Maternal Periconceptional Folic Acid Supplementation and Risk for Fetal Congenital Heart Defects.

OBJECTIVE: To determine the effects of maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid on the prevention of fetal congenital heart defects (CHDs). STUDY DESIGN: Data were drawn from a Prenatal Health Care System and a Birth Defects Surveillance System in a district of Beijing, China. A total of 63 969 singleton births, live or stillborn, 308 CHDs among them, during 2013 to 2018 were included. Associations between different patterns of supplementation and risk for total CHDs or main types of CHDs were evaluated with risk ratios (RRs). RESULTS: For folic acid or multiple micronutrients containing folic acid users compared with nonusers, the adjusted RRs (ARRs) for total CHDs, critical CHD, and ventricular septal defect (VSD) were 0.60 (95% CI, 0.44-0.83), 0.41 (95% CI, 0.26-0.67), and 0.47 (95% CI, 0.30-0.74), respectively. When we compared multiple micronutrients containing folic acid users with folic acid users, the ARRs were 0.84 (95% CI, 0.66-1.09), 0.64 (95% CI, 0.41-1.00), and 0.94 (95% CI, 0.63-1.41) for total CHDs, critical CHD, and VSD, respectively. We also found that, compared with supplementation initiated after conception, supplementation initiated before conception was associated with a lower risk for CHDs: the ARRs were 0.68 (95% CI, 0.48-0.95) for total CHDs and 0.26 (95% CI, 0.10-0.71) for critical CHD, but 1.08 (95% CI, 0.63-1.83) for VSD. CONCLUSIONS: Maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid seems to decrease the risk for CHDs, especially critical CHD, in offspring. Supplementation confers a greater protective effect when it is initiated before conception. We did not find any difference between folic acid and multiple micronutrients containing folic acid in terms of preventing CHDs.

Maternal serum level of manganese, single nucleotide polymorphisms, and risk of spontaneous preterm birth: A nested case-control study in China.

Manganese (Mn) is an essential trace element, but an excess or accumulation can be toxic. Until now, few studies have examined the effects of maternal Mn level on the risk of spontaneous preterm birth (SPB). The aims of this study were to examine the association between maternal Mn level and the risk of SPB at the early stage of pregnancy, and investigate whether this association was modified by single nucleotide polymorphisms (SNPs) in genes of superoxide dismutase (SOD) and catalase (CAT). We conducted a nested case-control study in three maternal and child health care hospitals in Shanxi province, China, from December 2009 to December 2013. From an overall cohort of 4229 women, 528 were included in our study, including 147 cases of SPB and 381 controls. Maternal blood samples were collected during 4-22 gestational weeks. The maternal serum concentrations of Mn was measured using inductively coupled plasma-mass spectrometry. We found the maternal Mn concentration in the case group (median: 1.55 ng/mL) was significantly higher than that in the control group (median: 1.27 ng/mL). Compared to the lowest level, the SPB risk was significantly increased to 1.44 (95%CI: 0.60-3.43), 2.42 (95%CI: 1.06-5.55) and 2.46 (95%CI: 1.08-5.62) respectively for the second, third and fourth quartiles in first trimester, but not significant in second trimester or overall. When exposure to a high Mn level, women who with AA (6.36, 95%CI: 1.57-25.71) and AG (3.04, 95%CI: 1.59-5.80) of rs2758352, with CC (2.34, 95%CI: 1.31-4.18) of rs699473, and with GG (2.26, 95%CI: 1.22-4.16) of rs769214 were more likely to develop a SPB, but not among women with other genotypes. In conclusion, high maternal serum Mn level is associated with the increased SPB risk in first trimester, and the association is modified by maternal SNPs of SOD2, SOD3 and CAT.

Concentrations of selected heavy metals in placental tissues and risk for neonatal orofacial clefts.

Orofacial clefts (OFCs) have multifactorial etiologies. Prenatal exposure to heavy metals can induce OFCs in animal models, but evidence from studies of human subjects is scarce. We examined whether concentrations of mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As) in placental tissues are associated with risk for OFCs in offspring. This population-based case-control study included 103 newborns affected by OFCs with available placental tissues and 206 controls randomly selected from 509 non-malformed newborns with available placenta samples, recruited in five rural counties in northern China. Sociodemographic information was collected using a structured questionnaire in face-to-face interviews. The concentrations of Hg, Cd, Pb, and As in placental tissues were analyzed using an inductively coupled plasma-mass spectrometry in helium mode. The median concentrations of Hg (7.4 ng/g), Cd (57.1 ng/g), and Pb (96.1 ng/g) were all statistically significantly higher in OFC cases than in controls (Hg 5.5 ng/g, Cd 38.6 ng/g, and Pb 67.9 ng/g, respectively); no differences were observed between the two groups in median concentrations of As. Concentrations above the median for all subjects were associated with a 2.33-fold (95% confidence interval [CI] 1.33-2.09) increased OFC risk for Cd and a 3.08-fold (95% CI 1.74-5.47) increased risk for Pb. The risk for OFCs increased with concentration tertiles, with an adjusted odds ratio of 3.06 (95% CI 1.36-6.88) for the second tertile and 8.18 (95% CI 6.64-18.37) for the highest tertile of Cd, and 3.88 (95% CI 1.78-8.42) for the second tertile and 5.17 (95% CI 2.37-11.29) for the highest tertile of Pb. The association between Hg concentration and OFC risk was borderline nonsignificant after adjusting for confounding factors. Prenatal exposure to Cd and Pb, as reflected by their concentrations in placental tissues, is associated with an increased risk for neonatal OFCs.

Impact of Periconceptional Folic Acid Supplementation on Low Birth Weight and Small-for-Gestational-Age Infants in China: A Large Prospective Cohort Study.

OBJECTIVES: To explore the effects of maternal folic acid supplementation alone during pregnancy on the incidence of low birth weight (LBW) and small-for-gestational-age (SGA) infant status. STUDY DESIGN: Data were derived from a large population-based cohort study performed in China to evaluate the prevention of neural tube defects with folic acid supplementation. The sample comprised 200 589 singleton live births registered in 2 southern Chinese provinces by mothers for whom detailed information on folic acid use was available. Gestational age was calculated from the first day of the last menstrual period. LBW was defined as a birth weight <2500 g. Infants were considered SGA when the age-adjusted birth weight was below the 10th percentile as defined by a national survey performed in 1998. Logistic regression was used to estimate the effects of folic acid after adjusting for the principal potential confounders. RESULTS: The overall incidence of LBW and SGA status was 2.18% and 5.82%, respectively. The incidence of LBW and SGA status was 2.09% and 5.73% in women who took folic acid, and 2.27% and 5.90% in those who did not. The adjusted risk ratios associated with folic acid use were 0.85 (95% CI: 0.80-0.90) for LBW and 0.93 (95% CI: 0.89-0.96) for SGA status. Folic acid use during pregnancy appeared to be particularly important to prevent LBW and SGA status. CONCLUSIONS: A maternal daily intake of 400 µg folic acid alone significantly reduced the risks of infant LBW and SGA status.

Maternal Hemoglobin Concentration during Gestation and Risk of Anemia in Infancy: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: This study examined the relationship between maternal hemoglobin (Hb) concentration and the risk of anemia in infancy. STUDY DESIGN: This analysis included 17 193 women who entered the trial when they were ≥20 years of age, no more than 20 weeks of gestation, had mild or no anemia, and delivered singleton live births. Maternal Hb concentrations were measured in the first trimester and during 24-28 weeks of gestation; infant Hb concentrations were measured at 5-7 months and 11-13 months of life. The associations between maternal Hb concentrations and infant Hb concentrations were examined. RESULTS: Maternal Hb concentrations measured during 24-28 weeks of gestation, but not in the first trimester, were correlated with infant Hb concentrations measured at either of the 2 post-partum periods. The risk of infant anemia at 5-7 months of age increased when maternal Hb concentration was ≤109 g/L during 24-28 weeks of gestation (aOR, 1.95; 95% CI, 1.59-2.40) and 11-13 months of age (aOR, 1.72; 95% CI, 1.36-2.18), whereas the risk of anemia during 5-7 months of age as well as 11-13 months in infancy decreased when maternal Hb level at 24-28 weeks of gestation was 120-129 g/L (aOR for 5-7 months, 0.74 [95% CI, 0.64-0.85]; aOR for 11-13 months, 0.72 [95% CI, 0.61-0.85]), or ≥130 g/L (aOR for 5-7 months, 0.75 [95% CI, 0.63-0.90]; aOR for 11-13 months, 0.89 [95% CI, 0.73-1.08]). CONCLUSIONS: Low maternal Hb concentration during 24-28 weeks of gestation was associated with an increased risk of anemia in infancy, whereas high maternal Hb concentration was associated with a reduced risk of anemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00133744.