Neural tube defects: Sex ratio changes after fortification with folic acid

Background: Historically, neural tube defects (NTDs) have predominated in female infants but the reasons remain unclear. In South America, the pre-folic acid fortification (FAF) rates of NTDs were around 18/10,000 births for females and 12/10,000 births for males, with an estimated sex ratio (male/female) of 0.67. During the post-FAF period, unpublished routine reports have indicated changes in the sex ratio for these defects while some descriptive reports are controversial. To date and to our knowledge, however, no studies specifically focusing on these changes to test this hypothesis directly have been undertaken. The aim of this study was to analyze changes in the sex ratio of infants with NTDs after FAF in South American countries. Materials and methods: With a descriptive cross-sectional study design, 2,597 infants with isolated NTDs born between 1990 and 2013 in 3 countries participating in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network were included: (Chile N = 521 and Argentina N = 1,619 [with FAF policies]; Venezuela N = 457 [without FAF policies; used as control]; total births = 2,229,561). The differences-in-differences method and Poisson regressions were used to evaluate the sex ratio shift from female to male before vs. after FAF, and to assess whether these differences were related to the fortification. Results and conclusions: In Chile and Argentina the prevalence of NTDs, particularly anencephaly and cervico-tho-racic spina bifida, showed a greater reduction rate in females than in males after FAF, resulting in a change of the sex ratio of infants with NTDs. Some mechanisms possibly involved in this differential reduction are proposed which might be useful to identify the pathogenesis of NTDs as a whole and specifically of those susceptible to the protective effect of folic acid.Fil: Poletta, Fernando Adrián. Ciudad Autónoma de Buenos Aires. Hospital Materno Infantil “Ramón Sardá”; Argentina. 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: Rittler, Monica. Ciudad Autónoma de Buenos Aires. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Saleme, Cesar. Ciudad Autónoma de Buenos Aires. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Campaña, Hebe. 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: 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; ArgentinaFil: Pawluk, Mariela Soledad. 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: Gimenez, Lucas Gabriel. 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, Viviana Raquel. 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. Ciudad Autónoma de Buenos Aires. Hospital Materno Infantil “Ramón Sardá”; Argentina. 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: López Camelo, Jorge Santiago. Ciudad Autónoma de Buenos Aires. Hospital Materno Infantil “Ramón Sardá”; Argentina. 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; Argentin

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

METACARPAL FRACTURES TREATMENT: COMPARASION BETWEEN KIRSCHNER WIRE AND INTRAMEDULLARY SCREW

ABSTRACT Introduction: Metacarpal fractures are common and can be treated surgically using Kirschner wires (K-wires) or intramedullary fixation with compression screws (IMCS). Objectives: Analyze the postsurgical results from treating the metacarpal extra-articular fractures through the retrograde Kirschner wire technique, and compare it with the intramedullary compression screw fixation. Methods: Retrospective and quantitative studies were to analyze patients’ medical records, and a postsurgical evaluation questionnaire was given to the patients, who were divided into K-wire and IMCS. Results: The period of immobilization with a splint took six weeks for the K-wire group and four weeks for the IMCS group. The average time for consolidation took, respectively, fifty-seven days and forty-seven days. The first group could restart their activities twenty-two days after the other, and the average force value of the treated hand, when compared with its contralateral, was 93.9% and 95.4%, respectively. Between the operated hand and its contralateral, there was a difference of 16° in the total measures of the metacarpophalangeal and interphalangeal joint's range of movement among the K-wire group and 5° among the IMCS group. Conclusion: The patients who participated in this study showed excellent results after surgery, and both treatments were proven to be safe and reliable. Evidence level III; Retrospective comparative study

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.Fil: Elias, Dario Ezequiel. 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: Gimenez, Lucas Gabriel. 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: Poletta, Fernando Adrián. 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: Campaña, Hebe. 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: 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; ArgentinaFil: Ratowiecki, Julia. 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: Pawluk, Mariela Soledad. 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: Rittler, Monica. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Santos, María Rita. 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: Uranga, Rocio. Centro de Educación Medica E Invest.clinicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal Especializado de Agudos y Cronicos San Juan de Dios.; ArgentinaFil: Heisecke Peralta, Silvina Lidia. 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, Viviana Raquel. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Saleme, Cesar. Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes; ArgentinaFil: 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: Krupitzki, Hugo Bernardo. 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: López Camelo, Jorge Santiago. 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; Argentin

Sex ratio changes for NTD cases and total births in Chile, Argentina, and Venezuela (1990–2013).

<p>NTD: neural tube defect; FAF: folic acid fortification; M/F: male/female; Sex ratio (male/female) for neural tube defect cases (full blue line), sex ratio for total births (dashed red line). Sex ratios estimated by multivariate regression models adjusted by hospital.</p

Sex ratio (M/F) changes for types of NTDs between FAF periods.

<p>Sex ratio (M/F) changes for types of NTDs between FAF periods.</p

Number of NTD cases by period (pre- and post- FAF) and sex of newborns.

<p>Number of NTD cases by period (pre- and post- FAF) and sex of newborns.</p

Reduction in NTD rates (per 10,000 births) between pre- and post-FAF periods, by sex and country.

<p>Reduction in NTD rates (per 10,000 births) between pre- and post-FAF periods, by sex and country.</p