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Article ; Online: Paternal age and risk for selected birth defects in a large South American sample.

Gili, Juan A / Rittler, Monica / Heisecke, Silvina / Campaña, Hebe / Giménez, Lucas / Santos, María Rita / Ratowiecki, Julia / Cosentino, Viviana / López Camelo, Jorge / Poletta, Fernando A

Birth defects research

2023 Volume 115, Issue 19, Page(s) 1866–1875

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Male ; Anus, Imperforate/epidemiology ; Paternal Age ; Risk Factors ; South America/epidemiology ; Polydactyly/epidemiology
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2104792-3
ISSN	2472-1727
ISSN (online)	2472-1727
DOI	10.1002/bdr2.2252
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Article: Gene-environment interactions and preterm birth predictors: A Bayesian network approach.

Elias, Dario E / Santos, Maria R / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Gili, Juan A / Ratowiecki, Julia / Cosentino, Viviana R / Uranga, Rocio / Málaga, Diana Rojas / Oliveira Netto, Alice Brinckmann / Brusius-Facchin, Ana Carolina / Saleme, César / Rittler, Mónica / Krupitzki, Hugo B / Camelo, Jorge S Lopez / Gimenez, Lucas G

Genetics and molecular biology

2024 Volume 46, Issue 4, Page(s) e20230090

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2024-01-19
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	1445712-x
ISSN	1678-4685 ; 1415-4757
ISSN (online)	1678-4685
ISSN	1415-4757
DOI	10.1590/1678-4685-GMB-2023-0090
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Zs.A 3079: Show issues

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Article ; Online: Genetic susceptibility for retinopathy of prematurity and its associated comorbidities.

Gimenez, Lucas G / Gili, Juan A / Elias, Darío E / Sagula, Rubén / Comas, Belén / Santos, María R / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Ratowiecki, Julia / Cosentino, Viviana R / Uranga, Rocío / Saleme, César / Negri, Mercedes / Rittler, Mónica / Zapata Barrios, Jorge / Krupitzki, Hugo B / López Camelo, Jorge S

Pediatric research

2024

Abstract: 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 ...

Abstract	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.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-024-03068-9
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Diseases during pregnancy in a large unselected South American sample.

Santos, María Rita / Campaña, Hebe / Heisecke, Silvina / Ratowiecki, Julia / Elías, Darío / Giménez, Lucas / Poletta, Fernando Adrián / Gili, Juan / Uranga, Rocío / Cosentino, Viviana / Krupitzki, Hugo / Rittler, Mónica / Camelo, Jorge López

Revista brasileira de epidemiologia = Brazilian journal of epidemiology

2022 Volume 25, Page(s) e220043

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Infant, Newborn ; Female ; Humans ; Pregnancy ; Cross-Sectional Studies ; Brazil
Language	English
Publishing date	2022-12-05
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2183366-7
ISSN	1980-5497 ; 1980-5497
ISSN (online)	1980-5497
ISSN	1980-5497
DOI	10.1590/1980-549720220043
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Article: Genes, exposures, and interactions on preterm birth risk: an exploratory study in an Argentine population.

Elias, Dario E / Santos, Maria R / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Gili, Juan A / Ratowiecki, Julia / Cosentino, Viviana / Uranga, Rocio / Málaga, Diana Rojas / Netto, Alice Brinckmann Oliveira / Brusius-Facchin, Ana Carolina / Saleme, César / Rittler, Mónica / Krupitzki, Hugo B / Camelo, Jorge S Lopez / Gimenez, Lucas G

Journal of community genetics

2022 Volume 13, Issue 6, Page(s) 557–565

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2022-08-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2543127-4
ISSN	1868-6001 ; 1868-310X
ISSN (online)	1868-6001
ISSN	1868-310X
DOI	10.1007/s12687-022-00605-z
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Article ; Online: Lethality of Birth Defects in Live Born Infants Categorized by Gestational Age and Birth Weight.

Rittler, Monica / Campaña, Hebe / Heisecke, Silvina / Ratowiecki, Julia / Elias, Dario / Gimenez, Lucas / Poletta, Fernando A / Gili, Juan / Pawluk, Mariela / Santos, Maria Rita / Uranga, Rocio / Cosentino, Viviana / Camelo, Jorge Lopez

American journal of perinatology

2021 Volume 40, Issue 13, Page(s) 1406–1412

Abstract: 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 (: Results: Overall fewer ... ...

Abstract	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 ( 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..
MeSH term(s)	Male ; Female ; Infant, Newborn ; Infant ; Humans ; Pregnancy ; Birth Weight ; Gestational Age ; Premature Birth ; Infant, Premature ; Infant, Small for Gestational Age ; Fetal Growth Retardation
Language	English
Publishing date	2021-10-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605671-4
ISSN	1098-8785 ; 0735-1631
ISSN (online)	1098-8785
ISSN	0735-1631
DOI	10.1055/s-0041-1735867
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Zs.A 1929: Show issues

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Article ; Online: Inequidades sociales en madres adolescentes y la relación con resultados perinatales adversos en poblaciones sudamericanas.

Ratowiecki, Julia / Santos, María Rita / Poletta, Fernando / Heisecke, Silvina / Elias, Dario / Gili, Juan / Gimenez, Lucas / Pawluk, Mariela / Uranga, Rocio / Cosentino, Viviana / Campaña, Hebe / Rittler, Mónica / Camelo, Jorge S López

Cadernos de saude publica

2021 Volume 36, Issue 12, Page(s) e00247719

Abstract: The aim was to explain differences in the rates of adverse perinatal events in teenage mothers with low and high schooling. The sample was collected from the Latin American Colaborative Study of Congenital Malformations (ECLAMC) database. From a total of ...

Title translation	Social inequities in teenage mothers and the relationship to adverse perinatal outcomes in South American populations.
Abstract	The aim was to explain differences in the rates of adverse perinatal events in teenage mothers with low and high schooling. The sample was collected from the Latin American Colaborative Study of Congenital Malformations (ECLAMC) database. From a total of 2,443,747 births in 93 hospitals, 66,755 live newborns without congenital malformations were recruited from 2000 to 2017. Teenage mothers were classified according to low, medium, and high schooling. A multivariate model was used that included reproductive history, access to health services, demographic and socioeconomic variables, and ethnic group. The Fairlie decomposition model was applied to quantify the contribution of explanatory variables to the adverse perinatal event rates. Of the 66,755 newborns analyzed, 21.1% (n = 14,078) were born to teenage mothers. Distribution of maternal schooling was 24.2%, 59.8%, and 16% for low, medium, and high schooling, respectively. The highest rates of adverse perinatal events were seen in teenage mothers with low schooling. The variable "access to health services" explained 35%, 37%, and 23% of the disparities in low birthweight, prematurity, and intrauterine growth restriction, respectively, among teenage mother with low and high schooling. Low number of prenatal visits was the only risk factor for the two levels of schooling and the variable that best explained the differences between the rates of adverse perinatal events. From the public health perspective, prenatal care represents a low-cost intervention with the possibility of increased implementation through adequate information for the population and systematic measures in primary care.
MeSH term(s)	Adolescent ; Brazil/epidemiology ; Female ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Mothers ; Pregnancy ; Pregnancy Outcome/epidemiology ; Pregnancy in Adolescence ; Prenatal Care
Language	Spanish
Publishing date	2021-01-11
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	1115730-6
ISSN	1678-4464 ; 0102-311X
ISSN (online)	1678-4464
ISSN	0102-311X
DOI	10.1590/0102-311X00247719
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Zs.A 4981: Show issues

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Article ; Online: Individual deprivation, regional deprivation, and risk for oral clefts in Argentina.

Pawluk, Mariela Soledad / Campaña, Hebe / Rittler, Monica / Poletta, Fernando Adrián / Cosentino, Viviana R / Gili, Juan Antonio / Gimenez, Lucas Gabriel / López Camelo, Jorge Santiago

Revista panamericana de salud publica = Pan American journal of public health

2018 Volume 41, Page(s) e110

Abstract: 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- ...

Abstract	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.
Language	English
Publishing date	2018-02-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1376934-0
ISSN	1680-5348 ; 1020-4989
ISSN (online)	1680-5348
ISSN	1020-4989
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Zs.A 4694: Show issues

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Article ; Online: A graph theory approach to analyze birth defect associations.

Elias, Dario / Campaña, Hebe / Poletta, Fernando / Heisecke, Silvina / Gili, Juan / Ratowiecki, Julia / Gimenez, Lucas / Pawluk, Mariela / Santos, Maria Rita / Cosentino, Viviana / Uranga, Rocio / Rittler, Monica / Lopez Camelo, Jorge

PloS one

2020 Volume 15, Issue 5, Page(s) e0233529

Abstract: Birth defects are prenatal morphological or functional anomalies. Associations among them are studied to identify their etiopathogenesis. The graph theory methods allow analyzing relationships among a complete set of anomalies. A graph consists of nodes ... ...

Abstract	Birth defects are prenatal morphological or functional anomalies. Associations among them are studied to identify their etiopathogenesis. The graph theory methods allow analyzing relationships among a complete set of anomalies. A graph consists of nodes which represent the entities (birth defects in the present work), and edges that join nodes indicating the relationships among them. The aim of the present study was to validate the graph theory methods to study birth defect associations. All birth defects monitoring records from the Estudio Colaborativo Latino Americano de Malformaciones Congénitas gathered between 1967 and 2017 were used. From around 5 million live and stillborn infants, 170,430 had one or more birth defects. Volume-adjusted Chi-Square was used to determine the association strength between two birth defects and to weight the graph edges. The complete birth defect graph showed a Log-Normal degree distribution and its characteristics differed from random, scale-free and small-world graphs. The graph comprised 118 nodes and 550 edges. Birth defects with the highest centrality values were nonspecific codes such as Other upper limb anomalies. After partition, the graph yielded 12 groups; most of them were recognizable and included conditions such as VATER and OEIS associations, and Patau syndrome. Our findings validate the graph theory methods to study birth defect associations. This method may contribute to identify underlying etiopathogeneses as well as to improve coding systems.
MeSH term(s)	Congenital Abnormalities/epidemiology ; Data Science/methods ; Databases, Factual ; Humans ; Infant, Newborn ; Statistical Distributions
Language	English
Publishing date	2020-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Study
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0233529
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Article ; Online: Preterm birth etiological pathways: a Bayesian networks and mediation analysis approach.

Elias, Dario / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Gili, Juan A / Ratowiecki, Julia / Pawluk, Mariela / Santos, Maria R / Cosentino, Viviana / Uranga, Rocio / Saleme, Cesar / Rittler, Monica / Krupitzki, Hugo B / Lopez Camelo, Jorge S / Gimenez, Lucas G

Pediatric research

2021 Volume 91, Issue 7, Page(s) 1882–1889

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adult ; Bayes Theorem ; Case-Control Studies ; Female ; Humans ; Infant, Newborn ; Mediation Analysis ; Pregnancy ; Premature Birth/epidemiology ; Premature Birth/etiology ; Risk Factors ; Uterine Hemorrhage/complications ; Young Adult
Language	English
Publishing date	2021-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-021-01659-4
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