Effect of Prepregnancy Maternal Overweight and Obesity on Pregnancy Outcome

Per Ovesen,
MD, DMSc,

Steen Rasmussen, and Ulrik Kesmodel,

MD, PhD

OBJECTIVE: To estimate the association between maternal overweight and obesity on complications during pregnancy and delivery in Denmark. METHODS: A population-based study on a cohort consisting of all Danish women giving birth to a singleton from 2004 through June 30, 2010 (N403,092) was undertaken. Women were identified from the Danish Medical Birth Registry, which contains data on 99.8% of all deliveries in Denmark. Maternal complications during pregnancy and delivery and fetal complications were classified according to the International Classification of Diseases, 10th Revision. RESULTS: The final study population consisted of 369,347 women, 20.9% being overweight (body mass index [BMI] 2529.9), 7.7% obese (BMI 30 35), and 4% severely obese (BMI higher than 35). Overweight, obese, and severely obese women had more complications than did normal weight women. Adjusted odds ratios (ORs) were significantly increased as follows: for gestational diabetes mellitus, 3.5, 7.7, and 11.0 for each BMI category; for preeclampsia 1.9, 3, and 4.4. Planned and especially emergency cesarean delivery was significantly increased with increasing BMI (OR ranging from 1.2 to 2.1). The risk of giving birth to a macrosomic neonate (greater than 4,500 g) increased significantly with increasing BMI (1.6, 2.2, and 2.7), as did the risks of having a neonate with a low Apgar score (1.3, 1.4, and 1.9) and having a stillborn fetus (1.4, 1.6, and 1.9). For shoulder dystocia the risk was significantly increased in the unadjusted analysis, but the significance disappeared in the adjusted analysis. No statistically significance was seen for hemorrhage and thrombosis.
From the Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark; and the Department of Health Statistics, National Board of Health, Copenhagen, Denmark. Corresponding author: Per Ovesen, MD, Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby, 8200 Aarhus N, Denmark; e-mail: Per.Ovesen@dadlnet.dk. Financial Disclosure The authors did not report any potential conflicts of interest. 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/11

CONCLUSION: This study shows a significant increased risk of a wide variety of pregnancy, birth, and neonatal complications in overweight, obese, and severely obese women.
(Obstet Gynecol 2011;118:30512) DOI: 10.1097/AOG.0b013e3182245d49

LEVEL OF EVIDENCE: II

orldwide there has been a dramatic increase in the prevalence of overweight (body mass index [BMI, calculated as weight (kg)/[height (m)]2] 25 and higher) and obesity (BMI 30 and higher) in women of child-bearing age. In the United States, 34% of women aged 20 to 39 years are obese and 59.5% are classified as overweight or obese.1 In Denmark, the percentage of overweight or obese women has increased from 22.1% in 1987 to 39.4% in 2001. For obesity the figures were 5.4% to 12.5%. The increase was particularly among young adults.2 Obesity is a known risk factor for many health problems, including type 2 diabetes mellitus, hypertension, coronary heart disease, and stroke.3 In addition to these problems, obese women have higher risk of complications during pregnancy and delivery. Furthermore, their obesity may have adversely affected the health of their offspring.4 To estimate the association between overweight and obesity on complications during pregnancy and delivery, we performed a population-based study on a cohort consisting of all Danish women giving birth to a singleton from 2004 through June 30, 2010. This very large data set allows us to improve precision in effect size and to include rare complications of pregnancy and delivery.

MATERIALS AND METHODS

The cohort consisted of all Danish women carrying and giving birth to a singleton from January 1, 2004, through June 30, 2010 (N403,092). Women were identified from the Danish Medical Birth Registry in which all deliveries in Denmark have been registered

VOL. 118, NO. 2, PART 1, AUGUST 2011

OBSTETRICS & GYNECOLOGY

305

since 1973. The database contains data on 99.8% of all deliveries in Denmark with a population of more than 5 million. The quality of the data has been found to be valid and reliable.5 Four women and their children were excluded because of double entry into the registry. Participants with obviously incorrect data registrations (BMI less than 10 or BMI more than 60: n267; or birth weight plus or minus 4 standard deviations: n3,410) were excluded. Data on BMI were missing for 30,064. In total, we excluded 33,745 participants (8.4% of the population). The final study population consisted of 369,347 women. Data in the Danish Medical Birth Registry are entered at birth by the midwife assisting at the delivery. For this study we used information on maternal characteristics including BMI, age, parity and smoking habits. Body mass index was calculated from self-reported prepregnancy weight and height (weight in kilograms divided by the square of height in meters) obtained during the first antenatal visit, and the participants were categorized according to maternal BMI. Underweight was defined as BMI less than 18.5, normal weight as BMI 18.524.9, overweight as BMI 2529.9, obesity BMI 30 34.9, and severe obesity as BMI 35 or higher. Parity was categorized as 0, 1, or 2 or more deliveries, and smoking as no smoking, 110 cigarettes per day, or more than 10 cigarettes per day. Maternal complications during pregnancy and delivery and fetal complications were classified according to the International Classification of Diseases 10th Revision. We identified pregnancies with a diagnosis of gestational diabetes mellitus (GDM) (O24.4), preeclampsia (O14), thrombosis (O871), or shoulder dystocia (O66). Hemorrhage was defined as more than 500 mL of postpartum hemorrhage (O72). Low Apgar score was defined as a score less than 7 at 5 minutes after birth. Stillbirth was defined as intrauterine death occurring after 22 completed weeks of

gestation (O364). Birth weight was measured and recorded at birth to the nearest 10 g. Cesarean delivery included all codes for this procedure (KMCA10AKMCA10E). The frequencies of the various outcomes of pregnancy were calculated within maternal BMI groups and multiple logistic regression models were constructed to examine the magnitude and significance of the independent effect of BMI. Risks are presented as unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals. Test for trend was evaluated by the Cochran-Armitage test for trend. Shoulder dystocia was analyzed only among vaginal deliveries. Analyses of all outcomes: GDM, preeclampsia, thrombosis, hemorrhage, shoulder dystocia, planned and emergency cesarean delivery, low Apgar score, stillbirth, and high birth weight more than 4,500 g were adjusted for maternal age, parity, smoking during pregnancy, gestational age, birth weight, GDM, sex of the fetus, and calendar year, except that analysis of high birth weight was not adjusted for birth weight, and analysis of GDM was not adjusted for GDM and birth weight. All analyses were performed in SAS 9 for Windows. The study was approved by the Danish Data Protection Agency.

RESULTS
Table 1 shows the maternal characteristics. The distribution of prepregnancy BMI for the 369,347 participants classified 15,776 as underweight (4.3%), 233,160 as normal weight (63.1%), 77,250 as overweight (20.9%), 28,492 as obese (7.7%), and 14,669 as severely obese (4%). Tables 2 and 3 show the unadjusted and adjusted risks of different obstetric and neonatal outcomes in the different BMI groups. The risk of gestational diabetes mellitus and preeclampsia were both considerably increased in the overweight and obese women compared with normal-weight women, whereas

Table 1. Maternal Characteristics in 369,347 Danish Women Giving Birth to a Singleton From 2004 to 2010
Prepregnancy BMI (kg/m2)
Maternal age (y) Primipara Prepregnancy BMI Smoking Smoking 10 or fewer cigarettes/d Smoking more than 10 cigarettes/d Duration of pregnancy (d) Birth weight (g)
BMI, body mass index. Data are meanstandard deviation or %.

Less than 18.5

29.25.2 49.0 4.3 20.2 13.3 6.9 276.213 3,289542

18.524
30.84.7 46.3 63.1 10.8 7.6 3.2 278.413 3,499542

2529
30.84.8 40.7 20.9 12.8 8.6 4.2 278.613 3,590567

3034
30.65.0 38.5 7.7 14.9 9.2 5.7 278.214 3,616595

35 and Higher
30.54.9 37.9 4.0 16 9.3 6.7 277.714 3,651622

306

Ovesen et al

BMI and Pregnancy Outcome in Danish Women

OBSTETRICS & GYNECOLOGY

thrombosis appeared to be increased only in the overweight women (Tables 2 and 3). Planned and especially emergency cesarean delivery were increased with increasing BMI, and hemorrhage was unaffected by BMI (Tables 2 and 3). Dividing the risk of hemorrhage into vaginal birth and cesarean delivery did not alter the conclusion (data not shown). The risk of giving birth to a macrosomic noenate (more than 4,500 g) increased with increasing BMI, as did the risks of having a neonate with a low Apgar score or a stillborn fetus (Tables 2 and 3). In the unadjusted analyses, the risk of shoulder dystocia was significantly increased in the overweight, obese, and severely obese women (Table 4), but in the adjusted analyses the association disappeared (Table 5). Adjustment for each of the covariates individually did not substantially change the significant estimates of the unadjusted analysis of shoulder dystocia, suggesting that the lack of association when adjusting for all covariates cannot be explained by a single factor but rather the interaction between several factors. All tests for trends, except for hemorrhage (P.06) and thrombosis (P.07), were significant, suggesting generally increasing risk with increasing BMI.

DISCUSSION
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 35% 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, OBrien et al observed a consistent and linear rise in the risk for preeclampsia with increasing prepregnancy BMI. The risk of preeclampsia doubled with each 57-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-, 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

VOL. 118, NO. 2, PART 1, AUGUST 2011

Ovesen et al

BMI and Pregnancy Outcome in Danish Women

307

Table 2. Unadjusted Association Between Maternal Body Mass Index and Adverse Pregnancy Outcomes
Birth Weight More Than 4,500 g* N Maternal BMI (kg/m2) Less than 18.5 18.524 2529 3034 35 and higher n OR 95% CI n Hemorrhage OR 95% CI n GDM OR 95% CI n Thrombosis OR 95% CI

15,776 233,160 77,250 28,492 14,669 369,347

125 5,697 3,160 1,489 940

0.32 1 1.70 2.20 2.73

0.270.38 1.631.78 2.082.33 2.552.94 P.001

989 15,019 5,182 1,840 968

0.97 1 1.04 1.00 1.02

0.911.04 1.011.08 0.951.05 0.961.10 P.06

116 2,185 2,423 1,898 1,363

0.78 1 3.42 7.54 10.83

0.650.95 3.233.63 7.098.03 10.1011.61 P.001

5 131 69 16 8

0.56 0.231.38 1 1.59 1.192.13 1.00 0.601.68 0.97 0.481.98 P.071

GDM, gestational diabetes mellitus; OR, odds ratio; CI, confidence interval; BMI, body mass index. * Comparison group: weight 3,000 3,999 g. Comparison group: no hemorrhage. Comparison group: no GDM. Comparison group: no thrombosis. Comparison group: no cesarean delivery. Comparison group: no preeclampsia. # Comparison group: Apgar score 710. ** Comparison group: no stillbirth. P for trend.

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.2326

Table 3. Adjusted Association Between Maternal Body Mass Index and Adverse Pregnancy Outcomes
Birth Weight More Than 4,500 g* N Maternal BMI (kg/m2) Less than 18.5 18.524 2529 3034 35 and higher n OR 95% CI n Hemorrhage OR 95% CI n GDM OR 95% CI n Thrombosis OR 95% CI

15,776 233,160 77,250 28,492 14,669 369,347

125 5,697 3,160 1,489 940

0.41 1 1.62 2.15 2.74

0.340.48 1.551.69 2.032.29 2.552.95

989 15,019 5,182 1,840 968

1.08 1 1.03 0.98 0.98

1.011.16 0.991.06 0.931.03 0.921.05

116 2,185 2,423 1,898 1,363

0.83 1 3.46 7.67 11.01

0.691.00 3.273.68 7.208.18 10.2511.82

5 131 69 16 8

0.58 1 1.59 0.97 0.91

0.241.43 1.182.13 0.571.64 0.441.87

GDM, gestational diabetes mellitus; OR, odds ratio; CI, confidence interval; BMI, body mass index. * Comparison group: weight 3,000 3,999 g. Comparison group: no hemorrhage. Comparison group: no GDM. Comparison group: no thrombosis. Comparison group: no cesarean delivery. Comparison group: no preeclampsia. # Comparison group: Apgar score 710. ** Comparison group: no stillbirth.

308

Ovesen et al

BMI and Pregnancy Outcome in Danish Women

OBSTETRICS & GYNECOLOGY

Table 2. Unadjusted Association Between Maternal Body Mass Index and Adverse Pregnancy Outcomes
Planned Cesarean Delivery n OR 95% CI Emergency Cesarean Delivery n OR 95% CI n Preeclampsia OR 95% CI Apgar 5 Less Than 7# n OR 95% CI n Stillbirth** OR 95% CI

1,273 19,749 7,937 3,378 1,996

0.95 1 1.24 1.45 1.70

0.991.01 1.201.27 1.401.51 1.621.79 P.001

1,275 22,974 9,672 4,180 2,529

0.80 1 1.31 1.57 1.91

0.760.85 1.281.34 1.521.63 1.821.99 P.001

308 7,217 3,921 2,184 1,561

0.62 0.560.70 1 1.67 1.611.74 2.60 2.472.73 3.73 3.523.95 P.001

79 1,254 523 207 153

0.93 0.741.17 1 1.26 1.141.40 1.35 1.171.57 1.95 1.652.30 P.001

44 589 277 121 82

1.10 0.811.50 1 1.42 1.231.64 1.68 1.382.01 2.22 1.762.80 P.001

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 metaanalysis it was concluded that overweight, obese, and morbidly obese pregnant women had significantly increased risk of hemorrhage compared with normalweight 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

Table 3. Adjusted Association Between Maternal Body Mass Index and Adverse Pregnancy Outcomes
Planned Cesarean Delivery n OR 95% CI Emergency Cesarean Delivery n OR 95% CI n Preeclampsia OR 95% CI Apgar 5 Less Than 7# n OR 95% CI n Stillbirth** OR 95% CI

1,273 19,749 7,937 3,378 1,996

1.06 1 1.16 1.29 1.44

0.991.12 1.121.19 1.241.34 1.371.52

1,275 22,974 9,672 4,180 2,529

0.81 1 1.41 1.73 2.11

0.770.86 1.371.44 1.671.80 2.012.21

308 7,217 3,921 2,184 1,561

0.58 1 1.87 3.01 4.44

0.520.65 1.791.95 2.863.17 4.174.72

79 1,254 523 207 153

0.82 1 1.32 1.41 1.94

0.651.04 1.191.47 1.221.64 1.632.32

44 589 277 121 82

0.75 1 1.39 1.60 1.86

0.531.06 1.181.65 1.272.01 1.392.47

VOL. 118, NO. 2, PART 1, AUGUST 2011

Ovesen et al

BMI and Pregnancy Outcome in Danish Women

309

Table 4. Unadjusted Association Between Maternal Body Mass Index and Shoulder Dystocia (Vaginal Delivery)
Shoulder Dystocia* N n OR 95% CI

Maternal BMI (kg/m2) Less than 18.5 13,228 91 18.524 190,437 1,625 2529 59,641 679 3034 20,934 283 35 or higher 10,144 174 294,384

0.81 0.651.00 1 1.33 1.221.46 1.59 1.401.80 2.03 1.732.37 P.001

OR, odds ratio; CI, confidence interval; BMI, body mass index. * Comparison group: no shoulder dystocia. P for trend.

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 normalweight, 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 Table 5. Adjusted Association Between Maternal Body Mass Index and Shoulder Dystocia (Vaginal Delivery)
Shoulder Dystocia* N
Maternal BMI (kg/m2) Less than 18.5 18.524 2529 3034 35 or higher 13,228 190,437 59,641 20,934 10,144 294,384

n
91 1,625 679 283 174

OR
1.39 1 1.02 1.06 1.16

95% CI
1.121.72 0.931.12 0.931.20 0.981.37

OR, odds ratio; CI, confidence interval; BMI, body mass index. * Comparison group: no shoulder dystocia.

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 normalweight 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 3739: OR 3.5; weeks 40 and more: OR 4.6).

310

Ovesen et al

BMI and Pregnancy Outcome in Danish Women

OBSTETRICS & GYNECOLOGY

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 metaanalysis 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. REFERENCES
1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999 2008. JAMA 2010;303:235 41.

2. Bendixen H, Holst C, Sorensen TI, Raben A, Bartels EM, Astrup A. Major increase in prevalence of overweight and obesity between 1987 and 2001 among Danish adults. Obes Res 2004;12:1464 72. 3. Visscher TL, Seidell JC. The public health impact of obesity. Annu Rev Public Health 2001;22:35575. 4. Catalano PM. Obesity and pregnancythe propagation of a viscous cycle? J Clin Endocrinol Metab 2003;88:3505 6. 5. Knudsen LB, Olsen J. The Danish Medical Birth Registry. Dan Med Bull 1998;45:320 3. 6. Weiss JL, Malone FD, Emig D, Ball RH, Nyberg DA, Comstock CH, et al. Obesity, obstetric complications and cesarean delivery ratea population-based screening study. Am J Obstet Gynecol 2004;190:10917. 7. Nohr EA, Vaeth M, Baker JL, Sorensen TI, Olsen J, Rasmussen KM. Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy. Am J Clin Nutr 2008;87:1750 9. 8. Nohr EA, Timpson NJ, Andersen CS, Davey Smith G, Olsen J, Sorensen TI. Severe obesity in young women and reproductive health: the Danish National Birth Cohort. PLoS One 2009;4:e8444. 9. Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, et al. Maternal obesity and risk of gestational diabetes mellitus. Diabetes Care 2007;30:2070 6. 10. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol 2004;103:219 24. 11. Jensen DM, Damm P, Sorensen B, Molsted-Pedersen L, Westergaard JG, Ovesen P, et al. Pregnancy outcome and prepregnancy body mass index in 2459 glucose-tolerant danish women. Am J Obstet Gynecol 2003;189:239 44. 12. OBrien TE, Ray JG, Chan WS. Maternal body mass index and the risk of preeclampsia: a systematic overview. Epidemiology 2003;14:368 74. 13. Walsh SW. Obesity: a risk factor for preeclampsia. Trends Endocrinol Metab 2007;18:36570. 14. Owens LA, OSullivan EP, Kirwan B, Avalos G, Gaffney G, Dunne F, et al. ATLANTIC DIP: The impact of obesity on pregnancy outcome in glucose-tolerant women. Diabetes Care 2010;33:5779. 15. Catalano PM. Management of obesity in pregnancy. Obstet Gynecol 2007;109(2 pt 1):419 33. 16. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477 86. 17. Larsen TB, Sorensen HT, Gislum M, Johnsen SP. Maternal smoking, obesity, and risk of venous thromboembolism during pregnancy and the puerperium: a population-based nested case-control study. Thromb Res 2007;120:5059. 18. Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008;6:90512. 19. Chu SY, Bachman DJ, Callaghan WM, Whitlock EP, Dietz PM, Berg CJ, et al. Association between obesity during pregnancy and increased use of health care. N Engl J Med 2008;358:144453. 20. Chu SY, Kim SY, Schmid CH, Dietz PM, Callaghan WM, Lau J, et al. Maternal obesity and risk of cesarean delivery: a meta-analysis. Obes Rev 2007;8:38594. 21. Brown K, Apuzzio J, Weiss G. Maternal obesity and associated reproductive consequences. Womens Health (Lond Engl) 2010;6:197203.

VOL. 118, NO. 2, PART 1, AUGUST 2011

Ovesen et al

BMI and Pregnancy Outcome in Danish Women

311

22. Poobalan AS, Aucott LS, Gurung T, Smith WC, Bhattacharya S. Obesity as an independent risk factor for elective and emergency caesarean delivery in nulliparous womensystematic review and meta-analysis of cohort studies. Obes Rev 2009;10: 28 35. 23. Perlow JH, Morgan MA. Massive maternal obesity and perioperative cesarean morbidity. Am J Obstet Gynecol 1994;170:5605. 24. Schneid-Kofman N, Sheiner E, Levy A, Holcberg G. Risk factors for wound infection following cesarean deliveries. Int J Gynaecol Obstet 2005;90:10 5. 25. Wall PD, Deucy EE, Glantz JC, Pressman EK. Vertical skin incisions and wound complications in the obese parturient. Obstet Gynecol 2003;102(5 pt 1):952 6. 26. Myles TD, Gooch J, Santolaya J. Obesity as an independent risk factor for infectious morbidity in patients who undergo cesarean delivery. Obstet Gynecol 2002;100(5 pt 1):959 64. 27. Sebire NJ, Jolly M, Harris JP, Wadsworth J, Joffe M, Beard RW, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord 2001;25:1175 82. 28. Heslehurst N, Simpson H, Ells LJ, Rankin J, Wilkinson J, Lang R, et al. The impact of maternal BMI status on pregnancy outcomes with immediate short-term obstetric resource implications: a meta-analysis. Obes Rev 2008;9:635 83. 29. Knight M, Callaghan WM, Berg C, Alexander S, BouvierColle MH, Ford JB, et al. Trends in postpartum hemorrhage in high resource countries: a review and recommendations from

30.

31.

32.

33.

34.

35.

36.

the International Postpartum Hemorrhage Collaborative Group. BMC Pregnancy Childbirth 2009;9:55. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006;195:1100 3. Ehrenberg HM, Mercer BM, Catalano PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol 2004;191:964 8. Orskou J, Kesmodel U, Henriksen TB, Secher NJ. An increasing proportion of infants weigh more than 4000 grams at birth. Acta Obstet Gynecol Scand 2001;80:931 6. Usha Kiran TS, Hemmadi S, Bethel J, Evans J. Outcome of pregnancy in a woman with an increased body mass index. BJOG 2005;112:768 72. Kristensen J, Vestergaard M, Wisborg K, Kesmodel U, Secher NJ. Pre-pregnancy weight and the risk of stillbirth and neonatal death. BJOG 2005;112:403 8. Nohr EA, Bech BH, Davies MJ, Frydenberg M, Henriksen TB, Olsen J. Prepregnancy obesity and fetal death: a study within the Danish National Birth Cohort. Obstet Gynecol 2005;106:250 9. Chu SY, Kim SY, Lau J, Schmid CH, Dietz PM, Callaghan WM, et al. Maternal obesity and risk of stillbirth: a metaanalysis. Am J Obstet Gynecol 2007;197:223 8.

37. McAdams MA, Van Dam RM, Hu FB. Comparison of selfreported and measured BMI as correlates of disease markers in US adults. Obesity (Silver Spring) 2007;15:188 96.

312

Ovesen et al

BMI and Pregnancy Outcome in Danish Women

OBSTETRICS & GYNECOLOGY