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We examined the risk of preterm birth in relation to prepregnancy BMI (kg/m2), waist circumference, adult weight gain, and gestational weight gain among African-American women.
Using prospective data from the Black Women's Health Study, we assessed the association between maternal anthropometric factors and preterm birth among 7,841 singletons born to women ages 21–44 in 1995–2003. We compared mothers of infants born three or more weeks early (597 spontaneous preterm births (SPTB); 517 medically-indicated preterm births (MPTB)) with mothers of 6,727 term infants. We used generalized estimating equation models to derive odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders.
Women with prepregnancy BMI <18 were at increased risk of SPTB and MPTB relative to normal weight women (BMI 20–24), and obese women (BMI ≥30) were at increased risk of MPTB. There were modest positive associations between waist circumference, a measure of central adiposity, and both preterm birth subtypes. Adult weight gain was also positively related to both preterm birth subtypes. Associations with SPTB were generally stronger for gestations of <32 weeks. Low gestational weight gain (<0.5 lbs/week) was associated with an increased risk of SPTB among normal weight and obese women. High gestational weight gain (≥1.5 lbs/week) was associated with increased risk of SPTB among overweight (BMI 25–29) and obese women.
Our data suggest that prepregnancy adiposity (overall and central), prepregnancy weight gain, and gestational weight gain influence risk of preterm birth among African-American women.
Preterm birth is two times more common among Black women than White women1–3 and is a leading cause of infant morbidity and mortality in the U.S.1, 4, 5 In 2006, preterm birth accounted for 12.8% of all births in the U.S. and its prevalence has been on the rise among single and multiple gestations.1 The ethnic disparity in preterm birth is not fully explained by established risk factors such as personal history of preterm birth, intrauterine infections, and low socioeconomic status.6
The prevalence of overweight and obesity has been increasing in the U.S., especially among Black women of childbearing age.7, 8 High body mass index (BMI, kg/m2), a measure of absolute body fat,9 is associated with markers of systemic inflammation (e.g., c-reactive protein),10–12 dyslipidemia,10, 13 and hyperinsulinemia and insulin resistance,14 all of which are associated with an increased risk of preterm birth. These findings suggest that obesity-related metabolic and endothelial disturbances could influence risk of preterm birth via several pathways.15 In addition, maternal obesity is positively associated with urogenital and intrauterine infections, which are thought to be a leading cause of preterm birth.16 On the other hand, obesity is inversely associated with short cervix,17, 18 another risk factor for preterm birth.
The obesity epidemic observed in recent decades has paralleled the increase in preterm birth rates. An unanswered question is whether obesity explains part of the increase in preterm birth. The literature on obesity in relation to preterm birth is mixed. While some studies have reported a positive association between overweight or obesity and preterm birth,19–23 others found no association24–31 or an inverse association.32–35 Most,19, 20, 22, 23, 36, 37 but not all32 studies, found a positive association between obesity and preterm birth at very early gestational ages (e.g., ≤32 weeks); two of the studies found a positive association among nulliparous women only.22, 23 In the studies that examined preterm birth subtypes separately,17, 21, 33, 38, 39 obesity was consistently associated with an increased risk of medically-indicated preterm birth17, 21, 33, 38, 39 but its influence on spontaneous preterm birth was unclear, with studies reporting no association,38, 39 an inverse association17, 33 and a positive association (for preterm premature rupture of membranes only).21
To our knowledge, no studies have examined whether adult weight gain, a correlate of systemic inflammation,40 increases preterm birth risk. Likewise, the relation of central adiposity to preterm birth has not been explored. Central adiposity, the distribution of excess fat in the upper trunk region, is often measured by waist circumference and is associated with hormonal and metabolic changes, including altered estrogen metabolism, insulin resistance, and hyperinsulinemia.41–43 Central obesity is more common in Black women than White women.44
Finally, there is conflicting evidence about the joint association of maternal weight gain during mid- to late- gestation and obesity with preterm birth: studies have reported both decreased36–38 and increased31 risks of preterm birth associated with low gestational weight gain among obese women. In addition, experts disagree as to whether the current Institute of Medicine guidelines for gestational weight gain45 are appropriate for Black women,46 with some arguing that Black women should strive for weight gain towards the upper end of the ranges recommended for white women of similar prepregnancy BMI to reduce risk of low birth weight.45 Although smaller studies of prepregnancy body weight and adverse pregnancy outcomes have included Black women,27, 37 only one stratified by race/ethnicity.27
Using data from the Black Women's Health Study, a U.S. prospective cohort study of approximately 59,000 Black women, we assessed the relation of selected anthropometric variables measured before pregnancy – BMI, waist circumference, and adult weight gain – with risk of spontaneous and medically-indicated preterm birth. We also examined the role of weight gain during pregnancy on risk of these preterm birth subtypes.
The Black Women's Health Study (BWHS) is an ongoing national prospective cohort study of 59,000 African-American women aged 21 to 69 at baseline (1995).47 Women were enrolled in 1995 through questionnaires mailed to subscribers of Essence magazine, members of Black professional organizations, and friends and relatives of respondents. The baseline questionnaire elicited information on demographic and behavioral characteristics, reproductive and contraceptive histories, anthropometric factors, health care utilization, and medical history. BWHS respondents live in various states across the country, with the majority residing in California, New York, Illinois, Michigan, Georgia, and New Jersey. The study is approved by the Institutional Review Board at Boston University Medical Center.
Every two years, participants are mailed a follow-up questionnaire to update their health information; follow-up through 2007 has exceeded 80%. We have compared respondents to nonrespondents for various cycles in order to assess whether there are selective losses. In 2001, for example, respondents were older than non-respondents (mean age: 39.2 vs. 37.2) and had slightly higher education levels (14.9 vs. 14.5 years), but were similar in every other factor assessed (e.g., BMI ≥30, 30% vs. 31%; parity ≥3, 20% vs. 20%).
We identified all women who reported a preterm birth during 1995–2003. On the 1997, 1999, 2001, and 2003 questionnaires, women were asked whether they had given birth to a live or still born child in the previous two years. For singleton live or still births, women were asked “did the doctor say this child was born at least 3 weeks early?” and, if yes, how early (3, 4, 5, 6, 7, 8, 9, or ≥10 weeks), and whether the birth was early due to preterm labor for no known reason or early rupture of membranes (spontaneous preterm birth (SPTB)) or medically-indicated labor or cesarean section (medically-indicated preterm birth (MPTB)). Due dates and birth dates were also elicited for a more precise estimate of gestational age.
Clinically, preterm birth is defined as a birth occurring <37 weeks of gestation from the date of the last menstrual period.48 In the BWHS, we defined preterm birth as a birth occurring “three or more weeks early.” The proportion of preterm birth in our sample (15.2%) is similar to the proportion in national data for Black babies born <37 weeks of gestation (15.6%).48 In a validation study carried out using registry data from the Massachusetts Department of Public Health, 21 of 23 (91.3%) BWHS participants from Massachusetts who reported a singleton preterm delivery during 1995–2003 had gestations ≤37 weeks documented by the registry (we prioritized the LMP estimate of gestational age, unless the clinical estimate was earlier). Moreover, 11 out of 12 reports of spontaneous preterm birth were corroborated by registry data. Finally, the distribution of birth weight among preterm births in the BWHS (birth weight from registry data: mean=2,320g,median=2,495g, interquartile range: 1,875g–2,778g) closely matches national data on Black babies,48 suggesting that our definition of preterm birth is consistent with the clinical definition.
In 1995, BWHS participants reported their height (feet and inches), current weight (pounds), weight at age 18 (pounds), waist circumference (inches) at the level of the umbilicus, and hip circumference (inches) at its widest location. Current weight was updated every two years by questionnaire. Adult weight gain was defined as the difference between current weight and weight at age 18 (kg). We used body mass index (BMI = weight (kg) divided by height squared (m2)) to measure overall obesity and waist circumference to estimate total abdominal fat.49 Although waist-to-hip ratio is used more widely in the medical literature, waist circumference provides an estimate of absolute abdominal adiposity, the component most correlated with metabolic abnormalities such as hyperinsulinemia, hypertension, and high triglyceride levels.49 Weight and BMI data were derived from the questionnaire prior to the questionnaire on which a woman reported the birth. (If the woman was currently pregnant at that time, data were taken from an earlier questionnaire.) Women were asked about their pregnancy weight gain using the following categories: <10, 10–14, 15–19, 20–24, 25–29, 30–34, 35–39, >39 pounds.
We used a gestational weight gain formula developed by Dietz et al.37 that accounts for expected weight gain per trimester and gestational age. Given that the rate of weight gain is typically low in the first trimester and is higher and linear in the second and third trimesters,45, 50assuming a constant rate of weight gain across trimesters would create an upward bias because women with shorter gestation would be misclassified as having lower weight gain. Therefore, in accordance with Dietz et al.,37 we estimated weight gain during the second and third trimesters by subtracting an expected average weight gain during the first trimester from total gestational weight gain and then dividing by gestational weeks minus 14 weeks. First-trimester weight gain was based on Institute of Medicine data,45 which estimates an average weight gain of 5 lbs for underweight women, 3.5 lbs for normal-weight women, and 2 lbs for overweight, obese, or very obese women.
In 2001, we conducted a validation study of anthropometric measures among 115 BWHS participants from the Washington D.C. area. The Spearman correlation between self-reported (mean=176 lbs) and technician-measured weight (mean=181 lbs) was 0.97. The correlation between self-reported (mean=64.4 inches) and technician-measured height (mean=64.0 inches) was 0.93. The correlation for self-reported versus technician-measured waist circumference was 0.75.
For gestational weight gain assessed in categories, the weighted kappa statistic was 0.55 for the comparison of self-reported vs. registry-supplied data from the Massachusetts Department of Public Health birth registry. When we converted the categorical BWHS gestational weight gain variable into a continuous variable using the midpoint of each category, and assigning 5 lbs. to the lowest category and 40 lbs. to the highest, the Spearman correlation coefficient was 0.56.
Data on participant's age at delivery, state of residence, gravidity (number of pregnancies), parity (number of births), smoking before and during pregnancy, previous preterm birth, participant born preterm, and maternal medical conditions (pregestational or gestational diabetes; pre-gestational or gestational hypertension; or thyroid conditions) were obtained on the baseline and follow-up questionnaires. Information on education was elicited in 1995 and marital status was elicited in 1995, 1997, and 1999.
Analyses were restricted to mothers ages 21–44 years who reported singleton births during 1995–2003 (N=8,718). Women who reported that they were currently pregnant at the time of the 1995 questionnaire (N=685) were excluded because their anthropometric measurements could have been influenced by pregnancy weight gain. Women with missing BMI data were also excluded (N=96). We examined spontaneous and medically-indicated preterm births separately because they are thought to have different etiologies. Women reporting preterm births without sufficient data to be classified with respect to preterm birth subtype were excluded (N=96), leaving 7,841 births for the present analysis (6,727 term, 597 SPTB, and 517 MPTB).
BMI categories were based on World Health Organization standards,51 with added cut points at the extremes. Obesity is defined as BMI ≥30 kg/m2. We categorized waist circumference into quintiles and adult weight gain into 10-kilogram increments. We categorized gestational weight gain as low (<0.5 lbs/week), average (0.5–1.4 lbs/week), and high (≥1.5 lbs/week) based on the Institute of Medicine's recommendation that women of average prepregnancy BMI gain 1 lb/week during the second and third trimesters.37, 45
Generalized estimating equation models52 were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between selected anthropometric factors (BMI, adult weight gain, waist circumference, and gestational weight gain) and each preterm birth subtype. These models account for any correlation resulting from the contribution of more than one birth per women (1,452 women contributed more than 1 birth to the analysis). Multivariable models were adjusted for time period (i.e., questionnaire cycle) and known or suspected risk factors for preterm birth, including maternal age at delivery, parity, years of education, marital status, smoking during pregnancy, previous preterm birth, and participant born preterm. Full multivariable models simultaneously controlled for BMI and waist circumference to assess their independent effects.
The analyses for SPTB were repeated using more stringent cut points for gestational age. Since the effect of obesity on pregnancy outcomes may operate through pre-gestational diabetes and hypertension, which have independent effects on pregnancy outcomes,53, 54 we performed separate analyses in which we controlled for maternal medical conditions – diabetes (pre-existing or gestational), hypertension (pre-existing or gestational), and thyroid conditions. Given that the relation between prepregnancy BMI and preterm birth may be modified by gestational weight gain31, 36–38 and parity,22, 23, 33 we assessed effect modification (statistical interaction) by average gestational weight gain per week in the 2nd and 3rd trimesters (<0.5, 0.5–1.4, ≥1.5) and parity (parous vs. nulliparous). Formal tests for interaction were conducted using the likelihood ratio test comparing models with and without cross-product terms between BMI and the effect modifier, all coded as polytomous categorical variables. All analyses were conducted using SAS version 9.1.
Prepregnancy BMI was positively associated with waist circumference, weight change since age 18, smoking during pregnancy, parity, previous preterm birth, and maternal medical conditions (diabetes, hypertension, and thyroid conditions) and inversely associated with gestational weight gain and educational attainment (Table 1). In addition to being associated with BMI, prepregnancy waist circumference was positively associated with smoking during pregnancy, being parous, being married or living as married, previous preterm birth, and maternal medical conditions, and inversely associated with educational attainment and gestational weight gain.
Data on the association of selected anthropometric factors with risk of SPTB and MPTB are shown in Table 2. Women with BMI <18 had more than 2-fold increased risk of SPTB relative to women with BMI 20–24 after adjustment for all risk factors including waist circumference (OR=2.72, 95%CI=1.43–5.17). Prepregnancy obesity was not associated with SPTB after adjustment for waist circumference (OR=1.15, 95%CI=0.75–1.77 for BMI ≥40). Both low and high BMI categories were associated with an increased risk of MPTB after adjustment for waist circumference: ORs for BMI <18 and ≥40 were 2.91 (95%CI=1.38–6.14) and 1.73 (95%CI=1.11, 2.71), respectively. In additional analyses (data not shown), adjustment for maternal medical conditions weakened the association between high BMI and MPTB (ORs for BMI 25–29, 30–34, 35–39, and ≥40 relative to 20–24 were: 1.01, 95%CI=0.78–1.30; 1.77, 95%CI=1.31–2.40; 1.35, 95%CI=0.88–2.06; and 1.12, 95%CI=0.70–1.78) but strengthened the association between low BMI and MPTB (BMI <18 relative to 20–24: OR=4.08, 95%CI=1.94–8.58).
We observed a positive association between waist circumference and SPTB that remained after adjustment for BMI (≥35 vs. <27 inches: OR=1.37, 95%CI=0.91–2.06), but there was little evidence of a dose-response relation. A positive association between waist circumference and MPTB (≥35 vs. <27 inches: OR=1.88, 95%CI=1.36–2.60) attenuated after adjustment for BMI (OR=1.30, 95%CI=0.87–1.95).
Weight gain of ≥30 kg since age 18 was positively associated with SPTB relative to weight gain of 0–9 kg (OR=1.58, 95%CI=1.18–2.12), but there was no dose-response relation (Table 2). Weight gain since age 18 was also positively associated with MPTB: ORs comparing 10–19, 20–29, and ≥30 with 0–9 kg were 1.26 (95%CI=0.99–1.61), 1.71 (95%CI=1.30–2.24), and 2.18 (95%CI=1.59–2.99). Further control for waist circumference did not alter the association of weight gain with MPTB, but attenuated that with SPTB (≥30 vs. 0–9 kg: OR=1.35, 95%CI=0.97–1.87).
Low and high gestational weight gain in the 2nd and 3rd trimesters were associated with an increased risk of SPTB (Table 2). The multivariable ORs for SPTB were 1.51 among women gaining <0.5 lbs/week during gestation (95%CI=1.17–1.97) and 1.42 for weight gain ≥1.5 lbs/week (95%CI=1.13–1.78) relative to a gain of 0.5–1.4 lbs/week. A similar pattern was observed for MPTB. Results were virtually unchanged after adjustment for maternal medical conditions.
Table 3 presents data on the association between anthropometric factors and risk of SPTB according to gestational age at the infant's birth. Associations of low pregregnancy BMI, high waist circumference, high weight gain since age 18, and low and high gestational weight gain with SPTB risk were generally strongest in the <32 week gestation category. In addition, obesity was associated with an increased risk of SPTB at <32 weeks gestation (BMI ≥40 vs. 20–24: OR=2.54, 95%CI=1.03–6.25). The association between high BMI and SPTB <32 weeks strengthened with further control for maternal medical conditions (data not shown); relative to BMI 20–24, multivariable ORs for BMI 25–29, 30–34, 35–39, and ≥40 were: 1.08 (95%CI=0.64–1.84), 2.18 (95%CI=1.24–3.83), 2.49 (95%CI=1.08–5.77), and 3.20 (95%CI=1.27–8.06).
Associations between gestational weight gain and SPTB, within levels of prepregnancy BMI and waist circumference, are shown in Table 4. Among normal weight women (BMI 20–24), low gestational weight gain (<0.5 lbs/wk) was associated with a greater than two-fold increased risk of SPTB (OR=2.62, 95%CI=1.62–4.26) relative to average weight gain (0.5–1.4 lbs/week); in contrast, high gestational weight gain (≥1.5 lbs/week) was not associated with an increased risk. Low gestational weight gain was also positively associated with SPTB among obese women (OR=1.55, 95%CI=1.02–2.35). Among overweight and obese women, high gestational weight gain (≥1.5 lbs/wk) was associated with an increased risk of SPTB: ORs were 1.90 (95%CI=1.27–2.85) and 2.93 (95%CI=1.86–4.63), respectively. Low gestational weight gain was associated with an increased risk of SPTB in both categories of prepregnancy waist circumference. Among women with high waist circumference, a strong positive association was observed between high gestational weight gain and SPTB risk (OR=3.68, 95%CI=2.13–6.35).
No appreciable differences in association were found by parity status for any of the anthropometric variables in relation to SPTB or MPTB (data not shown).
We found a positive association between prepregnancy BMI <18 kg/m2 and both SPTB and MPTB, but there were few women in that category of low BMI. Although high prepregnancy BMI was not associated with SPTB overall, it was associated with very early SPTB (<32 weeks). Most,19, 20, 22, 23, 36, 37 but not all32 studies, have reported a positive association between maternal obesity and very early preterm birth (all subtypes combined); two of these studies found a positive association among nulliparous women only.22, 23 In our data, the association of prepregnancy obesity with early preterm birth was present in both nulliparous and parous women. We observed a positive association between prepregnancy BMI and MPTB overall, but it weakened appreciably after adjustment for maternal medical conditions, suggesting the association is explained by conditions such as pre-gestational hypertension or diabetes. In contrast, the results for very early SPTB (<32 weeks) did not change with further adjustment for maternal medical conditions, suggesting a different mechanism for an effect. While many previous studies have found a positive association of obesity with MPTB,17, 21, 33, 38, 39 only one21 of five previous studies17, 21, 33, 38, 39 of SPTB showed a positive association with obesity.21
Our data suggest a modest positive association of waist circumference with SPTB and MPTB, but the results were not statistically significant and there was no evidence of a dose-response relation. There are no previous studies on this topic with which to compare our results. However, if the mechanism that explains this finding operates through insulin resistance or hyperinsulinemia, then our findings are supported by a recent study of pregnant women in which insulin levels were higher in pregnant women with upper-body (central) obesity than in pregnant women with lower-body obesity or lean pregnant women, following an oral glucose tolerance test.55
Adult weight gain was positively associated with risk of both SPTB and MPTB. To our knowledge, there are no previous studies examining adult weight gain in relation to preterm birth. Control for waist circumference attenuated the association between weight gain and SPTB. To the extent that risk of preterm birth is associated with systemic inflammation,10–12 there is biologic support for an association between adult weight gain and preterm birth, given the correlation between adult weight gain and systemic inflammation.40
In 1990, the Institute of Medicine published guidelines for gestational weight gain based on a woman's prepregnancy BMI.45 Women with prepregnancy BMI <19.8 were advised to gain 28–40 lbs (average: 0.7–1.0 lbs/week), those with BMI 19.8–26.0 were advised to gain 25–35 lbs (average: 0.6–0.9 lbs/week), and those with BMI 26.1–29.0 were advised to gain 15–25 lbs (0.4–0.6 lbs/week). A lower bound of 15 lbs (average ≥0.4 lbs/week) was recommended for women with BMI >29.0. It was also recommended that Black women gain at the upper end of the recommended ranges. These race-specific recommendations have been questioned because there is limited evidence that they reduce risk of small-for-gestational age births and some evidence that they increase risk of large-for-gestational age births.46, 56 In the present study, low and high gestational weight gain were associated with increased risks of both preterm birth subtypes, which is consistent with the literature.23 Low gestational weight gain was associated with an increased risk of SPTB among normal weight women and obese women. In addition, overweight or obese women with high weight gain during pregnancy had an increased risk of SPTB. These results are generally consistent with other studies that have shown low or average weight gain among obese women to be associated with reduced risk of preterm birth.36–38, 57 Therefore, our results suggest that weight gain recommendations should also incorporate an upper bound for obese women.
In our study, data on anthropometric variables and covariates were recorded before the index pregnancy, thereby avoiding differential exposure misclassification (e.g., recall bias). The ideal time to measure baseline BMI of a pregnant woman is before she has started gaining weight due to gestation. Because true prepregnancy BMI is seldom available in registries or hospital databases, which represent the largest sources of data from studies to date,20, 23, 32, 36 researchers often use BMI in early pregnancy. However, by the time a woman is seen for her first prenatal visit, she may have gained (or lost) several pounds compared with her true prepregnancy weight.22 While self-reported BMI and adult weight gain are subject to error, we observed high agreement between self-reported and technician-measured weight.58 Moreover, we observed reasonable agreement between self-reported and registry-supplied gestational weight gain.
We collected data on a wide range of potential confounders not routinely collected in large registries, including whether the participant herself was born preterm and whether she had a previous preterm birth, which allowed for better control of potential confounding variables. The large sample size of the present study permitted an informative assessment of risk factors in the overall dataset. Because there were small numbers in some categories when we stratified by gestational age and BMI, caution is needed when interpreting those results. Cohort retention was satisfactorily high, enough to reduce the influence of selection bias. We have assessed the potential for bias due to selective losses by comparing baseline characteristics of respondents and non-respondents and have found them to be similar in important characteristics, such as BMI and parity.
We were able to analyze preterm birth subtypes separately, which can clarify the etiologic role of the factors under study. However, preterm birth was self-reported and not based on clinical assessment. Moreover, it is unclear whether the self-reported gestational age information was based on ultrasound or LMP methods. It is reassuring that the BWHS validation study indicated good accuracy of self-reported preterm birth and the overall prevalence of preterm birth was comparable to the prevalence based on national data.48
The BWHS is a convenience sample of U.S. Black women. Because women must be literate to participate in a study that collects data by mailed questionnaires, most BWHS participants have completed high school or a higher level of education.47 Given that about 85% of Black women of the same ages nationally have graduated high school,59 the BWHS results should be generalizable to a large segment of the U.S. Black population.
The elucidation of risk factors for preterm birth is of great public health importance given its increasing prevalence in the U.S. and its strong influence on infant morbidity and mortality. The relation of obesity to preterm birth is especially relevant to African-American women because they are disproportionately affected by both conditions. Our data suggest that both overall and central adiposity, adult weight gain, and gestational weight gain influence the risk of preterm birth among African-American women. If our results are replicated in future studies, they offer the potential to improve birth outcomes through management of obesity and gestational weight gain.
This work was funded by National Cancer Institute grant CA58420 (PI: Rosenberg) and the Hood Foundation (PI: Wise). Validation data on gestational age and infant birth weight were obtained from the Massachusetts Department of Public Health. The authors would like to acknowledge the technical assistance of Mr. Kevin Foster from the Massachusetts Department of Public Health and Dr. Ghasi S. Phillips, as well as the ongoing contributions of BWHS participants and staff.