Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort

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Abstract
Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (β = 0.052, 95% CI 0.012–0.090, EV: β = 0.022, 95% CI 0.002–0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended. This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest. NTR4356.
Funding Information
  • Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center (09120011910046)

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