Indirect Effects of Neighbourhood Socioeconomic Status on Preterm Birth Risk in an Argentine Population.

BACKGROUND: Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to determine the indirect effects of neighbourhood socioeconomic status (NSES) on the risk of spontaneous PTB. METHODS: We carried out a retrospective case-control study including sociodemographic and obstetric data of multigravid women who gave birth at a maternity hospital in Tucumán, Argentina, between 2005 and 2010: 949 women without previous PTB nor pregnancy loss who delivered at term and 552 who had spontaneous PTB. NSES was estimated from the Unsatisfied Basic Needs index of census data. Variables selected through penalised regressions were used to create a data-driven Bayesian network; then, pathways were identified and mediation analyses performed. RESULTS: Maternal age less than 20 years mediated part of the protective effect of high NSES on spontaneous PTB [natural indirect effect (NIE) -0.0125, 95% confidence interval (CI) (-0.0208, -0.0041)] and on few prenatal visits (< 5) [NIE - 0.0095, 95% CI (-0.0166, -0.0025)]. These pathways showed greater sensitivity to unobserved confounders that affect the variables mediator-outcome in the same direction, and exposure-mediator in the opposite direction. They did not show sensitivity to observed potential confounders, nor to the parameterization used to define NSES. Meanwhile, urinary tract infections showed a trend in mediating the effect of low NSES on spontaneous PTB [NIE 0.0044, 95% CI (-0.0006, 0.0093), P 0.0834]. CONCLUSIONS: High NSES has protective indirect effects on spontaneous PTB risk, mainly associated with a lower frequency of teenage pregnancy.

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.

Gene-environment interactions and preterm birth predictors: A Bayesian network approach.

Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify gene-environment interactions associated with spontaneous PTB or its predictors. We carried out a retrospective case-control study including parental sociodemographic and obstetric data as well as newborn genetic variants of 69 preterm and 61 at term newborns born at a maternity hospital from Tucumán, Argentina, between 2005 and 2010. A data-driven Bayesian network including the main PTB predictors was created where we identified gene-environment interactions. We used logistic regressions to calculate the odds ratios and confidence intervals of the interactions. From the main PTB predictors (nine exposures and six genetic variants) we identified an interaction between low neighbourhood socioeconomic status and rs2074351 (PON1, genotype GG) variant that was associated with an increased risk of toxoplasmosis (odds ratio 12.51, confidence interval 95%: 1.71 - 91.36). The results of this exploratory study suggest that structural social disparities could influence the PTB risk by increasing the frequency of exposures that potentiate the risk associated with individual characteristics such as genetic traits. Future studies with larger sample sizes are necessary to confirm these findings.

Genes, exposures, and interactions on preterm birth risk: an exploratory study in an Argentine population.

Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify associations of spontaneous PTB with genetic variants, exposures, and interactions between and within them. We carried out a retrospective case-control study including parental sociodemographic and obstetric data, and fetal genetic variants. We sequenced the coding and flanking regions of five candidate genes from the placental blood cord of 69 preterm newborns and 61 at term newborns. We identify the characteristics with the greatest predictive power of PTB using penalized regressions, in which we include exposures (E), genetic variants (G), and two-way interactions. Few prenatal visits (< 5) was the main predictor of PTB from 26 G, 35 E, 299 G × G, 564 E × E, and 875 G × E evaluated terms. Within the fetal genetic characteristics, we observed associations of rs4845397 (KCNN3, allele T) variant; G × G interaction between rs12621551 (COL4A3, allele T) and rs73993878 (COL4A3, allele A), which showed sensitivity to anemia; and G × G interaction between rs11680670 (COL4A3, allele T) and rs2074351 (PON1, allele A), which showed sensitivity to vaginal discharge. The results of this exploratory study suggest that social disparities and metabolic pathways linked to uterine relaxation, inflammation/infections, and collagen metabolism would be involved in PTB etiology. Future studies with a larger sample size are necessary to confirm these findings and to analyze a greater number of exposures.

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.

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.

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.

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.

[Screening for symptoms of depression during postpartum and the long term follow up: temporal stability and associated factors]. / Detección de síntomas depresivos durante el postparto inmediato y el seguimiento a largo plazo: estabilidad temporal y factores asociados.

AIMS: To describe the frequency of depressive symptoms compatible with a postpartum depression diagnosis, the associated factors and the temporal stability. METHODS: During 2006-2007 398 hospitalized puerperal women who attended CEMIC were interviewed 5 days after childbirth using the Edinburgh Postnatal Depression Scale and a socio-demographic questionnaire. A logistic regression analysis was performed to identify associated factors with a positive screening. During the following 6-12 months a follow up was carried with two groups of similar characteristics. RESULTS: The frequency of depressive symptoms at post partum was 17.8% (cut off = 10). Depressive history and neonatal intensive care were significantly related to a positive screening. From the 110 interviewed women, 24 were positive in the follow-up. CONCLUSION: The prevalence of risk for postpartum depression in the sample of patients surveyed is within the parameters reported in international literature. At the 6 month follow up, 6 previously asymptomatic women during the first screening turned on positive. It is theorize the existence of potential postpartum depression cases that can manifest up to a year after childbirth.

Estimación del peso fetal en nuestra población: la precisión de los modelos originados en otras poblaciones / Estimation of fetal weight in our population: the precision of the models originate in other populations

Una de las principales variables en la morbimortalidad perinatal es el peso al nacer. El objetivo del siguiente trabajo es determinar la precisión de los modelos ecográficos actualmente más utilizados en la estimación del peso fetal en nuestra población. Se examinaron en forma retrospectiva durante un período de 36 meses un total de 200 embarazadas con gestaciones únicas que tuvieron un parto dentro de los 7 días posteriores a un examen ecográfico. El Diámetro Biparietal (DBP), la Longitud Femoral (LF) y la Circunferencia Abdominal (CA) fueron medidos en todos los casos. La estimación del peso fetal fue efectuada por cuatro métodos diferentes basados en el modelo de regresión lineal que utilizaron respectivamente el CA; CA-DBP; CA y LF; YDBP, LF y CA. Los resultados fueron comparados con el peso al nacer al momento del parto. El método de Shepard fue el que mostró mayor precisión en la estimación del peso fetal: Error porcentual: - 0,86; Desviación Estándar: 9,41. Los otros modelos presentaron diferentes variaciones para distintos rangos de peso al nacer. Todas las fórmulas demostraron una subestimación significativa a partir del séptimo día de intervalo entre el examen ecográfico y el momento del parto (AU)

Estimación del peso fetal en nuestra población: la precisión de los modelos originados en otras poblaciones / Estimation of fetal weight in our population: the precision of the models originate in other populations

Una de las principales variables en la morbimortalidad perinatal es el peso al nacer. El objetivo del siguiente trabajo es determinar la precisión de los modelos ecográficos actualmente más utilizados en la estimación del peso fetal en nuestra población. Se examinaron en forma retrospectiva durante un período de 36 meses un total de 200 embarazadas con gestaciones únicas que tuvieron un parto dentro de los 7 días posteriores a un examen ecográfico. El Diámetro Biparietal (DBP), la Longitud Femoral (LF) y la Circunferencia Abdominal (CA) fueron medidos en todos los casos. La estimación del peso fetal fue efectuada por cuatro métodos diferentes basados en el modelo de regresión lineal que utilizaron respectivamente el CA; CA-DBP; CA y LF; YDBP, LF y CA. Los resultados fueron comparados con el peso al nacer al momento del parto. El método de Shepard fue el que mostró mayor precisión en la estimación del peso fetal: Error porcentual: - 0,86; Desviación Estándar: 9,41. Los otros modelos presentaron diferentes variaciones para distintos rangos de peso al nacer. Todas las fórmulas demostraron una subestimación significativa a partir del séptimo día de intervalo entre el examen ecográfico y el momento del parto