Abstract

Introduction: Adverse pregnancy outcomes (APOs) have been linked with maternal mortality, higher risk of metabolic and cardiovascular diseases, and adverse neonatal outcomes. The World Health Organization recommends the adoption of a healthy lifestyle (maintaining a normal BMI, not smoking, regular exercise, healthy diet, avoiding harmful alcohol intake, and multivitamin supplementation) before conception to improve pregnancy health. However, the combined effect of these lifestyle factors on reducing APOs is unknown. Hypothesis: Adherence to healthy lifestyle prior to pregnancy may be associated with a lower risk of subsequent development of APOs. Methods: We followed 15,509 women without chronic diseases (27,135 pregnancies) and participating in an ongoing cohort in the United States, the Nurses’ Health Study II. Healthy lifestyle factors preceding pregnancy were prospectively assessed every 2 to 4 years from 1991 to 2009, using validated measures. Reproductive history was self-reported in 2001 and 2009. A composite outcome of APOs included miscarriage, ectopic pregnancy, gestational diabetes, gestational hypertension, preeclampsia, preterm birth, stillbirth, and low birth weight (<5.5 lbs). We estimated the relative risks (RRs) of APOs according to the number of healthy lifestyle factors (0-6), using Poisson regression models with generalized estimating equations, specifying an exchangeable correlation structure, adjusting for maternal age, race/ethnicity, year of birth, history of infertility, parity, and interpregnancy interval. Results: The mean (SD) maternal age was 35.1 (4.2) years. Nearly one in three pregnancies (N=9,702, 35.8%) were complicated with an APO. All healthy lifestyle factors, except alcohol consumption, were independently associated with APOs after mutual adjustment for each other. The combination of 6 low-risk factors (BMI=18.5-24.9 kg/m 2 , non-smoking, ≥150 minutes/week of moderate to vigorous physical activity, healthy eating (top 40% of Dietary Approaches to Stop Hypertension score), low-to-moderate alcohol intake (<15 g/day), and use of multivitamin) was inversely associated with risk of APOs, in a dose-dependent manner ( P trend<0.001). Compared to women who had 0 or 1 healthy lifestyle factors, those with 6 had a 45% lower risk of APOs (RR=0.55, 95% CI=0.44-0.68). The associations were stronger among women who were <35 years or had BMI <25 kg/m 2 but did not differ by parity. If the relationships were causal, 10% of APOs in the study population could have been prevented by the adoption of all 6 healthy lifestyle factors (population attributable risk=10%, 95% CI=6%-14%). Conclusions: Our findings suggest that pre-conception healthy lifestyle is associated with a substantially lower risk of APOs and could be an effective intervention for the prevention of APOs and their downstream long-term maternal and offspring health consequences.

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