Nonlinear Relationship Between Maternal and Cord Blood Vitamin B12 and Folate from a Chinese Population-Based Study.

Purpose: There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS). Materials and Methods: This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined. Results: Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P <0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94-2.06) and 2.4 (95% CI: 2.30-2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve. Conclusion: Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy.

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.

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884.

What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber ­ gut microbiota (Anaerostipes)­constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.

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.

The Association of Folic Acid, Iron Nutrition during Pregnancy and Congenital Heart Disease in Northwestern China: A Matched Case-Control Study.

Background: The purpose of this study was to investigate the relationship between folic acid and iron nutrition during pregnancy and congenital heart disease (CHD) in the offspring. Methods: Conditional logistic regression models and nonlinear mixed-effects models were used to analyze the effects of folic acid and iron nutrition during pregnancy on CHD in offspring. Results: After adjusting for confounders, folic acid or iron supplementation during pregnancy reduced the risk for fetal CHD (OR = 0.60 (0.45, 0.82) or 0.36 (0.27, 0.48)). Similarly, dietary iron intake during pregnancy (≥29 mg/d) was associated with a reduced risk of fetal CHD (OR = 0.64 (0.46, 0.88)). Additionally, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or iron (OR = 0.32 (0.16, 0.60)), women who supplemented both folic acid and iron had lower risk for newborns with CHD (OR = 0.22 (0.15, 0.34)). Similarly, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or higher dietary iron intake (≥29 mg/d) (OR = 0.60 (0.33, 1.09)), women who supplemented both folic acid and higher dietary iron intake (≥29 mg/d) had lower risk for the newborn with CHD (OR = 0.41 (0.28, 0.62)). The combined effects were significant in the multiplication model (OR = 0.35 (0.26, 0.48) or 0.66 (0.50, 0.85)) but not in the additive model. Conclusions: Our study found that folic acid and iron nutrition during pregnancy were associated with a reduced risk of CHD in the offspring and confirmed a statistically significant multiplicative interaction between folic acid and iron nutrition on the reduced risk of CHD in offspring.

Risk Assessment for Birth Defects in Offspring of Chinese Pregnant Women.

OBJECTIVE: This study aimed to develop a nomogram for the risk assessment of any type of birth defect in offspring using a large birth-defect database in Northwest China. METHODS: This study was based on a birth-defect survey, which included 29,204 eligible women who were pregnant between 2010 and 2013 in the Shaanxi province of Northwest China. The participants from central Shaanxi province were assigned to the training group, while the subjects from the south and north of Shaanxi province were assigned to the external validation group. The primary outcome was the occurrence of any type of birth defect in the offspring. A multivariate logistic regression model was used to establish a prediction nomogram, while the discrimination and calibration were evaluated by external validation. RESULTS: The multivariate analyses revealed that household registration, history of miscarriages, family history of birth defects, infection, taking medicine, pesticide exposure, folic acid supplementation, and single/twin pregnancy were significant factors in the occurrence of birth defects. The area under the receiver operating characteristic curve (AUC) in the prediction model was 0.682 (95% CI 0.653 to 0.710) in the training set. The validation set showed moderate discrimination, with an AUC of 0.651 (95% CI 0.614 to 0.689). Additionally, the prediction model had a good calibration (HL χ2 = 8.106, p= 0.323). CONCLUSIONS: We developed a nomogram risk model for any type of birth defect in a Chinese population based on important modifying factors in pregnant women. This risk-prediction model could be a tool for clinicians to assess the risk of birth defects and promote health education.

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.

Association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status: evidence from a cluster randomized controlled trial.

PURPOSE: Evidence about the effect of maternal vitamin B12 supplementation on offspring's vitamin B12 status is limited. The present interventional study sought to evaluate the association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status. METHODS: In an ongoing cluster randomized controlled trial conducted in three rural counties in northwest China, pregnant women < 20 weeks of gestation were randomized to three treatment groups: blank control, iron supplements, or vitamin B complex supplements. All women were administered folic acid supplements during the periconceptional period. In a sub-study, we collected cord blood samples of 331 participants from the control or vitamin B complex groups in the Xunyi county from January 2017 to December 2017. Plasma concentrations of folate, vitamin B12, and homocysteine were measured. Linear mixed models with a random intercept for cluster were used to compare biochemical indexes between groups after controlling for covariates. RESULTS: Compared with newborns whose mothers were in the control group, newborns of the vitamin B complex-supplemented women had significantly higher cord plasma vitamin B12 (P = 0.001) and lower homocysteine concentrations (P = 0.043). The association of antenatal vitamin B complex supplementation with cord blood vitamin B12 concentrations appeared to be more pronounced among newborns with high folate status than those with low folate status (Pinteraction = 0.060). CONCLUSIONS: Maternal vitamin B complex supplementation during pregnancy was associated with better neonatal vitamin B12 status in rural northwest China.

Maternal B-vitamin intake and B-vitamin supplementation during pregnancy in relation to neonatal congenital heart defects: a case-control study with propensity score matching.

BACKGROUND/OBJECTIVES: The effect of dietary folate intake or folic acid (FA) supplementation during pregnancy on neonatal congenital heart defects (CHDs) remains inconclusive. There are limited data about non-folate-B-vitamin intake and the risk of CHDs. Furthermore, few studies have investigated dietary B-vitamin intake and B-vitamin supplement use simultaneously in relation to the risk of CHDs. This study aimed to explore the associations between maternal folate, vitamin B6, and vitamin B12 intake (dietary intake, total intake from diet and supplements); B-vitamin supplement use during pregnancy; and the risk of CHDs using the propensity score matching (PSM) method. METHODS: We conducted a case-control study and included 760 cases and 1600 controls in Shaanxi Province, China. Diet, supplement use and other information were collected through a questionnaire interview. By using the 1:2 ratio PSM method, 396 cases were matched with 792 controls. Conditional logistic regression was used to investigate the associations between maternal B-vitamin intake and supplement use during pregnancy and CHDs. RESULTS: Higher maternal dietary and total intake of folate and vitamin B12 were associated with reduced risk of CHDs, and the tests for linear trend were significant. Compared with non-users, maternal FA + VB6 + VB12 containing supplement use during pregnancy (OR 0.61, 95%CI 0.40-0.94), FA supplement use during pregnancy (OR 0.70, 95%CI 0.50-0.98) and in the first trimester (OR 0.62, 95%CI 0.46-0.85) were associated with a lower risk of CHDs. CONCLUSIONS: The findings of this study suggest that a higher intake of folate and vitamin B12 during pregnancy reduces the risk of CHDs.

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.

Parameterization of the mid-trimester drop in blood pressure trajectory during pregnancy and its utility for predicting preeclampsia.

OBJECTIVES: The purpose of this study was to parameterize mid-trimester drop in blood pressure (BP) trajectory during pregnancy and to evaluate its utility for predicting preeclampsia. METHODS: To develop parametric models for BP trajectory during pregnancy, we used data from 7923 Chinese pregnant women with 24 810 routine antenatal care visits. Then, we evaluated the utility of BP trajectory parameters for predicting clinician-diagnosed preeclampsia in a separate sample of 3524 pregnant women from a randomized controlled trial of prenatal vitamin supplementation conducted in the same area. We focused on parameters related to the mid-trimester BP drop, including the gestational age and BP value at the nadir (lowest point), change in BP, velocity, and area under curve during two periods (from 12 weeks of gestation to the nadir and from the nadir to 33 weeks of gestation). RESULTS: All participants in our analysis had a mid-pregnancy drop in their SBP, DBP, and mean arterial pressure (MAP) trajectories. There were high correlations (|r| > 0.90) among trajectory parameters of the same BP measure. The final prediction model included selective parameters of SBP, DBP, and MAP trajectories, prepregnancy BMI and gestational age at the first antenatal care visit. The area under the receiver-operating curve for predicting preeclampsia was 0.886 (95% confidence interval 0.846--0.926) in the training dataset and 0.802 (0.708--0.895) in the validation dataset. CONCLUSION: Our novel BP trajectory parameters are informative and can predict preeclampsia at a clinically acceptable level.

Iron intake and iron status during pregnancy and risk of congenital heart defects: A case-control study.

BACKGROUND: The relationships between iron nutritional status and congenital heart defects (CHDs) among humans are still unclear. This study aimed to explore the associations of maternal iron intake during pregnancy and maternal and neonatal iron status with CHDs. METHODS: This hospital-based case-control study analyzed 474 cases and 948 controls in Shaanxi China. Eligible women waiting for delivery in the hospital were interviewed to report their diets and characteristics during pregnancy. We conveniently collected maternal blood before delivery and neonatal cord blood to get a subgroup of 50 cases and 100 controls. Mixed logistic regression models were used to estimate ORs (95%CIs) for CHDs associated with iron intake. Mixed linear regression models were used to assess the relationships between CHDs and iron status. RESULTS: Mothers whose fetuses have CHDs were less likely to have higher intakes of total iron and heme iron during pregnancy, and the tests for linear trend were significant (all P < 0.05). Mothers whose fetuses have CHDs were less likely to take iron supplements during pregnancy (OR = 0.28, 95%CI: 0.21, 0.36) and during the first trimester (OR = 0.32, 95%CI: 0.12, 0.84). Maternal SF and Hb concentrations before delivery were lower and maternal sTfR/SF before delivery was higher among the cases than the controls. CONCLUSIONS: Mothers whose fetuses have CHDs are less likely to have higher intakes of total iron and heme iron and take iron supplements during pregnancy compared to their counterparts. Maternal iron status before delivery is low among mothers whose fetuses have CHDs.

Maternal adherence to micronutrient supplementation before and during pregnancy in Northwest China: a large-scale population-based cross-sectional survey.

OBJECTIVES: To report the situation of maternal micronutrient supplementation before and during pregnancy in Northwest China and to examine the rates of and factors related to the adherence to micronutrient supplementation among pregnant women in this region, where dietary micronutrient intake is commonly insufficient. DESIGN: A large-scale population-based cross-sectional survey. SETTING: Twenty counties and ten districts of Shaanxi Province. PARTICIPANTS: A sample of 30 027 women were selected using a stratified multistage random sampling method. A total of 28 678 women were chosen for the final analysis after excluding those who did not provide clear information about nutritional supplementation before and during pregnancy. MAIN OUTCOME MEASURES: Maternal adherence to micronutrient supplementation (high and low) were the outcomes. They were determined by the start time and duration of use according to Chinese guidelines (for folic acid (FA) supplements) and WHO recommendations (for iron, calcium and multiple-micronutrient (MMN) supplements). RESULTS: In total, 83.9% of women took at least one kind of micronutrient supplement before or during pregnancy. FA (67.6%) and calcium (57.5%) were the primarily used micronutrient supplements; few participants used MMN (14.0%) or iron (5.4%). Adherence to supplementation of all micronutrients was low (7.4% for FA, 0.6% for iron, 11.7% for calcium and 2.7% for MMN). Higher educational levels, higher income levels, urban residence and better antenatal care (including pregnancy consultation and a higher frequency of antenatal visits) were associated with high adherence to micronutrient supplementation. CONCLUSION: Maternal micronutrient supplementation before and during pregnancy in Northwest China was way below standards recommended by the Chinese guidelines or WHO. Targeted health education and future nutritional guidelines are suggested to improve this situation, especially in pregnant women with disadvantaged sociodemographic conditions.

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.

A propensity-matched study of the association between optimal folic acid supplementation and birth defects in Shaanxi province, Northwestern China.

The association between folic acid supplementation and birth defects other than neural tube defects remains unclear. We utilized data from a large population-based survey to examine the association between folic acid supplementation and birth defects in Northwestern China. A total of 29,204 women with infants born between 2010 and 2013 were surveyed in Shaanxi province, Northwestern China, using a stratified multistage sampling method. Propensity scores were used to match 9,293 women with optimal folic acid supplementation with 9,293 women with nonoptimal folic acid supplementation, and the effects of optimal folic acid supplementation on birth defects were assessed by a conditional logistic regression model. After propensity score matching, the overall birth defect rate, cardiovascular system defect rate and nervous system defect rate for the women with optimal folic acid supplementation were lower than those for the women with nonoptimal folic acid supplementation (overall birth defects: OR = 0.71, 95% CI = 0.57-0.89, P = 0.003; cardiovascular system defects: OR = 0.65, 95% CI = 0.44-0.96, P = 0.032; nervous system defects: OR = 0.13, 95% CI = 0.02-0.99, P = 0.049). Optimal folic acid supplementation was associated with a decreased prevalence of birth defects, especially in the cardiovascular system and nervous system. Our findings have important implications for birth defect intervention with folic acid supplementation for countries with a high prevalence of birth defects, such as China.

Effect of maternal pre-pregnancy underweight and average gestational weight gain on physical growth and intellectual development of early school-aged children.

The aim of this study was to assess the effect of low maternal weight at pre-pregnancy and the average gestational weight gain on undernourished children and their intellectual development. From October 2012 to September 2013, we followed 1744 offspring of women who participated in a trial conducted from 2002 to 2006. Pregnant women recruited in the original trial could receive three prenatal health checks for free, at which maternal weight and height were measured. WISC-IV was used to estimate the intellectual development of children. Weight and height of both pregnant women and children were measured by trained anthropometrists using standard procedures. Having low maternal weight at pre-pregnancy was associated with an increased risk of undernutrition amongst children (underweight: OR = 2.02, 95%CI: 1.14-3.56, thinness: OR = 2.79, 95%CI: 1.50-5.17) and a decrease in verbal comprehension index (-2.70 points, 95%CI: -4.95-0.44) of children. The effect of average gestational weight gain on occurrences of underweight children (OR = 0.08, 95%CI: 0.01-0.55) was also found. We identified the effect of maternal pre-pregnancy underweight on impairment of the separate intellectual domains (verbal comprehension index) and increasing occurrence of undernourished children. Average gestational weight gain was positively associated with a decreased prevalence of underweight children but not with the intellectual development of children in rural China.

The different effects of prenatal nutrient supplementation on neonatal birth weights between urban and rural areas of northwest China: a crosssectional study.

BACKGROUND AND OBJECTIVES: The results of prenatal nutrient supplementation on birth weight are inconsistent in different areas. This study aimed to investigate whether the effects of prenatal iron plus folic acid and folic acid supplementation on neonatal birth weights differed between urban and rural areas of Northwest China. METHODS AND STUDY DESIGN: A stratified multistage random sampling method was used to recruit women between the ages of 15 and 49 and their offspring born between 2010 and 2013 from 10 urban areas and 20 rural areas of the Shaanxi Province of Northwest China. Information regarding socio-demographics and prenatal nutrient supplementation status was collected using a standardized questionnaire, and the neonatal birth weights were obtained from the birth certificates. Multilevel models were established separately for the urban and rural areas to assess the effects of prenatal nutrient supplementation on neonatal birth weights. RESULTS: The association between prenatal nutrient supplementation and neonatal birth weight was not statistically significant in urban areas. However, in rural areas, prenatal iron plus folic acid and folic acid supplementation increased the mean birth weights by 45.3 g (9.4 to 81.1 g, p=0.014) and 30.9 g (15.6 to 46.1 g, p<0.001), respectively. CONCLUSIONS: The effects of prenatal nutrient supplementation on neonatal birth weights differ between urban and rural areas of Northwest China. The different effects may be due to the different nutritional status of the urban and rural pregnant women. Prenatal nutrient supplementation may be a helpful way for improving neonatal birth weight in rural areas.

Multi-micronutrient supplementation during pregnancy for prevention of maternal anaemia and adverse birth outcomes in a high-altitude area: a prospective cohort study in rural Tibet of China.

Anaemia during pregnancy, characterised by Hb <110 g/l, is a specific risk factor for adverse maternal and perinatal outcomes in developing countries. The objective of this study was to determine the effectiveness of daily antenatal supplementation with multiple micronutrients (MMN) compared with folic acid (FA) on the occurrence of anaemia among pregnant women and their infants' health in a high-altitude area. A prospective cohort study was carried out in two rural counties in Tibet from 2007 to 2012. A total of 1149 eligible pregnant women were allocated daily supplementation with FA in one county and MMN containing a recommended allowance of twenty-three vitamins and minerals in another county starting ≤24 weeks of gestation and continuing until delivery. Compared with the FA group, prenatal supplementation with MMN was significantly associated with reduced odds of anaemia in the third trimester. This was demonstrated in the primary outcome, with an adjusted OR (AOR) of 0·63; 95 % CI 0·45, 0·88 and P=0·007 and also reduced odds of preterm delivery (AOR: 0·31; 95 % CI 0·15, 0·61; P=0·001). There was no difference between MMN and FA groups in mean birth weight (adjusted mean difference: 36·78; 95 % CI -19·42, 92·98 g; P=0·200), whereas MMN supplementation significantly reduced the odds of low-birth weight (LBW) babies (AOR: 0·58; 95 % CI 0·36, 0·91; P=0·019). In conclusion, the antenatal MMN supplementation in rural Tibet is associated with a reduction of maternal anaemia in the third trimester, and may potentially decrease the risk of preterm delivery and LBW babies.