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.

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 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.

Association between serum total bilirubin and Alzheimer's disease: A bidirectional Mendelian randomization study.

Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). As a potent antioxidant, serum bilirubin is decreased in AD and may be related to its pathogenesis, but the causal association between serum bilirubin and AD has not been reported. This was investigated in the present study by bidirectional two-sample Mendelian randomization (MR) analysis. Genetic instruments at the genome-wide significance level (P < 5 × 10-8) were selected from the United Kingdom Biobank (n = 342,829). Summary-level AD data were obtained from a large-scale genome-wide association study (n = 63,926). Causal estimates were evaluated using the inverse variance weighted (IVW) approach and other five complementary methods. MR-Egger, IVW and MR pleiotropy residual sum and outlier (MR-PRESSO) methods were used for sensitivity analyses. The results showed that there was no significant association between serum total bilirubin and AD (odds ratio=1.003, 95% confidence interval: 0.967-1.041, P = 0.865). Inverse MR revealed that serum total bilirubin was increased in AD (beta = 0.009, SE = 0.003, P = 0.010). These results indicate that serum total bilirubin is not causally associated with AD and cannot be used for screening or diagnosis, but can potentially serve as a biomarker of disease severity, and it needs further clinical studies.

Associations between thyroid function and gestational diabetes mellitus in Chinese pregnant women: a retrospective cohort study.

BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.

Fasting Plasma Glucose Mediates the Prospective Effect of Maternal Metal Level on Birth Outcomes: A Retrospective and Longitudinal Population-Based Cohort Study.

Objective: Previously, we found that the presence of maternal serum metals before the 24th week of gestation prospectively increased fasting plasma glucose (FPG) at 24-28 weeks. We further explored the prospective association between levels of metals and neonatal outcomes and assessed the mediating effects of FPG on these relationships. Methods: A total of 7,644 pregnant women were included in a retrospective cohort study, and the relationships between metals [manganese (Mn), copper (Cu), lead (Pb), zinc (Zn), and magnesium (Mg)] and birth outcomes were explored. Quantile and linear regressions were performed to detect the shifts and associations between metals and neonatal size distribution focused on the 10th, 50th, and 90th percentiles. Mediation analysis was performed to assess the mediating effect of FPG on metals and birth outcomes. Results: After adjustment, a 50% increase in Mn and Zn levels was related to a 0.136-cm (95% CI: 0.067-0.205) and 0.120-cm (95% CI: 0.046-0.193) increase in head circumference, respectively. Based on head circumference distribution, the magnitude of the association with Mn was smaller at the upper tail, while the magnitude of correlation with Zn was greater at the upper tail. A 50% increase in Mn and Zn levels was related to a 0.135-cm (95% CI: 0.058-0.212) and 0.095-cm (95% CI: 0.013-0.178) increase in chest circumference, respectively. The magnitude of the association with Mn increased with increasing chest circumference, while the magnitude of correlation with Zn decreased with increasing chest circumference. FPG explained 10.00% and 17.65% of the associations of Mn with head and chest circumference. A positive indirect effect of Zn associated with head circumference (0.004, 95% CI: 0.002-0.006) and chest circumference (0.005, 95% CI: 0.003-0.008) through FPG was also observed, and the estimated proportion of the mediating effect was 13.79% and 26.32%, respectively. Conclusion: Maternal serum Mn and Zn levels before the 24th week of gestation may prospectively increase the circumference of the neonatal head and chest. FPG at 24-28 weeks had positive mediating effects on these relationships. Further research is needed to identify a balance between maternal blood glucose and birth size.

Association Between Perceived Stress and Prenatal Depressive Symptoms: Moderating Effect of Social Support.

PURPOSE: Prenatal depressive symptoms are an important mental health problem during pregnancy. We aimed to explore the moderating role of social support on the association between perceived stress and prenatal depressive symptoms. MATERIALS AND METHODS: A cross-sectional study was conducted at an obstetrics clinic. A total of 1846 women completed a self-administered questionnaire, with a response rate of 91.8%. RESULTS: Of the 1846 participants, 28.2% reported prenatal depressive symptoms (Edinburgh postnatal depression scale score ≥ 9). After adjusting for demographic characteristics, gestational age, exercise, and passive smoking, both perceived stress (adjusted odds ratio (AOR): 1.210, 95% confidence interval (CI): 1.178-1.242) and social support (AOR: 0.950, 95% CI: 0.932-0.968) were associated with prenatal depressive symptoms. Moreover, social support had a moderating effect on the association between perceived stress and prenatal depressive symptoms (p < 0.001), and pregnant women with low social support were more likely to be affected by stress and experience prenatal depressive symptoms. CONCLUSION: Our study suggests that higher social support reduces the impact of stress on pregnant women, which in turn, decreases the risk of prenatal depressive symptoms. Therefore, interventions aimed at improving social support should be considered for the prevention and treatment of prenatal depressive symptoms.

Prospective association of metal levels with gestational diabetes mellitus and glucose: A retrospective cohort study from South China.

OBJECTIVE: To explore the prospective correlation between serum metals before 24 weeks' gestation and gestational diabetes mellitus (GDM) or glucose in the late second trimester among southern Chinese pregnant women. METHODS: A total of 8169 pregnant women were included in our retrospective cohort study. Logistic regression was used to investigate the relationships between metals (Manganese [Mn], copper [Cu], lead [Pb], calcium [Ca], zinc [Zn], magnesium [Mg]) and GDM. Quantile regression was performed to detect the shifts and associations with metals and three time-points glucose distribution of oral glucose tolerance test (OGTT) focused on the 10th, 50th, and 90th percentiles. Weighted quantile sum (WQS) regression was used to explore the relationship of metal mixtures and GDM as well as glucose. RESULTS: Maternal serum concentrations of metals were assessed at mean 16.55 ± 2.92 weeks' gestation. Women with under weight might have 25% decreased risk of GDM for every 50% increase in Cu concentration within the safe limits. A 50% increase in Mn and Zn levels was related to a 0.051 µmol/L (95% CI: 0.033-0.070) and 0.059 µmol/L (95% CI: 0.040-0.079) increase in mean fasting plasma glucose of OGTT (OGTT0), respectively. The magnitude of association with Mn was smaller at the upper tail of OGTT0 distribution, while the magnitude of correlation with Zn was greater at the upper tail. However, there was a 0.012 mmol/L (95% CI: -0.017 to -0.008), 0.028 mmol/L (95% CI: -0.049 to -0.007), and 0.036 mmol/L (95% CI: -0.057 to -0.016) decrease in mean OGTT0 levels for every 50% increase in Pb, Ca, and Mg, respectively. The negative association of Pb, Ca, and Mg was greater at the lower tail of OGTT0 distribution. No significant relationship was observed in Cu and mean OGTT0 level (-0.010 mmol/L, 95% CI: -0.021 to 0.001), however, it showed a protective effect at the upper tail (-0.034 mmol/L, 95% CI: -0.049 to -0.017). No obvious correlation was found between metals and postprandial glucose levels (OGTT1 and OGTT2 from OGTT). The WQS index was significantly related to OGTT0 (P < 0.001). The contribution of Mn (80.19%) to metal mixture index was the highest related to OGTT0, followed by Cu (19.81%). CONCLUSIONS: Higher Mn and Zn but lower Pb, Ca, and Mg concentrations within a certain range before 24 weeks' gestation might prospectively impair fasting plasma glucose during pregnancy; a greater focus is required on Mn. It could provide early markers of metal for predicting later glucose and suggest implement intervention for pregnant women.

The overexpression of MCPH1 inhibits cell growth through regulating cell cycle-related proteins and activating cytochrome c-caspase 3 signaling in cervical cancer.

MCPH1, initially identified as an hTERT repressor, has recently been implicated in mediating DNA damage response and maintaining chromosome integrity. This study is to investigate its potential role in the onset of cervical cancer. In the study, decreased expression of MCPH1 was observed in 19 of 31 cases (61.3%) at mRNA level and 44 of 63 cases (69.8%) at protein level of cervical tumor tissues compared with the paired nontumor tissues. Reduced MCPH1 protein expression was significantly associated with high-tumor grade (1 vs. 3 P = 0.013; 2 vs. 3 P = 0.047). In addition to inhibit SiHa cell migration and invasion, the overexpression of MCPH1 inhibited cervical cancer cells growth through inducing S phase arrest and mitochondrial apoptosis. Further analysis demonstrated cyclinA2/CDK2, CDC25C-cyclinB/CDC2, and p53/p21 pathways were involved in the MCPH1 overexpression-induced S phase arrest. Moreover, the overexpression of MCPH1 activated mitochondrial apoptosis through regulating several apoptosis-related proteins such as p53, Bcl-2, Bax, cytochrome c, caspase-3, and PARP-1. Our findings indicate that downregulated MCPH1 correlates with tumor progression in cervical cancer, and MCPH1 has an important role in regulating cell growth through regulating the cell cycle and apoptosis. Thus, it may be a crucial tumor suppressor gene and a novel candidate therapeutic target for cervical cancer.