Cumulative prevalence of biological and social risk factors at birth in a city in São Paulo / Prevalencia acumulada de factores de riesgo biológicos y sociales al nacer en una ciudad de São Paulo / Prevalência cumulativa dos fatores de risco biológicos e sociais ao nascer em município paulista

ABSTRACT Objective: to identify the cumulative prevalence of biological and social risk factors at birth. Method: a cross-sectional study, with retrospective data collection, carried out with live births in a medium-sized city, from January 2018 to July 2020. A database was used with information aimed at identifying social and biological risks after birth, assessed descriptively. Results: the sample consisted of 4,480 newborns, of which 78.9% were classified as at usual risk, and 21.1% as at risk. The cumulative prevalence showed that most newborns had more than one risk factor, with biological risks being the most prominent: need for admission to Intensive Care Unit, birth with less than 37 weeks of gestation and weight less than 2,500 g. Among the social risks, the following stand out: newborns who had a dead sibling aged less than 5 years old; head of family without income; mothers under 16 years old and who did not undergo prenatal care. The biological risk rate was 7.39 times higher than the social risk rate. Conclusion: the cumulative prevalence of the risks found was significant, with a considerable part of the sample presenting some biological risk.

RESUMEN Objetivo: identificar la prevalencia acumulada de factores de riesgo biológicos y sociales al nacer. Método: estudio transversal, con recolección de datos retrospectiva, realizado con nacidos vivos en un municipio de mediano porte, de enero de 2018 a julio de 2020. Se utilizó una base de datos con información destinada a identificar riesgos sociales y biológicos después del nacimiento, evaluados de forma descriptiva. Resultados: la muestra estuvo constituida por 4.480 recién nacidos, de los cuales el 78,9% fueron clasificados como de riesgo habitual y el 21,1% como de riesgo. La prevalencia acumulada mostró que la mayoría de los recién nacidos tenían más de un factor de riesgo, siendo los biológicos los más destacados: necesidad de hospitalización en Unidad de Cuidados Intensivos, nacimiento con menos de 37 semanas de gestación y peso inferior a 2.500 g. Entre los riesgos sociales se destacan: los recién nacidos que tuvieron un hermano menor de 5 años muerto; cabeza de familia sin ingresos; madres menores de 16 años y que no realizaron control prenatal. La tasa de riesgo biológico fue 7,39 veces superior a la tasa de riesgo social. Conclusión: la prevalencia acumulada de los riesgos encontrados fue significativa, presentando una parte considerable de la muestra algún riesgo biológico.

RESUMO Objetivo: identificar a prevalência cumulativa de fatores de riscos biológicos e sociais ao nascer. Método: estudo transversal, com coleta retrospectiva de dados, realizado com os nascidos vivos de um município de médio porte, no período de janeiro de 2018 a julho de 2020. Utilizou-se banco de dados com informações voltadas para a identificação de riscos sociais e biológicos após o nascimento, avaliados de forma descritiva. Resultados: a amostra foi composta por 4.480 recém-nascidos, sendo 78,9% classificados como bebês de risco habitual, e 21,1%, como de risco. A prevalência cumulativa evidenciou que a maior parte dos recém-nascidos possuía mais de um fator de risco, sendo os riscos biológicos com maior destaque: a necessidade de internação em Unidade de Terapia Intensiva, nascimento com menos de 37 semanas de gestação e peso menor que 2.500 g. Dentre os riscos sociais, evidencia-se: recém-nascidos que tiveram irmão morto com idade menor que 5 anos de idade; chefe de família sem renda; mães com menos de 16 anos e que não realizaram o pré-natal. A taxa de risco biológico foi 7,39 vezes maior que a taxa de risco social. Conclusão: a prevalência cumulativa dos riscos encontrados foi significativa com considerável parte da amostra, apresentando algum risco biológico

Late/post-term decidual basalis-derived mesenchymal stem/stromal cells show evidence of advanced ageing and downregulation of microRNA-516b-5p.

INTRODUCTION: The placenta is a short-lived organ, yet it shows signs of progressive ageing in the third trimester. Studies of ageing chorionic placental tissue have recently flourished, providing evidence of advanced ageing of tissues in the late/post-term (L/PT) period of gestation. However, ageing of the maternal aspect of the maternal-fetal interface, specifically the decidua basalis, is poorly understood. Here, we investigated whether the L/PT period was associated with advanced ageing and exhaustion of important decidua basalis mesenchymal stem/stromal cells (DMSCs) functions. METHODS: In this study, DMSCs were isolated and characterised from early term (ET) and L/PT placental tissue and they were then investigated by employing various MSC potency and ageing assays. RNA sequencing was also performed to screen for specific microRNAs that are associated with stem cell exhaustion and ageing between ET- and L/PT-DMSCs. RESULTS: L/PT-DMSCs, when compared to ET-DMSCs, showed significantly lower cell proliferation and a significant higher level of cell apoptosis. L/PT-DMSCs showed significantly lower resistance to oxidative stress and a significant decrease in antioxidant capacity compared with ET-DMSCs. Western blot analysis revealed increased expression of the stress-mediated P-p38MAPK protein in L/PT-DMSCs. RNA Sequencing showed microRNA (miR) miR-516b-5p, was present at significantly lower levels in L/PT-DMSCs. Inhibition of miR-516b-5p in ET-DMSCs revealed a decline in the ability of the inhibited cells to survive in extended cell culture. DISCUSSION: These data provide the first evidence of advanced ageing and exhaustion of important stem cell functions in L/PT-DMSCs, and the involvement of specific miRs in the DMSC ageing process.

Circulating angiogenic profiles and histo-morphological placental characteristics of uncomplicated post-date pregnancies.

INTRODUCTION: The objectives of this study were to describe the histo-morphology of post-date placentas in clinically uncomplicated pregnancies without adverse delivery outcomes and the association with maternal circulating pre-delivery Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), as well as the sFlt-1/PlGF ratio. METHODS: Post-date placentas (gestational week ≥40+2, n = 87) were macroscopically and histo-morphologically assessed according to the international, standardized Amsterdam Workshop Consensus Group criteria. Inter-rater agreement was evaluated by percentage of agreement. PlGF and sFlt-1 concentrations were available from maternal serum sampled close to delivery, and were compared by Mann-Whitney U test. Linear regression analyses were adjusted for predefined potential confounders. RESULTS: The majority of the post-date placentas showed morphological signs of delayed maturation. About half of the placentas showed increased syncytial knotting and fibrin. In placentas with increased presence of intervillous fibrin, median maternal PlGF level was significantly lower (p = 0.004), median sFlt-1 level higher and sFlt-1/PlGF ratio significantly higher (p = 0.002) compared to those with normal fibrin amounts. Increased placental syncytial knotting was associated with lower levels of PlGF, higher sFlt-1 and higher sFlt-1/PlGF ratio compared to those with normal knotting. DISCUSSION: Our standardized morphological study of post-date placentas in clinically healthy women with uncomplicated pregnancies and delivery outcomes revealed delayed maturation in the majority of placentas. Increased pre-delivery circulating anti-angiogenic profile was associated with increased intervillous fibrin and syncytial knotting. We propose that circulating maternal angiogenic biomarkers may be of future use in clinical post-date pregnancy assessment, as they reflect important aspects of placental health and function.

[Standard international recommendations for gestational weight gain: suitability for our population]. / Recomendaciones internacionales estándar sobre la ganancia de peso gestacional: adecuación a nuestra población.

INTRODUCTION: Background: gestational weight gain (GWG) is one of the most commonly used indicators in prenatal care, and probably the most influential factor in perinatal outcomes. Objective: to determine the extent to which the GWG of pregnant women from the Ribera Health Department (Valencia) meets GWG international standards as recommended by the U.S. Institute of Medicine (IOM). Methods: a retrospective observational study of a sample of 4,361 women who gave birth at Hospital Universitario de la Ribera between January 1, 2010 and December 31, 2015. Pregnant women were classified according to GWG international recommendations: adequate weight gain, above and below. Results: a higher GWG increases the risk of cesarean delivery or instrumental delivery (OR = 1.454, p < 0.001; OR = 1.442, p < 0.001, respectively), and of having a macrosomic or larger newborn for gestational age (OR = 3.851, p = 0.008; OR = 1.749, p < 0.001, respectively) as compared to an appropriate GWG. GWG is related to birth weight (p < 0.001). Conclusions: the GPG recommendations issued by the IOM are generally well adapted to pregnant women in our environment. It has been found that a GPG other than these recommendations increases the probability of obtaining poor perinatal outcomes. Nevertheless, a more personalized approach is needed, adapting international recommendations to prenatal control for each of the pre-pregnancy BMI categories.

INTRODUCCIÓN: Introducción: la ganancia de peso gestacional (GPG) es uno de los indicadores que más se utilizan en el control prenatal y quizás sea el factor que más influya en los resultados perinatales. Objetivo: determinar hasta qué punto se ajusta la GPG de las gestantes del Departamento de Salud de la Ribera (Valencia) a los estándares internacionales de GPG recomendados por el Institute of Medicine (IOM) de EE. UU. Métodos: estudio observacional retrospectivo sobre una muestra de 4361 mujeres cuyo parto tuvo lugar en el Hospital Universitario de la Ribera entre el 1 enero de 2010 y el 31 de diciembre de 2015. Las gestantes se clasificaron en función de la GPG según las recomendaciones internacionales: incremento de peso adecuado, superior e inferior. Resultados: una mayor GPG recomendada aumenta el riesgo de terminar el parto en cesárea o en parto instrumentado (OR = 1,454, p < 0,001; OR = 1,442, p < 0,001, respectivamente), y de obtener un recién nacido macrosómico o grande para la edad gestacional (OR = 3,851, p = 0,008; OR = 1,749, p < 0,001, respectivamente) con respecto a obtener una GPG adecuada. La GPG está relacionada con el peso al nacer (p < 0,001). Conclusiones: las recomendaciones de GPG emitidas por el IOM se adaptan en general a las gestantes de nuestro entorno. Se ha constatado que una GPG distinta a dichas recomendaciones aumenta la probabilidad de tener resultados perinatales desfavorables. Sin embargo, es necesaria una aproximación más personalizada, adaptando las recomendaciones internacionales al control prenatal en cada una de las categorías de IMC pregestacional.

Hospital admissions for lower respiratory tract infections after early-, late-, and post-term birth.

BACKGROUND: Recent data suggest that early-term births are associated with later respiratory morbidity (LRTI), and post-term births may decrease this risk. OBJECTIVES: The objective was to determine the impact of early-term, late-term, and post-term birth on hospital admission for LRTI up to the age of seven years. Additionally, we explored maternal and perinatal factors associated with the risk of admission for LRTIs. METHODS: The association of early-term (37+0 -38+6  weeks), late-term (41+0 -41+6  weeks), and post-term (≥42 weeks) birth with hospital admissions for lower respiratory tract infections (LRTI) in comparison with infants born full-term (39+0 -40+6  weeks) was assessed and early predictors of LRTI were established. The register study included 948 695 infants born in Finland in 1991-2008. Data were analysed in four-term subgroups. Hospital admissions for bronchiolitis/bronchitis and pneumonia were collected up to 7 years of age. Adjusted Cox proportional hazards models were used to assess risk factors of LRTI admissions. RESULTS: The rates of hospital admission in the early-, full-, late-, and post-term groups were 6.7%, 5.5%, 5.1%, and 4.8% for bronchiolitis/bronchitis, and 2.8%, 2.4%, 2.3%, and 2.3% for pneumonia. Early-term birth was associated with an increased risk of admission for bronchiolitis/bronchitis (hazard ratio HR 1.21, 95% confidence interval CI 1.18, 1.23) and pneumonia (HR 1.16, 95% CI 1.12, 1.20), while late-term (HR 0.93, 95% CI 0.91, 0.95) and post-term births (HR 0.89, 95% CI 0.85, 0.93) were associated with a decreased risk of bronchiolitis/bronchitis admission compared with the full-term group. Maternal age ≤ 20 years, smoking during pregnancy, male sex, caesarean delivery, small for gestational age, 1-minute Apgar score < 4, ventilator support, and neonatal antibiotic therapy were associated with an increased risk of LRTI admission, while being firstborn, born in a level-II hospital and in the Northern region was associated with decreased risk. CONCLUSION: Early-term birth was associated with a higher risk of all LRTI admissions while late-term and post-term births were associated with lower risk of bronchiolitis/bronchitis admission. Modifiable risk factors of LRTIs were smoking during pregnancy, birth by elective caesarean delivery, neonatal ventilator support, and antibiotic therapy.

Gestational age and childhood leukemia: A meta-analysis of epidemiologic studies.

OBJECTIVE: An increasing amount of evidence shows that childhood leukemia is initiated in utero. Birth characteristics initiated in utero, such as gestational age, may play a role in leukemogenesis. The purpose of our meta-analysis is to explore the association between gestational age and childhood leukemia. METHODS: Relevant studies up to 21 April 2017 were collected by searching PubMed and EMBASE databases. Subgroup analysis, sensitivity analysis and publication bias assessment were conducted. RESULTS: A total of 13 studies were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for preterm birth and postterm birth were 1.06 (0.98, 1.13) and 1.01 (0.90, 1.13) for childhood leukemia, 1.04 (0.97, 1.11) and 1.03 (0.95, 1.12) for acute lymphocytic leukemia (ALL), 1.20 (1.00, 1.44) and 1.20 (1.00, 1.43) for acute myeloid leukemia (AML), compared with full-term birth. Study type and study region were the reasons behind the heterogeneity. In subgroup analyses, the summary ORs with 95% CI for childhood leukemia and ALL were 1.23 (1.07, 1.41) and 1.21 (1.06, 1.39) for postterm birth in cohort studies. No significant changes in sensitivity analyses and no publication bias were observed in our analysis. CONCLUSION: Our results suggest that both preterm and postterm infants have an elevated risk of developing AML. In addition, postterm birth increased the risk of childhood leukemia and ALL in cohort studies. However, more studies are warranted to validate these results and explore the biologic mechanisms underlying these relationships.

Lifestyle interventions for the treatment of women with gestational diabetes.

BACKGROUND: Gestational diabetes (GDM) is glucose intolerance, first recognised in pregnancy and usually resolving after birth. GDM is associated with both short- and long-term adverse effects for the mother and her infant. Lifestyle interventions are the primary therapeutic strategy for many women with GDM. OBJECTIVES: To evaluate the effects of combined lifestyle interventions with or without pharmacotherapy in treating women with gestational diabetes. SEARCH METHODS: We searched the Pregnancy and Childbirth Group's Trials Register (14 May 2016), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (14th May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included only randomised controlled trials comparing a lifestyle intervention with usual care or another intervention for the treatment of pregnant women with GDM. Quasi-randomised trials were excluded. Cross-over trials were not eligible for inclusion. Women with pre-existing type 1 or type 2 diabetes were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. All selection of studies, data extraction was conducted independently by two review authors. MAIN RESULTS: Fifteen trials (in 45 reports) are included in this review (4501 women, 3768 infants). None of the trials were funded by a conditional grant from a pharmaceutical company. The lifestyle interventions included a wide variety of components such as education, diet, exercise and self-monitoring of blood glucose. The control group included usual antenatal care or diet alone. Using GRADE methodology, the quality of the evidence ranged from high to very low quality. The main reasons for downgrading evidence were inconsistency and risk of bias. We summarised the following data from the important outcomes of this review. Lifestyle intervention versus control groupFor the mother:There was no clear evidence of a difference between lifestyle intervention and control groups for the risk of hypertensive disorders of pregnancy (pre-eclampsia) (average risk ratio (RR) 0.70; 95% confidence interval (CI) 0.40 to 1.22; four trials, 2796 women; I2 = 79%, Tau2 = 0.23; low-quality evidence); caesarean section (average RR 0.90; 95% CI 0.78 to 1.05; 10 trials, 3545 women; I2 = 48%, Tau2 = 0.02; low-quality evidence); development of type 2 diabetes (up to a maximum of 10 years follow-up) (RR 0.98, 95% CI 0.54 to 1.76; two trials, 486 women; I2 = 16%; low-quality evidence); perineal trauma/tearing (RR 1.04, 95% CI 0.93 to 1.18; one trial, n = 1000 women; moderate-quality evidence) or induction of labour (average RR 1.20, 95% CI 0.99 to 1.46; four trials, n = 2699 women; I2 = 37%; high-quality evidence).More women in the lifestyle intervention group had met postpartum weight goals one year after birth than in the control group (RR 1.75, 95% CI 1.05 to 2.90; 156 women; one trial, low-quality evidence). Lifestyle interventions were associated with a decrease in the risk of postnatal depression compared with the control group (RR 0.49, 95% CI 0.31 to 0.78; one trial, n = 573 women; low-quality evidence).For the infant/child/adult:Lifestyle interventions were associated with a reduction in the risk of being born large-for-gestational age (LGA) (RR 0.60, 95% CI 0.50 to 0.71; six trials, 2994 infants; I2 = 4%; moderate-quality evidence). Birthweight and the incidence of macrosomia were lower in the lifestyle intervention group.Exposure to the lifestyle intervention was associated with decreased neonatal fat mass compared with the control group (mean difference (MD) -37.30 g, 95% CI -63.97 to -10.63; one trial, 958 infants; low-quality evidence). In childhood, there was no clear evidence of a difference between groups for body mass index (BMI) ≥ 85th percentile (RR 0.91, 95% CI 0.75 to 1.11; three trials, 767 children; I2 = 4%; moderate-quality evidence).There was no clear evidence of a difference between lifestyle intervention and control groups for the risk of perinatal death (RR 0.09, 95% CI 0.01 to 1.70; two trials, 1988 infants; low-quality evidence). Of 1988 infants, only five events were reported in total in the control group and there were no events in the lifestyle group. There was no clear evidence of a difference between lifestyle intervention and control groups for a composite of serious infant outcome/s (average RR 0.57, 95% CI 0.21 to 1.55; two trials, 1930 infants; I2 = 82%, Tau2 = 0.44; very low-quality evidence) or neonatal hypoglycaemia (average RR 0.99, 95% CI 0.65 to 1.52; six trials, 3000 infants; I2 = 48%, Tau2 = 0.12; moderate-quality evidence). Diabetes and adiposity in adulthood and neurosensory disability in later childhoodwere not prespecified or reported as outcomes for any of the trials included in this review. AUTHORS' CONCLUSIONS: Lifestyle interventions are the primary therapeutic strategy for women with GDM. Women receiving lifestyle interventions were less likely to have postnatal depression and were more likely to achieve postpartum weight goals. Exposure to lifestyle interventions was associated with a decreased risk of the baby being born LGA and decreased neonatal adiposity. Long-term maternal and childhood/adulthood outcomes were poorly reported.The value of lifestyle interventions in low-and middle-income countries or for different ethnicities remains unclear. The longer-term benefits or harms of lifestyle interventions remains unclear due to limited reporting.The contribution of individual components of lifestyle interventions could not be assessed. Ten per cent of participants also received some form of pharmacological therapy. Lifestyle interventions are useful as the primary therapeutic strategy and most commonly include healthy eating, physical activity and self-monitoring of blood glucose concentrations.Future research could focus on which specific interventions are most useful (as the sole intervention without pharmacological treatment), which health professionals should give them and the optimal format for providing the information. Evaluation of long-term outcomes for the mother and her child should be a priority when planning future trials. There has been no in-depth exploration of the costs 'saved' from reduction in risk of LGA/macrosomia and potential longer-term risks for the infants.

Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children.

OBJECTIVES: To examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD. STUDY DESIGN: A multicenter, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weight was categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with the birth weight distribution in the general US population. The severity of liver histology was assessed by birth weight category. RESULTS: Children with NAFLD (n = 538) had overrepresentation of both LBW and HBW compared with the general US population (LBW, 9.3%; NBW, 75.8%; HBW, 14.9% vs LBW, 6.1%; NBW, 83.5%; HBW 10.5%; P < .0001). Children with HBW had significantly greater odds of having more severe steatosis (OR, 1.82, 95% CI. 1.15-2.88) and nonalcoholic steatohepatitis (OR, 2.03; 95% CI, 1.21-3.40) compared with children with NBW. In addition, children with NAFLD and LBW had significantly greater odds of having advanced fibrosis (OR, 2.23; 95% CI, 1.08-4.62). CONCLUSION: Birth weight involves maternal and in utero factors that may have long-lasting consequences. Children with both LBW and HBW may be at increased risk for developing NAFLD. Among children with NAFLD, those with LBW or HBW appear to be at increased risk for more severe disease.

Comparison of Amniotic Fluid Cytokine Levels in Postterm and Term Pregnancy: a Prospective Study.

BACKGROUND: To evaluate amniotic fluid pro- and anti-inflammatory cytokine levels in women with postterm and term pregnancies in labor and not in labor. METHODS: The study involved three groups: postterm (Group 1, n = 29), term in labor (Group 2, n = 28), and control (Group 3, n = 30). All groups were compared with respect to age, gravidity, parity, obstetric history, gestation week, cervical dilatation and effacement, maternal serum C-reactive protein and white cell count, amniotic interleukin 4, 6, and 10 levels, birthweight, and cord blood pH. RESULTS: The amniotic fluid interleukin 10 level was 24.4 ± 8.8 pg/mL in the postterm group, 13.5 ± 5.1 pg/mL in the term in labor group, and 19.8 ± 5.4 pg/mL in the control group (p < 0.001). The amniotic fluid interleukin 4 level was 86.5 ± 57.7 pg/mL in the postterm group, 38.2 ± 29.2 pg/mL in the term in labor group, and 81.9 ± 68.4 pg/mL in the control group (p = 0.002). The amniotic fluid interleukin 6 level was 329 ± 135.1 pg/mL in the postterm group, 252.8 ± 138.7 pg/mL in the term in labor group, and 227.9 ± 114.4 pg/mL in the control group (p = 0.02). There was a positive correlation between gestational age and IL-10 levels (p < 0.05). CONCLUSIONS: Amniotic fluid IL-10 and IL-4 cytokine levels were increased in postterm pregnancy and they decreased with active labor.

Visfatin/Nampt and SIRT1: Roles in Postterm Delivery in Pregnancies Associated With Obesity.

Visfatin is both a systemic adipocytokine and the cytosolic enzyme, nicotinamide phosphoribosyl transferase (Nampt). This is a longevity protein, which extends the lifespan of human cells by activating sirtuin 1 (SIRT1). In this study, we sought a role for these proteins in obese pregnant women, who experience more postterm deliveries. Thus, 78 women (26 lean, 24 overweight, and 28 obese) were recruited and maternal blood and placental tissue collected prior to term labor. Plasma levels were measured by enzyme-linked immunosorbent assay and quantitative immunohistochemistry used for placenta. We confirmed maternal plasma interleukin 6 increased according to prepregnancy body mass index (BMI; P < .0001) and showed a linear relationship between BMI and syncytiotrophoblast visfatin/Nampt (P = .021) but not with its levels in maternal plasma. Both systemic and placental visfatin/Nampt were significantly associated with placental SIRT1 levels (P = .028 and .017). Thus, higher visfatin/Nampt may prevent a labor-associated decrease in SIRT1 leading to postterm delivery in obesity.

Perinatal outcomes following an earlier post-term labour induction policy: a historical cohort study.

OBJECTIVE: To assess the changes in perinatal outcomes in children born from 37 weeks of gestation after implementation of a more proactive labour induction practice from 2009. DESIGN: Register-based cohort study. SETTING: Denmark, 2000-12. POPULATION: Newborns from 37 weeks of gestation. METHODS: Perinatal outcomes were estimated using a logistic regression analysis with adjustment for gestational age, maternal age, parity, plurality, smoking and body mass index. MAIN OUTCOME MEASURES: Perinatal outcomes. RESULTS: A total of 770 926 infants were included. Labour induction from 37 weeks increased from 9.7% in 2000-02 to 22.5% in 2011-12. From 2003-05 to 2011-12, the risk of umbilical cord pH < 7.0 decreased by 23%; odds ratio (OR) 0.77 (95% confidence interval 0.67-0.89), and the adjusted OR of Apgar score < 7 at 5 minutes was unchanged. The risk of admission to neonatal intensive care units increased by 56%; OR 1.56 (1.47-1.66), whereas the risk of neonatal deaths decreased by 44%; OR 0.56 (0.45-0.70). The risk of cerebral palsy was from 2000-02 to 2009-10 reduced by 26%; OR 0.74 (0.60-0.90). The proportion of infants born with fetal weight ≥ 4500 g decreased by one-third; OR 0.68 (0.65-0.71). However, the risk of shoulder dystocia increased by 32%; OR 1.32 (1.21-1.44), whereas the risk of peripheral nerve injuries was reduced by 43%; OR 0.57 (0.45-0.73). CONCLUSION: The results suggest an overall improvement in perinatal outcomes as a result of a more proactive post-term labour induction practice.

Intrapartum and neonatal outcome of screening non-stress test (NST) compared with no screening NST in healthy women at 40-40 (+6) weeks of gestation.

AIM: The aim of this study was to compare the intrapartum and neonatal outcome between screening non-stress test (NST) and no screening NST groups in healthy pregnant women at a gestational age of 40-40(+6) weeks. METHODS: Healthy pregnant women, with a gestational age of 40-40(+6) weeks who had received antenatal care and delivered at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 1 July 2011 and 31 March 2013, were included in the study. The treatment group consisted of women who had had screening NST while no NST screening had been performed in the control group. The primary outcome was intrapartum and neonatal outcome, which included stillbirth, the incidence of non-reassuring fetal heart, neonatal morbidity (meconium aspiration, respiratory distress, neonatal asphyxia) and neonatal mortality. Secondary outcome was the cost-effectiveness of the NST screening. RESULTS: A total of 460 healthy pregnant women with a gestational age of 40-40(+6) weeks were included in the study. There were 228 cases in the NST screening group and 232 cases in the no NST screening group. There was no significant difference in the incidence of stillbirth, non-reassuring fetal heart, neonatal morbidity (meconium aspiration, respiratory distress, neonatal asphyxia) and neonatal mortality. The cost of NST plus neonatal care was higher in the NST screening group than the no NST screening group. CONCLUSION: Routine performing NST at the gestational age of 40-40(+6) weeks has no benefit in intrapartum and neonatal outcome.

Perinatal mortality by gestational week and size at birth in singleton pregnancies at and beyond term: a nationwide population-based cohort study.

BACKGROUND: Whether gestational age per se increases perinatal mortality in post-term pregnancy is unclear. We aimed at assessing gestational week specific perinatal mortality in small-for-gestational-age (SGA) and non-SGA term and post-term gestations, and specifically to evaluate whether the relation between post-term gestation and perinatal mortality differed before and after ultrasound was introduced as the standard method of gestational age estimation. METHODS: A population-based cohort study, using data from the Medical Birth Registry of Norway (MBRN), 1967-2006, was designed. Singleton births at 37 through 44 gestational weeks (n = 1 855 682), excluding preeclampsia, diabetes and fetal anomalies, were included. Odds ratios (OR) with 95% confidence intervals (CI) for perinatal mortality and stillbirth in SGA and non-SGA births by gestational week were calculated. RESULTS: SGA infants judged post-term by LMP had significantly higher perinatal mortality than post-term non-SGA infants at 40 weeks, independent of time period (highest during 1999-2006 [OR 9.8, 95% CI: 5.7-17.0]). When comparing years before (1967-1986) versus after (1987-2006) ultrasound was introduced, there was no decrease in the excess mortality for post-term SGA versus non-SGA births (ORs from 6.1 [95% CI: 5.2-7.1] to 6.7 [5.2-8.5]), while mortality at 40 weeks decreased significantly (ORs from 4.6, [4.0-5.3] to 3.2 [2.5-3.9]). When assessing stillbirth risk (1999-2006), more than 40% of SGA stillbirths (11/26) judged to be ≥41 weeks by LMP were shifted to lower gestational ages using ultrasound estimation. CONCLUSIONS: Mortality risk in post-term infants was strongly associated with growth restriction. Such infants may erroneously be judged younger than they are when using ultrasound estimation, so that the routine assessment for fetal wellbeing in the prolonged gestation may be given too late.

Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group.

STUDY QUESTIONS: What are the risks of adverse outcomes in singletons born after frozen-thawed embryo transfer (FET)? SUMMARY ANSWER: Singletons born after FET have a better perinatal outcome compared with singletons born after fresh IVF and ICSI as regards low birthweight (LBW) and preterm birth (PTB), but a worse perinatal outcome compared with singletons born after spontaneous conception. WHAT IS KNOWN ALREADY: Previous studies have shown a worse perinatal outcome in children born after IVF in general compared with children born after spontaneous conception. In singletons born after FET, a lower rate of PTB and LBW and a higher rate of large for gestational age (LGA) compared with singletons born after fresh IVF have been shown. STUDY DESIGN: A retrospective Nordic population-based cohort study of all singletons conceived after FET in Denmark, Norway and Sweden until December 2007 was performed. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Singletons born after FET (n = 6647) were compared with a control group of singletons born after fresh IVF and ICSI (n = 42 242) and singletons born after spontaneous conception (n = 288 542). Data on perinatal outcomes were obtained by linkage to the national Medical Birth Registries. Odds ratios were calculated for several perinatal outcomes and adjustments were made for maternal age, parity, year of birth, offspring sex and country of origin. MAIN RESULTS AND THE ROLE OF CHANCE: Singletons born after FET had a lower risk of LBW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.71-0.91), PTB (aOR 0.84, 95% CI 0.76-0.92), very PTB (VPTB; aOR 0.79, 95% CI 0.66-0.95) and small for gestational age (SGA; aOR 0.72, 95% CI 0.62-0.83), but a higher risk of post-term birth (aOR 1.40, 95% CI 1.27-1.55), LGA (aOR 1.45, 95% CI 1.27-1.64), macrosomia (aOR 1.58, 95% CI 1.39-1.80) and perinatal mortality (aOR 1.49, 95% CI 1.07-2.07) compared with singletons born after fresh IVF and ICSI. Compared with children conceived after spontaneous conception, singletons born after FET had a higher risk of LBW (aOR 1.27, 95% CI 1.13-1.43), very LBW (aOR 1.69, 95% CI 1.33-2.15), PTB (aOR 1.49, 95% CI 1.35-1.63), VPTB (aOR 2.68, 95% CI 2.24-3.22), SGA (aOR 1.18, 95% CI 1.03-1.35), LGA (aOR 1.29, 95% CI 1.15-1.45), macrosomia (aOR 1.29, 95% CI 1.15-1.45) and perinatal (aOR 1.39, 95% CI 1.03-1.87) neonatal (aOR 1.87, 95% CI 1.23-2.84) and infant mortality (aOR 1.92, 95% CI 1.36-2.72). When analyzing trends over time, the risk of being born LGA increased over time for singletons born after FET compared with singletons born after fresh IVF and ICSI (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: As in all observational studies, the possible role of residual confounding factors and bias should be considered. In this study, we were not able to control for confounding factors, such as BMI, smoking and reason for, or length of, infertility. WIDER IMPLICATIONS OF THE FINDINGS: Perinatal outcomes in this large population-based cohort of children born after FET from three Nordic countries compared with fresh IVF and ICSI and spontaneous conception were in agreement with the literature.

Pregnancy-associated plasma protein A levels and neonatal complications in post-date pregnancies.

OBJECTIVES: To assess the association between serum pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotropin (free ß-hCG) in the first trimester and perinatal complications in post-date pregnancies. METHODS: A total of 4948 women, who delivered after 40 gestational weeks, were included. Labour was not induced routinely until 42 weeks. Serum levels of PAPP-A and free ß-hCG were determined at the first-trimester screening for Down syndrome. Neonatal complications were obtained from specific registration forms filled out by senior neonatologists. RESULTS: In post-date pregnancies, PAPP-A < 0.4 multiples of the median was associated with Apgar score of less than 7 at 5 min (ORadj 5.4, 95% CI 2.0-14.3), admission to the neonatal intensive care unit (ORadj 1.5, 95% CI 1.0-2.3) and newborn hypoglycaemia (ORadj 3.4, 95% CI 1.8-6.4). In small for gestation (SGA) neonates, the risk of hypoglycaemia was further increased (OR 14.6, 95% CI 3.4-58.0). Similar analyses were made with free ß-hCG, but no statistically significant associations were found. CONCLUSIONS: Low first-trimester serum PAPP-A was associated with increased neonatal morbidity in post-date pregnancies, particularly in newborns with SGA. Thus, PAPP-A may qualify the timing of induction of labour in these pregnancies.

[Human recombinant erythropoietin therapy]. / Tratamiento con eritropoyetina humana recombinante.

Recombinant human erythropoietin (rHuEpo) has become the most widely used cytokine in the world. Following the success of its use in patients with end-stage renal disease, the usefulness of rHuEpo to ameliorate other anemias was assessed, including pediatric patients and newborn infants. The treatment or prevention of anemia of prematurity with rHuEpo resulted in a significant reduction in the number of transfusions and donor exposure. A clear definition of which premature babies must receive therapy needs yet to be established. Other indications in neonatal period include hyporegenerative and hemolytic anemias. With the exception of chronic renal failure, in older children the efficacy of rHuEpo has not been evaluated as in adults. While an impressive amount of studies were carried out during the last years in adult patients with cancer-related or HIV-infection-related anemias, allowing to establish clear conclusions on its efficacy, only a few trials with small number of patients have been reported in children. Up to date, results in pediatric patients suggest that rHuEpo therapy is as useful as in adult patients, but prospective, randomized trials including large number of patients are essential to achieve definitive conclusions. Results of studies designed to evaluate the efficacy of rHuEpo for sustaining an adequate dose of ribavirin in patients receiving treatment for hepatitis C are encouraging. The potential for use of the non-hematopoietic effects of rHuEpo in newborn infants is a novel and exciting issue. The role of rHuEpo as a tissue protective factor for central nervous system and intestinal mucosa is under exhaustive investigation.

Tratamiento con eritropoyetina humana recombinante / Human recombinant erythropoietin therapy

La eritropoyetina recombinante (rHuEPO) se ha transformado en la citoquina más utilizada terapéuticamente en el mundo. Luego del éxito obtenido en pacientes con insuficiencia renal terminal, se pudo establecer la utilidad de la terapia con rHuEPO para mejorar otras anemias, incluso en pacientes pediátricos y neonatos. El tratamiento o la prevención de la anemia del prematuro mediante el uso de rHuEPO llevó a una significativa reducción en cantidad de transfusiones y en exposición a dadores. Aún debe establecerse una clara definición sobre cuáles niños prematuros deben recibir tratamiento rutinariamente. Otras indicaciones en período neonatal incluyen anemias hiporregenerativas hemolíticas. La eficacia de la rHuEPO en niños mayores, con excepción de la insuficiencia renal crónica, no ha sido tan exhaustivamente evaluada como en adultos. Mientras que durante los últimos años se han realizado gran cantidad de estudios en adultos con anemia asociada al cáncer o a infección por HIV, permitiendo establecer conclusiones claras sobre su eficacia, sólo escasa cantidad de estudios con pequeño número de pacientes han sido realizados en niños. Hasta la fecha, los resultados sugieren que la terapia con rHuEPO en niños es tan útil como en adultos, pero la realización de estudios aleatorizados prospectivos incluyendo gran número de pacientes es esencial para alcanzar conclusiones definitivas. Los resultados de estudios dirigidos a evaluar la eficacia de la rHuEpo para mantener una dosis adecuada de ribavirina en pacientes en tratamiento por hepatitis C son alentadores. La utilización potencial de los efectos no hemopoyéticos de la rHuEPO en neonatos es un terreno novedoso y apasionante. El rol de la Epo como citoprotector para sistema nervioso central y mucosa intestinal está bajo investigación exhaustiva.

Effect of in utero growth retardation on lung function at follow-up of prematurely born infants.

The aim of the study was to determine if prematurely born children who had suffered intra-uterine growth retardation (IUGR) had more severe lung function abnormalities than those born an appropriate weight for gestational age (AGA). Analysis of the lung function results of 119 infants (median (range) gestational age of 30 (23-35) weeks) was undertaken. In total, 31 of the infants had suffered IUGR and were born small for gestational age (SGA). Functional residual capacity and airways resistance (Raw) were measured at a median post-natal age of 10 (6-24) months. Specific airway conductance (sGaw) was calculated from thoracic gas volume and Raw. The SGA children were born at a greater gestational age and had a lower body weight at testing than the AGA children. Raw and sGaw differed between the SGA and AGA children. Regression analysis demonstrated that lung volumes were significantly related to body weight at testing, Raw was related to IUGR, maternal smoking and bronchopulmonary dysplasia, and sGaw to maternal smoking. In conclusion, these results suggest that prematurely born infants who have suffered intra-uterine growth retardation may be at increased risk of impaired lung function at follow-up.

Acinar arterial changes with chronic lung disease of prematurity in the surfactant era.

Because echocardiographic studies on infants with chronic lung disease (CLD) suggest that pulmonary hypertension (PH) may contribute to its severity, we studied acinar arterial walls in the following surfactant-era infants: controls (n=38): 22-41 weeks of gestational age (GA), exposed briefly to oxygen and positive pressure ventilation, died within 48 hr of birth; prolonged rupture of fetal membranes (PROM) and persistent pulmonary hypertension (PPHN) (n=17); and SCORE (integrated area under curve of average daily FiO2 x average daily MAP) groups (<20, 20-69, and 70-500; mild, moderate, and severe clinical lung disease, respectively, n=35): 23-30 weeks GA, lived 7-79 days. Lungs were stained for elastic tissue and smooth muscle actin. Vessels were assessed for percent of vessel circumference with smooth muscle, extent of elastic laminae in the walls, and percent arterial wall thickness (%AWT) at three levels: terminal to respiratory bronchiole transition (TRB), alveolar duct, and saccule. At the alveolar ductal and saccular levels, percent arterial wall thickness (%AWT) in mild CLD (SCORE < 20) was less than controls (P < 0.05) and those with more severe CLD (SCORE 70-500), indicating that normal postnatal arterial wall thinning may be delayed, or there is remodeling associated with increased %AWT. Severe CLD infants also had a significantly higher percent of circumferential actin than those with milder disease (SCORE < or = 69) and controls. In moderate and severe CLD, there was an increase in extent of the elastic laminae compared to controls and mild CLD. These changes were also significantly greater in PROM and PPHN infants compared to even severe CLD. We conclude that PH is a real possibility in severe CLD infants after discharge at 36 weeks. Grading the severity of CLD at discharge, and echocardiographic studies, may guide subsequent oxygen therapy.