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.

2011-2021年江苏省金湖县和盱眙县围产儿出生缺陷监测结果分析

目的:探讨2011-2021年江苏省金湖县和盱眙县出生缺陷报告发生率及其变化趋势。方法:利用出生及出生缺陷监测项目2011-2021年数据进行横断面研究,应用Joinpoint模型分析出生缺陷报告发生率变化趋势,计算各时间段内年度变化百分比(APC)、整体时间内平均年度变化百分比(AAPC)。结果:2011-2021年金湖县出生缺陷报告发生率(341.3/万)高于盱眙县(212.8/万)。金湖县出生缺陷报告发生率整体呈上升趋势(AAPC=8.6%,P<0.05),2017-2021年上升迅速(APC=20.4%,P<0.05)。尚未发现盱眙县出生缺陷报告发生率存在时间趋势。出生缺陷报告发生率男性高于女性,母亲和父亲高龄组高于适龄组。金湖县前5位高发出生缺陷依次为先天性心脏病(144.4/万)、脐疝(51.2/万)、多指(趾)(28.7/万)、外耳其他畸形(11.6/万)、其他消化系统畸形(8.8/万)。盱眙县前5位高发出生缺陷依次为先天性心脏病(74.9/万)、外耳其他畸形(17.8/万)、多指(趾)(16.2万)、脐疝(10.5/万)、腹股沟疝(9.0/万)。结论:2011-2021年金湖县出生缺陷报告发生率整体呈上升趋势,且2017-2021年上升速度明显加快;尚未发现盱眙县出生缺陷报告发生率存在时间趋势。两县出生缺陷第1顺位均为先天性心脏病,且金湖县脐疝发生率较高。建议对高龄母亲和高龄父亲应做好孕前、孕期、分娩期的系统保健工作,以降低出生缺陷发生率。

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.

2018-2022年福建省泉州市围产儿死亡影响因素分析

目的 分析2018-2022年福建省泉州市围产儿死亡原因及影响因素,为制定针对性的干预措施提供依据。方法 收集2018年1月-2022年12月福建省泉州市30所医院的围产儿死亡资料及同期分娩的活产儿资料,采用单因素分析和logistic回归分析法对比分析围产儿死亡的影响因素。结果 2018-2022年泉州市共监测围产儿338 325例,围产儿死亡1 464例,围产儿死亡率为4.33‰。母亲居住地区为乡村(OR=3.956,95%CI:3.257~4.804)、患有妊娠合并症/并发症(OR=3.327,95%CI:2.639~4.194),以及出生缺陷(OR=125.297,95%CI:61.619~254.779)是围产儿死亡的危险因素(均P <0.001);母亲产检次数多是围产儿死亡的保护因素(OR=0.904,95%CI:0.880~0.929)。泉州市围产儿死亡原因前5顺位为出生缺陷、脐带因素、母亲因素、胎盘因素及出生窒息,占围产儿死亡的81.2%。结论 泉州市出生缺陷防控形势依然严峻,应将出生缺陷作为突破口,加强出生缺陷防控知识的普及,减少出生缺陷的发生;同时,应加强围产保健管理,及早识别围产儿死亡高危因素,及时干预,以进一步降低围产儿死亡率。

使用供体精子行IVF/ICSI-ET助孕的新生儿结局回顾性分析

目的探讨使用供体精子行体外受精/卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)助孕,是否会给新生儿结局带来不良影响。方法回顾性分析2011年4月至2021年4月于我院生殖医疗中心行IVF/ICSI-ET治疗后获临床妊娠并活产的6926例新生儿及其母亲的临床资料。根据不同精子来源分为两组:夫精组(n=6153)和供精组(n=773),比较两组不孕女性的一般资料、助孕资料、不同分娩胎数(单胎/双胎)及不同助孕方式(IVF/ICSI)的新生儿结局。结果两组间不孕女性的平均年龄比较无显著差异(P>0.05),供精组的平均不孕年限[(5.99±3.66)年vs.(4.57±3.13)年]、原发不孕女性占比(61.19%vs.40.32%)、IVF助孕受精方式占比(95.34%vs.83.16%)、移植优质胚胎率(96.63%vs.95.22%)、双胎分娩数占比(47.09%vs.42.16%)均显著高于夫精组(P<0.05);而体质量指数(BMI)显著低于夫精组[(21.15±2.69)kg/m^(2) vs.(21.57±2.82)kg/m^(2),P<0.05]。两组间平均移植胚胎数、新生儿性别比比较无显著差异(P>0.05);无论是不同分娩胎数(单胎或双胎),还是不同助孕方式(IVF/ICSI),两组间的新生儿在平均分娩孕周、平均新生儿体重、剖宫产率、胎儿早产率、巨大儿发生率、低体重儿发生率以及出生缺陷率方面比较均无显著差异(P>0.05);两组新生儿中最常见的出生缺陷类型均分布在循环系统和泌尿生殖系统。结论使用供体精子行IVF/ICSI-ET助孕并没有增加不良新生儿结局的风险,但仍需要在未来长期随访过程中密切关注子代安全并评估相关风险。

孕妇孕中期血清PAPP-A联合Inhibin-A水平预测出生缺陷的临床价值

目的:探讨孕中期孕妇血清妊娠相关蛋白A(PAPP-A)、抑制素A(Inhibin-A)表达水平及其预测出生缺陷的临床价值。方法:收集本院2021年1月—2024年5月定期产前检查并分娩的孕妇临床资料,其中妊娠结局为胎儿结构异常孕妇86例(异常组),妊娠结局为正常新生儿的孕妇90例(对照组),比较两组血清PAPP-A、Inhibin-A水平,Pearson分析异常组血清PAPP-A、Inhibin-A水平相关性,logistic分析发生出生缺陷的影响因素,受试者工作特征曲线分析血清PAPP-A联合Inhibin-A预测出生缺陷的临床价值。结果:异常组血清PAPP-A(7.33±1.48 ng/ml)低于对照组(9.56±1.74 ng/ml),Inhibin-A(478.25±93.48 pg/ml)高于对照组(365.87±81.51 pg/ml)(均P<0.05),异常组血清PAPP-A与Inhibin-A呈负相关(r=-0.340,P=0.001),异常组服用叶酸占比低于对照组,孕早期呼吸道感染、孕期贫血、饲养动物、吸烟占比均高于对照组(均P<0.05);服用叶酸、血清PAPP-A升高是出生缺陷发生的保护因素,孕早期呼吸道感染、孕期贫血、吸烟、血清Inhibin-A升高是出生缺陷发生的危险因素(均P<0.05)。血清PAPP-A预测出生缺陷的曲线下面积(AUC)为0.802,敏感性79.1%、特异性80.0%;血清Inhibin-A预测出生缺陷的AUC为0.803,敏感性74.4%、特异性81.1%,血清PAPP-A联合Inhibin-A预测出生缺陷的AUC为0.874,敏感性91.9%、特异性75.6%(P<0.05)。结论:孕妇孕中期血清PAPP-A降低、Inhibin-A水平升高不利于胎儿正常生长发育,孕中期血清PAPP-A联合Inhibin-A预测出生缺陷临床价值提高,提示临床未来可能用于出生缺陷的临床预测。

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.

Development of Technology and Equipment for Non-destructive Testing of Defects in Sewing Mandrels of a Three-roll Screw Mill 30-80

The conditions of heating and cooling of piercing mandrels made of 4X5MFS steel of a three-roll screw mill 30-80 in the production of a closed cavity of steel vessels of small volume are determined.It is established that multiple cycles of heating up to 600℃ and cooling with water up to 80℃ for about 7 seconds/1 cycle lead to the formation of ridges,shells and cracks on the surface and in the volume of the tool.The loss of structural strength of the material leads to the breakdown of the mandrel during the stitching process.The technique and equipment of magnetic powder control have been developed to establish the dynamics of the growth of internal and external defects of mandrels.An equation is obtained that allows determining the increase in the number of defects in the sewing tool of a screw rolling mill.The technology of non-destructive testing made it possible to develop a rational plan for replacing the sewing mandrels,which allows for predicting the appearance of defects leading to a complex breakdown of the deforming tool at the NPO Pribor machine-building enterprise.

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.

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.

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.

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.

PSO/ACO Algorithm-based Risk Assessment of Human Neural Tube Defects in Heshun County,China

Abstract Objective To develop a new technique for assessing the risk of birth defects, which are a major cause of infant mortality and disability in many parts of the world. Methods The region of interest in this study was Heshun County, the county in China with the highest rate of neural tube defects （NTDs）. A hybrid particle swarm optimization/ant colony optimization （PSO/ACO） algorithm was used to quantify the probability of NTDs occurring at villages with no births. The hybrid PSO/ACO algorithm is a form of artificial intelligence adapted for hierarchical classification. It is a powerful technique for modeling complex problems involving impacts of causes. Results The algorithm was easy to apply, with the accuracy of the results being 69.5%＋7.02% at the 95% confidence level. Conclusion The proposed method is simple to apply, has acceptable fault tolerance, and greatly enhances the accuracy of calculations.

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.

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.