Lysosome-related biomarkers in preeclampsia and cancers: Machine learning and bioinformatics analysis.

BACKGROUND: Lysosomes serve as regulatory hubs, and play a pivotal role in human diseases. However, the precise functions and mechanisms of action of lysosome-related genes remain unclear in preeclampsia and cancers. This study aimed to identify lysosome-related biomarkers in preeclampsia, and further explore the biomarkers shared between preeclampsia and cancers. MATERIALS AND METHODS: We obtained GSE60438 and GSE75010 datasets from the Gene Expression Omnibus database, pre-procesed them and merged them into a training cohort. The limma package in R was used to identify the differentially expressed mRNAs between the preeclampsia and normal control groups. Differentially expressed lysosome-related genes were identified by intersecting the differentially expressed mRNAs and lysosome-related genes obtained from Gene Ontology and GSEA databases. Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the DAVID database. The CIBERSORT method was used to analyze immune cell infiltration. Weighted gene co-expression analyses and three machine learning algorithm were used to identify lysosome-related diagnostic biomarkers. Lysosome-related diagnostic biomarkers were further validated in the testing cohort GSE25906. Nomogram diagnostic models for preeclampsia were constructed. In addition, pan-cancer analysis of lysosome-related diagnostic biomarkers were identified by was performed using the TIMER, Sangebox and TISIDB databases. Finally, the Drug-Gene Interaction, TheMarker and DSigDB Databases were used for drug-gene interactions analysis. RESULTS: A total of 11 differentially expressed lysosome-related genes were identified between the preeclampsia and control groups. Three molecular clusters connected to lysosome were identified, and enrichment analysis demonstrated their strong relevance to the development and progression of preeclampsia. Immune infiltration analysis revealed significant immunity heterogeneity among different clusters. GBA, OCRL, TLR7 and HEXB were identified as lysosome-related diagnostic biomarkers with high AUC values, and validated in the testing cohort GSE25906. Nomogram, calibration curve, and decision curve analysis confirmed the accuracy of predicting the occurrence of preeclampsia based on OCRL and HEXB. Pan-cancer analysis showed that GBA, OCRL, TLR7 and HEXB were associated with the prognosis of patients with various tumors and tumor immune cell infiltration. Twelve drugs were identified as potential drugs for the treatment of preeclampsia and cancers. CONCLUSION: This study identified GBA, OCRL, TLR7 and HEXB as potential lysosome-related diagnostic biomarkers shared between preeclampsia and cancers.

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.

Asia's Growing Contribution to Obesity Surgery Research: A 40-year Bibliometric Analysis.

Bariatric metabolic surgery's global research interest is growing, particularly in Asia due to its high obesity rates. This study focuses on Asia, especially China, analyzing 3904 publications (1221 from China) from 1980 to 2022. Research output accelerated until the COVID-19 pandemic, driven by economic growth and rising obesity rates. China led contributions from 2010, but Western Asia led when adjusted for population. An intra-regional research collaboration network emerged, driven by geographic proximity and similar economic environments. Keyword analysis highlighted emerging topics like "laparoscopic sleeve gastrectomy" and "non-alcoholic fatty liver disease," indicating a shift in focus. The study recommends disseminating research in top-tier journals to enhance visibility and impact.

Subsidized gestational diabetes mellitus screening and management program in rural China: a pragmatic multicenter, randomized controlled trial.

BACKGROUND: The increasing prevalence of gestational diabetes mellitus (GDM) is a major challenge, particularly in rural areas of China where control rates are suboptimal. This study aimed to evaluate the effectiveness of a GDM subsidy program in promoting GDM screening and management in these underserved regions. METHODS: This multicenter, randomized controlled trial (RCT) was conducted in obstetric clinics of six rural hospitals located in three provinces in China. Eligible participants were pregnant women in 24-28 weeks' gestation, without overt diabetes, with a singleton pregnancy, access to a telephone, and provided informed consent. Participants were randomly assigned in a 1:1 ratio to either the intervention or control groups using an internet-based, computer-generated randomization system. The intervention group received subsidized care for GDM, which included screening, blood glucose retesting, and lifestyle management, with financial assistance provided to health care providers. In contrast, the control group received usual care. The primary outcomes of this study were the combined maternal and neonatal complications associated with GDM, as defined by the occurrence of at least one pre-defined complication in either the mother or newborn. The secondary outcomes included the GDM screening rate, rates of glucose retesting for pregnant women diagnosed with GDM, dietary patterns, physical activity levels, gestational weight gain, and antenatal visit frequency for exploratory purposes. Primary and secondary outcomes were obtained for all participants with and without GDM. Binary outcomes were analyzed by the generalized linear model with a link of logistic, and odds ratios (OR) with 95% confidence intervals (CIs) were reported. Count outcomes were analyzed by Poisson regression, and incidence rate ratios with 95% CIs were reported. RESULTS: A total of 3294 pregnant women were randomly assigned to either the intervention group (n = 1649) or the control group (n = 1645) between 15 September 2018 and 30 September 2019. The proportion of pregnant women in the intervention group who suffered from combined maternal and/or neonatal complications was lower than in the control group with adjusted OR = 0.86 (0.80 to 0.94, P = 0.001), and a more significant difference was observed in the GDM subgroup (adjusted OR = 0.66, 95% CI 0.47 to 0.95, P = 0.025). No predefined safety or adverse events of ketosis or ketoacidosis associated with GDM management were detected in this study. Both the intervention and control groups had high GDM screening rates (intervention: 97.2% [1602/1649]; control: 94.5% [1555/1645], P < 0.001). Moreover, The intervention group showed a healthier lifestyle, with lower energy intake and more walking minutes (P values < 0.05), and more frequent blood glucose testing (1.5 vs. 0.4 visits; P = 0.001) compared to the control group. CONCLUSION: In rural China, a GDM care program that provided incentives for both pregnant women and healthcare providers resulted in improved maternal and neonatal health outcomes. Public health subsidy programs in China should consider incorporating GDM screening and management to further enhance reproductive health. TRIAL REGISTRATION: China Clinical Trials Registry ChiCTR1800017488. https://www.chictr.org.cn/.

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.

Association between diurnal temperature range and sperm quality: Evidence from a prospective cohort in Central China.

Inter-day temperature variability has been reported to be associated with sperm quality in a city-level exposure assessment study. However, studies exploring the impact of temperature variability within a single day on sperm quality at individual level are still lacking. The present study aims to bridge this research gap by analyzing the linear and non-linear associations between diurnal temperature range (DTR) exposure and sperm quality, utilizing data from the Anhui Prospective Assisted Reproduction Cohort. The study included 15,112 males (totaling 28,267 tests) and assessed individual exposure to various environmental factors (residential greenness, ambient particulate matter, sulfur dioxide, relative humidity, ambient temperature, and DTR) during the 0-90 day period before semen analysis. A combination of a linear mixed model, natural cubic splines, and subgroup analysis was employed. Significant "U"-shaped non-linear associations were observed between DTR exposure and total motility, sperm concentration, sperm count, total motile sperm count, and progressive motile sperm count. Lower DTR levels negatively impacted these parameters, whereas higher DTR levels showed a positive effect. Notably, these associations were more pronounced at ambient temperatures below 16.5 °C, while absent in warmer conditions. Sperm quality demonstrates increased sensitivity to DTR exposure in cooler environments. Therefore, implementing effective individual temperature management strategies is crucial for mitigating decreased sperm quality associated with DTR exposure, highlighting the potential benefits of government policies aimed at achieving carbon neutrality to enhance overall sperm quality in the general population.

Associations of exposure to ambient fine particulate matter constituents from different pollution sources with semen quality: Evidence from a prospective cohort.

The association between ambient fine particulate matter (PM2.5) exposure and semen quality remains inconclusive, possibly due to variations in pollution sources and PM2.5 compositions. Studies investigating the constituents of PM2.5 have been hindered by small sample sizes, and research exploring the relationships between PM2.5 pollution sources and semen quality is lacking. To address this gap, we conducted a comprehensive study based on the Anhui prospective assisted reproduction cohort to evaluate the associations between semen quality and the constituents and pollution sources of PM2.5. This study included 9013 semen samples from 4417 males in the urban districts of Hefei. The median concentrations of PM2.5 constituents, including eight metals and four water-soluble ions (WSIs), were measured for seven days per month at two monitoring stations during the 0-90-day exposure window. A linear mixed-effects model, weighted quantile sum regression, and positive matrix factorisation were used to evaluate the associations of the constituents and pollution sources of PM2.5 with semen quality. The results showed that exposure to PM2.5-bound metals (antimony, arsenic, cadmium, lead, and thallium) and WSIs (sulphate and chloride) were negatively associated with semen quality parameters. Moreover, mixtures of PM2.5-bound metals and WSIs were negatively associated with semen quality. Additionally, PM2.5 derived from traffic emissions was negatively associated with semen quality. In summary, our study revealed that ambient PM2.5 and its constituents, especially metals, were negatively associated with semen quality. Antimony, lead, and thallium emerged as the primary contributors to toxicity, and PM2.5 from traffic emissions was associated with decreased semen quality. These findings have important public health implications for the management of PM2.5 pollution in the context of male reproductive health.

Mesenchymal stem cells therapy improves ovarian function in premature ovarian failure: a systematic review and meta-analysis based on preclinical studies.

Background: Studies have revealed that the transplantation of mesenchymal stem cells (MSCs) might be a potential star candidate for premature ovarian failure (POF) in animal experiments. However, individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis to explore the potential of using MSCs in the treatment of POF in animals. Methods: Seven databases were searched for studies exploring the effect of the transplantation of MSCs on POF in animal models. The PRISMA guideline was followed, and the methodological quality was ensured using SYRCLE's risk of bias tool. RevMan 5.4 and STATA 12.0 software was performed to meta-analysis. Results: In total, 37 studies involving 1,079 animals were included. Significant associations were found for MSCs with the levels of E2 (SMD 2.69 [95% CI 1.97, 3.41]), FSH (-2.02, [-2.74, -1.30]), primary follicles (2.04, [1.17, 2.92]), secondary follicles (1.93, [1.05, 2.81]), and primordial follicles (2.38, [1.19, 3.57]. Other outcomes, such as AMH, LH, INHB, antral follicles, growing follicles, mature follicles, and early antral were also found to be significant. There was no difference in FSH/LH, corpus leteum, follicles, and estruc cycle. Conclusions: Our meta-analysis result indicated that the transplantation of MSCs might exert therapeutic effects on animal models of POF, and these effects might be associated with improving the disorder of the sexual cycle, modulating serum hormone expressions to a better state, and restoring ovarian function.

Preferences of pregnant individuals to undergo labor after one cesarean in southern China.

BACKGROUND: Labor after cesarean (LAC) remains an optional delivery method among healthy pregnant individuals. Exploring women's attitudes, preferences, reasons for previous cesarean delivery, and the incentives underlying pregnant individuals' preferences could help us understand their choice of delivery mode. In this study we evaluated the preferences and attitudes of eligible pregnant women regarding participation in a LAC in Foshan, China. METHODS: A cross-sectional survey was conducted among 438 pregnant individuals with one prior cesarean delivery (CD) who attended their antenatal examination at a tertiary hospital in southern China, between November 1, 2018, and October 31, 2019. Information on demographic characteristics, obstetric data, preferences for LAC, and incentives for LAC were analyzed. RESULTS: Overall, 85.4% (374/438) of women preferred LAC if they did not have contraindications before delivery, whereas 12.3% (54/438) refused and 2.3% (10/438) were unsure. Participants reported that the most important factors affecting their willingness to undergo LAC were safety indicators (i.e., "ability of hospitals to perform emergency cesarean delivery" [score of 9.28 ± 1.86]), followed by accessibility indicators (i.e., "priority bed arrangements" [score of 9.17 ± 1.84]). Logistic regression analysis indicated that neonatal wellbeing with the prior CD was an independent influencing factor (OR = 2.235 [95%CI: 1.115-4.845], p = 0.024) affecting willingness to access LAC in the subsequent pregnancy. CONCLUSIONS: We found a high preference for LAC among pregnant individuals without contraindications before delivery in southern China. Healthcare providers need to ensure access to LAC and increase pregnant individuals' LAC willingness through high-quality shared decsision-making in alignment with patient preferences.

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.

Prediction of vaginal birth after cesarean in China.

OBJECTIVE: This study aimed to develop and validate a prediction model of vaginal birth after cesarean delivery (VBAC) in China. METHODS: A nomogram for effective prediction of VBAC of singleton, cephalic and one previous low-transverse cesarean section deliveries was created by comparing the combinations of ultrasonographic and non-ultrasonographic factors from five hospitals between 2018 and 2019. RESULTS: A total of 1066 women were included. Of the women who underwent trial of labor after cesarean (TOLAC), 854 (80.1%) had a VBAC. Ultrasound factors included reached a higher area under the curve (AUC) combined with non-ultrasonographic factors. Of the three ultrasonographic factors analyzed, the best predictive factor for successful TOLAC was fetal abdominal circumference. A nomogram was generated with eight validated factors, including maternal age, gestational week, height, previous vaginal delivery, Bishop score, dilatation of the cervix at the time of admission, body mass index at delivery, and fetal abdominal circumference by ultrasound. The trained and validated AUC were 0.719 (95% confident interval 0.674-0.764) and 0.774 (95% confident interval 0.712-0.837), respectively. CONCLUSION: Our VBAC nomogram based on obstetric factors and fetal abdominal circumference obtained by ultrasound could be used to counsel women who are considering TOLAC.

Blood Type and Outcomes in Pregnant Women with Placenta Previa.

Background: Placenta previa increases the risks of obstetrical complications. Many studies have reported a link between various ABO blood types and pregnancy complications. This study is aimed at describing and comparing the characteristics and outcomes of women with placenta previa by ABO blood type. Methods: Data for this study was obtained from a retrospective cohort study between January 1, 2014, and June 30, 2019, of all clinically confirmed placenta previa in a university-based tertiary medical center. Both types of A, B, O, AB, and combining O and non-O blood types were compared to the characteristics and outcomes. Results: 1678 participants with placenta previa were included in this study. The highest participants were blood type O with 666 (39.7%), followed by type A with 508 (30.3%) and type B with 395 (23.5%), and the lowest participants were AB with 109 (6.5%). Blood type AB had a higher incidence of antepartum hemorrhage (p = 0.017), predelivery anemia (p = 0.036), and preterm birth (p = 0.015) in placenta previa women. Meanwhile, the incidence of rhesus D positive (97.9% vs. 95.8%, p = 0.012) and twins (5.0% vs. 2.7%, p = 0.011) was higher in the non-O group, and the incidence of neonatal asphyxia (5.9% vs. 9.2%, p = 0.016) was lower in the non-O group. Conclusion: Type AB blood may be a potential risk factor for women with placenta previa. This finding may help provide any obstetrician to predict the risk of complication for placenta previa women by the ABO blood types.

Walking or jogging during pregnancy increases the success rate of vaginal birth after cesarean delivery: A multicenter, retrospective cohort study.

OBJECTIVE: Exercise during pregnancy has been proven to reduce the risk of cesarean delivery. However, few studies have examined the relationship between walking or jogging during pregnancy and the success rate of vaginal birth after cesarean delivery (VBAC). This multicenter, retrospective cohort study aimed to determine the association between walking or jogging during pregnancy and the success rate of VBAC in women who underwent a trial of labor after cesarean delivery. METHODS: The study was conducted between January 2018 and December 2019 in Foshan, China. Univariate and multivariable analyses were performed on demographic and obstetric data collected from the electronic record system. RESULTS: Of 1080 women included in the final analysis, 80.4% underwent VBAC. In the multivariable analysis, women who walked or jogged ≥200 min/week during pregnancy had a higher likelihood of successful VBAC than women who did not exercise, after adjusting for two sets of confounders: Model 1: Adjusted odds ratio (OR), 1.74 (95% confidence interval [CI], 1.06-2.85) and model 2: Adjusted OR, 1.83 (95% CI, 1.09-3.06). CONCLUSIONS: Walking or jogging ≥200 min/week during pregnancy significantly reduces the risk of cesarean delivery among women who undergo a trial of labor after cesarean delivery.

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.

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.

Side-effects of oxytocin in postpartum hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the side-effects of oxytocin for the prevention of postpartum hemorrhage (PPH) in randomized controlled trials (RCTs). METHODS: Electronic databases (Web of Science, Embase, PubMed, Elsevier ScienceDirect, the Cochrane Library, and ClinicalTrials.gov) were searched from the beginning of indexing to Sep 2021. RCTs comparing oxytocin with non-oxytocin uterotonic agent(s) or non-pharmacologic interventions for the prevention of PPH were eligible. RESULTS: Overall, sixty-one RCTs meeting the inclusion criteria were included, involving 68834 participants. Twenty-seven types of side-effects were reported in this study. There were 24, 35, or 2 trials assessed as high medium and low quality, respectively. Compared with non-oxytocin, oxytocin had significantly lower risk for shivering (RR=0.31, 95% CI=0.23-0.41, n=36680), fever (RR=0.27, 95% CI=0.20-0.37, n=34031), and diarrhea (RR=0.48, 95% CI=0.35-0.66, n=30883). Other side-effects were not found associated with oxytocin. CONCLUSION: Oxytocin use was association with a significantly lower incidence of shivering, fever, and diarrhea events and did not increase risk of other side-effects during the third stage of labor. These observations may aid obstetricians and gynecologists in weighing up the benefits and risks associated with oxytocin in prevention and treatment of PPH during the third stage of labor.

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.