The association of Chinese and American antenatal care utilization indices with birth outcomes.

Objective: Few comparisons have been implemented between different prenatal care utilization indices and their effects on adverse outcomes. This study investigated the appropriateness of Chinese antenatal care (ANC) regulations and compared Chinese and American adequacy of prenatal care utilization (APNCU) scores. Methods: From 2010 to 2022, the medical records of 60,114 pregnant women were collected from the electronic medical record system (EMRS) in Zhoushan, China. ANC utilization was measured using the APNCU score and five times antenatal care (ANC5). Birth weight outcomes, including small for gestational age (SGA) and large for gestational age (LGA), low birth weight (LBW), macrosomia, birth weight, and preterm birth (PTB), were utilized as outcomes. Multinomial, linear, and logistic regression were used to analyze the association of ANC5 and APNCU with outcomes, respectively. Crossover analysis was implemented to compare the interaction between ANC5 and APNCU on the outcomes. Results: Women who received inadequate prenatal care had increased odds for PTB (ANC5: odds ratio (OR) = 1.12, 95% confidence interval (95%CI) = 1.03-1.21; APNCU: OR = 1.18, 95%CI: 1.07-1.29), delivering SGA infants (ANC5: OR = 1.13, 95%CI = 1.07-1.21; APNCU: OR = 1.11, 95%CI = 1.03-1.20). Crossover analysis revealed that inadequate prenatal care in APNCU only was significantly associated with an increased risk of PTB (OR = 1.48, 95%CI: 1.26-1.73). Conclusion: Women with inadequate prenatal care in ANC5 or APNCU were more likely to suffer from adverse birth outcomes, including PTB, birth weight loss, SGA, and LBW. It indicated that adequate prenatal care is necessary for pregnant women. However, there were interactions between ANC5 and APNCU on PTB, with inadequate prenatal care use by APNCU showing the highest risk of PTB. This indicates that APNCU would be a better tool for evaluating prenatal care use.

25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials. OBJECTIVE: Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association between 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP) and GDM risk. METHODS: Publicly accessible summary data from independent cohorts were used for two-sample MR. For 25(OH)D, we obtained data from UK Biobank, IEU and EBI, then performed a meta-analysis to enhance the statistical power (via METAL); for VDBP, data were obtained from the INTERVAL study; for GDM, data were obtained from FinnGen. The inverse variance weighted (IVW) approach was performed as the main analysis, together with several sensitivity analyses, such as MR-Egger, maximum likelihood, weighted median, and weighted mode. RESULTS: The IVW results revealed a weak negative causal connection between 25(OH)D and GDM risk [OR (95% CI) = 0.71 (0.50, 0.99), p = 0.046]. However, the causal association was unstable according to sensitivity analyses, and Cochran's Q test revealed significant heterogeneity. After removing BMI-related IVs, the causal association between 25(OH)D and GDM disappeared [OR (95% CI) = 0.76 (0.55, 1.06), p = 0.101]. In addition, our study found no proof to support the assumption that VDBP level was related to GDM risk causally [OR (95% CI) = 0.98 (0.93, 1.03), p = 0.408]. CONCLUSIONS: According to this study, a weak negative causal association between 25(OH)D and GDM risk was found, while we had little proof to support the link between VDBP and GDM. To further explore whether total or free 25(OH)D levels and GDM are causally related, GWAS data with an emphasis on women of reproductive age and other ethnic groups are required.

The associations of maternal liver biomarkers in early pregnancy with the risk of gestational diabetes mellitus: a prospective cohort study and Mendelian randomization analysis.

Background: Associations of liver function with the risk of gestational diabetes mellitus (GDM) remain unclear. This study aimed to examine the relationship and the potential causality between maternal liver biomarkers and the risk of subsequent GDM, as well as to evaluate the interaction between liver biomarkers and lipids on GDM risk. Methods: In an ongoing Zhoushan Pregnant Women Cohort, pregnant women who finished the first prenatal follow-up record, underwent liver function tests in early pregnancy, and completed the GDM screening were included in this study. Logistic regression models were used to investigate the association, and the inverse-variance weighted method supplemented with other methods of two-sample Mendelian randomization (MR) analysis was applied to deduce the causality. Results: Among 9,148 pregnant women, 1,668 (18.2%) developed GDM. In general, the highest quartile of liver function index (LFI), including ALT, AST, GGT, ALP, and hepatic steatosis index, was significantly associated with an increased risk of GDM (OR ranging from 1.29 to 3.15), especially an elevated risk of abnormal postprandial blood glucose level. Moreover, the causal link between ALT and GDM was confirmed by the MR analysis (OR=1.28, 95%CI:1.05-1.54). A significant interaction between AST/ALT and TG on GDM risk was observed (P interaction = 0.026). Conclusion: Elevated levels of LFI in early pregnancy were remarkably associated with an increased risk of GDM in our prospective cohort. Besides, a positive causal link between ALT and GDM was suggested.

Breastfeeding, Gestational Diabetes Mellitus, Size at Birth and Overweight/Obesity in Early Childhood.

Background: Breastfeeding appears to reduce the risk of childhood overweight/obesity. However, it remains unclear whether this protective effect persists among high-risk populations. This study aims to investigate the association of breastfeeding with the risk of overweight/obesity in early childhood and whether this association is altered by gestational diabetes mellitus (GDM) or size at birth. Methods: Feeding practices during the first 12 months of age and weight and length at 12-36 months of age were collected. Full breastfeeding includes exclusive and predominant breastfeeding. Children with body mass index (BMI) values greater than 1 standard deviation from the mean of sex- and age-specific BMI were classified as overweight/obese. Multiple generalized estimating equations models were applied to analyze the associations of full breastfeeding duration with overweight/obesity risk. Results: Among all participants (n = 9329), infants with a longer full-breastfeeding duration had a reduced risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Infants exposed to GDM and those born large for gestational age (LGA) had a higher risk of overweight/obesity in early childhood. Among infants of mothers with GDM (n = 1748), infants with full breastfeeding for greater than 6 months (aOR: 0.58; 95% CI: 0.44, 0.78) showed a decreased risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Among LGA infants (n = 1279), infants with full breastfeeding for 3-5 months (aOR: 0.66; 95% CI: 0.57, 0.76) and greater than 6 months (aOR: 0.70; 95% CI: 0.56, 0.88) showed a decreased risk of overweight/obesity in early childhood. Similar results were observed among LGA infants of mothers with GDM. Conclusions: Initiating and prolonging breastfeeding would reduce the risk of overweight/obesity in early childhood, and LGA infants and infants born to mothers with GDM would experience greater benefits.

Associations of maternal liver biomarkers in the first trimester with the risk of hypertensive disorders of pregnancy.

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (Pinteraction = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP.

Association of 25-Hydroxyvitamin D with Preterm Birth and Premature Rupture of Membranes: A Mendelian Randomization Study.

Low vitamin D (VitD) level is a risk factor for preterm birth (PTB), but the results of previous studies remained inconsistent, which may be influenced by the confounding factors and different types of PTB. We performed Mendelian randomization (MR) to uncover the association of 25-hydroxyvitamin D (25(OH)D) with PTB, premature rupture of membranes (PROM), and preterm premature rupture of membranes (PPROM). This study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from August 2011 to March 2022. Plasma 25(OH)D levels in three trimesters of pregnancy were measured. We conducted an MR analysis utilizing a genetic risk score (GRS) approach, which was based on VitD-associated single-nucleotide polymorphisms. The prospective cohort study included 3923 pregnant women. The prevalence of PTB, PROM, and PPROM were 6.09%, 13.18%, and 1.33%, respectively. Compared to those without vitamin D deficiency (VDD), only vaginally delivering pregnant women with VDD had a 2.69 (1.08-6.68) times risk of PTB. However, MR analysis did not support the association. One-unit higher GRS was not associated with an increased risk of PTB, regardless of the trimesters (OR [95% CI]: 1.01 [0.93-1.10], 1.06 [0.96-1.18], and 0.95 [0.82-1.10], respectively). When further taking PROM and PPROM as the outcomes, the MR analysis also showed no consistent evidence of a causal effect of VitD levels on the risk of them. Our MR analyses did not support a causal effect of 25(OH)D concentrations in the three trimesters on PTB, PROM, and PPROM.

The Association of Vitamin D during Pregnancy and mRNA Expression Levels of Inflammatory Factors with Preterm Birth and Prelabor Rupture of Membranes.

The aim of this study was to elucidate the association between vitamin D (VD) and the risk for preterm birth (PTB) and prelabor rupture of membranes (PROM). This study included two parts, with a cohort study and a case-control study. Plasma 25-hydroxyvitamin vitamin D [25(OH)D] levels in three trimesters in the cohort study and maternal 25(OH)D before delivery in the case-control study were measured. Quantitative real-time PCR was used to detect relative mRNA expression levels of the inflammatory factors associated with pyroptosis in peripheral blood mononuclear cell (PBMC), placenta and fetal membranes. Multinomial logistic regression and the Wilcoxon test were applied to analyze the associations. In the cohort study, 6381 pregnant women were included. We found that VD deficiency in T3 (PTB without PROM: OR = 1.90, 95% CI: 1.02-3.55, Term PROM (TPROM): OR = 0.76, 95% CI: 0.59-0.98) and less change of 25(OH)D between T1 and T3 (PTB without PROM: OR = 2.32, 95% CI: 1.07-5.06, TPROM: OR = 0.73, 95% CI: 0.56-0.96) were associated with the increased risk of PTB without PROM, while there was a decreased risk of TPROM. Neither VD, nor the increase of VD during pregnancy was associated with the premature rupture of membranes preterm delivery (PPROM). In the case-control study, there were no associations between VD during delivery and PTB or PROM (TPROM: OR = 1.33, 95% CI: 0.52-3.44); PTB without PROM: OR = 1.66, 95% CI: 0.33-8.19; PPROM: OR = 1.19, 95% CI: 0.42-3.40). The mRNA expression of NLRP1 (NOD-like receptor thermal protein domain associated protein 1) (p = 0.0165) in PBMC in the TPROM group was higher than that in the term group, and IL-18 (p = 0.0064) was lower than that in the term group. Plasma 25(OH)D in T3 and the increase of 25(OH)D between T1 and T3 were associated with a lower risk for PTB without PROM but a higher risk for TPROM. Further studies are warranted to clarify the association between VD and PTB and PROM and its mechanism.