The interrelatedness of cognitive abilities in very preterm and full-term born children at 5.5 years of age: a psychometric network analysis approach.

BACKGROUND: Very preterm (VP) birth is associated with a considerable risk for cognitive impairment, putting children at a disadvantage in academic and everyday life. Despite lower cognitive ability on the group level, there are large individual differences among VP born children. Contemporary theories define intelligence as a network of reciprocally connected cognitive abilities. Therefore, intelligence was studied as a network of interrelated abilities to provide insight into interindividual differences. We described and compared the network of cognitive abilities, including strength of interrelations between and the relative importance of abilities, of VP and full-term (FT) born children and VP children with below-average and average-high intelligence at 5.5 years. METHODS: A total of 2,253 VP children from the EPIPAGE-2 cohort and 578 FT controls who participated in the 5.5-year-follow-up were eligible for inclusion. The WPPSI-IV was used to measure verbal comprehension, visuospatial abilities, fluid reasoning, working memory, and processing speed. Psychometric network analysis was applied to analyse the data. RESULTS: Cognitive abilities were densely and positively interconnected in all networks, but the strength of connections differed between networks. The cognitive network of VP children was more strongly interconnected than that of FT children. Furthermore, VP children with below average IQ had a more strongly connected network than VP children with average-high IQ. Contrary to our expectations, working memory had the least central role in all networks. CONCLUSIONS: In line with the ability differentiation hypothesis, children with higher levels of cognitive ability had a less interconnected and more specialised cognitive structure. Composite intelligence scores may therefore mask domain-specific deficits, particularly in children at risk for cognitive impairments (e.g., VP born children), even when general intelligence is unimpaired. In children with strongly and densely connected networks, domain-specific deficits may have a larger overall impact, resulting in lower intelligence levels.

Neurodevelopment at 2 years and umbilical artery Doppler in cases of very preterm birth after prenatal hypertensive disorder or suspected fetal growth restriction: EPIPAGE-2 prospective population-based cohort study.

OBJECTIVE: To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders. METHODS: The study population comprised all very preterm (22-31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods. RESULTS: The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4-93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8-1.9). CONCLUSION: Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Prognostic value of diffusion-weighted magnetic resonance imaging of brain in fetal growth restriction: results of prospective multicenter study.

OBJECTIVE: To measure prospectively apparent diffusion coefficient (ADC) values between 28 and 32 weeks of gestation in different cerebral territories of fetuses with estimated fetal weight (EFW) ≤ 5th centile, and analyze their association with adverse perinatal outcome. METHODS: This was a prospective study involving six tertiary-level perinatal centers. In the period 22 November 2016 to 11 September 2017, we included singleton, small-for-gestational-age (SGA) fetuses with EFW ≤ 5th percentile, between 28 and 32 weeks of gestation, regardless of the umbilical artery Doppler and maternal uterine artery Doppler findings. A fetal magnetic resonance imaging (MRI) examination with diffusion-weighted sequences (DWI) was performed within 14 days following inclusion and before 32 weeks. ADC values were calculated in the frontal and occipital white matter, basal ganglia and cerebellar hemispheres. An ultrasound examination was performed within 1 week prior to the MRI examination. The primary outcome was a composite measure of adverse perinatal outcome, defined as any of the following: perinatal death; admission to neonatal intensive care unit with mechanical ventilation > 48 h; necrotizing enterocolitis; Grade III-IV intraventricular hemorrhage; periventricular leukomalacia. A univariate comparison of median ADC values in all cerebral territories between fetuses with and those without adverse perinatal outcome was performed. The association between ADC values and adverse perinatal outcome was then analyzed using multilevel logistic regression models to adjust for other common prognostic factors for growth-restricted fetuses. RESULTS: MRI was performed in 64 patients, of whom five were excluded owing to fetal movement artifacts on DWI and two were excluded for termination of pregnancy with no link to fetal growth restriction (FGR). One intrauterine death occurred secondary to severe FGR. Among the 56 liveborn neonates, delivered at a mean ± SD gestational age of 33.6 ± 3.0 weeks, with a mean birth weight of 1441 ± 566 g, four neonatal deaths occurred. In addition, two neonates required prolonged mechanical ventilation, one of whom also developed necrotizing enterocolitis. Overall, therefore, seven out of 57 (12.3%) cases had an adverse perinatal outcome (95% CI, 3.8-20.8%). The ADC values in the frontal region were significantly lower in the group with adverse perinatal outcome vs those in the group with favorable outcome (mean values of both hemispheres, 1.68 vs 1.78 × 10-3 mm2 /s; P = 0.04). No significant difference in ADC values was observed between the two groups in any other cerebral territory. A cut-off value of 1.70 × 10-3 mm2 /s was associated with a sensitivity of 57% (95% CI, 18-90%), a specificity of 78% (95% CI, 63-88%), a positive predictive value of 27% (95% CI, 8-55%) and a negative predictive value of 93% (95% CI, 80-98%) for the prediction of adverse perinatal outcome. A mean frontal ADC value < 1.70 × 10-3 mm2 /s was not associated significantly with an increased risk of adverse perinatal outcome, either in the univariate analysis (P = 0.07), or when adjusting for gestational age at MRI and fetal sex (odds ratio (OR), 6.06 (95% CI, 0.9-37.1), P = 0.051) or for umbilical artery Doppler (OR, 6.08 (95% CI, 0.89-41.44)). CONCLUSION: This first prospective, multicenter, cohort study using DWI in the setting of SGA found lower ADC values in the frontal white-matter territory in fetuses with, compared with those without, adverse perinatal outcome. To determine the prognostic value of these changes, further standardized evaluation of the neurodevelopment of children born with growth restriction is required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Efficacy of antenatal corticosteroids in preterm twins: the EPIPAGE-2 cohort study.

OBJECTIVES: To investigate the efficacy of antenatal corticosteroid (ACS) therapy on short-term neonatal outcomes in preterm twins, and further document the influence of the ACS-to-delivery interval. DESIGN: EPIPAGE-2 is a nationwide observational multicentre prospective cohort study of neonates born between 22 and 34 completed weeks of gestation. SETTING: All French maternity units, except in a single administrative region, between March and December 2011. POPULATION: A total of 750 twin neonates born between 24 and 31 weeks of gestation. METHODS: Exposure to ACSs was examined in four groups: single complete course, with an ACS administration-to-delivery interval of ≤7 days; single complete course, with an ACS-to-delivery interval of >7 days; repeated courses; or no ACS treatment. MAIN OUTCOME MEASURES: Neonatal outcomes analysed were severe bronchopulmonary dysplasia, periventricular leukomalacia or intraventricular haemorrhage grade III/IV, in-hospital mortality, and a composite indicator of severe outcomes. RESULTS: Compared with no ACSs, in multivariable analysis, a single course of ACSs with an administration-to-delivery interval of ≤7 days was significantly associated with a reduced rate of periventricular leukomalacia or intraventricular haemorrhage grade III/IV (aOR 0.2; CI 95% 0.1-0.5), in-hospital mortality (0.3; 0.1-0.6), and the composite indicator (0.1; 0.1-0.3), whereas a single course of ACDs with an administration-to-delivery interval of >7 days did not significantly reduce the frequency of in-hospital mortality (0.7; 0.3-1.8). No significant differences in terms of benefit or risk were found when comparing repeated courses with a single complete course. CONCLUSION: In preterm twins, a single complete course of antenatal corticosteroids was associated with an improvement of severe neurological outcome, whereas reduced in-hospital mortality was seen only when the ACS-to-delivery interval was ≤7 days. TWEETABLE ABSTRACT: A single complete course of antenatal steroids reduced severe neurological morbidity in preterm twins (24-31 weeks).

Gestational age at diagnosis of early-onset fetal growth restriction and impact on management and survival: a population-based cohort study.

OBJECTIVE: To investigate the impact of gestational age (GA) at diagnosis of fetal growth restriction (FGR) on obstetric management and rates of live birth and survival for very preterm infants with early-onset FGR. DESIGN: Population-based cohort study. SETTING: All maternity units in 25 French regions in 2011. POPULATION: Fetuses diagnosed with FGR before 28 weeks of gestation among singleton births between 22 and 31 weeks of gestation without severe congenital anomalies. METHODS: We studied the effects of GA at diagnosis on perinatal management and outcomes. We used multivariable regression to identify antenatal factors (maternal characteristics, ultrasound measurements and sex) associated with the probability of live birth. MAIN OUTCOMES MEASURES: Live birth and survival to discharge from neonatal care. RESULTS: A total of 436 of 3698 fetuses were diagnosed with FGR before 28 weeks (11.8%); 66.9% were live born and 54.4% survived to discharge. 50% were live born when diagnosis occurred before 25 weeks, 66% at 25 weeks and >90% at 26 and 27 weeks of gestation. In all, 94.1% of live births were by prelabour caesarean, principally for maternal indications before 26 weeks. Low GA at diagnosis, an estimated fetal weight or abdominal circumference below the third centile and male sex were adversely associated with live birth in adjusted models. CONCLUSION: Gestational age at FGR diagnosis had an impact on the probability of live birth and survival, after consideration of other perinatal characteristics. Investigations of the outcomes of births with early-onset FGR need to include stillbirths and information on the GA at which FGR is diagnosed. TWEETABLE ABSTRACT: Evaluations of active management of pregnancies with early onset growth restriction should include stillbirths.

Lower risk of atopic dermatitis among infants born extremely preterm compared with higher gestational age.

BACKGROUND: It is not yet known whether the risk of developing atopic dermatitis (AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a large sample of extremely preterm infants (< 29 weeks' gestation). OBJECTIVES: To determine whether the risk of AD is influenced by preterm birth. METHODS: We investigated the relationship between gestational age (GA) and AD using data from two independent population-based cohorts, including a total of 2329 preterm infants, of whom 479 were born extremely preterm. RESULTS: There was a lower percentage of children with AD in the extremely preterm group compared with those born at a greater GA (Epipage cohort, 2-year outcome: 13·3% for 24-28 weeks, 17·6% for 29-32 weeks, 21·8% for 33-34 weeks, P = 0·02; LIFT cohort, 5-year outcome: 11% for 24-28 weeks, 21·5% for 29-32 weeks, 19·6% for 33-34 weeks, P = 0·11). After adjusting for confounding variables, a lower GA (< 29 weeks) was significantly associated with decreased risk of AD in the Epipage cohort [adjusted odds ratio (aOR) 0·57, 95% confidence interval (CI) 0·37-0·87; P = 0·009] and the LIFT cohort (aOR 0·41, 95% CI 0·18-0·90; P = 0·03). CONCLUSIONS: Very low GA (< 29 weeks) was associated with a lower risk of AD compared with higher GA (29-34 weeks) and full-term birth.

Umbilical cord blood procalcitonin as a risk factor for mortality in very premature infants.

Fetal inflammatory response syndrome is implicated as a cause of fetal or neonatal injury. We analyzed the relationship between the procalcitonin umbilical cord blood level and neonatal outcome. A total of 237 preterms born in a level III perinatal medicine unit of a French university hospital were enrolled in a prospective observational study. Measurement of the procalcitonin umbilical cord blood level was performed at birth. After hospitalization, surviving infants were enrolled in the regional follow-up program. Outcome data were recorded on standardized questionnaires. The main outcome measures were neonatal mortality and impaired functional outcome at 2 years of corrected age. The terciles of procalcitonin levels were calculated. Preterm infants of the third tercile were defined as infants with elevated procalcitonin. Among the 237 infants, 13 (5.5%) died during the neonatal period, 20 (8.4%) were lost to follow-up, and 31 (13.1%) were classified as having an impaired functional outcome. After adjustment, elevated cord blood procalcitonin (>0.33 ng/ml) was significantly associated with an increase in mortality (adjusted odds ratio [aOR] = 8.3 [1.4-48]; p = 0.018), but not with the 2-year impaired functional outcome (aOR = 1.0 [0.4-2.5]; p = 0.93). Elevated umbilical blood cord procalcitonin concentration is an independent risk factor of mortality in preterm infants at less than 33 weeks' gestation.

Ofloxacin: new applications for the prevention of urinary tract infections in renal graft recipients.

BACKGROUND: Urinary tract infections (UTIs), the most common form of bacterial infection in kidney transplant recipients, recently have been demonstrated to be detrimental for long-term graft outcome. Therefore, reinforcing antibiotic prophylaxis might be vital, in addition to basic hygiene recommendations, surgical care, and prophylaxis by trimethoprim-sulfamethoxazole. METHODS: In 2006, a Legionella pneumophila contamination of our department's water pipes meant that all the patients undergoing renal transplantation underwent a 1-month regimen of ofloxacin (OFLO) (200 mg every other day). We took this opportunity to measure the incidence of UTI, including acute pyelonephritis (APN), in 100 consecutive patients transplanted before (n = 50) and after (n = 50) this treatment decision was reached. We also studied the antimicrobial resistance profiles in our department and in the rest of the hospital. RESULTS: No patient developed Legionnaire's disease. A dramatic decrease in the incidence of UTI (-63%) was also seen in patients undergoing OFLO treatment. Logistic regression analysis demonstrated that the use of OFLO was independently associated with a reduction in UTI (odd ratio [OR] = 0.31%, 95% confidence interval [CI] 0.11-0.84, P = 0.02) and APN (OR = 0.21%, 95% CI 0.07-0.98, P = 0.045). This protection was sustained during the whole first year post transplantation. As for resistance rates, we observed a decrease in the susceptibility of Pseudomonas aeruginosa to ciprofloxacin in our nephrology department, compared with that observed in the rest of the hospital. The incidence of multi-resistant bacteria was stable. DISCUSSION: Our unintentional extension of prophylactic antibiotherapy with OFLO gave rise to a dramatic decrease in the 1-year incidence of UTI and APN in kidney recipients. Emergence of resistant strains is, however, a major concern.

Diffuse alveolar haemorrhage: factors associated with in-hospital and long-term mortality.

Diffuse alveolar haemorrhage (DAH) is a feature of several immune and nonimmune disorders. Reported prognosis is poor, with in-hospital mortality ranging from 20% to 100%. Early identification of prognostic factors may be useful in the initiation of appropriate treatment. We retrospectively analysed the charts of all patients referred to a university hospital for DAH between 1980 and 2008. Variables associated with in-hospital and long-term mortality were determined using a logistic regression model and the Kaplan-Meier method, respectively. Immunosuppressed patients were excluded. Overall, 97 patients were included in the study. In-hospital mortality was 24.7%. Factors associated with in-hospital mortality were shock (OR 77.5, 95% CI 8.9-677.2), glomerular filtration rate <60 mL x min(-1) (OR 11.2, 95% CI 1.8-68.4) and plasmatic lactate dehydrogenase level more than twice the normal value (OR 12.1, 95% CI 1.7-84.3). Mortality among discharged patients was 16.4% with a median follow-up duration of 34 months. Factors associated with increased long-term mortality in univariate analysis were age over 60 yrs (p = 0.026), cardiovascular comorbidity (p = 0.027) and end-stage renal failure with dependence on haemodialysis (p = 0.026). Patients with immune and nonimmune DAH had similar outcomes. Early outcome depended on nonpulmonary organ failures. Conversely, late outcome was related to age, cardiac comorbidities and the need for haemodialysis.

Neurodevelopment of children born very preterm and free of severe disabilities: the Nord-Pas de Calais Epipage cohort study.

AIM: To describe the development of very preterm children free of cerebral palsy or severe sensory impairment in the domains of gross and fine motor functions, language and sociability at a corrected age of 2 years; to identify factors associated with performances in each domain. METHODS: A total of 347 children born in 1997 before 33 weeks of gestation, part of the EPIPAGE population-based cohort study, had their psychomotor development assessed with the Brunet-Lezine scale. RESULTS: The study population had a mean gestational age of 30.1 +/- 2.0 weeks. Lower developmental quotients (DQ) were observed in the study group compared to the reference sample (96 +/- 13 vs 104 +/- 8, p < 0.01). Fine motor function, language and sociability were all affected with a p value <0.01. Multivariate analysis showed that duration of intubation and parents' educational and occupational levels were the only variables significantly related to each developmental domain (p < 0.01). CONCLUSIONS: Children very preterm and free of severe disabilities had mild delays in multiple areas of development. The mechanisms by which neonatal factors played a role need further investigation. However socioeconomic status had a great impact on development and our results underline the need for improved support of socioeconomically disadvantaged parents after a preterm birth.

[Propositions for perinatal care at extremely low gestational ages - Working group on "Extremely low gestational ages" for SFMP, CNGOF, and SFN]. / Propositions sur la prise en charge en cas d'extrême prématurité ­ Le groupe de travail « Extrême Prématurité ¼ pour la SFMP, le CNGOF et la SFN.

OBJECTIVES: International literature suggests that active perinatal management at extremely low gestational ages improves survival without increasing the risk of impairment in survivors, compared to less active management. Although these results are limited to a small number of countries, they question current practices in France. New propositions on perinatal management of extremely preterm infants have carried out by the French Society of Perinatal Medicine, the French Society of Neonatology and the National College of French Obstetricians and Gynecologists. METHODS: This group was set up in 2015 on the initiative of the professional societies and in collaboration with parents' and users' associations. The work was based on a review of the literature on the prognosis of extremely preterm children, as well as on recommendations by European societies. Based on this information, a text was produced, submitted to all members of the working group and definitively validated in April 2019. RESULTS: This text offers a decision-making guideline for the management at extremely low gestational ages. Its principles are: the administration of steroids independently of management (resuscitation or comfort care); a prognostic evaluation and a collegial decision, outside the context of the emergency; a consensus on the information to be given to parents before going to inform them and gather their opinion. CONCLUSIONS: These new propositions will contribute to modifying perinatal care at extremely low gestational ages in France.

Impact of the use of antenatal corticosteroids on mortality, cerebral lesions and 5-year neurodevelopmental outcomes of very preterm infants: the EPIPAGE cohort study.

OBJECTIVE: To assess the impact of antenatal corticosteroids (ACS) on neonatal mortality, cerebral lesions and 5-year neurodevelopmental outcome of infants born at 24-27 and 28-32 weeks of gestational age (GA). DESIGN: Observational population-based study including all births at GAs between 22 and 32 weeks in 1997 in nine regions of France. Survivors were assessed at the age of 5 years. SAMPLE AND METHODS: The population enrolled in the follow up comprised 2323 infants; there were 23 deaths before age 5 years and outcome at 5 years was available for up to 1781 subjects. Two GA subgroups (24-27 and 28-32 weeks of GA) were analysed separately. Propensity scores were used to reduce bias in the estimation of the association between ACS treatment and outcomes. MAIN OUTCOME MEASURES: Neonatal death, neonatal white matter injury, cerebral palsy, mental processing composite (MPC) of the Kaufman Assessment Battery for Children test and behavioural difficulties at 5 years. RESULTS: In the 28- to 32-week GA subgroup, there was a significant association between ACS and a decreased risk of both neonatal death (OR = 0.61 [0.41-0.91]) and white matter injury (OR = 0.60 [0.46-0.79]) but only a nonsignificant trend for improved 5-year outcome (cerebral palsy, MPC < 70). In the 24- to 27-week GA subgroup, ACS was associated with a significant decrease risk of neonatal death (OR = 0.43 [0.27-0.68]) but there was only a trend for a lower risk of white matter injury and no beneficial impact on outcome at 5 years. Limiting the analysis to only those who received complete courses of ACS did not modify the results. CONCLUSION: The study shows that ACS therapy greatly increases the survival of very preterm infants, including the most immature, but there is little evidence that ACS affects long-term neurodevelopmental and behavioural outcome in 28- to 32-week survivors, and none in <28-week survivors.

[Synchronous bilateral breast cancer: risk factors, diagnosis, histology and treatment]. / Cancers du sein bilatéraux synchrones: facteurs de risque, diagnostic, histologie, traitement.

OBJECTIVE: Synchronous bilateral breast carcinoma (SBBC) is not uncommon. Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The purpose of this study was to evaluate risk factors, diagnostic circumstances, histological characteristics and therapeutic methods for SBBC. PATIENTS AND METHODS: Between July 1992 and May 2006, 62 patients with SBBC were treated at Tenon hospital (Paris, France). Population was divided into two sub-groups corresponding with two successive periods. Epidemiological characteristics, diagnostic circumstances, therapeutic methods and histological characteristics were analysed. RESULTS: Global incidence of SBBC during this period was 2.6%. The patients presenting a CSBS had a family antecedent of breast cancer in 23.7% of the cases. The most frequent situation associated a palpable tumour and an infraclinic contralateral lesion (43.5%). MRI made diagnosis possible in seven tumours. Among the patients 38.7% had a bilateral mastectomy and 33.9% profited from the technique of the ganglion sentinel. The proportions of invasive lobular carcinomas and the multifocal tumours were 17.7%. The tumours had the same histological type in 78.3% of the cases and the expression of oestrogen receptors was identical in 91.4% of the cases. DISCUSSION AND CONCLUSION: The principal risk factors of CSBS are a family history of breast cancer, the histological type lobular invasive and the multifocal character of the first tumour. A conservative surgery is possible as well as the use of the technique of the ganglion sentinel. The CSBS have histological similarities, probably due to environmental factors.

[Is it possible to protect the preterm infant brain and to decrease later neurodevelopmental disabilities?]. / Est-il possible de protéger le cerveau de l'enfant né prématuré et de diminuer le taux de séquelles neuro-développementales ?

With improving neonatal survival for very premature babies, the challenge for neonatalogists is to ameliorate outcome of surviving babies. Several pharmacological molecules have been shown to have protective effects in different types of in vitro or in vivo animal models of acquired cerebral brain damages. However translational research and conduction of therapeutic trials in human remain difficult due to failure to recognize start of deleterious cascade leading to cerebral damage and additional toxic effect of potential protective molecules. This review concentrates on best evidence emerging in recent years on prevention on brain damage by early drug administration. It has been shown in two randomised trials that prenatal low-dose of magnesium sulphate does not increase paediatric mortality in very-preterm infants and has non significant neuroprotective effects on occurrence of motor dysfunction (with a 0.62 odds ratio in the French trial Premag and 0.71 relative risk in the Australian trial ACTOMgSO4), justifying that magnesium sulphate should be discussed as a stand-alone treatment or as part of a combination treatment, at least in the context of clinical trials. Antenatal corticosteroid therapy increases the survival of very-preterm infants, including the most immature. Moreover in an observational recent study of the Epipage cohort, it has been observed a significant decrease in white matter injury in the 28-32 weeks' gestation group but no effect on long term outcome and behaviour. Conversely in the most immature of the 24-27 weeks' gestation group, no effect has been detected either in white matter injury incidence or in long term outcome rates. Caffeine has a protective effect since a decrease in cerebral palsy has been noted in the caffeine group in a randomised trial studying caffeine versus placebo. For what concern other widely used potential protective molecules during the perinatal period, there is no evidence of cerebral protection with indometacine, nitric oxide, eythropoietin, phenobarbital, and etamsylate. Due to their specific properties, a careful evaluation of aspirin, anaesthetic drugs and tocolytics should be done in the next months.

Palivizumab administration in preterm infants in France: EPIPAGE-2 cohort study.

BACKGROUND: Several countries, including France, have restricted the indications for monoclonal antibodies directed against respiratory syncytial virus (RSV) compared to the marketing authorization (MA). No new data concerning use of palivizumab on a national scale have been published since the 2007 update of the national guidelines. OBJECTIVES: To describe palivizumab administration for RSV prophylaxis during the first RSV season in infants born prematurely in France in 2011. METHODS: Infants from the national population-based cohort EPIPAGE-2 born at≤34 weeks' gestation, discharged home before 31 March 2012 and followed-up at 1year were included. The RSV season ran from 1 October 2011 to 31 March 2012. Prophylaxis was deemed "initiated" if the infant had received at least one dose of palivizumab during this period and "complete" if it had received at least five doses or as many doses as the number of exposed months. The reference documents were the MA and French Transparency Committee guidelines (TC). RESULTS: Prophylaxis was indicated in 3586 of 3608 infants (99.7%) according to the MA and 1315 of 3608 (16.7%) according to the TC. A total of 1906 infants (26.6%) received at least one dose of palivizumab. The overall rate of conformity with TC indications was 85%, but was lower for infants born at 27-32 weeks' gestation. The rate of complete prophylaxis was 77.2%. The factors associated with prophylaxis initiation were low gestational age, low birthweight, high maternal educational level, type of neonatal unit, and date at discharge. Factors associated with complete prophylaxis were respiratory impairment, high educational level, and characteristics related to living conditions (absence of siblings at home, type of childcare). CONCLUSIONS: Palivizumab administration in France generally conformed with TC guidelines, but could be further improved for infants born at 27-32 weeks' gestation without bronchopulmonary dysplasia.

Impact of clinical and/or histological chorioamnionitis on neurodevelopmental outcomes in preterm infants: A literature review.

OBJECTIVE: To determine the impact of clinical and/or histological chorioamnionitis on neurodevelopmental outcomes in premature infants. METHODS: A review of the literature appeared in PubMed between 1997 and 2016 was conducted to examine the association between clinical and/or histological chorioamnionitis and neurologic impairment in the neonates (intraventricular hemorrhage, periventricular leukomalacia and white matter damage) and in infants (cerebral palsy and neurodevelopmental delay). RESULTS: The first meta-analysis published in 2000 observed that clinical chorioamnionitis was associated with cystic periventricular leukomalacia and cerebral palsy and that histologic chorioamnionitis was associated with periventricular leukomalacia only. A second meta-analysis in 2010 found that cerebral palsy was associated with both clinical and histological chorioamnionitis. But most recent studies over the last decade based on large cohorts found no effect of chorioamnionitis on neurological outcomes, even if they had several methodological limitations. CONCLUSION: According to the findings of the most recent studies, clinical or histological chorioamnionitis does not seem to be associated with neonatal white matter injuries, or with cerebral palsy. Further studies are needed to assess the impact of chorioamnionitis on long-term neurological development.

[Difficulties with the follow-up of a cohort of very preterm infants: The EPIPAGE Paris-Petite-Couronne population]. / Difficultés de suivi d'une cohorte d'enfants nés grands prématurés : EPIPAGE Paris-Petite-Couronne.

OBJECTIVES: To describe the characteristics of the children of parents who did not respond to a follow-up questionnaire in a cohort of very preterm infants (EPIPAGE study) and to explore the reasons why they did not complete the questionnaires. METHODS: The non-respondents (N = 176) were the parents who did not return the questionnaires at 1 and 2 years. Contacts were organised by telephone calls and at home visits. RESULTS: The families of the non-respondents presented more socioeconomic difficulties and their children were born more preterm than those followed up without difficulties. The efforts made to contact the non-respondents revealed that their families were often confronted with major adverse socioeconomic difficulties, had severe illnesses and psychological troubles. Half of the children of the non-respondents were finally examined at the 5-year assessment. They showed lower performances at the cognitive development test and a poorer health status than the children of the respondents. CONCLUSION: When the follow-up does not include the initial population in its totality, the socioeconomic difficulties are underestimated and probably also the rate of sequelae associated with very preterm delivery.

[Epidemiology and risk factors of preterm birth]. / Épidémiologie et facteurs de risque de la prématurité.

OBJECTIVE: To synthesize the available evidence regarding the incidence and several risk factors of preterm birth. To describe neonatal outcomes according to gestational age and to the context of delivery. MATERIALS AND METHODS: Consultation of the Medline database. RESULTS: In 2010, 11% of live births (15 million babies) occurred before 37 completed weeks of gestation worldwide. About 85% of these births were moderate to late preterm babies (32-36 weeks), 10% were very preterm babies (28-31 weeks) and 5% were extremely preterm babies (<28 weeks). In France, premature birth concerns 60,000 neonates every year, 12,000 of whom are born before 32 completed weeks of gestation. Half of them are delivered after spontaneous onset of labor or preterm premature rupture of the membranes, and the other half are provider-initiated preterm births. Several maternal factors are associated with preterm birth, including sociodemographic, obstetrical, psychological, and genetic factors; paternal and environmental factors are also involved. Gestational age is highly associated with neonatal mortality and with short- and long-term morbidities. Pregnancy complications and the context of delivery also have an impact on neonatal outcomes. CONCLUSION: Preterm birth is one of the leading cause of the under-five mortality and of neurodevelopmental impairment worldwide; it remains a major public health issue.

[Neuroprotection for preterm infants with antenatal magnesium sulphate]. / Protection cérébrale de l'enfant né prématuré par le sulfate de magnésium.

OBJECTIVE: To evaluate in preterm born children the neuroprotective benefits and the risks, at short- and long-term outcome, of the antenatal administration of magnesium sulphate (MgSO4) in women at imminent risk of preterm delivery. MATERIAL AND METHODS: Computer databases Medline, the Cochrane Library and the recommendations of various international scientific societies. RESULTS: Given the demonstrated benefit of antenatal MgSO4 intravenous administration on the reduction of cerebral palsy rates and the improvement of motor development in children born preterm, it is recommended for all women whose imminent delivery is expected or programmed before 32 weeks of gestation (WG) (grade A). The analysis of the literature finds no argument for greater benefit of antenatal MgSO4 administration in sub-groups of gestational age, or depending on the type of pregnancy (single or multiple pregnancy) or with the cause of preterm birth (NP2). Its administration is recommended before 32 WG, if single or multiple pregnancy, whatever the cause of prematurity (grade B). It is recommended 4g loading dose (professional consensus). With a loading dose of 4g intravenous (IV) in 20min, the serum magnesium is lower than with intramuscular suggesting a preference for the IV route (professional consensus). It is proposed to use a maintenance dose of 1g/h until delivery with a maximum recommended duration of 12hours without exceeding a cumulative dose of 50g (professional consensus). These doses are without severe adverse maternal side effects or adverse effects in newborns at short- and medium-term outcome (NP1). CONCLUSION: It is recommended to administer magnesium sulfate to the women at high risk of imminent preterm birth before 32 WG, whether expected or planned (grade A), with a 4g IV loading dose followed by a maintenance dose of 1g/h for 12hours (professional consensus), the pregnancy is single or multiple, whatever the cause of prematurity (professional consensus).

Delivery room management of extremely preterm infants: the EPIPAGE-2 study.

OBJECTIVE: To analyse the delivery room management of babies born between 22 and 26 weeks of completed gestational age and to identify the factors associated with the withholding or withdrawal of intensive care. STUDY DESIGN: Population-based cohort study. PATIENTS AND METHODS: Our study population comprised 2145 births between 22 and 26 completed weeks enrolled in the EPIPAGE-2 study, a French cohort of very preterm infants born in 2011. The primary outcome measure was withholding or withdrawal of intensive care in the delivery room. RESULTS: Among infants born alive at 22-23 weeks, intensive care was withheld or withdrawn for >90%. At 24 weeks, resuscitative measures were withheld or withdrawn for 38%, at 25 weeks for 8% and at 26 weeks for 3%. Other factors besides gestational age at birth associated with this withholding or withdrawal for infants born at 24-26 weeks were birth weight <600 g, emergency delivery (within 24 h of the mother's admission) and singleton pregnancy. Although rates of withholding or withdrawal of intensive care varied substantially between maternity units (from 0% to 100%), the variability was primarily explained by differences in distributions of gestational age at birth. CONCLUSIONS: Although gestational age is only one factor predicting survival of preterm infants, practices in France appear to be based primarily on this factor, which thus has direct effects on the survival of extremely preterm infants. The ethical implications of basing life and death decisions only on gestational age before 25 weeks require further examination.