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Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) infants and has been associated with impaired neurodevelopment. Some research suggests that adverse effects of EUGR may be more severe in boys. We investigated EUGR and neurodevelopment at 2 years of corrected age (CA) by sex in a VPT birth cohort. Data come from a population-based cohort of children born <32 weeks' gestation from 11 European countries and followed up at 2 years CA. Postnatal growth during the neonatal hospitalization was measured with: (1) birthweight and discharge-weight Z-score differences using Fenton charts (2) weight-gain velocity using Patel's model. Published cut-offs were used to define EUGR as none, moderate or severe. Neurodevelopmental impairment was assessed using a parent-report questionnaire, with standardized questions/instruments on motor function, vision, hearing and non-verbal cognition. We estimated relative risks (RR) adjusting for maternal and neonatal characteristics overall and by sex. Among 4197 infants, the prevalence of moderate to severe impairment at 2 years CA was 17.7%. Severe EUGR was associated with neurodevelopmental impairment in the overall sample and the interaction with sex was significant. For boys, adjusted RR were 1.57 (95% Confidence Intervals (CI): 1.18–2.09) for Fenton's delta Z-score and 1.50 (95% CI: 1.12–2.01) for Patel's weight-gain velocity, while for girls they were 0.97 (0.76–1.22) and 1.12 (0.90–1.40) respectively. EUGR was associated with poor neurodevelopment at 2 years among VPT boys but not girls. Understanding why boys are more susceptible to the effects of poor growth is needed to develop appropriate healthcare strategies. [ABSTRACT FROM AUTHOR]

The survival rate of infants born before 25 weeks of gestational age in France is extremely low compared with that of many other countries: 0%, 1%, and 31% at 22, 23, and 24 weeks' in the last national cohort study. A non-optimal regionalization and variations in practice are prevalent. Some parents in social media and support groups have reported feeling lost and confused with mixed messages leading to lack of trust. These data kindled a major debate in France around perinatal management leading to an investigation exploring neonatologists' perspectives and ways to improve care. The majority (81%) of the responding neonatologists reported more active care and higher survival rates than in 2011, although others continued preferring delivery room comfort care and limited NICU treatment at or before 24 weeks. The desire to improve was an overarching theme in all the respondents' answers to open-ended questions. Barriers to active care included an absence of expertise and of benchmarking to guide optimal care, and limited resources in the NICU and during follow-up - all leading to self-fulfilling prophecies of poor prognosis. Optimization of regionalization, perinatal teamwork and parental involvement, fostering experience by creating specific perinatal centers, stimulating benchmarking, and working with policy makers to allow better long-term outcomes could enable higher survival. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between histologic chorioamnionitis (HCA) and bronchopulmonary dysplasia (BPD) in very preterm infants, both in a general population and for those born after spontaneous preterm labor and after preterm premature rupture of membranes (pPROM).Study Design: This study included 2513 live born singletons delivered at 24-31 weeks of gestation from a national prospective population-based cohort of preterm births; 1731 placenta reports were available. HCA was defined as neutrophil infiltrates in the amnion, chorion of the membranes, or chorionic plate, associated or not with funisitis. The main outcome measure was moderate or severe BPD. Analyses involved logistic regressions and multiple imputation for missing data.Results: The incidence of HCA was 28.4% overall: 38% in cases of preterm labor, 64% in cases of pPROM, and less than 5% in cases of vascular disorders. Overall, the risk of BPD after adjustment for gestational age, sex, and antenatal steroids was reduced for infants with HCA (HCA alone: aOR 0.6 [95% CI 0.4-0.9]; associated with funisitis: aOR 0.5 [95% CI 0.3-0.8]). This finding was explained by the high rate of BPD and low rate of chorioamnionitis among children with fetal growth restriction. HCA was not associated with BPD in the preterm labor (13.4% vs 8.5%; aOR 0.9; 95% CI 0.5-1.8) or in the pPROM group (12.9% vs 12.1%; aOR 0.6; 95% CI 0.3-1.3).Conclusion: In homogeneous groups of infants born after preterm labor or pPROM, HCA is not associated with BPD. [ABSTRACT FROM AUTHOR]

Background: Fetal growth restriction is defined using ultrasound parameters during pregnancy or as a low birthweight for gestational age after birth, but these definitions are not always concordant.Objective: The purpose of this study was to investigate fetal and neonatal outcomes based on antenatal vs postnatal assessments of growth restriction.Study Design: From the EPIPAGE 2 population-based prospective study of very preterm births in France in 2011, we included 2919 singleton nonanomalous infants 24-31 weeks gestational age. We constituted 4 groups based on whether the infant was suspected with fetal growth restriction during pregnancy and/or was small for gestational age with a birthweight <10th percentile of intrauterine norms by sex: 1) suspected with fetal growth restriction/small for gestational age 2) not suspected with fetal growth restriction/small for gestational age 3) suspected with fetal growth restriction/not small for gestational age and 4) not suspected with fetal growth restriction/not small for gestational age. We estimated relative risks of perinatal mortality and morbidity for these groups adjusting for maternal and neonatal characteristics.Results: We found that 22.2% of infants were suspected with fetal growth restriction/small for gestational age, that 11.4% infants were not suspected with fetal growth restriction/small for gestational age, that 3.0% infants were suspected with fetal growth restriction/not small for gestational age, and that 63.4% infants were not suspected with fetal growth restriction/not small for gestational age. Compared with infants who were not suspected with fetal growth restriction/not small-for-gestational-age infants, small-for-gestational-age infants suspected and not suspected with fetal growth restriction had higher risks of stillbirth or termination of pregnancy (adjusted relative risk, 2.0 [95% confidence interval, 1.6-2.5] and adjusted relative risk, 2.8 [95% confidence interval, 2.2-3.4], respectively), in-hospital death (adjusted relative risk, 2.8 [95% confidence interval, 2.0-3.7] and adjusted relative risk, 2.0 [95% confidence interval, 1.5-2.8], respectively), and bronchopulmonary dysplasia (adjusted relative risk, 1.3 [95% confidence interval, 1.2-1.4] and adjusted relative risk, 1.3 [95% confidence interval, 1.1-1.4], respectively), but not severe brain lesions. Risks were not increased for infants suspected with fetal growth restriction but not small-for-gestational-age.Conclusion: Antenatal and postnatal assessments of fetal growth restriction were not concordant for 14% of very preterm infants. In these cases, birthweight appears to be the more relevant parameter for the identification of infants with higher risks of adverse short-term outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of being small for gestational age (SGA) on very preterm mortality and morbidity rates by using different birthweight percentile thresholds and whether these effects differ by the cause of the preterm birth. Study design: The study included singletons and twins alive at onset of labor between 24 and 31 weeks of gestation without congenital anomalies from the Models of Organising Access to Intensive Care for very preterm births very preterm cohort in 10 European regions in 2003 (n = 4525). Outcomes were mortality, intraventricular hemorrhage grade III and IV, cystic periventricular leukomalacia, and bronchopulmonary dysplasia (BPD). Birthweight percentiles in 6 classes were analyzed by pregnancy complication. Results: The mortality rate was higher for infants with birthweights <25th percentile when compared with the 50th to 74th percentile (adjusted odds ratio, 3.98 [95% CI, 2.79-5.67] for <10th; adjusted odds ratio, 2.15 [95% CI, 1.54-3.00] for 10th-24th). BPD declined continuously with increasing birthweight. There was no association for periventricular leukomalacia or intraventricular hemorrhage. Seventy-five percent of infants with birthweights <10th percentile were from pregnancies complicated by hypertension or indicated deliveries associated with growth restriction. However, stratifying for pregnancy complications yielded similar risk patterns. Conclusions: A 25th percentile cutoff point was a means of identifying infants at higher risk of death and a continuous measure better described risks of BPD. Lower birthweights were associated with poor outcomes regardless of pregnancy complications. [ABSTRACT FROM AUTHOR]

After discussion with the parents, periviable infants can receive either active treatment or palliative care. The rate of active treatment in France is lower than in other developed countries, as is the survival rate of infants in this gestational age range. This study's main objective was to assess the effect of a standardized perinatal management protocol (EXPRIM) on the neonatal outcome of children born before 27 weeks of gestation. A before-and-after study was conducted in the two level-3 hospitals of the Risks and Pregnancy DHU to compare two 16-month periods. The EXPRIM protocol was based on routine administration of prenatal corticosteroid therapy and a scheduled combined obstetric-pediatric group prenatal prognostic evaluation, not based solely on gestational age. The study included all births between 22 weeks and 26 weeks + 6 days of gestation, except in utero deaths diagnosed at admission and medical terminations of pregnancy for fetal malformation, both excluded. The principal endpoint was survival without severe neonatal morbidity. The study included 267 women: 116 (128 newborns) in period 1 and 151 (172 newborns) in period 2. The median gestational age at admission to the maternity unit was 2.5 days younger in period 2, and the number of women admitted at 22–23 weeks doubled in period 2 (59 vs 29, respectively). Overall, the rates of live births, NICU transfer, and survival without severe morbidity were similar during the two periods. More infants were liveborn between 22 and 24 weeks in period 2 (66 vs 43). Of all newborns transferred to the NICU, 26 (29%) survived without severe morbidity in period 1 and 46 (39%) in period 2. After multivariate analysis, survival without severe morbidity did not differ significantly. Implementation of the EXPRIM protocol led to active treatment of more mothers and their children at the border of viability, and increased the number of children who survived without severe morbidity even if, overall, there was no statistically significant difference in percentage. [ABSTRACT FROM AUTHOR]

To determine the prevalence, short-term prognosis and pharmacologic management of pulmonary hypertension (PH) among very preterm infants born before 32 weeks gestation (WG). In the EPIPAGE-2 French national prospective population-based cohort of preterm infants born in 2011, those presenting with PH were identified and prevalence was estimated using multiple imputation. The primary outcome was survival without severe morbidity at discharge and was compared between infants with or without PH after adjusting for confounders, using generalized estimating equations models. Subgroup analysis was performed according to gestational age (GA) groups. Among 3383 eligible infants, 3222 were analyzed. The prevalence of PH was 6.0 % (95 % CI, 5.2–6.9), 14.5 % in infants born at 22–27+6 WG vs 2.7 % in infants born at 28–31+6 WG (P <.001). The primary outcome (survival without severe morbidity at discharge) occurred in 30.2 % of infants with PH vs 80.2 % of infants without PH (P <.001). Adjusted incidence rate ratios for survival without severe morbidity among infants with PH were 0.42 (0.32–0.57) and 0.52 (0.39–0.69) in infants born at 22–27+6 weeks gestation and those born at 28–31+6 weeks, respectively. Among infants with PH, 92.2 % (95 % CI, 87.7–95.2) received sedation and/or analgesia, 63.5 % (95 % CI, 56.6–69.9) received inhaled NO and 57.6 % (95 % CI, 50.9–64.0) received hemodynamic treatments. In this population-based cohort of very preterm infants, the prevalence of PH was 6 %. PH was associated with a significant decrease of survival without severe morbidity in this population. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the impact of extreme preterm premature rupture of membranes (PPROM) <25 weeks of gestation on preterm child outcome. Study design: Retrospective study comparing the neonatal and 2-year outcomes of infants exposed to extremely PPROM <25 weeks with a non-exposed group of neonates in a tertiary care referral centre located in Paris, France, between 2003 and 2007. All women with singleton pregnancy and PPROM between 150/7 and 246/7 weeks of gestation were recruited. For each infant born alive, the next inborn neonate matched for gestational age and sex was selected as a control among neonates born alive after spontaneous preterm labour with intact membranes. The main outcome measures were neonatal outcome assessed by a combined criterion of adverse neonatal outcomes and the two-year neurodevelopmental outcome assessed by developmental Brunet–Lézine tests and neurological examinations. Results: In 78 cases of extremely PPROM, 22 live births occurred at a mean gestational age of 265/7 weeks. The percentage of neonates with adverse neonatal outcomes was significantly higher among PPROM than non-exposed cases (68.2 versus 27.3%). At 2 years of age, children from the PPROM group were more likely to have delayed acquisitions (64.3 versus 15.8%) and behavioural disorders (57.1 versus 15.8%). Mean Brunet–Lézine language score was significantly lower among those infants (78.9 versus 96.8). Conclusion: PPROM <25 weeks is associated with increased neonatal mortality and morbidity and with increased risks of delayed acquisitions, behavioural disorders and lower language performance scores at 2 years in comparison with matched preterm neonates born after spontaneous preterm labour with intact membranes. [Copyright &y& Elsevier]

Humans share adaptative capacities to stress with other species, as demonstrated on amphibians: the physiological response to experimental water volume and food deprivation results in the activation of the endocrine axes that drive metamorphosis, in particular the neuroendocrine stress system. Unfavorable effects may, however, occur, probably due to inappropriate timing and/or duration of stress: recent experiments are converging to show a profound impairment of hippocampal functioning in the offspring of mothers exposed to prenatal stress. Moreover, fetal changes are likely one of the risk factors for a number of diseases in adulthood. [Copyright &y& Elsevier]

This review is an attempt to provide an integrative view for the biological changes triggered by fetal stress through a multidisciplinary approach. Acceleration of brain and lung maturation in certain risk pregnancies was first described clinically and confirmed by biochemical, electrophysiological and experimental data. Moreover, new experimental findings suggest that a fetal clock centrally mediated by fetal nutritional status could determine timing of parturition. However, some skepticism persisted about the usefulness of this body of knowledge for obstetrical management in developed countries. The interest concerning this adaptation to intrauterine stress was later renewed from various sources, as developed in Part II. [Copyright &y& Elsevier]

Summary: Neonatal cancer is rare and comprises a heterogeneous group of neoplasms with substantial histological diversity. Almost all types of paediatric cancer can occur in fetuses and neonates; however, the presentation and behaviour of neonatal tumours often differs from that in older children, leading to differences in diagnosis and management. The causes of neonatal cancer are unclear, but genetic factors probably have a key role. Other congenital abnormalities are frequently present. Teratoma and neuroblastoma are the most common histological types of neonatal cancer, with soft-tissue sarcoma, leukaemia, renal tumours, and brain tumours also among the more frequent types. Prenatal detection, most often on routine ultrasound or in the context of a known predisposition syndrome, is becoming more common. Treatment options pose challenges because of the particular vulnerability of the population. Neonatal cancer raises diagnostic, therapeutic, and ethical issues, and management requires a multidisciplinary approach. [ABSTRACT FROM AUTHOR]