Gestational Diabetes During and After Pregnancy

15. Maternal Comorbidities During Gestational Diabetes Mellitus: Obstetrical Complications, Prematurity, and Delivery

Cristiane Guberman and Siri L. Kjos1

(1)

Department of Obstetrics and Gynecology, Harbor UCLA Medical Center, Torrance, CA 90509, USA

Siri L. Kjos

Email: skjos@obgyn.humc.edu

Abstract

This chapter reviews obstetrical and delivery complications in the setting of gestational diabetes (GDM) e.g., preterm labor, the risk of shoulder dystocia, respiratory distress, shoulder dystocia, birth trauma, and cesarean delivery. We evaluate various approaches and interventions that may minimize undesirable outcomes.

15.1 Introduction

This chapter reviews obstetrical and delivery complications in the setting of gestational diabetes (GDM) e.g., preterm labor, the risk of shoulder dystocia, respiratory distress, shoulder dystocia, birth trauma, and cesarean delivery. We evaluate various approaches and interventions that may minimize undesirable outcomes.

15.2 Preterm Delivery

Preterm delivery, defined as delivery before 37 weeks of gestation, has increased by approximately one third over the last 25 years, to 12.8% of deliveries in 2006, with about three-quarters of these occurring between 34 and 36 weeks.1 Preterm births can be categorized into spontaneous vs. indicated.2 Indicated preterm births, accounting for ∼25% of preterm births,3 occur when a medical or obstetrical condition exists which creates an undue risk for the mother, the fetus, or both.

Is preterm delivery increased in women with GDM? Preeclampsia and hypertensive disease are the most common indications for pre-term delivery, accounting for approximately half of preterm births3 and occur more frequently in women with GDM, as discussed in the chapter on hypertensive disorders during pregnancy. In a large case–control study, after adjustment for weight, age, ethnicity, and prenatal care, GDM was found to be significantly associated with an increased risk of hypertensive disorders compared to control women, including severe preeclampsia (odds ratio (OR) 1.5, 95% CI 1.1, 2.1), mild preeclampsia (OR 1.5, 95% CI 1.3, 1.8) and gestational hypertension (OR 1.4, 95% CI 1.2, 1.6).4 The association between GDM and eclampsia, a rare complication of preeclampsia, was not significant (OR 1.3, 95% CI 0.5, 3.2). The recent Hyperglycemia and Pregnancy Outcomes (HAPO) observational study, with blinded glucose tolerance testing in over 25,000 women with normal to mild GDM, found a significant relationship between increasing glucose levels and preeclampsia.5 Hypertensive disorders of pregnancy can also induce obstetrical complications, e.g., intrauterine growth restriction or abruption, which by themselves require preterm delivery. Indicated deliveries in diabetic women due to poor glycemic control or renal disease are less commonly seen in pregnancies complicated by GDM.

Spontaneous preterm birth occurs in the absence of maternal or fetal conditions prompting delivery and accounts for approximately 75% of preterm birth.3 Spontaneous preterm birth does not appear to be increased in women with GDM. In a controlled study examining 550 consecutive deliveries in women with intensively managed GDM, the rate of preterm delivery was 6.2% compared with 6.5% in controls.6In the blinded observational HAPO study there was a small, but significant positive association between increased 1- and 2-h postglucose challenge levels and preterm delivery before 37 weeks.5 The accompanying trial did not differentiate between spontaneous and indicated preterm birth. GDM may not be a risk factor in spontaneous preterm birth, possibly because GDM women have increased frequency of prenatal visits and monitoring along with a low incidence of maternal underweight, itself a risk factor for spontaneous pre-term birth.7

15.3 Term Delivery

Obstetrical complications relating to delivery at term include stillbirth, shoulder dystocia, birth trauma, and cesarean delivery. Women with GDM often have coexisting morbidities such as older maternal age, higher parity, hypertension, obesity, and a history of a prior large-for-gestational age (LGA) infant, stillbirth, or cesarean delivery, all of which are independently associated with increased obstetric complications.8 Many of these same factors are indications for early and second trimester GDM screening.9 When addressing obstetrical complications, it is important to try to assess the independent contributions of the diagnosis and treatment of GDM above the woman’s baseline risk factors for newborn and maternal morbidity.

When and how should women with GDM be delivered? The question of when and by which route a woman whose pregnancy is complicated by GDM should be delivered needs to evaluate each risk factor and their interactions. It may be safer to pursue expectant management with the fetus remaining in-utero. Expectant management also increases the risk of stillbirth, continued accelerated growth, and a LGA infant. In turn, LGA infants have greater risk of shoulder dystocia, birth trauma, labor induction, and cesarean delivery. The alternative option to schedule delivery at near term or early term can increase newborn complications such as respiratory distress, transient tachypnea of the newborn (TTN), or jaundice. While evidence-based guidelines are lacking, it is unlikely that one clear answer will emerge, as one must consider the individual comorbidities, glycemic control, obstetrical history, and the patient’s own desires. The major risks associated with GDM will be considered independently to assist the practitioner to develop an individualized delivery plan to minimize risk.

Risk of stillbirth: Historically, women with pre-existing diabetes have been induced near term or prior to their estimated due date to avoid intrauterine fetal demise (IUFD). The pathophysiology of diabetes-associated IUFD is well documented in pregnant women with type 1 and type 2 diabetes, and is related to fetal hyperglycemia, hyperinsulinemia, and acidosis.10,11 In 1973, O’Sullivan et al12 observed that women with untreated GDM had a fourfold increase in stillbirth, which initiated the strategy of euglycemic treatment goals for women with GDM – similar to treatment of women with pregestational diabetes – using insulin therapy and induction of labor at or near term to avoid stillbirth. Since the 1980s, the ability to achieve normal glucose levels with self-monitoring of blood glucose and insulin therapy and the advent of weekly or bi-weekly antepartum fetal testing has reduced the diabetic stillbirth rate to rates near those in pregnancies of healthy women.13 Both of these management strategies developed concurrently, and largely without randomized trials, and both have become the standard of care in diabetic pregnancies.15

The most common antepartum fetal surveillance is the twice weekly nonstress test (NST) employing continuous external fetal heart rate monitoring coupled with evaluation of amniotic fluid volume (AFI), summing four quadrants of amniotic fluid measured by ultrasound. When such tests are equivocal, more complex tests such as the biophysical profile, contraction stress, or Doppler evaluation of the umbilical artery can be undertaken. When the fetal heart rate pattern during the NST demonstrates spontaneous accelerations, and moderate variability and absent decelerations, fetal hypoxia can be excluded. Conversely, when the fetal heart rate variability is moderate to absent, decelerations are present, or amniotic fluid volume is reduced, fetal hypoxia cannot be excluded.14 Women with mild GDM generally do not start testing until term (37–38 weeks); women requiring medical therapy or having other high risk factors, e.g., prior stillbirth or hypertension, begin testing at 32–34 weeks.15 Several large series1620following this strategy have demonstrated excellent perinatal outcomes with a low false-negative results, i.e., in-utero demise within days of a normal test. These strategies have also prompted delivery prior to the onset of labor when testing was nonreassuring or suspicious for fetal jeopardy in approximately 9–13% of tested pregnancies.17, 21 It is unlikely that randomized controlled trials will ever be done to validate the need for antepartum testing in women with GDM or diabetes. Such a trial would require an enormous cohort, as stillbirth is an extremely rare event, with one study reporting a rate 1.4 per 1,000 births in a tested population consisting primarily of GDM.17 Despite the lack of rigorous study, the widespread acceptance and excellent perinatal outcome associated with antepartum testing have established it as a de facto standard of practice.

The Fifth International Workshop Conference on GDM10 recognized that there was insufficient data to make evidence-based recommendations for intensive antepartum fetal monitoring, or whether any monitoring method was superior in women with GDM. They did endorse maternal self-monitoring of fetal movements, or “daily kick counts,” during the last 8–10 weeks of pregnancy, with any reduction in the perception of fetal movements requiring immediate medical evaluation. This recommendation was a change from the prior conference recommendations, which endorsed intensive antepartum surveillance.21 This change in view has come from the low stillbirth rates in women with GDM who meet glycemic targets with medical nutritional therapy and physical activity regimens alone, and in whom fetal growth is appropriate for gestational age. For women with more severe GDM, they recommended that the method and frequency of fetal surveillance should be guided by the severity of maternal hyperglycemia or the presence of other adverse risk factors.

Risk of respiratory distress syndrome and transient tachypnea of the newborn: Elective delivery in late preterm or early term infants, as previously advocated in diabetic women to reduce stillbirth risk, has been associated with an increase in both respiratory distress syndrome (RDS)22 and TTN. Delayed biochemical lung maturation in offspring of diabetic gestations23 has been associated with fetal hyperinsulinemia24 and hyperglycemia25 in clinical and animal studies.26,27 Fetal lung maturity can be determined by the measurement of surfactant in the amniotic fluid and has proved to be a useful adjunct in decreasing the risk of neonatal respiratory distress.2830 Current obstetrical practices, including accurate pregnancy dating, delaying delivery until term, and achieving euglycemic control have virtually eliminated neonatal respiratory distress (<1%) in the infant of the diabetic mother and makes any randomized controlled trial unlikely. In a historically controlled prospective trial, 1,585 term diabetic women (primarily with GDM) with reliable dating criteria were prospectively enrolled to undergo delivery without amniocentesis documentation of fetal lung maturation.31 In women with GDM, the incidence of RDS (0.8% vs. 0.8%) and TTN (1.3% vs.0.8%) was similar to rates in term historical controls that had undergone amniocentesis prior to delivery. Cesarean delivery was the only independent predictor of RDS (adjusted RR 2.21, 95% CI, 2.04–2.27). The Fifth International Workshop Conference on GDM did not recommend assessment of fetal lung maturation after 38 weeks of gestation in reliably dated and well-controlled patients; if delivery is indicated at an earlier gestational age for maternal or fetal indications, delivery should be effected without regard to lung maturity testing.10

Whenever possible, elective cesarean delivery in all pregnancies should be delayed until 39 completed weeks of gestation if possible.32 Cesarean delivery of infants delivered near term and early term, at gestational ages of 34, 35, 36, and 37 weeks was associated with progessively decreasing risk of requiring supplemental oxygen (ORs: 18.67, 8.76, 4.95, and 2.04 respectively) or ventilatory assistance (ORs 19.8, 9.04, 5.24, and 2.35 respectively) compared with cesarean deliveries at 38–40 weeks.33 Furthermore, in term infants there was an increase in risk for each week a cesarean delivery occurred before 39 completed weeks: the OR for RDS at 37 completed weeks compared with 38 completed weeks was 1.74; for 38 weeks compared with 39 weeks the OR was 2.4.34 Elective cesarean without labor compared with cesarean after labor was also associated with increased risk of RDS (35.5/10,000, vs. 12.2/1,000, OR 2.9). In another study, a randomized trial examining the administration of antenatal corticosteroids to normal term infants (37–41 weeks, n = 942) undergoing elective cesarean deliveries compared with placebo controls found a significant reduction in RDS (0.002% vs. 0.11%, RR 0.21) and TTN (0.021% vs. 0.041%, RR 0.54) with antenatal corticosteroids.35 The authors conclude that when considering an elective cesarean delivery at term, the increased risk of admission with respiratory distress should be considered and discussed with the mother. The 50% reduction in respiratory distress achieved by antenatal steroids is similar to delaying cesarean delivery until 39 completed weeks of gestation. These studies reinforce the American College of Obstetricians and Gynecologists (ACOG) recommendation to perform elective cesarean deliveries after 39 completed weeks in all women. Antenatal steroid therapy for threatened preterm labor is recommended before 34 completed weeks and should not be withheld from women with GDM.36 It is likely that increased glucose monitoring and additional or increased insulin therapy may be required during the 48-h course of therapy in more severe GDM.

Risk of shoulder dystocia and infant birth trauma. Shoulder dystocia is defined as the need for additional obstetrical maneuvers to effect delivery of the shoulders when gentle downward traction on the fetal head fails.37 The risk for shoulder dystocia increases with increasing birth weights in both diabetic and nondiabetic pregnancies. Nesbitt et al examined 1992 birth data from California by birth weight categories by diabetic (primarily GDM) and nondiabetic pregnancies and by spontaneous and operative vaginal deliveries.38 The rates of shoulder dystocia were higher in diabetic women compared with nondiabetic women for each 250 g increase in birth weight for spontaneous deliveries. For birth weights categories starting at 3,500, 3,750, 4,000, 4,250, 4,500, and 4,750 g the respective rates were 3.0, 5.8, 8.4, 12.3, 19.9, and 23.5%. These rates were further increased with operative vaginal deliveries: 4.0, 8.5, 12.2, 16.7, 27.3, and 34.8%, respectively. The increased risk of shoulder dystocia in infants of similar birth weights born to diabetic vs. nondiabetic mothers is likely related to the increased truncal obesity,39larger shoulder diameter40 in infants of diabetic mothers, and higher rates of maternal obesity.41Several studies have evaluated use of ultrasound prior to delivery to assist in the prediction of birth weight and shoulder dystocia. In order to assess whether ultrasound was possibly being more accurate than clinical estimates in obese diabetic women, Sacks42 reviewed the predictive ability of ultrasound examination to identify macrosomic birth weights (4,000–4,500 g). While studies demonstrated that 71–82% of expected fetal weights (EFWs) were within 10% of actual birth weights, the sensitivity (68–80%), specificity (78–96%), and negative predictive value (81–87%) were limited. Combining the ultrasound EFW (>4,000 g) with clinical risk factors for macrosomia and excess amniotic fluid volume may improve the weight prediction.43 Similarly studies have attempted to use various ultrasound methods to predict shoulder dystocia, all with limited accuracy.44 One recent and simple method found that positive difference (≥2.6 cm) between the abdominal diameter and biparietal diameter was associated with shoulder dystocia in almost 40% of diabetic women.45 Despite many studies, the occurrence of a shoulder dystocia remains an unpredictable emergency more common in diabetic women.40,46 The obstetrician and delivery staff should consider and be ready to institute a preplanned sequence of maneuvers to release the shoulder.

Birth trauma to the infant, e.g., fracture of the humerus or clavicle, brachial plexus palsy, or facial palsy is more likely to occur during a difficult delivery complicated by shoulder dystocia. Rates of 20–40% have been reported in series examining cases of shoulder dystocia women with diabetes. The most serious injury is brachial plexus injury, which occurs infrequently with shoulder dystocia, ranging from 4 to 13% percent.41, 44, 4749 Most cases of brachial plexus palsy resolve spontaneously in early infancy, and of the remaining 5–7%, three-quarters will achieve the restoration of upper arm function when surgical correction is undertaken within the first year of life.50Interestingly, large population surveys have found that only one quarter to almost one half of brachial palsy cases are associated with identified shoulder dystocias during delivery.5153 Brachial plexus injuries have also occurred with cesarean deliveries.54

Should cesarean delivery be offered to prevent shoulder dystocia when macrosomia is suspected in diabetic women? To date, there are no randomized controlled trials that compare trial of labor with primary cesarean delivery in diabetic women with estimated fetal weights (EFW) 4,000–4,500 g. ACOG does not recommend primary cesarean delivery unless the EFW >4,500 g in diabetic women40 while other published opinions select thresholds from 4,000 to 4,500 g.58,59 One controlled study evaluated a protocol of cesarean delivery for ultrasound EFW >4,250 g and labor induction for LGA growth (>90th percentile at 38 weeks).55 Following these guidelines, 11% of the diabetic population underwent cesarean section or induction for macrosomia, and the rate of shoulder dystocia was decreased significantly (1.5%) compared with historical controls 3 years earlier (2.8%). In a similar study, a 3-fold decrease in risk of shoulder dystocia supported the policy of offering cesarean delivery for diabetic women in whom the EFW was 4,250 g or more.56 This approach may lower perinatal morbidity at the expense of the mother whose risk of cesarean delivery increases at least twofold.57 - 59 The increased operative risk has persisted despite improved glycemic control and normalized growth of infants. One randomized controlled trial in women with diet-controlled GDM targeted pregnancies at high risk for LGA infants by abdominal circumference measurements ≥75th percentile for gestational age. Aggressive insulin therapy with lower glycemic targets compared with diet therapy alone was successful in reducing the LGA rate (13% vs. 45%) but resulted in a paradoxical increase in cesarean delivery (43% vs. 17%).60 Similarly in the Toronto Tri-Hospital study, women with identified and treated GDM were compared with women with blinded testing of glucose tolerance. Those with GDM had a twofold increased risk of cesarean delivery after adjustment for multiple risk factors.61 The women with treated GDM had a lower rate (10.5%) of macrosomia but a higher rate (34%) of cesarean delivery, compared with women with untreated borderline GDM, who had a 29% macrosomia rate with a 30% cesarean rate. Macrosomia was found to be a risk factor for cesarean delivery in the untreated borderline GDM group, but was found to have no impact on risk of cesarean delivery in women with known, treated GDM. The authors suggest that the diagnosis of GDM in and of itself may lower the obstetrician’s threshold for cesarean delivery.

15.4 Should Women with GDM be Managed Expectantly or Induced?

Currently there is no evidence-based guideline for timing and route of delivery to minimize both maternal and neonatal complications in GDM pregnancies. A single best strategy has proved elusive, in large part due to the many variables which must be considered, i.e., the fetal condition, estimated fetal weight, prior maternal history of macrosomia, shoulder dystocia, or cesarean delivery, severity and control of diabetes, coexisting disease, the estimated chance of successful labor induction, and the personal biases of both the woman and her doctor. While historical factors such as prior cesarean deliveries and prepregnancy weight are not modifiable after conception, many risk factors have been minimized by today’s obstetrical care, notably fetal overgrowth and risk of stillbirth. Logically, as these two factors are normalized, one should be able to allow pregnancies with GDM to await spontaneous labor.

In nondiabetic women with ultrasound EFW >4,000 g, randomization to induction vs. elective cesarean delivery reduced neither primary cesarean rates nor neonatal morbidity.62 The only randomized controlled trial in women with well-controlled insulin treated diabetes (93% with GDM) without evidence of macrosomia and in good control, evaluated the effect of expectant management vs. active labor induction on cesarean delivery and neonatal morbidity.63 Expectant management increased the gestational age of delivery by 1 week without a significant reduction in cesarean delivery (31% vs. 25%, respectively). However, all indices of fetal growth, whether birth weight, macrosomia or LGA infants, were significantly increased with expectant management. Even when gestational age at delivery and maternal weight were controlled the birth weight was significantly increased with expectant management, suggesting that a subset of infants continue to have accelerated growth in-utero, and further prolongation of gestation magnifies this growth. Almost half (49%) of those randomize to expectant management subsequently underwent delivery before spontaneous labor for either obstetrical or medical indications. The low threshold for intervention demonstrated by obstetricians in this study may be similar to the low threshold for cesarean delivery demonstrated in other studies.6164

A Cochrane database review of this topic64 concluded that the policy of induction of labor at 38 weeks of gestation in diabetic mothers treated with insulin was associated with the reduction in birth weight above 4,000 g and above the 90th percentile. That intervention did not increase risk of cesarean section and neonatal morbidity remained the same on the two groups. This suggested that there might be a little advantage in delaying delivery beyond 38–39 weeks and induction of labor might be a reasonable option, but more trials are necessary with a larger sample size to evaluate elective delivery in these women. The Fifth International Workshop Conference on GDM also noted that some studies suggest that delivery past 38 weeks can lead to an increase in the rate of LGA infants without reducing the rate of cesarean deliveries.10 They also state that there is no data supporting delivery prior to 38 weeks gestation in the absence of objective evidence of maternal or fetal compromise. Nor is there any data to indicate whether there is greater risk of perinatal morbidity/mortality in infants of women with well-controlled GDM if pregnancy is allowed to proceed past 40 weeks gestation. Increasingly, the best strategy to minimize both maternal and newborn morbidity appears to normalize maternal glucose and normalize fetal growth, avoiding LGA and disproportionate growth.

The risk of cesarean delivery: As discussed, women with GDM have an approximate twofold increased risk of cesarean delivery after adjusting for confounding factors including maternal age, body mass index, and birth weight.65,66 When practitioners are blinded to glucose results, both the Toronto Tri-Hospital65 and HAPO studies5 found a linear increased risk of cesarean delivery and increased birth weight or LGA rate with untreated increasing levels of glucose. In addition to the risk associated with GDM per se, these women often have other independent risk factors for cesarean delivery. A retrospective analysis of 5,735 women with gestational and pregestational diabetes found 11 independent predictors of cesarean delivery.67 Eight of these were not modifiable: prior cesarean delivery (RR 5.34), no prior live birth (RR 3.17), no prior vaginal delivery (RR 2.28), prior stillbirth (RR 1.71), maternal age ≥35 years (RR 1.53), requiring insulin during pregnancy (RR 1.53), highest fasting plasma glucose before therapy (RR 1.04), and preeclampsia/hypertension (RR 2.56). The remaining three were potentially modifiable: labor induction (RR 3.32), birth weight (RR 1.12 per 250g) and predelivery body mass index (BMI) (RR 1.03 per kg/m2). In summary, studies examining protocols to reduce cesarean delivery will need to address these multiple predictors to lower morbidity.

Obesity (BMI ≥30 kg/m2) is common in women with GDM and in and of itself markedly increases the maternal perinatal morbidity, i.e., the risk of cesarean delivery, anesthesia risk and time, wound infection and dehiscence, postpartum fever, postpartum hemorrhage and postpartum deep venous thrombophlebitis (DVT).68,69 No prospective trials evaluate how best to decrease these morbidities. Some authors recommend a vertical skin incision over a low transverse incision for better exposure, while others believe vertical incisions are more painful, have slower recovery, and a higher incidence of evisceration. One retrospective study examining postoperative complications in women with BMI >35 kg/m2 undergoing primary cesarean found a higher rate of wound complications (34.6% vs. 9.4%) with vertical vs. transverse skin incisions.70 Data is equally conflicting regarding the closure of the subcutaneous tissue or use of subcutaneous drains. One randomized controlled trial in obese women undergoing cesarean section found subcutaneous suture or drainage decreased the incidence of postoperative wound complications when subcutaneous tissue exceeded 2 cm.71 In contrast, the ACOG Committee Opinion suggesting subcutaneous closure may increase the risk of wound disruption.72 Lastly, postpartum obese women should receive DVT prophylaxis including early ambulation and compression stockings. The data is incomplete as to whether postoperative heparin therapy is appropriate for the obese parturient.

15.5 Summary

Over the last 30 years, technological and patient care developments, in glucose monitoring and insulin administration, ultrasound evaluation of fetal growth and weight, antepartum fetal surveillance, evaluation of fetal lung maturation, labor induction, and cesarean delivery have contributed to a reduction in perinatal morbidity for women with GDM and their newborns. As many of these factors developed simultaneously, e.g., improved glycemic control and antepartum surveillance, it is difficult to assess the independent contribution of each. The historical risks of stillbirth and RDS are now rare in pregnancies complicated by GDM, and increasingly permit spontaneous delivery at term. Today, it is possible to normalize maternal glucose levels through the use of self blood glucose monitoring, medical nutritional therapy and medical therapy. The best way to decrease risks of shoulder dystocia and cesarean delivery is to reduce the risk of LGA infants. New strategies, demonstrated in RCTs, use ultrasound to monitor fetal growth, to modify glycemic targets have been shown to significantly reduce LGA and SGA growth.73Similarly, new recommendations for maternal weight gain may reduce both the risk of GDM and LGA infants and maternal cesarean rates and postoperative complications. In the near future, new international diagnostic criteria5 for GDM will be based on maternal and newborn morbidity. New developments, and the continued push for evaluation of evidence-based care protocols will decrease obstetrical complications in women with GDM and their offspring.

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