Genetic susceptibility for retinopathy of prematurity and its associated comorbidities.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the leading cause of child blindness. Preterm newborns of very low gestational age (GA) and very low birth weight are at the greatest risk. Our objective was to evaluate the role of genetic variants associated with ROP risk and its comorbidities in an Argentinian sample of premature infants. METHODS: A sample of 437 preterm infants <33 weeks GA, born at a maternity hospital in Tucumán, Argentina, 2005-2010, was analyzed. Environmental factors, perinatal outcomes, and fourteen single nucleotide polymorphisms associated with ROP were evaluated, comparing ROP with non-ROP newborns. A lasso logistic regression was performed to select variables; then, a conditional logistic regression was used to identify ROP maternal and perinatal risk factors adjusting by maternal and gestational ages, respectively. RESULTS: ROP maternal risk factors were alcohol intake, periodontal infections, and severe stress. Respiratory distress, sepsis, and intracranial hemorrhage were the ROP perinatal risk factors. Markers rs186085 of EPAS1 and rs427832 of AGTR1 were significantly associated with ROP newborns. CONCLUSION: We identified three maternal and three perinatal risk factors associated with ROP. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP. IMPACT: Genetic and environmental risk factors associated with ROP and its comorbidities are evaluated in a Latin American population. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP. Three maternal and three perinatal risk factors associated with ROP were also identified. A matrix of significant relationships among genetic markers and comorbidities is presented. Reported data may help develop more effective preventive measures for ROP in the Latin American region.

Neonatal anthropometry of malformed newborns: A large South American population-based study.

BACKGROUND: Population-based anthropometric evaluation of malformed newborns is scarce. OBJECTIVES: To evaluate malformed newborns' foetal growth using the ICD 10 malformations' classification. METHODS: A study including 33,769 newborns (14,857 malformed and 18,912 nonmalformed), selected from 678,840 births from nine South American countries, period 2010-2018, was conducted. Prevalence of severe small and small for gestational age was calculated for malformed and nonmalformed newborns classified by preterm birth categories. Prevalence and relative risk (RR) with its 95% confidence interval (CI) were calculated. The associations between anthropometric phenotypes and congenital malformations were evaluated with generalized linear models. RESULTS: Prevalence of preterm and term severe small and small for gestational age newborns was higher in malformed than that in nonmalformed neonates. For grouped ICD 10 malformations categories, the RR for severe small for gestational age was 2.88 (95% CI 2.51, 3.30) and 2.10 (95% CI 1.92, 2.30) for small for gestational age. For at-term and preterm malformed newborns, the RR for severe small for gestational age was 2.21 (95% CI 1.87, 2.61) and 3.21 (95% CI 2.52, 4.10), respectively; for small for gestational age, the RR was 2.31 (95% CI 2.11, 2.53) for at-term newborns and 2.58 (95% CI 2.16, 3.08) for preterm ones. CONCLUSIONS: Prevalence and relative risk of severe small and small for gestational age vary according to the group of malformations and gestational age; they increase in congenital malformations of the nervous, respiratory and digestive systems, and in chromosomal abnormalities and are lower for malformations of eye, ear, face and neck and cleft lip and palate. Foetal growth considered together with malformed newborns' gestational age would allow for inferring different risks of morbidity and mortality.

Preterm birth etiological pathways: a Bayesian networks and mediation analysis approach.

BACKGROUND: The aim of this study was to determine the mediating effect of spontaneous preterm birth (PTB) main predictors that would allow to suggest etiological pathways. METHODS: We carried out a case-control study, including sociodemographic characteristics, habits, health care, and obstetric data of multiparous women who gave birth at a maternity hospital from Tucumán, Argentina, between 2005 and 2010: 998 women without previous PTB who delivered at term and 562 who delivered preterm. We selected factors with the greatest predictive power using a penalized logistic regression model. A data-driven Bayesian network including the selected factors was created where we identified pathways and performed mediation analyses. RESULTS: We identified three PTB pathways whose natural indirect effect was greater than zero with a 95% confidence interval: maternal age less than 20 years mediated by few prenatal visits, vaginal bleeding in the first trimester mediated by vaginal bleeding in the second trimester, and urinary tract infection mediated by vaginal bleeding in the second trimester. The effect mediated in these pathways showed greater sensitivity to confounders affecting the variables mediator-outcome and exposure-mediator in the same direction. CONCLUSION: The identified pathways suggest PTB etiological lines related to social disparities and exposure to genitourinary tract infections. IMPACT: Few prenatal visits (<5) and vaginal bleeding are two of the main predictors for spontaneous preterm birth in the studied population. Few prenatal visits mediates part of the risk associated with maternal age less than 20 years and vaginal bleeding in the second trimester mediates part of the risk associated with vaginal bleeding in the first trimester and with urinary tract infection. Social disparities and exposure to genitourinary tract infections would be etiological lines of spontaneous preterm birth.

Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs.

BACKGROUND: Esophageal atresia (EA) affects around 2.3-2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. METHODS: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s-2010s. RESULTS: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1-90.5) at 1-month, 84.5% (95% CI 83.0-85.9) at 1-year and 82.7% (95% CI 81.2-84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. CONCLUSIONS: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies.

Analysis of Mortality among Neonates and Children with Spina Bifida: An International Registry-Based Study, 2001-2012.

BACKGROUND: Medical advancements have resulted in better survival and life expectancy among those with spina bifida, but a significantly increased risk of perinatal and postnatal mortality for individuals with spina bifida remains. OBJECTIVES: To examine stillbirth and infant and child mortality among those affected by spina bifida using data from multiple countries. METHODS: We conducted an observational study, using data from 24 population- and hospital-based surveillance registries in 18 countries contributing as members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Cases of spina bifida that resulted in livebirths or stillbirths from 20 weeks' gestation or elective termination of pregnancy for fetal anomaly (ETOPFA) were included. Among liveborn spina bifida cases, we calculated mortality at different ages as number of deaths among liveborn cases divided by total number of liveborn cases with spina bifida. As a secondary outcome measure, we estimated the prevalence of spina bifida per 10 000 total births. The 95% confidence interval for the prevalence estimate was estimated using the Poisson approximation of binomial distribution. RESULTS: Between years 2001 and 2012, the overall first-week mortality proportion was 6.9% (95% CI 6.3, 7.7) and was lower in programmes operating in countries with policies that allowed ETOPFA compared with their counterparts (5.9% vs. 8.4%). The majority of first-week mortality occurred on the first day of life. In programmes where information on long-term mortality was available through linkage to administrative databases, survival at 5 years of age was 90%-96% in Europe, and 86%-96% in North America. CONCLUSIONS: Our multi-country study showed a high proportion of stillbirth and infant and child deaths among those with spina bifida. Effective folic acid interventions could prevent many cases of spina bifida, thereby preventing associated childhood morbidity and mortality.

Limb body wall complex: Its delineation and relationship with amniotic bands using clustering methods.

BACKGROUND: Despite the numerous reports on the limb body wall complex (LBWC), this association has never been adequately defined. Amniotic bands (AB) are frequently present but their role remains unclear. Since most reports were based on clinical and often subjective diagnoses, the aim of this work was to define LBWC and the role of AB, minimizing subjectivity. METHODS: Data were obtained from the ECLAMC maternity hospitals network database. A total of 450 live and stillborn infants, born during 1967-2013, with AB or the LBWC were selected. A hierarchical cluster analysis was used to classify cases into homogeneous groups (sharing similar associated defects); robustness of the classification was confirmed with a discriminant analysis. The frequency of associated defects was compared among groups; those whose frequency differed significantly were included in a logistic regression to establish their association within each group. RESULTS: The cluster analysis identified two groups: a body wall defect (BWD) predominating in one, AB in the other. These groups were further divided into: BWD (cases with only BWD), AB (with only AB), BWD + AB, and NONE (with neither). Association with caudal defects and lower limb amelia was observed for BWD, with cephalic defects and upper limb amputations for BWD + AB. CONCLUSIONS: The results, obtained with the least possible subjectivity, indicated that BWD and BWD + AB are different conditions. Since BWD specifically associates with amelia, we propose that this defect and not any limb deficiency should be considered as inclusion criterium and that it should be included in the BWD acronym as LBWC.

Prevalencia del bajo peso al nacer en un escenario de depresión económica en Argentina / Prevalence of low birth weight in a scenario of economic depression in Argentina

Introducción. El bajo peso al nacer (BPN) es considerado un indicador general de salud por su relación con complicaciones en la vida del recién nacido y por ser una de las primeras causas de mortalidad infantil. Es multifactorial y, entre sus determinantes, se incluyen los socioeconómicos. Objetivo. Evaluar el impacto de la desigualdad económica sobre la prevalencia del BPN, cuantificando el efecto diferencial según edad y educación materna y nivel de atención. Población y métodos. Estudio epidemiológico de diseño transversal, en el cual se analizaron los nacimientos ocurridos en Argentina desde 2001 a 2013 con datos obtenidos del Registro Nacional de los nacimientos, perteneciente a la Dirección de Estadísticas e Información en Salud (DEIS). Se estudió la variación temporal de la prevalencia de recién nacidos con BPN (< 2500 gramos) y su relación con indicadores demográficos y socioeconómicos. Se evaluó su asociación a través de modelos de regresión logística. Resultados. Se incluyeron 9 001 960 nacimientos. Se observó un incremento en la prevalencia de recién nacidos con BPN durante la crisis económica de 2001 -de un 6% en 2002 y un 7% en 2003-. Fue heterogéneo y tuvo mayor impacto en hospitales públicos (razón de prevalencia -RP-= 1,03) y madres adolescentes (RP= 1,07) y ningún impacto sobre la educación materna baja (RP= 0,99). Conclusiones. El impacto de la desigualdad socioeconómica sobre la prevalencia de bajo peso fue significativo y heterogéneo, más importante en hospitales públicos y madres en edades extremas.

Introduction. Low birth weight (LBW) is considered a general indicator of health because it is related to complications in the life of a newborn infant and is one of the leading causes of infant mortality. It is a multifactorial indicator, and its determinants include socioeconomic factors. Objective. To assess the impact of economic inequality on the prevalence of LBW by quantifying its differential effect by maternal age, level of maternal education, and level of care. Population and methods. Epidemiological, cross-sectional study that analyzed all births occurred in Argentina between 2001 and 2013 based on data provided by the National Registry of births, corresponding to the Health Statistics and Information Department. The temporal variation in the prevalence of LBW newborn infants (< 2500 grams) and its relation to demographic and socioeconomic indicators were studied. Its association was assessed using logistic regression models. Results. A total of 9 001 960births were included. The prevalence of LBW newborn infants during the 2001 economic crisis increased -6% in 2002 and 7% in 2003- The impact was heterogeneous and higher on public hospitals (--1;PR--3; = 1.03) and adolescent mothers (PR=1.07), but no impact was observed on a low level of maternal education (PR= 0.99). Conclusions. The impact of socioeconomic inequality on the prevalence of LBW was significant and heterogeneous, especially on public hospitals and mothers at the extremes of maternal age.

Prevalence of low birth weight in a scenario of economic depression in Argentina. / Prevalencia del bajo peso al nacer en un escenario de depresión económica en Argentina.

INTRODUCTION: Low birth weight (LBW) is considered a general indicator of health because it is related to complications in the life of a newborn infant and is one of the leading causes of infant mortality. It is a multifactorial indicator, and its determinants include socioeconomic factors. OBJECTIVE: To assess the impact of economic inequality on the prevalence of LBW by quantifying its differential effect by maternal age, level of maternal education, and level of care. POPULATION AND METHODS: Epidemiological, cross-sectional study that analyzed all births occurred in Argentina between 2001 and 2013 based on data provided by the National Registry of births, corresponding to the Health Statistics and Information Department. The temporal variation in the prevalence of LBW newborn infants (< 2500 grams) and its relation to demographic and socioeconomic indicators were studied. Its association was assessed using logistic regression models. RESULTS: A total of 9 001 960births were included. The prevalence of LBW newborn infants during the 2001 economic crisis increased -6% in 2002 and 7% in 2003- The impact was heterogeneous and higher on public hospitals (|-1;PR|-3; = 1.03) and adolescent mothers (PR=1.07), but no impact was observed on a low level of maternal education (PR= 0.99). CONCLUSIONS: The impact of socioeconomic inequality on the prevalence of LBW was significant and heterogeneous, especially on public hospitals and mothers at the extremes of maternal age.

Introducción. El bajo peso al nacer (BPN) es considerado un indicador general de salud por su relación con complicaciones en la vida del recién nacido y por ser una de las primeras causas de mortalidad infantil. Es multifactorial y, entre sus determinantes, se incluyen los socioeconómicos. Objetivo. Evaluar el impacto de la desigualdad económica sobre la prevalencia del BPN, cuantificando el efecto diferencial según edad y educación materna y nivel de atención. Población y métodos. Estudio epidemiológico de diseño transversal, en el cual se analizaron los nacimientos ocurridos en Argentina desde 2001 a 2013 con datos obtenidos del Registro Nacional de los nacimientos, perteneciente a la Dirección de Estadísticas e Información en Salud (DEIS). Se estudió la variación temporal de la prevalencia de recién nacidos con BPN (< 2500 gramos) y su relación con indicadores demográficos y socioeconómicos. Se evaluó su asociación a través de modelos de regresión logística. Resultados. Se incluyeron 9 001 960 nacimientos. Se observó un incremento en la prevalencia de recién nacidos con BPN durante la crisis económica de 2001 -de un 6% en 2002 y un 7% en 2003-. Fue heterogéneo y tuvo mayor impacto en hospitales públicos (razón de prevalencia -RP-= 1,03) y madres adolescentes (RP= 1,07) y ningún impacto sobre la educación materna baja (RP= 0,99). Conclusiones. El impacto de la desigualdad socioeconómica sobre la prevalencia de bajo peso fue significativo y heterogéneo, más importante en hospitales públicos y madres en edades extremas.

Neural tube defects: Sex ratio changes after fortification with folic acid.

BACKGROUND: Historically, neural tube defects (NTDs) have predominated in female infants but the reasons remain unclear. In South America, the pre- folic acid fortification (FAF) rates of NTDs were around 18/10,000 births for females and 12/10,000 births for males, with an estimated sex ratio (male/female) of 0.67. During the post- FAF period, unpublished routine reports have indicated changes in the sex ratio for these defects while some descriptive reports are controversial. To date and to our knowledge, however, no studies specifically focusing on these changes to test this hypothesis directly have been undertaken. The aim of this study was to analyze changes in the sex ratio of infants with NTDs after FAF in South American countries. MATERIALS AND METHODS: With a descriptive cross-sectional study design, 2,597 infants with isolated NTDs born between 1990 and 2013 in 3 countries participating in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network were included: (Chile N = 521 and Argentina N = 1,619 [with FAF policies]; Venezuela N = 457 [without FAF policies; used as control]; total births = 2,229,561). The differences-in-differences method and Poisson regressions were used to evaluate the sex ratio shift from female to male before vs. after FAF, and to assess whether these differences were related to the fortification. RESULTS AND CONCLUSIONS: In Chile and Argentina the prevalence of NTDs, particularly anencephaly and cervico-thoracic spina bifida, showed a greater reduction rate in females than in males after FAF, resulting in a change of the sex ratio of infants with NTDs. Some mechanisms possibly involved in this differential reduction are proposed which might be useful to identify the pathogenesis of NTDs as a whole and specifically of those susceptible to the protective effect of folic acid.

Explaining ethnic disparities in preterm birth in Argentina and Ecuador.

Little is understood about racial/ethnic disparities in infant health in South America. We quantified the extent to which the disparity in preterm birth (PTB; <37 gestational weeks) rate between infants of Native only ancestry and those of European only ancestry in Argentina and Ecuador are explained by household socio-economic, demographic, healthcare use, and geographic location indicators. The samples included 5199 infants born between 2000 and 2011 from Argentina and 1579 infants born between 2001 and 2011 from Ecuador. An Oaxaca-Blinder type decomposition model adapted to binary outcomes was estimated to explain the disparity in PTB risk across groups of variables and specific variables. Maternal use of prenatal care services significantly explained the PTB disparity, by nearly 57% and 30% in Argentina and Ecuador, respectively. Household socio-economic status explained an additional 26% of the PTB disparity in Argentina. Differences in maternal use of prenatal care may partly explain ethnic disparities in PTB in Argentina and Ecuador. Improving access to prenatal care may reduce ethnic disparities in PTB risk in these countries.

Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study.

Objective To describe the prevalence and clinical spectrum of microcephaly in South America for the period 2005-14, before the start of the Zika epidemic in 2015, as a baseline for future surveillance as the Zika epidemic spreads and as other infectious causes may emerge in future.Design Prevalence and case-control study.Data sources ECLAMC (Latin American Collaborative Study of Congenital Malformations) database derived from 107 hospitals in 10 South American countries, 2005 to 2014. Data on microcephaly cases, four non-malformed controls per case, and all hospital births (all births for hospital based prevalence, resident within municipality for population based prevalence). For 2010-14, head circumference data were available and compared with Intergrowth charts.Results 552 microcephaly cases were registered, giving a hospital based prevalence of 4.4 (95% confidence interval 4.1 to 4.9) per 10 000 births and a population based prevalence of 3.0 (2.7 to 3.4) per 10 000. Prevalence varied significantly between countries and between regions and hospitals within countries. Thirty two per cent (n=175) of cases were prenatally diagnosed; 29% (n=159) were perinatal deaths. Twenty three per cent (n=128) were associated with a diagnosed genetic syndrome, 34% (n=189) polymalformed without a syndrome diagnosis, 12% (n=65) with associated neural malformations, and 26% (n=145) microcephaly only. In addition, 3.8% (n=21) had a STORCH (syphilis, toxoplasmosis, other including HIV, rubella, cytomegalovirus, and herpes simplex) infection diagnosis and 2.0% (n=11) had consanguineous parents. Head circumference measurements available for 184/235 cases in 2010-14 showed 45% (n=82) more than 3 SD below the mean, 24% (n=44) between 3 SD and 2 SD below the mean, and 32% (n=58) larger than -2 SD.Conclusion Extrapolated to the nearly 7 million annual births in South America, an estimated 2000-2500 microcephaly cases were diagnosed among births each year before the Zika epidemic began in 2015. Clinicians are using more than simple metrics to make microcephaly diagnoses. Endemic infections are important enduring causes of microcephaly.

Maternal Education Gradients in Infant Health in Four South American Countries.

Objective We investigate gradients (i.e. differences) in infant health outcomes by maternal education in Argentina, Brazil, Chile, and Venezuela and explore channels related to father's education, household labor outcomes, and maternal health, fertility, and use of prenatal services and technology. Methods We employ secondary interview and birth record data similarly collected across a network of birth hospitals from the early 1980s through 2011 within the Latin American Collaborative Study of Congenital Anomalies (ECLAMC). Focusing on children without birth defects, we estimate gradients in several infant health outcomes including birth weight, gestational age, and hospital discharge status by maternal education using ordinary least squares regression models adjusting for several demographic factors. To explore channels, we add as covariates father's education, parental occupational activity, maternal health and fertility history, and use of prenatal services and technology and evaluate changes in the coefficient of maternal education. We use the same models for each country sample. Results We find important differences in gradients across countries. We find evidence for educational gradients in preterm birth in three countries but weaker evidence for gradients in fetal growth. The extent to which observed household and maternal factors explain these gradients based on changes in the regression coefficient of maternal education when controlling for these factors as covariates also varies between countries. In contrast, we generally find evidence across all countries that higher maternal education is associated with increased use of prenatal care services and technology. Conclusions Our findings suggest that differences in infant health by maternal education and their underlying mechanisms vary and are not necessarily generalizable across countries. However, the positive association between maternal education and use of prenatal services and technology is more consistent across examined countries.

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population.

BackgroundPreterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation as follows: idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB.MethodsTwenty-four single-nucleotide polymorphisms (SNPs) were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 were PTB-PPROM, and 210 were PTB-M. These data were analyzed with a Family-Based Association.ResultsPTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, three SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M.ConclusionOur study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes.

The impact of unemployment cycles on child and maternal health in Argentina.

OBJECTIVES: The purpose of this study is to examine the effects of economic cycles in Argentina on infant and maternal health between 1994 and 2006, a period that spans the major economic crisis in 1999-2002. METHODS: We evaluate the effects of province-level unemployment rates on several infant health outcomes, including birth weight, gestational age, fetal growth rate, and hospital discharge status after birth in a sample of 15,000 infants born in 13 provinces. Maternal health and healthcare outcomes include acute and chronic illnesses, infectious diseases, and use of prenatal visits and technology. Regression models control for hospital and year fixed effects and province-specific time trends. RESULTS: Unemployment rise reduces fetal growth rate particularly among high educated parents. Also, maternal poverty-related infectious diseases increase, although reporting of acute illnesses declines (an effect more pronounced among low educated parents). There is also some evidence for reduced access to prenatal care and technology among less educated parents with higher unemployment. CONCLUSIONS: Unemployment rise in Argentina has adversely affected certain infant and maternal health outcomes, but several measures show no evidence of significant change.

Maternal and neonatal epidemiological features in clinical subtypes of preterm birth.

OBJECTIVE: This study was designed to characterize and compare the maternal and newborn epidemiological characteristics through analysis of environmental factors, sociodemographic characteristics and clinical characteristics between the different clinical subtypes of preterm birth (PTB): Idiopathic (PTB-I), premature rupture of the membranes (PTB-PPROM) and medically indicated (PTB-M). The two subtypes PTB-I and PTB-PPROM grouped are called spontaneous preterm births (PTB-S). METHODS: A retrospective, observational study was conducted in 1.291 preterm nonmalformed singleton live-born children to nulliparous and multiparous mother's in Tucumán-Argentina between 2005 and 2010. Over 50 maternal variables and 10 newborn variables were compared between the different clinical subtypes. The comparisons were done to identify heterogeneity between subtypes of preterm birth: (PTB-S) versus (PTB-M), and within spontaneous subtype: (PTB-I) versus (PTB-PPROM). In the same way, two conditional logistic multivariate regressions were used to compare the odds ratio (OR) between PTB-S and PTB-M, as well as PTB-I and PTB-PPROM. We matched for maternal age when comparing maternal variables and gestational age when comparing infant variables. RESULTS: The PTB-I subtype was characterized by younger mothers of lower socio-economic status, PTB-PPROM was characterized by environmental factors resulting from inflammatory processes, and PTB-M was characterized by increased maternal or fetal risk pregnancies. CONCLUSIONS: The main risk factor for PTB-I and PTB-M was having had a prior preterm delivery; however, previous spontaneous abortion was not a risk factor, suggesting a reproductive selection mechanism.

Gastroschisis and young mothers: What makes them different from other mothers of the same age?

BACKGROUND: Although young maternal age has been identified as a risk factor for gastroschisis, its role remains undisclosed. To our knowledge, the differences between young mothers of infants with gastroschisis and young mothers of infants with other pregnancy outcomes have not been established. The aim of this work was to compare characteristics of young mothers whose newborn had gastroschisis with same aged mothers of malformed and nonmalformed control infants, diagnosed within the ECLAMC maternity hospital network. METHODS: Data base records of live and stillborn infants of one of three groups (with isolated gastroschisis, with 1 of 5 other isolated birth defects, and nonmalformed), and whose mothers were younger than 20 years, were selected. Secular trends were obtained for all birth defects; frequencies and odds ratios (OR) of demographic and reproductive variables were compared among the 3 groups. Significantly associated variables were adjusted with a multivariate regression. RESULTS: The association was higher with gastroschisis 1) than with other birth defects for African ancestry, smoking, adequate prenatal control and diagnosis 2) than with nonmalformed controls for maternal illnesses and alcohol 3) and than both for previous pregnancy loss and medication, mainly sex hormones. After adjustment, only previous pregnancy loss maintained its significance when compared with malformed (OR = 2.34; 1.37-3.97; P = 0.002), as well as with nonmalformed (OR = 3.43; 2.07-5.66; P < 0.001) controls. CONCLUSION: A previous pregnancy loss was identified as the main risk factor for gastroschisis, while an increased use of sex hormones, perhaps related to the previous loss, could trigger a disruptive mechanism, due to their thrombophilic effect.

Asociación entre polimorfismos del gen NAT2 y fisura labiopalatina no sindrómica en Argentina / Association between NAT2 polymorphisms with non-syndromic cleft lip with or without cleft palate in Argentina

Background: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment. Aim: To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP. Material and Methods: We analyzed *5 (481C>T), *6 (590G>A) and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT). Results: TDT showed a positive association between allele *5 and NSCLP (odds ratio = 1,6; p = 0,03). Conclusions: The presence of *5 allele is significantly higher in cases with congenital NSCLP.

Disparities in birth weight and gestational age by ethnic ancestry in South American countries.

OBJECTIVES: We examine disparities in birth weight and gestational age by ethnic ancestry in 2000-2011 in eight South American countries. METHODS: The sample included 60,480 singleton live births. Regression models were estimated to evaluate differences in birth outcomes by ethnic ancestry controlling for time trends. RESULTS: Significant disparities were found in seven countries. In four countries-Brazil, Ecuador, Uruguay, and Venezuela-we found significant disparities in both low birth weight and preterm birth. Disparities in preterm birth alone were observed in Argentina, Bolivia, and Colombia. Several differences in continuous birth weight, gestational age, and fetal growth rate were also observed. There were no systematic patterns of disparities between the evaluated ethnic ancestry groups across the study countries, in that no racial/ethnic group consistently had the best or worst outcomes in all countries. CONCLUSIONS: Racial/ethnic disparities in infant health are common in several South American countries. Differences across countries suggest that racial/ethnic disparities are driven by social and economic mechanisms. Researchers and policymakers should acknowledge these disparities and develop research and policy programs to effectively target them.

Determinantes sociales adversos y riesgo para anomalías congénitas seleccionadas / Adverse social determinants and risk for congenital anomalies

Introducción. Diferentes trabajos han relacionando condiciones sociales adversas a nivel familiar y regional con resultados perinatales (mortalidad neonatal, bajo peso y prematuridad), sin embargo, pocos estudiaron el efecto de la pobreza sobre anomalías congénitas. Objetivo. Evaluar el riesgo de ocurrencia de 25 anomalías congénitas y determinantes sociales adversos según el nivel socioeconómico de la familia y de la región. Población y métodos. Estudio caso-control exploratorio, en el que se utilizaron datos del Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). La muestra consistió en 3786 recién nacidos vivos con una única malformación y 13 344 controles, seleccionados entre 546 129 nacimientos, ocurridos en 39 hospitales de Argentina durante el período 1992-2001. Se estimaron los riesgos (OR) directos, indirectos (a través de la región de residencia) y la interacción entre el nivel socioeconómico individual y residencial para cada uno de los 25 defectos congénitos. Resultados. Los defectos labio leporino con/sin paladar hendido (OR= 1,43) y comunicación interventricular (OR= 1,38) mostraron un riesgo significativamente mayor en el nivel socioeconómico más bajo. Los niveles socioeconómicos bajos se asociaron de manera significativa con una mayor frecuencia de consanguinidad parental, ancestros nativos, edad materna menor de 19 años, más de 4 embarazos, bajo número de visitas prenatales y residencia en regiones desfavorables. Conclusión. La fisura labial con o sin paladar hendido y los defectos del tabique interventricular estuvieron asociados significativamente con un nivel socioeconómico más bajo. La falta de planificación familiar, de control prenatal y la exposición a agentes ambientales o teratógenos pueden explicar estos hallazgos.

Introduction. Different studies have related familiar and regional adverse social conditions to perinatal outcome (neonatal mortality, low birth weight and prematurity); however, few studies have studied the effect of poverty on congenital anomalies. Objective. To assess the hazard ratio of 25 congenital anomalies and adverse social determinants as per the socioeconomic level of families and regions. Population and methods. Exploratory, case-control study using data from the Latin-American Collaborative Study of Congenital Malformations (Estudio Colaborativo Latinoamericano deMalformaciones Congenitas, ECLAMC). The sample consisted of 3786live newborninfantswitha singlemalformation and 13 344 controls selected among 546 129 births occurred in 39 hospitals from Argentina in the 19922001 period. Both direct and indirect (residence) risks (OR) were estimated, together with the interaction between the individual and residential socioeconomic levels for each of the 25 congenital anomalies. Results.Cleft lip with/without cleft palate (OR= 1.43) and ventricular septal defect (OR= 1.38) showed a significantly higher risk in the lower socioeconomic level. Low socioeconomic levels were significantly associated with a higher frequency of parental sibship (blood relationship); native descent; maternal age younger than 19 years old; more than four pregnancies; a low number of antenatal care visits; and residence in deprived regions. Conclusion. Cleft lip with/without cleft palate and ventricular septal defects were significantly associated with a lower socioeconomic level. Lack of family planning and antenatal care; and exposure to environmental or teratogenic agents may account for these findings.

Determinantes sociales adversos y riesgo para anomalías congénitas seleccionadas / Adverse social determinants and risk for congenital anomalies

Introducción. Diferentes trabajos han relacionando condiciones sociales adversas a nivel familiar y regional con resultados perinatales (mortalidad neonatal, bajo peso y prematuridad), sin embargo, pocos estudiaron el efecto de la pobreza sobre anomalías congénitas. Objetivo. Evaluar el riesgo de ocurrencia de 25 anomalías congénitas y determinantes sociales adversos según el nivel socioeconómico de la familia y de la región. Población y métodos. Estudio caso-control exploratorio, en el que se utilizaron datos del Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). La muestra consistió en 3786 recién nacidos vivos con una única malformación y 13 344 controles, seleccionados entre 546 129 nacimientos, ocurridos en 39 hospitales de Argentina durante el período 1992-2001. Se estimaron los riesgos (OR) directos, indirectos (a través de la región de residencia) y la interacción entre el nivel socioeconómico individual y residencial para cada uno de los 25 defectos congénitos. Resultados. Los defectos labio leporino con/sin paladar hendido (OR= 1,43) y comunicación interventricular (OR= 1,38) mostraron un riesgo significativamente mayor en el nivel socioeconómico más bajo. Los niveles socioeconómicos bajos se asociaron de manera significativa con una mayor frecuencia de consanguinidad parental, ancestros nativos, edad materna menor de 19 años, más de 4 embarazos, bajo número de visitas prenatales y residencia en regiones desfavorables. Conclusión. La fisura labial con o sin paladar hendido y los defectos del tabique interventricular estuvieron asociados significativamente con un nivel socioeconómico más bajo. La falta de planificación familiar, de control prenatal y la exposición a agentes ambientales o teratógenos pueden explicar estos hallazgos.(AU)

Introduction. Different studies have related familiar and regional adverse social conditions to perinatal outcome (neonatal mortality, low birth weight and prematurity); however, few studies have studied the effect of poverty on congenital anomalies. Objective. To assess the hazard ratio of 25 congenital anomalies and adverse social determinants as per the socioeconomic level of families and regions. Population and methods. Exploratory, case-control study using data from the Latin-American Collaborative Study of Congenital Malformations (Estudio Colaborativo Latinoamericano deMalformaciones Congenitas, ECLAMC). The sample consisted of 3786live newborninfantswitha singlemalformation and 13 344 controls selected among 546 129 births occurred in 39 hospitals from Argentina in the 19922001 period. Both direct and indirect (residence) risks (OR) were estimated, together with the interaction between the individual and residential socioeconomic levels for each of the 25 congenital anomalies. Results.Cleft lip with/without cleft palate (OR= 1.43) and ventricular septal defect (OR= 1.38) showed a significantly higher risk in the lower socioeconomic level. Low socioeconomic levels were significantly associated with a higher frequency of parental sibship (blood relationship); native descent; maternal age younger than 19 years old; more than four pregnancies; a low number of antenatal care visits; and residence in deprived regions. Conclusion. Cleft lip with/without cleft palate and ventricular septal defects were significantly associated with a lower socioeconomic level. Lack of family planning and antenatal care; and exposure to environmental or teratogenic agents may account for these findings.(AU)