Disease burden and attributable risk factors of neonatal disorders and their specific causes in China from 1990 to 2019 and its prediction to 2024.

BACKGROUND: Neonatal health is a cornerstone for the healthy development of the next generation and a driving force for the progress of population and society in the future. Updated information on the burden of neonatal disorders (NDs) are of great importance for evidence-based health care planning in China, whereas such an estimate has been lacking at national level. This study aims to estimate the temporal trends and the attributable burdens of selected risk factors of NDs and their specific causes in China from 1990 to 2019, and to predict the possible trends between 2020 and 2024. METHODS: Data was explored from the Global Burden of Disease study (GBD) 2019. Six measures were used: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute numbers and age-standardized rates (with 95% uncertainty intervals) were calculated. The specific causes of NDs mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). An autoregressive integrated moving average (ARIMA) model was used to forecast disease burden from 2020 to 2024. RESULTS: There were notable decreasing trends in the number of deaths (84.3%), incidence (30.3%), DALYs (73.5%) and YLLs (84.3%), while increasing trends in the number of prevalence (102.3%) and YLDs (172.7%) from 1990 to 2019, respectively. The corresponding age-standardized rates changed by -74.9%, 0.1%, -65.8%, -74.9%, 86.8% and 155.1%, respectively. Four specific causes of NDs followed some similar and different patterns. The prediction results of the ARIMA model shown that all measures still maintained the original trends in the next five years. Low birth weight, short gestation, ambient particulate matter pollution and household air pollution from solid fuels were the four leading risk factors. CONCLUSION: The health burden due to NDs is declining and is likely to continue to decline in the future in China. Delaying the increasing burden of disability may be the next target of concern. Targeted prevention and control strategies for specific causes of NDs are urgently needed to reduce the disease burden.

Global, regional, and national time trends in incidence for migraine, from 1990 to 2019: an age-period-cohort analysis for the GBD 2019.

BACKGROUND: The majority of epidemiological studies on migraine have been conducted in a specific country or region, and there is a lack of globally comparable data. We aim to report the latest information on global migraine incidence overview trends from 1990 to 2019. METHODS: In this study, the available data were obtained from the Global Burden of Disease 2019. We present temporal trends in migraine for the world and its 204 countries and territories over the past 30 years. Meanwhile, an age-period-cohort model be used to estimate net drifts (overall annual percentage change), local drifts (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. RESULTS: In 2019, the global incidence of migraine increased to 87.6 million (95% UI: 76.6, 98.7), with an increase of 40.1% compared to 1990. India, China, United States of America, and Indonesia had the highest number of incidences, accounting for 43.6% of incidences globally. Females experienced a higher incidence than males, the highest incidence rate was observed in the 10-14 age group. However, there was a gradual transition in the age distribution of incidence from teenagers to middle-aged populations. The net drift of incidence rate ranged from 3.45% (95% CI: 2.38, 4.54) in high-middle Socio-demographic Index (SDI) regions to -4.02% (95% CI: -4.79, -3.18) in low SDI regions, 9 of 204 countries showed increasing trends (net drifts and its 95% CI were > 0) in incidence rate. The age-period-cohort analysis results showed that the relative risk of incidence rate generally showed unfavorable trends over time and in successively birth cohorts among high-, high-middle-, and middle SDI regions, but low-middle- and low-SDI regions keep stable. CONCLUSIONS: Migraine is still an important contributor to the global burden of neurological disorders worldwide. Temporal trends in migraine incidence are not commensurate with socioeconomic development and vary widely across countries. Both sexes and all age groups should get healthcare to address the growing migraine population, especially adolescents and females.

Prevalence of Malnutrition in Children with Congenital Heart Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the global prevalence of malnutrition in children with congenital heart disease (CHD). STUDY DESIGN: A systematic review and meta-analysis were performed. Web of Science, PubMed, Embase, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine disc databases were searched for studies published through April 2021. Random-effect model meta-analyses were performed to derive the pooled the prevalence of preoperative underweight, stunting, and wasting in children with CHD. Time-trend analyses of postoperative malnutrition prevalence were undertaken. Subgroup and sensitivity analyses were conducted to explore sources of heterogeneity. Egger test and funnel plots were used to explore public bias. RESULTS: A total of 39 studies were included in this meta-analysis. The pooled estimates of preoperative malnutrition in children with CHD were 27.4% (95% CI, 21.7-34.0) for underweight, 24.4% (95% CI, 19.5-30.0) for stunting, and 24.8% (95% CI, 19.3-31.3) for wasting. Catch-up growth was found in the postoperative period among some children. Different continents were identified as heterogeneity moderators by subgroup analyses. CONCLUSIONS: Children with CHD have a high prevalence of preoperative malnutrition and some show catch-up growth postoperatively. These data can be used as benchmarks in efforts to improve the nutritional status of children with CHD.

Effect of maternal alcohol consumption during the pre-pregnancy/early-pregnancy period on congenital heart disease: A prospective cohort study in Central China.

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.

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

BACKGROUND: MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations. METHODS: A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association. RESULTS: Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure. CONCLUSIONS: Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings. TRIAL REGISTRATION: Registration number: ChiCTR1800016635 .

Association of periconceptional folate supplements and FOLR1 and FOLR2 gene polymorphisms with risk of congenital heart disease in offspring: A hospital-based case-control study. / æ¯äº²å›´å­•æœŸæœç”¨å¶é ¸åŠFOLR1和FOLR2åŸºå› å¤šæ€æ€§ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— å ³è”çš„ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling. METHODS: A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene. RESULTS: Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1). CONCLUSIONS: Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.

[Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring]. / 母亲MTHFD1及MTHFD2åŸºå› å¤šæ€æ€§ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— çš„å ³è”.

OBJECTIVES: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD. RESULTS: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05). CONCLUSIONS: Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring.

BACKGROUND: Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. RESULTS: Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95-19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77-9.71]). And six haplotypes of G-C (involving rs4846048 and rs2274976), A-C (involving rs1801133 and rs4846052), G-T (involving rs1801133 and rs4846052), G-T-G (involving rs2066470, rs3737964 and rs535107), A-C-G (involving rs2066470, rs3737964 and rs535107) and G-C-G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene-gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. CONCLUSIONS: Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.

Association of maternal folate use and reduced folate carrier gene polymorphisms with the risk of congenital heart disease in offspring.

Although it is generally recognized that genetic and environmental factors are associated with the risk of congenital heart disease (CHD), the mechanism remains largely uncertain. This study aimed to investigate the association of maternal folate use, the time when folate use was started, and polymorphisms of the reduced folate carrier (RFC1) gene with the risk of CHD in offspring of Chinese descent, which can help provide new insight into the etiology of folate-related birth defects. A case-control study of 683 mothers of CHD patients and 740 mothers of healthy children was performed. The present study showed that mothers who did not use folate were at a significantly increased risk of CHD (OR=2.04; 95% CI: 1.42-2.93). When compared with those who started using folate prior to conception, mothers who started using folate from the first trimester of pregnancy (OR=1.90; 95% CI: 1.43-2.54) or from the second trimester of pregnancy (OR=8.92; 95% CI: 4.20-18.97) had a significantly higher risk of CHD. Maternal RFC1 gene polymorphisms at rs2236484 (AG vs AA: OR=1.79 [95% CI: 1.33-2.39]; GG vs AA: OR=1.64 [95% CI: 1.15-2.35]) and rs2330183 (CT vs CC: OR=1.54 [95% CI: 1.14-2.09]) were also significantly associated with CHD risk. Additionally, the risk of CHD was significantly decreased among mothers who had variant genotypes but used folate when compared with those who had variant genotypes and did not use folate.Conclusion: In those of Chinese descent, maternal folate use and the time when use started are significantly associated with the risk of CHD in offspring. Furthermore, maternal folate supplementation may help to offset some of the risks of CHD in offspring due to maternal RFC1 genetic variants. What is Known: • Folate use could help prevent CHD, but the relationship between the time when folate use is started and CHD has not received sufficient attention. • Studies have assessed the associations of folate metabolism-related genes with CHD, but genes involved in cellular transportation of folate, such as the RFC1 gene, have not garnered enough attention. What is New: • In those of Chinese descents, the time when folate use is started is significantly associated with the risk of CHD in offspring. • Maternal RFC1 polymorphisms were significantly associated with the risk of CHD. • Folate supplementation may help to offset some risks of CHD due to RFC1 genetic variants.

Risk factors for preterm birth: a prospective cohort study. / æ—©äº§å±é™©å› ç´ çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the incidence of preterm birth and risk factors for preterm birth. METHODS: A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth. RESULTS: A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (P<0.05). Additionally, the pregnant women whose spouses were older, had a higher body mass index or smoked had an increased risk for preterm birth (P<0.05). A higher level of education of pregnant women or their spouses and lower gravidity were protective factors against preterm birth (P<0.05). CONCLUSIONS: There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.

Birth prevalence of congenital heart disease in China, 1980-2019: a systematic review and meta-analysis of 617 studies.

To assess the birth prevalence and spatial distribution of congenital heart disease (CHD) in China by conducting a complete overview and using spatial epidemiological methods. Unrestricted searches were conducted on seven electronic databases, with an end-date parameter of May 2019. Data on the birth prevalence of CHD and its subtypes were collected and combined using either the random-effect model or fixed-effect model. Subgroup sensitivity analyses were performed to explore potential heterogeneity moderators. The three-dimensional trend analysis and a visualization of CHD birth prevalence among different provinces were performed to describe the spatial distribution characteristics. Total 617 studies involving 76,961,354 births and 201,934 CHD individuals were included. Overall, total CHD birth prevalence increased continuously over time, from 0.201‰ in 1980-1984 to 4.905‰ in 2015-2019. The study on the high-income provinces, population-based monitoring model, male births, and urban regions reported a significantly higher prevalence of total CHD compared with upper-middle-income provinces, hospital-based monitoring model, female births, and rural regions, respectively. National CHD birth prevalence increased gradually from western region to eastern region, but decreased gradually from southern to northern region. Relevant heterogeneity moderators including gender, geographic region, income levels, and monitoring models have been identified by subgroup analyses. Sensitivity analysis yielded consistent results. Total CHD birth prevalence in China increases continuously in the past 40 years. Significant differences in gender, geographical regions, income levels, and monitoring models were found. In the future, population wide prospective birth defect registries covering the entire Chinese population need to determine the exact birth prevalence.

Maternal homocysteine and folate levels and risk of recurrent spontaneous abortion: A meta-analysis of observational studies.

AIM: The aim of the study was to review and summarize the epidemiologic evidence on the associations of homocysteine (HCY) and folate with the risk of recurrent spontaneous abortion (RSA). METHODS: This review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Google Scholar, Cochrane Libraries and Chinese databases were searched through May 2019 to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the combined standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: Twenty-three studies involving 2052 RSA cases and 1476 healthy controls were included. Overall, women with RSA compared with those without RSA were at a significantly higher level of HCY both in plasma (SMD = 1.34; 95% CI: 0.76-1.93) and in serum (SMD = 1.46; 95% CI: 1.02-1.91), but lower level of folate both in serum (SMD = -1.63; 95% CI: -2.51 to -0.75) and in red blood cells (SMD = -1.30; 95% CI: -1.76 to -0.85). However, a statistically significant association between plasma folate and risk of RSA was not been observed (SMD = -0.82; 95% CI: -1.73 to 0.09). These findings have to be viewed with caution for the significant heterogeneity (I2 : from 88 to 98%). CONCLUSION: High HCY levels in both plasma and serum as well as low folate levels in serum and red blood cells are significantly associated with risk of RSA, which indicates that measures to reduce HCY levels or folate supplementation may help to reduce the risk of RSA. However, prospective studies are needed to confirm our findings.

[Association of maternal diabetes mellitus and UCP2 gene polymorphisms with congenital heart disease in offspring: a case-control study].

OBJECTIVE: To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05). CONCLUSIONS: Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.

Cancer risk among children conceived by fertility treatment.

Prior studies on the association between fertility treatment and childhood cancer risk have generated inconsistent results. We performed a systematic review and meta-analysis of observation studies to summarize the evidence regarding the relation of fertility treatment with childhood cancer risk. A systematic literature search of several databases was conducted through April 2018 to identify relevant studies. The outcomes of interest included overall cancer, haematological malignancies, neural tumours, other solid tumours, and eight specific cancers. The overall risk estimates and corresponding 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Sixteen cohort and thirteen case-control studies were included. Results showed that children conceived by fertility treatment had significantly higher risk for developing overall cancer (relative risk [RR]: 1.16, 95% CI: 1.01, 1.32), haematological malignancies (RR: 1.39, 95% CI: 1.21, 1.60) and other solid tumours (RR: 1.57, 95% CI: 1.14, 2.16). For specific cancers, fertility treatment was associated with a significantly increased risk of leukaemia (RR: 1.31, 95% CI: 1.09, 1.57) and hepatic tumours (RR: 2.26, 95% CI: 1.32, 3.85). Sensitivity analysis validated evidence of the robustness of the findings. The results may demonstrate a possible association between fertility treatment and an increased risk of cancer among the offspring. However, the findings cannot say whether this increased risk is due to the subfertility itself or to the fertility treatment. Further research is needed to address the underlying mechanisms.

Influence of nitrogen availability on Cd accumulation and acclimation strategy of Populus leaves under Cd exposure.

Nitrogen (N) plays crucial roles in chlorophyll concentration, photosynthesis, and stress tolerance of plant leaves. This study conducted a greenhouse experiment combined with Cd and N treatments to elucidate the mechanism underlying the influence of N on Cd accumulation and acclimation strategy in Populus leaves. Chlorophyll concentration and net photosynthetic rates (A) in leaves were unaltered by Cd exposure regardless of N condition. Nitrogen availability alter acclimation strategy of poplar leaves under cadmium exposure. Under sufficient N, Cd accumulation in leaves was elevated with increased intensity and duration of Cd exposure; Cd accumulation reached ca. 28 µg g-1 dry weight and 260 µg plant-1 after 60 days of exposure to high level of Cd (20 mg Cd kg-1 soil), and this finding indicates a large potential for Cd phytoextraction. Poplar leaves exhibited high capacity for antioxidant defense and stress tolerance and avoided oxidative damage under high Cd exposure. The levels of phytohormones and antioxidants in leaves and the relative expressions of critical genes encoding antioxidant enzymes were up-regulated under sufficient N condition. Nitrogen deficiency decreased chlorophyll concentration and net photosynthetic rates (A) and interfered with the production of N metabolites, resulting in a low level of phytohormones and antioxidants that are responsible for stress tolerance. The low levels of Cd accumulation in leaves may be a self-protecting strategy to prevent severe oxidative damage due to the decreased capacities for stress tolerance under N deficiency.

Risk of congenital heart defects in offspring exposed to maternal diabetes mellitus: an updated systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis was performed to assess the risk of congenital heart defects (CHDs) and its specific phenotypes associated with maternal diabetes mellitus (DM) including pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM). METHODS: PubMed, Embase, Medline, Google Scholar, Cochrane Libraries, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Fulltext Database and China Biology Medicine disc were searched from the inception dates to 15 December 2018, to identify case-control or cohort studies assessing the association between maternal DM and risk of CHDs. The exposure of interest was maternal DM; the outcomes of interest were CHDs and its specific phenotypes. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analyses were performed to explore potential heterogeneity moderators. RESULTS: Total 52 studies, which involved 259,917 patients with CHDs among 16,929,835 participants, were included for analysis. Overall, mothers with DM compared with those without DM had a significantly higher risk of CHDs in offspring [odds ratios (OR) = 2.71, 95% confidence intervals (CI) 2.28-3.23]. When data were restricted to different types of DM, a significantly increased risk of CHDs was observed among mothers with PGDM (OR = 3.18, 95% CI 2.77-3.65) and GDM (OR = 1.98, 95% CI 1.66-2.36). Our study suggested the risk of CHDs was significantly higher among mothers with PGDM than those with GDM. Additionally, this study suggested maternal DM was significantly associated with most phenotypes of CHDs; of these, double outlet of the right ventricle (OR = 10.89; 95% CI 8.77-13.53), atrioventricular septal defect (OR = 5.74; 95% CI 3.20-10.27) and truncus arteriosus (OR = 5.06; 95% CI 2.65-9.65) were identified as the first three of the most common phenotypes of CHDs associated with maternal DM. CONCLUSIONS: The maternal DM including PGDM and GDM are significantly associated with risk of CHDs and its most phenotypes. The PGDM seems to be more likely to cause CHDs in offspring than GDM. Further studies are needed to clarify the underlying mechanisms.

[Impact of in vitro fertilization-embryo transfer on adverse pregnancy outcomes: A prospective cohort study].

OBJECTIVE: To evaluate whether the in vitro fertilization-embryo transfer (IVF-ET) procedures could increases the risks of adverse pregnancy outcomes (APOs) in offspring.
 Methods: A hospital-based prospective cohort design was conducted, which contained a control group of singleton pregnancies with indicators of subfertility who were still conceived naturally after using simple medical treatment (e.g. minimal medical intervention or ovulation induction), and an exposure group consisted of singleton pregnancies who had a history of infertility and IVF-ET treatment. All factors different between two groups in the univariate analysis were included in the multivariable logistic regression to evaluate the independent effect of IVF-ET procedures themselves on APOs.
 Results: After controlling for confounding factors by using multivariate logistic regression analysis, our results showed that pregnancies after IVF-ET experienced a higher risk of preterm birth (OR=1.28, 95% CI 1.05 to 1.56), low birth weight (OR=1.69, 95% CI 1.27 to 2.31), perinatal mortality (OR=5.33, 95% CI 2.44 to 11.81), and congenital malformations (OR=1.83, 95% CI 1.12 to 2.94).
 Conclusion: The IVF-ET operational factors may increase the risk of APOs.

[Association of single nucleotide polymorphisms of transcription factors with congenital heart diseases in the Chinese population: a Meta analysis].

OBJECTIVE: To study the association of single nucleotide polymorphisms (SNPs) of transcription factors (NKX2.5, GATA4, TBX5, and FOG2) with congenital heart disease (CHD) in the Chinese population. METHODS: PubMed, Google Scholar, CNKI, Wanfang Data, and Weipu Data were searched for articles on the association of SNPs of target genes with CHD in the Chinese population. If one locus was mentioned in at least two articles, the random or fixed effect model was used to perform a pooled analysis of study results and to calculate the pooled OR and its 95%CI. If a locus was mentioned in only one article, related data were extracted from this article to analyze the association between the SNPs of this locus and CHD. RESULTS: Twenty-three articles were included. The Meta analysis showed that there were significant differences between the CHD and control groups in the genotype and allele frequencies of GATA4 rs1139244 and rs867858 and the genotype frequency of GATA4 rs904018, while there were no significant differences in the SNPs of the other genetic loci between the two groups. The single-article analysis showed that there were significant differences between the two groups in the allele frequencies of NKX2.5 rs118026695/rs703752, GATA4 rs884662/rs12825/rs12458/rs3203358/rs4841588, and TBX5 rs6489956. There were no significant differences in the SNPs of FOG2 locus between the two groups. CONCLUSIONS: The SNPs of some loci in NKX2.5, GATA4, and TBX5 are associated with CHD in the Chinese population, but the association between the SNPs of FOG2 locus and the development of CHD has not been found yet.

Maternal anaemia during early pregnancy and the risk of neonatal outcomes: a prospective cohort study in Central China.

BACKGROUND: The purpose of this study was to explore the association between anaemia during early pregnancy and the risk of neonatal outcomes. METHODS: We collected clinical data from pregnant women (≥18 years) who received their first antenatal care between 8 and 14 weeks of gestation in Hunan Provincial Maternal and Child Health Care Hospital. Multiple logistic regression models and restricted cubic spline regression models were used to analyse the association between anaemia during early pregnancy and the risk of neonatal outcomes. In addition, sensitivity analysis was further performed to assess the robustness of the results. RESULTS: The prospective cohort study ultimately included 34 087 singleton pregnancies. In this study, the rate of anaemia during early pregnancy was 16.3%. Our data showed that there was a positive relationship between the rate of preterm birth, low birth weight as well as small for gestational age (SGA) and the severity of maternal anaemia (Ptrend<0.05). After adjustment, the association of early pregnancy anaemia and haemoglobin (Hb) levels with the risk of preterm birth (mild anaemia adjusted OR (aOR) 1.37 (95% CI 1.25 to 1.52), moderate anaemia aOR 1.54 (95% CI 1.35 to 1.76) and severe anaemia aOR 4.03 (95% CI 2.67 to 6.08), respectively), low birth weight (mild anaemia aOR 1.61 (95% CI 1.44 to 1.79), moderate anaemia aOR 2.01 (95% CI 1.75 to 2.30) and severe anaemia aOR 6.11 (95% CI 3.99 to 9.36), respectively) and SGA (mild anaemia aOR 1.37 (95% CI 1.25 to 1.52), moderate anaemia aOR 1.54 (95% CI 1.35 to 1.76) and severe anaemia aOR 2.61 (95% CI 1.74 to 4.50), respectively; Pnon-linear<0.05) was observed. However, no association was found between early pregnancy anaemia or Hb levels and the risk of congenital malformations. Sensitivity analysis verified the stability of the results. CONCLUSIONS: Maternal anaemia during early pregnancy was associated with an increased risk of preterm birth, low birth weight and SGA and their rates may increase with the severity of maternal anaemia. TRIAL REGISTRATION NUMBER: ChiCTR1800016635.

A simple scoring system for the prediction of early pregnancy loss developed by following 13,977 infertile patients after in vitro fertilization.

A retrospective study was conducted to investigate a convenient simple scoring system for the prediction of early pregnancy loss (EPL) based on simple demographics. A total of 13,977 women undergoing transvaginal ultrasound scans on Days 27-29 after in vitro fertilization-embryo transfer (IVF-ET) from June 2016 and December 2017 were included. The first trimester pregnancy outcome was recorded at 12 weeks of gestation. The areas under the curve of this scoring system were 0.884 (95% confidence interval (CI) 0.870-0.899) and 0.890 (95% CI 0.878-0.903) in the training set and test set, respectively. The score totals ranged from -8 to 14 points. A score of 5 points, which offered the highest predictive accuracy (94.01%) and corresponded to a 30% miscarriage risk, was chosen as the cutoff value, with a sensitivity of 62.84%, specificity of 98.79%, positive predictive value (PPV) of 88.87% and negative predictive value (NPV) of 94.54% for the prediction of EPL in the training set. In the test set, a score of 5 points had a sensitivity of 64.69%, specificity of 98.78%, PPV of 89.87% and NPV of 93.62%, and 93.91% of the cases were correctly predicted. Therefore, the simple scoring system using conventionally collected data can be conveniently used to predict EPL after ET. However, considering the limitations, its predictive value needs to be further verified in future clinical practice.