Mariela S. Pawluk

Prevalencia al nacimiento de 27 anomalías congénitas seleccionadas, en 7 regiones geográficas de la Argentina

OBJECTIVE The aim of the present work was to estimate the frequency of 27 birth defects in 7 geographical regions of Argentina. MATERIAL AND METHODS Observational, cross-sectional, descriptive design. A sample of 21,844 new born with birth defects was selected, ascertained from 855,220 births, between 1994 and 2007, in 59 hospitals belonging to the ECLAMC network. In order to identify regions of high frequency a Poisson regression was used, adjusted by different hospitals from the same region. The model included a time variable to detect secular trends and 6 dummy variables for 7 predefined geographical regions: Metropolitana (MET); Pampa (PAM); Centro (CEN); Cuyo (CUY); Noroeste (NOA); Nordeste (NEA) and Patagonia (PAT). RESULTS High frequencies regional analysis showed the following significant results: PAM: severe hypospadias; CEN: spina bifida, microtia, cleft lip with cleft palate, polycystic kidney, postaxial polydactyly and Down syndrome; CUY: postaxial polydactyly; NOA: omphalocele, gastroschisis, cleft lip without cleft palate, cleft lip with cleft palate, anorectal atresia/stenosis, indeterminate sex, preaxial polydactyly and pectoral agenesis; PAT: cleft lip without cleft palate. CONCLUSION Out of the 27 congenital anomalies analyzed, fourteen showed a frequency significatively higher in one or more regions.

Disparities in Birth Weight and Gestational Age by Ethnic Ancestry in South American countries

ObjectivesWe examine disparities in birth weight and gestational age by ethnic ancestry in 2000–2011 in eight South American countries.MethodsThe sample included 60,480 singleton live births. Regression models were estimated to evaluate differences in birth outcomes by ethnic ancestry controlling for time trends.ResultsSignificant 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.ConclusionsRacial/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.

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.

Maternal and neonatal epidemiological features in clinical subtypes of preterm birth

Abstract 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.

Is Gravidity 4+ a Risk Factor for Oral Clefts? A Case-Control Study in Eight South American Countries Using Structural Equation Modeling

Background There is disagreement about the association between cleft lip with or without cleft palate and multigravidity, which could be explained by differences of adjusting for maternal age, Amerindian ancestry, and socioeconomic status. Objective The aim was to evaluate gravidity 4+ (four or more gestations) as a risk factor for cleft lip with or without cleft palate in South America. Design We used a matched (1:1) case-control study with structural equation modeling for related causes. Data were obtained from 1,371,575 consecutive newborn infants weighing ≥500 g who were born in the hospitals of the Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC) network between 1982 and 1999. There were a total of 1,271 cases with cleft lip with or without cleft palate (excluding midline and atypical cleft lip with or without cleft palate). A total of 1,227 case-control pairs were obtained, matched by maternal age, newborn gender, and year and place of birth. Potential confounders and intermediary variables were analyzed with structural equation modeling. Results The crude risk of gravidity 4+ was 1.41 and the 95% confidence interval was 1.14 to 1.61. When applying structural equation modeling, the effect of multigravidity on the risk of cleft lip with or without cleft palate was 1.22 and the 95% confidence interval was 0.91 to 1.39. Conclusions Multigravid mothers (more than four gestations) showed no greater risk of bearing children who had cleft lip with or without cleft palate than mothers with two or three births. Therefore, the often observed and reported association between multigravidity and oral clefts likely reflects the effect of other risk factors related to low socioeconomic status in South American populations.

High Birth Prevalence Rates for Congenital Anomalies in South American Regions.

© 2015 Wolters Kluwer Health, Inc. All rights reserved. www.epidem.com | e53 exists between confounding bias reduction and increased bias and variance due to nonpositivity.4 to investigate this trade-off weights were progressively truncated for each method, and as levels of weight truncation increased, the marginal structural model effect estimates became more similar to the estimate from ordinary adjustment for timevarying covariates (table). the detailed analysis is presented in the eAppendix (http://links.lww.com/eDe/A939). to assess the relation between weight truncation and confounder imbalance, the inverse probability weights were used to fit a weighted exposure model with the R2 expected to be approximately zero.5 to find the level of truncation leading to a minimal confounder imbalance (lowest R2), this analysis was repeated for different levels of weight truncation. the normal exposure model (before weighting) had a R2 of 0.51, while refitting this exposure model with untruncated weights resulted in an increased R2 of 0.54. this indicates that untruncated weights from the normal model increased confounder imbalance. For the normal inverse probability weighted model, the minimum imbalance was observed at 4% truncation (R2 = 0.124). this indicates that there is still an association between confounders and exposure after weighting which may be due to exposure model misspecification. Noting the level of imbalance estimated by the weighted exposure model only quantifies imbalance with respect to that particular specification and distributional form of the exposure model, methods to assess balance with respect to separate confounders could be used.6 Despite large differences in weight distributions between methods for obtaining inverse probability weighting for continuous exposures, different methods yielded similar exposure–outcome effect estimates. However, these results should be interpreted cautiously since large untruncated weights, and remaining imbalance after truncation, suggest that nonpositivity (possibly with respect to a combination of confounders) may invalidate estimates. ACKNOWLEDGMENTS The authors thank P. M. C. Klein Klouwenberg, MD, PharmD, and W. Pasma, DVM, Department of Intensive Care Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands, for their support and assistance in data acquisition and data management.

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

ABSTRACT 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.

Descriptive analysis of high birth prevalence rate geographical clusters of congenital anomalies in South America.

BACKGROUND The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and sociocultural variations throughout the world. In South America (SA), high birth prevalence regions of congenital anomalies have been observed. The aim of this study was to identify, describe, and characterize geographical clusters of congenital anomalies in SA. METHODS This observational descriptive study is based on clinical epidemiological data registered by the Latin-American Collaborative Study of Congenital Malformations network. Between 1995 and 2012, a total of 25,082 malformed newborns were ascertained from 2,557,424 births at 129 hospitals in SA. The spatial scan statistic was used to determine geographical regions with high BPR of CAs. The BPR was obtained with a Poisson regression model. Odds ratios were estimated for several risk factors inside the geographical clusters. RESULTS We confirmed the existence of high BPR regions of CAs in SA. Indicators of low socioeconomic conditions, such as a low maternal education, extreme age childbearing, infectious diseases, and medicine use during pregnancy were detected as risk factors inside these regions. Native and African ancestries with high frequency of consanguineous marriages could explain partially these high BPR clusters. CONCLUSION The recognition of clusters could be a starting point in the identification of susceptibility genes associated with the occurrence of CA in high BPR regions.

Minor anomalies: can they predict specific major defects? A study based on 23 major and 14 minor anomalies in over 25,000 newborns with birth defects.

BACKGROUND Minor anomalies (mAs) are morphological features with little clinical relevance that have been mentioned as possible predictors of major defects (MDs). OBJECTIVES To identify the preferential associations between selected MDs and mAs and to establish if mAs can serve as predictors for specific MDs. STUDY DESIGN Information of newborns with birth defects was obtained from the ECLAMC (Latin American Collaborative Study of Congenital Malformations) database. The sample consisted of 27,247 live- and stillborn newborns with multiple malformations that included at least one of the selected MDs or mAs. The odds ratio and predictive values were calculated for significant associations, and concurrence rates in first degree relatives. RESULTS A total of 33 significant minor-major associations were identified. Single umbilical artery (SUA) and preauricular tags were the most frequent mAs; the former was associated with 10 MDs, the latter only with microtia. The highest positive predictive value was shown by SUA for anal atresia. Newborns with preauricular tags had significantly more relatives with microtia than expected. CONCLUSIONS No new relevant associations between MDs and mAs were identified and few mAs seem to serve as predictors for specific MDs in the same newborn. However, preauricular tags can predict the occurrence of microtia in other family members.