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Objective: To determine the prevalence, short-term prognosis and pharmacologic management of pulmonary hypertension (PH) among very preterm infants born before 32 weeks gestation (WG)., Study Design: 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., Results: 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., Conclusion: 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., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: In 2016, the American Academy of Pediatrics defined the brief resolved unexplained event (BRUE) of high and low risk to characterize fainting in infants under 1 year of age. In the case of low-risk BRUE, it is recommended to perform no further systematic examination, but to monitor the child with a saturometer in the emergency room for 1-4 h., Objective: The objective of this study was to identify events corresponding to high- and low-risk BRUE criteria for infants admitted to the Angers University Hospital Center, and to analyze their medical care., Method: We conducted an observational, retrospective, descriptive and single-center study of the population of infants younger than 1 year admitted for an unexplained event to the Pediatric Emergency Department of Angers University Hospital Center between 1 January 2017 and 31 December 2019. Two patient databases were crossed to identify patients., Results: Among the 203 patients presenting for fainting, 54 patients met the criteria for BRUE, including 40 high-risk BRUE and 14 low-risk BRUE cases. All complementary examinations performed on low-risk BRUE children were normal. Two of these patients had a recurrence of non-severe fainting several months after the first episode., Conclusion: Identification of infants according to the BRUE criteria helps to harmonize practices and to limit the number of complementary examinations or hospitalizations for low-risk BRUE., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Preterm delivery is a risk factor for suboptimal neurodevelopment. Pregnancies conceived after medically assisted reproduction-which includes in vitro fertilization, with or without intracytoplasmic insemination, and induction of ovulation followed by intrauterine insemination or timed intercourse-have a higher risk of preterm delivery. Few studies have evaluated the outcome at >2 years of age of such preterm-born children., Objective: To evaluate neurodevelopmental outcome at 5½ years of age of children born preterm according to the mode of conception (spontaneous vs medically assisted reproduction)., Study Design: A total of 4349 children born between 24 and 34 weeks of gestation who survived to 5½ years of age in the 2011 French prospective national cohort study "EPIPAGE-2" were included: 814 in the medically assisted reproduction group (433 by in vitro fertilization, with or without intracytoplasmic insemination, and 381 by induction of ovulation) and 3535 in the spontaneously conceived group. The studied neurodevelopmental outcomes were sensory (hearing and vision) impairments, cerebral palsy, cognition, and developmental coordination disorders. Multivariate analyses were performed with generalized estimating equation models adjusted for gestational age, antenatal steroids, and social characteristics. All analyses were performed following multiple imputation. Sensitivity analyses were performed with the populations of singletons and cases with complete data., Results: No differences in cerebral palsy (adjusted odds ratio, 1.00; 95% confidence interval, 0.67-1.49), neurodevelopmental impairment (adjusted odds ratio, 1.09; 95% confidence interval, 0.82-1.45), or developmental coordination disorders (adjusted odds ratio, 0.75; 95% confidence interval, 0.50-1.12) were found between children born following medically assisted reproduction and children born following spontaneous conception after adjustment for sociodemographic factors. For proportions of children with an intelligence quotient below 1 and 2 standard deviations, there were no differences between those born after medically assisted reproduction and those born after spontaneous pregnancy (respectively, adjusted odds ratio, 0.99; 95% confidence interval, 0.80-1.23 and adjusted odds ratio, 1.14; 95% confidence interval, 0.83-1.56). In subgroup analyses, no differences were observed between children born following induction of ovulation or in vitro fertilization and those conceived spontaneously. Sensitivity analyses were consistent with the main results., Conclusion: In this cohort of preterm-born children, there was no evidence of an impact of the mode of conception on neurodevelopmental outcomes at 5½ years of age., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome., Methods: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076., Findings: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia., Interpretation: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction., Funding: French Ministry of Health., Competing Interests: Declaration of interests TS reports receiving consulting fees from Dilafor. LS reports receiving consulting fees from Dilafor; lecture fees from Bayer, GlaxoSmithKline, and Sigvaris; and lecture and consulting fees from Ferring Pharmaceuticals. AJV reprts receiving consulting fees from Norgine. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. TAKE HOME MESSAGES., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: It has been suggested that mitochondria play a crucial role in sustaining pregnancy and foetal growth. The aim of the study was to assess the influence of mitochondrial functions and genetics on placental insufficiency diseases., Methods: A total of 115 patients were recruited, subdivided into 74 placenta samples and 41 maternal blood samples: placental insufficiency diseases including intra uterine growth restriction (IUGR) (n = 35), preeclampsia (PE) (n = 13), IUGR associated to PE (PER) (n = 25); and controls (n = 42). Haplogroups were determined for all patients. Eighty-six placenta samples were studied for quantitative and qualitative analyses of mtDNA: IUGR (n = 25), PE (n = 1), PER (n = 18) and controls (n = 42). Sixteen placenta samples were selected for functional analysis: IUGR (n = 6), PER (n = 2) and controls (n = 8)., Results: Mitochondrial DNA copy numbers and rearrangements and haplogroup distribution were not significantly altered in the patient group. Enzyme activity and expression of respiratory chain complexes were also comparable between both groups., Discussion: Our results do not argue in favour of a mitochondrial involvement in placental insufficiency, suggesting that the glycolytic pathway may represent a key energetic source in placental insufficiency diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: An increased risk of small-for-gestational-age infants after maternal bariatric surgery has been shown. The risk of micronutrients deficiencies in these neonates is unclear., Objective: To screen for micronutrients deficiencies in newborns of mothers with gastric bypass., Settings: University hospital in Angers, France., Methods: This study compared the clinical and cord blood biological characteristics of 56 newborns of mothers with prior Roux-en-Y gastric bypass (RYGB) and 56 newborns of nonobese healthy mothers after normal pregnancy (controls), followed between January 3, 2008 and October 31, 2012. Cord blood micronutrients concentrations from controls were used for establishing normative data. After RYGB, the women took daily micronutrients supplements., Results: RYGB mothers lost 18.1±6.3 kg/m 2 of body mass index (BMI) in the 11-69 months between surgery and pregnancy onset (percentage of excess weight loss 79±20%), reaching BMI of 30.1±6.0 kg/m 2 compared with 22.3±4.0 kg/m 2 in the controls (P<.05). Neonates born to RYGB mothers were small-for-gestational-age in 23% of cases versus 3.6% in the control group (P<.01). A higher percentage of RYGB neonates had cord blood concentrations below the 2.5 percentile for calcium (19% versus 2%), zinc (13% versus 3%,), iron (19% versus 2%), and vitamin A (13% versus 3%), and over the 97.5 percentile for magnesium (13% versus 3%), vitamin E (16% versus 3%), 25-hydroxy-vitamin D (13% versus 2%), and vitamin B12 (14% versus 2%) (P<.05 for all comparisons)., Conclusion: Neonates from RYGB mothers showed cord blood micronutrient differences compared with neonates from healthy mothers. The comparison with neonates from morbidly obese women is still to be done., (Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To describe early complications and management of newborns during the first month of life., Methods: This systematic evidence review is based on Pubmed search, Cochrane library and experts recommendations., Results: There is no optimal time for maternity discharge for low risk newborn in regard of the literature. It depends more on the organisation of the post-discharge follow-up (professional consensus). Extreme hyperbilirubinemia expose to neonatal mortality and severe neurodevelopmental impairment for survivors (level of evidence: 1). Neonatal hyperbilirubinemia occurs in almost all newborns and may be benign if its progression is monitored (transcutaneous bilirubinometer, capillar or venous bilirubin level) at least 24hours after any early discharge (professional consensus). Asymptomatic newborns with high risks of neonatal sepsis have to be closely monitored during the first 48hours of life (professional consensus). Clinical assessment (heart murmure and femoral pulse) at least 24hours after any early discharge and at any clinical examination almost up to 1 month after birth is recommended to detect possible congenital heart disease (professional consensus). Serial clinical examination of the hips by a trained clinician in the periodic health examination of all infants until they are walking independently is recommended (professional consensus). Neonatal screening blood tests are recommended between 60 and 84hours of life in every newborns, can be advanced between 48 and 60hours if necessary but never before 48hours of life (professional consensus). Neonatal screening of deafness is recommended in every newborns and has to be assessed before maternity discharge (professional consensus). All these data have to be reported in the newborn personal medical file (professional consensus)., Conclusion: Early discharge has to be prepared during the prenatal period in order to ensure care continuity at home and to avoid any severe neonatal outcome., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the post-partum management of women and their newborn whatever the mode of delivery., Material and Methods: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted., Results: Because breastfeeding is associated with a decrease in neonatal morbidity (lower frequency of cardiovascular diseases, infectious, atopic or infantile obesity) (EL2) and an improvement in the cognitive development of children (EL2), exclusive and extended breastfeeding is recommended (grade B) between 4 to 6 months (Professional consensus). In order to increase the rate of breastfeeding initiation and its duration, it is recommended that health professionals work closely with mothers in their project (grade A) and to promote breastfeeding on demand (grade B). There is no scientific evidence to recommend non-pharmacological measures of inhibition of lactation (Professional consensus). Pharmacological treatments for inhibition of lactation should not be given routinely to women who do not wish to breastfeed (Professional consensus). Because of potentially serious adverse effects, bromocriptin is contraindicated in inhibiting lactation (Professional consensus). For women aware of the risks of pharmacological treatment of inhibition of lactation, lisuride and cabergolin are the preferred drugs (Professional consensus). Whatever the mode of delivery, numeration blood count is not systematically recommended in a general population (Professional consensus). Anemia must be sought only in women with bleeding or symptoms of anemia (Professional consensus). The only treatment of post-dural puncture headache is the blood patch (EL2), it must not be carried out before 48 h (Professional consensus). Women vaccination status and their family is to be assessed in the early post-partum (Professional consensus). Immediate postoperative monitoring after caesarean delivery should be performed in the recovery room, but in exceptional circumstances, it may be performed in the delivery unit provided safety rules are maintained and regulatory authorities are informed (Professional consensus). An analgesic multimodal protocol developed by the medical team should be available and oral way should be favored (Professional consensus) (grade B). For every cesarean delivery, thromboprophylaxis with elastic stockings applied on the morning of the surgery and kept for at least 7 postoperative days is recommended (Professional consensus) with or without the addition of LMWH according to the presence or not of additional risk factors, and depending on the risk factor (major, minor). Early postoperative rehabilitation is encouraged (Professional consensus). Postpartum visit should be planned 6 to 8 weeks after delivery and can be performed by an obstetrician, a gynecologist, a general practitioner or a midwife, after normal pregnancy and delivery (Professional consensus). Starting effective contraception later 21 days after delivery in women who do not want closely spaced pregnancy is recommended (grade B), and to prescribe it at the maternity (Professional consensus). According to the postpartum risk of venous thromboembolism, the combined hormonal contraceptive use before six postpartum weeks is not recommended (grade B). Rehabilitation in asymptomatic women in order to prevent urinary or anal incontinence in medium or long-term is not recommended (Expert consensus). Pelvic-floor rehabilitation using pelvic-floor muscle contraction exercises is recommended to treat persistent urinary incontinence at 3 months postpartum (grade A), regardless of the type of incontinence. Postpartum pelvic-floor rehabilitation is recommended to treat anal incontinence (grade C). Postpartum pelvic-floor rehabilitation is not recommended to treat or prevent prolapse (grade C) or dyspareunia (grade C). The optimal time for maternity discharge for low risk newborn depends more on the organisation of the post-discharge follow up (Professional consensus). The months following the birth are a transitional period, and psychological alterations concern all parents (EL2). It is more difficult in case of psychosocial risk factors (EL2). In situations of proven psychological difficulties, the impact on the psycho-emotional development of children can be important (EL3). Among these difficulties, postpartum depression is the most common situation. However, the risk is generally higher in the perinatal period for all mental disorders (EL3)., Conclusion: Postpartum is, for clinicians, a unique and privileged opportunity to address the physical, psychological, social and somatic health of their patients., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Prompt initiation of appropriate neonatal resuscitation skills is critical for the neonate experiencing difficulty transitioning to extra-uterine life. Expertise in neonatal resuscitation is essential for personnel involved in the care of newborns, above all for midwives who are sometimes alone to initiate the first resuscitation. The use of simulation training is considered to be an indispensable tool to address these challenges, not only in continuing education but also in midwifery education., Objective: The aim of this study was to evaluate the impact and efficiency of high-fidelity simulation for neonatal resuscitation in midwifery education., Methods: This was a prospective monocentric study conducted in the Angers university hospital between October and December 2012 and included two groups of midwifery students (n=40) who received high-fidelity simulation as part of their basic midwifery education. Participants' perceptions of the knowledge, skills, and confidence gained following training in high-fidelity simulation for neonatal resuscitation were determined using a pre-/post-test questionnaire design completed during the training and also several months after the course, as well as after the students had begun working. A satisfaction survey to evaluate this training was also completed at the same time., Results: With a good participation rate (67.5%), the survey showed a high degree of satisfaction among the participants. This training was described as facilitating their hire in one third of cases. A significant increase in self-assessment of skills scores was observed between the pre-test and post-test (P<0.001), the pre-test and the distance test (P<0.001), and the post-test and distance test (P=0.007). Although a decrease in the median score was observed on the knowledge questionnaire given as a post-test, this median remained significantly higher than that obtained on the pre-test (P=0.03)., Conclusion: The significant improvement in knowledge during the session and its preservation after a few months confirmed the efficacy of this teaching method. The simulation training increased the participants' perceptions of their knowledge, skills, and confidence in conducting neonatal resuscitation. These preliminary results are very encouraging and argue in favor of generalizing this teaching method. However, this training could be more profitable if it was proposed earlier in the midwifery curriculum and organized with a multidisciplinary team (pediatric and anesthesia residents)., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: The optimal age for assessing language difficulties in premature children remains unclear., Aims: To determine the most predictive and earliest screening tool for later language difficulties on children born preterm., Study Design: A prospective population-based study in the Loire Infant Follow-up Team LIFT SUBJECTS: All children born <35weeks of gestation between 2003 and 2005 were assessed at corrected ages by four screening tools: the Ages & Stages Questionnaire (ASQ) communication scale at 18 and 24months, the language items of Brunet Lezine test at 24months, and the "Epreuves de Repérage des Troubles du Langage" (ERTL) at 4years., Outcome Measures: After 5years, the kindergarten teacher evaluated the vocabulary, grammar and pronunciation capacities of the child in comparison with the classroom performances., Results: Among 1957 infants enrolled at discharge, 947 were assessed by their teacher with 12.2% (n=116) of language difficulties. Full data at all time points were available for 426 infants. The area under curve of the receiver operator characteristic curve obtained for the ASQ communication scale at 18months was significantly lower (0.65±0.09) than that obtained at 24months (0.77±0.08) and the languages items of Brunet Lezine test at 24months (0.77±0.08), and the ERTL at 4years (0.76±0.09). The optimal cut-off value for ASQ communication at 24months is ≤45 [sensitivity of 0.79 (95%CI: 0.70-0.86); specificity of 0.63 (95%CI: 0.59-0.66)]., Conclusions: The Ages & Stages Questionnaire communication scale at 24 corrected months appears as an acceptable test at an early time point to identify preterm children at risk of later language difficulties., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To evaluate long-term outcome after history of intra-uterine growth restriction (IUGR) and/or birth small for gestational age (SGA)., Methods: This systematic evidence review is based on Pubmed search, Cochrane library and experts recommendations., Results: Neurodevelopmental evaluation at 2 years is lower in those infants, born premature or not. SGA is associated with a high risk of minor cognitive deficiencies, hyperactivity or attention deficit disorders at 5 years or scholar difficulties at 8 years. Those infants are at high risk of metabolic syndrome in adulthood. Most of them will catch up at 6 months for weight and 12 months for height. Even if IUGR is associated with high risk of bronchodysplasia, up to this day, the review of literature did not permit to evaluate respiratory outcome. Adults born SGA have good quality of live and normal professional insertion. One cohort study and more and more animal studies suggest potential trans generational effects., Conclusion: Infants born SGA and/or with history of IUGR are at high risk of minor cognitive deficiencies and scholar difficulties. They are also at high risk of metabolic syndrome in adulthood. However, prematurity seems to have a higher effect than IUGR and/or SGA on long-term outcomes., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To describe early complications and management of the small for gestational age (SGA) neonate., Methods: This systematic evidence review is based on Pubmed search, Cochrane library and experts recommendations. Words included in the search mainly were: small for gestational age, intrauterine growth restriction, fetal growth restriction, very low birth weight infants, neonatal management, neonatal outcome, neonatal morbidity, neonatal mortality, Results: Neonatal mortality relative risk among SGA infants is 2-4 times higher than adapted for gestational age (AGA) newborn infants, at any gestational age. SGA infants had an increased risk for perinatal asphyxia, hypothermia and hypoglycaemia during their first days of life. In the SGA preterm population, bronchopulmonary dysplasia, pulmonary hypertension and necrotising enterocolitis are significantly more frequent as compared with AGA population. Periventricular leukomalacia is not significantly different between SGA and AGA infants whereas intraventricular hemorrhage and retinopathy risks are discussed. Adaptive problems require paediatric contact before birth. Early management of the small for gestational age includes intervention to prevent hypothermia, the use of pressure controlled ventilator if needed, and close blood glucose monitoring., Conclusions: SGA infants had excess neonatal mortality and morbidity in comparison with adapted ones for gestational age (AGA) infants, especially for preterm infants., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)