Very rare defects: What can we learn?

The International Clearinghouse for Birth Defects Surveillance and Research conducted a study on very rare defects (VRDs) to test methodologies in their population surveillance and to increase the knowledge of their epidemiology. Eight VRDs: acardia (AC), amelia (AM), bladder exstrophy (BE), cloaca exstrophy (CE), conjoined twins (CT), cyclopia (CY), "true" phocomelia (PH), and sirenomelia (SI) were selected, all of whom showed prevalences in the order of 1/100,000 births, except for BE: 1/48,000 births. Materials in this investigation from 25 million pregnancy outcomes, were provided by 22 Clearinghouse-member programs. The study protocol provided a working definition, a summary of the phenotypic characteristic, and a list of ICD-9 and ICD-10 codes for each VRDs. Learned lessons include: (1) The suspected associations of decreasing risk with advancing maternal age in AM and SI, and increasing risk in BE, and increasing frequency of twins in SI, were confirmed. (2) Morphologically similar defects showed dissimilar epidemiological characteristics, namely, AM and PH, and BE and CE. (3) Heterogeneity in total prevalences for most VRDs among different surveillance programs were attributed to operational reasons, except for SI and CT in which Amerindian ethnicity seems to be associated with higher prevalence. (4) Verbatim description is essential and must be stored in electronic files. In addition to codes. (5) Dysmorphologists or clinical geneticists are an essential part of the coordinating team of the surveillance program. (6) ICD coding system is insufficient. (7) Surveillance programs should be a valuable source of information on exposures to risk factors during pregnancy.Fil: Castilla, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Oswaldo Cruz; Brasil. Centro de Educación Medica E Invest.clinicas; Argentina. Instituto Nacional de Genética Médica Populacional; Brasil. Centre of the International Clearinghouse for Birth Defects Surveillance and Research; ItaliaFil: Mastroiacovo, Pierpaolo. Centre of the International Clearinghouse for Birth Defects and Research ; Itali

Néstor O. Bianchi

Semblantearlo a Bianchi es tarea sencilla, casi cobarde, por la transparencia del hombre. Un hombre íntegro y genuino no puede dejar de ser transparente ya que nada oculta ni nada simula. Las cosas son como son y también lo es él delante de ellas. Bianchi dice lo que piensa sin preocuparse mucho con lo que puedan pensar los que lo escuchan. Para algunos, puede decir un escándalo, una incorrección ideológica, política o hasta ecológica (¡Horror!), pero él lo hace desde la inocencia del que no vislumbra el pecado por estar más allá del mismo.Instituto Multidisciplinario de Biología Celula

Risk factors and demographics for microtia in South America: a case-control analysis

BACKGROUND: The etiopathogenesis of microtia is still unknown in the majority of the cases, particularly for individuals presenting with isolated microtia. Our aim was to evaluate potential risk factors for this condition using a case–control approach. METHODS: We analyzed data from 1,194 live births with isolated microtia enrolled in the ECLAMC study (Estudio Colaborativo Latino Americano de Malformaciones Congénitas) from 1982 to 2011 and their respective controls. Odds ratios (ORs) were estimated with logistic regression models along with 95% confidence intervals for the resulting OR estimates controlling for the effects of potential confounders (sex, maternal age, hospital, and year of birth) for an adjusted OR (aOR). RESULTS: Multiparity was associated with a higher risk of microtia compared with primiparity (aOR, 1.5; 95% confidence interval [CI], 1.2–1.8), with women who had eight or more prior pregnancies having the highest risk (aOR, 2.8; 95% CI, 1.6–5.2). Women who presented with cold-like symptoms were at higher risk for microtia (aOR, 2.2; 95% CI, 1.2–3.9) as well as those that used tobacco or alcohol during pregnancy (aOR, 1.7; 95% CI, 1.1–2.6 and aOR, 1.4; 95% CI, 0.9–2.1, respectively). The association with alcohol use appeared to be limited to those women who reported binge drinking during pregnancy (aOR, 1.4; 95% CI, 0.7–3.1). Cases from hospitals at low altitude (<2500 m) tended to have more severe types of microtia than those from hospitals at high altitude. CONCLUSION: These results support the hypothesis that, in addition to teratogens, other nongenetic risk factors contribute to the occurrence of isolated microtia.Fil: Luquetti, Daniela. University of Washington; Estados Unidos. Seattle Children; Estados UnidosFil: Saltzman, Babette S.. Seattle Children; Estados UnidosFil: López Camelo, Jorge Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Dutra, Maria da Graça. Instituto Oswaldo Cruz; BrasilFil: Castilla, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina. Instituto Nacional de Genética Médica Populacional; Brasi

The impact of altitude on infant health in South America

Several studies report that altitude reduces birth weight. However, much remains unknown about effects in various altitude ranges and about the heterogeneity in altitude effects by fetal health endowments. This study estimates the effects of altitude in South America on the means and quantiles of birth weight and gestational age separately for two large samples born at altitude ranges of 5 to 1,280mand 1,854 to 3,600 m. The study finds significant negative altitude effects on birth weight and gestational age in the low-altitude sample and on birth weight in the high-altitude sample. Altitude effects are larger for infants with very low fetal health endowments. The study finds differences in the effects of several inputs such as socioeconomic status and maternal fertility history and health between the two altitude samples. The study highlights the importance of adverse altitude effects on infant health when evaluating the costs and returns of policies that change the number of individuals who reside at higher altitude in both low and high altitude ranges.Fil: Wehbya, George L.. University of Iowa; Estados UnidosFil: Castilla, Eduardo Enrique. Fundación Oswaldo Cruz; Brasil. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: López Camelo, Jorge Santiago. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentin

Racial gaps in child health insurance coverage in four south American countries: The role of wealth, human capital, and other household characteristics

Objective. To evaluate the extent of racial gaps in child health insurance coverage in South America and study the contribution of wealth, human capital, and other household characteristics to accounting for racial disparities in insurance coverage. Data Sources/Study Setting. Primary data collected between 2005 and 2006 in 30 pediatric practices in Argentina, Brazil, Ecuador, and Chile. Design. Country-specific regression models are used to assess differences in insurance coverage by race. A decomposition model is used to quantify the extent to which wealth, human capital, and other household characteristics account for racial disparities in insurance coverage. Data Collection/Extraction Methods. In-person interviews were conducted with the mothers of 2,365 children. Principal Findings. The majority of children have no insurance coverage except in Chile. Large racial disparities in insurance coverage are observed. Household wealth is the single most important household-level factor accounting for racial disparities in coverage and is significantly and positively associated with coverage, followed by maternal education and employment/occupational status. Geographic differences account for the largest part of racial disparities in insurance coverage in Argentina and Ecuador. Conclusions. Increasing the coverage of children in less affluent families is important for reducing racial gaps in health insurance coverage in the study countries.Fil: Wehby, George. University of Iowa; Estados UnidosFil: Murray, Jeffrey C.. University of Iowa; Estados UnidosFil: McCarthy, Ann Marie. University of Iowa; Estados UnidosFil: Castilla, Eduardo Enrique. Centro de Educación Medica E Invest.clinicas; Argentina. Fundación Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Preferential associated anomalies in 818 cases of microtia in South america

The etiology of microtia remains unknown in most cases. The identification of patterns of associated anomalies (i.e., other anomalies that occur with a given congenital anomaly in a higher than expected frequency), is a methodology that has been used for research into the etiology of birth defects. We conducted a study based on cases of microtia that were diagnosed from more than 5 million live (LB)- and stillbirths (SB) examined in hospitals participating in ECLAMC (Latin American Collaborative Study of Congenital Malformations) between 1967 and 2009. We identified 818 LB and SB with microtia and at least one additional non-related major congenital anomaly (cases) and 15,969 LB and SB with two or more unrelated major congenital anomalies except microtia (controls). A logistic regression analysis was performed to identify the congenital anomalies preferentially associated with microtia. Preferential associations were observed for 10 congenital anomalies, most of them in the craniofacial region, including facial asymmetry, choanal atresia, and eyelid colobomata. The analysis by type of microtia showed that for anomalies such as cleft lip and palate, macrostomia, and limb reduction defects, the frequency increased with the severity of the microtia. In contrast, for other anomalies the frequency tended to be the same across all types of microtia. Based on these results we will integrate data on the developmental pathways related to preferentially associated congenital anomalies for future studies investigating the etiology of microtia.Fil: Luquetti, Daniela V.. University of Washington; Estados Unidos. Seattle Children’s Research Institute; Estados UnidosFil: Cox, Thimoty C.. Monash University; Australia. University of Washington; Estados UnidosFil: López Camelo, Jorge Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Dutra, Maria da Graça. Instituto Oswaldo Cruz; BrasilFil: Cunningham, Michael L.. University of Washington; Estados Unidos. Seattle Children’s Research Institute; Estados UnidosFil: Castilla, Eduardo Enrique. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina. Instituto Oswaldo Cruz; Brasil. Instituto Nacional de Genética Médica Populacional; Brasi

Complex segregation analysis of 1,792 cleft lip and palate families in South America: 1967-1997

Os estudos sobre fendas lábio-palatinas (FL/P) demonstram existir uma maior incidência do defeito nas famílias de afetados, mas seu modo de herança permanece indefinido. Esse trabalho apresenta os resultados de uma análise de segregação complexa realizada em 1.792 famílias sul-americanas que possuíam um recém-nascido com FL/P. Essas crianças foram registradas entre 1967 e 1997 e os nascimentos foram consecutivos. Um modelo sem um locus principal foi o que melhor se adequou às famílias de FL/P estudadas. Esse resultado está de acordo com estudos anteriores que mostraram uma significativa associação entre vários loci de suscetibilidade e FL/P, indicando que os genes relacionados com FL/P, isoladamente, contribuem pouco para o risco desse defeito.Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk

Análise de segregação complexa de 1.792 famílias com fenda lábio-palatina na América do Sul: 1967-1997

Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk.Os estudos sobre fendas lábio-palatinas (FL/P) demonstram existir uma maior incidência do defeito nas famílias de afetados, mas seu modo de herança permanece indefinido. Esse trabalho apresenta os resultados de uma análise de segregação complexa realizada em 1.792 famílias sul-americanas que possuíam um recém-nascido com FL/P. Essas crianças foram registradas entre 1967 e 1997 e os nascimentos foram consecutivos. Um modelo sem um locus principal foi o que melhor se adequou às famílias de FL/P estudadas. Esse resultado está de acordo com estudos anteriores que mostraram uma significativa associação entre vários loci de suscetibilidade e FL/P, indicando que os genes relacionados com FL/P, isoladamente, contribuem pouco para o risco desse defeito

Quantile effects of prenatal care utilization on birth weight in Argentina

The effects of prenatal care utilization on birth weight (BW) may vary by unobserved fetal health endowments. This heterogeneity will be masked by estimating the effects at BW mean but can be evaluated by estimating the effects at BW quantiles as fetal health endowment is a strong correlate with the BW quantile order. We estimated the effects of prenatal care visits and delay before prenatal care initiation, on BW mean and quantiles using a sample of infants from Argentina. Self-selection into prenatal care was modeled using 2SLS and instrumental variable quantile regression. Results suggest that the 'mean' effect of prenatal care utilization largely underestimates the effects at lower BW quantiles. About 35 and 77 g increase in BW mean and 0.1 quantile respectively, per visit and about 30 and 139 g decrease in BW mean and 0.1 quantile respectively, per week delayed, were estimated. Ignoring self-selection into prenatal care resulted in underestimation of mean and quantile effects. Results highlight the limitation of analyses focused on 'mean effects' in the presence of treatment heterogeneity and emphasize the importance of identifying women at risk for having infants at lower BW quantiles as they may benefit most from earlier and more intensive prenatal care.Instituto Multidisciplinario de Biología Celula

Prenatal care effectiveness and utilization in Brazil

The impact of prenatal care use on birth outcomes has been understudied in South American countries. This study assessed the effects of various measures of prenatal care use on birth weight (BW) and gestational age outcomes using samples of infants born without and with common birth defects from Brazil, and evaluated the demand for prenatal care. Prenatal visits improved BW in the group without birth defects through increasing both fetal growth rate and gestational age, but prenatal care visits had an insignificant effect on BW in the group with birth defects when adjusting for gestational age. Prenatal care delay had no effects on BW in both infant groups but increased preterm birth risk in the group without birth defects. Inadequate care versus intermediate care also increased LBW risk in the group without birth effects. Quantile regression analyses revealed that prenatal care visits had larger effects at low compared with high BW quantiles. Several other prenatal factors and covariates such as multivitamin use and number of previous live births had significant effects on the studied outcomes. The number of prenatal care visits was significantly affected by several maternal health and fertility indicators. Significant geographic differences in utilization were observed as well. The study suggests that more frequent use of prenatal care can increase BW significantly in Brazil, especially among pregnancies that are uncomplicated with birth defects but that are at high risk for low birth weight. Further research is needed to understand the effects of prenatal care use for pregnancies that are complicated with birth defects.Instituto Multidisciplinario de Biología Celula