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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. [ABSTRACT FROM AUTHOR]

Background: Loss to follow-up is a major challenge for very preterm (VPT) cohorts; attrition is associated with social disadvantage and parents with impaired children may participate less in research. We investigated the impact of loss to follow-up on the estimated prevalence of neurodevelopmental impairment in a VPT cohort using different methodological approaches.Methods: This study includes births < 32 weeks of gestational age (GA) from 4 regions in the UK and Portugal participating in a European birth cohort (N = 1737 survivors). Data on maternal characteristics, pregnancy complications, neonatal outcomes and neighborhood deprivation were collected at baseline. Neurodevelopment was assessed at 2 years of corrected age (CA) using standardized parent-report measures. We applied (1) multiple imputation (MI) and (2) inverse probability weighting (IPW) to estimate the impact of non-response on the prevalence of moderate to severe neurodevelopmental impairment and assessed violations of the missing at random (MAR) assumption using the delta method.Results: 54.2% of children were followed-up. Follow-up was less likely when mothers were younger, multiparous, foreign-born, did not breastfeed and came from deprived areas. The prevalence of neurodevelopmental impairment was 18.4% (95% confidence interval (CI):15.9-21.1) and increased to 20.4% (95%CI: 17.3-23.4) and 20.0% (95%CI:16.9-23.1) for MI and IPW models, respectively. Simulating strong violations of MAR (children with impairments being 50% less likely to be followed-up) raised estimates to 23.6 (95%CI:20.1-27.1) CONCLUSIONS: In a VPT cohort with high loss to follow-up, correcting for attrition yielded modest increased estimates of neurodevelopmental impairment at 2 years CA; estimates were relatively robust to violations of the MAR assumption. [ABSTRACT FROM AUTHOR]

Keywords: diffusion-weighted imaging; fetal growth restriction; FGR; intrauterine growth restriction; IUGR; perinatal outcome; SGA; small-for-gestational age EN diffusion-weighted imaging fetal growth restriction FGR intrauterine growth restriction IUGR perinatal outcome SGA small-for-gestational age 893 900 8 12/03/20 20201201 NES 201201 CONTRIBUTION B What are the novel findings of this work? Among children who were affected by FGR prenatally, neurodevelopmental impairment is associated with specific neurostructural changes visible on magnetic resonance imaging (MRI)9,10. Model 1 included the ADC values adjusting for gestational age at the time of MRI and infant sex, and Model 2 involved further adjustment for umbilical artery Doppler. However, gestational age at MRI was included in this analysis, as ADC values change throughout pregnancy18. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Data from a case-control survey in Europe, carried out between 1994 and 1997, were used to investigate the risk factors for spontaneous abortions at 14-21 weeks (late abortions), according to the vital status of the fetus before the onset of labour. Late abortions included 62 involving a fetus alive before the onset of labour, 216 late abortions of a fetus already dead, together with 4592 control pregnancies at term (>/=37 weeks) from seven countries. Histories of induced abortion, spontaneous abortion and preterm birth were more closely associated with late abortion of a live fetus than with late abortion of a dead fetus. Women aged >/=35 years and women living alone had a much higher risk of late abortions than women aged 20-24 years and married women, regardless of the vital status of the fetus before labour. These results provide evidence that obstetric history and socio-demographic factors are risk factors for late abortions but differences are observed according to the vital status of the fetus before labour. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the prognostic factors for conception after myomectomy carried out in cases of infertility. A total of 91 infertile patients presenting at least one subserous or intramural myoma measuring >2 cm underwent myomectomy. The characteristics of the patients, myomata and associated infertility factors were collected in a uniform and systematic way. A postal questionnaire was sent to patients. For each of the various factors studied, the specific cumulative probability of spontaneous intrauterine conception was estimated using the Kaplan-Meier method. Multiple regression analysis was then carried out using Cox's proportional hazards model. The cumulative probability of spontaneous intrauterine conception at 2 years follow-up was 44% (95% confidence interval: 32-56%). The cumulative probability of conception was less after removal of a posterior or intramural myoma, after a sutured hysterotomy, and when accompanied by a male factor, associated tubal or ovulation pathology. The cumulative probability of conception was greater after ablation of myomata responsible for menometrorrhagia. The size, deforming effect on the cavity and age played no role in our sample. Our results indirectly suggest that post myomectomy adhesions could have an adverse effect on fertility. Myomata responsible for menometrorrhagia are also the cause of infertility. In the presence of an associated male, tubal or ovulatory factor, the results were poor and it was not possible to determine if a myomectomy should be performed in these cases in order to enhance fertility. [ABSTRACT FROM AUTHOR]

To analyse the relation between unemployment and the psychological distress of mothers one year after childbirth. Multicentric survey concerning births occurring between September 1993 and July 1994. In France: two maternity units in the Parisian area and one in Champagne-Ardennes, in the east of France, comprising both urban and rural areas. Primipara and secondipara women were interviewed three times: at birth by a face to face interview, five months and 12 months after the birth, by postal questionnaires, with a 83% response rate for the two postal questionnaires. The analysis includes 632 women who answered all three stages of the survey. Psychological distress was mainly assessed one year after birth by the 12-item General Health Questionnaire. After adjustment for unwanted pregnancy, marital conflicts, marital status, hospitalisation of the baby during the last year, lack of confiding relationship, depressive or anxious troubles before pregnancy, age, educational level and parity, unemployed women had an excess of psychological distress compared with employed women (OR = 1.87; 95% CI = 1.12, 3.13). The ratios for housewives were very close to those of employed women. Among the unemployed women, 60% had recently been without a job, since a few months before or after the birth. An excess of psychological distress among unemployed compared with employed women was observed in all social groups defined by the current or last occupation, but with various extents. Psychological distress was specially linked to the employment status in the group of women with the more qualified occupations. Even after a birth, when women are very much involved in their maternal role, those seeking a job have worse mental health than those in a stable situation, either employed or housewives. In France, the unemployment rate among young women is high. It is specially important that social regulations protecting employment during and after pregnancy are adequately applied. Employers, legislators, such as medical doctors, have to be aware to this situation. [ABSTRACT FROM AUTHOR]

Summary: The immature brain is highly susceptible to the consequences of very preterm birth with a high rate of long-term neurodisabilities in survivors and high use of specific outpatient services to limit the functional effects of the disabilities. To assess the economic burden for the social and health care system, it is necessary to inventory the community supports and need for special education or rehabilitation used by preterm children. Such studies are few and were done only in extremely low-birthweight or extremely preterm newborns in the United States. Objective: To study the rates of specific outpatient services and special education at 5 years of age and between 5 and 8 years of age in a geographically-defined population of children born very preterm. Design, Setting and Patients: 2901 liveborn children before 33 weeks’gestation (WG) and one control group of 666 liveborn children at 39-40WG were included in nine regions of France in 1997 corresponding to more than one third of all births. At five years, these children had a medical examination and were evaluated by a psychologist at local centres organised for the study in every region. Cognitive function was assessed by the mental processing composite scale (PMC) of the Kauffmann Assessement Battery for Children test, which is considered to be equivalent to intelligence quotient and behavioral difficulties using the Strength and Difficulties questionnaire completed by the parents. Data for dependence or compensatory aids, i.e. occupational therapy or physical therapy, speech therapy, psychologist or psychiatrist visits, orthoptic therapy, wearing glasses, wearing hearing aid, specific equipment to walk (walker, wheelchair…), orthopaedic treatment or anti-epileptic treatment were collected from parents. At eight years, a postal questionnaire was sent to the parents to collect data on specific outpatient services and special treatments at home and school. Stata software was used (version 9.0). Main outcome measures. Parent Questionnaire for identifying children with chronic conditions and specific health care needs at 5 and 8 years and categorization of developmental neurodisabilities based on examination of children and psychometric evaluation at 5 years. Results: At 5 years data were obtained for respectively 1817 and 396 children born before 33WG or at 39-40WG, which represent 80% of the very preterm children and 71% of the at term children. At 8 years we obtained data for 63% of the very preterm children and 59% of the at term children. At 5 years, care in a rehabilitation center and/or specific outpatient services were required for 41% of children born between 24 and 28WG, 32% of children born between 24 and 32WG and 15% of those born at 39-40WG. Between 5 and 8 years, these figures were respectively 61%, 50% and 36%. In the very preterm group, rates of specific outpatient services were higher than 80% if the child had a motor and/or a neurosensory deficit. In case of cognitive deficiencies (PMC < 85), rates of specific outpatient services were low at 37% at 5 years and increases at 63% between 5 and 8 years. Conclusion: Compared to the children born at term, the very preterm children have considerable educational needs, which are inversely related to gestational age at birth and to age of the children at the time of reporting. Despite economic burden, efforts to improve access to services are necessary, in particular in case of cognitive impairment. [Copyright &y& Elsevier]

Summary: 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. [Copyright &y& Elsevier]

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)., (© 2017 Royal College of Obstetricians and Gynaecologists.)

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., (© 2017 Royal College of Obstetricians and Gynaecologists.)

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 (MgSO 4 ) 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 MgSO 4 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 MgSO 4 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)., (Copyright © 2016. Published by Elsevier Masson SAS.)