In this study we demonstrate that maternal prepregnancy overweight, obesity, and severe obesity are linked to increased risk for many adverse pregnancy outcomes. It is well known that overweight, obesity, and severe obesity increase morbidity for both mother and neonate and are associated with a variety of adverse pregnancy outcomes.
Gestational diabetes mellitus is characterized by insulin resistance and inadequate insulin secretion, resulting in hyperglycemia. Obese women are more insulin resistant than normal-weight women and the risk for gestational diabetes mellitus is positively associated with obesity in pregnancy, with one study reporting the OR of developing GDM to be 2.6 for obese women and 4.0 for morbidly obese women, respectively.6 Nohr et al reported an increased risk for GDM in overweight women of 1.7 times, and 5.1 in obese women.7,8 Chu et al included 20 studies in a meta-analysis and found that the risk of developing GDM was increased 3.6 times in obese compared with normal-weight women, and 8.6 times in the severely obese.9 This is in line with our findings for GDM with an increased risk of 3.5 in overweight women, 7.7 in obese women, and 11.0 in severely obese women.
Preeclampsia complicates 3–5% of all pregnancies and obesity is a consistent risk factor for preeclampsia, approximately three times higher than in normal-weight women,6–8,10,11 but the mechanisms involved are not known. In an overview of 13 cohort studies including nearly 1.4 million women, O'Brien et al observed a consistent and linear rise in the risk for preeclampsia with increasing prepregnancy BMI. The risk of preeclampsia doubled with each 5–7-point increase in BMI.12 Both obesity and preeclampsia are associated with increased markers of inflammation such as C-reactive protein and inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and interleukin-8. These shared features suggest that obesity is a risk factor for preeclampsia because of preexisting inflammation.13
Preeclampsia is more common in obese women with GDM than in women without GDM. The coexistence of these two metabolic disorders suggests a similar underlying mechanism. In a recent publication from Ireland, the risk of preeclampsia increased from 2.7% in normal-weight women to 6% in obese, glucose-tolerant women.14 Furthermore, tight glucose control in women with GDM reduces the risk for preeclampsia.15,16 In our study we controlled for GDM and still found an increased risk for preeclampsia of 1.9 in the overweight group, 3.0 in the obese group, and 4.4 in the severely obese group.
Maternal obesity is associated with a significantly increased risk of thrombosis during both the antenatal and postnatal periods. A case–control study in Denmark, including 129 women with deep vein thrombosis or pulmonary embolism during pregnancy or the puerperium and 258 controls showed a significant association between BMI 30 or higher and venous thrombosis (OR 5.3).17 As both immobility and obesity are associated with thrombosis, the combination increases the risk considerably. This interaction has been demonstrated by a large case–control study that reported an OR of 62.3 for antenatal venous thrombosis and 40.1 for postnatal thrombosis in women with a BMI 25 or higher where there was evidence of immobilization, compared with women with a BMI less than 25 and no immobilization.18 We found that the risk of thrombosis was increased only in the overweight women (OR 1.6), but not in the obese or severely obese women. An explanation for this difference could be that in Denmark all obese women who are immobilized during pregnancy or after cesarean delivery are treated with prophylactic anticoagulation.
The risk of cesarean delivery and associated morbidities are increased in obese women. In a Danish study, the proportion of cesarean delivery increased from 14.7% in normal-weight women to 22% in obese women (OR 2.7),11 whereas in an American population the figures were 21.3% (BMI 20–25), 32.6% in obese (BMI 30–35), 36.9% in very obese (BMI 35–40), and 45.2% in extremely obese women (BMI more than 40).19
A meta-analysis performed by Chu et al in 2007 estimated that the risk of having a cesarean delivery was approximately two and three times higher among obese and severely obese women, respectively, compared with women of normal weight. In addition, the majority of these deliveries were performed during the first stage of labor and based on indications of dystocia and fetal distress.20 Our study showed that the ORs of planned cesarean delivery were 1.2 in the overweight women, 1.3 in the obese women, and 1.4 in the severely obese women. The ORs for emergency cesarean delivery were 1.4, 1.7, and 2.1, respectively. The reason for this increased rate of cesarean delivery in obese women is unknown but could be related to increased maternal pelvic soft tissue, fetal macrosomia, and intrapartum complications (eg, inability to adequately monitor the fetus and contractions).21 In a recent review including 11 papers, cesarean delivery risk was increased by 50% in overweight women and was more than doubled for obese women compared with women with normal BMI.22 Obese women undergoing cesarean delivery experience more complications, including blood loss more than 1,000 mL, increased operative time, increased postoperative wound infection, and endometritis.23–26
Raised BMI is a reported risk factor for postpartum hemorrhage. In a large study from the United Kingdom, the risk of postpartum hemorrhage rose with increasing BMI, with an OR of 1.16 in the overweight group and 1.39 in the obese group.27 In a Swedish study, the risk for postpartum hemorrhage also increased with high BMI.10 In a recent meta-analysis it was concluded that overweight, obese, and morbidly obese pregnant women had significantly increased risk of hemorrhage compared with normal-weight women, with an overall OR of 1.24.28
This is in contrast with our findings, as we found no increased risk in any of the overweight or obese groups. In the U.K. study, the percentage of hemorrhage was 10.4% in the normal-weight group, 13.2% in the overweight group, and 17.1% in the obese group.27 In the Swedish study, the percentages were 5.7% in the control group, 6.0% in the obese group (BMI 29–35), 5.2% in the severely obese group (BMI 35–40),and 5.5% in the morbidly obese women (BMI more than 40).10 The Swedish figures are more in line with our results, with 6.4% having more than 500 mL bleeding postpartum in the normal-weight women, and 6.7% in the overweight, 6.5% in the obese, and 6.6% in the severely obese women. A well-known problem is different definitions of postpartum hemorrhage. Neither the U.K. study nor the Swedish study had any definition of postpartum hemorrhage; furthermore, it is well known that it is clinically difficult to accurately estimate blood loss, particularly in obstetric scenarios. In Denmark, blood loss considered to be less than 500 mL is usually measured by clinical judgment only, whereas greater blood loss is usually measured by weighing pads, linen, and so forth. Whereas small amounts of blood loss may be underestimated,29 greater blood loss most likely would tend to be more precise. Still, the misclassification would be expected to be independent of BMI, and hence would cause bias toward the null.
Maternal obesity is a well-known risk factor for fetal macrosomia. Owens et al found that the percentage of macrosomic neonates (more than 4,000 g) to increased from 15.5% to 21.4% to 27.8% in normal-weight, overweight, and obese women, respectively.14 In the studies by Sebire et al27 and Nohr et al,8 the risk of neonates who were large for gestational age (LGA) was increased by a factor 2.3. Sewell et al demonstrates that obese women with normal glucose tolerance had neonates who were heavier than those born to normal-weight women because of increased fat mass, not lean body mass.30
Maternal diabetes is also a well-known risk factor for macrosomia. Ehrenberg et al examined the relative contribution of obesity and diabetes for the prevalence of LGA neonates (more than 90 percentile) at birth, and found that pregestational diabetes had a greater effect on the frequency of LGA than did maternal obesity (OR 4.4 and 1.6, respectively). Nevertheless, more LGA neonates are born to obese women than to women with diabetes, because maternal obesity is much more prevalent than diabetes (46.7% compared with 4.1%).31 Several countries have reported an increase in mean birth weight over the past decade and an increase in the proportion of macrosomic neonates. In Denmark, the percentage of neonates born with birth weights higher than 4,000 g increased from 16.7% in 1990 to 20.0% in 1999.32 One explanation for this increase could be the increase in maternal BMI over the same period. Our study is in accordance with these studies as we report increased macrosomia (birth weight more than 4,500g) with increasing maternal BMI, also when we adjusted for GDM.
Although relatively rare, shoulder dystocia is a feared complication, which in a Swedish study increased from 0.1% to 0.3% (OR 2.14) in the normal-weight mothers compared with the obese mothers.10 Usha Kiran et al reported an increase from 0.5% in overweight women to 1.5% in obese women (OR 2.9).33 On the other hand, Jensen et al did not find an increased risk for shoulder dystocia in obese mothers.11 In our study, the crude percentage of shoulder dystocia was 1.1 in the overweight group, 1.4% in the obese group, and 1.7% in the severely obese women, and hence the risk was significantly increased in the unadjusted calculation. However, in the adjusted analyses the significance disappeared. The increased use of ultrasonography to detect macrosomia and interventions such as induction of labor or cesarean delivery could explain a decrease in this complication.
Sebire et al reported increased risk of low Apgar score for overweight and obese women.27 Also, Nohr et al observes that neonates born to obese women had a higher risk of low Apgar score.8 Likewise, we found an increasing risk of low Apgar with increasing BMI.
Two Danish studies showed that the risk for stillbirth among obese women was significantly higher compared with normal-weight women. In a study of 24,505 singleton pregnancies, the overall rate of stillbirth was 4.6 per 1,000 deliveries. Compared with women of normal weight, the relative risk of stillbirth in obese women was nearly tripled (OR 2.8).34 In another study of 54,505 pregnancies, the risk of stillbirth was 2.8 per 1,000. The risk for stillbirth among obese women was significantly higher as gestational age advanced (weeks 28–36: OR 2.1; weeks 37–39: OR 3.5; weeks 40 and more: OR 4.6). Furthermore, obesity was associated with a five-fold increase in risk of stillbirth with placental dysfunction.35 Chu et al included nine studies in a meta-analysis and found the OR of stillbirth to be 2.07 among obese pregnant women compared with normal-weight pregnant women.36 These figures are in accordance with our observation of increasing risk for stillbirth with increasing maternal obesity.
Our study has several strengths: first, the magnitude of participants, covering a nationwide population. We included 369,347 participants, which to our knowledge is the largest study to date. The large number allowed for detailed risk assessments, including rare complications such as thrombosis (0.06% in this study), stillbirth (0.3%), low Apgar (0.6%), and shoulder dystocia (0.97%). An additional strength of the present study includes the completeness of data and avoidance of selection bias because of the nationwide nature of the study. The population in Denmark is relatively homogeneous (more than 90% white), leaving less room for confounding, and all citizens have free access to health services on an equal term. We excluded participants with obviously incorrect data. These cases constituted only 0.9% of the total population, thus, they are unlikely to have had a significant effect on the conclusions.
A limitation of this study is that we relied on self-reported prepregnancy BMI at the first antenatal visit. Overweight and obese women may have underreported their weight,37 but this report would most likely be independent of subsequent adverse outcomes, and hence lead to nondifferential misclassification, that is, bias risks toward the null. Considering that we found mostly increased risk of many adverse outcomes, the true risks would be even greater.
This study shows a significant increased risk of a wide variety of pregnancy, birth, and neonatal complications in overweight and obese women, which confirms and extends the results of most other studies. Obesity in pregnancy has disadvantages for the mother, fetus, and newborn. Moreover, maternal obesity is responsible for increased obesity in offspring, thereby possibly inducing a trans-generational effect. As the obesity epidemic also affects women of child-bearing age, it is of vital importance to address prepregnancy care and weight-management programs to prevent this increase and consequently reduce obesity among future generations.
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© 2011 by The American College of Obstetricians and Gynecologists.
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