[Association between maternal reduced folate carrier gene polymorphisms and congenital heart disease in offspring: a case-control study].

OBJECTIVE: To study the association between maternal reduced folate carrier (RFC) gene polymorphisms and congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA:OR=1.91, 95%CI:1.45-2.51; GG vs AA: OR=1.96, 95%CI:1.40-2.75) and rs2330183 (CT vs CC:OR=1.39, 95%CI:1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G (OR=1.21, 95%CI:1.03-1.41) and T-G (OR=1.25, 95%CI:1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD (P < 0.05). CONCLUSIONS: Maternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.

Novel two-step derivation method for the synchronous analysis of inherited metabolic disorders using urine.

The aim of the present study was to conduct preliminary clinical screening and monitoring using a novel two-step derivatization process of urine in five categories of inherited metabolic disease (IMD). Urine samples (100 µl, containing 2.5 mmol/l creatinine) were taken from patients with IMDs. The collected urine was then treated using a two-step derivatization method (with oximation and silylation at room temperature), where urea and protein were removed. In the first step of the derivatization, α-ketoacids and α-aldehyde acids were prepared by oximation using novel oximation reagents. The second-step of the derivatization was that residues were silylated for analysis. Urine samples were examined using gas chromatography/mass spectrometry (GC/MS) and a retention time-locking technique. The simultaneous analysis and identification of >400 metabolites in >130 types of IMD was possible from the GC/MS results, where the IMDs included phenylketonuria, ornithine transcarbamylase deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, ß-ureidopropionase deficiency and mitochondrial metabolic disorders. This method was demonstrated to have good repeatability. Considering α-ketoglutarate (α-KG) as an example, the relative standard deviations (RSDs) of the α-KG retention time and peak area were 0.8 and 3.9%, respectively, the blank spiked recovery rate was between 89.6 and 99.8%, and the RSD was ≤7.5% (n=5). The method facilitates the analysis of thermally non-stable and semi-volatile metabolites in urine, and greatly expands the range of materials that can be synchronously screened by GC/MS. Furthermore, it provides a comprehensive, effective and reliable biochemical analysis platform for the pathological research of IMDs.

Worldwide prevalence of adverse pregnancy outcomes associated with in vitro fertilization/intracytoplasmic sperm injection among multiple births: a systematic review and meta-analysis based on cohort studies.

PURPOSE: To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among multiple births conceived with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: PubMed, Google Scholar, Cochrane Libraries and Chinese databases were searched through May 2016 for cohort studies assessing adverse pregnancy outcomes associated with IVF/ICSI multiple births. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. RESULTS: Sixty-four studies, with 60,210 IVF/ICSI multiple births and 146,737 spontaneously conceived multiple births, were selected for analysis. Among IVF/ICSI multiple births, the pooled estimates were 51.5% [95% confidence interval (CI): 48.7-54.3] for preterm birth, 12.1% (95% CI: 10.4-14.1) for very preterm birth, 49.8% (95% CI: 47.6-52.0) for low birth weight, 8.4% (95% CI: 7.1-9.9) for very low birth weight, 16.2% (95% CI: 12.9-20.1) for small for gestational age, 3.0% (95% CI: 2.5-3.7) for perinatal mortality and 4.7% (95% CI: 4.0-5.6) for congenital malformations. When the data were restricted to twins, the pooled estimates also showed a high prevalence of adverse outcomes. There was a similar prevalence of poor outcomes among multiple births conceived with IVF/ICSI and naturally (all P ≥ 0.0792). Significant differences in different continents, countries, and income groups were found. CONCLUSIONS: The IVF/ICSI multiple pregnancies have a high prevalence of adverse pregnancy outcomes. However, population-wide prospective adverse outcomes registries covering the entire world population for IVF/ICSI pregnancies are needed to determine the exact perinatal prevalence.

Worldwide prevalence of adverse pregnancy outcomes among singleton pregnancies after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis.

PURPOSE: The worldwide prevalence of adverse pregnancy outcomes (APOs) in singleton pregnancies after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is suggested to vary; however, a complete overview is missing. The aim of this review is to estimate the worldwide prevalence of APOs associated with IVF/ICSI singleton pregnancies. METHODS: PubMed, Google Scholar, Cochrane Libraries, and Chinese databases were searched for studies assessing APOs among IVF/ICSI singleton births through March 2016. The prevalence estimates were summarized and analyzed by meta-analysis. RESULTS: Fifty-two cohort studies, with 181,741 IVF/ICSI singleton births and 4,636,508 spontaneously conceived singleton births, were selected for analysis. Among IVF/ICSI singleton pregnancies, pooled estimates were 10.9% [95% confidence interval (CI) 10.0-11.8] for preterm birth, 2.4% (95% CI 1.9-3.0) for very preterm birth, 8.7% (95% CI 7.4-10.2) for low birth weight, 2.0% (95% CI 1.5-2.6) for very low birth weight, 7.1% (95% CI 5.5-9.2) for small for gestational age, 1.1% (95% CI 0.9-1.3) for perinatal mortality, and 5.7% (95% CI 4.7-6.9) for congenital malformations. The IVF/ICSI singleton pregnancies have higher prevalence of APOs compared with those conceived naturally (all P = 0.000). Significant differences in different continents, countries, income groups, and type of assisted conception were found. CONCLUSIONS: The IVF/ICSI singleton pregnancies are at a higher prevalence of adverse perinatal outcomes compared with those conceived naturally. Important geographical differences were found. Yet, population-wide prospective APO registries covering the entire world population for IVF/ICSI pregnancies are needed to determine the exact perinatal prevalence.