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PubMed1983

Evaluation of the association between birth defects and exposure to ambient vinyl chloride.

Birth defects incidence for infants born to residents of Shawinigan, Canada in 1966-1979 were significantly higher than in three comparison communities. Since there has been a vinyl chloride polymerization plant in this town since 1943 from which ten cases of angiosarcoma of the liver have been identified, this study explores the possible association between exposure to vinyl chloride monomer (VCM) in ambient air and the occurrence of birth defects in the community. The excess of birth defects fluctuated seasonally in a way that corresponded to changes in VCM concentration in the environment. Mothers who gave birth to malformed children were younger on average in Shawinigan than in the comparison communities. However, there was no excess of still-births in Shawinigan. The excess in birth defects involved most organ systems, and variation in birth-defect rates among school districts could not be accounted for by estimates of VCM in the atmosphere. The occupational and residential histories of parents who gave birth to malformed infants were compared with those of parents of normal infants. The two groups did not differ in occupational exposure or closeness of residence to the vinyl chloride polymerization plant. Some descriptive data from this study raised the hypothesis of an association between VCM in the air and birth defects in the exposed community, but as a whole, within the sample size available, such an association could not be substantiated.

Abnormalities, Drug-Induced↗
PubMed1999

Parental consanguinity as a cause for increased incidence of births defects in a study of 238,942 consecutive births.

The risk for birth defects in the offspring of first-cousin matings has been estimated to increase sharply compared to non consanguineous marriages. As a general decline in the frequency of consanguineous marriages was observed in this century, one wonders whether consanguinity is still a factor in the appearance of birth defects in developed countries. Based on our registry of congenital anomalies we tried to answer to this question. In the population studied in North-Eastern France a consanguineous mating was known in 1.21% of the cases with congenital anomalies, vs. 0.27% in controls, (p < 0.001). The frequency of the malformations recorded paralleled the degree of consanguinity: out of 89 malformed children, 51 were seen in first-cousins mating (10.3 times more frequent than in offspring of non consanguineous couples), 17 in second-cousins marriages and 18 in more distant relatives mating. Three were uncle-niece marriage. Excluding known mendelian conditions these numbers were 73, 36, 17 and 17 respectively and the corresponding relative risk were 3.68, 3.01, 3.41 and 4.89 respectively. Therefore there is a negative dose-response effect between level of inbreeding and risk of congenital malformations. Consanguineous mothers were more often pregnant than non consanguineous mothers (p < 0.01) and they had more stillbirths than non consanguineous mothers. These results show that consanguinity is still a factor of birth defects and they must be taken into account for genetic counseling of inbred marriages, in developed countries.

Congenital Abnormalities↗
PubMed1999

Laterality patterns in infants with external birth defects.

The lateral distribution of external birth defects has not been reported in a comprehensive way, and patterns in this distribution have not been examined. This study presents the lateral distribution of 6,390 unilateral defects from among 102 defect categories in data collected by the Metropolitan Atlanta Congenital Defects Program. Among all defects, 49% (95% CI 48-51%) were right-sided. Among males and females, 51% (95% CI 50-53%) and 47% (95% CI 46-49%) of the defects, respectively, were right-sided. Of the 102 defect types, 57 had an excess of defects on the right side of the body; 39 had an excess of defects on the left side; and 6 were equally distributed. The excess on the right side was statistically significant for inguinal hernia, incarcerated inguinal hernia, microtia, preauricular sinus, talipes calcaneovalgus, and lambdoidal craniosynostosis. For the left side, the excess was statistically significant for preauricular tags, cleft lip, fused lip and cleft gum, cleft lip with cleft palate, congenital hip dysplasia, unstable hip, absent forearm or hand, anomaly of the knee, and skin tags. The percentage of right-sided defects among case subjects with unilateral defects was correlated with the percentage of males among all case subjects (r = 0.24, P < 0.05). Among male case subjects with unilateral defects, the correlation coefficient was 0.31 (P < 0. 01), and among females with unilateral defects, it was 0.11 (P > 0. 10). Differences in the lateral distribution of specific birth defects may be due to subtle differences in morphogenesis on the left and right sides of the embryo brought about by establishment of left-right asymmetry prior to organogenesis. The fact that more defect categories were right-sided than left-sided may be related to the observation that mitochondrial maturation in rat embryos is delayed on the right side. The right side, therefore, may be more susceptible than the left to defects caused by prenatal hypoxia. The significant correlation between the percentage right-sided and percentage male may then also be related to the observation that male sex hormones lower the mitochondrial respiration rate in rats and increase rat sensitivity to chemical hypoxia. Investigators should consider reporting the laterality of specific defects in both laboratory and epidemiological studies of birth defects. Right- and left-sided defects should perhaps be considered separately in etiologic studies of birth defects. Teratology 60:265-271, 1999. Published 1999 Wiley-Liss, Inc.

Animals↗
PubMed2002

Prevalence of birth defects and parental work in Singapore live births from 1994 to 1998: a population-based study.

The aims of the study were to assess the prevalence of birth defects (BDs) among different occupational groups and non-working parents, and to identify possible risk factors associated with BDs in Singapore live births born between 1 January 1994 and 31 December 1998. To do this, information on live births (from the Singapore National Registry of Births and Deaths) and BD cases [from the National Birth Defects Register (NBDR)] was obtained from 1 January 1994 to 31 December 1998. There were a total of 237 755 live births in Singapore between 1 January 1994 and 31 December 1998. Over the same period, 3293 cases of BDs were reported to the NBDR, giving an overall rate of 13.9 per 1000 live births. A downward trend with time was noted. Of the live born with BDs in this series, 36.7% presented with multiple anomalies. The overall occurrence of malformation (per 1000 live births) among working versus non-working mothers was 13.4 versus 14.2, respectively, and 13.8 for working fathers compared with 16.8 for non-working fathers. Parents in the occupational group 'Legislators, Senior Officers & Managers' had the lowest prevalence rates of congenital anomalies (9.4 per 1000 for mothers and 10.3 per 1000 for fathers), while the 'Agricultural & Fishery Workers' had the highest rates (40.0 per 1000 for mothers and 23.4 per 1000 for fathers). However, the very small number of workers in this latter group makes the rate unreliable. The prevalence of BDs in Singapore is comparable to those in other countries. Parental work per se is not correlated with BDs.

Adult↗
PubMed2003

Do multivitamin supplements attenuate the risk for diabetes-associated birth defects?

OBJECTIVE: To evaluate whether the risk for birth defects associated with maternal diabetes is attenuated by use of multivitamin supplements during the periconceptional period. METHODS: In the population-based Atlanta Birth Defects Case-Control Study, we identified case infants who had nonsyndromic birth defects that were reported to be associated with diabetes (n = 3278) and were born during 1968-1980 to residents of metropolitan Atlanta. Controls were infants without birth defects (n = 3029). Maternal diabetes was defined as reported diabetes with onset before the date of birth of the index infant, and periconceptional use of multivitamins was defined as reported regular use of multivitamin supplements from 3 months before pregnancy through the first 3 months of pregnancy. RESULTS: Offspring of mothers with diabetes had an increased risk for selected birth defects. However, the increased risk was limited to offspring of mothers who had diabetes and had not taken multivitamins during the periconceptional period (odds ratio: 3.93; 95% confidence interval: 1.79-8.63). Offspring of mothers who had diabetes and had taken multivitamins during the periconceptional period had no increased risk for birth defects (odds ratio: 0.15; 95% confidence interval: 0.00-1.99). CONCLUSIONS: Periconceptional use of multivitamin supplements may reduce the risk for birth defects among offspring of mothers with diabetes.

Adult↗
PubMed2001

The relation between small size for gestational age and the sex ratio of children with birth defects.

BACKGROUND: Infants with birth defects are more likely to be born small for gestational age (SGA) than are other infants. This study describes a relation noted between the percentage SGA and the percentage male among children with various defect types. The data source was case records collected by the Metropolitan Atlanta Congenital Defects Program, a population-based, active surveillance system, during 1968 through 1998. METHODS: The study calculated the correlation between the percentage male and the percentage SGA for isolated cases of 44 different defect types for male-dominant and female-dominant defects separately. RESULTS: The correlation coefficient was -0.47 (P < 0.01) for male-dominant defects and 0.20 (P > 0.05) for female-dominant defects. Male-dominant defects were more likely to show less than 15% SGA and more likely to show the strongest risk differences by sex. CONCLUSIONS: These results are consistent with genetic causation of strongly skewed sex ratios, at least among male-dominant defects. Review of the literature suggests that defects with sex ratios closer to 1 are likely to have lower recurrence risks and therefore are less likely to be inherited than are other defects with skewed sex ratios. Sex ratios closer to 1 and a high percentage SGA may be markers of acquired or environmental birth defects.

Animals↗
PubMed1999

A population-based study of survival and childbearing among female subjects with birth defects and the risk of recurrence in their children.

BACKGROUND AND METHODS: Persons with birth defects are at high risk for death during the perinatal period and infancy. Less is known about the later survival or reproduction of such persons. We studied a cohort that comprised 8192 women and adolescent girls with registered birth defects and 451,241 women and adolescent girls with no birth defects, all of whom were born in Norway from 1967 through 1982. The rate of survival was determined through 1992, and the rate of childbearing was determined through October 1997. We also estimated the risk of birth defects in the children of these subjects. RESULTS: Among the subjects with birth defects, 80 percent survived to 15 years of age, as compared with 98 percent of those with no birth defects. Among the surviving subjects, 53 percent of those with birth defects gave birth to at least one infant by the age of 30 years, as compared with 67 percent of those with no birth defects. The subjects with birth defects were one third less likely to give birth by the age of 30 than those with no birth defects. The children of the subjects with birth defects had a significantly higher risk of birth defects than the children of those with no birth defects (relative risk, 1.6; 95 percent confidence interval, 1.3 to 2.1). This increased risk was confined entirely to the specific defect carried by the mother, with the relative risk of recurrence varying from 5.5 to 82 according to the defect. In contrast, there was no increase in the risk of having an infant with a different type of defect. CONCLUSIONS: Women and girls with birth defects have decreased survival as compared with those with no birth defects, especially in the first years of life, and are less likely to have children. In addition, they have an increased risk of having children with the same defect.

Adolescent↗
PubMed2005

[Birth defects and health strategies in Brazil: an overview].

Birth defects have increased progressively in Brazil, shifting from the fifth to the second cause of infant mortality from 1980 to 2000, thus highlighting the need for specific health policy strategies. Some governmental and nongovernmental actions related to birth defects in Brazil include information services on teratogenic agents and inborn errors of metabolism, monitoring of birth defects, neonatal screening and treatment of some genetic diseases, and rubella immunization. In addition, flour fortification with folic acid for prevention of certain birth defects has begun recently. Despite the importance of such initiatives, it is still difficult to view birth defects from a comprehensive perspective. A specific national policy on birth defects must be formulated. Active participation is needed by the Ministry of Health, using existing genetic services as the backbone, in order to develop a regionalized, hierarchical, and functional network related to birth defects in Brazil.

Brazil↗
PubMed2006

Residential mobility patterns and exposure misclassification in epidemiologic studies of birth defects.

Many studies of environmental exposures and birth defects use mothers' addresses at delivery as a proxy for the exposure. The validity of these studies is questionable because birth defects generally occur within 8 weeks of conception and the mother's address at delivery may differ from her address early in pregnancy. In order to assess the extent of this bias, we examined the pattern of maternal residential mobility over the span of 3 months prior to conception through delivery, and associated maternal socio-demographic characteristics. We linked Texas subjects from a national case-control study of birth defects with their corresponding records from the Texas Birth Defects Registry and the Texas live birth certificates. Logistic regression analyses were conducted to assess maternal socio-demographic factors related to mobility during pregnancy. Overall, 33% of case and 31% of control mothers changed residence between conception and delivery. The pattern of mobility was similar for both case and control mothers for each pregnancy period. Multivariate analyses indicated that for case mothers, older age (OR=0.39, 95% CI=0.21-0.70), higher household income (OR=0.35, 95% CI=0.18-0.68), Hispanic ethnicity (OR=0.64, 95% CI=0.44-0.92), and higher parity (OR=0.59, 95% CI=0.38-0.94) were indicators of lower mobility during pregnancy. For control mothers, the same pattern of association was present, however, only older age was significantly associated with low rates of mobility. Studies of birth defects using maternal address at delivery as a proxy for maternal environmental exposures during pregnancy may be subject to considerable nondifferential exposure misclassification due to maternal mobility during pregnancy.

Adolescent↗
PubMed1990

Evaluation of birth defect histories obtained through maternal interviews.

Etiologic studies of birth defects often use family history information provided by parents of patients. The validity of this information has not been adequately assessed. Using data from the Atlanta Birth Defects Case-Control study, we evaluated sensitivity, specificity, and positive predictive value of mothers' responses regarding the presence of birth defects in their offspring. A total of 4929 mothers of infants with major structural defects ascertained by the Metropolitan Atlanta Congenital Defects Program and a total of 3,029 mothers of normal infants were asked whether their babies had had a birth defect or a health problem diagnosed during the first year of life. Interviewers and coders of maternal responses were blinded to the case-control status of infants. Sensitivity (the proportion of case mothers who gave responses that could be coded as denoting a major birth defect) was 61%. Specificity (the proportion of control mothers who gave responses that could not be coded as denoting a major birth defect) was 98%. The positive predictive value (the proportion of mothers who gave a major-birth-defect response who in fact had babies with major birth defects) was estimated as 47%. Sensitivity, specificity, and positive predictive value varied by maternal sociodemographic factors such as race and education, as well as by type of defect. These results suggest that family history data obtained through maternal interviews should be cautiously interpreted and, if not properly validated, may alter estimates of recurrence risks.

Case-Control Studies↗
PubMed1995

Risk factors for birth defects in Singapore: a case control study.

To explore possible risk factors for birth defects, a matched case-control study was carried out at Kandang Kerbau Hospital in Singapore from January 1986 to December 1988. Cases and controls were selected from livebirths born in that hospital during that period. Cases were babies who were clinically detected as having defects at birth and the diagnosis reconfirmed at 6 weeks post partum. Each case was matched to a control by maternal age, ethnic background of mother, the same class of maternity ward and time of delivery. Five hundred and seventy-two matched pairs were accrued for the study. The parents of both cases and controls were interviewed at 6 weeks post partum. Information on the medical and birth history of both mother and baby was obtained from medical records. Using conditional logistic regression analysis to adjust for potential confounders, the strongest risk factors for birth defects were family history of birth defects (OR 3.3; 95% CI 1.8-6.4) and parents having a previous abnormal baby (OR 2.4; 95% CI 1.1-5.3). Other notable risk factors included drug history during pregnancy (OR 1.2; 95% CI 0.8-2.0), the ingestion of traditional medicine during pregnancy (OR 1.4; 95% CI 1.0-2.0), injuries or accidents during pregnancy (OR 2.2; 95% CI 1.5-3.2) and maternal diabetes mellitus (OR 1.3, 95% CI 0.3-7.1). Mothers in professional occupations (OR 1.4, 95% CI 0.7-2.6) and those in production occupation (OR 1.2, 95% CI 0.9-1.7) had an increased risk for birth defects compared to housewives.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗
PubMed2001

Ascertainment of pregnancies terminated because of birth defects: effect on completeness of adding a new source of data.

BACKGROUND: When evaluating preventive programs such as folate promotion and rubella vaccination, it is critically important to include terminations of pregnancy for neural tube defects and congenital rubella syndrome. Data from birth defects registries are often used for this purpose. The Western Australian Birth Defects Registry ascertains cases of birth defects in livebirths, stillbirths, and terminations of pregnancy for fetal abnormality, using multiple sources of ascertainment. METHODS: Data on terminations of pregnancy for fetal abnormality from the Western Australian Hospital Morbidity Data System 1980-1997 (not previously available to the Registry) were used to estimate the completeness of ascertainment of such cases by the Registry. Ascertainment-adjusted prevalences were calculated using capture-recapture methods. RESULTS: A total of 702 terminations with birth defects were identified among hospital discharges, most of which were already known to the Registry (87.9%). Of the 85 new cases, seven had a neural tube defect, 23 had a chromosomal defect, and 12 had confirmed maternal rubella infection during pregnancy. The ascertainment-adjusted prevalence was not importantly [corrected] different for birth defects overall or for these individual conditions, although the 95% confidence intervals for all birth defects, and for all chromosomal defects, did not include the prevalence based on registered cases only. CONCLUSIONS: The Western Australian Birth Defects Registry ascertains a high proportion of pregnancies terminated for fetal abnormality, and should therefore be a reliable source of data with which to assist in monitoring the effectiveness of preventive programs.

Abortion, Induced↗
PubMedDate not supplied

Evaluation of the hospital discharge diagnoses index and the birth certificate as sources of information on birth defects.

The hospital discharge diagnoses index (DI) for newborns and the birth certificate were evaluated as sources of information about birth defects by comparing them with the same births in the case registry of the California Birth Defects Monitoring Program (CBDMP). The CBDMP is an active surveillance system; the staff visit hospitals to identify children with birth defects diagnosed in the first year of life. The study population comprised 66,481 live births to residents of five counties in the San Francisco Bay area in 1983. Of these infants, 2,543 had at least one birth defect noted on the DI, and 1,623 were in the CBDMP registry; 1,020 with defects noted on the DI were also in the CBDMP registry. For this same population, 399 infants had one or more defects noted on the birth certificate; 304 of these were also in the CBDMP registry. Reporting of birth defects on the birth certificate was poor for every condition. Reporting on the DI was most reliable for oral clefts and chromosomal defects; for these defects, the DI omitted one-third of the cases but had identified only about 10 percent false-positive (that is, unverified) cases. Major central nervous system malformations were less well reported, with about one-third of them false-positive. For all other birth defects, the DI either omitted more than half of the cases, or more than half of the cases reported were false-positive cases. These findings raise questions about the validity of analytic studies of birth defects if the data are obtained only from the DI or the birth certificate.

Birth Certificates↗
PubMed2004

Patterns of chromosomal translocations identified by a birth defects registry, Hawaii, 1986-2000.

Using a birth defects registry, this investigation examined the distribution of translocations by type of translocation, chromosomes involved in the translocation, pregnancy outcome, method of diagnosis, inheritance, and diagnosis of major structural birth defects. A total of 121 cases were identified through a statewide population-based birth defects registry. The translocations were reciprocal in 89 (73.6%) cases, Robertsonian in 32 (26.4%) cases, balanced in 86 (71.1%) cases, and unbalanced in 35 (28.9%) cases. Live births accounted for 76 (88.4%) of balanced translocations and 22 (62.9%) of unbalanced translocations. Diagnosis was made by amniocentesis or chorionic villus sampling in 72 (83.7%) of balanced translocations and 11 (31.4%) of unbalanced translocations. Of cases of known inheritance, the translocation was of maternal origin in 38 (46.3%) cases, paternal origin in 25 (30.5%) cases, and de novo in 19 (23.2%) cases. Major structural birth defects were diagnosed in 17 (19.8%) of balanced translocations and 20 (57.1%) of unbalanced translocations. Translocations were more likely to be reciprocal, balanced, and of maternal origin. Infants and fetuses with unbalanced translocations were less likely to be live births and diagnosed by amniocentesis or chorionic villus sampling and more likely to be diagnosed with major structural birth defects.

Amniocentesis↗
PubMed2001

Survival and reproduction among males with birth defects and risk of recurrence in their children.

CONTEXT: Few systematic data exist on survival and reproduction among males with birth defects and their contribution to occurrence of birth defects in the next generation. OBJECTIVE: To estimate survival of males with registered birth defects, their subsequent reproduction rates, and their risk of transmitting birth defects to their offspring. DESIGN AND SETTING: Population-based cohort study of data from the Medical Birth Registry of Norway. SUBJECTS: A total of 486 207 males born in Norway between 1967 and 1982, 12 292 of whom had a recorded birth defect. MAIN OUTCOME MEASURES: Survival rates through 1992, reproduction rates through 1998, and risk of birth defects among offspring of males with vs without birth defects. RESULTS: Survival through 1992 was lower among males with birth defects (84% vs 97%). Compared with males without birth defects, affected males were 28% less likely to have had a child. Among offspring of affected males, 5.1% had a registered birth defect compared with 2.1% of offspring of males without birth defects (relative risk [RR], 2.4; 95% confidence interval [CI], 1.9-3.0). Offspring of affected fathers had an increased risk of the same defect as their fathers (RR, 6.5; 95% CI, 4.0-10.4) and an increased risk of dissimilar defects (RR, 1.8; 95% CI, 1.3-2.5). CONCLUSIONS: Compared with unaffected males, males with birth defects have higher mortality and survivors are less likely to have a child. Fathers with birth defects are significantly more likely than unaffected fathers to have an affected child.

Adolescent↗
PubMed2002

The use of birth defect registries for etiological research: a review.

BACKGROUND: Birth defect registries are often used for etiological research. Either as hypotheses-generating studies, or studies directed at one specific association between a risk factor and a birth defect in order to confirm or refute possible associations. METHODS: A literature search in Medline was performed looking for studies using birth defect registries for studying different risk factors. RESULTS: A brief summary of study design for etiological research with registration data is given. Subsequently, the different studies performed are discussed according to the risk factors investigated. Different aspects of the studies are listed and discussed. For each of the risk factors, the usefulness of birth defect registries to study the specific risk factor is discussed. Registries are dependent on the factors that are included in the registry or recorded in different databases. Most studies have looked at risk factors with readily available data, such as maternal age, illnesses and drugs. There is also wide use of other registers with exposure data on, for example, the environment. CONCLUSIONS: Birth defect registries have been used in the evaluation of many possible risk factors for birth defects. They have also been used in rebutting alarms in the media on possible clusters and risk factors.

Journal Article↗
PubMed2004

Assisted reproductive technologies and the risk of birth defects--a systematic review.

BACKGROUND: The risk of birth defects in infants born following assisted reproductive technology (ART) treatment is a controversial question. Most publications examining the prevalence of birth defects in ICSI and IVF infants compared to spontaneously conceived infants have serious methodological limitations; despite this, most researchers have concluded that there is no increased risk. METHODS: We carried out a systematic review to identify all papers published by March 2003 with data relating to the prevalence of birth defects in infants conceived following IVF and/or ICSI compared with spontaneously conceived infants. Independent expert reviewers used criteria defined a priori to determine whether studies were suitable for inclusion in a meta-analysis. Fixed effects meta-analysis was performed for all studies and reviewer-selected studies. RESULTS: Twenty-five studies were identified for review. Two-thirds of these showed a 25% or greater increased risk of birth defects in ART infants. The results of meta-analyses of the seven reviewer-selected studies and of all 25 studies suggest a statistically significant 30-40% increased risk of birth defects associated with ART. CONCLUSIONS: Pooled results from all suitable published studies suggest that children born following ART are at increased risk of birth defects compared with spontaneous conceptions. This information should be made available to couples seeking ART treatment.

Congenital Abnormalities↗
PubMed2005

Influence of prenatal diagnosis and pregnancy termination of fetuses with birth defects on the perinatal mortality rate in Victoria, Australia.

Historical data show that in Victoria birth defects have accounted for approximately 25% of all perinatal deaths. Terminations of pregnancies (TOPs) for birth defects occurring at > or =20 weeks gestation are included in the population-based perinatal data collection. These are classified as stillbirths or neonatal deaths. Some would have survived the perinatal period if no termination had taken place, and as a result they have the effect of increasing the perinatal mortality rate (PMR). Conversely, TOPs <20 weeks gestation, of fetuses with lethal birth defects that would have resulted in a perinatal death, are not included in the statistics and therefore reduce the PMR. The aim of this study was to examine the effect on the PMR of TOPs following the prenatal detection of birth defects, taking into account the severity or 'lethality' of the birth defects. Data on live births, stillbirths, neonatal deaths and TOPs carried out because of a birth defect were collected from the Victorian Birth Defects Register (BDR) for 1989-2000. Birth defects were categorised into three groups, according to the estimated likelihood of a baby with that condition dying in the perinatal period: a 'lethal' birth defect was one where there was >50% likelihood of death, 'possibly lethal' 15-50% and 'non-lethal' less than 15%. Based on these 'lethality' groups and associated assumptions about average survival rates beyond the neonatal period, the PMR was recalculated. TOPs for 'non-lethal' birth defects at > or =20 weeks gestation increased the PMR by 3.8%. TOPs for 'lethal' birth defects <20 weeks decreased the PMR by 14.4%. The net effect on the overall PMR from TOPs for birth defects was a 10.6% decrease.

Abortion, Induced↗