Department of Epidemiology, Boston University School of Public Health, Boston, MA USA.
Center for Birth Defects Research and Prevention, Massachusetts Department of Public Health, Boston, MA USA.
Am J Clin Nutr. 2021 Jun 1;113(6):1688-1699. doi: 10.1093/ajcn/nqaa436.
Research suggests short interpregnancy intervals increase risks for adverse perinatal outcomes, including some birth defects. A hypothesized cause is nutritional depletion, including folic acid (FA).
We evaluated associations between short interpregnancy intervals, alone and in combination with FA intake, and the occurrence of select malformations.
Data were from the National Birth Defects Prevention Study (US case-control, 1997-2011). Participants included multiparous women whose prior pregnancy resulted in live birth. Cases included 8 noncardiac and 6 cardiac defect groups (n = 3219); controls were nonmalformed live-borns (n = 2508). We categorized interpregnancy interval (<6, 6-11, 12-17, and 18-23 mo) and periconceptional FA intake [no FA supplement use and dietary folate equivalents (DFE) <400 µg/d, no FA supplement use and DFE ≥400 µg/d, or any FA supplement use]. We controlled for age, race/ethnicity, income, pregnancy intention, and study center. ORs <0.8 or >1.2 were considered to represent potentially meaningful associations.
ORs for <6 compared with 18-23 mo were >1.2 for 4/8 noncardiac and 3/6 cardiac malformations. Among participants with any FA supplement use, ORs comparing <6 with 6-23 mo were <1.2 for most defects. Conversely, most ORs were >1.2 for <6 mo + no FA supplement use and DFE <400 µg/d compared with 6-23 mo + any FA supplement use. Magnitude and precision varied by defect.
Short interpregnancy intervals were associated with a trend of higher risks for several defects, notably in the absence of FA supplement use. To our knowledge, our study is the first to provide preliminary empirical support that these etiologies may be related to shorter interpregnancy intervals and possible nutritional deficiencies. Because FA intake is highly correlated with other nutrients, and because our estimates were generally imprecise, more research with larger sample sizes is needed to better understand the role of FA compared with other nutrients in each defect-specific etiology.
研究表明，妊娠间隔过短会增加不良围产期结局的风险，包括一些出生缺陷。一个假设的原因是营养耗竭，包括叶酸（FA）。
我们评估了妊娠间隔过短，单独和与 FA 摄入相结合，与某些畸形发生的关联。
数据来自美国国家出生缺陷预防研究（病例对照，1997-2011 年）。参与者包括多胎产妇，其先前的妊娠导致活产。病例包括 8 个非心脏缺陷组和 6 个心脏缺陷组（n=3219）；对照组为无畸形的活产儿（n=2508）。我们将妊娠间隔（<6、6-11、12-17 和 18-23 个月）和围孕期 FA 摄入（无 FA 补充剂使用和膳食叶酸当量（DFE）<400 µg/d、无 FA 补充剂使用和 DFE≥400 µg/d 或任何 FA 补充剂使用）进行分类。我们控制了年龄、种族/民族、收入、妊娠意图和研究中心。OR<0.8 或>1.2 被认为代表有意义的关联。
与 18-23 个月相比，<6 个月的 OR 对于 4/8 个非心脏缺陷和 3/6 个心脏缺陷均>1.2。在使用任何 FA 补充剂的参与者中，与 6-23 个月相比，<6 个月与大多数缺陷的 OR<1.2。相反，与 6-23 个月+任何 FA 补充剂使用相比，<6 个月+无 FA 补充剂使用和 DFE<400 µg/d 的大多数 OR>1.2。严重程度和精度因缺陷而异。
妊娠间隔过短与几种缺陷的风险升高趋势相关，尤其是在没有 FA 补充剂使用的情况下。据我们所知，我们的研究首次提供了初步的实证支持，表明这些病因可能与妊娠间隔较短和可能的营养缺乏有关。由于 FA 摄入与其他营养素高度相关，而且我们的估计通常不够精确，因此需要更大样本量的更多研究来更好地了解 FA 与其他营养素在每个特定缺陷病因中的作用。
