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? What is new? What is the impact? Graphical abstract

Objective To examine the impact of antenatal supplementation with multiple micronutrients or iron and folic acid compared with folic acid alone on birth weight, duration of gestation, and maternal haemoglobin concentration in the third trimester. Design Cluster randomised double blind controlled trial. Setting Two rural counties in north west China. Participants 5828 pregnant women and 4697 live births. Interventions Villages were randomised for all pregnant women to take either daily folic acid (control), iron with folic acid, or multiple micronutrients with a recommended allowance of 15 vitamins and minerals. Main outcome measures Birth weight, length, and head circumference measured within 72 hours after delivery. Neonatal survival assessed at the six week follow-up visit. Results Birth weight was 42 g (95% confidence interval 7 to 78 g) higher in the multiple micronutrients group compared with the folic acid group. Duration of gestation was 0.23 weeks (0.10 to 0.36 weeks) longer in the iron-folic acid group and 0.19 weeks (0.06 to 0.32 weeks) longer in the multiple micronutrients group. Iron-folic acid was associated with a significantly reduced risk of early preterm delivery (<34 weeks) (relative risk 0.50, 0.27 to 0.94, P=0.031). There was a significant increase in haemoglobin concentration in both iron-folic acid (5.0 g/l, 2.0 to 8.0 g/l, P=0.001) and multiple micronutrients (6.9 g/l, 4.1 to 9.6 g/l, P<0.001) groups compared with folic acid alone. In post hoc analyses there were no significant differences for perinatal mortality, but iron-folic acid was associated with a significantly reduced early neonatal mortality by 54% (relative risk 0.46, 0.21 to 0.98). Conclusion In rural populations in China antenatal supplementation with iron-folic acid was associated with longer gestation and a reduction in early neonatal mortality compared with folic acid. Multiple micronutrients were associated with modestly increased birth weight compared with folic acid, but, despite this weight gain, there was no significant reduction in early neonatal mortality. Pregnant women in developing countries need sufficient doses of iron in nutrient supplements to maximise reductions in neonatal mortality. Trial registration ISRCTN08850194.

OBJECTIVE. We investigated the benefits of maternal multimicronutrient supplementation during gestation on the mental and psychomotor development of infants. METHODS. In a double-blind, randomized, controlled trial, pregnant women (N = 5828) in 2 rural counties in western China were assigned randomly to receive multimicronutrient (5 minerals and 10 vitamins at levels approximating the recommended daily allowance), folic acid plus iron, or folic acid supplementation daily from ∼14 weeks of gestation until delivery. We assessed a subset of the newborns (N = 1305) from the 3 supplementation groups by measuring their mental and psychomotor development with the Bayley Scales of Infant Development, at 3, 6, and 12 months of age. Multilevel analyses were used to compare the mental development and psychomotor development raw scores at 3, 6, and 12 months. RESULTS. Multimicronutrient supplementation was associated with mean increases in mental development raw scores for infants at 1 year of age of 1.00 and 1.22 points, compared with folic acid only and folic acid plus iron supplementation, respectively. However, supplementation did not increase significantly the psychomotor development raw scores up to 1 year of age. CONCLUSION. Compared with iron and folic acid supplementation, the administration of multimicronutrients to pregnant women improved the mental development of their children at 1 year of age.

There are still inconsistent conclusions about the association of prenatal alcohol drinking with congenital heart defects (CHDs). We conducted this meta-analysis to investigate the association between prenatal alcohol exposure and the risk of overall CHDs and the CHDs subtypes. Case-control and cohort studies published before March 2015 were searched through PubMed and Embase. Two authors independently extracted data and scored the study quality according to the Newcastle-0ttawa Scale. The pooled ORs and 95%CI were estimated using the random-effects model and heterogeneity was assessed by the Q test and I² statistic. A total of 20 studies were finally included. The results provided no evidence of the association between prenatal alcohol exposure and the risk of overall CHDs (OR = 1.06, 95%CI = 0.93–1.22), ventricular septal defects (VSDs) (OR = 1.04, 95%CI = 0.86–1.25), or atrial septal defects (ASDs) (OR = 1.40, 95%CI = 0.88–2.23). However, prenatal alcohol drinking was marginally significantly associated with conotruncal defects (CTDs) (OR = 1.24, 95%CI = 0.97–1.59) and statistically significantly associated with d-Transposition of the Great Arteries (dTGA) (OR = 1.64, 95%CI = 1.17–2.30). Moreover, both prenatal heavy drinking and binge drinking have a strong association with overall CHDs (heavy drinking: OR = 3.76, 95%CI = 1.00–14.10; binge drinking: OR = 2.49, 95%CI = 1.04–5.97), and prenatal moderate drinking has a modest association with CTDs (OR = 1.35, 95%CI = 1.05–1.75) and dTGA (OR = 1.86, 95%CI = 1.09–3.20). In conclusion, the results suggested that prenatal alcohol exposure was not associated with overall CHDs or some subtypes, whereas marginally significant association was found for CTDs and statistically significant association was found for dTGA. Further prospective studies with large population and better designs are needed to explore the association of prenatal alcohol exposure with CHDs including the subtypes in specific groups.

Birth weight and related outcomes have profound influences on life cycle health, but the effect of maternal hemoglobin concentration during pregnancy on birth weight is still unclear. This study aims to reveal the associations between maternal hemoglobin concentrations in different trimesters of pregnancy and neonatal birth weight, LBW, and SGA. This was a prospective study based on a cluster-randomized controlled trial conducted from July 2015 to December 2019 in rural areas of Northwest China. Information on maternal socio-demographic status, health-related factors, antenatal visits, and neonatal birth outcomes were collected. A total of 3748 women and their babies were included in the final analysis. A total of 65.1% and 46.3% of the participants had anemia or hemoglobin ≥ 130 g/L during pregnancy. In the third trimester, maternal hemoglobin concentration was associated with birth weight in an inverted U-shaped curve and with the risks of LBW and SGA in extended U-shaped curves. The relatively higher birth weight and lower risks for LBW and SGA were observed when hemoglobin concentration was 100–110 g/L. When maternal hemoglobin was 130 g/L, the neonatal birth weight was more than 100 g lower than that when the maternal hemoglobin was 100 g/L. In conclusion, both low and high hemoglobin concentrations in the third trimester could be adverse to fetal weight growth and increase the risks of LBW and SGA, respectively. In addition to severe anemia, maternal hemoglobin >130 g/L in the third trimester should be paid great attention to in the practice of maternal and child health care.