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.

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.

[Evaluation of the functionality and subjective well-being of bipolar patients with the Functioning Assessment Short Test (FAST) and the World Health Organization - Five Well- Being Index (WHO-5)]. / Evaluación de la funcionalidad y el bienestar subjetivo de pacientes bipolares con el Functioning Assessment Short Test (FAST) y el World Health Organization - Five Well-Being Index (WHO-5).

INTRODUCTION: Bipolar Disorders (BD) are a mood disorders group charactered by recurrent manic or hypomanic episodes, alternating with depressive episodes. Its prevalence is 4%, and several studies have shown that they generate disability. There are effective therapeutic options for acute episodes. However, the ultimate goal is to achieve functional recovery and adequate well-being. MATERIAL AND METHODS: There was done in Buenos Aires, Argentina a cross-sectional study comparing psychosocial functioning, with the Functioning Assessment Short Test (FAST) and subjective well-being with the Five Well-Being Index (WHO-5), among a sample of stabilized BD patients undergoing treatment at the Center of Medical Education and Clinical Research (Centro de Educación Médica e Investigaciones Clínicas) and the Bipolar Foundation (Fundación Bipolares de Argentina), with a control group. RESULTS: A total of 102 BD patients and 52 controls where included. The FAST mean for patients and controls was 20.71 and 9.73 respectively (P=0.0000). The WHO-5 mean for patients was 59.11 and 69.76 for controls (P=0.0011). More than 70% of the patients presented functional alteration (FAST ≥12), and almost 35% presented inadequate subjective well-being (WHO-5 ≤52). Depressive symptoms conditioned worse scores on both scales. FAST scores were better among those who participated in mutual aid groups (P=0.026). While patients who underwent psychoeducation and those who received anticonvulsant drugs, presented better WHO-5 scores (P = 0.028 and P=0.048 respectively). CONCLUSIONS: Patients with BD showed poor Functionality and poor Well-being despite being stabilized. There is direct relationship between both conditions. Depressive symptoms generated worst scores on the scales.

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.

[Omission of causes of maternal death in death certificates in Argentina: nationwide observational studyOmissão do registro de causas maternas de morte na Argentina: estudo observacional de alcance nacional]. / Omisión de registros de causas maternas de muerte en Argentina: estudio observacional de alcance nacional.

OBJECTIVE: To determine the magnitude and characteristics of the omission of causes of maternal death in death certificates in Argentina, and to re-estimate the maternal mortality ratio (MMR) for the year 2014. METHODS: Cross-sectional study. Retrospective review of medical records of women of childbearing age who died from causes suspected of concealing maternal deaths in public, social security, and private institutions in all jurisdictions of the country between 1 January and 31 December 2014. The cause of death recorded in the death certificate was reclassified. Outcome measures included: percentage of records with an omission, structure of causes of death, location, time of death with respect to the reproductive process, and gestational age. The RMM was re-estimated on the basis of the results. RESULTS: Of a sample of 1,176 cases, 969 medical records (82.4%) were analyzed, identifying 60 cases in which the cause of maternal death was omitted (48 maternal deaths, 12 late maternal deaths). Omissions were found in 14.2% of maternal deaths and 33.3% of late maternal deaths. The new estimated MMR for 2014 varied between 43.3 and 47.2 deaths per 100,000 live births. CONCLUSIONS: The omission of causes of maternal death in death certificates in Argentina may be less frequent than international agencies have reported, with differences in omission between regions. Efforts must be made to emphasize the importance of filling out death certificates correctly.

OBJETIVO: Determinar a dimensão e as características da omissão do registro de causas maternas de morte na Argentina e realizar uma nova estimativa da taxa de mortalidade materna (TMM) para o ano 2014. MÉTODOS: Estudo de corte transversal com a revisão retrospectiva dos registros médicos de mulheres em idade reprodutiva que morreram por causas com suspeita de encobrir mortes maternas em instituições da rede pública e previdência social e instituições particulares em todas as jurisdições do país entre 1º. de janeiro e 31 de dezembro de 2014. Foi feita a reclassificação da causa de morte atribuída no Informe Estatístico de Óbitos. As medidas de resultados foram porcentagem de omissão do registro, estrutura de causas de mortes maternas, local, momento da morte em relação ao processo reprodutivo e idade gestacional. Foi realizada uma nova estimativa da TMM com base nos resultados. RESULTADOS: Foram analisados 969 registros médicos (82,4%) de uma amostra de 1.176 casos. Foram identificados 60 casos em que houve omissão da causa materna de morte (48 mortes maternas, 12 mortes maternas tardias). Verificou-se uma porcentagem de omissão de 14,2% para as mortes maternas e 33,3% para as mortes maternas tardias. A nova TMM estimada para o ano 2014 oscilou entre 43,3 e 47,2 mortes por 100.000 nascidos vivos. CONCLUSÕES: A omissão de registro de causas maternas de morte na Argentina pode ser menor que a informada pelas agências internacionais. Existe diferença de omissão entre as regiões. São necessários esforços que enfatizem a importância do preenchimento correto da certidão de óbito.

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

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.

[Patient's suicide: Emotional impact on healthcare professionals and changes in their behavior]. / Impacto emocional y cambios en la conducta profesional a causa del suicidio de pacientes.

The objective of the study was to assess the emotional impact on healthcare professionals and changes in their behavior as a result of patients' suicide in Argentina. An anonymous survey was e-mailed to healthcare professionals registered in CEMIC University Institute Department of Psychiatry database. A total of 250 responses were obtained. Among respondents, 50.6% had provided treatment to patients that committed suicide. The rate rose to 62.5% among psychiatrists. The professionals that gave an affirmative response were assessed with Horowitz Impact of Event Scale to determine the severity of trauma. The mean score for the sample was 19.6 (mild severity), with a higher mean observed in women (21.2). A difference was found in the group of younger professionals (20-29 years), who revealed a higher impact of event, with moderate severity (29.0). This difference was numerical and failed to be statistically significant (chi2 (4)=8.2110 p=0.084). Only 11.5% of respondents referred to the need to undergo treatment as a result of a patient's suicide-related death. However, 41.5% experienced a negative impact on their physical or mental health. About 60% of professionals made changes in their clinical practice after a patient's suicide. About 80% of respondents admitted they had not received enough training about suicide. Acknowledging these difficulties and providing support to healthcare professionals is crucial to face these challenges.

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.

[Use of scales in depression patients in clinical practice in Argentina]. / Uso de escalas en depresión en la práctica clínica en Argentina.

Although depression is a treatable cause of suffering, disability and death, its identifcation and treatment continue to be a challenge in clinical practice and a severe problem for global public health. The main objective of this study was to investigate the frequency with which mental health professionals use scales to assess depressive patients in Argentina and to determine the reasons that constrain such practice. Between July and September 2012 a national survey was conducted by e-mail. Professionals registered in the database of the Argentine Association of Psychiatrists were invited to participate in the survey. Responses were obtained from 243 professionals. Of the total respondents, only 8.7% said they always used scales to assess depressive patients. The reasons recorded by most respondents why scales were not used were: lack of time and the belief that they do not help in clinical practice. Despite the fact that treatment guidelines for depression recommend the use of scales to optimize the assessment and treatment of depressive disorders, this does not seem to be the usual behavior in clinical practice in our country.

[QUICK INVENTORY OF DEPRESSIVE SYMPTOMATOLOGY SELF-REPORT IN THE CLINICAL PRACTICE OF DEPRESSIVE PATIENTS]. / Cuestionario breve de sintomatolog!a depresiva autoadministrado en la práctica clinica de pacientes depresivos.

INTRODUCTION: To determine the intensity of depressive disorder is helpful to make treatment decisions. The purpose of this study is to establish the correlation between the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) and Montgomery Asberg Depression Rating Scale (MADRS), in order to measure the depression intensity in outpatients from two urban areas in Argentina. METHOD: Over an 18-month period, 67 outpatients from the current clinical practice were included in the study. They first presented with a diagnosis of nonpsychotic major depressive disorder, according to the DSM-IV-TR criteria. Both the QIDS-SR16 and MADRS were administered. RESULTS: The internal consistency of the QIDS-SR16 was acceptable, with the Cronbach's alpha being 0.74. Criterion validity was estimated through the correlation between both scales and was 0.84 (p<0.0001), while gamma statistics for the ordinal comparison of categories was 0.95, thus showing a high correlation. CONCLUSION: The study findings show that the correlation between the two analyzed questionnaires allows determining depression intensity in patients from our setting. These findings further allow analyzing the usefulness of the scale for several depressive subtypes. As far as training and administration, the QIDS-SR16 is less time-consuming.

Feasibility and safety study of a new device (Odón device) for assisted vaginal deliveries: study protocol.

BACKGROUND: Intrapartum complications are responsible for approximately half of all maternal deaths, and two million stillbirth and neonatal deaths per year. Prolonged second stage of labour is associated with potentially fatal maternal complications such as haemorrhage and infection and it is a major cause of stillbirth and newborn morbidity and mortality. Currently, the three main options for managing prolonged second stage of labour are forceps, vacuum extractor and caesarean section. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for caesarean section) and/or highly trained staff which are often not available in low resource settings. The specific aim of the proposed study is to test the safety and feasibility of a new device (Odón device) to effectively deliver the fetus during prolonged second stage of labour. The Odón device is a low-cost technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care and reducing maternal and perinatal morbidity and mortality in low resource settings. METHODS/DESIGN: This will be a hospital-based, multicenter prospective phase 1 cohort study with no control group. Delivery with the Odón device will be attempted under normal labour and non-emergency conditions on all the women enrolled in the study. One-hundred and thirty pregnant women will be recruited in tertiary care facilities in Argentina. Safety will be assessed by examining maternal and infant outcomes until discharge. Feasibility will be evaluated by observing successful expulsion of the fetal head after one-time application of the device under standardized conditions (full cervical dilation, anterior presentation, +2 station, normal fetal heart rate). TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier: ACTRN12613000141741.

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.

[Clinical-pathological features and gene profile in colorectal cancer]. / Caracteres clínico-patológicos y perfil genético en el carcinoma colorrectal.

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.

[Screening for symptoms of depression during postpartum and the long term follow up: temporal stability and associated factors]. / Detección de síntomas depresivos durante el postparto inmediato y el seguimiento a largo plazo: estabilidad temporal y factores asociados.

AIMS: To describe the frequency of depressive symptoms compatible with a postpartum depression diagnosis, the associated factors and the temporal stability. METHODS: During 2006-2007 398 hospitalized puerperal women who attended CEMIC were interviewed 5 days after childbirth using the Edinburgh Postnatal Depression Scale and a socio-demographic questionnaire. A logistic regression analysis was performed to identify associated factors with a positive screening. During the following 6-12 months a follow up was carried with two groups of similar characteristics. RESULTS: The frequency of depressive symptoms at post partum was 17.8% (cut off = 10). Depressive history and neonatal intensive care were significantly related to a positive screening. From the 110 interviewed women, 24 were positive in the follow-up. CONCLUSION: The prevalence of risk for postpartum depression in the sample of patients surveyed is within the parameters reported in international literature. At the 6 month follow up, 6 previously asymptomatic women during the first screening turned on positive. It is theorize the existence of potential postpartum depression cases that can manifest up to a year after childbirth.

Clinical implementation of a cervical cancer screening program via co-testing at a university hospital.

The Human Papillomavirus (HPV) test is a crucial technology for cervical cancer prevention because it enables programs to identify women with high-risk HPV infection who are at risk of developing cervical cancer. Current U.S. Preventive Services Task Force recommendations include cervical cancer screening every three years with cervical cytology alone or every five years with either high-risk HPV testing alone or high-risk HPV testing combined with cytology (co-testing). In Argentina, 7,548 new cervical cancer cases are diagnosed each year with 3,932 deaths attributed to this cause. Our study aims to show the clinical implementation of a cervical cancer screening program by concurrent HPV testing and cervical cytology (co-testing); and to evaluate the possible cervical cancer screening scenarios for Latin America, focusing on their performance and average cost. A cervical cancer screening five year program via co-testing algorithm (Hybrid-2-Capture/cytology) was performed on women aged 30-65 years old at a university hospital. Statistical analysis included a multinomial logistic regression, and two cancer screening classification alternatives were tested (cytology-reflex and HPV-reflex). A total of 2,273 women were included, 91.11% of the participants were double-negative, 2.55% double-positive, 5.90% positive-Hybrid-2-Capture-/negative-cytology, and 0.44% negative-Hybrid-2-Capture/positive-cytology. A thorough follow-up was performed in the positive-Hybrid-2-Capture group. Despite our efforts, 21 (10.93%) were lost, mainly because of changes on their health insurance coverage which excluded them from our screening algorithm. Of the 171 women with positive-Hybrid-2-Capture results and follow-up, 68 (39.77%) cleared the virus infection, 64 (37.43%) showed viral persistence, and 39 (22.81%) were adequately treated after detection via colposcopy/biopsy of histological HSIL (High-Grade Squamous Intraepithelial Lesion). The prevalence of high-risk HPV in this population was 192 women (8.45%), with HSIL histology detection rates of 17 per 1,000 screened women. A multinomial logistic regression analysis was performed over the women with positive-Hybrid-2-Capture considering the follow up (clearance, persistence and HSIL) as dependent variable, and the cytology test results (positive- or negative-cytology and Atypical Squamous Cells of Undetermined Significance, ASC-US) as independent variable. The model supported a direct association between cytology test results and follow up: negative-cytology/clearance, ASC-US/persistence, and positive-cytology/HSIL with the following probabilities of occurrence for these pairs 0.5, 0.647 and 0.647, respectively. Cytology could be considered a prognostic-factor in women with a positive-Hybrid-2-Capture. These findings suggest that the introduction of co-testing could diminish the burden of cervical cancer in low-and middle-income-countries, acting as a tool against inequity in healthcare.

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.

Prenatal sonographic detection of birth defects in 18 hospitals from South America.

OBJECTIVE: The purpose of this study was to assess the accuracy of prenatal sonographic diagnosis of birth defects and the gestational age at detection according to the health insurance schemes of mothers in 450 malformed neonates from 18 South American hospitals on the basis of prenatal sonographic records. METHODS: Between July 2000 and December 2003, 18 hospitals included in the Latin American Collaborative Study of Congenital Malformations (13 from Argentina [8 public and 5 nonpublic], 3 from Brazil [2 public and 1 nonpublic], 1 from Chile [nonpublic], and 1 from Venezuela [public]) voluntarily participated in this prospective observational study, recording fetuses with sonographically detected malformations. Prenatal sonographic descriptions of anomalies were compared with those recorded at birth. RESULTS: Of 812 anomalies detected at birth, 457 had been prenatally detected (detection rate, 56.3%; 95% confidence interval, 52.8%-59.8%). Before 24 gestational weeks, anencephaly had the highest detection rate. Cleft lip and clubfoot were more easily detected when associated with other anomalies. The detection rates for central nervous system and renourinary malformations were greater than 80%. Detection rates between both health insurance schemes (public and nonpublic) did not show significant differences, but anencephaly, spina bifida, renourinary defects, and cleft lip with or without cleft palate were detected earlier in patients from nonpublic rather than in public hospitals. CONCLUSIONS: For specific anomalies, South America shows similar levels of prenatal sonographic detection as developed countries. Detection rates during pregnancy were similar for public and nonpublic hospitals, whereas cases were diagnosed earlier in patients from nonpublic hospitals.