Association between iron status, preeclampsia and gestational hypertension: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Several recent observational studies have reported that iron overload during pregnancy is associated with preeclampsia (PE) and gestational hypertension (GH). However, the causal association between iron status, PE, and GH is still not clear. METHODS: We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) summary statistics of iron status, included serum iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) from the largest available GWAS meta-analysis, and the summary statistics of PE and GH were obtained from the FinnGen consortium. Fixed-effect inverse variance weighted (IVW), random-effect IVW, maximum likelihood (ML), MR-Egger regression, weighted median, and MR-PRESSO methods were used. RESULTS: A total of 21, 58, 28, and 22 SNPs were used as IVs for serum iron, ferritin, TIBC, and TSAT, respectively. The F-statistics of IVs ranged from 95.23 to 421.36. The results of the fixed effects IVW method suggested that for per SD unit increase in serum iron, the risk of PE increases by 24 % (OR = 1.24, 95 % CI: 1.03-1.50, P = 0.02). No significant heterogeneity or horizontal pleiotropy was found. The association between ferritin, TIBC, TSAT and PE were statistically insignificant (P>0.05). Furthermore, the results of each MR methods do not support a causal association between iron status and GH, nor a reverse causal association between PE and GH and iron status. CONCLUSION: This two-sample MR study provides evidence supporting a causal association between serum iron level and PE.

Higher Plasma Copper Exposure was Adversely Associated with Skeletal Muscle Indicators in Chinese Children Aged 6-9 Years: A Cross-Sectional Study.

It is unclear whether blood concentrations of copper (Cu), magnesium (Mg), and calcium (Ca) influence skeletal muscle mass and strength in children. We aimed to explore the associations between plasma Cu, Mg, and Ca and skeletal muscle indicators in Chinese children. A total of 452 children aged 6 to 9 years old were recruited for this cross-sectional study. Whole body lean soft tissue mass (WLSTM), trunk lean soft tissue mass (TLSTM), and appendicular skeletal muscle mass (ASMM) were measured using dual-energy X-ray absorptiometry. Parameters of these indicators divided by Height2 (Ht2) and Weight (Wt) at the corresponding sites were calculated. Handgrip strength was also measured. Parameters of skeletal muscle indicators and handgrip strength that were below the sex-specific 20th percentile were considered low levels. Plasma concentrations of Cu, Mg, and Ca were measured using ICP-MS. After adjusting for several potential covariates, among the total subjects, for every one standard deviation increase in Cu concentrations, there was a 0.939% decrease in WLSTM/Wt, a 0.415% decrease in TLSTM/Wt, and a 0.47% decrease in ASMM/Wt. For every one standard deviation increase in Cu concentrations, there was a higher odd (OR: 1.36, 95%CI 1.06, 1.75) of low WLSTM/Wt, TLSTM/Wt (OR: 1.33, 95%CI 1.03, 1.71), ASMM/Ht2 (OR: 1.32, 95%CI 1.02, 1.69), as well as ASMM/Wt (OR: 1.56, 95%CI 1.23, 1.99). No significant associations were found between Mg, Ca, and most skeletal muscle indicators. Higher plasma Cu concentrations were adversely associated with skeletal muscle indicators at multiple sites in Chinese children.

Associations of maternal serum concentration of iron-related indicators with gestational diabetes mellitus in Chinese: A pilot prospective cohort study.

BACKGROUND: We aimed to provide a comprehensive understanding of the associations between iron metabolism and gestational diabetes mellitus (GDM) by examining multiple iron-related indicators. METHODS: We conducted a prospective study involving 907 Chinese pregnant women. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of iron-related indicators during the first trimester (≤ 14 weeks of gestation). GDM outcomes were measured through oral glucose tolerance tests (OGTT) conducted between weeks 24 and 28 of gestation. RESULTS: Subjects with iron-related indicators below the 10th percentile (except for serum iron and soluble transferrin receptor) had a higher risk of GDM compared to normal subjects (10th-90th percentiles). The ORs (95 %CI; p-value) were 1.88 (1.10, 3.20; P=0.020) for ferritin, 1.88 (1.10, 3.19; P=0.020) for hepcidin. Higher levels of ferritin (> 90th percentile) were associated with a higher risk of abnormal fasting blood glucose, while lower levels (< 10th percentile) of ferritin, hepcidin, and transferrin were associated with a higher risk of one-hour postprandial glucose ≥ 8.6 mmol/L in the OGTT. CONCLUSIONS: Lower levels (< 10th percentiles) of several iron-related indicators (ferritin, hepcidin, and transferrin) were associated with a higher risk of GDM and abnormal blood glucose compared to normal subjects.

Association between interpregnancy interval and adverse perinatal outcomes among subsequent twin pregnancies: a nationwide population-based study.

BACKGROUND: The existing evidence on the association between interpregnancy interval (IPI) and pregnancy outcomes primarily focuses on singleton pregnancies, with limited research on twin pregnancies. OBJECTIVE: This study aimed to investigate the association between IPI and adverse perinatal outcomes in twin pregnancies. STUDY DESIGN: This population-based, retrospective cohort study analyzed data from the National Center for Health Statistics in the United States between 2016 and 2020. We included multiparous women aged 18 to 45 years with live-born twins without congenital anomalies, born between 26 and 42 weeks of gestation. Poisson regression models, adjusted for potential confounders, were used to evaluate the associations between IPI and adverse outcomes, including preterm birth (PTB) <36 weeks, small for gestational age (SGA), neonatal intensive care unit (NICU) admission, neonatal composite morbidity, and infant death. Missing data on covariates were managed using multiple imputations. Dose-response analyses were performed using the restricted cubic splines (RCS) approach. Subgroup analyses were stratified by maternal age, parity, and combination of neonatal sex. Sensitivity analyses were conducted using complete data and excluding pregnancies with intervening events during the IPI. RESULTS: A total of 143,014 twin pregnancies were included in the analysis. Compared to the referent group (IPI of 18-23 months), an IPI of less than 6 months was associated with an increased risk of PTB<36 weeks (RR, 1.21; 95% confidence interval [95% CI]: 1.17-1.25), SGA (RR, 1.11; 95% CI: 1.03-1.18), neonatal composite morbidity (RR, 1.19; 95% CI: 1.12-1.27), NICU admission (RR, 1.18; 95% CI: 1.14-1.22), and infant death (RR, 1.29; 95% CI: 1.05-1.60). An IPI of 5 years or more was associated with an increased risk of PTB<36 weeks (RR, 1.18; 95% CI: 1.15-1.21), SGA (RR, 1.24; 95% CI: 1.18-1.30), neonatal composite morbidity (RR, 1.10; 95% CI: 1.05-1.15), and NICU admission (RR, 1.14; 95% CI: 1.11-1.17). The dose-response analyses showed that these outcomes had U-shaped or J-shaped associations with IPI. The associations between IPI and the outcomes slightly differed by advanced maternal age, parity, and combination of neonatal sex. The sensitivity analyses yielded similar results to the main findings. CONCLUSION: Extreme IPI, less than 6 months or more than 5 years, was associated with adverse outcomes in twin pregnancies. IPI could be used as a predictor for risk stratification in high-risk twin pregnancies.

Optimal gestational weight change associated with improved perinatal outcomes in women with gestational diabetes mellitus: a population-based study in the United States.

BACKGROUND: Optimal gestational weight change (GWC) is little known among pregnant women with gestational diabetes mellitus (GDM). OBJECTIVES: This study aimed to explore the optimal GWC ranges for women with GDM and validate these ranges compared with the Institute of Medicine (IOM) guidelines. METHODS: A population-based cohort study using natality data from the National Center for Health Statistics in the United States included 1,338,460 mother-infant pairs with GDM from 2014 to 2020. Poisson regression models were performed to identify GWC ranges (GDM targets) associated with acceptable risks (<10% increase) for a severity-weighted composite outcome including preterm birth (PTB) <37 wk, large for gestational age (LGA, birthweight >90th percentile) and small for gestational age (SGA, birthweight <10th percentile). These targets were validated in individual outcomes including PTB, LGA, SGA, hypertensive disorders of pregnancy, neonatal intensive care unit admission, and neonatal respiratory morbidity, and compared with the IOM guidelines using logistic regression models with population-attributable fractions (PAFs) calculated. RESULTS: The severity-weighted composite outcome had a U-shaped or a J-shaped relationship with GWC across body mass index categories. The GDM targets were 14.1 to 20.3 kg, 9.0 to 17.0 kg, 4.8 to 13.8 kg, -0.8 to 10.8 kg, -2.4 to 8.2 kg, and -8.3 to 6.0 kg for underweight, normal weight, overweight, class 1 obesity, class 2 obesity, and class 3 obesity, respectively. GWC outside the GDM or the IOM targets was associated with increased adverse perinatal outcomes in validation analyses. PAFs indicated that the IOM guidelines reduced a similar or higher proportion of adverse perinatal outcomes compared with the GDM targets for women with GDM, except for those with class 2 and 3 obesity. CONCLUSIONS: The IOM guidelines are generally applicable for women with GDM, except for women with moderate and severe obesity. The optimal GWC ranges for women with GDM and moderate to severe obesity may be lower than the IOM guidelines.

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study.

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

Factors and outcomes for placental anomalies: An umbrella review of systematic reviews and meta-analyses.

Background: Placental anomalies, including placenta previa (PP), placenta accreta spectrum disorders (PAS), and vase previa (VP), are associated with several adverse foetal-neonatal and maternal complications. However, there is still a lack of robust evidence on the pathogenesis and adverse outcomes of the diseases. Through this umbrella review, we aimed to systematically review existing meta-analyses exploring the factors and outcomes for pregnancy women with placental anomalies. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to February 2023. We used AMSTAR 2 to assess the quality of the reviews and estimated the pooled risk and 95% confidence intervals (CIs) for each meta-analysis. Results: We included 34 meta-analyses and extracted 55 factors (27 for PP, 22 for PAS, and 6 for VP) and 16 outcomes (12 for PP, and 4 for VP) to assess their credibility. Seven factors (maternal cocaine use (for PP), uterine leiomyoma (for PP), prior abortion (spontaneous) (PP), threatened miscarriage (PP), maternal obesity (PP), maternal smoking (PAS), male foetus (PAS)) had high epidemiological evidence. Twelve factors and six outcomes had moderate epidemiological evidence. Twenty-two factors and eight outcomes showed significant association, but with weak credibility. Conclusions: We found varying levels of evidence for placental anomalies of different factors and outcomes in this umbrella review. Registration: PROSPERO: CRD42022300160.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Cohort Profile: Guangzhou Nutrition and Health Study (GNHS): A Population-Based Multi-Omics Study.

BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Associations of Dietary Anthocyanidins Intake with Bone Health in Children: A Cross-Sectional Study.

PURPOSE: Bone health and body composition share several common mechanisms like oxidative stress and inflammation. Anthocyanins have antioxidant and anti-inflammatory properties. We have reported that anthocyanins are associated with better body composition in children, but the associations with bone health have not been elucidated. We aimed to explore the association of anthocyanins with bone mineral content (BMC) and bone mineral density (BMD) at multiple sites in children. METHODS: In this cross-sectional study, 452 Chinese children aged 6-9 years were recruited. A validated 79-item food frequency questionnaire was used to collect dietary information. BMC and BMD at multiple sites (whole body; whole body excluding head, WBEH; limbs; arms; legs) were measured by dual-energy X-ray. RESULTS: Higher dietary intake of total anthocyanidins (per one standard deviation increase) was associated with a 1.28-13.6 g (1.31-1.60%, compared to median) higher BMC at all sites and a 3.61-6.96 mg (0.65-0.90%) higher BMD at the whole body, WBEH, and arm sites after controlling for a number of possible covariates. The results were similar and more pronounced for cyanidin, but not for delphinidin and peonidin. Higher dietary intake of cyanidin (per one standard deviation increase) was associated with a 1.33-15.4 g (1.48-1.68%) higher BMC at all sites and a 4.15-7.77 mg (0.66-1.00%) higher BMD at all sites except the legs. No statistically significant associations with BMC or BMD were found for dietary intake of delphinidin and peonidin. CONCLUSIONS: Higher dietary intake of total anthocyanidins and cyanidins were associated with higher BMC and BMD in Chinese children.

Role of breastfeeding on maternal and childhood cancers: An umbrella review of meta-analyses.

Background: Multiple studies and meta-analyses have claimed that breastfeeding is inversely correlated with maternal and childhood cancers. These results could either be causal or confounded by shared risk factors. By conducting an umbrella review, we aimed to consolidate the relationship between breastfeeding and maternal and childhood cancers. Methods: We searched PubMed, Embase, Web of Science, Elsevier ScienceDirect, and Cochrane Library databases from inception to December 2022. Two reviewers independently extracted the data and assessed the quality of the studies using standardised forms. We considered two types of breastfeeding comparisons ("ever" vs "never" breastfeeding; and "longest" vs "shortest" duration). We estimated the pooled risk and 95% confidence interval (CI) for each meta-analysis. Results: We included seventeen meta-analyses with 55 comparisons. There was an inverse correlation between breastfeeding and childhood leukaemia (pooled risk = 0.90, 95% CI = 0.81-0.99), neuroblastoma (pooled risk = 0.81, 95% CI = 0.71-0.93), maternal ovarian cancer (pooled risk = 0.76, CI = 0.71-0.81), breast cancer (pooled risk = 0.85, 95% CI = 0.82-0.88), and oesophageal cancer (pooled risk = 0.67, 95% CI = 0.54-0.81) for "ever" vs "never" breastfeeding; and with childhood leukaemia (pooled risk = 0.94, 95% CI = 0.89-0.98), and maternal ovarian cancer (pooled risk = 0.84, 95% CI = 0.78-0.90) and breast cancer (pooled risk = 0.92, 95% CI = 0.89-0.96) for "longest" vs "shortest" breastfeeding duration. Conclusions: We found evidence that breastfeeding may reduce the risk of maternal breast cancer, ovarian cancers, and childhood leukaemia, suggesting positive implications for influencing women's decision in breastfeeding. Registration: PROSPERO (CRD42021255608).

Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study.

Background and Aims: The association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study. Methods: We included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia. Results: After adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1. Conclusion: Higher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women.

Association of maternal pre-pregnancy dietary intake with adverse maternal and neonatal outcomes: A systematic review and meta-analysis of prospective studies.

This study aimed to summarize the evidence regarding the effects of dietary intake before conception on pregnancy outcomes by performing a systematic review and meta-analysis of prospective studies. Electronic databases were searched from inception up to August 2021. Overall, 65 studies involving 831 798 participants were included and 38 studies were quantitatively pooled. With regard to maternal outcomes, pre-pregnancy intake of fried food, fast food, red and processed meat, heme iron and a low-carbohydrate dietary pattern was positively associated with the risk of gestational diabetes mellitus (GDM) (all P < 0.05). However, a high dietary fiber intake and folic acid supplementation were negatively associated with GDM risk (both P < 0.05). With regard to neonatal outcomes, maternal caffeine intake before pregnancy significantly increased the risk of spontaneous abortion, while folic acid supplementation had protective effects on total adverse neonatal outcomes, preterm birth, and small-for-gestational age (SGA, all P < 0.05). However, no significant associations were found between adverse pregnancy outcomes (i.e., GDM and SGA) and the pre-pregnancy dietary intake of sugar-sweetened beverages, potato, fish, and carbohydrates and the Healthy Eating Index. Our study suggests that maintaining a healthy diet before conception has significant beneficial effects on pregnancy outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1989658.

Optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus: a population-based study in the United States.

BACKGROUND: There is limited evidence regarding optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus. OBJECTIVE: This study aimed to examine the association between gestational weight gain and perinatal outcomes among women with gestational diabetes mellitus and twin pregnancies and to explore the gestational weight gain targets by prepregnancy body mass index category. STUDY DESIGN: A national population-based cohort study of twin pregnancies with gestational diabetes mellitus was conducted between 2014 and 2020. Women with gestational diabetes mellitus aged between 18 and 45 years with live-born twins without congenital malformations between 24 and 42 weeks of gestation were included in the analysis. Two approaches were used to determine the optimal gestational weight gain targets by body mass index category: an interquartile range method to calculate targets in low-risk gestational diabetes mellitus pregnancies and a logistic model method to identify the odds ratio targets at which a composite adverse outcome decreased. RESULTS: Of 29,308 women with gestational diabetes mellitus and twin pregnancies, 8239 (28.1%) were normal-weight, 7626 (26.0%) were overweight, and 13,443 (45.9%) were obese. The continuous standardized gestational weight gain by 36 weeks was associated with preterm birth <36 weeks, large-for-gestational-age infants, small-for-gestational-age infants, and gestational hypertensive disorders. The interquartile range targets were 13.6 to 20.9 kg, 10.9 to 20.4 kg, and 7.7 to 17.7 kg for normal-weight, overweight, and obese women, respectively. The odds ratio targets were 14.1 to 20.0 kg, 12.1 to 16.0 kg, and 6.1 to 12.0 kg for normal-weight, overweight, and obese women, respectively. Gestational weight gain outside these targets was associated with preterm birth <36 weeks, large-for-gestational-age and small-for-gestational-age infants, and gestational hypertensive disorders, and exhibited significant population attributable fractions for preterm birth <36 weeks, large-for-gestational-age infants, and gestational hypertensive disorders across body mass index categories. CONCLUSION: Compared with the Institute of Medicine guidelines, more stringent gestational weight gain targets would be beneficial for improved perinatal outcomes in women with gestational diabetes mellitus and twin pregnancies.

Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study.

BACKGROUND: Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. METHODS: A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n=13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. RESULTS: Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64-0.89, P = 8.03 × 10-4). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60-0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62-0.93, P = 8.76 × 10-3), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10-3), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10-3), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74-0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. CONCLUSIONS: This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms.

Perinatal outcomes among twin pregnancies with gestational diabetes mellitus: A nine-year retrospective cohort study.

Objective: To compare the outcomes between gestational diabetes mellitus (GDM) vs. non-GDM twin gestations. Methods: A retrospective cohort study of 2,151 twin pregnancies was performed in a tertiary hospital in Foshan, China, 2012-2020. Pregnancy and neonatal outcomes were compared between women with vs. without GDM using 1:1 propensity score matching (PSM) and multivariable logistic models. For neonatal outcomes, generalized estimating equation (GEE) approach was used to address the intertwin correlation. Results: Of the 2,151 participants, 472 women (21.9%) were diagnosed with GDM. Women with GDM were older and more likely to be overweight or obese, and more likely have chronic hypertension, assisted pregnancies and dichorionic twins. In the PSM cohort of 942 pregnancies, there was no statistical difference when comparing GDM twin pregnancies and non-GDM in any of the perinatal outcomes, especially in terms of preterm birth (PTB) <37 weeks (P = 0.715), large for gestational age (LGA) (P = 0.521) and neonatal respiratory distress (NRDS) (P = 0.206). In the entire cohort, no significant adjusted ORs for these outcomes were obtained from logistic regression models adjusted for confounders (aOR for PTB < 37 weeks: 1.25, 95% CI: 0.98-1.58; aOR for LGA: 1.26, 95% CI: 0.88-1.82; and aOR for NRDS, 1.05, 95% CI: 0.68-1.64). Conclusion: Twin pregnancies with GDM and adequate prenatal care have comparable perinatal outcomes to those without.

Plant-based diets and body composition in Chinese omnivorous children aged 6-9 years old: A cross-sectional study.

Evidence suggests that plant-based diets are beneficial for alleviating metabolic diseases. Childhood is a crucial period for body growth and development. However, it is unknown whether adherence to a plant-based diet is related to a healthy body composition in children. We aimed to assess the relationship between a plant-based diet and body composition in children. A total of 452 Chinese children aged 6-9 years old participated in this cross-sectional study. Lean mass (LM), fat mass, and fat mass percentage (FMP) were assessed via dual-energy X-ray absorptiometry. An age- and sex-specific abdominal FMP ≥85th percentile was defined as abdominal obesity. Handgrip strength was measured using a hydraulic hand dynamometer. A validated 79-item food frequency questionnaire was used to collect dietary information. Overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) scores were calculated. After adjusting for potential covariates, a higher hPDI score (per 10-score increment) was associated with a higher LM in the android area (0.038 kg, 3.2%), gynoid area (0.048 kg, 1.9%), and trunk (0.102 kg, 1.2%) and with a lower FMP (1.18%) in the android area. In contrast, a higher uPDI score (per 10-score increment) was associated with a lower LM in the trunk (0.091 kg, 1.1%) and android area (0.023 kg, 1.9%) and with a higher FMP (0.74%) in the android area. No significant associations were observed between the overall PDI and body composition or abdominal obesity. After stratifying by sex, higher (vs. lower) hPDI scores was associated with lower abdominal obesity risk in girls and higher handgrip strength in boys. In conclusion, in this cross-sectional study, we found that stronger adherence to a healthful plant-based diet, and less adherence to an unhealthful plant-based diet was associated with better body composition in Chinese omnivorous children aged 6-9 years old. Our results highlight the need to distinguish between healthy and unhealthy plant foods within investigating how to obtain a healthy body composition in children.

Interaction of n-3 polyunsaturated fatty acids with host CD36 genetic variant for gut microbiome and blood lipids in human cohorts.

BACKGROUND & AIMS: Previous studies suggest an interaction of CD36 genetic variant rs1527483 with n-3 polyunsaturated fatty acids (PUFAs) to modulate blood lipids. However, successful replication is lacking and the role of gut microbiome remains unclear. Here, we aimed to replicate these gene-diet interactions on blood lipids and investigate their possible associations with gut microbiome. METHODS: We evaluated the n-3 PUFA-rs1527483 interaction on blood lipids in two population-based cohorts (n = 4,786). We profiled fecal microbiome and short-chain fatty acids among 1,368 participants. The associations between n-3 PUFAs and bacterial alpha-diversity, taxonomies and short-chain fatty acids by rs1527483 genotypes were analyzed using regression models. RESULTS: CD36 rs1527483-GG carriers responded better to high n-3 PUFA exposure; higher blood HDL-C (beta (95% CI): 0.05 (0.01, 0.08) mmol/L) and lower TG (log-transformed, beta (95% CI): -0.08 (-0.14, -0.02)) were observed among participants whose n-3 PUFA exposure ranked in the top quartile comparing with those in the bottom quartile. We identified docosahexaenoic acid (DHA) as the driven individual n-3 PUFA biomarker, which showed interaction with rs1527483. Among the rs1527483-GG carriers, but not other genotype groups, DHA exposure was positively associated with bacterial Faith's phylogenetic diversity, Observed OTUs, Shannon's diversity index, Dorea, Coriobacteriales Incertae Sedis spp, and fecal propionic acid levels. Another independent longitudinal cohort validated the DHA-rs1527483 interaction on gut microbiome. The identified microbial features were correlated with blood lipids, and the host biosynthesis and metabolism pathways of bile acids and aromatic amino acids. CONCLUSIONS: The present study found that higher n-3 PUFAs were associated with improved blood lipids and gut microbial features only among rs1527483-GG carriers. These findings highlight a potential role of gut microbiome to link the CD36 genetic variant, n-3 PUFAs and blood lipids, revealing a new research direction to interpret the gene-diet interaction for cardiometabolic health.

Association of Optimal Gestational Weight Gain Ranges With Perinatal Outcomes Across Body Mass Index Categories in Twin Pregnancies.

Importance: The existing gestational weight gain (GWG) recommendations for twin pregnancies are lacking for underweight individuals and are not stratified by obesity class. Objective: To identify optimal GWG ranges associated with reduced adverse perinatal outcomes stratified by prepregnancy body mass index (BMI) categories in twin pregnancies. Design, Setting and Participants: This population-based cohort study of twin pregnancies using data from the National Center for Health Statistics was conducted between January 1, 2014, and December 31, 2018. Statistical analysis was performed from October 24, 2021, to May 7, 2022. The study population comprised 262 604 individuals between 18 and 45 years of age with live-born twins without congenital malformation between 24 and 42 weeks of gestation. Two approaches were used to determine the optimal GWG ranges: a statistics-based approach calculating IQRs of GWG in a low-risk population, and an outcome-based approach identifying GWG thresholds below or above which an adverse perinatal outcome increased. Exposure: Gestational weight gain. Main Outcomes and Measures: Preterm birth less than 36 weeks, gestational hypertensive disorders, small for gestational age status, large for gestational age status, and a composite outcome defined as any occurrence of the individual outcomes. Results: The main sample comprised 200 810 individuals with twin pregnancies (mean [SD] maternal age, 30.4 [5.5] years; 1624 [0.8%] American Indian or Alaska Native, 13 031 [6.5%] Asian or Pacific Islander, 36 423 [18.1%] Black, and 149 732 [74.6%] White; and 137 409 [68.4%] multiparous). In the low-risk subgroup (n = 61 794), the IQRs of the total GWG after 36 weeks of gestation as assessed using a statistics-based approach and based on BMI group were 15.9 to 22.7 kg for underweight, 15.4 to 22.7 kg for normal weight, 12.7 to 22.2 kg for overweight, 10.0 to 20.0 kg for class 1 obesity, 7.7 to 18.1 kg for class 2 obesity, and 5.9 to 16.3 kg for class 3 obesity. The absolute risk of the composite outcome showed U-shaped associations with GWG across BMI categories. The optimal GWG ranges by 36 weeks identified using an outcome-based approach and BMI group were 17.5 to 24.9 kg for underweight, 15.0 to 24.9 kg for normal weight, 15.0 to 24.9 kg for overweight, 10.0 to 19.9 kg for class 1 obesity, 7.5 to 17.4 kg for class 2 obesity, and 5.0 to 9.9 kg for class 3 obesity. The multivariable logistic models assessed using the validation sample (n = 49 275) showed that GWG defined outside those optimal ranges was associated with preterm birth at less than 36 weeks, gestational hypertensive disorders, and small or large for gestational age. Conclusions and Relevance: This population-based cohort study found that optimal GWG ranges were similar for individuals with underweight and normal weight but decreased with increasing severity of obesity. The current US Institute of Medicine GWG recommendations may be too high for individuals with moderate or severe obesity.

Assessment of different thresholds of birthweight discordance for early neonatal outcomes: retrospective analysis of 2348 twin pregnancies.

BACKGROUND: The optimal threshold of birthweight discordance (BWD) remains controversial. This study aimed to evaluate the associations between BWD at different thresholds and early neonatal outcomes and to assess their predictive accuracy. METHODS: This was a retrospective cohort study using a birthweight data with the chorionicity information of 2348 liveborn twin pairs at a gestational age of ≥26 weeks, from 2012 to 2018. The percentage of BWD was calculated by dividing the actual birthweight difference by the weight of the larger twin and multiplying by 100. Outcomes of interest included neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome (NRDS), ventilator support and a composite outcome combining major morbidities and neonatal death. Logistic regression models were performed to estimate the association between neonatal outcomes and BWD with different thresholds (≥15.0%, ≥20.0%, ≥25% and ≥ 30%). Generalized estimated equation (GEE) models were used to address intertwin correlation. Restrictive cubic spline (RCS) models were established to draw the dose-response relationship between BWD and the odds ratios of outcomes. Clustered receiver operating characteristic (ROC) curve analyses were performed to assess the predictive accuracy. RESULTS: Of 2348 twin pairs, including 1946 dichorionic twin pairs and 402 monochorionic twin pairs, BWD was significantly associated with NICU admission, regardless of the thresholds used. The incidence of NRDS, ventilator support and the composite outcome were significantly higher when a threshold of ≥20% or greater was chosen. The dose-response relationship showed nonlinear growth in the risk of adverse neonatal outcomes with increasing BWD. ROC analyses showed a low significant AUROC of 0.569 (95% CI: 0.526-0.612) for predicting NICU admission but no significant AUROCs for predicting other outcomes. A BWD of ≥30% provided a moderate increase in the likelihood of NICU admission [positive likelihood ratio (LR+) = 5.77]. CONCLUSION: Although BWD is independently associated with adverse neonatal outcomes, it is not a single predictor for neonatal outcomes given the weak discriminative ability to predict neonatal outcomes. A cutoff of 30% is more practical for risk stratification among twin gestations.