The role of maternal age on adverse pregnancy outcomes among primiparous women with singleton birth: a retrospective cohort study in urban areas of China.

BACKGROUND: Both young and advanced maternal age pregnancies have strong associations with adverse pregnancy outcomes; however, there is limited understanding of how these associations present in an urban environment in China. This study aimed to analyze the associations between maternal age and pregnancy outcomes among Chinese urban women. METHODS: We performed a population-based study consisting of 60,209 singleton pregnancies of primiparous women whose newborns were delivered after 20 weeks' gestation between January 2012 and December 2015 in urban areas of China. Participants were divided into six groups (19 or younger, 20-24, 25-29, 30-34, 35-39, 40 or older). Pregnancy outcomes include gestational diabetes mellitus (GDM), preeclampsia, placental abruption, placenta previa, premature rupture of membrane (PROM), postpartum hemorrhage, preterm birth, low birthweight, small for gestational age (SGA), large for gestational age (LGA), fetal distress, congenital microtia, and fetal death. Logistic regression models were used to assess the role of maternal age on the risk of adverse pregnancy outcomes with women aged 25-29 years as the reference group. RESULTS: The risks of GDM, preeclampsia, placenta previa, and postpartum hemorrhage were decreased for women at a young maternal age and increased for women with advanced maternal age. Both young and advanced maternal age increased the risk of preterm birth and low birthweight. Young maternal age was also associated with increased risk of SGA (aOR 1.64, 95% CI 1.46-1.83) and fetal death (aOR 2.08, 95% CI 1.35-3.20). Maternal age over 40 years elevated the odds of placental abruption (aOR 3.44, 95% CI 1.47-8.03), LGA (aOR 1.47, 95% CI 1.09-1.98), fetal death (aOR 2.67, 95% CI 1.16-6.14), and congenital microtia (aOR 13.92, 95% CI 3.91-49.57). There were positive linear associations between maternal age and GDM, preeclampsia, placental abruption, placenta previa, PROM, postpartum hemorrhage, preterm birth, LGA and fetal distress (all P for linear trend < .05), and a negative linear association between maternal age and SGA (P for linear trend < .001). The analysis of the associations between maternal age and adverse fetal outcomes showed U-shape for preterm birth, low birth weight, SGA, fetal death and congenital microtia (all P for quadratic trend < .001). CONCLUSIONS: Advanced maternal age predisposes women to adverse obstetric outcomes. Young maternal age manifests a bidirectional effect on adverse pregnancy outcomes. The findings may contribute to improving women's antenatal care and management.

Effect of gestational diabetes mellitus on pregnancy outcomes among younger and older women and its additive interaction with advanced maternal age.

Background: The prevalence of gestational diabetes mellitus (GDM) and advanced maternal age (AMA, ≥ 35 years) has shown an increasing trend worldwide. This study aimed to evaluate the risk of pregnancy outcomes among younger (20-34 years) and older (≥ 35 years) women with GDM and further analyze the epidemiologic interaction of GDM and AMA on these outcomes. Methods: This historical cohort study included 105 683 singleton pregnant women aged 20 years or older between January 2012 and December 2015 in China. Stratified by maternal age, the associations between GDM and pregnancy outcomes were analyzed by performing logistic regression. Epidemiologic interactions were assessed by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) with their 95% confidence intervals (95%CIs). Results: Among younger women, individuals with GDM had a higher risk of all maternal outcomes, preterm birth (relative risk [RR] 1.67, 95%CI 1.50-1.85), low birthweight (RR 1.24, 95%CI 1.09-1.41), large for gestational age (RR 1.51, 95%CI 1.40-1.63), macrosomia (RR 1.54, 95%CI 1.31-1.79), and fetal distress (RR 1.56, 95%CI 1.37-1.77) than those without GDM. Among older women, GDM increased the risk of gestational hypertension (RR 2.17, 95%CI 1.65-2.83), preeclampsia (RR 2.30, 95%CI 1.81-2.93), polyhydramnios (RR 3.46, 95%CI 2.01-5.96), cesarean delivery (RR 1.18, 95%CI 1.10-1.25), preterm birth (RR 1.35, 95%CI 1.14-1.60), large for gestational age (RR 1.40, 95%CI 1.23-1.60), macrosomia (RR 1.65, 95%CI 1.28-2.14) and fetal distress (RR 1.46, 95%CI 1.12-1.90). Additive interactions of GDM and AMA on polyhydramnios and preeclampsia were found, with RERI of 3.11 (95%CI 0.05-6.16) and 1.43 (95%CI 0.09-2.77), AP of 0.51 (95%CI 0.22-0.80) and 0.27 (95%CI 0.07-0.46), and SI of 2.59 (95%CI 1.17-5.77) and 1.49 (95%CI 1.07-2.07), respectively. Conclusion: GDM is an independent risk factor for multiple adverse pregnancy outcomes, and may exert additive interactions with AMA on the risk of polyhydramnios and preeclampsia.

Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression.

Microcystin-LR (MCLR) is an aquatic toxin, which could lead to the development of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are considered important regulatory elements in the occurrence and development of cancer. However, the roles and mechanisms of lncRNAs during the process of HCC, induced by MCLR, remain elusive. Here, we identified a novel lncRNA, namely lnc-GCLC-1 (lncGCLC), which is in close proximity to the chromosome location of glutamate-cysteine ligase catalytic subunit (GCLC). We then investigated the role of lncGCLC in MCLR-induced malignant transformation of WRL68, a human hepatic cell line. During MCLR-induced cell transformation, the expression of lncGCLC and GCLC decreased continuously, accompanied with a consistently high expression of miR-122-5p. Knockdown of lncGCLC promoted cell proliferation, migration and invasion, but reduced cell apoptosis. A xenograft nude mouse model demonstrated that knockdown of lncGCLC promoted tumor growth. Furthermore, knockdown of lncGCLC significantly upregulated miR-122-5p expression, suppressed GCLC expression and GSH levels, and enhanced oxidative DNA damages. More importantly, the expression of lncGCLC in human HCC tissues was significantly downregulated in the high-microcystin exposure group, and positively associated with GCLC level in HCC tissues. Together, these findings suggest that lncGCLC plays an anti-oncogenic role in MCLR-induced malignant transformation by regulating GCLC expression.

Pregnancy outcomes in women affected by fetal alpha-thalassemia: a case control study.

To evaluate the possible associations between fetal α-thalassemia and risk of adverse pregnancy outcomes using a provincial woman-child health service information database in China. This was a case control study (N = 438,747) in which we compared all singleton pregnancies of women with or without the α-thalassemia trait from May 2016 to May 2020, and where women with the trait were further allocated to a normal fetal group, a group of fetuses with the α-thalassemia trait, and a fetal group with hemoglobin H (HbH) disease according to the results of fetal DNA analysis. With thalassemic women whose fetuses were normal as the reference, fetuses in the HbH disease group showed a higher increase in the odds of Apgar scores being < 7 at 1 min (adjusted odds ratio [aOR], 2.79; 1.03-7.59) and 5 min (aOR, 4.56; 1.07-19.40). With non-thalassemic women as the reference, these trends were more obvious (aOR, 4.83; 2.55-9.16; aOR, 6.24; 2.75-14.18, respectively); whereas the normal fetal group was more likely to be diagnosed with postpartum hemorrhage (aOR, 1.66; 1.10-2.50). In addition, fetal HbH disease and gestational age were two independent factors influencing low Apgar scores, and their combination reflected medium accuracy in Apgar predictions.

Down-regulation of GCLC is involved in microcystin-LR-induced malignant transformation of human liver cells.

Microcystin-LR (MCLR) is a potent hepatotoxin which could lead to the development of hepatocellular carcinoma. However, the mechanisms of its carcinogenic action remain obscure. The catalytic subunit of glutamylcysteine ligase (GCLC) primarily regulates de novo synthesis of glutathione and is central to the antioxidant capacity of the cell, but emerging data suggest that the GCLC expression is associated with cancer development. The purpose of this study was to investigate the role and molecular mechanisms of GCLC in MCLR-induced malignant transformation of a human liver cell line WRL68. During MCLR-induced cell transformation, the expression of GCLC and activity of glutamate-cysteine ligase (GCL) decreased continuously, accompanied with consistent low levels of glutathione (GSH) but high levels of oxidative DNA damages. Furthermore, MCLR markedly inhibited protein phosphatase 2 A (PP2 A), and increased the level of GCLC phosphorylation. In contrast, overexpression of GCLC significantly enhanced the levels of GSH, inhibited oxidative DNA damages, and suppressed MCLR-induced cell invasion and migration, as well as tumor growth in nude mice. GCLC overexpression partially attenuated MCLR-induced PP2 A inhibition. Together, the current results suggest that down-regulation of GCLC is involved in MCLR-induced malignant transformation of human liver cells by inducing oxidative stress.

NBS1 rs2735383 polymorphism is associated with an increased risk of laryngeal carcinoma.

BACKGROUND: Nijmegen breakage syndrome 1 (NBS1), as a key protein in the DNA double-strand breaks (DSBs) repair pathway, plays an important role in maintaining genomic stability. Although single nucleotide polymorphisms (SNPs) in NBS1 have frequently been studied in multiple cancers, the relationships of two functional NBS1 polymorphisms (rs2735383 and rs1805794) with laryngeal carcinoma are yet unclear. Therefore, in the present study, we performed a case-control study including 342 cases and 345 controls to analyze the associations between two polymorphisms of NBS1 and the risk of laryngeal carcinoma. METHODS: We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotypes of the functional SNPs in NBS1 gene. RESULTS: In comparison with the homozygous rs2735383GG genotype, the CC genotype was significantly associated with an increased risk of laryngeal carcinoma (adjusted OR = 1.884, 95%CI = 1.215-2.921). The rs2735383C variant genotypes (GC + CC) conferred a 1.410-fold increased risk of laryngeal carcinoma (adjusted OR = 1.410, 95%CI = 1.004-1.980). Furthermore, when compared to rs2735383GG genotype in laryngeal carcinoma tissues, the combined GC and CC genotypes exerted a significantly lower mRNA level of NBS1 (P = 0.003). In contrast, no significant association was found between rs1805794G > C polymorphism and cancer risk (adjusted OR = 1.074, 95%CI = 0.759-1.518 for GC; adjusted OR = 1.100, 95%CI = 0.678-1.787 for CC; adjusted OR = 1.079, 95%CI = 0.774-1.505 for GC + CC). CONCLUSIONS: These findings indicate that rs2735383G > C polymorphism in NBS1 may play a crucial role in the development of laryngeal carcinoma.