Background: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. Methods: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. Results: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44–1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21–1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08–5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33–0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36–0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. Conclusions: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. Trial registration: Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Background. Evidence for the association between maternal thyroxine concentration and the risk of fetal congenital heart defects (CHDs) is absent. We aimed to study the association of maternal free and total thyroxine (FT4 and TT4) concentrations and the free-to-total thyroxine proportion (FTT4P, ) with the risk of CHD. Methods. The study was a hospital-based cohort study of 52,047 women who received a universal thyroid function test between 2012 and 2016. CHD was screened by ultrasound between 20 and 24 weeks of gestation or diagnosed until the 42^nd day of birth. Adjusted odds ratios (ORs) of fetal CHD were estimated for maternal FT4 and TT4 concentrations or the FTT4P by multivariate logistic regression. Results. A total of 41,647 women with singleton pregnancies were included for the analysis and 215 CHD cases were detected. The FT4 concentration was significantly associated with a higher risk of CHDs (OR, 1.04, 95 confidence interval (CI): 1.01 to 1.07). Each 1 higher FTT4P was related to a 1.41-fold (95 CI: 0.27 to 3.59) higher risk of CHDs. The association became stronger for women with a thyroid function test performed between 12 and 18 weeks of gestation (OR=1.05 (95 CI: 1.01 to 1.09) for the FT4 concentration and 3.32 (95 CI: 1.43 to 7.73) for the FTT4P). Conclusions. A higher FT4 concentration or FTT4P, measured between 12 and 18 weeks of gestation, was associated with an increased risk of CHDs. These findings may provide new insights into the mechanisms of CHDs and evidence for clinical decisions related to thyroid function tests.

The establishment and maintenance of pregnancy encompass a series of complex and high-energy-consuming physiological processes, resulting in a significant energy demand. Fatty acids, one of the most essential nutrients, play a crucial role in energy supply via oxidation and perform critical biological functions such as anti-inflammatory and anti-oxidant effects, which substantially impact human health. Disordered fatty acid metabolism can cause anomalies in fetal growth and development, as well as a range of pregnancy problems, which can influence the health of both the mother and the fetus. In this review, we innovatively explore the relationship between fatty acid metabolism abnormalities and pregnancy complications, emphasizing the potential of dietary interventions with polyunsaturated fatty acids in improving pregnancy outcomes. These findings provide important evidence for clinical interventions and enhance the understanding and practical application of health management during pregnancy.

Preterm labour is a common pregnancy complication contributing to major maternal and fetal morbidity and mortality. We have found microRNA (miR)-212-3p, a potential infection-associated molecule, was significantly over-expressed during human preterm labour. However, the mechanism remains unknown. In this study, we have adopted a lipopolysaccharide (LPS)-induced Institute of Cancer Research murine preterm model to examine the role of miR-212-3p in the infection-induced preterm labour. Myometrial miR-212-3p expression was increased by nearly 4-fold in the term labour group (P = 0.10) and 12-fold (P = 0.03) in the LPS-induced preterm labour group compared with the non-labour group. In vitro cellular experiments confirmed that a series of pro-inflammatory cytokines, including interleukin (IL)1B (P = 0.02) and IL-6 (P = 0.01), rather than LPS (P = 0.08) itself could significantly upregulate miR-212-3p expression in human myometrial smooth muscle cells. Methyl-CpG-binding protein 2 (MeCP2), as a target gene of miR-212-3p confirmed by our dual luciferase assay, influenced myocyte contractility and connexin 43 expression which is an important contraction-associated protein. Therefore, we conclude that miR-212-3p may be involved in infection-induced preterm labour through MeCP2 and it is a promoting molecule and novel target for the diagnosis and treatment of preterm labour in the future.

Purpose: This study aimed to reveal the interrelationships among vaginal microorganisms, metabolism, and inflammatory factors in premature pregnant women.Methods: A total of 77 pregnant women were enrolled and divided into a preterm birth group (n = 23) and a full-term birth group (n = 54) according to the gestational week of delivery. Blood samples and vaginal secretion samples were collected before the onset of labor or after rupture of membranes for blood index testing, 16S RNA sequencing of vaginal secretion samples, and untargeted metabolite determination.Results: Compared with the full-term group, the preterm group exhibited significantly elevated inflammatory markers (SII 689 vs. 1,061, p < 0.001) and decreased vaginal microbiota α diversity (Shannon index 3.56 vs. 2.65). Meanwhile, the abundance of Firmicutes was increased (54.96% vs. 76.73%), primarily comprising Lactobacillus jensenii, which was negatively correlated with gestational week; metabolomics identified 83 significantly differential metabolites, including upregulated tyrosine-arginine, cholesterol sulfate, and benzene compounds such as 2,4-dichlorophenol. KEGG analysis revealed that pathways such as kynurenine, steroids, lipids, and microbial metabolism were significantly activated in the preterm birth group. Omics association analysis revealed significant correlations among microbiota, metabolites, and inflammatory markers. For example, Lactobacillus jensenii and inflammatory metabolites such as arginine-lysine, sulfamethoxazole, 5-aminovaleric acid, and epoxiconazole were all positively correlated with SII (p < 0.05).Conclusion: The results suggest that an imbalance in vaginal microbiota, particularly the abnormal proliferation of Lactobacillus jensenii, as well as amino acid and lipid metabolism may be associated with inflammation-induced preterm birth.

Prokineticin 1 (PROK1) is a secreted protein involved in a range of physiological activities such as cell proliferation, migration, angiogenesis, and neuronal cell proliferation. Emerging evidences show that PROK1/PROK receptors (PROKRs) are expressed by trophoblasts, and decidual stroma cells at the maternal-fetal interface. PROK1 plays a critical role in successful pregnancy establishment by regulating the decidualization, implantation and placental development. Dysregulation of prokineticin signaling has been described in certain pathological states associated with pregnancy, including pre-eclampsia, recurrent miscarriage and fetal growth restriction. In this review, the expression and pleiotropic roles of PROK1 under physiological and pathological pregnancy conditions are discussed.