From the 1Department of Internal Medicine, Division of Cardiology, the 2Departments of Pharmaceutics, and 3Epidemiology, and the 4Department of Internal Medicine, Division of Endocrinology, University of Washington, Seattle, Washington.
Supported by grant number 1KL2RR025015–01 from the National Center for Research Resources, a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research (P.P., Y.S.L., K.E.F.-S.).
The authors thank Dr. Melissa Schiff, a consultant who provided input with data analysis and models, Bill O'Brien, who provided invaluable assistance through computer programming and management of the Department of Health (DOH) data, and the DOH itself, which provided the data for analysis.
Corresponding author: Karen E. Foster-Schubert, Veterans Affairs Puget Sound Health Care System, Endocrinology (111), 1660 South Columbian Way, Seattle, WA 98108; e-mail: firstname.lastname@example.org.
Financial Disclosure The authors did not report any potential conflicts of interest.
Approximately 1.3 million newborns were delivered by cesarean in 2005. The cesarean delivery rate has risen steadily during the past several decades, from 5.5% in 1970 to 30.3% in 2005,1 resulting in a $15–16 billion dollar increase in costs to the health care system.2 Cesarean delivery carries maternal and neonatal risks. Risks for the mother include a higher prevalence of placental abnormalities in subsequent pregnancies,3,4 inherent surgical risks,5–7 thromboembolic events,8,9 and maternal mortality.10 Fetal and neonatal risks associated with cesarean delivery include iatrogenic prematurity,11 birth trauma,12 and respiratory complications.13,14 Cesarean deliveries are performed for a variety of reasons, ranging from maternal choice to clear medical indications necessary for ensuring optimal maternal and neonatal outcomes.2 Identification of women who are at increased risk for cesarean delivery and minimizing any modifiable risk factors they have becomes a very important step toward decreasing rates of cesarean delivery and ultimately improving maternal and neonatal outcomes.
Among those at higher risk for cesarean delivery are women with gestational diabetes mellitus (GDM).15 Defined as glucose intolerance with onset during pregnancy, GDM complicates between 2% and 5% of all pregnancies.16 Obesity and weight gain are important and modifiable risk factors for GDM and also are associated independently with increased rates of cesarean delivery.4 Complex physiologic processes underlying mechanisms of glucose intolerance create a metabolic environment that increases the propensity to further weight gain over time.17 Thus, a woman with a history of GDM is more likely to gain weight and hence has the potential to be at even higher risk for cesarean delivery with her future pregnancies.
We therefore sought to estimate among women with GDM whether weight change between pregnancies (interpregnancy weight change) influences the risk of cesarean delivery in the subsequent pregnancy. We hypothesized that women who gained more weight (more than 10 lb) would be at greater risk than those who remained relatively weight-stable (±10 lb), whereas those who lost weight (more than 10 lb) might be at decreased risk.
MATERIALS AND METHODS
We identified participants for this population-based, retrospective cohort study from the Washington State longitudinal births database, which is comprised of linked birth-certificate data for all women with at least two singleton births in Washington State between 1992 and 2005. The Institutional Review Board of the Washington State Department of Health approved the use of these data for the current study. For our analysis, eligible participants included women with two consecutive live births between 1992 and 2005, diagnosis of GDM at the baseline pregnancy, and vaginal delivery of a live neonate during the baseline pregnancy. Diagnosis of GDM and vaginal delivery were identified by checkbox format and abstracted from the birth certificates. The diagnosis of GDM typically is made when an abnormal response to an oral glucose load is identified at a prenatal visit between 24 and 28 weeks of gestation. We cannot verify how the screening for GDM was done or how the diagnosis of GDM was made because specific practices were not documented. We excluded women with established diabetes at the baseline pregnancy and women whose baseline pregnancy did not result in a live singleton birth. We excluded women who had undergone cesarean delivery at the baseline pregnancy, although we could not exclude women who, in theory, may have had a cesarean delivery before 1992 or a cesarean delivery out of state before our baseline ascertainment. In addition, we excluded women with a medical indication for cesarean delivery during the subsequent pregnancy (genital herpes, nonvertex or breech presentation, placenta previa, and abruptio placenta).
Our exposure of interest was interpregnancy weight change. The interpregnancy weight change for each woman was calculated (prepregnancy weight at subsequent pregnancy-prepregnancy weight at baseline pregnancy) and assigned to one of the following three categories: weight loss (more than 10 lb), weight stable (±10 lb), or weight gain (more than 10 lb). Prepregnancy weight is typically the weight measured at the first prenatal visit. However, it is possible that for some women in our cohort prepregnancy weights were self-reported. The outcome of cesarean delivery for the subsequent birth was identified using the checkbox format on the birth certificate.
Using multiple logistic regression, we calculated the odds ratio (OR) and 95% confidence interval (CI) for cesarean delivery separately, comparing the weight-loss and weight-gain groups with the weight-stable group (reference group). We identified important variables for which to adjust in our analyses a priori based on current evidence. Specifically, we included the following confounding variables in our regression analyses (for the subsequent birth unless otherwise noted): maternal age (younger than 25 years, 25–34, 35 or older), maternal race/ethnicity (white, African American, Hispanic, Asian, or other), maternal education (less than 12 years, 12–15, 16 or more), interbirth interval (less than 12 months, 12–35, 36 or more), prepregnancy weight at the baseline pregnancy (less than 100 lb, 100–149, 150–199, 200 or more), weight gain during the baseline and subsequent pregnancy (loss, 0–14 lb, 15–24, 25–34, 35 or more), smoking during pregnancy (no/yes), and year of birth (subsequent neonate).
We evaluated the dose-response relationship between interpregnancy weight gain tertiles on the risk of cesarean delivery. Finally, a subanalysis was performed examining the effects of interpregnancy weight change using change in body mass index (BMI) between baseline pregnancy and subsequent pregnancy (prepregnancy BMI at subsequent pregnancy-prepregnancy BMI at baseline pregnancy) among the 83% of participants for whom BMI data were available as an additional means to explore our hypothesized associations between interpregnancy weight change and cesarean delivery. Categorization of BMI was based on a previous study by Villamor et al evaluating the relationship of interpregnancy BMI change with risk of adverse pregnancy outcomes in a large Swedish cohort.18 All statistical analyses were performed using Stata 10.0 (StataCorp LP, College Station, TX).
From the 1992 to 2005 Washington State longitudinal birth records, 2,753 women were identified with a GDM diagnosis and vaginal delivery at the baseline pregnancy. We excluded women with risk factors for cesarean delivery (genital herpes [n=81], nonvertex or breech presentation [n=78], placenta previa [n=3], and abruptio placenta [n=10]) at their subsequent pregnancies. Among the eligible 2,581 women, 281 (10.9%) lost more than 10 lb, 1,394 (54.0%) were weight-stable (±10 lb), and 906 (35.1%) gained more than 10 lb between their baseline and subsequent pregnancies. The average interpregnancy weight loss among the women in the weight-loss category was 27±19 lb. The average interpregnancy weight gain among women in the weight-gain category was 26±17 lb.
Women whose weight changed by more than 10 lb between pregnancies tended to be younger than those whose weight remained stable (Table 1). African-American and Hispanic women tended to gain more than 10 lb between their baseline and subsequent pregnancies compared with white and Asian women (42% and 41% compared with 35% and 23% within racial/ethnic groups, respectively). Although most women in our cohort were high school graduates, 19% of women who gained weight between pregnancies had less than a high school education compared with 12% of women who lost weight and 14% of women were weight-stable. Women who gained weight between pregnancies were more likely to have an interbirth interval of more than 3 years relative to women who lost weight or were weight-stable.
Interpregnancy weight change was significantly related to the prevalence of recurrent GDM. Among women who gained weight between pregnancies, 44% were diagnosed with GDM during their subsequent pregnancy compared with 31% of women who lost weight before their subsequent pregnancy and 37% who were weight-stable. Women who were in the weight-gain group tended to gain greater amounts of weight (34±15 lb) during their baseline pregnancy compared with women in the weight-loss (22±13 lb) or weight-stable (27±12 lb) groups. In contrast, at the subsequent pregnancy, women in the weight-gain group gained less weight (23±13 lb) compared with women in the weight-loss (33±16 lb) or weight-stable (28±13 lb) groups. Women in the weight-gain group were also more likely to weigh more than 200 lb at their subsequent pregnancy (data not shown).
Approximately 5% of women who were weight-stable or lost weight between pregnancies underwent cesarean delivery compared with 10% of women who gained weight (Table 2). Women who gained more than 10 lb between pregnancies were twice as likely to undergo a cesarean delivery at their subsequent pregnancy (unadjusted OR 1.92, 95% CI 1.39–2.66).
After adjusting for potential confounders, women who gained more than 10 lb between pregnancies remained more than 70% more likely to undergo cesarean delivery at their subsequent pregnancy in comparison with weight-stable women (adjusted OR 1.70, 95% CI 1.16–2.49, 9.7% of women who gained weight). Meanwhile, women who lost more than 10 lb between pregnancies were not significantly more or less likely to undergo cesarean delivery compared with weight-stable women (adjusted OR 0.55, 95% CI 0.28–1.10, 4.7% of women who lost weight). We evaluated the dose-response relationship to further evaluate support for a potential causal relationship between interpregnancy weight gain in women with GDM and risk of cesarean delivery. We divided the weight-gain group into tertiles (gained 11–16 lb, gained 17–27 lb, gained more than 27 lb) to examine this relationship. Comparing each category of weight gain with the weight-stable group, there was a progressive increase in the estimated risk for cesarean delivery with increasing tertiles of weight gain (Table 3, P trend=.001).
Among the eligible 2,581 women, BMI data were available during the first and subsequent pregnancies for 2,147 women (83%), such that we could calculate the interpregnancy change in BMI. Body mass index data were missing for 434 women (17%) owing to incomplete ascertainment of height. Women whose BMIs increased three units or more between the first and subsequent pregnancy were at a twofold increased risk for cesarean delivery, although, after adjustment, the OR was slightly attenuated (adjusted OR 1.74, 95% CI 1.04–2.91) (Table 4).
Gestational diabetes mellitus, obesity, and excessive weight gain are all independent risk factors for cesarean delivery. Previous studies examined the relative effect of GDM, obesity, or weight change separately on the risk of cesarean delivery.15,16,19 However, we are not aware of any previous studies that have assessed interpregnancy weight gain on the risk of cesarean delivery in a subsequent pregnancy among women with a history of GDM, a population we hypothesized would be at particularly high risk. For women in our study who lost or maintained their weight between pregnancies, the prevalence of cesarean delivery for the subsequent pregnancy was approximately 5%, whereas it was 10% among women who gained weight. Our estimates agree with the published values ranging from 5% to 10% when restricting to women without previous history of cesarean delivery after accounting for obesity-related risk factors.15 We found that women with a history of GDM who gained more than 10 lb between pregnancies had a 70% increased risk of cesarean delivery after adjusting for confounding factors. Further, we found an elevated risk when the analysis was performed using BMI as a measure of body weight. Villamor et al demonstrated that increased interpregnancy BMI change resulted in increased risk of cesarean delivery and other adverse pregnancy outcomes in a large, Swedish, population-based study.18 These congruent results lend further support to the association of interpregnancy weight gain and increased cesarean delivery rates for women with a history of GDM; however our BMI results should be interpreted with some caution given the high percentage of missing data.
Other investigators have demonstrated a relationship between prepregnancy weight and the risk of cesarean delivery. Women weighing 200–299 lb and more than 300 lb had an increased risk of 1.89 (95% CI 1.81–1.97) and 2.59 (95% CI 2.13–3.15), respectively, of having a cesarean delivery compared with women weighing 150–199 lb.20 Similarly, obesity (BMI 30 kg/m2 or higher) increased the risk of cesarean delivery by 2.5-fold (95% CI 1.68–3.71).15 Prepregnancy weight did not modify the relationship between interpregnancy weight gain and cesarean risk in our analysis (P=.60). Our restricted patient population (women with previously diagnosed GDM) may explain these seemingly incongruent findings. Women with GDM are typically overweight or obese, thus it becomes difficult to determine the contribution of prepregnancy weight as an independent risk factor in this population.
Our findings should be considered in the context of several limitations. This is a retrospective cohort study, and so inferring a causal relationship is limited owing to factors such as incomplete ascertainment, misclassification, and measurement error. Birth-certificate data have inherent limitations, including missing information, misclassification of covariates, inaccurate determination of prepregnancy weight, and lack of information on how GDM is diagnosed. An important limitation lies in the classification of the exposure, interpregnancy weight change. The prepregnancy weight reported on the birth certificate typically is derived from the recorded weight at the first prenatal visit but also may be self-reported. Women are known to underestimate their weight, and women who are overweight underestimate their weight to a greater degree.21 This underestimation could result in differential misclassification if the effect was to minimize their weight so that their interpregnancy weight change decreased enough to categorize them as weight-stable rather than as weight gainers. This would result in an attenuated OR of cesarean delivery. Weight gain is usually minimal during the first trimester, so a first-trimester weight would be a reasonable estimate of the true prepregnancy weight. However, this would not be the case for a weight recorded after the first trimester. We evaluated this effect by excluding women whose first prenatal visit was after the first trimester in either pregnancy (n=793). The adjusted OR for women who gained more than 10 lb was 2.28 (95% CI 1.41–3.68). The adjusted OR for women who lost weight was 0.57 (95% CI 0.24–1.35). Consistency between the results of this subanalysis and our overall results suggests that this is not an important source of bias. Finally, although others have found that race/ethnicity is an important factor modifying the relationship between obesity and cesarean delivery rates,19 we were unable to assess this relationship because white women represented more than 70% of participants in our study.
Despite these limitations, we feel these data were adequate to evaluate the relationship between interpregnancy weight change and cesarean delivery in our population. Decreasing the rate of cesarean delivery is an important step toward decreasing morbidity and mortality for neonates and mothers as well as decreasing health care costs. Obstetric and other medical providers should counsel women with GDM about not gaining excessive weight between pregnancies. Adding the prospect of future cesarean delivery to the other risks associated with GDM and weight gain will give women a very tangible reason to make lifestyle changes.
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© 2009 by The American College of Obstetricians and Gynecologists.