Juan Antonio Gili

Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population

Objective:To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture.Study Design:Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males.Result:Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; P=0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; P=0.01). Gestational age associated with PTB in PGR rs1942836 at 32–36 weeks (P=0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes.Conclusion:This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB.

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.

Mortalidad infantil por anencefalia en la Argentina: Análisis espacial y temporal (1998-2007)

OBJECTIVE Analyze the spatial and temporal distribution of infant mortality by anencephaly in Argentina in relation with folic acid fortification phases. POPULATION AND METHODS Data came from certificates of live births and deaths in children under 1 year, for the 1998-2007 period (Argentine Ministry of Health). The infant mortality rate attributable to anencephaly for Argentina, geographical regions, provinces and departments were estimated according to the different phases of mandatory fortification with folic acid. Secular trend of infant mortality rate attributable to anencephaly and death risk due to anencephaly, spatial distribution by infant mortality rate attributable to anencephaly cluster and its correlation to latitude and longitude were also analyzed. RESULTS Reduced risk of mortality due to anencephaly (53%) was observed at national level. The greatest decline occurred in Cuyo (69%) and lowest in the Northeast (35%) at regional level. Considerable infant mortality rate attributable to anencephaly heterogeneity was found at departmental level and less at provincial level. A cluster of 5.15/10 000 infant mortality rate attributable to anencephaly was identified in the northeast of Buenos Aires province, consisting of 29 departments, significantly different from the rest of the country. CONCLUSIONS While there was a statistically significant negative secular trend of infant mortality rate attributable to anencephaly, spatial disparities persist. The geographical distribution of anencephaly would guide the search for environmental/ genetic risk factors and strengthen primary prevention strategies, through mandatory fortification, folate intake and folic acid supplementation.

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.

Consumo y exposición al humo de tabaco en mujeres embarazadas de Ecuador

OBJETIVOS: Determinar la frecuencia de tabaquismo y exposicion ambiental al humo de tabaco en mujeres embarazadas de Ecuador y describir los perfiles sociodemograficos asociados con esos factores de riesgo perinatal. METODOS: Estudio descriptivo transversal mediante una encuesta aplicada a mujeres de 18 a 46 anos con mas de 3 meses de embarazo que asistieron entre octubre de 2004 y septiembre de 2005 a sus consultas de seguimiento en siete servicios de maternidad de seis ciudades de Ecuador. Se analizaron los datos demograficos y de exposicion medioambiental (variables independientes) y su relacion con el habito de fumar cigarrillos y la exposicion ambiental al humo de tabaco. RESULTADOS: De las 746 mujeres analizadas, 53,3% habia fumado ocasionalmente y 4,3% habia fumado habitualmente; de estas, 75,0% habia dejado de fumar antes o durante el embarazo. De las encuestadas, 12,9% estuvo expuesta con frecuencia o siempre al humo de tabaco en ambientes cerrados. Tener mayor educacion (11 anos o mas) y un nivel socioeconomico medio o alto, ser caucasica y considerar aceptable que las mujeres de su comunidad fumen se asocio significativa y directamente con el habito de fumar cigarrillos (P < 0,001). En general, 12,9% de las mujeres estuvo expuesta al humo de tabaco y esto se asocio significativamente con ser soltera y cohabitar con fumadores o trabajadores vinculados con la industria del tabaco (P < 0,001). CONCLUSIONES: Se deben disenar e implementar medidas especificas dirigidas no solo a estimular el abandono de este habito en las embarazadas, sino tambien a prevenir que las mujeres en edad reproductiva comiencen a fumar y controlar el entorno fumador en el hogar.

Study on the prevalence and neonatal lethality in patients with selected congenital anomalies as per the data of the National Registry of Congenital Anomalies of Argentina

INTRODUCTION Congenital anomalies (CAs) account for 26% of infant mortality in Argentina. The lethality rate for CAs measures the risk of death among affected infants. OBJECTIVES To describe the prevalence at birth of a group of selected CAs, to estimate the neonatal lethality rate, and to examine its association with different variables. POPULATION AND METHODS The study was conducted using data provided by the National Registry of Congenital Anomalies. Prevalences of encephalocele, spina bifida, gastroschisis, omphalocele, diaphragmatic hernia, esophageal atresia, intestinal atresia, or anorectal malformation were estimated (2009-2013 period). Lethality was assessed at 7 and 28 days of life in affected infants with an isolated anomaly (2013). Association with the following variables was analyzed: sex, gestational age, birth weight, antenatal ultrasound screening, percentage of unmet basic needs in the district where the mother lives, geographic region, and level of care at the hospital where the delivery took place. RESULTS Gastroschisis was the most prevalent CA (8.53/10,000 births), while diaphragmatic hernia was the CA with the highest neonatal lethality rate (66.67%). Out of all selected CAs, there was a significant association between an higher gestational age and survival at 7 days -OR: 0.81 (0.70-0.95)- and survival at 28 days -OR: 0.79 (95% confidence interval |-CI-|: 0.68-0.91)-. A higher percentage of unmet basic needs was associated with a higher lethality for diaphragmatic hernia -OR: 1.59 (95% CI: 1.30-1.95)- and for intestinal atresia or anorectal malformation -OR: 16.00 (95% CI: 1.63-157.24)-. CONCLUSIONS The high prevalence of gastroschisis is consistent with the increase observed globally. Prematurity and a high percentage of unmet basic needs increased the risk of death among affected infants.

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.

Environmental Risk Factors and Perinatal Outcomes in Preterm Newborns, According to Family Recurrence of Prematurity

OBJECTIVE We analyzed the role of environmental risk factors, sociodemographic characteristics, clinical characteristics, and reproductive history in preterm births and their associated perinatal outcomes in families classified according to their histories of preterm recurrence among siblings. STUDY DESIGN A retrospective study was conducted at Nuestra Señora de la Merced Maternity Hospital in the city of Tucumán, Argentina. A total of 348 preterm, non-malformed, singleton children born to multipara women were reviewed. The family history score described by Khoury was applied, and families were classified as having no, medium, or high genetic aggregation. RESULTS Families with no familial aggregation showed a higher rate of short length of cohabitation, maternal urinary tract infections during the current pregnancy, and maternal history of miscarriage during the previous pregnancy. Families with a high level of aggregation had a significantly higher incidence of pregnancy complications, such as diabetes, hypertension, and immunologic disorders. CONCLUSION Reproductive histories clearly differed between the groups, suggesting both a different response to environmental challenges based on genetic susceptibility and the activation of different pathophysiological pathways to determine the duration of pregnancy in each woman.