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Objective: To compare the obstetric outcomes of women treated with in vitro fertilization (IVF), women with indicators of subfertility but without assisted reproductive technologies, and fertile women with singleton pregnancies. Methods: A prospective cohort study was conducted from March 2013 to February 2016 at the Hunan Provincial Maternal and Child Health Hospital in China. Finally, 1260 eligible mothers were recruited into the IVF group, 1899 into the subfertile group, and 2480 into the fertile group. Results: Compared to the fertile group, gestational diabetes mellitus (adjusted odds ratio [aOR] = 2.36; 95% confidence interval [CI]: 1.67-3.34), pregnancy-induced hypertension (aOR = 2.23; 95% CI: 1.37-3.64), placenta previa (aOR = 4.11; 95% CI: 2.12-7.96), premature rupture of membranes (aOR = 4.60; 95% CI: 2.71-7.81), anemia in pregnancy (aOR = 2.17; 95% CI: 1.42-3.31), preterm birth (PTB; aOR = 2.19; 95% CI: 1.59-3.02), low birth weight (aOR = 2.82; 95% CI: 2.02-3.94), perinatal mortality (aOR = 2.72; 95% CI: 1.67-4.03), and congenital malformations (aOR = 6.07; 95% CI: 3.14-11.72) were evidently increased in the IVF group, while placenta previa (aOR = 1.67; 95% CI: 1.05-2.67), PTB (aOR = 1.31; 95% CI: 1.05-1.64), low birth weight (aOR = 1.42; 95% CI: 1.12-1.81), and congenital malformations (aOR = 2.03; 95% CI: 1.28-3.21) were also increased in the subfertile group. Additionally, the IVF group compared to the subfertile group was at a higher risk of gestational diabetes mellitus (aOR = 1.40; 95% CI: 1.08-1.83), premature rupture of membranes (aOR = 1.45; 95% CI: 1.00-2.10), PTB (aOR = 1.26; 95% CI: 1.01-1.58), low birth weight (aOR = 1.75; 95% CI: 1.36-2.24), perinatal mortality (aOR = 1.95; 95% CI: 1.02- 3.46), and congenital malformations (aOR = 1.81; 95% CI: 1.12-2.92). Conclusion: An increased risk of adverse outcomes in IVF pregnancies may be a result of the IVF procedures themselves and the infertility itself together. [ABSTRACT FROM AUTHOR]

Although the phenylalanine/tyrosine ratio in blood has been the gold standard for diagnosis of phenylketonuria (PKU), the disadvantages of invasive sample collection and false positive error limited the application of this discriminator in the diagnosis of PKU to some extent. The aim of this study was to develop a new standard with high sensitivity and specificity in a less invasive manner for diagnosing PKU. In this study, an improved oximation-silylation method together with GC/MS was utilized to obtain the urinary metabolomic information in 47 PKU patients compared with 47 non-PKU controls. Compared with conventional oximation-silylation methods, the present approach possesses the advantages of shorter reaction time and higher reaction efficiency at a considerably lower temperature, which is beneficial to the derivatization of some thermally unstable compounds, such as phenylpyruvic acid. Ninety-seven peaks in the chromatograms were identified as endogenous metabolites by the National Institute of Standards and Technology (NIST) mass spectra library, including amino acids, organic acids, carbohydrates, amides, and fatty acids. After normalization of data using creatinine as internal standard, 19 differentially expressed compounds with p values of <0.05 were selected by independent-sample t test for the separation of the PKU group and the control group. A principal component analysis (PCA) model constructed by these differentially expressed compounds showed that the PKU group can be discriminated from the control group. Receiver-operating characteristic (ROC) analysis with area under the curve (AUC), specificity, and sensitivity of each PKU marker obtained from these differentially expressed compounds was used to evaluate the possibility of using these markers for diagnosing PKU. The largest value of AUC (0.987) with high specificity (0.936) and sensitivity (1.000) was obtained by the ROC curve of phenylacetic acid at its cutoff value (17.244 mmol/mol creatinine), which showed that phenylacetic acid may be used as a reliable discriminator for the diagnosis of PKU. The low false positive rate (1-specificity, 0.064) can be eliminated or at least greatly reduced by simultaneously referring to other markers, especially phenylpyruvic acid, a unique marker in PKU. Additionally, this standard was obtained with high sensitivity and specificity in a less invasive manner for diagnosing PKU compared with the Phe/Tyr ratio. Therefore, we conclude that urinary metabolomic information based on the improved oximation-silylation method together with GC/MS may be reliable for the diagnosis and differential diagnosis of PKU. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association between assisted reproductive technology (ART) and risk of congenital malformations (CM) by conducting a meta-analysis of cohort studies. Methods: PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through August 2014 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. Results: Fifty-seven studies involving 119,874 infants conceived following ART and 1,212,320 infants conceived naturally were included in the analysis. The ART-conceived infants were associated with a higher risk of CM [relative risk (RR) = 1.33; 95 % confidence interval (CI) 1.24-1.43] when compared with those conceived naturally. When data were restricted to singleton births (RR = 1.38; 95 % CI 1.30-1.47), major CM (RR = 1.47; 95 % CI 1.29-1.68), matched/adjusted studies (RR = 1.37; 95 % CI 1.27-1.47) or high quality studies (RR = 1.40; 95 % CI 1.27-1.55), the increased risk of CM still existed in ART pregnancies. Additionally, an increased risk of CM was also found when the ART twin (RR = 1.18; 95 % CI 1.06-1.32) or multiple births (RR = 1.16; 95 % CI 1.05-1.27) were separately compared with spontaneously conceived twin or multiple births. Substantial heterogeneity was observed across studies ( I = 68, 44, 39, and 33 % for all infants, singletons, twins and multiples, respectively). Whether confounding factors were matched or adjusted, study quality and sample size as the first three of the most relevant heterogeneity moderators have been identified. No evidence of publication bias was observed ( P > 0.10). Conclusions: The ART-conceived infants have a higher risk of CM compared with those conceived naturally. However, these estimates have to be viewed with caution because of heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient. Case presentation: Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as "pathogenic". c.1415T > G (p.V472G) located in extra-cellular region, was classified as "likely pathogenic". Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband's prenatal phenotype. Conclusion: The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition. [ABSTRACT FROM AUTHOR]

Objective: To examine whether dichorionic twin pregnancies after assisted reproductive technology (ART) were at higher risk of adverse obstetric outcomes compared with those conceived naturally.Design: Meta-analysis.Setting: University-affiliated teaching hospital.Patient(s): Dichorionic twin pregnancies conceived with ART and naturally.Intervention(s): Studies comparing obstetric outcomes in dichorionic twin pregnancies conceived by ART and naturally were identified by searching PubMed, Google Scholar, Cochrane Libraries, and Chinese databases through July 2015 with no restrictions. Either a fixed-effects or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Main Outcome Measure(s): Maternal complications and adverse pregnancy outcomes.Result(s): Fifteen cohort studies involving 6,420 dichorionic twins after ART and 13,650 dichorionic twins conceived naturally were included. Most of maternal complications were similar in both groups, but placenta previa (relative risk [RR] = 2.99, 95% confidence interval [CI] 1.51-5.92; I(2) = 0) was significantly more common in the ART group. For neonatal outcomes, the ART group experienced higher risk of preterm birth (RR = 1.13, 95% CI 1.00-1.29; I(2) = 75%), very preterm birth (RR = 1.39, 95% CI 1.07-1.82; I(2) = 71%), low birth weight (RR = 1.11, 95% CI 1.00-1.23; I(2) = 61%), and congenital malformations (RR = 1.26, 95% CI 1.09-1.46; I(2) = 26%). In addition, the ART group had a higher proportion of elective cesarean sections (RR = 1.79, 95% CI 1.49-2.16; I(2) = 60%), but had a similar proportion for emergency cesarean sections. Relevant heterogeneity moderators have been identified by subgroup analysis. No evidence of publication bias was observed.Conclusion(s): The rates of placenta previa, elective cesarean section, preterm birth, very preterm birth, low birth weight, and congenital malformations were significantly higher in dichorionic twin pregnancies after ART. [ABSTRACT FROM AUTHOR]

Image super-resolution from low-resolution fundus image has valuable applications in clinical practices. The popular methods yield unsatisfactory results when the fundus images are contaminated due to the bleeding or plaques caused by eye diseases. To this end, we propose a style-guided UNet (SGUNet) which incorporates a series of style-guided U-shape block (SUB) for fundus image super-resolution. Each SUB consists of trunk and mask branches. The proposed trunk branch is a U-shape structure that intends to enlarge the receptive field by down-sampling via large-stride convolution, and fuses the complementary information under the different receptive fields. The mask branch then dynamically estimates the relative importance of individual potential styles to reweigh the feature maps according to the significance of the potential styles. To fully leverage the hierarchical features, a dense feature fusion scheme is introduced by concatenating the output of preceding SUBs. We extensively validate the proposed network on low-resolution retina dataset with adversely affected by diseases. The experimental results demonstrate that our SGUNet achieves superior performance with excellent robustness and high accuracy by comparing with six popular methods. [ABSTRACT FROM AUTHOR]

Postpartum depression affects about 10-20% of newly delivered women, which is harmful for both mothers and infants. However, the current diagnosis of postpartum depression depends on the subjective judgment of a practitioner, which may lead to misdiagnosis. Hence, an appended objective diagnosis index may help the practitioner to improve diagnosis. A metabolomic study can find biomarkers as an objective index to facilitate disease diagnosis. Forty-nine postpartum depressed patients and 50 healthy controls were recruited into this study. The metabolites in urine were scanned with LC-Q-TOF-MS. The metabolomic data were analyzed with a multivariate statistical analysis method. Data from 40 patients and 40 controls were used for partial least square-discriminate analysis (PLS-DA). The urine metabolomic profiles of patients were different from those of controls. The PLS-DA model was validated by a permutation test, and the model could accurately classify the other 9 patients and 10 controls in T-prediction. Ten differentiating metabolites were found as main contributors to this difference, which are involved in amino acid metabolism, neurotransmitter metabolism, bacteria population, etc. Some of these potential biomarkers, such as 4-hydroxyhippuric acid, homocysteine, and tyrosine, showed relatively high sensitivities and specificities. The metabolic profile alteration induced by postpartum depression was found, and some of the differentiating metabolites may serve as biomarkers to facilitate the diagnosis of postpartum depression. [ABSTRACT FROM AUTHOR]

Objective: To determine whether there are any increases in pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies after assisted reproductive technology (ART) compared with those conceived naturally.Design: Meta-analysis.Setting: University-affiliated teaching hospital.Patient(s): Singleton pregnancies conceived with ART and naturally.Intervention(s): PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through March 2015 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Main Outcome Measure(s): Pregnancy-related complications and adverse pregnancy outcomes.Result(s): Fifty cohort studies comprising 161,370 ART and 2,280,241 spontaneously conceived singleton pregnancies were identified. The ART singleton pregnancies had a significantly increased risk of pregnancy-induced hypertension (relative risk [RR] 1.30, 95% confidence interval [CI] 1.04-1.62; I(2) = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I(2) = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I(2) = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I(2) = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I(2) = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I(2) = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I(2) = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I(2) = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I(2) = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I(2)=80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I(2) = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I(2) = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I(2) = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I(2) = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I(2)=45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I(2)=41%). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed.Conclusion(s): The ART singleton pregnancies are associated with higher risks of adverse obstetric outcomes. Obstetricians should manage these pregnancies as high risk. [ABSTRACT FROM AUTHOR]

Objective To provide an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology (ART) vs. spontaneous conception. Design Meta-analysis. Setting University-affiliated teaching hospital. Patient(s) Multiple pregnancies conceived by ART or naturally. Intervention(s) Searches through October 2014 were conducted on PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Data, to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. Main Outcome Measure(s) Pregnancy-related complications and adverse pregnancy outcomes. Result(s) Thirty-nine cohort studies involving 146,008 multiple births were included in the meta-analysis. Multiple pregnancies from ART were associated with a higher risk of premature rupture of membranes (relative risk [RR] = 1.20, 95% confidence interval [CI]: 1.05–1.37; I 2 = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04–1.19; I 2 = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25–2.55; I 2 = 42%); preterm birth (RR = 1.08, 95% CI: 1.03–1.14; I 2 = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04–1.34; I 2 = 79%); low birth weight (RR = 1.04, 95% CI: 1.01–1.07; I 2 = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01–1.25; I 2 = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02–1.22; I 2 = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed. Conclusion(s) Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that multiple pregnancies generated via ART, vs. spontaneous conception, are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes. Further research is needed to determine which aspect of ART poses the most risk and how this risk can be minimized. [ABSTRACT FROM AUTHOR]

Evidence of associations between maternal alcohol consumption and congenital heart disease (CHD) are mixed. Previous studies have been potentially biased due to recall bias or unmeasured confounding. This study aimed to examine the association of maternal alcohol consumption in 3 months before pregnancy and in early pregnancy with risks of offspring congenital heart disease (CHD) and its seven common subtypes. A prospective cohort study was conducted in Central China. From 03/13/2013 to 12/31/2019, a total of 44,048 pregnant women with singleton pregnancies at 8-14 gestational weeks were included and followed to 3 months postpartum. 564 births were diagnosed with CHD at the end of follow-up. Multivariable modified Poisson regression models were used to estimate the relative risks (RRs) of CHD in offspring exposed to maternal alcohol consumption during the pre-pregnancy and early-pregnancy period, adjusting for confounders identified by directed acyclic graphs. In the multivariable analyses, increased risks of CHDs were found in offspring exposed to maternal alcohol consumption both in 3 months before pregnancy (adjusted-RR:3.14; 95% confidence intervals[CIs]:2.30-4.28) and in early pregnancy (adjusted-RR:1.86; 95%CIs:1.13-3.05). More specifically, the offspring exposed to maternal alcohol consumption in 3 months before pregnancy had the highest increased risk of Tetralogy of Fallot (adjusted-RR:8.62; 95%CIs:3.61-20.61). These findings persisted in analyses that were further adjusted for the other behavior variables other than the characteristic being assessed, and were also confirmed by sensitivity analyses. Our study supports the need for continued efforts for public health messages surrounding the potential risks of alcohol consumption prior to or during pregnancy. [ABSTRACT FROM AUTHOR]

• The present study identified gender-related metabolic disturbances in patients with ASD. • The sex differences in metabolite levels may be associated with the implication of sex hormone. • The creatinine:creatine ratio may be a potential predictor of ASD in female subjects. Autism spectrum disorders (ASD) are a highly heterogeneous group of neurodevelopmental disorders that are more commonly diagnosed in boys than in girls. The reasons for gender differences in ASD are unknown and no definitive current evidence can explain male predominance. Therefore, in search for laboratory biomarkers responsible for ASD, a comprehensive metabolomics study was performed by metabolic profiling of urine samples in 51 ASD subjects and 51 age- and sex-matched children with typical development. Orthogonal partial least-squares discriminant analysis (OPLS-DA) models with poor quality failed to perform the analysis based on gender in the ASD and control groups. OPLS-DA models based on single-sex samples, especially in female subjects, had better clustering between the ASD and control groups with an increase in the R2 and Q2 values compared with those in the whole group. Significantly increased levels of adenine, 2-Methylguanosine, creatinine, and 7alpha-hydroxytestololactone and a decrease in creatine were observed in the female ASD subjects. In particular, 7alpha-hydroxytestololactone, which has a structure similar to that of testolactone, was positively correlated with adenine (Pearson correlation coefficient, r = 0.738, p < 0.01), creatinine (r = 0.826, p < 0.01), and 2-Methylguanosine (r = 0.757, p < 0.01) and negatively correlated with creatine (r=-0.413, p < 0.05). A receiver operating characteristic curve analysis using the creatinine:creatine ratio yielded an area under the curve of 0.913 (95% CI: 0.806–1). These metabolites may be sex-related or sex-sensitive to an extent and can be valuable for identification of the molecular pathways involved in the gender bias in manifestation of ASD. The creatinine:creatine ratio has a potential to be a good predictor of ASD in the female subjects. [ABSTRACT FROM AUTHOR]

Background: Drowning is still the primary cause of death in children under 5 years old, however, little is known about the drowning of Hunan province children. This study identifies the previously unpublished incidence and characteristics of fatal drowning in children of Hunan Province, and provide a basis for formulating strategies for children's survival, development and protection.Methods: Data were collected through sampling with the multistage stratified cluster. The case group included all fatal frowning children under 5 years old in 13 districts between October 2015 and September 2016. The control group was matched 1:1.The epidemic features and influencing factors of fatal drowning were analyzed retrospectively according to descriptive analysis, conditional univariate and multivariate logistic regression analysis.Results: For children aged 0-4 years, the fatal drowning was 16.1/100000 in Hunan Province. Drowning rates were higher for boys than girls. The proportion of rural areas is much higher than that of urban areas. The 1-2 years age-group was the highest of all age groups. Fatal drowning mainly occurred in summer. The three leading drowning locations were pond, ditch and well. Playing close to the water were the leading activities that preceded fatal drowning. Multivariate logistic regression analysis showed that: children with primary caregiver education in high school and above (OR = 0.05) have a lower risk of fatal drowning; children with full-time care (OR = 0.17) have a lower risk; children who received unintentional drowning safety education (OR = 0.23) have a lower risk of fatal drowning. Children who were always swimming or playing near the water in the past 6 months (OR = 3.13) have a higher risk of fatal drowning.Conclusion: The fatal drowning among children under 5 years is the result of the interaction of multiple factors. A significant number of child deaths could have been prevented if parents and other close relatives had been more concerned about the safety of their children. We should develop health education plans for villagers to warn them of the dangers of drowning and preventive measures. [ABSTRACT FROM AUTHOR]