Birth defects in newborns and stillborns: An example of the Brazilian reality

Background: This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects. Methods. For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases. Result: The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death. Conclusions: The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments. © 2011 Fett-Conte et al; licensee BioMed Central Ltd.

Birth defects in newborns and stillborns: an example of the Brazilian reality

Abstract Background This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects. Methods For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases. Result The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death. Conclusions The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments.

Failures and complications in patients with birth defects restored with fixed dental prostheses and single crowns on teeth and/or implants

OBJECTIVES: To assess retrospectively, over at least 5 years, the incidences of technical and biological complications and failures in young adult patients with birth defects affecting the formation of teeth. MATERIAL AND METHODS: All insurance cases with a birth defect that had crowns and fixed dental prostheses (FDPs) inserted more than 5 years ago were contacted and asked to participate in a reexamination. RESULTS: The median age of the patients was 19.3 years (range 16.6-24.7 years) when prosthetic treatment was initiated. Over the median observation period of 15.7 years (range 7.4-24.9 years) and considering the treatment needs at the reexamination, 19 out of 33 patients (58%) with reconstructions on teeth remained free from all failures or complications. From the patients with FDPs and single unit crowns (SCs) on implants followed over a median observation period of 8 years (range 4.6-15.3 years), eight out of 17% or 47% needed a retreatment or repair at some point due to a failure or a complication. From the three groups of patients, the cases with amelogenesis/dentinogenesis imperfecta demonstrated the highest failure and complication rates. In the cases with cleft lip, alveolus and palate (CLAP) or hypodontia/oligodontia, 71% of the SCs and 73% of the FDPs on teeth (FDP T) remained complication free over a median observation period of about 16 years. Sixty-two percent of the SCs and 64% of the FDPs on implants remained complication free over 8 years. Complications occurred earlier with implant-supported reconstructions. CONCLUSIONS: Because healthy, pristine teeth can be left unprepared, implant-supported SCs and FDPs are the treatment choice in young adults with birth defects resulting in tooth agenesis and in whom the edentulous spaces cannot be closed by means of orthodontic therapy. However, the trend for earlier and more frequent complications with implant-supported reconstructions in young adults, expecting many years of function with the reconstructions, has to be weighed against the benefits of keeping teeth unprepared. In cases with CLAP in which anatomical conditions render implant placement difficult and in which teeth adjacent to the cleft require esthetic corrections, the conventional FDP T still remains the treatment of choice.

Cumulative costs for the prosthetic reconstructions and maintenance in young adult patients with birth defects affecting the formation of teeth

OBJECTIVES: To assess retrospectively the cumulative costs for the long-term oral rehabilitation of patients with birth defects affecting the development of teeth. METHODS: Patients with birth defects who had received fixed reconstructions on teeth and/or implants > or =5 years ago were asked to participate in a comprehensive clinical, radiographic and economic evaluation. RESULTS: From the 45 patients included, 18 were cases with a cleft lip and palate, five had amelogenesis/dentinogenesis imperfecta and 22 were cases with hypodontia/oligodontia. The initial costs for the first oral rehabilitation (before the age of 20) had been covered by the Swiss Insurance for Disability. The costs for the initial rehabilitation of the 45 cases amounted to 407,584 CHF (39% for laboratory fees). Linear regression analyses for the initial treatment costs per replaced tooth revealed the formula 731 CHF+(811 CHF x units) on teeth and 3369 CHF+(1183 CHF x units) for reconstructions on implants (P<.001). Fifty-eight percent of the patients with tooth-supported reconstructions remained free from failures/complications (median observation 15.7 years). Forty-seven percent of the patients with implant-supported reconstructions remained free from failures/complications (median observation 8 years). The long-term cumulative treatment costs for implant cases, however, were not statistically significantly different compared with cases reconstructed with tooth-supported fixed reconstructions. Twenty-seven percent of the initial treatment costs were needed to cover supportive periodontal therapy as well as the treatment of technical/biological complications and failures. CONCLUSION: Insurance companies should accept to cover implant-supported reconstructions because there is no need to prepare healthy teeth, fewer tooth units need to be replaced and the cumulative long-term costs seem to be similar compared with cases restored on teeth.

Birth defects among surviving children under seven years of age in Tianjin, China

Birth defects are a leading cause of infant mortality in the developed countries. They are also of increasing concern in many developing countries, such as China. However, prevalence and causes of birth defects in China are inadequately understood.^ The purpose of the present study was to estimated prevalence of birth defects in surviving children under seven years of age in Tianjin, China and investigate determinants of birth defects in the study area.^ The present study took place in Tianjin, China in 1986, involving 22,081 surviving children under seven years of age. Children with birth defects were ascertained through physical examinations by physicians during household visits and ascertainment of birth defects was verified through multiple sources. Of 22,081 surviving children, 524 had birth defects (23.7 per 1,000). The study noted a striking discrepancy in the prevalence of birth defects between urban and rural area. The prevalence of birth defects was 16.3 per 1,000 in the urban and 33.2 per 1,000 in the rural area.^ Using cases of birth defects ascertained from surviving children, a case-control study was carried out. The study observed that first-trimester maternal flu was associated with increased risk of both major and minor birth defects in children after controlling for other maternal factors (adjusted odds ratio (OR) = 8.7, 95% confidence interval (CI) = 4.3-17.3; OR = 3.6, 95% CI = 1.7-7.5). This association could be biased by different reporting of exposure between mothers of children with birth defects and mothers of children without defects. This study indicated that maternal flu was also associated with congenital heart defects and polydactyly after controlling for other maternal factors (adjusted OR = 32.3, 95% CI = 13.3-78.3; adjusted OR = 5.5, 95% CI = 1.1-27.7). The associations remained when affected controls (children with similar birth defects other than congenital heart defects or polydactyly) were used (adjusted OR = 4.3, 95% CI = 1.2-15.3; OR = 1.4, 95% CI = 1.4-7.9). A weak association between first-trimester vaginal bleeding and selected groups of birth defects was found in this study, but the association may be confounded by other factors. Maternal smoking during pregnancy was modestly associated with cleft lip with or without cleft palate (OR = 1.4, 95% = 0.4-4.9), but the association may be due to chance. Some major limitations in this study warrant caution in interpretation of the findings, especially the causal relation. ^

The association between maternal use of spermicides, condoms, intra-uterine devices or progesterone and major structural birth defects

Birth defects occur in 1 of every 33 babies born in the United States, and are the leading cause of infant death. Mothers using contraceptives that become pregnant may continue to use their contraceptives after their first missed menstrual period, thus exposing their baby in utero to the contraceptive product. Progesterone is also sometimes prescribed during the first trimester of pregnancy to mothers with a history of miscarriages or infertility problems. To ensure the safety of these products, it is important to investigate whether there is an increased occurrence of babies born with birth defects to mothers using various contraceptive methods or progesterone in early pregnancy. Using data from the National Birth Defects Prevention Study (NBDPS), an ongoing multi-state, population based case-control study, this study assessed maternal exposures to IUDs, spermicides, condoms and progesterone in early pregnancy. ^ Progesterone used for threatened miscarriage during the first three months of pregnancy was associated with an increased occurrence of hypoplastic left heart (adjusted odds ratios (OR) 2.24, 95% CI 1.13-4.21), perimembranous ventricular septal defects (OR 1.64, 95% CI 1.10-2.41), septal associations (OR 2.52, 95% CI 1.45-4.24), esophageal atresia (OR 1.82, 95% CI 1.04-3.08), and hypospadias (OR 2.12, 95% CI 1.41-3.18). Mothers using progesterone for injectable contraception had increased (OR > 2.5), but insignificant odds ratios for anencephaly, septal associations, small intestinal atresias and omphalocel. Progesterone used for fertility was not associated with an increased occurrence of any birth defects examined. ^ Mothers using progesterone for fertility assistance and threatened miscarriage were very similar with respect to their demographics and pregnancy history. They also both reported similar types of progesterone. Thus, if progesterone was a causal risk factor for birth defects we would have expected to observe similar increases in risk among mothers using progesterone for both indications. Because we predominantly observed increased associations among mothers using progesterone for threatened miscarriage but not fertility assistance, it is possible the increased associations we observed were confounded by indication (i.e. progesterone was administered for vaginal bleeding which occurred as a sequelae to the formation of a congenital anomaly. ^ No significant increased associations were observed between maternal spermicide use during pregnancy and 26 of 27 types of structural malformations. While multiple statistical tests were performed we observed first trimester maternal spermicide use to be associated with a significant increased occurrence of perimembranous ventricular septal defects (OR 2.21, 95% CI 1.16-4.21). A decreased occurrence (OR < 1.0) was observed for several categories of birth defects among mothers who conceived in the first cycle after discontinuing the use of spermicides (22 of 28) or male condoms (23 of 33). ^ Overall the percent of IUD use was similar between mothers of controls and mothers of all cases in aggregate (crude OR 1.05, 95% CI 0.61-1.84). Power was limited to detect significant associations between IUD use and birth defects, however mothers using an IUD in the month immediately prior to conception or during pregnancy were not associated with an increase of birth defects. Limb defects and amniotic band sequence previously reported to be associated with IUD use during pregnancy were not found to occur among any mothers reporting the use of an IUD during pregnancy.^

AN INVESTIGATION OF THE IMPACT OF CHILDREN WITH BIRTH DEFECTS ON STRESS IN THEIR FAMILIES

A child with a birth defect places physical, financial and emotional stress upon the family. The purpose of this study was to assess the impact of a mildly handicapped child on the family's coping abilities.^ Two groups, 101 mothers of children with birth defects and 107 mothers of intact children, completed the Holroyd Questionnaire on Resources and Stress and the Luborsky Social Assets Scale. From these groups, 86 pairs were matched on four factors: the age (two to eight years) and sex of the study child and the mother's education and marital status.^ The children with birth defects had completed the diagnostic evaluation at the Meyer Center for Developmental Pediatrics, Texas Children's Hospital. Children with severe defects were excluded. The mean I.Q of the group was 88, s.d. 17; 17 children were mildly retarded and 35 had an I.Q. of 100 or above; areas of dysfunction included motor abnormalities, behavior disturbance, speech problems, and sensory impairments.^ The expected direction and statistically significant differences were obtained from the data for the matched pairs on the Q.R.S. scales. The mothers of children with a birth defect reported poor health, a negative attitude toward the child, being over-protective, financial problems and feeling a lack of social support and family integration. They perceived the child as socially obtrusive, limited as to occupational opportunities, and as having a difficult personality.^ The functioning levels of the handicapped children contributed to the respondent's problems. The child with behavior and speech problems but adequate intelligence was a situation which resulted in a poor health/mood of the mother. The mother's pessimism was related to the child's low intelligence.^ The social assets of the respondents with intact children were significantly higher than those of respondents of handicapped children. There was no relationship between the total social assets score and the scores on the Q.R.S. for mothers of handicapped children. These mothers did report poorer physical conditions, more smoking, and quarreling of their parents as they grew up. ^

Spatial distribution of orofacial cleft birth defects and uranium-radium concentrations in tap water in Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala Counties, Texas

Background Past and recent evidence shows that radionuclides in drinking water may be a public health concern. Developmental thresholds for birth defects with respect to chronic low level domestic radiation exposures, such as through drinking water, have not been definitely recognized, and there is a strong need to address this deficiency in information. In this study we examined the geographic distribution of orofacial cleft birth defects in and around uranium mining district Counties in South Texas (Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala), from 1999 to 2007. The probable association of cleft birth defect rates by ZIP codes classified according to uranium and radium concentrations in drinking water supplies was evaluated. Similar associations between orofacial cleft birth defects and radium/radon in drinking water were reported earlier by Cech and co-investigators in another of the Gulf Coast region (Harris County, Texas).50, 55 Since substantial uranium mining activity existed and still exists in South Texas, contamination of drinking water sources with radiation and its relation to birth defects is a ground for concern. ^ Methods Residential addresses of orofacial cleft birth defect cases, as well as live births within the twenty Counties during 1999-2007 were geocoded and mapped. Prevalence rates were calculated by ZIP codes and were mapped accordingly. Locations of drinking water supplies were also geocoded and mapped. ZIP codes were stratified as having high combined uranium (≥30μg/L) vs. low combined uranium (<30μg/L). Likewise, ZIP codes having the uranium isotope, Ra-226 in drinking water, were also stratified as having elevated radium (≥3 pCi/L) vs. low radium (<3 pCi/L). A linear regression was performed using STATA® generalized linear model (GLM) program to evaluate the probable association between cleft birth defect rates by ZIP codes and concentration of uranium and radium via domestic water supply. These rates were further adjusted for potentially confounding variables such as maternal age, education, occupation, and ethnicity. ^ Results This study showed higher rates of cleft births in ZIP codes classified as having high combined uranium versus ZIP codes having low combined uranium. The model was further improved by adding radium stratified as explained above. Adjustment for maternal age and ethnicity did not substantially affect the statistical significance of uranium or radium concentrations in household water supplies. ^ Conclusion Although this study lacks individual exposure levels, the findings suggest a significant association between elevated uranium and radium concentrations in tap water and high orofacial birth defect rates by ZIP codes. Future case-control studies that can measure individual exposure levels and adjust for contending risk factors could result in a better understanding of the exposure-disease association.^

Prevention of birth defects in a national study

The following analyses covered two main objectives focused on the prevention of and identification of risk factors for birth defects, the leading cause of infant mortality. All analyses utilized data from the National Birth Defects Prevention Study (NBDPS), an ongoing, population-based, case-control study of major structural birth defects. ^ The first objective was to identify predictors of folic acid supplementation among women of reproductive age. To meet this objective, a previous analysis of potential predictors of periconcecptional folic acid use in the NBDPS was repeated using data from more recent years (1997-2000 versus 2001-2005). The results of these analyses were consistent with the initial analyses, indicating that folic acid use is associated with maternal race/ethnicity, age, education, pregnancy awareness, smoking status, first prenatal care visit, previous live births, and fertility treatments). In addition, data from NBDPS controls were used to identify predictors of preconceptional folic acid use, since supplementation is optimally initiated prior to pregnancy (rather than after conception). These analyses indicated that maternal race/ethnicity, education, age, nativity, employment status, income, number of dependents, smoking, and birth control are significantly associated with preconceptional folic acid supplementation. Ultimately the results of these analyses can be used to guide the development of targeted interventions for preconceptional folic acid use. ^ The second objective was to investigate the association between parental Hispanic acculturation and the risk of gastroschisis, a congenital malformation of the abdominal wall, in offspring. Significant association were not observed for mothers < 20 years of age at conception. Among mothers ≥ 20 years of age, white parents were at a decreased risk of having a child with gastroschisis as compared to Hispanic parents who were born in the United States (US) [odd ratios (ORs) ranging from 0.60 to 0.55] and Hispanics parents who predominantly spoke English (ORs ranging from 0.65 to 0.58). Compared to Hispanic mothers born in the US, the risk of gastroschisis was lower among Hispanic mothers who had lived in the US < 5 years (OR=0.36, 95% CI: 0.42, 0.81) at the time of delivery and Hispanic mothers who migrated to the US at ≥ 20 years of age (OR=0.48, 95% CI: 0.26, 0.89). The results of these analyses provide further evidence that the risk of gastroschisis in offspring is associated with parent Hispanic ethnicity and, among Hispanics, with the degree of parental acculturation. Future studies should focus on characteristic differences between less and more acculturated parents to better understand the relationship between acculturation and gastroschisis.^

A comparative state policy analysis of the adoption of birth defects surveillance legislation

Birth defects are the leading cause of infant mortality in the United States and are a major cause of lifetime disability. However, efforts to understand their causes have been hampered by a lack of population-specific data. During 1990–2004, 22 state legislatures responded to this need by proposing birth defects surveillance legislation (BDSL). The contrast between these states and those that did not pass BDSL provides an opportunity to better understand conditions associated with US public health policy diffusion. ^ This study identifies key state-specific determinants that predict: (1) the introduction of birth defects surveillance legislation (BDSL) onto states' formal legislative agenda, and (2) the successful adoption of these laws. Secondary aims were to interpret these findings in a theoretically sound framework and to incorporate evidence from three analytical approaches. ^ The study begins with a comparative case study of Texas and Oregon (states with divergent BDSL outcomes), including a review of historical documentation and content analysis of key informant interviews. After selecting and operationalizing explanatory variables suggested by the case study, Qualitative Comparative Analysis (QCA) was applied to publically available data to describe important patterns of variation among 37 states. Results from logistic regression were compared to determine whether the two methods produced consistent findings. ^ Themes emerging from the comparative case study included differing budgetary conditions and the significance of relationships within policy issue networks. However, the QCA and statistical analysis pointed to the importance of political parties and contrasting societal contexts. Notably, state policies that allow greater access to citizen-driven ballot initiatives were consistently associated with lower likelihood of introducing BDSL. ^ Methodologically, these results indicate that a case study approach, while important for eliciting valuable context-specific detail, may fail to detect the influence of overarching, systemic variables, such as party competition. However, QCA and statistical analyses were limited by a lack of existing data to operationalize policy issue networks, and thus may have downplayed the impact of personal interactions. ^ This study contributes to the field of health policy studies in three ways. First, it emphasizes the importance of collegial and consistent relationships among policy issue network members. Second, it calls attention to political party systems in predicting policy outcomes. Finally, a novel approach to interpreting state data in a theoretically significant manner (QCA) has been demonstrated.^

The association between parity and selected structural birth defects

BACKGROUND: Parity is a risk factor in neonatal morbidity and mortality. This dissertation examined the association between first births and selected birth defects. The first aim was to assess the risk of 66 birth defects among first births and third or greater births. The second aim was to determine if maternal race, maternal age, infant sex or infant birth weight modify the association between first births and selected birth defects. METHODS: The Texas Birth Defects Registry provided data for 1999-2009. For the first aim, odds ratios were calculated for each birth defect. For the second aim, analysis was restricted to the ten birth defects significantly associated with first births. Stratified analyses were conducted and interaction terms were added to logistic regression models to assess whether differences in the odds ratios for the effect of first birth were statistically significant across strata. RESULTS: Findings for the first aim showed that first births had significantly increased odds of having an infant with 24 of the 66 birth defects. Third or greater births had significantly increased odds of having four of the 66 birth defects. For the second aim, a number of significant effect modifiers were observed. For patent ductus arteriosis, obstructive urinary defects and gastroschisis, the effect of first births was significantly modified by black or U.S.-born Hispanic mothers. The effect of first birth was also significantly modified among mothers ≥30 years for mitral valve insufficiency, atrial septal defect and congenital hip dislocation. The effect of first births was significantly modified among infants with low birth weight for hypospadias, congenital hip dislocation and gastroschisis. CONCLUSIONS: First births were associated with an elevated risk of 24 categories of birth defects. For some of the birth defects studied, the effect of first birth is modified by maternal age, maternal race and low birth weight. Knowledge of the increased risk for birth defects among women having their first birth allows physicians and midwives to provide better patient care and spur further research into the etiology of associated birth defects. This knowledge may bring about interventions prior to conception in populations most likely to conceive.^

The new dysmorphology: application of insights from basic developmental biology to the understanding of human birth defects.

Information obtained from studies of developmental and cellular processes in lower organisms is beginning to make significant contributions to the understanding of the pathogenesis of human birth defects, and it is now becoming possible to treat birth defects as inborn errors of development. Mutations in genes for transcription factors, receptors, cell adhesion molecules, intercellular junctions, molecules involved in signal transduction, growth factors, structural proteins, enzymes, and transporters have been identified in genetically caused human malformations and dysplasias. The identification of these mutations and the analysis of their developmental effects have been greatly facilitated by the existence of natural or engineered models in the mouse and even of related mutations in Drosophila, and in some instances a remarkable conservation of function in development has been observed, even between widely separated species.

Birth defects in Illinois : a report on mortality and county-specific prevalence at birth /

"June 1997."

Birth defects in Chicago and the state of Illinois, 1989-1993 /

"October 1994."

Birth defects and other adverse pregnancy outcomes in Illinois, 2001-2005 : a report on county-specific incidence /

" ... supported by grant/cooperative agreement number U50/CCU523303 from the U.S. Centers for Disease Control and Prevention."--Page ii.