Learning objectives
• To review nutritional requirements and explain the role of the main nutrient groups in human health.
• To identify how and why nutrient requirements might change during pregnancy.
• To describe how the fetus adapts to low nutrient levels.
• To relate undernutrition to outcome of pregnancy.
• To discuss other factors that may affect weight gain in pregnancy and birth weight.
• To discuss how maternal diet and health affect the fetus in the short and long term.
Introduction
It is common for pregnancy to affect a woman's sense of well-being. Some aspects of health may be affected positively and others negatively. The role of nutrition, both before, during and after pregnancy, is important for the health of both the mother and fetus. Pregnant women are often receptive to advice and may make changes to their diet which may persist (Anderson, 2001). Maternal stressors, including perceived stress, chronic and acute stresses related to life events, work-related stress and pregnancy-related anxiety, as well as nutritional stress, are associated with adverse outcomes of pregnancy such as low birth weight (LBW), prematurity and intrauterine growth retardation (IUGR; Hobel and Culhane, 2003). Although stress, of all types, is a risk for preterm birth and premature labour, not all stressed women deliver prematurely suggesting that pregnant women (or their fetuses) have differing vulnerability to the effects of stress. Optimal fetal nutrition is implicated in a range of health outcomes affecting birth weight, growth in infancy and childhood and the risk for later adult disease. The relationship between maternal and fetal nutrition is complex but the arguments that nutrient intake in pregnancy should be optimal seem well founded.
Chapter case study
Both Zara and James follow a vegetarian diet and try to lead a healthy lifestyle. At her first visit to the midwife, Zara was calculated as having a body mass index (BMI) of 24, which the midwife calculated from what Zara reported as her non-pregnant weight. During the pregnancy, Zara's baby appeared to be growing as expected and her midwife has measured Zara's uterine growth in centimetres using the symphysis pubis as the reference point; as expected, the fundal height has increased by 1 cm per week of pregnancy.
At 34 weeks; gestation, Zara is concerned that she only seems to have gained 4.5 kg over her non-pregnant weight unlike her sister who has put on over 10 kg and has been told by her midwife that her baby is a little bit on the small side.
• What factors could explain the differences in weight gain between Zara and her sister?
• What are the benefits of calculating the BMI of pregnant mothers and why is it preferable to calculate the BMI using the non-pregnant values if they are available?
• Does Zara's smaller weight gain give any cause for concern?
• What other reasons could explain why Zara's sister appears to have gained a lot more weight than Zara has?
Overview of nutrition
Growth, development and optimal health rely on good nutrition and an adequate quality and quantity of nutrients for the cells. However, diet is influenced by many factors including wealth, religion, culture, and geographical and social factors. The insoluble macromolecules of food must be digested into soluble and absorbable subunits (see Chapter 1). The major components of the diet, or macronutrients, are carbohydrates, proteins and fats. Essential micronutrients are vitamins and minerals. Water is also an essential part of the diet.
Carbohydrates
Carbohydrates are the major energy source in the majority of human diets, but the amount and type of carbohydrate consumed varies amongst different population groups. With increased affluence in the Western world, there is a tendency to increase the proportion of fat in the diet at the expense of carbohydrate. There are two major types of carbohydrate: polysaccharides (or complex carbohydrates) and simple sugars (monosaccharides and disaccharides).
Monosaccharides, such as glucose, fructose and galactose, are not usually consumed in high quantities although they do occur in fruit. The major source of carbohydrate in the diet is usually starch from plant sources, plus some glycogen from animal liver and muscle. Dietary disaccharides include sucrose (table sugar), lactose (in milk) and maltose, which occurs in malt, beer and some sprouting seeds. Most starchy foods are high in carbohydrate and low in fat. With increasing affluence, added sugars tend to contribute more to the carbohydrate content at the expense of polysaccharides; soft drinks and sweet snacks may constitute a significant part of the carbohydrate intake.
Carbohydrates have differing effects on blood glucose levels and carbohydrate-rich foods can be compared using glycaemic index (GI) ranking. GI values for different foods are calculated by comparing their effect on blood glucose with the effects of a reference food (usually glucose or white bread). Carbohydrates with high GI are digested quickly and absorbed faster so the blood glucose response is fast. Carbohydrates that break down slowly, and result in a slow and sustained release of glucose into the circulation, have a low GI. Low GI foods prolong carbohydrate absorption, attenuate insulin secretion, increase the translocation of the insulin-responsive glucose transporter (GLUT4) to the cell membrane; they also result in more colonic fermentation of carbohydrate and beneficial short-chain fatty acid production High GI foods provide a rapid rise in blood sugar levels and are recommended for post-exercise energy recovery, whereas low GI foods release energy slowly and steadily and increase satiety and are appropriate for diabetics, dieters and endurance athletes. Health benefits of a low GI diet include reduced risk of obesity, diabetes and cardiovascular diseases and lowered incidence of colorectal cancers (Brand-Miller et al., 2009).
Many carbohydrate-rich foods contain indigestible non-starch polysaccharides (NSP or ‘dietary fibre’). Dietary fibre is indigestible carbohydrate. Insoluble fibre promotes the formation of bulkier and softer faecal stools. Soluble fibre slows absorption of glucose and reduces blood cholesterol levels; it is associated with increased insulin sensitivity and decreased incidence of gut diseases. Soluble fibre forms a viscous gel with water and so protects against constipation as makes the faecal stools softer. Foods rich in complex carbohydrates include cereal grains, starchy vegetables, legumes, seeds and wholegrain cereals, all of which contain reasonable proportions (3–15%) of NSP. Most other vegetables, and most fruits, contain small amounts of both starch and NSP and variable amounts of sugars. Most foods that are not highly processed, with the exception of honey and dried fruits, do not contain much sugar, whereas most processed foods contain added sugars, usually sucrose.
Proteins
Proteins are made up of 20 types of amino acids linked together by peptide bonds. Indispensable or essential amino acids are those that cannot be synthesized from other amino acids in adequate amounts and, therefore, are required in the diet (Table 12.1). There are conditions, in which requirement is high or there is limited ability to interconvert amino acids, that result in an amino acid that can usually be synthesized from an indispensable amino acid being required in the diet. These amino acids are described as being conditionally indispensable, for instance premature babies with immature enzyme function or under conditions of stress may require amino acids that they will be able to synthesize when they are older.
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Table 12.1 Amino acids |
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aConditionally essential or essential only at certain ages or in certain conditions. |
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Essential Amino Acids |
Conditionally Essential Amino Acids |
Non-Essential Amino Acids |
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Lysine |
Cysteine |
Alanine |
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Threonine |
Tyrosine |
Glutamic acid |
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Histidine |
Arginine |
Aspartic acid |
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Isoleucine |
Citrullinea |
Glycine |
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Leucine |
Taurinea |
Serine |
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Methionine |
Carnitine |
Proline |
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Phenylalanine |
Glutamine |
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Tryptophan |
Asparagine |
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Valine |
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Protein quality depends on the proportion of dietary protein that is absorbed across the gut (digestibility) and the ratio of the essential amino acids in the protein. A protein that is absorbed completely and utilized completely because the indispensable amino acids are in the optimum proportion for synthesis of new proteins is described as a high-quality protein, with a net protein utilization (NPU) value of 1.0 or 100%. Human milk and whole egg have an NPU of 1.0, whereas the overall protein availability in the Western diet is typically 0.7. The NPU of diets dependent on poor-quality proteins, such as those based on cassava (made from tapioca root), can be as low as 0.5.
In the absence of alternative sources of energy, protein can be metabolized as an energy source. Excess protein in the diet will also be used as a metabolic fuel. An adult is usually in nitrogen balance: protein intake is equal to protein breakdown so nitrogen in the diet is equal to excreted levels of nitrogen. Under conditions of growth and protein synthesis, there is a net accumulation of protein, and hence nitrogen, which is described as a state of positive nitrogen balance. States of growth, including pregnancy, result in positive nitrogen balance. Negative nitrogen balance usually indicates tissue breakdown or nutrient deficiency resulting in energy generation from protein sources. Illness and trauma cause negative nitrogen balance, although it also occurs with reduced activity and decreasing muscle mass and during uterine involution (see Chapter 13).
Fat
Fat is used for energy requirements. There is also a requirement for essential fatty acids, which cannot be synthesized by the body. These are the precursors of long-chain fatty acids and their metabolic products, prostaglandins and leukotrienes. Fat also provides the vehicle for absorption of fat-soluble vitamins. Most fat is present in the diet as triglycerides; a triglyceride is a glycerol molecule with three fatty acids (Fig. 12.1). There is a range of fatty acids of different chain length and degree of saturation, which is related to the number of double bonds in the fatty acid molecule. Saturated fatty acids have no double bonds, monounsaturated fatty acids have one double bond and polyunsaturated fatty acids have two or more double bonds. The body handles fatty acids differently depending on their length and the degree of saturation (Fig. 12.1C). Fats in foods are formed of triglycerides containing a combination of different fatty acids, but are described by the predominant type. For instance, olive oil is particularly rich in monounsaturated fatty acids (with single double bonds).
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Fig. 12.1 Structure of fats: (A) a saturated fatty acid; (B) a triglyceride; (C) the fatty acid cycle. |
Saturated fats are usually solid at room temperature and are usually of animal origin, although coconut and palm oils and cocoa butter have a high level of saturated fatty acids. Saturated fats become rancid very slowly so they store well. Unsaturated fats are usually liquid at room temperature and mostly of plant origin. The C=C double bond is not very stable so it oxidizes easily and the fat becomes rancid. In food processing, unsaturated vegetable oils are hydrogenated (have hydrogen atoms added to saturate the C=C bonds), which makes the fat harder and extends the shelf-life and flavour stability. Unsaturated fatty acids from vegetable and most animal sources naturally adopt a cisconfiguration, although ruminants produce some trans fatty acids which are thus found in low concentrations in milk and meat from ruminant animals. Positional isomerism, where the fatty acid has the same length and number and position of double bonds, but the hydrogen atoms either lie on the same side of the double bond (cisconfiguration) or on alternate sides (trans configuration) (Fig. 12.2). Hydrogenation and heating can convert the cis bonds to the trans isomeric forms. Many cellular processes depend on the fluidity of the membrane lipids which depends on the properties of fatty acid chains. Saturated fatty acids are more ordered and rigid. The double bonds of unsaturated fatty acids produce bends in the fatty acid which means that the fatty acids of the membrane pack less tightly together, thus conferring a greater degree of fluidity and flexibility to the cell membrane. Trans fatty acids are straighter and are more like saturated fatty acids in conformation even though they have double bonds. Cholesterol also inserts into the cell membrane bilayer and affects fluidity.
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Fig. 12.2 (A) Cis and (B) trans isomerism of fatty acids. |
Diets high in saturated fat are associated with an increased incidence of atherosclerosis (damage to arterial blood vessels, causing hardening and plaque formation) and an increase in low-density lipoprotein (LDL) cholesterol levels which is a biomarker for heart disease. Diets higher in polyunsaturated fat are associated with increased high-density lipoprotein (HDL) cholesterol levels and an increased HDL:LDL cholesterol ratio which is associated with more favourable cardiovascular health. Trans fatty acids are implicated in increased risk of myocardial infarction and other cardiovascular problems. HDL levels are also increased by oestrogen (so they are higher in women) and by moderate alcohol intake and exercise.
There are two polyunsaturated fatty acids that are indispensable (‘essential’) in the diet as they cannot be synthesized by the body. These are linoleic acid (18:2, ω-6; chain length of 18 carbons and two double bonds, the first of which is at the carbon atom in the omega position 6 of the chain) and α-linoleic acid (18:3, ω-3; chain length of 18 carbons and three double bonds, the first of which is at the carbon atom in the omega position 3 of the chain). The body can further elongate and desaturate (lengthen and add more double bonds to) these essential fatty acids. However, there are two things to note. First, the fetus has limited ability to elongate and desaturate fatty acids so it is dependent on placental supply for both long-chain polyunsaturated fatty acids (LCPUFA) and the indispensable fatty acids. Second, the enzymes involved in the pathways of elongation and desaturation of the indispensable fatty acids into their longer chain metabolites are competitive. This means that the ratio of ω-6 fatty acids to ω-3 fatty acids is important for optimal development.
Vitamins
Vitamins are organic substances required in small amounts for metabolism, growth and maintenance; they are not synthesized by the body (either at all or in adequate amounts) and so are essential nutrients. Vitamins do not provide sources of energy but act as regulators of metabolic processes. They can be divided into water-soluble (Table 12.2) and fat-soluble vitamins (Table 12.3). The fat-soluble vitamins are more stable than water-soluble vitamins and are stored in the body, so when taken in excess they are more likely to cause toxicity than water-soluble vitamins. As B vitamins function as coenzymes in energy metabolism, requirement for B vitamins increases in parallel with increased energy consumption. Vitamins A, C and E function as antioxidants protecting cells from free-radical damage.
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Table 12.2 Water-soluble vitamins |
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Vitamin |
Role |
Source |
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Thiamin (B1) |
Carbohydrate metabolism |
Pork, wheat germ, yeast |
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Riboflavin (B2) |
Protein metabolism |
Offal, milk, grains, legumes, eggs, vegetables |
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Niacin (B3) |
Production of energy from glucose; synthesis of fatty acids |
Meat, nuts, legumes |
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Pyridoxine (B6) |
Synthesis and catabolism of amino acids; synthesis of antibodies and neurotransmitters |
Pork, offal, grains, legumes, potatoes, bananas |
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Cyanocobalamine (B12) |
Reactions preceding use of folic acid in DNA synthesis |
Animal and dairy products, eggs, yeast |
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Folate |
Formation of DNA |
Liver, green leafy vegetables, kidney beans, oranges, melon |
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Pantothenic acid |
Metabolism; synthesis of acetylcholine |
Liver, egg yolk, milk, dried and spouting beans |
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Biotin |
Synthesis of fatty acids, amino acids and purines (required for DNA and RNA) |
Offal, egg yolk, tomatoes |
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C |
Collagen formation, tissue formation and integrity, antioxidant, iron absorption |
Citrus fruit, tomatoes, other fruit and vegetables |
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Table 12.3 Fat-soluble vitamins |
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Vitamin |
Role |
Source |
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A |
Visual perception (rhodopsin synthesis); growth of epithelial tissue and bones, antioxidant |
Liver, kidney, egg yolk |
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D |
Hormone involved in bone mineralization and calcium homeostasis |
Synthesized in skin, fish oils |
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E |
Tissue growth + integrity of cell membranes; antioxidant |
Vegetable oils, grains, milk, eggs, fish, meat |
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K |
Synthesis of blood-clotting factors; bone metabolism |
Gut flora, liver, green leafy vegetables |
Minerals
Minerals regulate body function and are essential to good health. They are inorganic and become part of the body structure (Table 12.4). Excessive intake of minerals can be toxic or lead to illness indirectly because of the competitive nature of mineral absorption in the body. For example, excess iron can lead to zinc deficiency and excess zinc can lead to copper deficiency.
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Table 12.4 Minerals |
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Mineral |
Function |
Dietary Source |
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Sodium (Na) |
Extracellular ion essential for the generation of action potentials; required in the active transport of small molecules into the cell |
Table salt (NaCl) |
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Potassium (K) |
Intracellular ion essential for the generation of action potentials; utilized by the cell to maintain ion concentration gradients |
Meat, milk, fruits, vegetables |
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Calcium (Ca) |
Bone and teeth structural component; essential for blood clotting, muscle contraction and nerve impulse conduction |
Dairy products, fortified flour, cereals, green vegetables |
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Chlorine (Cl) |
Cation in body fluids; gastric acid excretions |
Salt (NaCl) |
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Phosphorus (P) |
Structural component of bones and teeth; essential for formation of ATP for energy storage |
Meat, dairy products cereals, bread |
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Magnesium (Mg) |
Required by some enzyme activities; present in cells, body fluids and bone |
Vegetables, milk, cereals, bread |
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Iron (Fe) |
Transfer of oxygen in haemoglobin molecule; oxidation processes; electron transfer chain |
Meat, vegetables, flour |
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Zinc |
Enzyme activity; growth and development of the immune system; spermatogenesis; tissue growth |
Oysters, steak, crab meat, red meat, milk products |
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Iodide |
Thyroid hormones |
Seafood, iodized table salt |
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Copper |
Constituent of enzymes; energy production and release |
Legumes, grains, nuts and seeds, offal |
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Manganese |
Synthesis of urea; conversion of pyruvate in TCA cycle |
Plant products |
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Fluoride |
Essential to reduce decay in bone and tooth tissues |
Fluoridated drinking water |
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Chromium |
Carbohydrate and lipid metabolism |
Unrefined foods, brewer's yeast, whole grains and nuts |
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Selenium |
Antioxidant; catalyst for the production of thyroid hormone |
Liver, shellfish, fish meat |
Preconceptual nutritional status
The sensitivity of the hypothalamus to environmental influences, such as nutrient availability, was probably of immense importance in promoting pregnancy in seasons when the fetus and infant had optimal chances of survival. Weight loss affects cyclical ovarian function in women. Anorexia nervosa disrupts the hypothalamic–pituitary–ovarian axis (see Chapter 4) and may cause amenorrhoea. Amenorrhoea related to inadequate nutrient intake is often reported in ballet dancers, competitive runners and other athletes (Frisch, 1990). It not only affects the ovulatory cycle but also can result in low levels of oestrogens, which reduce bone density and predispose to osteoporosis. It has been suggested that the menarche depended on women reaching a ‘critical weight’ (Frisch and McArthur, 1974). However, low body weight is not always associated with amenorrhoea. Conversely, dieting, high energy expenditure, nutrient restriction or erratic eating patterns (such as crash dieting and binging) can suppress normal reproductive cycles in women even if their weight stays within a normal range (Coad, 2003).
A minimal level of nutrient intake and fuel metabolism seem to be required to maintain reproductive functions, particularly the pulse generating secretion of gonadotrophin-releasing hormone (GnRH; see Chapter 4). Fluctuations in body fat can also disturb the transport and metabolism of the steroid hormones, which are fat soluble. Nutrient deficiency may itself suppress appetite. Studies in animals suggest optimal pregnancy outcome may depend on long-term nutritional status rather than a period of ‘flushing’ or short-term good-quality diet (Wynn and Wynn, 1991). Although restricted nutrient intake can suppress reproductive function, excess energy intake may also be disruptive. Obesity, in both men (Hammoud et al., 2008) and women (Zain and Norman, 2008), also affects fertility and conception rate. Polycystic ovary syndrome (PCOS), which often causes anovulation (see Chapter 6), is frequently associated with insulin resistance and hyperinsulinaemia even in the absence of obesity (Hirschberg, 2009). However, the symptoms and effects of PCOS on reproduction are more severe with increased body weight. In PCOS, increased obesity disrupts normal production of steroid hormones and affects carbohydrate handling.
A woman's weight, particularly if it is related to her height, indicates her nutritional status to some degree. Weight loss and nutrient fluctuation caused by self-imposed dieting, affecting reproductive function, may be the cause of infertility in a large proportion of the women seeking fertility treatment. Maternal nutritional status can be assessed by calculation of body mass index (BMI; Box 12.1). BMI is correlated to fat mass (and health prognosis) but there are limitations to its use; BMI tends to overestimate fat mass in individuals who are active and have a high muscle mass and to underestimate fat in individuals who are sedentary. There are also racial differences in the correlation between BMI and fat mass; individuals from African and Polynesian races have less fat per BMI class compared with individuals from Caucasian races, whereas individuals from Asian races tend to have more fat. Whilst it is clear that the time to pregnancy is longer for underweight and overweight women, there is no consensus about the optimal BMI. A BMI of less than 18.5 kg/m2 is not associated with good fertility or pregnancy outcome (Gesink Law et al., 2007). A BMI of greater than 30 kg/m2 in a prepregnant woman is considered a considerable risk factor in the obstetric management of the pregnancy as well as affecting fertility (Lee and Koren, 2010). The higher incidence of obesity in the general population is reflected in the increased number of pregnant obese women who have more pregnancy-related complications such as hypertension, pre-eclampsia and gestational diabetes. Surgery for severe obesity is consequently becoming more commonplace. Bariatric (weight loss) surgery (such as gastric banding or gastric bypass) is an effective treatment for obesity which can restore fertility but as there may be initial nutritional compromise, it is recommended that women leave 2 years after the surgery before conceiving (Shah and Ginsburg, 2010).
Box 12.1
The body mass index
Body mass index (BMI) is used to indicate nutritional status and risk factors associated with obesity. It is a ratio of weight (measured in kilograms) against height (measured in metres squared).
Calculation:
Interpretation:
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Grade |
BMIa |
Definition |
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– |
<20 |
Underweight |
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0 |
20–24.9 |
Desirable weight |
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I |
25–29.9 |
Overweight |
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II |
30–39.9 |
Mild obesity |
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III |
40 |
Severe obesity |
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aNormal: 19.8–26.0. |
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A healthy shape is considered to be that usually associated with a BMI of 20–25 kg/m2. Waist circumference and waist to height ratios are also used as indicators of healthy shape. A waist circumference of less than 80 cm is considered healthy in women and less than 94 cm in adult men, with waist circumferences above 88 and 102 cm, respectively, indicating risk. A waist:height ratio of less than 0.5 is also considered healthy with a ratio greater than 0.6 indicating risk to health.
Maternal protein intake affects gonadotrophin secretion and ovulatory maturation (Wynn and Wynn, 1991). Diets with abnormally high protein content and also those with very low protein content affect the menstrual cycle and fertility. It is possible that high-protein diets may cause one of the coenzymes involved in protein metabolism to become limiting. It is also suggested that low levels of B vitamins depress pituitary hormone secretion. Both embryonic development, especially early in gestation, and follicular development involve a rapid rate of protein synthesis and cell division, which are associated with a high energy and nutrient requirement. Preconceptual nutrient deficiency may retard development of the follicle and corpus luteum, affecting subsequent embryonic growth, even if the level of deficiency is not adequate to cause infertility. Excess intakes of some nutrients may increase mutation rate. Nutrient deficiency also affects male fertility, by altering DNA synthesis and rates of cell division. Selenium availability may be an important factor in male fertility.
Whether the mother enters pregnancy with high nutritional stores may affect the outcome of the pregnancy. Placental size in humans appears to be governed by genetic growth potential, anoxia and nutrient availability. In sheep, a period of poor nutrition early in gestation increases placental size, presumably as an adaptive mechanism to increase nutrient extraction (McCrabb et al., 1992). Provided this nutrient restriction is transient and the sheep are then returned to richer pasture, the increase in placental size is associated with an increase in lamb birth weight. In humans, an increased placental:fetal weight ratio is associated with poorer outcome and long-term health prognosis (Barker, 1998). However, larger babies have larger placentas but in proportion to their birth weight. Morning sickness may produce a period of poor nutrition in early pregnancy, which could stimulate placental growth (Coad et al., 2002). Provided the woman entered pregnancy with good nutrient stores and the effects on nutrient consumption were limited, nausea in pregnancy could promote placental enlargement and positively affect the fetal growth trajectory. An adequate interpregnancy interval may be important to allow replenishment of maternal stores, especially of vitamins such as folate.
Case study 12.1 looks at an example of assessing nutritional status in pregnancy.
Case study 12.1
Fiona informs the midwife at the booking appointment that she has a healthy balanced diet.
• How can the midwife assess that this is an accurate statement?
• What observations can help the midwife assess Fiona's nutritional status?
• Are there any other factors that might affect Fiona's description of her diet?
• Are there any perceptions of what is a ‘healthy balanced diet’ that may actually be potentially harmful and if so what are they and why should they be avoided?
Non-nutritional factors affecting reproductive function
Food can provide nutrition but it is also the source of a number of maternal infections (Box 12.2). Pregnant women are advised to be particularly careful about food hygiene (Derbyshire, 2010). Although nutrient intake and weight gain are associated with clear effects on birth weight, a number of other factors have been shown to affect fetal size and growth potential (Box 12.3).
Box 12.2
Food safety
Listeriosis
• Caused by: bacterium Listeria monocytogenes
• Possible effects: miscarriage, stillbirth and neonatal death, brain damage, premature delivery, maternal mortality, meconium before 37 weeks gestation
• Sources: soil, soft cheeses, pate, raw seafood, cold meats, poultry, cook-chill food
Note: bacteria can multiply at low temperatures so women are recommended to thoroughly reheat refrigerated left-overs
Salmonellosis
• Caused by: Salmonella enteric
• Possible effects: maternal high fever, vomiting, diarrhoea and dehydration associated with food poisoning may increase the risk of preterm labour or miscarriage
• Source: raw meat, poultry and eggs, foods made from raw eggs such as mousses and sauces
Note: survives in soft-boiled eggs and mayonnaise, cross-contamination by uncooked foods or utensils is common
Toxoplasmosis
• Caused by: Toxoplasma gondii
• Possible effects: congenital mental retardation or blindness, neonatal convulsions, visual and hearing loss, haematological abnormalities, enlarged spleen and liver
• Sources: soil, raw or undercooked meat, cats' faeces and litter trays, goats' milk
Campylobacters
• Caused by: Campylobacter jejuni and C. coli.
• Possible effects: preterm delivery, intrauterine death
• Sources: undercooked poultry, unpasteurized milk
Box 12.3
Factors affecting weight gain in pregnancy or birth weight
• Maternal diet before and during pregnancy
• Maternal size, particularly lean body mass
• Age (younger women tend to gain more weight but pregnancy in adolescents is associated with an increased likelihood of an LBW baby)
• Birth order (first babies tend to be slightly smaller)
• Parity (multigravidae tend to gain less weight)
• Fetal sex (male babies tend to be an average of 150 g heavier)
• Nicotine (both smoking and tobacco chewing are associated with decreased birth weight)
• Alcohol (regular alcohol consumption is associated with lower birth weight)
• Hypoxia (high altitude and chronic maternal anaemia depress birth weight)
Age affects cell proliferation and gamete formation. Some diseases accelerate premature ageing of the germ cells. These include diabetes, parental gene mutation, multiple sclerosis, ulcerative colitis and Crohn's disease (Wynn and Wynn, 1991). Smoking, drugs, alcohol and radiation all affect cell division; indeed, smoking is probably the most important single factor influencing incidence of LBW babies in developed countries (Chiriboga, 2003). Viruses are mutagenic and have long been associated with abnormal fetal development. Sexually transmitted diseases (STDs) can cause pelvic inflammatory disease, which may affect fertility and pregnancy outcome. Diseases caused by larger organisms, such as syphilis and gonorrhoea, are relatively easy to diagnose and treat. However, STDs caused by smaller microorganisms, such as chlamydia, papilloma, HIV, herpes and mycoplasmas, are difficult to eradicate. STD prevalence is associated with increased mobility of the population.
Nutritional requirements in pregnancy
Energy requirements
The nutritional costs of pregnancy can be theoretically calculated by estimating the cost of the new maternal tissues (particularly maternal fat deposition) and the tissues of the conceptus (fetus, placenta, membranes and other tissues) – the ‘capital gains’ – and the metabolic costs of maintaining these growing tissues – the ‘running costs’ (Campbell-Brown and Hytten, 1998). Tissue accrued (based on an assumed body fat retention of 3.8 kg) accounts for about 185 MJ (50000 kcal), and increased metabolism accounts for about 150 MJ (36000 kcal), bringing the total specific cost of pregnancy to about 335 MJ (80000 kcal) (Fig. 12.3). As more studies about nutritional requirements during pregnancy are performed, the recommended daily allowances of energy and other nutrients have progressively decreased. However, recommended allowances are intended to be a standard against which the nutritional status of a population, rather than that of an individual person, can be assessed.
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Fig. 12.3 The cumulative energy costs of pregnancy. (Reproduced with permission from Hytten, 1991.) |
Energy requirements during the pregnancy are highest in the middle (from 10 to 30 weeks) when maternal fat stores are being assimilated. During the last 10 weeks of the pregnancy, the rapid growth of the fetus has a high energy requirement but the rate of maternal fat storage is decreased (and often maternal intake is limited). In effect, the increased nutritional requirements of the pregnancy are spread fairly evenly over the later three-quarters of the pregnancy. The daily increase in energy requirement is calculated to be about 1.2 MJ (300 kcal) over the final three-quarters of pregnancy (Campbell-Brown and Hytten, 1998). This is calculated from the total cost of the pregnancy, estimated to be 335 MJ (80000 kcal) divided by 270 days of pregnancy. The reported energy consumed in pregnancy by women ‘eating to appetite’ (with free access to food) is about 0.8 MJ (200 kcal) extra per day, less than the theoretical expected cost of the pregnancy. Many women, including those in developing countries and the poorer parts of affluent countries, successfully reproduce supported by energy intakes which appear to be well below the recommended levels. Some of this discrepancy is likely to be due to under-reporting of energy intake in pregnancy because of changed eating habits or subject fatigue in research studies.
Some of the additional energy requirements of pregnancy could be met by increased efficiency of maternal metabolism (decreased basal metabolic rate (BMR) or diet-induced thermogenesis (DIT) or the thermic effect of food (TEF)) and decreased activity-related energy expenditure (Forsum and Löf, 2007). However the BMR response to pregnancy is varied (while it is usually stimulated, it may be depressed or unchanged) and DIT (the increase in energy expenditure due to food consumption) probably remains unaltered. Decreased activity-related energy expenditure could make up a considerable proportion of the energy balance but women who are normally sedentary have little flexibility to further reduce their physical activity during pregnancy (Butte and King, 2005). Decreased energy expenditure in the second and third trimesters of pregnancy has been observed in the Five Country Study of pregnant women (Lawrence et al., 1987), which compared women living in Scotland, Holland, the Gambia, the Philippines and Thailand. Leisure activities and the rate at which heavy work was done decreased. Women who have a long history of poor nutrition, for instance those in subsistence farming communities, seem to be able to adapt more to sparing nutrients and economizing to support the cost of the pregnancy. This may be because these women are more physically active and so can decrease their energy expenditure by a greater degree. However many pregnant women living in developing countries are not able to reduce their activity. Physiological adaptation, for instance the lower resistance blood circulation, may alter the efficiency of energy metabolism in pregnancy (Forsum and Löf, 2007).
Dieting or deliberate energy restriction is not appropriate for most pregnant women; it is unlikely to be beneficial and may harm the fetus. Historically, women at risk of developing pre-eclampsia and obese women were recommended to limit their energy intake and weight gain. However, energy restriction has no effect on the development of pre-eclampsia; excessive weight gain is the result, not the cause, of the underlying clinical pathology. Inadequate energy intake, particularly in the first trimester, is associated with an increased incidence of LBW infants and congenital abnormalities (Carmichael et al., 2003). Excessive weight loss and fat mobilization in pregnancy can produce metabolites that can create metabolic stress and are detrimental to fetal development. Maternal health and later lactational capability may be compromised by dietary restriction in pregnancy. In obese women, energy restriction can be associated with lower infant birth weight (Merialdi et al., 2003). However, if obese women are motivated by their pregnant state to follow dietary recommendations and improve their diet, many will lose body fat.
Protein requirements
Protein requirements increase in pregnancy, to support maternal tissue synthesis and fetal growth. Metabolic adaptations enhancing the efficiency of protein synthesis are evident from early pregnancy onwards (Duggleby and Jackson, 2002). Low-protein diets are associated with an adverse outcome of pregnancy but low protein intakes are unlikely in affluent developed countries. Protein requirements for the growth of maternal tissues and the growth of the conceptus were calculated to be about 925 g (Campbell-Brown and Hytten, 1998) but have been reassessed to be closer to 500–700 g (Williamson, 2006). The increased protein synthesis, and therefore increased dietary requirement, in late pregnancy is about 6 g/day. In Britain and other developed countries, where the average NPU value is 0.7, this is equivalent to about 8–9 g of additional dietary protein being required to maintain nitrogen balance.
During the pregnancy, there is a fall in blood protein levels from about 70–60 g/L. Much of this fall is due to decreased plasma albumin concentration resulting from haemodilution. Albumin functions as a non-specific carrier of lipophilic substances such as some drugs, hormones, free fatty acids, unconjugated bilirubin and some ions. It has an important role in maintaining the plasma osmotic pressure. The fall in plasma colloid osmotic pressure increases movement of water out of the blood vessels (see Chapter 1), thus increasing lower limb oedema and affecting glomerular filtration rate (GFR). Plasma globulins increase in pregnancy.
Plasma levels of most amino acids fall in pregnancy. The most marked falls are observed in glucogenic amino acids, which can be used to form glucose, then those involved in the urea cycle and then the ketogenic branched-chain amino acids. Amino acids are actively transported across the placenta. The transfer of amino acids across the placenta is only just adequate for fetal protein synthesis so any factor adversely affecting amino acid transport mechanisms has the potential to limit growth. Imbalances in maternal amino acid concentration will be reflected by placental uptake. For instance, women with phenylketonuria (PKU) are advised to resume a low-phenylalanine diet (and take tyrosine supplements) prior to conception as high levels of phenylalanine can harm the fetus, even if the fetus does not have PKU. High phenylalanine levels in pregnancy are associated with fetal IUGR, congenital heart disease, microcephaly and mental retardation. The amino acid methionine is involved in folate metabolism; women who have higher dietary intakes of methionine seem to be at lower risk of delivering a baby with a neural tube defect (NTD; Shoob et al., 2001). Good sources of methionine tend to be foods such as animal proteins that are rich in other amino acids and total protein, iron, zinc and calcium.
The optimum birth weight in humans can be considered to be within the range of birth weights associated with the lowest incidence of perinatal mortality and morbidity, in the range 3500–4500 g (Wynn and Wynn, 1991). Mothers of babies in the optimal birth-weight range tend to eat more protein than women who give birth to babies with lower birth weight. Maternal intakes of B vitamins and some minerals, particularly magnesium, have been found to correlate well with birth weight (Wynn and Wynn, 1991). The main regulator of fetal growth seems to be availability of nutrients, which can affect growth directly by changing the availability of substrates required for growth, or indirectly by altering hormonal control of growth.
The normal protein intake of women in most developed countries, who regularly consume foods such as lean meat and poultry, fish, reduced-fat milk products, wholegrains and legumes as part of a balanced and varied diet, appears to be sufficient to provide the additional requirements of pregnancy. Vegetarian and vegan women must ensure a range of wholegrains and legumes are consumed daily to provide adequate protein. The U.S. Institute of Medicine (2002) recommends an additional 25 g of protein per day for pregnancy in addition to the recommended daily intake (RDI) of 46 g of protein per day (0.80 g/kg/day), a total RDI of 71 g of protein per day for pregnant women (or 1.1 g/kg/day). Women with twin pregnancies are recommended to consume an additional 50 g of protein per day together with an appropriate energy increment to optimize efficient utilization of the protein (Institute of Medicine, 2002). Women with very low energy intakes may be at risk of inadequate protein intake. The use of formulated protein supplements, powders or high-protein formulated beverages should be discouraged because clinical studies suggest they may be potentially harmful to the fetus (Kramer and Kakuma, 2003). Some popular weight-restriction diets have promoted high protein intake. However, the fetus has limited ability to detoxify ammonia and excrete urea, particularly during the vulnerable periods of organogenesis in the first trimester. In experimental animals, high protein intakes and apparent high levels of ammonia have been associated with increased rates of congenital abnormalities.
Fat requirements
In pregnancy, plasma lipids alter markedly. Levels of free fatty acids, triacylglycerides, cholesterol, lipoproteins and phospholipids transiently fall early in pregnancy and then rise (Butte, 2000). The changes in handling of lipids are orchestrated by hormonal changes and are associated with changed insulin resistance during the pregnancy (Robinson et al., 1992). The initial low maternal levels of fatty acids reflect maternal fat storage, which is highest early in pregnancy when maternal maintenance costs of pregnancy and fetal growth are relatively low (Campbell-Brown and Hytten, 1998). This appears to anticipate requirements later in pregnancy. In the later stages of pregnancy, when fetal requirements are maximal, maternal nutrient intake could be restricted by lack of availability of food or by restricted capacity for eating and gastrointestinal disturbances. Maternal fat stores, which are 3.5 kg on average, can subsidize a considerable part of the pregnancy. Oxidation of 3.5 kg of fat could theoretically produce 132 MJ (30000 kcal).
During early gestation the fetus depends on placental transfer for fatty acid requirements (Herrera and Amusquivar, 2000). Lipids are transported across the placenta as lipoprotein complexes, classified by their density (Fig. 12.4). Triglyceride levels increase throughout gestation. Placental uptake of triglycerides occurs in the form of very low-density lipoproteins (VLDL). Placental lipase may hydrolyse VLDL, releasing the products for energy metabolism by the fetus (Robinson et al., 1992). The rising level of maternal fatty acids in the third trimester probably reflects mobilization of maternal fat stores. In later gestation, maternal fatty acids are predominantly used for maternal metabolism and ketone body synthesis. The more mature fetus can synthesis fatty acids de novo, using ketone bodies as fuels and lipogenic substrates.
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Fig. 12.4 Classification of lipoprotein complexes. (Reproduced with permission from Saffrey and Stewart, 1997.) |
LCPUFA requirements of pregnant women are particularly high, especially in the third trimester when fetal brain and nervous tissue growth is maximal; accretion of DHA into the developing nervous system and fetal brain is high. Arachidonic acid (20:4, ω-6) is essential for neonatal growth and is the precursor for eicosanoids, prostaglandins and leukotrienes, and docosahexaenoic acid (DHA; 22:6, ω-3) has a key role in fetal brain development and visual function. Therefore, fetal demand for indispensable fatty acids (linoleic acid, 18:2, ω-6; and α-linoleic acid, 18:3, ω-3) must be met from either maternal intake or be released from maternal adipose tissue. The placenta transports the indispensable fatty acids and their preformed long-chain derivatives, arachidonic acid and DHA from the maternal circulation to the fetus. Low maternal intake of these indispensable fatty acids is correlated with reduced neonatal growth (Herrera, 2002). Oestrogen increases the conversion of essential fatty acids to long-chain fatty acids.
Consumption of fish, and therefore DHA, in pregnancy is associated with a reduced incidence of pre-eclampsia, LBW and preterm delivery (Makrides, 2009), probably because ω-3 fatty acids from marine sources inhibit ω-6-derived eicosanoids involved in cervical ripening and the initiation of parturition. Women who eat more marine foods also seem less likely to develop pregnancy-induced hypertension (Al et al., 2000). These positive effects of fish consumption on gestational duration and fetal development have generated much interest in requirements of LCPUFA for optimal outcome of pregnancy. However, it is not clear that supplementation with LCPUFA or fish oil might be beneficial as excess intake of LCPUFA can potentially increase the risk of oxidative damage (Herrera, 2002). The higher the content of PUFAs in the diet, the more likely damaging free radicals will be formed which are potentially toxic and can reduce antioxidant capacity.
Western diets are relatively rich in ω-6 fatty acids but poor in ω-3 fatty acids and intake of preformed DHA is low, so the supply of DHA to the fetus may be compromised. The ratio of ω-6 fatty acids to ω-3 fatty acids is estimated to be significantly higher than it was in the Neolithic era when the big brain of modern man evolved. Obese women with insulin resistance and thin women with little body fat are likely to be even more dependent on dietary DHA. Eating fish in pregnancy would increase DHA intake but much of the advice about fish liver oils containing vitamin A and not consuming an excess of fish in case of heavy metal contamination of fish has led pregnant women to avoid fish totally in pregnancy rather than increase their intake because they are pregnant.
A high fat intake is not recommended in pregnancy as there is an association between increased fat intake and the development of glucose abnormalities (Saldana et al., 2004). Ketonaemia appears to have a negative effect on fetal development and later intellectual performance (Rizzo et al., 1991). High-fat, low-carbohydrate diets are not optimal for pregnancy; it is suggested that a diet <30% fat and >50% carbohydrate reduces the risk of glucose intolerance and gestational diabetes.
Carbohydrate requirements
Adequate carbohydrate intake is important in pregnancy to ensure adequate glucose for maternal brain metabolism and transfer to the fetus but normal diets are usually rich in carbohydrates so there is no changed recommendation for pregnancy. Metabolism of carbohydrates and lipids alters, under hormonal influence, throughout pregnancy to ensure that the fetus receives a continuous supply of nutrients despite maternal intake being intermittent (Butte, 2000). Maternal glucose concentration is maintained at a significantly higher level in later pregnancy by increased hepatic glucose production in order to meet the increasing requirements of the placenta and fetus. The developing fetus utilizes glucose as its primary energy-producing substrate but it can also metabolize maternally derived ketoacids.
Maternal pre-existing diabetes (type 1 or type 2, but not gestational diabetes which develops later in pregnancy), high sucrose intake or prepregnancy obesity are all associated with an increased risk of NTD (Shaw et al., 2003). This is probably because the embryo does not have pancreatic function when the neural tube is developing and closing so it is unable to regulate excess of glucose at this time; high glucose levels lead to oxidative stress and embryonic depletion of inositol which can also affect neural tube development (Baker et al., 1990). The developing embryo may also be vulnerable to the effects of maternal hypoglycaemia following hyperglycaemia. Thus, good control of glucose metabolism in early pregnancy, which is more is likely to be achieved by a diet higher in foods with low GI, lowers the risk of congenital abnormalities. Gestational diabetes, because it becomes evident in the second half of pregnancy after embryonic development is completed, is not associated with an increased risk of congenital abnormalities but a high carbohydrate (low fat) diet with plentiful low GI foods is associated with a decrease in newborn macrosomia (Romon et al., 2001).
Adequate dietary fibre is particularly important in pregnancy because the high progesterone levels affect smooth muscle tone and result in a decreased rate of gastrointestinal transit. This has advantages for nutrient absorption as gut contents are in contact with sites of absorption for longer times but water is also absorbed to a greater extent, which often results in constipation. Recommending that pregnant women increase their intake of complex carbohydrates, such as wholemeal or wholegrain breads, cereals, legumes, fruit and vegetables, would provide carbohydrate with good sources of fibre. Promoting foods high in fibre helps to address problems of constipation as well as generally increasing carbohydrate intake. The other advantage of this is that many foods with higher fibre content also have a lower GI, which is particularly important for women who have, or are risk of developing, diabetes. Increasing intake of complex carbohydrate also has the positive outcome of displacing intakes of fat and added sugars.
Vitamins and minerals
It is thought that a range of micronutrient deficiencies might contribute to congenital malformations and the failure of human embryos to implant or survive (Keen et al., 2003). However, supplementation needs to be evaluated carefully as nutrient–nutrient interactions can be detrimental and some micronutrients are toxic in excess. Thus, both micronutrient deficiency and excess are associated with adverse pregnancy outcome. Levels of fat-soluble vitamins increase during pregnancy and levels of water-soluble vitamins fall. However, levels of vitamin A fall but levels of carotenoids rise. Fat-soluble vitamins cross the placenta more readily than water-soluble vitamins and their transport increases with gestational length; decreased levels of maternal plasma levels may be due to haemodilution rather than to increased uptake by maternal and fetal tissue. Thus, lower circulating levels of nutrients in pregnancy cannot be simply interpreted as indicating a deficiency. It is suggested that hormonal resetting of homeostatic mechanisms favours transfer of nutrients to the fetus (Campbell-Brown and Hytten, 1998). Low levels of nutrients in maternal plasma may limit maternal cell uptake while optimizing placental uptake. The placenta can extract nutrients from maternal plasma and transfer them to the fetus, maintaining transport against a concentration gradient. Thus, fetal concentration of vitamins may be 5–10 times the level in maternal blood. The ‘pump’ mechanisms of the placenta appear to be specific for vitamins; most minerals are not transported by similar mechanisms.
A good-quality maternal diet is probably able to provide the increased vitamin and mineral requirements of the pregnancy, particularly if energy intake is increased from a source of high-nutrient-density food. However, a poor-quality diet may adversely affect both fetal growth and the establishment of adequate stores for neonatal growth. Micronutrient requirements increase slightly in pregnancy but, unless the woman is at the threshold of a deficiency, most women consuming a varied and balanced diet should have adequate reserve. The possible exceptions to this generalization are iron and calcium nutritional status which should be assessed early in antenatal care. Periconceptual folate requirements are higher than can usually be provided by the diet. Vitamin A potentially presents some challenges in pregnancy, as both deficiency and excess are teratogenic. Certain subgroups within the population are at increased risk of vitamin D deficiency, such as Asian women.
Folate and folic acid
‘Folate’ is a generic term applied to dietary sources of related compounds that have the same biological activity in the body. Dietary folates are vulnerable to being broken down during food preparation. Folic acid is a synthetic form which is more bioavailable and more stable. Folate deficiency in early pregnancy is teratogenic and is associated with an increased incidence of NTDs; it can also cause megaloblastic anaemia of pregnancy, cervical dysplasia and atherosclerosis (Stover, 2004). There is a well-established protective effect of folic acid supplements that significantly reduce the incidence of NTDs and they may also reduce the incidence of other congenital abnormalities such as cleft lip. Poor folate intake is also associated with other negative pregnancy outcomes including LBW, abruptio placentae and increased risk of miscarriage.
Folate is involved in single-carbon transfer reactions in the metabolism of nucleic and amino acids, and hence the synthesis of DNA, RNA and proteins. Requirements for folate increase in pregnancy because the number of single-carbon transfer reactions increases, for instance for nucleotide synthesis and cell division. Blood folate levels fall in pregnancy, reflecting the high rate of DNA synthesis and cell division. Any factor that reduces DNA, RNA and protein synthesis increases the risk of congenital malformations, which are usually associated with a reduced cell number rather than a reduced cell size.
There is considerable interaction between folate and other vitamins, such as choline and vitamins B6 and B12, which also have a role in single-carbon methyl donation and, thus, recycling homocysteine to methionine. Deficiency of any of these vitamins can contribute to hyperhomocysteinaemia. Raised levels of homocysteine in pregnancy are associated with complications and adverse outcomes of pregnancy such as an increased risk of pre-eclampsia, NTDs and other congenital abnormalities, LBW and preterm delivery, placental abruption and spontaneous pregnancy loss (Holmes, 2003).
NTDs are the most common congenital abnormality resulting from failure of the neural tube to close effectively between 22 and 27 days postconception, which is usually before women realize they are pregnant. Increased intake of folic acid periconceptually overcomes unidentified abnormalities in folate utilization (Boddie et al., 2000) which are related to mutations of genes expressing enzymes in the folate metabolic pathways of genetically predisposed women. The incidence of NTD is 1.6 per 10000 livebirths in England and 3.1 per 10000 in Wales; NTDs are a clinical reason for offering termination of pregnancy so the actual incidence of pregnancies affected by NTDs is higher than the livebirth rate suggests.
Folic acid supplements, of 400 μg/day, are recommended for all pregnant women or women who might become pregnant. It is recommended that women who are at higher risk for pregnancy affected by NTD (because they have previously had an NTD-affected pregnancy, have a family history of NTD, have insulin-dependent diabetes, or are taking anticonvulsants known to affect folate metabolism) take a high-dose folic acid supplement (those who have already had one conception affected by a NTD should consume 4 mg folic acid per day to reduce the risk of recurrence). Although pregnant women seem aware of campaigns recommending increased folic acid consumption, many seem reluctant to take it (Health Education Authority, 1996). Possibly advice to supplement the diet with folic acid may appear to conflict with the usual health advice to avoid unnecessary drugs in pregnancy. Renaming folic acid as ‘vitamin B9’ as is done in some parts of Europe might alter the perception of folic acid as a drug.
The levels of folic acid that are associated with reduced incidence of NTD are significantly higher than those that could be easily achieved from the diet. It is difficult to increase levels of folate-rich food to the level recommended (Cuskelly et al., 1996). Increased consumption of folate to reduce the risk of NTD is recommended 4 weeks before and 12 weeks after conception, which presents difficulties in many developed countries like the United Kingdom because about half of all pregnancies are unplanned.
The argument for supplementing a staple food, such as bread or flour, with folic acid (Wald and Bower, 1995) has been strengthened by the other advantages of increasing folate consumption. Folate is important in maintaining optimal levels of homocysteine; hyperhomocysteinaemia (accumulation of circulating homocysteine) is associated with cardiovascular disease, stroke, depression, Alzheimer's disease and some types of cancer. However, folic acid supplementation can mask the symptoms of pernicious anaemia due to low vitamin B12 intake which can delay the diagnosis of deficiency, increasing the risk of permanent neurological damage. Some drugs are folate antagonists and so increase the risk of NTDs (Pimentel, 2000). These include anti-epileptic drugs (such as carbamazepine and valproate), retinoids (used to treat acne) and some anti-tumour agents. Women who are pregnant with more than one fetus, breastfeeding women nursing more than one infant and those women with a high alcohol intake or are on chronic anticonvulsant or methotrexate therapy have increased requirement for folate.
Case study 12.2 looks at the issue of folic acid supplementation.
Case study 12.2
Jane seeks preconceptual nutritional counselling. She has had a previous miscarriage and is keen to improve the quality of her diet. Jane expresses concern about taking drugs in pregnancy, including folic acid, and is adamant that the human race could not have evolved requiring nutrients that could not be provided by a healthy diet.
• How might a midwife summarize the characteristics of a balanced diet?
• What rich sources of folate could be identified and how might consumption be increased?
• Is the connection between a previous miscarriage and diet valid?
• How could Jane's fears about folic acid supplementation be addressed?
Vitamin A
Vitamin A (retinal) status in pregnancy is positively correlated with outcome of pregnancy in terms of infant size and gestational length. Requirements for vitamin A are highest in the third trimester of pregnancy when fetal growth is highest. It is involved in vision, reproduction, gene expression, embryological development, growth, immune function, integrity of the epithelium and bone remodelling. Both deficiency and excess of vitamin A in pregnancy can cause fetal abnormalities. Low vitamin A status in pregnancy is associated with increased maternal mortality, decreased birth weight and increased risk of congenital abnormalities (Ramakrishnan et al., 1999). A high vitamin A intake is also associated with teratogenicity; this occurs in the first trimester and causes birth defects deriving from cranial neural crest cells such as craniofacial deformations (cleft lip and palate) and abnormalities of the central nervous system (not NTDs), heart and thymus.
Changes in animal husbandry, and increased use of growth-promoting agents and vitamin supplements given to animals, may make the livers of farmed animals considerably richer in vitamin A than they used to be. Birth defects in humans have been associated with the use of vitamin A analogues for treatment of acne. Women taking medications for the treatment of dermatological problems such as acne should check whether the medication contains large doses of vitamin A and, if so, discontinue its use prior to and during pregnancy. With some acne preparations, it is recommended that conception be avoided for a year after stopping treatment. Preformed vitamin A (retinal) is only available from animal-derived foods. Pro-vitamin A from carotenoids in coloured fruit and vegetables is not efficiently converted into retinal so pregnant women who avoid dairy products and meat need to consume at least five servings of fruit and vegetables per day and to select rich sources of carotenoids. No adverse effects of carotenoids from normal dietary levels of intake have been reported.
Vitamin D
Vitamin D maintains serum calcium and phosphorus concentrations within the range that optimizes bone health, by affecting the absorption of these minerals from the small intestine, their mobilization from bone and calcium resorption by the kidney. Vitamin D is synthesized in the skin; dietary requirements depend on exposure to sunlight. In pregnancy, vitamin D requirements increase substantially. Vitamin D deficiency in pregnancy is associated with decreased fetal growth and later increased risk of osteoporosis via the effect on maternal calcium homeostasis and increased neonatal vulnerability to rickets (Kovacs, 2008).
Dietary vitamin D is required for those individuals whose skin is not adequately exposed to sunlight (Hollis and Wagner, 2004). Women who are regularly exposed to sunlight are much less dependent on dietary sources of vitamin D. Risk factors for low vitamin D are low socioeconomic status, being covered or otherwise restricting access to ultraviolet light, and having a low educational level. Synthesis of vitamin D is affected by the season of the year and the amount of UV light. Less vitamin D is synthesized in the skin of dark-skinned people as melanin absorbs ultraviolet light. Being housebound or not exposing the face, hands and body to sunlight for cultural or religious reasons will limit vitamin D synthesis. Pregnant women who do not receive regular exposure to sunlight (estimated to be about 30–40 min of exposure of face and arms each day) are recommended to have a supplement of 10.0 μg (or 400 IU) of vitamin D per day by many authorities. However this level is under scrutiny and supplements at least 10 times this (which is possible to achieve naturally from sun exposure) are suggested as being optimal for long-term fetal health (including protection against auto-immune disorders) and to protect the mother against gestational diabetes, hypertension and pre-eclampsia (Hollis, 2007). It is prudent to recommend that exposure to sunlight is in the morning or late afternoon to reduce the risk of sunburn and excessive exposure to harmful UVR. It is not known to what extent the use of sunscreen affects vitamin D synthesis but pregnant women are encouraged to routinely use sunscreen during the middle of the day. Public health messages about sun avoidance to reduce the risk of melanoma have contributed to an increasing level of vitamin D insufficiency.
Vitamin K
Vitamin K is a coenzyme used in the synthesis of a number of proteins involved in bone metabolism and the blood coagulation cascade. Use of drugs that interfere with metabolism of vitamin K, such as warfarin, can increase the risk of fetal intraventricular haemorrhage, cerebral microbleedings, microencephaly and mental retardation. Anti-epileptic treatments can inhibit placental transport of vitamin K affecting fetal synthesis of clotting factors and increasing risk of haemorrhage. For this reason, it is recommended that pregnant women with epilepsy take a vitamin K supplement in the month before delivery and during labour. In addition, microbial synthesis of vitamin K may be compromised by the use of broad-spectrum antibiotic therapy (particularly if it is required for a prolonged period).
Vitamin B12
Vitamin B12 is a coenzyme involved in homocysteine-to-methionine conversion and for the reaction that converts L-methylmalonyl-coenzyme A to succinyl-CoA. Vitamin B12 is involved in maternal and fetal erythropoiesis so requirements are increased particularly in the first two trimesters. Deficiency of vitamin B12 increases the risk of neurological abnormalities in the fetus. Absorption of vitamin B12 may increase in pregnancy; the fetus is dependent on maternal dietary intake (Allen, 2002). The placenta concentrates vitamin B12 and then transfers it to the fetus down a concentration gradient so fetal levels of vitamin B12 are about double maternal levels. The placenta preferentially transports newly absorbed vitamin B12 rather than that from maternal liver stores, so transfer to the fetus may be compromised even though the mother shows no overt signs of deficiency.
Plants do not synthesize vitamin B12 so strict vegetarians and those people who consume low amounts of animal products are more likely to be deficient. Plant foods exposed to vitamin B12-producing bacteria, or contaminated with soil, insects or other substances containing B12 or foods fortified with vitamin B12 are the only dietary sources for strict vegetarians. Fetal levels of vitamin B12 may be compromised even if the mother has only recently become a vegetarian. Pregnant women who are strict vegetarians need to take vitamin B12 supplements or eat foods that have been fortified with vitamin B12, and continue doing so while they are breastfeeding. Infants are less tolerant to vitamin B12 deficiency than adults; breastfed infants may develop severe megaloblastic anaemia and neurological damage, even if their vitamin B12-deficient mothers are not showing clinical signs of deficiency. The first symptoms of infant vitamin B12 deficiency are drowsiness, repetitive vomiting, swallowing problems, severe constipation and tremor (particularly involving tongue, face, pharynx and legs). Progression to unconsciousness, coma and, ultimately, death can be swift.
Vitamin C
Vitamin C is a water-soluble antioxidant and a cofactor for enzymes involved in the synthesis of collagen, neurotransmitters and carnitine. It is involved in the recycling of vitamin E and also enhances absorption of non-haem iron. Haemodilution in pregnancy results in plasma vitamin C concentration falling. Pregnant women have increased vitamin C requirements to ensure adequate transfer to the fetus and maternal needs are met. The placenta transports ascorbate from the maternal circulation, oxidizes it and transfers it to the fetus (Choi and Rose, 1989). Vitamin C deficiency is associated with premature rupture of the placental membranes (Siega-Riz et al., 2003), preterm delivery (Ramakrishnan et al., 1999) and infection (Casanueva et al., 1993). Intervention studies have shown reduced incidence of pre-eclampsia in at-risk women supplemented with vitamin C and vitamin E (Chappell et al., 2002). Additional vitamin C is recommended for pregnant women exposed to increased oxidative stress; these include smokers and women who use recreational drugs or consume significant qualities of alcohol or regularly take aspirin (Cogswell et al., 2003).
Calcium
Calcium requirements increase mostly in the third trimester when the fetal skeleton develops rapidly, incorporating a total of about 30 g of calcium. However, this is a tiny proportion of the calcium deposited in the maternal skeleton, which can act as a reservoir if dietary calcium is low. However, if the mother's own skeleton is still growing, as in adolescent pregnancy, there may be competition between the maternal and fetal skeletons for calcium. Young girls who become pregnant within 2 years of starting to menstruate are most at risk as demineralization of maternal bone may be particularly detrimental when peak bone mass is being accrued.
Vitamin D concentrations rise in pregnancy, resulting in increased intestinal calcium absorption, and calcium retention is increased; this occurs in advance of mineralization of the fetal skeleton. Calcium supplementation has been used therapeutically during pregnancy to prevent hypertensive disorders and related problems. Calcium is one of the main nutrients which need to be considered in the antenatal assessment; it is not uncommon for women of reproductive age to have an intake that is below the recommended intake. Pregnant adolescents are particularly at risk of inadequate intake of calcium as are women of all ages who do not consume dairy products. Pregnant women should be encouraged to consume at least three servings of calcium-rich foods a day. Although dietary sources of calcium are preferable, it may be necessary for women who avoid dairy produce and other calcium-rich foods to be prescribed a calcium supplement. Calcium supplementation in pregnancy for women who have a low calcium intake may protect against hypotensive disorders and pre-eclampsia (Hofmeyr et al., 2010). Women who are prescribed both iron and calcium supplements should avoid taking them at the same time of day to maximize absorption of both.
Iron
The requirements for additional iron in pregnancy remain controversial (see Chapter 11). First-trimester iron requirements are lower than for non-pregnant women due to menstrual savings but requirements are markedly higher by the third trimester (Hallberg, 2001). It is estimated that about 600 mg of iron are required for the fetus and placenta and blood lost at parturition (Campbell-Brown and Hytten, 1998). The expansion of maternal red blood cell mass accounts for about 290 mg of iron (Letsky, 1998), but this expansion probably accommodates for the blood lost at parturition. Amenorrhoea of pregnancy saves about 120 mg of iron, which is not lost in menstruation, and iron absorption increases.
Iron depletion (low iron stores) or deficiency (anaemia) appears to be common in pregnant women and the consequences are significant for both mother and fetus. Maternal anaemia increases risk of morbidity and mortality, and is associated with risk of heart failure, haemorrhage and infection. The risks of fetal death, perinatal mortality, preterm delivery and lower birth weight are also increased (Scholl and Reilly, 2000). Maternal iron deficiency affects cognition, behaviour, motor development and activity of offspring (Allen, 1997), probably irreversibly. Infants of iron-deficient mothers are more likely to have low iron stores and be susceptible to iron deficiency themselves. Maternal iron deficiency affects the mother's physical work capacity and interaction with the infant.
There are two pathways of iron absorption; haem and non-haem iron absorption (Fig. 12.5). Haem iron from meat is highly bioavailable and affected to a negligible degree by other components of the diet. However, most dietary iron is non-haem iron, absorption of which varies with other dietary constituents, particularly those which influence the reduction of the insoluble ferric iron to soluble ferrous iron. Vitamin C and other organic acids significantly enhance dietary absorption of non-haem iron, as does the presence of meat, fish or poultry, though the mechanism is not clear. Inhibitors of non-haem absorption bind iron and render it less available; these include phytate (in legumes, grains and rice), polyphenols (in tea and coffee, grains, oregano and red wine) and vegetable proteins such as those in soybeans. Calcium inhibits absorption of both haem and non-haem iron with a dose-related effect. Non-haem iron is transported across the gut by the same divalent metal transporter which also transports other metals such as zinc and copper; this means that supplementation with one metal can affect the absorption of the others. The bioavailability of iron from meat is significantly higher than from plant-based foods, and the meat and other animal proteins enhance non-haem iron absorption, so individuals who consume omnivorous diets absorb more iron than do vegans or vegetarians.
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Fig. 12.5 Pathways of iron absorption. Haem iron from meat, poultry and fish is absorbed efficiently via the haem tran porter, whereas absorption of non-haem iron is affected by other dietary components. For instance, vitamin C enhances the conversion of Fe3+ (ferric iron) to the more soluble Fe2+ (ferrous iron) which is better absorbed. Some dietary components, such as phytate and polyphenols, bind to the iron and make it less available. Non-haem iron is transported across the gut wall via the divalent metal transporter (DMT). Zinc and copper can compete for transport by DMT and therefore inhibit iron absorption. |
Risk factors for iron deficiency in pregnancy include depleted iron stores prior to pregnancy (usually related to menstrual loss), not eating meat, chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin (resulting in gastrointestinal lesions), low intake of factors which increase iron absorption (particularly vitamin C) and high intake of factors which decrease absorption. Iron deficiency is more likely with low socioeconomic status, poorer educational attainment and multiple gestation; adolescent women and those with a short interpregnancy interval are also at increased risk of iron deficiency. Use of oral contraceptives prior to pregnancy tends to result in a favourable iron status because menstrual loss is limited.
Pregnant women who are at risk of iron deficiency are usually prescribed iron supplements. Some women experience gastrointestinal effects in response to supplementary iron. Absorption of iron is best in the absence of other food (empty stomach) but may be associated with more side-effects. Low-dose supplements are associated with fewer side-effects and ferrous gluconate appears to be less irritating. However, iron is potentially toxic in excess; concerns focus on iron overload causing the generation of free radicals which can cause cellular damage and on the possible increased susceptibility to infection of women who are not iron deficient. Thus, iron supplementation should always be prescribed on the basis of biological criteria rather than being administered routinely.
Haemochromatosis is the most common genetic disorder affecting Caucasian populations (Heath and Fairweather-Tait, 2003); it is a recessively inherited disease resulting in iron overload. The clinical effects of haemochromatosis, due to deposition of iron in the liver, heart and pancreas, are not usually manifest or of concern in women of childbearing age as menstrual losses help to maintain iron balance. However, routine assessment of blood parameters such as transferrin saturation in pregnant women could help to identify those women who might be at risk in later life.
To meet the additional requirements of pregnancy, women need to markedly increase their intake of iron-rich foods and the dietary factors that promote iron absorption. Nutritional assessment and dietary advice for pregnant women should take into consideration both sources of iron and the intake of factors affecting non-haem iron absorption. Timing of consumption of foods can influence nutrient–nutrient interaction. For instance, drinking fruit juice (high vitamin C content) with a good iron source will favour absorption, and drinking tea, which has a high tannin level, should be avoided with iron sources. Vegetarian and vegan women may find it difficult to meet their iron requirements solely from food sources; they should consume grains, vegetables and legumes, and have vitamin C-rich foods or drinks (raw fruits, fruit juice or vegetables) with meals. As adolescents have a higher iron requirement, this group is particularly vulnerable in being able to achieve an adequate iron intake particularly in the latter part of pregnancy and especially if they avoid meat. Supplementation may be necessary for those with low iron stores and/or low dietary iron intakes, but supplementation must always be given in conjunction with appropriate dietary advice, and under supervision from a health professional. There are concerns about excessive intake of supplementary iron and its potential effects on free-radical generation; also, the implications of iron supplementation on zinc and copper status need to be considered.
Zinc
Zinc is involved in cell proliferation, protein synthesis, protection from oxidative damage, apoptosis, hormone binding (by means of zinc fingers) and transcription, and is thus likely to affect embryonic and fetal development (Keen et al., 2003). Zinc deficiency in pregnancy is teratogenic; it is associated with increased risk of congenital abnormality (including NTDs) and other complications of pregnancy and delivery including haemorrhage, hypertension, pre- and post-term pregnancy and prolonged labour, growth retardation, retarded neurogenesis, neurobehavioural and immunological development and premature delivery (Mahomed et al., 2007). Iron supplementation can decrease zinc absorption, and zinc in excess may induce a secondary copper deficiency, as there is competition for the divalent metal transporters. Bioavailability of zinc in foods is particularly affected by high phytate content in foods such as cereal grains, legumes and nuts.
Selenium
Selenium forms part of the enzyme glutathione peroxidase, which metabolizes hydrogen peroxide formed from polyunsaturated fatty acids. Selenium is incorporated into proteins to make selenoproteins, some of which function as antioxidant enzymes preventing cellular damage from free radicals (natural by-products of oxygen metabolism). Other selenoproteins are involved in thyroid hormone metabolism (Thomson, 2004). The requirement for selenium is uncertain; a relatively low intake of selenium is required to prevent Keshan disease, a cardiomyopathy, but higher intakes of selenium may be protective against cancer and cardiovascular disease, by protecting against free-radical damage. Pregnant women have increased selenium requirements to allow for growth of the embryo and increased selenoprotein synthesis and tissue accumulation. The placenta actively transports selenium to the fetus (Hytten and Leitch, 1971), but it is not known whether maternal absorption of selenium increases in pregnancy. Requirements for selenium are increased with increased oxidative stress such as that caused by smoking and intense exercise. The main sources of selenium are fish and seafood, meat and poultry, eggs, dairy produce and bread.
Magnesium
Magnesium status has been implicated in the incidence of preterm labour (via uterine hyperirritability), pregnancy-induced hypertension, fetal growth retardation, cerebral palsy and mental retardation (Institute of Medicine, 1997). Studies of women from poor socioeconomic backgrounds, who have a higher risk of poor pregnancy outcome, have observed low intakes of magnesium (Doyle et al., 1989). Some intervention studies have found that magnesium supplementation increases birth weight (Merialdi et al., 2003). Magnesium forms part of the chlorophyll molecule so green vegetables such as spinach are rich in magnesium; other sources include nuts, seeds, wholegrains, wheat bran, wheat germ and breakfast cereals, dairy products, dried fruit and hard water. Women who consume a wide variety of foods including plenty of fruit and vegetables are unlikely to be deficient in magnesium.
Iodine
Iodine is a component of the thyroid hormones thyroxine (T4) and its active form 3,3′,5-tri-iodothyronine (T3), which are important in growth and development and in energy production. Pregnant women have increased requirements for iodine as the fetus has a high requirement and maternal renal clearance is increased. The fetal brain is very vulnerable to maternal hypothyroidism; iodine deficiency is the major cause of preventable mental retardation worldwide. In pregnancy, severe iodine deficiency is associated with LBW and preterm delivery, congenital abnormalities, increased pregnancy loss, stillbirth, increased perinatal and infant mortality, psychomotor, speech and hearing defects, dwarfism, spastic diplegia, cretinism and mental retardation (Zimmermann and Delange, 2004). Mild-to-moderate iodine deficiency during pregnancy adversely affects both maternal and infant thyroid function and has implications for the mental development of the infant. Marginal iodine deficiency in pregnancy may be associated with impaired development but small effects on mental development such as IQ score reduced by a few points are difficult to assess, particularly as it is difficult to measure dietary iodine intake. Although iodized table salt is mandatory in the United Kingdom, individuals are consuming less salt for well-founded health reasons, consumption of commercially produced and processed foods which do not contain iodized salt has increased and there is reduced use of iodophors for cleaning equipment in the dairy industry. It has been proposed that pregnant women and women planning pregnancy should take an iodine-containing supplement of about 150 μg/day to optimise development of the fetus (Zimmermann, 2009) and these are becoming more available in many countries.
Undernutrition in pregnancy
In experimental animals, maternal undernutrition in pregnancy usually leads to decreased birth weight. Maternal weight gain in human pregnancy is positively associated with birth weight and developmental outcome. However, in nutritional assessment it is important to determine prepregnancy weight from objective data and to assess the level of oedema. Women who are underweight have an increased risk of pregnancy loss and small babies that have increased morbidity and mortality. It is difficult to dissociate the effects of a poor diet in pregnancy from other variables. Women who consume a poor diet in pregnancy are likely to have consumed a poor diet before pregnancy and more likely to have had a poorer diet during their own growth and development. Many of them are shorter than average and a poor diet is associated with an increased incidence of smoking. Maternal shortness is also associated with a poorer social background, young maternal age and less formal education.
Diet quality
Although most nutritional studies have focused on energy requirements and consumption in pregnancy, the quality of the diet as well as the quantity may be important. In Britain, nutrient-deficiency diseases are rare but the quality of the diet varies markedly (see below). Mothers of LBW babies have not only low energy intakes but also diets of low nutrient density. Even in affluent countries, many women have daily intakes of B vitamins below the recommended level. Lifestyle changes, such as car ownership and less-active work patterns, mean energy requirements fall. However, nutrient requirements may not fall in parallel; indeed pollution and smoking increase requirements of certain nutrients. This means that, although energy consumption needs to fall to match reduced energy expenditure, the density of nutrients within the diet may need to increase to ensure that requirements are met.
Supplementation
Nutrient supplementation studies of the diet in pregnancy have produced inconsistent and inconclusive results. High-density protein supplementation depresses birth weight (Rush, 1989). Lower concentrations of protein have disappointingly small effects. Some of the studies are probably methodologically flawed and supplements may be used as alternatives rather than increasing nutrient consumption, or the target group may not consume them. Supplementation in the second and third trimesters of pregnancy may be too late to have an effect on birth weight; however, it may benefit maternal health and work potential and improve breastfeeding efficiency. Earlier supplementation may have a greater effect because nutrient support of early follicular development and maternal nutrient stores prior to conception may programme the fetal growth trajectory. More research studies investigating the effectiveness of supplements on the outcomes of pregnancy are needed particularly for those nutrients where intake is more likely to be compromised such as iodine, DHA, folate and choline (Zeisel, 2009).
Fetal adaptation to undernutrition
Subjected to inadequate substrate levels of either nutrients or oxygen, the fetus adapts by changing its metabolic activity in order to survive in utero and to optimize chances of surviving after birth in a nutritionally poor environment. Slowing of growth and reducing energy expenditure are part of this adaptation. Growth accounts for a large proportion of energy expenditure. Adapting to a lower growth trajectory means that nutrient requirement decreases and available nutrient levels may then be adequate. The placenta, which has a high nutrient and oxygen requirement itself, may also adapt. Although a number of adult-onset diseases are associated with impaired fetal nutrition (Fig. 12.6), they tend not to affect reproductive ability as they cause pathological problems late in life. Animal studies have demonstrated that marginal malnourishment for many generations requires optimal nutrition for several generations before normal size and behaviour are expressed (Stewart et al., 1980). This intergenerational effect may be one of the reasons why dietary supplementation in pregnancy has such a small effect on outcome.
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Fig. 12.6 Association of adult-onset diseases and impaired fetal nutrition. |
Malnutrition
Interesting results come from studies looking at the effect of nutrient deprivation on previously well-nourished women. The Dutch Hunger Winter, from September 1944 to May 1945, was due to the Nazi blockade of food supplies exacerbated by very severe winter weather conditions. The severe nutritional deficiency affected fertility and birth weights and the birth rate fell dramatically, by about 50%, 9 months later (Lumley, 1992 and Stein and Susser, 1975a). This was due both to effects on ovulation and an increased incidence of pregnancy failure. Congenital malformation rate increased among babies conceived during the famine and in the following 4 months, which demonstrates the importance of good preconceptual nutrition. However, many women were already pregnant at the time of the food shortage. If the women were deprived of energy in the second half of their pregnancy, the birth weight of their babies was reduced by 350 g on average. These babies were thin but of normal length. They appeared to develop and grow normally. However, in adulthood the male babies who had been exposed to deficiency late in development had lower rates of obesity compared with those who had experienced restricted nutrient levels early in development (Ravelli et al., 1976). Young women who had been exposed to nutrient deficiency early in gestation, but not later, had normal birth weights themselves. However, their babies were smaller than expected (Stein and Susser, 1975b). Adults of lower birth weight have increased risk of developing type 2 diabetes mellitus, heart disease, hypertension, obstructive lung disease, hypercholesterolaemia and renal disease (Godfrey and Barker, 2000). However, results from the longer, more severe, Leningrad siege do not show any association between intrauterine malnutrition and glucose intolerance and coronary heart disease in adulthood (Stanner et al., 1997).
Transient nutrient deficiency may alter fetal growth patterns without affecting final birth weight very much (Harding and Johnson, 1995). Birth weight is a crude outcome measure of optimal gestational growth and development. Suboptimal maternal body composition and nutrient intake can have a long-term effect on the offspring without necessarily affecting size at birth (Godfrey, 2001). Birth weight does not differentiate between the more subtle effects of nutrition on body composition and development of specific tissues and organs. It may not identify growth restriction; a similar birth weight can be attained with different growth trajectories. For instance, if an infant does not reach its potential birth weight but is born above 2500 g, it will not be classified as being of LBW even though its growth is not optimal. Nutrient deprivation before pregnancy or early in gestation affects brain growth and development in animals, which suggests that ‘programming’ of later brain growth is determined by nutrient availability before the demand for nutrients occurs. Lung growth is affected by later nutritional deficiency; lung weight and composition, muscle function, defence mechanisms and surfactant production are all susceptible to nutritional insult in late pregnancy.
Maternal obesity
Maternal obesity is associated with larger babies, macrosomia and increased perinatal mortality. Large-for-gestational-age babies are not longer in length but have increased deposition of adipose tissue. Routine antenatal care is more difficult in obese women, and labour is more likely to be prolonged and unsuccessful. Obese women are at higher risk of disorders such as hypertension, thromboembolism, pre-eclampsia and gestational diabetes. Obese women tend to have increased problems during delivery with more caesarean sections and associated problems; operative delivery is more complicated and there is increased risk in the puerperium (Yogev and Catalano, 2009). Maternal obesity is also associated with an increased incidence of congenital malformations (Prentice and Goldberg, 1996), particularly NTD. In obese women, folic acid seems to lose its protective effect.
Lifestyle issues
Alcohol
Alcohol readily crosses the placenta so maternal alcohol levels determine alcohol levels in fetal blood and may affect embryonic development, growth, fetal brain function and later behaviour. Exposure of the fetus to alcohol can cause long-term behavioural and developmental problems; particular periods of embryonic development may be more vulnerable than others and patterns of drinking (such as regular or binge drinking) may determine the extent of the effect. Whether there is a ‘safe’ limit of alcohol exposure is uncertain; other dietary factors and genetics also play a role in the effects of alcohol. Therefore, it is prudent to advise all pregnant women to avoid alcohol completely if possible. Also, total abstinence is often found easier to adhere to.
Fetal alcohol syndrome, the most easily recognizable outcome of fetal alcohol exposure, is characterized by intrauterine and postnatal growth retardation, characteristic unusual facial features and adverse effects on brain function leading to mental retardation and/or behavioural disturbances. It occurs if the fetus is exposed to regular heavy alcohol intake or to very high alcohol concentrations at critical periods in development. However, fetuses exposed to lower amounts of alcohol may also be affected with fetal alcohol spectrum disorder which results in a range of symptoms that can be more difficult to diagnose definitively. These symptoms include attention deficit hyperactivity disorder (ADHD), inability to foresee consequences and learn from previous experience, inappropriate or immature behaviour, lack of organization, learning difficulties, poor abstract thinking, poor adaptability, poor impulse control, poor judgement and communication problems (Koren et al., 2003). Infants exposed to alcohol in utero may demonstrate withdrawal symptoms after birth such as hyperactivity, excessive crying, irritability, weak sucking, disturbed sleep, tremors and seizures.
Alcohol consumption is commonly under-reported and, in recent years, standard serving sizes and usual alcohol content of alcoholic beverages such as wine and lagers have increased making the recommendations based on alcohol units difficult to follow. It can be difficult to reassure women who have had a small amount of alcohol before realizing that they were pregnant and still maintain advocacy for abstinence (Koren et al., 2003).
Smoking
Although some women stop or reduce smoking when they become pregnant, a significant proportion continue to smoke throughout pregnancy. Smoking (and environmental or second-hand tobacco smoke) is associated with increased early spontaneous abortion and placental complications such as miscarriage placental abruption, sudden infant death syndrome, growth restriction and decreased birth weight, preterm delivery and long-term behavioural and psychiatric disorders (Shea and Steiner, 2008). The physiological mechanisms are not clear but both nicotine and carbon monoxide are vasoconstrictors and may affect blood flow to placental and fetal tissues. Nicotine can increase maternal blood pressure and heart rate which may compromise uterine blood flow. Carbon monoxide binds to haemoglobin forming carboxyhaemoglobin which can cause fetal hypoxia and is implicated in sudden infant death syndrome (Haustein, 1999). Cigarette smoke also contains lead, cadmium and thiocyanate all of which are potentially hazardous to the fetus. Cigarette smoke is a source of free radicals and oxidative stress. Smoking is also thought to affect absorption of micronutrients and to increase nutrient utilization (Cogswell et al., 2003). Thus, smoking increases maternal micronutrient requirements but may also decrease the appetite and food consumption. Smokers are more likely to consume alcohol and other substances which interact with nutrient metabolism and are less likely to take nutrient supplements. Many women who smoke in pregnancy or who quit smoking during pregnancy and resume in the postpartum period are influenced by weight concerns (Levine and Marcus, 2004). The most effective therapies for smoking cessation in pregnancy are behavioural interventions; more evidence is required about the effectiveness and safety of pharmacological treatment (Schneider et al., 2010).
Caffeine
Caffeine is a mild stimulant present in beverages, such as coffee, tea and cola, chocolate and medications such as cold remedies, allergy preparations, headache medications, diuretics and stimulants. Caffeine in pregnancy is associated with increased risk of fertility problems, congenital abnormalities, pregnancy loss, growth retardation and behavioural problems (Greenwood et al., 2010). Caffeine is readily transported across the placenta but the liver enzyme involved in caffeine metabolism is not expressed by the placenta or fetal liver (Olsen and Bech, 2008). In addition, some individuals metabolise caffeine more slowly. It is currently recommended that pregnant women limit their caffeine consumption to 200 mg/day. The caffeine content of tea and coffee ranges markedly but 200 mg caffeine is roughly equivalent to two mugs of instant coffee, one and a half mugs of filter coffee, four average mugs of tea, five cans of regular cola drinks, about two and a half cans of ‘energy’ drinks and 200 g of plain chocolate (caffeine in milk chocolate is about half that in plain chocolate).
Drug use, medication, herbs and ‘smart’ drinks
Most medications prescribed to pregnant or breastfeeding women will have been evaluated for safety and the maternal benefit weighed against the risk of the drug being transported across the placenta and affecting the fetus. No drug is without side-effects (Shehata and Nelson-Piercy, 2000) and anxiety about birth defects is a major parental concern. Anti-anxiety drugs, antidepressants, and neuroleptic drugs may affect neurotransmitter function of the developing central nervous system. Many recreational drugs such as amphetamines, heroin, marijuana and hallucinogens are harmful in pregnancy. It is important that pregnant women discuss their condition with health practitioners including pharmacists.
Many women use herbs and herbal teas during pregnancy, possibly because they want to control their health without using other medication or because their midwife has recommended them (Low Dog, 2009). They are easy to access and are perceived to be safe; use of the internet has brought more information about their use into the public domain. A number of herbs have pharmacological actions and the safety and effectiveness of others are not known; there are also concerns about quality control and contamination. Some herbs are known to be unsuitable in pregnancy; for instance, raspberry leaf tea can stimulate contractions and is used to induce labour. Other herbs that should be avoided in pregnancy include black cohosh, pennyroyal, mugwort, Ma Huang or ephedra. Pregnant women are recommended to choose herbal teas made with ingredients that are a normal part of their diet such as mint, blackcurrant or orange extracts and avoid unfamiliar substances. Herbal teas should preferably be purchased from reputable sources.
Carbonated drinks are not harmful for pregnant and breastfeeding women per se; carbonation itself does not present problems. Carbonated drinks are usually not nutrient dense and may contribute only sugars; they may displace drinks which could provide more nutrients. Other ingredients in ‘smart’ drinks (also known as ‘new age’, ‘designer’ or ‘energy’ drinks) may be of concern. High levels of caffeine are commonly added to energy drinks. Guarana, a Brazilian berry extract, is a stimulant related to caffeine. Ginseng is not recommended for pregnant women. Many of the smart drinks also contain higher levels of amino acids and vitamins than are considered optimal for pregnant women.
Exercise
Pregnant women who exercise have reduced fat gain, more rapid weight loss after pregnancy, improved mood and improved sleep patterns (Kramer, 2002). It is suggested that labour progresses faster and more effectively in women who exercise, reducing the need for induction, pain relief and operative delivery (Olson et al., 2009). However, all women tend to decrease their activity as pregnancy progresses. Physiological adaptations to exercise during pregnancy protect the fetus, maintain placental and fetal tissue perfusion and oxygenation and facilitate nutrient delivery (Clapp, 2000). Exercise begun in early pregnancy enhances placental development and fetal growth, whereas initiating significant exercise programmes later in pregnancy may reduce fetoplacental growth (Clapp et al., 2000). Women should therefore be encouraged to begin or continue low-volume exercise throughout pregnancy but decrease exercise towards the end of gestation to optimize outcome.
The aim should be to maintain a good fitness level during pregnancy rather than to reach peak fitness or train for competitive events. Moderate aerobic and strength-conditioning exercises (such as swimming, yoga, stretching, biking and walking) as part of a healthy lifestyle are considered safe and beneficial for both healthy normal- and over-weight pregnant women (DeMaio and Magann, 2009). Exercise may also be useful in the prevention and treatment of maternal and fetal complications of pregnancy such as gestational diabetes and pre-eclampsia (Weissgerber et al., 2006). Activities which minimize the risk of loss of balance and fetal trauma are recommended (Davies et al., 2003), whereas activities that result in respiratory stress (hyperventilation) or hyperthermia should be avoided. Certain activities such as contact sports and walking or running on rocky or unstable ground should be avoided (as joint laxity and centre of gravity are affected by pregnancy). In late pregnancy, exercises that involve lying on the back are best avoided as the weight of the uterus can impede venous return to the heart and may cause postural hypotension (see Chapter 11). Women are advised to seek advice before starting an exercise programme in pregnancy and to seek immediate advice for any injury. Pregnant women with certain conditions such as a history of bleeding or preterm labour, placenta praevia (where the placenta is low in the uterus), anaemia, pre-eclampsia or hypertension, and medical conditions which limit cardiovascular reserve may be advised to avoid exercise programmes. Pregnant women taking part in physical activity should wear appropriate footwear, take frequent breaks and avoid exercising in extremely hot weather.
There are differences in physiological responses to exercise in pregnant women who are acclimatized to high altitude (live at high altitude) and pregnant visitors to high altitude (Entin and Coffin, 2004). Fetal oxygenation does not seem to be affected by air travel but exercise at high altitude may be associated with hyperventilation and pregnancy complications such as dehydration, bleeding and preterm labour.
Work and stress
Strenuous work and physical stress can potentially influence micronutrient status and outcome of pregnancy. Women in employment may be at risk of compromised diets because they have less time for shopping and cooking. Peak energy expenditure, length of time spent standing (which has been shown to affect patterns of meals consumed) and type of activity (for instance, lifting may result in greater intra-abdominal pressure) may be more significant. Particular occupations, long and/or irregular working hours and shift work have been implicated in being associated with a poorer outcome of pregnancy (Shaw, 2003). Psychological stress can increase the risk of birth defects, early onset pre-eclampsia, preterm delivery and LBW (Triche and Hossain, 2007).
Key points
• The diet before pregnancy, as well as that consumed during pregnancy, can affect the nutrient status of the woman.
• The increased energy requirements of pregnancy can be met by a combination of increasing intake, decreasing activity and changing metabolism.
• A good-quality, nutrient-dense diet can supply the additional protein, vitamin and mineral requirements of pregnancy.
• Energy restriction and obesity affect reproductive function: both male and female fertility and fetal growth.
• Pregnancy-induced hormonal changes, including insulin resistance, affect transfer of nutrients to the placenta and fetus.
• Adaptation to poor nutrition in pregnancy results in changes in growth in utero and birth weight and may be linked to disease in adult life.
Application to practice
Advice on nutrition in pregnancy is important before and during pregnancy, and also for subsequent pregnancies.
Women who have a poor history of nutrition are at risk and the midwife needs to be aware of this to aid in the detection of problems associated with poor dietary intake.
Women with low body fat may have problems conceiving and so active weight gain may need to be encouraged to optimise conception.
Women with high body fat may also have problems conceiving (see Chapter 6). Obese women are at much higher risk from complications during pregnancy, delivery and the postnatal period.
Annotated further reading
Barker, D.J.P., Fetal and infant origins of adult disease. (1992) BMJ Books, London .
Describes the research underlying the fetal origins of adult disease (the Barker Hypothesis) in a compilation of the 31 key papers in this area.
In: (Editor: Bhatia, J.) Perinatal nutrition: optimizing infant health and development (2004) CRC Press.
This book examines the role of maternal nutrition in fetal and infant growth and development and longer term health prospects, considering micronutrient supplementation and dietary recommendations.
Carlson, S.; Aupperle, P., Nutrient requirements and fetal development: recommendations for best outcomes, J Fam Pract 56 (2007) S1–S6.
A good background to the roles and requirements for DHA in pregnancy which addresses issues related to supplementation in pregnancy and lactation and identifies research questions which need to be considered.
In: (Editor: Langley Evans, S.) Fetal nutrition and adult disease: programming of chronic disease through fetal exposure to undernutrition (2004) CABI Publishing.
A research-based textbook which describes the epidemiological evidence, animal studies and likely biological mechanisms behind the hypothesis that maternal nutrition in pregnancy can be the cause of programming of lifelong disease risk such as heart disease, stroke, diabetes and hypertension.
Molloy, A.M.; Kirke, P.N.; Brody, L.C.; Scott, J.M.; Mills, J.L., Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development, Food Nutr Bull 29 (2008) S101–S111.
An in-depth discussion about the importance of folate and vitamin B12 nutrition in pregnancy and lactation.
In: (Editors: Symonds, M.E.; Ramsay, M.M.) Maternal-fetal nutrition during pregnancy and lactation (2010) CUP, Cambridge.
A detailed consideration of the nutritional requirements for each stage of fetal development and growth, and the implications if these are not met; a good synthesis of the underlying theory and scientific background with the clinical applications.
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