Recently, it has been recognised that there is an increased rate of stillbirth in obese women. This association persists even after allowing for the confounding effects of diabetes and hypertension in obesity.
Obesity is a major medical problem and is becoming more prevalent. Indeed, obesity is now so common in the developed world that it is recognised as one of the most significant contributors to poor health. This recognition applies over all areas of health, including obstetrics. The Australian Bureau of Statistics found, in the period 2011–12, 63 per cent of Australians over the age of 18 were classified as overweight or obese. Obesity, including maternal obesity, is even more common in rural and remote regions compared to metropolitan areas. Some cultural groups, including Indigenous Australians, have higher rates of obesity than the population average.
It has long been recognised that obesity is a risk factor for adverse perinatal outcomes. The incidence of virtually all pregnancy complications is increased for both the obese mother and her fetus. Significant risks exist at each stage of pregnancy and also in the puerperium.1 It is established that maternal obesity is associated with increased rates of gestational diabetes, pre-eclampsia and large-for-dates infants, among other risks.
Obesity is a problem at all stages of reproduction, beginning with increased rates of infertility and subsequent higher spontaneous early and recurrent early miscarriages compared with women in the healthy weight range. In pregnancies achieved with the assistance of reproductive technologies, obese women have greater rates of pregnancy loss in the first six weeks than normal BMI controls (22 per cent versus 12 per cent; p= 0.03).2
In later pregnancy, numerous studies have demonstrated an increased incidence of antepartum stillbirth in obese women, even after excluding diabetic or hypertensive pregnancies. Sebire and colleagues studied 287 213 completed singleton pregnancies in London in 2001.3 Of these women, 176 923 were in the normal weight range (BMI 20 to 25), 79 014 had a BMI of 25 to 30, and 31 276 had a BMI greater than 30. After accounting for confounding factors, the risk of intrauterine death was 1.10 (99 per cent CI 0.94–1.28) in the overweight group, and 1.40 (99 per cent CI 1.14–1.71) in those with BMI greater than 30.
A meta-analysis by Chu and colleagues published in 2007 estimated the odds for a stillbirth were 1.47 (95 per cent CI 1.08–1.94) and 2.07 (95 per cent CI 1.59–2.74) higher in overweight (BMI 25–30) and obese (BMI >30) women, respectively, compared with normal weight (BMI 20–25) controls, again after allowing for maternal medical conditions during pregnancy.4 More recently, examining the obese group in more detail and breaking the BMI> 30 group into Class I (BMI 30–35), Class II (BMI 35–40), and Class III (BMI 40) has shown an increasing risk of stillbirth with increasing level of obesity.5 If pre-pregnancy obesity is also combined with excessive weight gain during pregnancy there is even higher risk of adverse pregnancy outcomes. When obese women have excessive gestational weight gain (using the Institute of Medicine criteria), there is a doubling of caesarean section rates compared to obese women who have normal gestational weight gain.6
It is essential that weight gain in pregnancy is monitored, although programs to control intra-pregnancy weight gain have shown limited success. A small Australian study was able to reduce gestational weight gain and gestational diabetes with relatively simple interventions7, although others have not been able to show success with similar programs.
While excessive intra-pregnancy weight gain is associated with increased adverse perinatal outcomes, weight gain between pregnancies has also been associated with increased risk. Villamor and Cnattingius investigated inter-pregnancy weight gain between the first and second pregnancy.8 Even modest BMI gains after the initial booking visit in the first pregnancy until the booking visit during the second pregnancy were associated with increased rates of adverse pregnancy outcomes. These risks were present even in women who were considered in a normal BMI group in both pregnancies.
Villamor and Cnattingius found the risks for pre-eclampsia, hypertension, gestational diabetes and large-for-gestational age infants started to rise with inter-pregnancy weight gains of between one and two BMI units, and continued to increase progressively thereafter. The odds of stillbirth were 63 per cent higher in women who had inter-pregnancy weight gain of three or more BMI units, compared to those who had inter-pregnancy weight gain of less than one BMI unit. This association remained after adjustment for other co-morbidities. When term (37 weeks and beyond) and preterm (before 37 weeks) stillbirths were examined separately, there was a significant linear association between increasing inter-pregnancy weight gain and term stillbirth, but this association was not noted for preterm stillbirth.
Even among obese populations it appears there may be women who are at even greater risk for stillbirth. Salihu found an increased risk of stillbirth in black obese women compared with white obese women.9 In both racial groups, the risk of stillbirth increased progressively with increasing BMI. However, at all levels of obesity there was a disparity in black-white comparison, with black women having increased risks of obesity-related stillbirth compared with white women. In contrast, a study from Auckland noted that while Pacific women had an overall increased risk of stillbirth compared with European women, there was no racial difference in stillbirth rates after adjusting for other confounders such as poverty.10
It is recognised that there is an increased rate of stillbirth in adolescent populations (<18 years), owing to a variety of health, socioeconomic and behavioural issues. However, the obese adolescent pregnant patient may be at even greater risk, with a recent study showing a relative risk stillbirth of 1.8 for obese (>30 BMI) adolescents when compared with normal and overweight adolescents.11
In multiple pregnancy, obesity is associated with higher rates of stillbirth, with the rates of both partial loss (one fetus) and complete loss (both fetuses) being elevated when compared to normal weight mothers with a twin gestation. The risks appear to be amplified in triplet gestations, with obese women (BMI >30) having a four-fold risk of stillbirth compared with normal weight mothers with triplets.12
The pathophysiological mechanisms leading to stillbirth in obese women are unclear. It is known that obesity increases the risk of gestational diabetes and hypertensive disorders, and these are established risks for stillbirth. However, most studies suggest the increase in stillbirth with obesity cannot be fully explained by these conditions. Several biological pathways have been suggested to explain the observed increase in stillbirth rates. Perinatal obesity may increase hyperlipidaemia, leading to reduced prostacyclin secretion and enhanced thromboxane production with resultant vasoconstriction, platelet aggregation and decreased placental perfusion. The addition of insulin resistance decreases fibrinolytic activity with possible increased rates of placental thrombosis and further decreased perfusion. Thus, the increased rate of stillbirth may result from feto-placental dysfunction with consequent impaired placental blood flow.4,5,13 Studies have also reported that obese pregnant women have more sleep-related disordered breathing episodes, including snoring, apnoea-hypoxia events and oxygen desaturation events, when compared to non-obese pregnant women.14 These respiratory changes may lead to increased pregnancy-related hypertensive disorders, fetal growth restriction and fetal loss.
It has been proposed that a proportion of the increased risk of adverse perinatal outcomes in obese women relates to a lack of perception of reductions in fetal movements and consequent delayed attendance for monitoring.4 The association of maternal obesity with stillbirth may also reflect differences in socioeconomic status; and quality, availability and uptake of antenatal care between obese and non-obese women. All investigations, including cardiotocography (CTG) and ultrasound, are technically more difficult and potentially more difficult to interpret in obese mothers. These difficulties, combined with a reluctance to induce labour in morbidly obese women owing to known high failure rate, may lead to hesitation in attempting to deliver women, thus increasing the risk of late stillbirth.
In view of the association between obesity and stillbirth, it is clear the most important intervention for these women is weight loss prior to becoming pregnant. Limiting intra-pregnancy and inter-pregnancy weight gain is also of paramount importance. Unfortunately, for many people, traditional weight-loss programs with alteration of diet and increased exercise frequently fail. Bariatric surgery, in appropriately counselled patients, has been shown to be effective in weight loss and subsequent reduction of medical morbidity.15 However, in Australia, bariatric surgery is largely confined to metropolitan areas and the private sector. Many patients are geographically and financially unable to access this treatment.
In our specialty, obstetricians will appreciate the opportunity for pre-pregnancy counselling of obese patients and early referral once pregnant. Obstetricians will be even more grateful if our fertility colleagues do not use assisted reproductive technology in obese patients. The obese patients who present in pregnancy should be strongly encouraged and supported to adhere to the Institute of Medicine guidelines for weight gain in pregnancy.
Acknowledgment of the increased stillbirth risk will lead to a greater level of vigilance, an appropriate level of obstetric care and increased fetal monitoring in the third trimester. What this increased monitoring should entail is not universally agreed upon. One group has suggested starting CTG monitoring at 32–34 weeks and serial fetal growth assessments by ultrasound in the third trimester.16 Although such an approach seems intuitive, there is no evidence, as yet, to support such a policy.
Given that one suggested pathophysiological mechanism of stillbirth involves early feto-placental dysfunction, there is a role for research into early intervention in this group of women. Should all obese pregnant women be treated with low-dose aspirin? Another possible cause relates to increased sleep apnoea: do all morbidly obese women need sleep studies and possibly CPAP? Should all pregnant women with BMI of greater than 40 be delivered electively by caesarean section at 39 weeks if they have not laboured prior to this? There are many unresolved questions.
Stillbirth is a tragic occurrence and the association of stillbirth with obesity is a further reason that we need to urgently address the epidemic of overweight and obesity in our society. Obesity is a complex area with multiple contributing causes for each individual and many causative factors in our communities from food production, packaging and advertising, through to issues such as the physical layout of our towns, schools and workplaces. Significant reductions in obesity rates, leading to better outcomes in all areas of medicine including obstetrics, will ultimately require major societal change.