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.

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.

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.

Lethality of Birth Defects in Live Born Infants Categorized by Gestational Age and Birth Weight.

OBJECTIVE: This study aimed to describe lethality of birth defects (BDs) in newborns categorized by gestational age and birth weight and to identify BDs associated with prematurity. STUDY DESIGN: Live born infants (n = 16,452) with isolated BDs classified by severity, and 42,511 healthy controls were assigned to categories: adequate growth, preterm, or small for gestational age (SGA). Proportion of cases and BDs' lethality rates were obtained by category and compared with controls. RESULTS: Overall fewer malformed than nonmalformed infants were of adequate growth, while the opposite occurred in the preterm and SGA categories where gastroschisis and esophageal atresia were among the most outstanding defects. For most severe BDs, the early neonatal death rate was higher than control values in all categories; for mild defects, except cleft lip in the preterm category, they did not differ. Diaphragmatic hernia showed the highest lethality values, while those of spina bifida were among the lowest. Talipes, hypospadias, and septal heart defects were mild defects significantly associated with prematurity. CONCLUSION: Although reasons, such as induced preterm delivery of fetuses with certain anomalies, could partially account for their high prematurity rates, susceptibility to preterm birth might exist through underlying mechanisms related with the defects. The identification of BDs associated with prematurity should serve to improve measures that prevent preterm birth especially of fetuses at risk. KEY POINTS: · Some BDs predispose to prematurity.. · Prematurity is an additional risk factor for mortality in infants with mild defects.. · Lethality values should be adjusted by gestational age and birth weight..

Genetic variation in the E6 and E7 genes of human papillomavirus type 16 in northeastern Argentina.

The province of Misiones is considered a region with a high mortality rate due to cervical cancer (CC). To gain insight into this problem, we explored the association between genetic variation in the E6 and E7 oncogenes of HPV16 and the risk of CC. We studied 160 women with cytological diagnoses of negative for intraepithelial lesion or malignity, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion/CC and a positive test for HPV16 infection. The genetic characterization of E6 and E7 genes was undertaken through PCR amplification and direct Sanger sequencing. Phylogenetic classification was conducted using Bayesian methods. To estimate the odds ratio (OR) for an association between genetic variants in the E6 and E7 genes and the risk of CC, we used ordinal logistic regression adjusted by age. The final data set comprised 112 samples. Diagnostic single-nucleotide polymorphisms (SNPs) and phylogenetic trees confirmed the presence of Lineage A (95.5%) and D (4.5%) in the samples. For the E6 gene, we identified eleven different sequences, with the most common ones being Lineage A E6 350G (58.9%) and E6 350T (37.5%). The E6 350G was associated with progression to HSIL/CC, with an OR of 19.41 (4.95-76.10). The E7 gene was more conserved than E6, probably due to the functional constraints of this small protein. Our results confirmed the association of the E6 350G SNP with a higher risk of developing CC. These data will contribute to understanding the biological bases of CC incidence in this region.

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.

Preterm birth and genitourinary tract infections: assessing gene-environment interaction.

BACKGROUND: Preterm birth (PTB) is the leading cause of perinatal morbimortality worldwide. Genetic and environmental factors could raise PTB risk. The aim of this study was to analyze the contribution of the statistical interaction between genes and vaginal-urinary tract infections (VI-UTI) to the risk of PTB by clinical subtype. METHODS: Twenty-four SNPs were genotyped in 18 candidate genes from 352 fetal triads and 106 maternal triads. Statistical interactions were evaluated with conditional logistic regression models based on genotypic transmission/disequilibrium test. RESULTS: In PTB-idiopathic subtype mothers exposed to UTI, fetal SNPs rs11686474 (FSHR), rs4458044 (CRHR1, allele G), rs883319 (KCNN3), and maternal SNP rs1882435 (COL4A3) showed a nominal significant increment in prematurity risk. In preterm premature rupture of membranes (PPROM), fetal SNP rs2277698 (TIMP2) showed a nominal significant risk increment. In mothers exposed to VI, fetal SNP rs5742612 (IGF1) in PTB-PPROM and maternal SNP rs4458044 (CRHR1, allele C) in spontaneous PTB showed nominal significant increment in prematurity risk. CONCLUSIONS: Certain maternal and fetal genes linked to infectious/inflammatory and hormonal regulation processes increase prematurity risk according to clinical subtype when mothers are exposed to UTI or VI. These findings may help in the understanding of PTB etiology and PTB prevention. IMPACT: Preterm birth is a major cause of perinatal morbimortality worldwide and its etiology remains unknown. This work provides evidence on the statistical interaction of six genes with gestational vaginal or urinary infections leading to the occurrence of preterm births. Statistical interactions vary according to infection type, genotype (maternal and fetal), and clinical subtype of prematurity. Certain maternal and fetal genetic variants of genes linked to infectious/inflammatory and hormonal regulation processes would increase the risk of prematurity according to clinical subtype and infection type. Our findings may help in the study of etiology of preterm birth and its prevention.

Individual deprivation, regional deprivation, and risk for oral clefts in Argentina.

OBJECTIVE: The aim of this study was to analyze the effects of individual low socioeconomic status (SES) and deprived geographical area (GA) on the occurrence of isolated cleft lip with or without cleft palate (CL±P) in Argentina. METHODS: This case-control study included 577 newborns with isolated CL±P and 13 344 healthy controls, born between 1992 and 2001, from a total population of 546 129 births in 39 hospitals in Argentina. Census data on unsatisfied basic needs were used to establish the degree of geographical area deprivation. An SES index for each individual was established, using maternal age, gravidity, low paternal and maternal education, and low-level paternal occupation. Logistic regression was used to assess the effects of low SES and of deprived GA on CL±P. RESULTS: A slightly increased risk of CL±P was observed in mothers with a low SES, while a deprived GA showed no effect. Native ancestry, acute maternal illnesses, and poor prenatal care were significant risk factors for CL±P for the mothers with low SES, after using propensity scores to adjust for the demographic characteristics in cases and controls. CONCLUSIONS: Low individual SES slightly increased the risk for CL±P, but a deprived GA did not have that effect. There was no interaction between individual SES and deprived GA. Factors related to low individual SES-including poor prenatal care, low parental education, lack of information, and lifestyle factors-should be primarily targeted as risk factors for CL±P rather than factors related to a deprived place of residence.

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.

Sirenomelia in Argentina: Prevalence, geographic clusters and temporal trends analysis.

BACKGROUND: Sirenomelia is a severe malformation of the lower body characterized by a single medial lower limb and a variable combination of visceral abnormalities. Given that Sirenomelia is a very rare birth defect, epidemiological studies are scarce. The aim of this study is to evaluate prevalence, geographic clusters and time trends of sirenomelia in Argentina, using data from the National Network of Congenital Anomalies of Argentina (RENAC) from November 2009 until December 2014. METHODS: This is a descriptive study using data from the RENAC, a hospital-based surveillance system for newborns affected with major morphological congenital anomalies. We calculated sirenomelia prevalence throughout the period, searched for geographical clusters, and evaluated time trends. RESULTS: The prevalence of confirmed cases of sirenomelia throughout the period was 2.35 per 100,000 births. Cluster analysis showed no statistically significant geographical aggregates. Time-trends analysis showed that the prevalence was higher in years 2009 to 2010. CONCLUSION: The observed prevalence was higher than the observed in previous epidemiological studies in other geographic regions. We observed a likely real increase in the initial period of our study. We used strict diagnostic criteria, excluding cases that only had clinical diagnosis of sirenomelia. Therefore, real prevalence could be even higher. This study did not show any geographic clusters. Because etiology of sirenomelia has not yet been established, studies of epidemiological features of this defect may contribute to define its causes. Birth Defects Research (Part A) 106:604-611, 2016. © 2016 Wiley Periodicals, Inc.

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.

Biosocial correlates and spatial distribution of consanguinity in South America.

OBJECTIVE: To analyze potential biosocial factors in consanguineous unions according to the level of consanguinity and its spatial distribution in South America. METHODS: The data used came from the Latin American Collaborative Study of Congenital Malformations. Information on 126,213 nonmalformed newborns out of 6,014,749 births was used. This information was collected between 1967 and 2011 at 204 hospitals in 116 cities in 10 South American countries. The spatial scan statistic was performed under a model of nonhierarchical k-means segmentation, based on statistically significant clusters, areas with levels of high, medium, and low consanguinity were determined. RESULTS: Consanguinity in South America is heterogeneously distributed, with two groups of high consanguinity, in northwestern Venezuela and southeast of Brazil, and two clusters of low consanguinity located in the south of the continent, mainly Argentina. The socio-demographic factors associated with consanguinity influence the population structure in areas of high consanguinity. CONCLUSIONS: This study demonstrates that consanguinity in the South American continent is strongly associated with a greater magnitude of poverty in the area of high consanguinity. Am. J. Hum. Biol. 28:405-411, 2016. © 2015 Wiley Periodicals, Inc.

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.

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.

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.

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.

Paternal age and risk for selected birth defects in a large South American sample.

BACKGROUND: The relationship between maternal age (MA) and birth defects (BD) has been extensively studied while much less research, mostly with discordant results, has focused on the risk of paternal age (PA) for BD. Furthermore, no consensus has been reached on the best way to control the association of PA with MA. OBJECTIVES: The aim of the study was to evaluate the risk of PA increase, at 1-year intervals, for selected BD, especially controlling for the confounding effect of MA. METHODS: The sample comprised of 27,944 liveborns presenting 1 of 18 selected isolated BD. Conditional logistic regressions were applied to evaluate the risk of advanced PA and its yearly increase, adjusting by MA and other variables. RESULTS: Of the 18 analyzed BD, only the risk for preaxial polydactyly (PreP) showed a significant association with increasing PA, while advanced MA was of low risk. For esophageal and anal atresia, associations with both PA and MA increases were observed. CONCLUSIONS: Results support the hypothesis of advanced PA as a risk factor for PreP and helps clarify the so far unexplained nonrandom association between this defect and Down syndrome.

Diseases during pregnancy in a large unselected South American sample.

OBJECTIVE: Our aim was to describe the prevalence of diseases during pregnancy and the association between fetal exposure to the most frequent maternal diseases and the risk of preterm (PTB) and/or small for gestational age (SGA) newborns in an unselected sample of women who gave birth in South American countries. METHODS: We conducted a descriptive, cross-sectional study including 56,232 mothers of non-malformed infants born between 2002 and 2016, using data from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Diseases with higher- than-expected PTB/SGA frequencies were identified. Odds ratios of confounding variables for diseases and birth outcomes were calculated with a multivariable logistic regression. RESULTS: Of the 14 most reported diseases, hypertension, genitourinary infection, epilepsy, hypothyroidism, diabetes, and HIV/AIDS showed higher PTB and/or SGA frequencies. Advanced and low maternal age, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with PTB, while advanced maternal age, primigravidity, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with SGA. After adjusting for the associated variables, the identified illnesses maintained their association with PTB and all, except epilepsy, with SGA. CONCLUSION: The description of an unselected population of mothers allowed identifying the most frequent diseases occurring during gestation and their impact on pregnancy outcomes. Six diseases were associated with PTB and two with SGA newborns. To the best of our knowledge, there are no similar reports about women not intentionally selected by specific diseases during pregnancy in South American populations.

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.

Analysis of early neonatal case fatality rate among newborns with congenital hydrocephalus, a 2000-2014 multi-country registry-based study.

BACKGROUND: Congenital hydrocephalus (CH) comprises a heterogeneous group of birth anomalies with a wide-ranging prevalence across geographic regions and registry type. The aim of the present study was to analyze the early neonatal case fatality rate (CFR) and total birth prevalence of newborns diagnosed with CH. METHODS: Data were provided by 25 registries from four continents participating in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) on births ascertained between 2000 and 2014. Two CH rates were calculated using a Poisson distribution: early neonatal CFR (death within 7 days) per 100 liveborn CH cases (CFR) and total birth prevalence rate (BPR) per 10,000 births (including live births and stillbirths) (BPR). Heterogeneity between registries was calculated using a meta-analysis approach with random effects. Temporal trends in CFR and BPR within registries were evaluated through Poisson regression modeling. RESULTS: A total of 13,112 CH cases among 19,293,280 total births were analyzed. The early neonatal CFR was 5.9 per 100 liveborn cases, 95% confidence interval (CI): 5.4-6.8. The CFR among syndromic cases was 2.7 times (95% CI: 2.2-3.3) higher than among non-syndromic cases (10.4% [95% CI: 9.3-11.7] and 4.4% [95% CI: 3.7-5.2], respectively). The total BPR was 6.8 per 10,000 births (95% CI: 6.7-6.9). Stratified by elective termination of pregnancy for fetal anomalies (ETOPFA), region and system, higher CFR were observed alongside higher BPR rates. The early neonatal CFR and total BPR did not show temporal variation, with the exception of a CFR decrease in one registry. CONCLUSIONS: Findings of early neonatal CFR and total BPR were highly heterogeneous among registries participating in ICBDSR. Most registries with higher CFR also had higher BPR. Differences were attributable to type of registry (hospital-based vs. population-based), ETOPFA (allowed yes or no) and geographical regions. These findings contribute to the understanding of regional differences of CH occurrence and early neonatal deaths.