Combined Effects of Prepregnancy Body Mass Index and Weight Gain During Pregnancy on the Risk of Preterm Delivery.

Abstract


Background:

The association between excessive gestational weight gain and preterm delivery is unclear, as is the association between low gestational weight gain and preterm delivery among overweight and obese women.

Methods:

Using data from the Pregnancy Risk Assessment Monitoring System in 21 states, we estimated the risk of very (20–31 weeks) and moderately (32–36 weeks) preterm delivery associated with a combination of prepregnancy body mass index (BMI) and gestational weight gain among 113,019 women who delivered a singleton infant during 1996–2001. We categorized average weight gain (kilograms per week) as very low (less than 0.12), low (0.12–0.22), moderate (0.23–0.68), high (0.69–0.79), or very high (more than 0.79). We categorized prepregnancy BMI (kg/m2) as underweight (less than 19.8), normal (19.8–26.0), overweight (26.1–28.9), obese (29.0–34.9), or very obese (more than or =35.0). We examined associations for all women and for all women with no complications adjusting for covariates.

Results:

There was a strong association between very low weight gain and very preterm delivery that varied by prepregnancy BMI, with the strongest association among underweight women and the weakest among very obese women. Very low weight gain was not associated with moderately preterm delivery for overweight or obese women. Women with very high weight gain had approximately twice the odds of very preterm delivery, regardless of prepregnancy BMI.

Conclusions:

This study supports concerns about very low weight gain during pregnancy, even among overweight and obese women, and also suggests that high weight gain, regardless of prepregnancy BMI, deserves further investigation.

Introduction

Preterm delivery (before 37 weeks of gestation) persists in being one of the greatest contributors to infant mortality in the United States. Efforts to prevent this event have been relatively unsuccessful. Both low pregnancy weight gain and underweight prepregnancy body mass index (BMI; weight [kg]/height[m2]) are well-established risk factors for delivering before term. Recent studies have found that low pregnancy weight gain among underweight or normal-weight women increases preterm delivery risk, but the evidence regarding overweight and obese women has been equivocal. This lack of clear evidence may be due in part to different measures of weight gain, limited sample size, and different reference groups. Evidence for an effect of excessive weight gain on preterm delivery has also been equivocal. Although a few studies suggest such an association, they defined excessive weight gain differently, measured weight gain at different periods during pregnancy, inconsistently assessed interaction with BMI, and were restricted to low-income women.

The objective of this study was to estimate the combined effects of prepregnancy BMI and pregnancy weight gain on preterm delivery of singleton births. Some risk factors for very preterm delivery differ from those for moderately preterm delivery, and so we examined these outcomes separately.

DISCUSSION

This is the first published study to examine the combined effect of prepregnancy BMI and weight gain during pregnancy for very preterm and moderately preterm delivery. Consistent with previous studies, we found that low weight gain among underweight and normal-weight women was associated with increased risk of preterm delivery. The magnitude of the association was greater for very preterm delivery than for moderately preterm delivery. In addition, very low weight gain (less than 0.12 kg/wk) was a risk factor for very preterm delivery among all BMI groups, including overweight and obese women; however, the magnitude of the odds ratios decreased as BMI increased. In addition, we found that excess weight gain (more than 0.79 kg/wk) among all BMI groups was associated with increased risk for very preterm delivery. Excess weight gain among under- and normal-weight women also increased the risk of moderately preterm delivery. When using net weight gain, our findings were similar to those for total weight gain.

Among women who gained very little during pregnancy, we found a generally declining risk for preterm delivery with increasing prepregnancy BMI. This suggests that having access to stored fat may protect against preterm delivery when weight gain is less than optimal. A similar association has been found for infant birth weight. Although weight restriction early in pregnancy has been associated with preterm delivery among sheep, it is unknown whether weight restriction later in pregnancy has the same effect, or whether this effect translates to humans. Some studies, however, suggest that fasting (which may be related to weight restriction) during late gestation may stimulate early preterm delivery.

A review of 5 trials of supplementation with energy or protein during pregnancy among women at risk found only a modest reduction in preterm delivery. This suggests that simply increasing energy consumption during pregnancy does not lower the preterm delivery risk, perhaps because weight gain during pregnancy is multifaceted. In addition to representing energy stores, low weight gain may indicate deficiencies in micronutrients, a lack of expansion of plasma volume, infection, or other unidentified problems. The hypothesis that multiple mechanisms are at play is further supported by associations between low weight gain and both moderately and very preterm delivery. Moderately and very preterm deliveries are thought to represent some overlapping and some etiologically distinct outcomes: infection and inflammation are thought to be a greater underlying cause of very preterm delivery. The stronger association of low weight gain with very preterm delivery suggests that exploring the associations among prepregnancy weight, gestational weight gain, markers for infection or inflammation, and preterm delivery might be productive.

There are no clear biologic mechanisms for the link between excessive weight gain during pregnancy and preterm delivery. Other studies with adequate power have found results similar to ours. Excess weight gain may be associated with preterm delivery because it is a marker for edema, which, in turn, is a marker for preeclampsia. However, when we restricted our analysis to women without hypertension (presumably excluding most women with preeclampsia), the associations remained. One study found the association only with excessive third-trimester weight gain and only among women with normal prepregnancy BMI.

In our study, after excluding women with hypertension, diabetes, or a SGA infant, we found an association with moderately preterm delivery for underweight and normal-weight women. Obesity and excess weight gain among postmenopausal women have been associated with at least one marker of inflammation, C-reactive protein, and a substantial percentage of preterm delivery is thought to be inflammatory in origin. It is unknown whether excess pregnancy weight gain is associated with inflammation. Our finding also may be an artifact of the lack of precision in our measurement of estimated weight gain in the second and third trimester. However, if real, our finding is relevant to a large proportion of pregnant women; in our population-based sample, more than one in 10 women gained more than 0.79 kg/wk during pregnancy.

This study benefited from a large sample size that allowed examination of preterm risks among overweight, obese, and very obese women separately, and assessment of risks for very and moderately preterm delivery. It was limited, however, by its measure of pregnancy weight gain. As reported on the birth certificate, total weight gain does not indicate weight gain by trimester. We assumed a constant rate of weight gain in the second and third trimesters, although studies have indicated that average third-trimester gain is slightly lower than average second-trimester gain. Our method of calculating estimated second- and third-trimester gain could not adjust for this difference. Thus, mothers of term infants might have slightly lower weight gain rates than mothers of very preterm infants due to longer exposure to lower rate of weight gain in the third trimester.

A recent U.S. study found the mean weight gain among normal BMI women with term deliveries was 0.56 kg/wk in the second trimester and 0.50 kg/wk in the third trimester. Thus, for a woman who delivered at 40 weeks, the average weight gain in the second and third trimester would be 0.53 kg/wk, but for a woman who delivered at 26 weeks, the average weight gain would be 0.56 kg/wk. Although this bias may have contributed to the finding regarding excess weight gain, it is unlikely to have accounted for the entire association. Additionally, we assumed a set weight gain in the first trimester based on prepregnancy BMI as proposed by the IOM. We took this approach to account for potential bias of lower weight gain among women who deliver preterm because the lower rate of weight gain during the first trimester would have disproportionately contributed to the weight gain rate. We acknowledge there is likely misclassification of the weight gain rate, because some women will have gained more or less than what was assumed for the first trimester. We are unaware of any literature indicating this misclassification is differential among women delivering preterm and term infants.

Birth certificate data have other limitations. Problems with LMP-based gestational age reported on the birth certificate are well documented. We used 2 additional measures, clinical estimate and mother's report of due date, to check consistency with the LMP-based estimate. We also evaluated the birth weight distribution by gestational week and found no bimodal distribution, suggesting the misclassification with LMP-based gestational age was addressed by our gestational-age algorithm. Other birth certificate variables such as hypertension and diabetes are known to be underreported. Our final sample, in which we excluded complications, may have included preterm births related to these unreported conditions; thus, residual confounding may have remained. However, the magnitude of this bias, if present, would likely be insufficient to account for the entire association found in this analysis. Ideally, we would have liked to analyze these data by medically indicated and spontaneous preterm delivery, but PRAMS and the birth certificate lack this information. We tried to address this distinction by excluding women with the most common causes of medically indicated preterm delivery (hypertension, diabetes, and SGA). However, given the overlapping causes of both medically indicated and spontaneous preterm delivery, and the unknown etiology of the weight gain association with preterm delivery, it is unclear how including both types of preterm delivery might have affected our results.

One study found that after medically indicated preterm births were excluded, the association between low prepregnancy BMI and low weight gain with preterm delivery was strengthened. We found a similar effect after our exclusions for missing information on weight gain during pregnancy, gestational age, or prepregnancy BMI. Variables in which the excluded women differed from those included were adjusted for in the logistic models, and this adjustment did not alter the observed associations. However, the generalizability of our study may be limited if the associations differ in the excluded women by unmeasured variables. Our preterm delivery rate is lower than the national rate because we excluded multiple births and our gestational age algorithm was a more restrictive criterion than using LMP alone.

In summary, very low weight gain was associated with moderately preterm delivery for the lowest BMI groups and with very preterm delivery among all BMI groups. In addition, although the strength of the association between excessive weight gain and preterm delivery was not as strong as the association for low weight gain, excessive weight gain affects a much greater proportion of the population and deserves further study. Further understanding of these associations is needed because it remains unclear whether they are causal and therefore amenable to nutritional interventions.