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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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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: 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: Asociación entre polimorfismos del gen NAT2 y fisura labiopalatina no sindrómica en Argentina.

Santos, María Rita / Ramallo, Virginia / Muzzio, Marina / Camelo, Jorge S López / Bailliet, Graciela

Revista medica de Chile

2015 Volume 143, Issue 4, Page(s) 444–450

Abstract: Background: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, ...

Title translation	Association between NAT2 polymorphisms with non-syndromic cleft lip with or without cleft palate in Argentina.
Abstract	Background: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment. Aim: To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP. Material and methods: We analyzed 5 (481C>T), 6 (590G>A) and 7 (857G>A) alleles which determine the slow acetylator phenotype and 4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT). Results: TDT showed a positive association between allele 5 and NSCLP (odds ratio = 1,6; p = 0,03). Conclusions:* The presence of *5 allele is significantly higher in cases with congenital NSCLP.
MeSH term(s)	Alleles ; Amplified Fragment Length Polymorphism Analysis ; Analysis of Variance ; Argentina ; Arylamine N-Acetyltransferase/genetics ; Cleft Lip/genetics ; Cleft Palate/genetics ; Fathers ; Female ; Genetic Carrier Screening ; Genetic Predisposition to Disease ; Genotype ; Humans ; Linkage Disequilibrium ; Male ; Mothers ; Polymorphism, Restriction Fragment Length/genetics
Chemical Substances	Arylamine N-Acetyltransferase (EC 2.3.1.5) ; NAT2 protein, human (EC 2.3.1.5)
Language	Spanish
Publishing date	2015-04
Publishing country	Chile
Document type	Journal Article
ZDB-ID	732136-3
ISSN	0717-6163 ; 0034-9887
ISSN (online)	0717-6163
ISSN	0034-9887
DOI	10.4067/S0034-98872015000400005
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Article ; Online: Sentinel phenotype for rubella embryopathy: time-space distribution in Brazil.

Orioli, Iêda Maria / Camelo, Jorge S López / Rittler, Monica / Castilla, Eduardo E

Cadernos de saude publica

2012 Volume 27, Issue 10, Page(s) 1961–1968

Abstract: The dyad comprising eye anomalies and congenital heart defects in the same newborn has been proposed as the best sentinel phenotype for the early detection of rubella embryopathy. Time-space birth prevalence distributions of the eye-heart dyad were ... ...

Abstract	The dyad comprising eye anomalies and congenital heart defects in the same newborn has been proposed as the best sentinel phenotype for the early detection of rubella embryopathy. Time-space birth prevalence distributions of the eye-heart dyad were described in 36 Brazilian hospitals from the Latin-American Collaborative Study of Congenital Anomalies - ECLAMC network, for the period 1994-2008. Seventy dyad cases observed among 554,531 births showed seasonal variation (Χ² = 5.84; p < 0.05), suggesting an environmental etiology, with an increase in cases in October-March and acrophase in December. The secular distribution of dyad prevalence rates was consistent with the distribution of rubella cases in Brazil, showing a decrease from 1994 to 2004, followed by an increase until 2008. Two geographic clusters were identified, one with high and the other with low dyad prevalence. In the high prevalence cluster, a secular increase was observed, starting in 1999, matching the rubella epidemic waves observed in Brazil in 1998-2000 and 2006.
MeSH term(s)	Brazil/epidemiology ; Early Diagnosis ; Eye Abnormalities/epidemiology ; Eye Abnormalities/virology ; Heart Defects, Congenital/epidemiology ; Humans ; Infant, Newborn ; Phenotype ; Rubella Syndrome, Congenital/embryology ; Rubella Syndrome, Congenital/epidemiology ; Space-Time Clustering
Language	English
Publishing date	2012-01-03
Publishing country	Brazil
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1115730-6
ISSN	1678-4464 ; 0102-311X
ISSN (online)	1678-4464
ISSN	0102-311X
DOI	10.1590/s0102-311x2011001000009
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Zs.A 4981: Show issues

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

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

Pediatric research

2020 Volume 90, Issue 3, Page(s) 678–683

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Gene-Environment Interaction ; Genital Diseases/epidemiology ; Genital Diseases/genetics ; Humans ; Infant, Newborn ; Polymorphism, Single Nucleotide ; Premature Birth ; Risk Factors ; Urinary Tract Infections/epidemiology ; Urinary Tract Infections/genetics
Language	English
Publishing date	2020-10-18
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/s41390-020-01200-z
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Article ; Online: Association between a Maternal History of Miscarriages and Birth Defects.

Campaña, Hebe / Rittler, Monica / Gili, Juan A / Poletta, Fernando A / Pawluk, Mariela S / Gimenez, Lucas G / Cosentino, Viviana R / Castilla, Eduardo E / Camelo, Jorge S López

Birth defects research

2017 Volume 109, Issue 4, Page(s) 254–261

Abstract: Background: Some studies, mainly in the older literature, observed a significant association between miscarriages and birth defects (BDs) occurring in the same sibship. However, few studies examined the BD/miscarriage relationship in depth. In addition ... ...

Abstract	Background: Some studies, mainly in the older literature, observed a significant association between miscarriages and birth defects (BDs) occurring in the same sibship. However, few studies examined the BD/miscarriage relationship in depth. In addition nothing has been added to the underlying mechanisms possibly linking both events. The purpose of this work was to identify specific BDs associated with maternal miscarriages. In particular, it examined whether the risk depended on the number of losses, and to suggest the existence of specific factors for each BD/miscarriage association observed. Methods: The study relied on the Latin American Collaborative Study on Congenital Malformations (ECLAMC) database registries including 26,906 live and stillborn infants with one of 19 selected isolated BDs and 93,853 normal controls. Infants born to primigravid mothers were excluded from the present study. Demographic and reproductive variables were compared between control mothers With and Without previous miscarriages. The number, frequency, and distribution of miscarriages were observed for each BD and controls. A conditional logistic regression was applied to evaluate the miscarriage risk for each BD. Results: Control mothers with previous miscarriages were older, had had more pregnancies, and were less educated. Three risk patterns of miscarriages were observed: a very high risk of miscarriages associated with gastroschisis, omphalocele, and talipes; only one miscarriage associated with spina bifida, and two or more miscarriages associated with hypospadias. Conclusion: These three patterns suggest that different factors underly each BD/miscarriage association: infertility for hypospadias, vascular disruption for gastroschisis and talipes, while for spina bifida, the much debated trophoblastic cell residue theory could not be discarded. Birth Defects Research 109:254-261, 2017. © 2017 Wiley Periodicals, Inc.
Language	English
Publishing date	2017-03-01
Publishing country	United States
Document type	Journal Article
ISSN	2472-1727
ISSN (online)	2472-1727
DOI	10.1002/bdra.23563
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Article: Risks of congenital anomalies in large for gestational age infants.

Lapunzina, Pablo / Camelo, Jorge S López / Rittler, Monica / Castilla, Eduardo E

The Journal of pediatrics

2002 Volume 140, Issue 2, Page(s) 200–204

Abstract: Objectives: To evaluate the association between large for gestational age (LGA) and demographic and medical risk factors as well as specific types of congenital anomalies.: Study design: A retrospective, case-control study on 2,149,617 consecutive ... ...

Abstract	Objectives: To evaluate the association between large for gestational age (LGA) and demographic and medical risk factors as well as specific types of congenital anomalies. Study design: A retrospective, case-control study on 2,149,617 consecutive births was conducted. LGA was defined as 1.64 SD above the mean weight for gestational age, adjusted by sex and altitude. Risk factor frequency distributions were compared between LGA and normal birth weight neonates. Associations between LGA and 41 infants with isolated congenital anomalies were evaluated. Results: Of 31,897 neonates with congenital anomalies, 1800 were LGA. Five anomalies were associated with LGA: talipes calcaneovalgus, hydrocephaly, combined angiomatoses, hip subluxation, and non-brown-pigmented nevi. Multiparity, vaginal bleeding, diabetes, and delivery by cesarean section were more frequent in LGA than in appropriate for gestational age infants' mothers. Several maternal but no paternal factors were statistically associated with an increased risk for LGA infants. Conclusions: The clinical observation that nevi are more commonly observed in LGA patients was supported. The higher frequencies of hip subluxation and talipes calcaneovalgus among LGA neonates reinforces their pathogenesis as deformations, whereas those of combined angiomatoses and hydrocephaly could reflect increased fluid or body mass.
MeSH term(s)	Birth Weight ; Clubfoot/epidemiology ; Congenital Abnormalities/epidemiology ; Female ; Gestational Age ; Hip Dislocation, Congenital/epidemiology ; Humans ; Infant, Newborn ; Male ; Nevus/epidemiology ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2002-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1067/mpd.2002.121696
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Article: Environmental Risk Factors and Perinatal Outcomes in Preterm Newborns, According to Family Recurrence of Prematurity

Krupitzki, Hugo B. / Gadow, Enrique C. / Gili, Juan A. / Comas, Belén / Cosentino, Viviana R. / Saleme, César / Murray, Jeffrey C. / Camelo, Jorge S. Lopez

American Journal of Perinatology

2012 Volume 30, Issue 06, Page(s) 451–462

Abstract: 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 ... ...

Abstract	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, nonmalformed, 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.
Keywords	preterm birth ; familial aggregation ; pregnancy
Language	English
Publishing date	2012-11-06
Publisher	Thieme Medical Publishers
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	605671-4
ISSN	1098-8785 ; 0735-1631
ISSN (online)	1098-8785
ISSN	0735-1631
DOI	10.1055/s-0032-1326990
Database	Thieme publisher's database

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