal of triglycerides from circulation. Increased fat storage in early pregnancy results in hypertrophy of adipose cells. During fasting, ketogenesis is increased as the triglycerides are utilized.

Later pregnancy

As the pregnancy progresses, the fetal placental unit grows and levels of placental hormones, which are antagonistic to insulin, increase. Therefore maternal tissues exhibit decreased sensitivity, or resistance, to insulin, which means that insulin is less effective at stimulating glucose uptake. Pregnancy-induced insulin resistance affects adipocytes to a lesser degree. The dominant effect in the second and third trimesters is related to the high levels of hPL, but human placental growth hormone, prolactin, cortisol and progesterone are also involved. Tumour necrosis factor α (TNFα), resistin and leptin may also be involved in the increased insulin resistance that develops in pregnancy. Levels of hPL increase markedly after 20 weeks. hPL is a very potent insulin antagonist with effects similar to those of growth hormone. Raised hPL results in decreased peripheral tissue responses to insulin and therefore increased circulating levels of glucose and amino acids, which are available for transport to the fetus. hPL increases lipolysis and nitrogen retention, decreases urinary potassium excretion and increases calcium excretion.

Progesterone augments insulin secretion, increasing fasting levels, but decreases peripheral insulin effectiveness. Cortisol inhibits glucose uptake and oxidation, increases liver glucose production and possibly augments glucagon secretion. Therefore, in later pregnancy, fasting results in mobilization of maternal triacylglyceride stores leading to a marked increase in levels of maternal fatty acids. This provides an alternative substrate for maternal metabolism so glucose is spared for central nervous system and fetal requirements. As tissue uptake of glucose is suppressed so levels of glucose are raised, which stimulate insulin release from the pancreas. Hyperinsulinaemia is a normal development in the later part of pregnancy; levels of insulin double by the third trimester. The raised level of insulin is important in stimulating protein synthesis. Raised insulin levels counteract the effect of the antagonistic hormones so maternal plasma glucose is maintained at levels similar to prepregnant levels. Insulin sensitivity rebounds after the delivery of the placenta. Women with insulin-dependent diabetes mellitus (IDDM) need to have a marked increase in insulin dose to compensate for the pregnancy-induced resistance to insulin.

In the postabsorptive states between meals, gluconeogenesis and fat mobilization provide substrates for maternal metabolism and placental transfer. Maternal cells metabolize the increased ketones and free fatty acids, thus sparing glucose and amino acids for placental uptake. As blood sugar increases in the pregnancy, it can exceed the transport maxima of the nephrons (i.e. the capacity to reabsorb the glucose from the glomerular filtrate) so some glucose is excreted in the urine. A degree of glucosuria is normal in pregnancy. As renal absorption of glucose is limited (so there are increased losses) and hepatic gluconeogenesis is decreased, hypoglycaemia, hypoalaninaemia and hyperinsulinaemia result.

Gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that begins or was first recognized in pregnancy. It is the extreme end of the spectrum of normal physiological changes in pregnancy and is increasing with the increased prevalence of overweight and obesity in the population. Gaining excess weight during pregnancy also increases the risk of GDM (Morisset et al., 2010). GDM is due to the inability of the maternal pancreas to increase insulin secretion enough to counter the pregnancy-induced insulin resistance. Inability to produce adequate insulin at this stage of pregnancy is probably due to a limitation of the pancreatic β-cells (which may be related to the pregnant woman's own pancreatic development in utero). Inadequate secretion of insulin, and altered carbohydrate metabolism, may become evident again when there is further demand for insulin, as in a subsequent pregnancy or in later life, and is particularly associated with increased body weight (and therefore cell number). GDM (or delivery of an infant weighing more than 4.5 kg) is a risk factor both for future pregnancies and for prediabetes and type 2 diabetes mellitus. Indeed as GDM appears to represent an early stage in the progression to type 2 diabetes, it has been suggested that follow-up of women affected in pregnancy offers an opportunity to prevent type 2 diabetes and cardiovascular disease (Di Cianni et al., 2010). Infants of diabetic mothers and those with either macrosomia or microsomia also have an increased diabetogenic tendency and are more likely to develop obesity, metabolic syndrome and type 2 diabetes themselves (Reece, 2010). In women who develop gestational diabetes, strict dietary control is important in reducing adverse effects on the fetus. A moderate energy restriction (about 30% of total energy) can benefit glucose metabolism without causing ketonaemia in obese women with GDM (Metzger and Freinkel, 1987). If refractory to dietary treatment, some women with GDM may require insulin therapy as well. Diabetic women and women who require insulin therapy for GDM are at higher risk in pregnancy with problems associated with abnormal blood glucose levels such as increased risk of infection.

Case study 11.5 is an example of raised glucose levels in pregnancy.

Case study 11.5

Cathy is expecting her fourth baby. At 28 weeks' gestation, a random blood glucose revealed a blood glucose level of 11 mol/L. Cathy looks well and, as in all her other pregnancies, says she feels exceptionally healthy. Cathy is referred to the consultant clinic for further investigations. Her previous baby was delivered at 37 weeks' gestation weighing 4.960 kg.

• What is the provisional diagnosis and what investigations will be carried out to confirm this diagnosis?

• What physiological interactions between the mother and fetus are occurring that could explain this phenomenon?

• How can the midwife best explain these to Cathy and what advice should she be given?

• What are the possible consequences for Cathy and her baby if no further investigations are carried out and no treatment advised?

Key points

• The physiological adaptation to pregnancy is mediated by the increase of steroid hormone secretion. Steroid hormones are initially produced from the corpus luteum under the influence of hCG and subsequently from the placenta.

• The maternal endocrine system is affected by the increase in steroid hormones so other hormones augment the effects of oestrogen and progesterone. For instance, secretion of MSH and cortisol increases in pregnancy, affecting skin pigmentation and improving some pathological conditions such as eczema.

• Generally early physiological changes in pregnancy are regulated by hormonal changes, whereas later changes may be due to structural effects of the enlarging uterus.

• Reproductive system: under the influence of oestrogen, the uterus increases in size and vascularization, and spontaneous uterine contractions are suppressed. The breasts undergo development in preparation for lactation.

• Cardiovascular system: physiological changes are particularly marked in this system, meeting the increased demands of the maternal and fetal tissues. The vascular system expands as progesterone stimulates vasodilation of the vascular smooth muscle and oestrogen stimulates angiogenesis and increased blood flow. The RAS responds to the underfilled vascular system by increasing sodium and water retention; thus blood volume increases by about 40%. Plasma expansion is greater than blood cell increase leading to overall haemodilution.

• Cardiac output increases early in pregnancy, initially as a result of increased heart rate, which is subsequently followed by increased stroke volume. Myocontractility is increased throughout pregnancy, which stimulates a degree of ventricular hypertrophy.

• Blood pressure decreases in early pregnancy, reaching a minimum in mid-pregnancy, and then returns close to prepregnant values towards term. The effects of posture on blood pressure are marked in pregnancy.

• The dilution of plasma proteins increases the formation of oedema. The ratio of clotting factors changes so bleeding time decreases.

• Respiratory system: excursion of the diaphragm alters as the rib cage flares increasing the efficiency of inspiration. Progesterone affects the sensitivity of the chemoreceptors, which increases respiratory drive. Therefore, hyperventilation is normal in pregnancy and results in lower circulating carbon dioxide levels and higher concentrations of cations, which facilitate exchange across the placenta.

• Gastrointestinal system: progesterone stimulates appetite and thirst and affects the sensitivity of the taste buds. Progesterone also affects the smooth muscle of the gut, which alters motility and transit time. This can result in increased efficiency of absorption but may also cause nausea and constipation. Decreased tone of lower oesophageal sphincter may result in reflux and heartburn.

• Skin: the increase in MSH levels results in increased pigmentation of the nipple and areola, the linea nigra and possibly chloasma. Increased blood flow to the skin, which is important in heat regulation, affects growth of hair and nails and may cause congestion of the mucous membranes.

• Skeleton: posture is affected by changed weight distribution and altered composition of the cartilage and connective tissue resulting in an exaggerated curvature of the spine.

• Metabolism: maternal metabolism is affected by altered thyroid hormone secretion and altered responses to insulin. In the first half of pregnancy, increased sensitivity to insulin favours deposition of maternal fat stores. In the second half of pregnancy, insulin resistance results in raised levels of substrates in the maternal plasma, which favour placental transport and fetal growth. Extremes of insulin resistance result in gestational diabetes mellitus.

Application to practice

Women experience many changes within their bodies and naturally will seek explanations and reassurance from the midwife as the changes occur. The midwife should use her knowledge of the physiological changes to aid her in assessing whether the pregnancy is progressing normally.

Annotated further reading

Blackburn, S.T., Maternal, fetal, and neonatal physiology: a clinical perspective. ed 3 (2007) Saunders, Philadelphia .

An excellent in-depth description of physiological adaptation to pregnancy and consequent development of the fetus and neonate that draws from physiological research studies. The chapters are clearly organized by physiological systems and link physiological concepts to clinical applications including the assessment and management of low- and high-risk pregnancies.

Calderwood, C.J.; Thanoon, O.I., Thromboembolism and thrombophilia in pregnancy, Obstet Gyn Reproduct Med 19 (2010) 339–343.

A recent review of the risk factors and management of venous thromboembolism in pregnancy and the association between thrombophilias and adverse pregnancy outcomes.

Chamberlain, G.; Steer, P., Turnbull's obstetrics. ed 3 (2001) Churchill Livingstone, New York .

A comprehensive textbook with a medical approach to obstetric principles and practice and the development of clinical protocols.

Creasy, R.K.; Resnik, R.I.J., Maternal–fetal medicine: principles and practice. ed 5 (2003) Saunders, Philadelphia .

Covers all disciplines pertinent to obstetricians including genetics and genetic testing, fetal and placental growth and development, epidemiology, immunology, physiological adaptation to pregnancy as well as clinical applications and medical complications in pregnancy.

Freyer, A.M., Drug-prescribing challenges during pregnancy, Obstet Gyn Reproduct Med 18 (2008) 180–186.

A brief but insightful discussion about challenges to drug-prescribing in pregnancy covering issues such as preconception counselling, compliance, evidence about drug safety, fetal and maternal changes affecting drug handling and the role of the placenta.

Gilbert, E.S.; Harmon, J.S., Manual of high risk pregnancy and delivery. ed 5 (2010) Mosby, St Louis .

This book is an excellent reference for midwives who provide high-risk care in practice and it details many of the pathological problems that can arise during pregnancy and delivery.

Goland, S.; Barakat, M.; Khatri, N.; et al., Pregnancy in Marfan syndrome: maternal and fetal risk and recommendations for patient assessment and management, Cardiol Rev 17 (2009) 253–262.

This paper provides a review of current clinical information and provides recommendations for the management of patients with Marfan syndrome during pregnancy.

McCarthy, F.P.; Kenny, L.C., Hypertension in pregnancy, Obstet Gyn Reproduct Med 19 (2009) 136–141.

A practice-based review covering the classification and diagnosis of hypertension and its management.

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