The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth Outcomes: A Prospective Study in Chinese.

BACKGROUND: The effect of iron supplementation during pregnancy on birth outcomes may vary with maternal genetic background and needs more investigation. OBJECTIVES: This prospective study aimed to evaluate the interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes. METHODS: This was a substudy from a community-based randomized control trial conducted in Northwest China, which included 860 women from the 2 micronutrient supplementation groups (folic acid [FA] and FA + iron group). Maternal peripheral blood, sociodemographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms in iron metabolism-related genes were genotyped. The alleles associated with decreased iron/hemoglobin status were used as the effect alleles. The genetic risk score (GRS) that reflected the genetic risk of low iron/hemoglobin status was estimated using the unweighted and weighted methods. Generalized estimating equations with small-sample corrections were applied to evaluate the interactions between iron supplementation and SNPs/GRS on birth outcomes. RESULTS: There were significant interactions between maternal iron supplementation and rs7385804 (P = 0.009), rs149411 (P = 0.035), rs4820268 (P = 0.031), the unweighted GRS (P = 0.018), and the weighted GRS (P = 0.009) on birth weight. Compared with FA supplementation only, FA + iron supplementation significantly increased birth weight among women with more effect alleles in rs7385804 (ß: 88.8 g, 95% CI: 9.2, 168.3) and the GRSs (the highest unweighted GRS, ß: 135.5 g, 95% CI: 7.7, 263.4; the highest weighted GRS, ß: 145.9 g, 95% CI: 43.4, 248.5); it had a trend of decreasing birth weight and increasing low birth weight risk among women with fewer effect alleles. CONCLUSIONS: In our population, maternal genetic background related to iron metabolism plays a significant role in determining the efficacy of iron supplementation. Routine iron supplementation could be more beneficial to fetal weight growth among mothers with higher genetic risk for low iron/hemoglobin status.

Association of maternity formula supplementation during pregnancy with small for gestational age birth in Chinese newborns.

OBJECTIVES: This study aimed to explore the association between maternity formula supplementation and small for gestational age (SGA) status in Chinese newborns. METHODS: Data were from a population-based cross-sectional survey conducted in Shaanxi, Northwest China between August and December 2013. A total of 27 780 women pregnant with singletons and 356 with twins were included in this survey. Information on use of maternity formulas fortified with vitamins, folic acid, pantothenic acid, calcium, iron, zinc, and docosahexaenoic acid (DHA) was collected. SGA was defined as birthweight <10th percentile of fetal growth. Generalized linear models and estimating equation models were used to estimate crude odds ratios (ORs) or adjusted ORs with 95% confidence intervals (CIs) for SGA. RESULTS: The rate of maternity formula supplementation during the entire pregnancy was 13.0% in the overall population. There was no significant association between maternal formula supplementation during pregnancy and the risk of total SGA birth (OR: 1.00; 95% CI, 0.90-1.11; P = 0.950). However, maternity formula supplementation during pregnancy was related to a lower risk of SGA for twins (OR: 0.49; 95% CI, 0.31-0.80; P = 0.004), twin A (OR: 0.50; 95% CI, 0.25-0.98; P = 0.045), and twin B (OR: 0.48; 95% CI, 0.25-0.95; P = 0.034). Furthermore, maternity formula supplementation during the first trimester was inversely associated with the risk of SGA birth of twins (OR: 0.32; 95% CI, 0.15-0.65; P = 0.002). CONCLUSIONS: No significant association was observed between maternity formula supplementation and total SGA birth. However, women supplemented with maternal formula during pregnancy, especially during the first trimester, may have a reduced risk of SGA birth of twins.

Maternal Zinc, Copper, and Selenium Intakes during Pregnancy and Congenital Heart Defects.

The effects of zinc, copper, and selenium on human congenital heart defects (CHDs) remain unclear. This study aimed to investigate the associations of the maternal total, dietary, and supplemental intakes of zinc, copper, and selenium during pregnancy with CHDs. A hospital-based case-control study was performed, including 474 cases and 948 controls in Northwest China. Eligible participants waiting for delivery were interviewed to report their diets and characteristics in pregnancy. Mixed logistic regression was adopted to examine associations and interactions between maternal intakes and CHDs. Higher total intakes of zinc, selenium, zinc to copper ratio, and selenium to copper ratio during pregnancy were associated with lower risks of total CHDs and the subtypes, and the tests for trend were significant (all p < 0.05). The significantly inverse associations with CHDs were also observed for dietary intakes of zinc, selenium, zinc to copper ratio, selenium to copper ratio, and zinc and selenium supplements use during pregnancy and in the first trimester. Moreover, high zinc and high selenium, even with low or high copper, showed a significantly reduced risk of total CHDs. Efforts to promote zinc and selenium intakes during pregnancy need to be strengthened to reduce the incidence of CHDs in the Chinese population.

Association between maternal iron supplementation and newborn birth weight: a quantile regression analysis.

OBJECTIVE: Our study aimed to explore the association between maternal iron supplementation and newborn birth weight (BW) in Shaanxi Province using quantile regression (QR). METHOD: The data used in this study were derived from a large cross-sectional survey of a population in Shaanxi Province, Northwest China. A total of 28,209 women and their infants were selected using a stratified multistage random sampling method. The effect of iron supplementation on the newborn BW was assessed by a multiple linear regression model and QR. RESULTS: A total of 5.15% of the women took iron supplements during pregnancy. Multiple linear regression showed that the iron supplementation during pregnancy had positive effects on the BW, with an average increase of 43.07 g (ß = 43.07, t = 3.55, and p < 0.001). The QR showed that the iron supplementation during pregnancy was associated with an increased newborn BW from very low to higher percentiles (quantiles: 0 ~ 0.40), with the ß ranging from 136.51 to 43.86. As the percentiles of the BW increased, the neonatal BW gain gradually declined in the iron supplementation group compared with the group that did not receive iron supplementation (quantiles: 0 ~ 0.40, with the ß ranging from 136.51 to 43.86). Iron supplementation was more effective among women who suffered from anemia during pregnancy (ß = 45.84, t = 2.05, and p = 0.04; quantiles: 0 ~ 0.15, 0.30, 0.80, with ß ranging from 150.00 to 39.29) than it was in any other group (ß = 38.18, t = 2.62, and p = 0.009; quantiles: 0 ~ 0.15, with ß ranging from 133.33 to 28.32). CONCLUSIONS: Iron supplementation during pregnancy is associated with an increased newborn BW, and the effect was more obvious in the newborns with the lower BW and newborns whose mothers suffered from anemia during pregnancy.

Associations between maternal calcium intake from diet and supplements during pregnancy and the risk of preterm birth in a Chinese population.

BACKGROUND/OBJECTIVES: Preterm birth is a global public health priority related to maternal nutrition. The effect of maternal calcium intake during pregnancy on preterm birth is inconclusive and data is lacking in China. We aimed to estimate the role of calcium intake from diet and supplements on preterm birth in the Chinese population. METHODS: We used data of 7195 women from a large-scale cross-sectional study in Northwest China. Dietary intake was evaluated via a validated food frequency questionnaire, and other information was collected by a structured questionnaire. Generalized estimating equation models were used to estimate the relationship between calcium intake and preterm birth. RESULTS: Inadequate dietary calcium intake was universal in our population (85.9%), and no association was found between daily dietary calcium intake and preterm birth. Maternal calcium supplementation was significantly associated with reduced risk of preterm birth (OR 0.72, 95% CI 0.60, 0.87, P = 0.001), particularly among women who commenced calcium supplementation in the second and third trimester of pregnancy with longer duration (OR 0.62, 95% CI 0.42, 0.91, P = 0.015). Higher daily calcium intake from supplements was linked with lower preterm birth risk (every 100 mg increase: OR 0.87, 95% CI 0.79, 0.96, P = 0.004). There is a negative association between daily total calcium intake and preterm birth among calcium supplement users (every 100 mg increase: OR 0.91, 95% CI 0.84, 0.97, P = 0.007). CONCLUSIONS: In conclusion, appropriate calcium supplementation during pregnancy could be beneficial in the prevention of preterm birth, and it might be suitable for implementing in low calcium intake areas of China.

Maternal folic acid supplementation and more prominent birth weight gain in twin birth compared with singleton birth: a cross-sectional study in northwest China.

OBJECTIVE: To investigate the association of folic acid (FA) supplementation with birth weight, the risk of small for gestational age (SGA) and low birth weight (LBW) in singleton and twin pregnancy. DESIGN: A population-based cross-sectional survey. SETTING: Twenty counties and ten districts in Shaanxi Province of northwestern China, 2013. PARTICIPANTS: 28 174 pregnant women with their infants, covering 27 818 single live births and 356 twin live births. RESULTS: The prevalence of FA supplementation in singletons and twins was 63·9 and 66·3 %. The mean birth weight was 3267 (sd 459·1) g, 2525 (sd 534·0) g and 2494 (sd 539·5) g; the prevalence of SGA was 14·3, 51·4 and 53·4 %; the prevalence of LBW was 3·4, 42·4 and 46·6 % among singleton, twin A and twin B, respectively. Compared with non-users, women with FA supplementation were (ß 17·3, 95 % CI 6·1, 28·4; ß 166·3, 95 % CI 69·1, 263·5) associated with increased birth weight, lower risk of SGA (OR 0·85, 95 % CI 0·80, 0·92; OR 0·45, 95 % CI 0·30, 0·68) and LBW (OR 0·82, 95 % CI 0·71, 0·95; OR 0·50, 95 % CI 0·33, 0·75) in singletons and twins, and more prominent effects in twins. Moreover, there were significant interactions between FA supplementation and plurality on birth weight, SGA and LBW. CONCLUSIONS: The present study suggests the association of periconceptional 0·4 mg/d FA supplementation with increased birth weight and reduced risk of SGA and LBW in both singletons and twins, and this association may be more prominent in twins.

The association of maternal dietary folate intake and folic acid supplementation with small-for-gestational-age births: a cross-sectional study in Northwest China.

The effect of maternal folate intake on small-for-gestational-age (SGA) births remains inconclusive. The present study aimed to investigate the associations of maternal folate intake from diet and supplements with the risk of SGA births using data from a cross-sectional study in Shaanxi Province of Northwest China. A total of 7307 women who were within 12 months (median 3; 10th-90th percentile 0-7) after delivery were included. Two-level models were adopted to examine the associations of folate (dietary folate, supplemental folic acid and total folate) intake with the risk of SGA births and birth weight Z score, controlling for a minimum set of confounders that were identified in a directed acyclic graph. Results showed that a higher supplemental folic acid intake during the first trimester was negatively associated with the risk of SGA births (≤60 d v. non-use: OR 0·80; 95 % CI 0·66, 0·96; >60 d v. non-use: OR 0·78; 95 % CI 0·65, 0·94; Ptrend = 0·010; per 10-d increase: OR 0·97; 95 % CI 0·95, 0·99). A higher total folate intake during pregnancy was associated with a reduced risk of SGA births (highest tertile v. lowest tertile: OR 0·77; 95 % CI 0·64, 0·94; Ptrend = 0·010; per one-unit increase in the log-transformed value: OR 0·81; 95 % CI 0·69, 0·95). A similar pattern was observed for the birth weight Z score. Our study suggested that folic acid supplementation during the first trimester and a higher total folate intake during pregnancy were associated with a reduced risk of SGA births.