Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population

Background. Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation: Idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTBM). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB. Methods. 24 SNPs were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 PTB-PPROM, and 210 PTB-M. These data were analyzed with a Family-Based Association. Results. PTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, 3 SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTBPPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M. Conclusions. Our 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

Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study

Peer reviewe

Genome-wide analysis of DNA methylation in human amnion

The amnion is a specialized tissue in contact with the amniotic fluid, which is in a constantly changing state. To investigate the importance of epigenetic events in this tissue in the physiology and pathophysiology of pregnancy, we performed genome-wide DNA methylation profiling of human amnion from term (with and without labor) and preterm deliveries. Using the Illumina Infinium HumanMethylation27 BeadChip, we identified genes exhibiting differential methylation associated with normal labor and preterm birth. Functional analysis of the differentially methylated genes revealed biologically relevant enriched gene sets. Bisulfite sequencing analysis of the promoter region of the oxytocin receptor (OXTR) gene detected two CpG dinucleotides showing significant methylation differences among the three groups of samples. Hypermethylation of the CpG island of the solute carrier family 30 member 3 (SLC30A3) gene in preterm amnion was confirmed by methylation-specific PCR. This work provides preliminary evidence that DNA methylation changes in the amnion may be at least partially involved in the physiological process of labor and the etiology of preterm birth and suggests that DNA methylation profiles, in combination with other biological data, may provide valuable insight into the mechanisms underlying normal and pathological pregnancies. © 2013 Jinsil Kim et al.Fil: Kim, Jinsil. University of Iowa; Estados UnidosFil: Pitlick, Mitchell M.. University of Iowa; Estados UnidosFil: Christine, Paul J.. University of Iowa; Estados UnidosFil: Schaefer, Amanda R.. University of Iowa; Estados UnidosFil: Saleme, Cesar. Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes; ArgentinaFil: Comas, Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Cosentino, Viviana Raquel. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Gadow, Enrique Curt. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Murray, Jeffrey C.. University of Iowa; Estados Unido

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

Objective: To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture. Study Design: Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. Result: Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; P=0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; P=0.01). Gestational age associated with PTB in PGR rs1942836 at 32-36 weeks (P=0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. Conclusion: This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB.Fil: Mann, P. C.. University of Iowa; Estados UnidosFil: Cooper, M. E.. University of Pittsburgh; Estados UnidosFil: Ryckman, K. K.. University of Iowa; Estados UnidosFil: Comas, Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Instituto Oswaldo Cruz; Brasil. Fundación Oswaldo Cruz; BrasilFil: Gili, Juan Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina. Instituto Oswaldo Cruz; Brasil. Fundación Oswaldo Cruz; BrasilFil: Crumley, S.. University of Iowa; Estados UnidosFil: Bream, E. N. A.. University of Iowa; Estados UnidosFil: Byers, H. M.. University of Iowa; Estados UnidosFil: Piester, T.. University of Iowa; Estados UnidosFil: Schaefer, Ana Soledad. University of Iowa; Estados UnidosFil: Christine, P. J.. University of Iowa; Estados UnidosFil: Lawrence, A.. University of Iowa; Estados UnidosFil: Schaa, K. L.. University of Iowa; Estados UnidosFil: Kelsey, K. J. P.. University of Iowa; Estados UnidosFil: Berends, S. K.. University of Iowa; Estados UnidosFil: Momany, A. M.. University of Iowa; Estados UnidosFil: Gadow, Enrique Curt. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Cosentino, V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Castilla, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Fundación Oswaldo Cruz; Brasil. Instituto Oswaldo Cruz; BrasilFil: López Camelo, Jorge Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Saleme, César. Provincia de Tucumán. Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes; ArgentinaFil: Day, L. J.. University of Iowa; Estados UnidosFil: England, S. K.. University of Iowa; Estados UnidosFil: Marazita, M. L.. University of Pittsburgh; Estados UnidosFil: Dagle, J. M.. University of Iowa; Estados UnidosFil: Murray, J. C.. University of Iowa; Estados Unido

Odon device for instrumental vaginal deliveries: results of a medical device pilot clinical study

Abstract Background A prolonged and complicated second stage of labour is associated with serious perinatal complications. The Odon device is an innovation intended to perform instrumental vaginal delivery presently under development. We present an evaluation of the feasibility and safety of delivery with early prototypes of this device from an early terminated clinical study. Methods Hospital-based, multi-phased, open-label, pilot clinical study with no control group in tertiary hospitals in Argentina and South Africa. Multiparous and nulliparous women, with uncomplicated singleton pregnancies, were enrolled during the third trimester of pregnancy. Delivery with Odon device was attempted under non-emergency conditions during the second stage of labour. The feasibility outcome was delivery with the Odon device defined as successful expulsion of the fetal head after one-time application of the device. Results Of the 49 women enrolled, the Odon device was inserted successfully in 46 (93%), and successful Odon device delivery as defined above was achieved in 35 (71%) women. Vaginal, first and second degree perineal tears occurred in 29 (59%) women. Four women had cervical tears. No third or fourth degree perineal tears were observed. All neonates were born alive and vigorous. No adverse maternal or infant outcomes were observed at 6-weeks follow-up for all dyads, and at 1 year for the first 30 dyads. Conclusions Delivery using the Odon device is feasible. Observed genital tears could be due to the device or the process of delivery and assessment bias. Evaluating the effectiveness and safety of the further developed prototype of the BD Odon Device™ will require a randomized-controlled trial. Trial registration ANZCTR ACTRN12613000141741 Registered 06 February 2013. Retrospectively registered

Replication of a genome-wide association study of birth weight in preterm neonates

OBJECTIVE: To examine associations in a preterm population between rs9883204 in ADCY5 and rs900400 near LEKR1 and CCNL1 with birth weight. Both markers were associated with birth weight in a term population in a recent genome-wide association (GWA) study by Freathy et al. STUDY DESIGN: A meta-analysis of mother and infant samples was performed for associations of rs900400 and rs9883204 with birth weight in 393 families from the U.S., 265 families from Argentina and 735 mother-infant pairs from Denmark. Z scores adjusted for infant sex and gestational age were generated for each population separately and regressed on allele counts. Association evidence was combined across sites by inverse-variance weighted meta-analysis. RESULTS: Each additional C allele of rs900400 (LEKR1/CCNL1) in infants was marginally associated with a 0.069 standard deviation (SD) lower birth weight (95% CI = −0.159 – 0.022, P = 0.068). This result was slightly more pronounced after adjusting for smoking (P = 0.036). There were no significant associations identified with rs9883204 or in maternal samples. CONCLUSIONS: These results indicate the potential importance of this marker on birth weight irrespective of gestational age