An Analysis of Specific Categories of Birth Defects and Developmental Disabilities for Children of Participants of the Air Force Health Study

Background: The Air Force Health Study collected reproductive outcomes for live-born children of male Air Force veterans of the Vietnam War. Methods: Dioxin values for participants were obtained from blood samples. Analyses were conducted of occurrence of 16 specific categories of birth defects and developmental disabilities. Children were categorized as conceived before and after the start of participants’ Vietnam War service. Children conceived before the start of Vietnam War service were treated as being conceived when their fathers had unquantifiable dioxin values. Children conceived after the start of Vietnam War service for participants with missing dioxin values were excluded from primary analyses, but were used to assess the impact of their exclusion on conclusions. Correlation between values for specific categories for multiple children fathered by the same participant was accounted for. The dose-response relationship was treated as a step function increasing for dioxin values larger than adaptively identified individual thresholds changing with the specific category. Results: For 15 of 16 specific categories, the probability of occurrence increased substantially for a sufficiently high dioxin level above identified thresholds. Exclusion of children due to missing dioxin likely did not affect these results. Conclusions: Results supported the conclusion of substantial adverse effects on a wide variety of specific categories of birth defects and developmental disabilities due to sufficiently high exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War. Results may hold more generally, but might also have been affected by a variety of limitations.

Birth defects in pregestational diabetes:Defect range,glycemic threshold and pathogenesis

Currently,60 million women of reproductive age(18-44 years old) worldwide,and approximately 3 million American women have diabetes mellitus,and it has been estimated that this number will double by 2030.Pregestational diabetes mellitus(PGD) is a significant public health problem that increases the risk for structural birth defects affecting both maternal and neonatal pregnancy outcome.The most common types of human structural birth defects associated with PGD are congenital heart defects and central nervous system defects.However,diabetes can induce birth defects in any other fetal organ.In general,the rate of birth defects increases linearly with the degree of maternal hyperglycemia,which is the major factor that mediates teratogenicity of PGD.Stringent prenatal care and glycemic control are effective means to reduce birth defects in PGD pregnancies,but cannot reduce the incidence of birth defects to the rate of that is seen in the nondiabetic population.Studies in animal models have revealed that PGD induces oxidative stress,which activates cellular stress signalling leading to dysregulation of gene expression and excess apoptosis in the target organs,including the neural tube and embryonic heart.Activation of the apoptosis signalregulating kinase 1(ASK1)-forkhead transcription factor 3a(Fox O3a)-caspase 8 pathway causes apoptosis in the developing neural tube leading to neural tube defects(NTDs).ASK1 activates the c-Jun-N-Terminal kinase 1/2(JNK1/2),which leads to activation of the unfolded protein response and endoplasmic reticulum(ER) stress.Deletion of the ASK1 gene,the JNK1 gene,or the JNK2 gene,or inhibition of ER stress by 4-Phenylbutyric acid abrogates diabetes-induced apoptosis and reduces the formation of NTDs.Antioxidants,such as thioredoxin,which inhibits the ASK1-Fox O3a-caspase 8 pathway or ER stress inhibitors,may prevent PGD-induced birth defects.

Correlation Between Birth Defects and Dietary Nutrition Status in a High Incidence Area of China

Objective To investigate the association between birth defects and dietary nutrient intake in a high risk area of China. Methods A dietary survey was performed and serum folic acid was measured in women whose pregnancy was affected by neural tube defects （NTDs） or unaffected by any birth defects （BDs） in Zhongyang and Jiaokou Counties in Shanxi Province of China. ResuIts The local average consumption of foods including dark green vegetables, fruits, fat and meat, and nutrient intake （e.g. energy, protein, retinol, riboflavin, vitamin E, and selenium） were lower than the national average level. In women of childbearing age, these regions, the intake of nutrients was much lower than the recommended nutrient intake （9%-77%）. The case-control dietary nutrition study of women whose pregnancy was affected by BDs （including NTDs and congenital heart defects） demonstrated that, in early pregnancy, adequate nutrition （i.e. eating meat, fresh vegetables, fruit more than once a week） was a protective factor, while eating germinated potatoes was a risk factor. The geometrical mean （pS- p95） of serum folic acid in women with NTD birth defects was 9.6 nmol/L （3.6, 23.03）, which was significantly lower than that in normal women （14.03 nmol/L）. Conclusion Women of childbearing age in the two counties of Shanxi Province, China, have a marked insufficient intake of some nutrients, especially folic acid, zinc, vitamins A and B12. This nutrient deficiency may be an important risk factor for the high prevalence of birth defects in these regions. Therefore, adequate dietary nutrition in early pregnancy can prevent BDs.

Spatiotemporal Property Analysis of Birth Defects in Wuxi,China

Objective To describe the temporal trends and spatial patterns of birth defects occurring in Wuxi, a developed region of China. Methods Wavelet analysis was used to decompose the temporal trends of birth defect prevalence based on the birth defect rates over the past 16 years. Birth defect cases with detailed personal and family information were geo-coded and the relative risk in each village was calculated. General G statistic was used to test the spatial property with different scales. Results Wavelet analysis showed an increasing temporal trend of birth defects in this region. Clustering analysis revealed that changes continued in the spatial patterns with different scales. Conclusion Wuxi is confronted with severe challenges to reduce birth defect prevalence. The risk factors are stable and show no change with spatial scale but an increasing temporal trend. Interventions should be focused on villages with a higher prevalence of birth defects.

Demographic Characteristics and Environmental Risk Factors Exposure of Birth Defects in Pregnant Women: A Population-based Study

Worldwide, the incidence of birth defects in low-income countries is 6.42%, while in middle-income and high-income countries it is 5.57% and 4.72%, respectively;approximately 303, 000 newborns die from birth defects each year. In China, the incidence of birth defects is about 5.6%, and around 8.14 million people have congenital disabilities, accounting for 9.6% of total disabled people[1]. Birth defect remains a major clinical and public health challenge because of its high fatality rate and protracted and severe sequela.

Application Research of “3+1” Mode for Birth Defects Monitoring

Objective To explore the ＂3＋1＂ monitoring mode for birth defects and quality control measures based on the population, and to obtain the related information data for birth defects.Methods With the community population as the basis, adopting the unified monitoring scheme dominant by the leadership and administration of government, with districts （counties） as the monitoring sites, the ＂3＋1 ＂ monitoring mode for birth defects was based on a complete monitoring team with the combination of villages/residents＇ committees, townships （towns）, counties （districts） and the municipality. Demonstration research was carried out in the pilot districts/counties in Chongqing City.Results Birth defects population monitoring system based on population and family planning management and service network was established, and during 2005 and 2006.application research was carried out for the monitoring methods among birth defects population in the pilot districts （counties）, obtaining the relevant information in regional birth defects, with a monitoring coverage of over 99%. Conclusion Fully utilizing the birth management functions of Population and Famlty Planning System and the advantages of service networks, long term, dynamic birth defects monitoring system based on community population was established, with the integration of birth defects monitoring and regular reproductive health services, obtaining overall birth defects occurrence information in details, providing scientific basis for the government to formulate scientific, practical, economic and effective birth defects intervention policy, so as to improve the quality of the population.

A Reassessment of Birth Defects for Children of Participants of the Air Force Health Study

The Air Force Health Study (AFHS), also called the Ranch Hand Study, investigated the impact of exposure to dioxin the toxic contaminant in Agent Orange on health, survival, and reproductive outcomes of male Air Force Vietnam War veterans. It was concluded that available reproductive outcome data did not provide support for an adverse association with paternal dioxin exposure. A more extensive set of AFHS data was used to reassess this conclusion, restricting to the case of birth defects in children fathered after the start of the first Vietnam War tour. Analyses started by repeating published analyses, followed by assessing decisions made in those analyses, for example, of excluding participants with dioxin levels below the detectable limit, using a threshold of 10 parts per trillion for a high dioxin level, and not adjusting for multiple conceptions/children of the same participant. Using data for all participants with measured dioxin levels, both veterans who served in Operation Ranch Hand and other non-Ranch Hand veterans, and after accounting for correlation within children of the same participant, the occurrence for children fathered after the start of the first tour of a major defect, a non-major defect, and multiple defects depended significantly on participants having a high dioxin level. These conclusions were not changed by consideration of covariates. In contrast to prior published analyses, the more extensive AFHS data provided support for an adverse effect of paternal dioxin exposure on birth defects. However, the study had many limitations that could have affected the conclusions.

Observed prevalence and risk factors of birth defects in Shanghai, China

AIM To investigate the prevalence and related risk factors of birth defects in Shanghai. METHODS This report describes a population-based study of all births at the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China from January 2008 to December 2014. A logistic regression analysis was used to identify the parameters that are independently associated with birth defects. RESULTS A total of 82814 births, including 824 cases of birth defects, were recorded. The rate of birth defects was 0.995 per 100 births. In the multivariable regression analysis, neonatal birth defects were likely to be associated with higher gravidity [odds ratio(OR), 1.099, 95%CI: 1.024-1.178], premature birth(OR = 1.905, 95%CI: 1.501-2.418), low birth weight(OR = 3.844, 95%CI: 3.004-4.919), twin births or higher order multiple pregnancies(OR = 1.477, 95%CI: 1.107-1.969), cesarean delivery(OR = 1.184, 95%CI: 1.016-1.380) and registration as part of a migrant population(OR = 1.380, 95%CI: 1.167-1.632). Female infants were less likely to have birth defects than male infants(OR = 0.710, 95%CI: 0.616-0.818). CONCLUSION Higher gravidity, premature birth, lower birth weight,twin births or higher order multiple pregnancies, and registration as part of a migrant population are independent predictors of birth defects.

Effect of Pathoanatomic Diagnosis on the Quality of Birth Defects Surveillance in China

Objective To provide evidence for more accurate diagnosis of birth defects based on the pathoauatomy of congenital malformations. Methods Data used in this study were obtained fi＇om Luliang City Hospital and three county hospitals of Shanxi province between February 2004 and March 2006. Autopsy and pathological examination of 160 dead fetuses and stillbirths were performed. Photos of dead fetuses and stillbirths were taken, tissues were cut into sections for pathological examination under microscope, all pathological information was recorded, and percentage of birth defects was calculated. Results The proportion of dead fetuses and stillbirths with or without congenital malformations was 84.4% （135/160） and 15.6% （25/160）, respectively. There were 16 categories of major external and internal birth defects in 135 cases of such defects. Congenital heart defects, anencephaly and spina bifida had a higher prevalence rate in the study period. The prevalence rate of non-malformation death and birth defects 〈 28 gestational weeks and internal anomalies ≥ 28 gestational weeks was 14.61% （61/4175） and 17.25% （72/4175）, respectively. A total of 413 in situ anomalies were found in 135 cases of autopsy. Spina bifida, anencephaly, congenital heart defects, aplasia or accessory lobe of lung, renal agenesis and dysplasis and congenital hydrocephaly were more closely associated with severe malformations than with mitis malformations. The cases of dead fetuses and stillbirths with multiple malformations （/〉 2 in situ anomalies） had a higher proportion （74.1%）, whereas those with isolated malformations had a lower proportion （25.93%）. Conclusion The occurrence of congenital malformations in different embryonic developmental stages affects multiple organs. Postmortem examination of internal and multiple malformations of fetal deaths and stillbirths can provide more accurate diagnostic information for birth defects.

Construction of HMI Network System for Individualized Maternity Intervention Service against Birth Defects in Community

The paper expounds the community maternity service system against birth defects, from the viewpoint of individualized service in family planning. We have utilized modern information technology to develop health management information （HMI） network with individualized maternity, and to establish the community service system for intervention of birth dejects. The service system applied the concept of modern health management information to implementing informational management for screening, treatment, following up, outcome monitoring, so as to provide a base for promotion of health, diagnosis, treatment as well as scientific research, with the prenatal screening of Down＇s syndrome as a model. The introduction to informational network during the processes of service has been carried out with regards to its composition, function and application, while introducing the effects of computerized case record individualized in prevention, management and research of Down＇s syndrome.

Risk Factors for Birth Defects: A Conditional LogisticRegression Analysis of a Case-Control Study in Guang-dong Province of China

Information was obtained from the same questionnaire (23 risk factors listed) of cases and controls. We used a multivariate logistic model, which described variables significantly increased risk of birth defects. The risk factors included maternal educational levels, medicine taken during pregnancy and antenatal care. It was suggested to strengthen antenatal care was the main preventive measure against birth defects.

A Hospital-Based Cross-Sectional Study Assessing the Relation between Time of Birth and Perinatal Outcome

Objectives:?Investigating the relation between perinatal outcomes and?hospital working shifts.?Methods:?We conducted a cross-sectional study at Philippe Maguilen Senghor health center (PMSHC) in Dakar, Senegal from January, 1st?2011 to December, 31th 2018. The study population was comprised of all mothers who had delivered at PMSHC and their newborns after completing 22 weeks of gestation. Time of delivery was?divided into three periods of working hours: morning shift (deliveries occurred between 7 am and 4:59 pm);evening shift from 5 pm to 10:59 pm and night shift from 11?pm to 6:59 am.?Maternal outcomes were assessed by mode of delivery, epsisotomy and perineal injuries.?The Apgar scoring system was used to assess newborns at first minute after they were born. Other adverse perinatal outcomes included fresh stillbirth, neonatal referral and early neonatal death. Data were analyzed using Statistical Package for Social Science software (SPSS 24, Mac version).?Results:?A total of 48,270 mothers and their newborns met eligibility criteria. Caesarean section deliveries were less likely to occur during evening (OR 0.84, 95% CI;0.79?-?0.89, p = 0.001) and night shifts (OR 0.45, CI;0.47?-?0.53, p = 0.001).?Evening shift deliveries had 1.1 the odds of poor perinatal outcome (Apgar score ?- 1.18, p = 0.012). No significant difference was found in the odds of neonate referrals and deaths across the three shifts.?Night shift deliveries had 1.1 the odds of perineal injuries compared to morning shift deliveries (OR 1.11, 95% CI;1.04?- 1.18, p = 0.001, for episiotomy and OR, 1.14;95% CI, 1.04?- 1.26, p = 0.008, for perineal tears). Conclusion:?Off-hours deliveries, particularly during the night shift, were significantly associated with higher proportions of perineal injuries compared to morning shift.?However, no significant difference was found in the odds of neonate referrals and deaths across the three shifts.?Our findings suggest to set up a Neonatology unit at the CSPMS as well as a perinatal network across the country.

The Relationship between Drug－and Chemical－exposure and Birth Defects during Pregnancy

A case-control study was conducted in 36 hospitals of the urban and suburban areas of shanghai about the relationships between birth defects and drug use and chemical exposures during pregnancy in the period of july 1987-December 1990.The case group was composed if 1,609 subjects,and the control group 3,218 cases.On stall'stical analysl's,it was.found that a correlation ed'sted between birth defects and the intake Of APC and diazepam,and the exposure to pesticides,organic solvents.benzene,synthetic resin and physical.factors(noises)on foe part of foe mother.and the exposure to harmful chemicals and physical factors and the smoking of 20 or more cigarettes a day on the part Of the father.It is also found that foe familial heredilary history of the parents and multigravavidity,malnutrition,common colds,hepatitis and diarrhea during pregnancy may also be relaied to the birth defects.

Comparison of Perinatal Outcomes in Late Preterm Spontaneous and Indicated Preterm Birth Neonates

Objective: We aimed to compare the perinatal outcomes in late preterm spontaneous and indicated birth neonates. Methods: We studied 289 late preterm births, classified as either aspontaneous late preterm birth (sLPTB) group (preterm labor with intact membranes and preterm premature rupture of membranes) or an indicated late preterm birth (iLPTB) group (hypertensive disorder in pregnancy, placental causes, and maternal diseases), according to the delivery indication. We then compared the maternal and neonatal characteristics and perinatal outcomes, including the Apgar score, admission to the neonatal intensive care unit (NICU) or special care nursery (SCN), duration of NICU stay, and the rate of composite morbidity (antibiotic use, hypoglycemia, hypocalcemia, hyperbilirubinemia requiring phototherapy, respiratory support, and respiratory distress syndrome). Results: A total of 198 neonates were in the sLPTB group and 91 were in the iLPTB group. In spite of greater gestational age at the time of delivery in the iLPTB group, the mean birth weight was lower than that in the sLPTB group. Additionally, the iLPTB group showed lower Apgar scores, and higher rates of NICU or SCN admission, respiratory support, and hypoglycemia, but there was no difference in the rate of composite morbidity between the two groups. Conclusion: iLPTB neonates had lower birth weights despite greater gestational age than those in the sLPTB group, but there was no difference in the rate of composite morbidity between the two groups.

Clinical study of different fertilization methods of assisted reproductive technology on neonatal birth defects

Objective:To investigate the incidence of neonatal birth defects in assisted reproductive technology(ART)by in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI).Methods:The clinical data of 4229 cases of singleton deliver by infertile patients under 35 years old who received IVF/ICSI-ET in our center were analyzed.According to different fertilization methods,they were divided into IVF group(2967 cases)and ICSI group(1262 cases).The general situation of birth,birth defects and the location of defects were compared between the two groups.Results:a total of 38 cases of neonatal birth defects were found,the incidence of birth defects was 0.89%,including 30 cases(1.01%)in IVF group and 8 cases(0.64%)in ICSI group.There was no significant difference in the incidence of birth defects between the two groups(P>0.05).There was also no significant difference in birth weight,gestational age and gender ratio between the two groups(P>0.05).Conclusion:Different fertilization methods in assisted reproductive technology do not increase the incidence of neonatal birth defects.

Adaptive Regression for Nonlinear Interrupted Time Series Analyses with Application to Birth Defects in Children of Vietnam War Veterans

The purpose of this article is to provide an overview of adaptive regression modeling and demonstrate its use in conducting nonlinear analyses of interrupted time series (ITS) data. Adaptive regression modeling is based on heuristic search over alternative models for data controlled by likelihood-cross validation (LCV) scores with larger scores indicating better models. Extended linear mixed models are used for correlated data like ITS data. Power transforms of predictor variables are used to account for nonlinearity. The use of adaptive regression modeling for assessing ITS effects is demonstrated using data on annual proportions of major birth defects in children fathered by male Air Force veterans of the Vietnam War over a 59-year period. The interruption for this ITS is conception after versus before the start of a participant’s first tour in the Vietnam War. Whether the ITS effect is related to dioxin exposure is also addressed. Dioxin is a highly toxic contaminant of the herbicide Agent Orange used in the Vietnam War. The core findings of the reported analyses are that a substantial adverse ITS interruption effect is identified and that this adverse effect can reasonably be attributed to participants having a high dioxin exposure level. Moreover, these results indicate that adaptive regression modeling can identify nonlinear ITS effects in general situations that can lead to consequential insights into nonlinear relationships over time, possibly varying with other available predictors.

Perinatal prevalence of birth defects in the Mainland of China,2000–2021:a systematic review and meta-analysis

Background Although birth defects are of great concern globally,the latest national prevalence has not yet been quantified in China.We conducted a systematic review and meta-analysis to estimate the perinatal prevalence of birth defects in the Mainland of China between 2000 and 2021.Methods We performed a systematic literature search of six databases for relevant articles published between January 1,2000,and March 1,2023.We included published studies that reported data on the perinatal prevalence of birth defects in the Mainland of China.The DerSimonian and Laird random-effects models were used to estimate the pooled prevalence and its 95%confidence interval(CI).We also conducted subgroup analyses and univariable meta-regressions to explore differences in prevalence by time period,geographic region,and other characteristics.Results We included 254 studies reporting the perinatal prevalence of birth defects and 86 studies reporting only the prevalence of specific types of birth defects.Based on 254 studies covering 74,307,037 perinatal births and 985,115 cases with birth defects,the pooled perinatal prevalence of birth defects was 122.54(95%CI 116.20–128.89)per 10,000 perinatal births in the Mainland of China during 2000–2021.Overall,the perinatal prevalence of birth defects increased from 95.60(86.51–104.69)per 10,000 in 2000–2004 to 208.94(175.67–242.22)per 10,000 in 2020–2021.There were also significant disparities among different geographical regions.Congenital heart defects(33.35 per 10,000),clefts of the lip and/or palate(13.52 per 10,000),polydactyly(12.82 per 10,000),neural tube defects(12.82 per 10,000),and inborn errors of metabolism(11.41 per 10,000)were the five most common types of birth defects.The perinatal prevalence among males was significantly higher than that among females(β=2.44×10^(−3),P=0.003);a higher perinatal prevalence of birth defects was observed among perinatal births whose mothers were≥35 years(β=4.34×10^(−3),P<0.001).Conclusion Comprehensive and sustained efforts are needed to strengthen surveillance and detection of birth defects,improve prenatal and postnatal healthcare,and promote rehabilitation,especially in underdeveloped areas.

Bayesian mapping of neural tube defects prevalence in Heshun County, Shanxi Province, China during 1998～2001

Objective: To estimate the prevalence rates of neural tube defects (NTDs) in Heshun County, Shanxi Province, China by Bayesian smoothing technique. Methods: A total of 80 infants in the study area who were diagnosed with NTDs were analyzed. Two mapping techniques were then used. Firstly, the GIS software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of empirical Bayes estimation. Results: The classical statistical approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. The maps produced by the Bayesian technique indicate the tendency of villages in the southeastern region to produce higher prevalence or risk values. Conclusions: The Bayesian smoothing technique addresses the issue of heterogeneity in the population at risk and it is therefore recommended for use in explorative mapping of birth defects. This approach provides procedures to identify spatial health risk levels and assists in generating hypothesis that will be investigated in further detail.

Application of GIS-Based Spatial Filtering Method for Neural Tube Defects Disease Mapping

This study is to assess the prevalence rates spatial pattern of neural tube defects with geographic information system and spatial filtering technique. A total of 80 infants who diagnosed from neural tube defects in the area being studied between 1998 and 2001 were analyzed. Firstly, the geographic information system （GIS） software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of spatial filtering. We evaluated that the effect of changes in spatial filtering radius size was assessed by creating maps based on various filtering radius sizes. The 3 miles or larger filtering radius gives better section variability than the 2 and 2.5 miles or smaller ones. The maps produced by the spatial filtering technique indicate that prevalence rates in the villages in the southeastern region are to produce higher prevalence than that in the other regions. The smoothed maps based on Heshun County display a more adequate data representation than the raw prevalence rate map.