Spontaneous preterm birth: preconceptional nutrition matters

During a recent trip, I couldn't help observing the bulging waistlines of even the fairly well-to-do in Newport, Martha’s Vineyard, and Nantucket. It was a stark reminder that although the obesity epidemic in the United States has leveled off, nearly 36% of adults have a body mass index (BMI) ≥30 and thus are considered obese.¹ Seeing several rather large pregnant women also reinforced the importance of a recent JAMA article that establishes a clear association between obesity and extremely early spontaneous preterm births.²

Scope of the problem

We are all very familiar with the general health risks attendant obesity, including an increased prevalence of cardiovascular diseases including hypertension, myocardial infarction, and stroke; as well as increased rates of diabetes, osteoarthritis, and certain cancers (eg, endometrial and breast). Indeed, analysis of the Framingham Heart Study suggests that nonsmoking women who are obese at age 40 have a 7-year reduction in life expectancy.³

We are also increasingly aware of the reproductive sequelae of obesity. Obese women have significantly higher rates of preeclampsia, gestational hypertension, and gestational diabetes, which increase with increasing BMI.⁴ The fetuses of obese women are also at increased risk of congenital anomalies, death, and macrosomia, and, when there is maternal hypertension, intrauterine growth restriction.^5,6

A recently published study confirms increased rates of labor induction accruing obesity, from 25.3% in women with normal BMI to 42.9% in women with BMI ≥40.0, odds ratio (OR) 1.67 (95% CI, 1.43­­–1.93).⁷ Similarly, rates of primary cesarean delivery rise with increasing BMI and are highest among morbidly obese women (36.2% vs. 22.1% in women with normal BMI, OR 1.46 [95% CI, 1.23–1.73]).⁸

Obesity and spontaneous preterm birth

About the only major obstetrical outcome that seemed immune from the obesity epidemic was spontaneous preterm birth, although it has been appreciated for some time that obesity increases rates of indicated prematurity in women with hypertension and diabetes. Indeed, underweight women seemed at greater risk of spontaneous preterm birth. Well, this illusion also has recently been shattered.

Exploiting the epidemiological power of the nationwide Swedish Medical Birth Registry, Cnattingius and associates analyzed the association between early pregnancy BMI and risk of preterm birth in 1.6 million women with live singleton births.² Preterm births were stratified as extremely preterm (22–27 weeks), very preterm (28–31 weeks) and moderately preterm (32–36 weeks). Outcomes were further analyzed based on spontaneous and medically indicated preterm births. In the latter, obesity was associated with all 3 preterm birth categories but only in women with pre-existing hypertension or diabetes. In contrast, after adjusting for confounding, obesity was most closely linked to spontaneous extremely preterm births.

Compared with normal-weight women, therefore, those with BMI values of 25–30 had an OR for spontaneous extremely preterm birth of 1.26 (95% CI, 1.15–1.37), while those with BMI values of 30–35 had an OR of 1.58 (95% CI, 1.39–1.79). Moreover, women with BMIs of 35–40 and ≥40 had ORs for extremely preterm birth of 2.01 (95% CI, 1.66–2.45) and 2.99 (95% CI, 2.28–3.92), respectively.

Thus, there is a clear “dose-response” effect of obesity, suggesting strong biological plausibility. The authors also allude to potential obesity-related pathogenic mechanisms, including an exaggerated inflammatory response to subclinical genital tract infections. Consistent with this thesis, they found that the strongest links between obesity and spontaneous preterm birth were for preterm premature rupture of membranes. This study also confirmed the long-held observation that underweight women (BMI <18.5) have a modestly increased risk of very and moderately preterm birth, a setting in which fetal stress may play the dominant pathogenic role.

Many prior studies and meta-analyses link obesity with indicated preterm birth.⁹ One prior study also links increasing levels of obesity with increasing risk of very and extremely preterm births, especially in African Americans, but the report did not differentiate between spontaneous and indicated preterm births.¹⁰ Thus, the Cnattingius et al. report suggests an additional powerful tool to prevent precisely those spontaneous preterm births most likely to result in perinatal mortality and severe morbidity: weight loss.

Prevention strategies

Clearly weight loss is most easily accomplished before conception. Because indicated preterm births among obese patients are almost exclusively limited to those with hypertension and diabetes, and given that weight loss reduces the prevalence and/or severity of both conditions,^11,12 we can be reasonably confident that preconceptional weight loss will reduce the occurrence of medically indicated prematurity. Based on the Cnattingius et al. study, we can now also be reasonably confident that reduction in BMI from >40 to normal before conception will reduce the risk of spontaneous extremely preterm birth, perhaps 3-fold!

Unfortunately, however, most of us see obese patients once they are pregnant and only inconsistently in the preconceptional period. So what's to be gained by achieving gestational weight loss in obese patients? At least from a prematurity perspective, the answer seems to be not much. Beyerlein et al. found that gestational weight loss in obese patients was associated with increased risk of preterm birth.¹³

Another recent study suggests that while weight gain above the Institute of Medicine (IOM) recommendations is indeed harmful, reduced weight gain in obese patients has no discernible impact on spontaneous preterm birth rates.¹⁴ The authors analyzed 8293 pregnancies, of which 9.5% had weight gain below, 17.5% within, and 73% above IOM guidelines. Not surprisingly, across all BMI categories, excess gestational weight gain led to increased risk of complications such as hypertension, diabetes, cesarean delivery, and macrosomia. However, after adjusting for confounders, obese women who gained less than the IOM recommendations were found not to have reduced rates of either indicated or spontaneous preterm births.

Take-home message

Beyond the myriad adverse long-term health effects triggered by obesity, it has now been clearly linked to virtually all the major adverse maternal and fetal outcomes of pregnancy, including gestational diabetes, preeclampsia, macrosomia, excess cesarean delivery rates, congenital anomalies, fetal death, indicated preterm birth, and now spontaneous extremely preterm birth. Furthermore, waiting until an obese patient is pregnant to attempt to ameliorate the effects of obesity is probably too late. Aggressive preconceptional weight loss is needed.

Lastly, attainment of a normal preconceptional BMI will also likely prevent obesity and related long-term health effects in the developing child.¹⁵ In short, preconceptional nutrition matters.

For more on obesity and weight gain in pregnancy, see the July 2013 cover story here.

References

1. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 2012; 307(5):491-497.

2. Cnattingius S, Villamor E, Johansson S, et al. Maternal obesity and risk of preterm delivery. JAMA. 2013;309(22):2362-2370.

3. Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L; NEDCOM, the Netherlands Epidemiology and Demography Compression of Morbidity Research Group. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med. 2003;138(1):24-32.

4. Weiss JL, Malone FD, Emig D, et al. Obesity, obstetric complications and cesarean delivery rate–a population-based screening study. FASTER Research Consortium. Am J Obstet Gynecol. 2004;190:1091–1097.

5. Stothard KJ, Tennant PW, Bell R, Rankin J. Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. JAMA. 2009;301:636–650.

6. Tenenbaum-Gavish K, Hod M. Impact of Maternal Obesity on Fetal Health. Fetal Diagn Ther. 2013 Jun 11. [Epub ahead of print]).

7. El-Chaar D, Finkelstein SA, Tu X, et al. The impact of increasing obesity class on obstetrical outcomes. J Obstet Gynaecol Can. 2013;35(3):224-233.

8. Paiva LV, Nomura RM, Dias MC, Zugaib M. Maternal obesity in high-risk pregnancies and postpartum infectious complications. Rev Assoc Med Bras. 2012;58(4):453-458.

9. McDonald SD, Han Z, Mulla S, Beyene J; Knowledge Synthesis Group. Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses. BMJ. 2010;341:c3428.

10. Salihu H, Mbah AK, Alio AP, et al. Nulliparity and preterm birth in the era of obesity epidemic. J Matern Fetal Neonatal Med. 2010;23(12):1444-1450.

11. Williamson DF, Parnuk E, Thues M, et al. Modest intentional weight loss increases life expectancy in overweight women. Am J Epidemiol. 1995;141:1128-1141.

12. Fortenberry K, Ricks J, Kovach FE. Clinical inquiry. How much does weight loss affect hypertension? J Fam Pract. 2013;62(5):258-259.

13. Beyerlein A, Schiessl B, Lack N, von Kries R. Associations of gestational weight loss with birth-related outcome: a retrospective cohort study. BJOG. 2011;118(1):55-61.

14. Johnson J, Clifton RG, Roberts JM, et al.; Eunice Kennedy Shriver National Institute of Child Health; Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Pregnancy outcomes with weight gain above or below the 2009 Institute of Medicine guidelines. Obstet Gynecol. 2013;121(5):969-975.

15. O'Reilly JR, Reynolds RM. The risk of maternal obesity to the long-term health of the offspring. Clin Endocrinol (Oxf). 2013;78(1):9-16.