Overweight and obesity are significant pregnancy health concerns, as 64.3% of reproductive age females in the United States are overweight or obese based on World Health Organization body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) criteria.1 Maternal overweight and obesity are associated with an increased risk for metabolic complications such as gestational diabetes and preeclampsia as well as cesarean delivery. Offspring of these mothers are at increased risk of fetal overgrowth, excess childhood adiposity, and the possibility of long-term risks for obesity and metabolic dysfunction.2–4 Importantly, maternal obesity is also associated with an increased risk for stillbirth and neonatal death.5
In 2009, the Institute of Medicine (IOM, now known as the National Academy of Medicine) revised the gestational weight gain guidelines, recommending that overweight women should gain 15–25 pounds and obese women should gain 11–20 pounds across gestation to meet the needs of pregnancy.6 Yet, several authors have recommended either very limited weight gain, or even weight loss among obese women during pregnancy to optimize pregnancy outcomes.7–9 However, recent studies have challenged this by finding that weight loss or weight gain less than 11 pounds during gestation is associated with an increased risk of small-for-gestational-age (SGA) birth weight and decreases in neonatal fat mass, lean mass, and head circumference.10 Contradictory findings may be due to the variability of weight gain across gestation. Most weight gain studies assessed total weight gain across gestation, which ignores what may be important gestational age-related differences and limits any opportunity to intervene during pregnancy. We therefore set out to evaluate the relationship between inadequate or excessive gestational weight gain in the first and second trimester on adverse perinatal outcomes, and to evaluate the association of weight gain in the third trimester with fetal growth.
We conducted a retrospective study of overweight and obese women with singleton gestations delivered at Magee-Womens Hospital of UPMC (University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania) from October 1, 2012 until August 30, 2014. Derivation of the study cohort is shown in Figure 1. We included women who had at least one measured weight between 24 and 28 weeks of gestation and documented prenatal care in the general obstetrics, midwifery, and maternal–fetal medicine clinics in our hospital system. These clinics encompassed diverse practice settings including hospital and community-based clinics with both academic and private practice models, and all women delivered at Magee-Womens Hospital (University of Pittsburgh Medical Center). Only the first delivery was included if women had multiple deliveries during the study period. We excluded women who did not have prenatal care documented in the outpatient record because the majority of these women were transferred to our facility for acute specialty care and were therefore a unique, high-risk population. We also excluded women who did not have either a self-reported prepregnancy weight or a measured weight before 13 weeks of gestation and women with pregestational diabetes. Thus, 5,814 women were included in this analysis. This study was reviewed and approved by the University of Pittsburgh institutional review board, which granted waivers of informed consent.
Demographic information and delivery data were collected from the Magee Obstetric Maternal and Infant database, which includes variables for all deliveries at Magee-Womens Hospital of UPMC in Pittsburgh, Pennsylvania. Data from the Magee Obstetric Maternal and Infant database were supplemented with information electronically extracted from the electronic medical record. We performed a validation study in which we manually abstracted the charts of a computer-generated, randomly selected sample of 300 women and compared these results to the data from the Magee Obstetric Maternal and Infant database and digitally abstracted information. Manually abstracted and database data demonstrated almost perfect agreement, with kappa scores above 0.85 for all clinical, demographic, and outcome variables other than hypertensive disorders of pregnancy, which had a kappa score of 0.72. Our manual validation study did not identify any cases where results of gestational diabetes screening were missed by the electronic data capture.
Demographic and other variables were abstracted from the medical record and Magee Obstetric Maternal and Infant database. Gestational age was calculated using the estimated date of delivery as assigned in clinical care. Family history of diabetes in a first-degree relative, tobacco use, and a history of gestational diabetes mellitus (GDM) were available in the medical record as collected during routine clinical care. Prepregnancy weight was obtained by patient self-report in the electronic medical record at the first prenatal visit in 5,302 of 5,814 (91.2%) of patients, and the reported prepregnancy weight had a strong correlation with the measured weight at the first prenatal visit (r=0.98, P<.001) The first trimester measured weight was used as a proxy in 512 of 5,814 (8.8%) of women where the patient-reported prepregnancy weight was not available. Maternal prepregnancy overweight and obesity was reported as an index of weight for height (BMI). Overweight was defined as a BMI of 25.0 to less than 30, class 1 obesity 30 to less than 35, class 2 obesity 35 to less than 40, and class 3 obesity was a BMI of 40 or higher using the World Health Organization guidelines for classification of BMI. We followed the IOM guidelines for first and second-trimester weight gain to determine inadequate, adequate, or excessive early gestational weight gain.11 These recommendations assume a weight gain of 1.1–4.4 pounds in the first trimester. To calculate inadequate weight gain, we used a weight gain of 1.1 lb for the first trimester along with the lower limit of the BMI-specific weekly gain up to 24–28 weeks of gestation (0.5 lb for overweight women and 0.4 lb for obese women). We then calculated excess weight gain using a weight gain of 4.4 lb in the first trimester along with the upper limit of the BMI-specific weekly gain up to 24–28 weeks of gestation (0.7 lb for overweight women and 0.6 lb for obese women).
We also sought to evaluate the effect of third-trimester weight gain on outcomes in women with inadequate, adequate, or excess early gestational weight gain. Because of the narrow definition of adequate weight gain in the third trimester (between 0.5 and 0.7 pounds per week for overweight women or 0.4–0.6 pounds per week for obese women), we found that the majority of women had either inadequate or excessive weight gain after 28 weeks of gestation. We therefore classified weight gain in the third trimester according to whether it was below, at, or above the recommended weight gain per week in the third trimester (0.6 lb per week for overweight women and 0.5 lb per week for obese women).
Our primary outcome was the prevalence of SGA (10th percentile or less for gestational age) or large-for-gestational-age (LGA, 90th percentile or above for gestational age) birth weight between overweight and obese women who had inadequate, adequate, or excessive weight gain before 28 weeks of gestation. Both SGA and LGA birth weight status were defined using US national birth weight data by fetal sex and corrected for implausible estimates of pregnancy dating.12 We also compared the incidence of hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, or chronic hypertension with superimposed preeclampsia) as defined by International Classification of Diseases, 9th Revision, Clinical Modification codes (642.3, 642.4, 642.5, 642.6, 642.7), gestational diabetes as diagnosed by the Carpenter-Coustan criteria,13 cesarean delivery, preterm birth before 37 weeks of gestation, and rates of a neonatal composite morbidity which included neonatal intensive care unit (NICU) admission, need for mechanical ventilation, neonatal hypoglycemia (defined as a blood glucose value of less than 40 mg/dL within the first 24 hours of life), and jaundice requiring phototherapy.
Statistical analyses were completed using Stata 14 software package Special Edition. Distributions of variables were tested for normality using visual inspection of histograms. Women who had inadequate, adequate, or excessive gestational weight gain before 28 weeks of gestation were compared using the χ2 statistic, Fisher's exact test, or analysis of variance as appropriate. We next assessed the relationship between inadequate, adequate, or excessive weight gain and birth weight and adverse pregnancy outcomes using logistic or multinomial regression models as appropriate. We selected covariates a priori that were known to be associated with our outcomes of interest and routinely available at the first prenatal visit. Covariates included maternal race, prepregnancy BMI, nulliparity, public insurance, chronic hypertension, and smoking. Because GDM, chronic hypertension, and smoking may influence the fetal growth trajectory, we also conducted a series of sensitivity analysis excluding women with each of these diagnoses. Stratified analyses were conducted to assess the effect of inadequate, adequate, or excessive weight gain on perinatal outcomes in women who are overweight or who have class 1, 2, or 3 obesity. Finally, we examined whether weight gain below, at, or above the weight gain per week recommended in the third trimester (0.6 lb per week for overweight women and 0.5 lb per week for obese women) in the third trimester modified the risk for SGA or LGA birth weight among women with inadequate, adequate, or excessive weight gain before 24–28 weeks of gestation. We next used logistic regression analyses within early pregnancy weight gain strata to assess whether weight gain below, at, or above the IOM recommendations in the third trimester was associated with SGA or LGA birth weight after adjusting for maternal race, prepregnancy BMI, nulliparity, public insurance, chronic hypertension, and smoking. Two-sided P values less than .05 were considered statistically significant in all analyses.
Overall 5,814 of 6,873 (84.6%) of eligible overweight or obese women had a prenatal weight measured between 24 and 28 weeks of gestation. Women with a measured weight in this timeframe had lower prepregnancy BMIs (31.6±5.9 vs 32.5±6.6, P<.001), were slightly older (29.5±5.6 vs 29.1±6.1 years, P=.03), more likely to be white (69.4% vs 60.1%, P<.001), more likely to have private insurance (59.9% vs 44.7%, P<.001), and less likely to smoke (23.3% vs 26.1%, P=.05) when compared with women without a measured weight between 24 and 28 weeks of gestation. Of the 5,814 women who were overweight or obese in our primary analysis, 1,428 (24.6%) had inadequate weight gain, 1,280 (22.0%) had adequate weight gain, and 3,106 (53.4%) had excess gestational weight gain before 28 weeks of gestation.
Women with inadequate weight gain were slightly younger than women with adequate or excessive weight gain, and they were also more likely to be black, have public insurance, and less likely to be nulliparous (Table 1). Women with excessive weight gain were slightly older, more likely to be white, less likely to have public insurance, and more likely to be nulliparous (Table 1). Women with inadequate weight gain had a higher prepregnancy BMI and were more likely to have class 2 or 3 obesity, whereas those women with excessive weight gain had a lower mean prepregnancy BMI and they were more likely to be overweight. There were modest differences in 50-g glucose challenge test results as well as the 2- and 3-hour results on the 100-g oral glucose tolerance test among groups (Table 1). As expected, women with inadequate weight gain before 28 weeks of gestation gained less weight up to that point, gained less weight in the third trimester, and also gained less weight across gestation; women with excessive weight gain gained more weight before 28 weeks of gestation, in the third trimester, and across gestation (Table 1). Weight loss across gestation occurred in 15.4% of women with inadequate weight gain before 28 weeks of gestation but was rare in women with either adequate or excessive weight gain before 28 weeks of gestation (Table 1).
Small for gestational age birth weight was more common in women with inadequate weight gain before 28 weeks of gestation compared with those with adequate or excessive weight gain (188/1,361 [13.8%] vs 117/1,239 [9.4%] vs 191/2,976 [6.4%], P<.001); LGA birth weight was most common in women with excessive weight gain compared with those with adequate or inadequate weight gain (429/2,976 [14.4%] vs 114/1,239 [9.2%] vs 99/1,361 [7.3%], P<.001). These differences persisted after adjustment for covariates, such that women with inadequate weight gain before 28 weeks of gestation were more likely to deliver a neonate with SGA birth weight (adjusted odds ratio [aOR] 1.59, 95% CI 1.23–2.06) and less likely to deliver a neonate with LGA birth weight (aOR 0.73, 95% CI 0.54–0.98). In contrast, those with excessive weight gain were less likely to deliver a neonate with SGA birth weight (aOR 0.66, 95% CI 0.52–0.85) and more likely to deliver an LGA neonate (aOR 1.66, 95% CI 1.32–2.1). When we excluded women with either GDM, chronic hypertension, or smoking, these results were unchanged, demonstrating that these associations were independent of other diagnoses that may be associated with abnormal fetal growth (data not shown). When we performed the analysis while stratifying for classes of obesity, inadequate weight gain before 28 weeks of gestation was associated with an increased prevalence of SGA and a decreased prevalence of LGA in all women except for those with class 3 obesity, whereas excess gestational weight gain was associated with higher rates of LGA birth weight in both women who were overweight and had class 1 obesity (Table 2).
There were differences in the risk for hypertensive disorders of pregnancy among women with adequate, inadequate, and excessive weight gain before 28 weeks of gestation (195/1,280 [15.2%] vs 209/1,428 [14.6%] vs 550/3,106 [17.7%], P=.02) (Table 3). After adjusting for covariates, excessive weight gain before 28 weeks of gestation was associated with a higher risk for hypertensive disorders of pregnancy (aOR 1.23, 95% CI 1.02–1.48) (Table 3). Importantly, there were no differences in rates of GDM, preterm birth, cesarean delivery, or neonatal morbidity among women with adequate, inadequate, or excessive gestational weight gain before 28 weeks of gestation.
Differences in rates of SGA and LGA birth weight were our most consistent finding across BMI categories, so we next evaluated the effect of third trimester weight gain on the prevalence of these outcomes in the 5,361 women (92% of the overall cohort) who had both a maternal weight at delivery available to calculate third trimester weight gain and a birth weight. As shown in Table 4, the risk of LGA was higher in women with higher gestational weight gain in the third trimester after adjusting for covariates regardless of the adequacy of earlier weight gain. Rates of SGA birth weight were similar between women with higher or lower third trimester weight gain regardless of early pregnancy weight gain category.
We found that the timing of gestational weight gain is associated with birth outcomes in overweight and obese pregnant women. Specifically, inadequate early weight gain was associated with an increased risk for SGA and a decreased risk for LGA birth weight, whereas excessive early gestational weight gain was associated with decreased risk for SGA and an increased risk for LGA. Our findings also suggest that low weight gain in the third trimester was associated with a decreased risk of LGA, regardless of early gestational weight gain. Conversely, the risk for SGA was not altered regardless of higher or lower third trimester gestational weight gain.
These findings provide information that may have direct implications for prenatal care. Prior work in women with obesity has demonstrated that the risk for SGA is low and rarely diagnosed before 32 weeks of gestation,14 but our data suggest that women who were overweight or obese and inadequate weight gain before 28 weeks of gestation may be at increased risk for SGA birth weight. Pregnant women who are overweight or obese are also at increased risk for fetal overgrowth, even in the absence of gestational diabetes.15 Interventions across gestation have had only a modest effect on the risk for fetal overgrowth,16,17 but our study suggests that lower weight gain in the third trimester could reduce the risk of LGA. These findings are important, as identification of weight gain patterns by 28 weeks of gestation may help customize ultrasound surveillance, prenatal care, and nutritional counseling in the third trimester to improve neonatal outcomes.
Our data are consistent with what is known regarding weight gain across gestation, and they bolster prior findings on the association between limited gestational weight gain and the risk of SGA birth weight. Although several authors have suggested that lower weight gain, no weight gain, or weight loss across gestation might be appropriate for women who are overweight or obese,7–9,18 others have demonstrated that weight loss in obese women resulted in decreased risk for LGA but increased risk for SGA.19–21 Catalano, et al demonstrated that weight loss or gain less than or equal to 5 kg across gestation was associated with an increased risk for SGA and decreases in neonatal fat mass, lean mass, and head circumference.10 Similarly, a recent meta-analysis of more than 1 million women reported that inadequate weight gain across gestation in obese women was associated with an increased risk of SGA.22 Inadequate weight gain before 28 weeks of gestation occurred in a quarter of women in our study, making these questions of significant consequence.
Our results also add to the body of literature suggesting that the timing of gestational weight gain is important. Early excess gestational weight gain has been linked to increased body fat at birth,23 which may have implications for long-term metabolic health. Studies from China that included only a small number of women who were overweight or obese found that early gestational weight gain has a greater effect on birth weight compared with later gestational weight gain.24,25 However, there is limited data focusing specifically on women who are overweight or obese. Catov et al26 found that in a cohort of 650 predominantly African American women who were overweight or obese, high early gestational weight gain was associated with LGA regardless of later gain. Their results also indicated that low early weight gain followed by high weight gain later in gestation may be associated with a reduced risk for SGA.26 However, our findings suggest that among women with inadequate weight gain before 28 weeks of gestation, even weight gain at or above the current recommendations in the third trimester is inadequate to reduce the risk for SGA birth weight. Plasticity in the fetal growth trajectory could have long term implications, because childhood obesity rates have tripled over the past 30 years, and this risk is particularly high among neonates born to women who are overweight or obese.26 Both LGA and SGA neonates are at risk for childhood obesity, and further research is needed to understand the maternal metabolic characteristics that lead to the extremes of fetal growth.27–29 Despite these differences in birth weight category, rates of neonatal morbidity were similar among groups.
Timing of gestational weight also appears to affect adverse maternal outcomes. Excessive weight gain up to 28 weeks of gestation was associated with an increased risk for hypertensive disorders of pregnancy. Prior work has shown that in normotensive women, gestational weight gain in early pregnancy correlates with higher blood pressures, providing a potential link between weight changes and hypertensive disorders of pregnancy.30 By comparison, lower gestational weight gain before 28 weeks of gestation did not decrease the risk for GDM. This finding is significant because several of the studies designed to prevent GDM via lifestyle interventions have not been successful despite some success in limiting gestational weight gain.17,31
Strengths of our study include the large population and the careful validation of demographic, clinical, and outcome data. Limitations include maternal self-report of prepregnancy weight. This applied to a small proportion of our cohort (less than 9%), and prepregnancy weight was highly correlated with early pregnancy weight in the remainder of the study population. In addition, we were unable to examine later gestation weight gain as inadequate, adequate, or excessive because of the small number of women who were classified as having adequate weight gain. However, this may reflect a limitation of the current guidelines and we were still able to provide a weight gain cut-off with a potential for clinical use. The women in our study were predominantly white, and this is of importance because there may be racial differences in the relationship between obesity, gestational weight gain, and birth weight category.32 The exclusion of women with missing weight measurements at 24–28 weeks of gestation has the potential to introduce bias into our study population. Our study was also limited by the use of routinely collected clinical weight measurements, which is likely to produce random measurement error but unlikely to introduce bias. Conversely, one advantage is that our results can be easily translated into clinical practice as they mirror the results obtained in routine clinical practice.
Our results provide evidence regarding the significant effect of gestational weight gain in the first and second trimesters on the prevalence of SGA and LGA birth weight, indicating that the importance of optimizing weight gain must be stressed from early gestation. Our results also suggest that modifying weight gain in the third trimester may reduce the risk of LGA birth weight, and interventional trials are needed to further evaluate this hypothesis.
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