The impact of chorionicity on pregnancy outcome and neurodevelopment at 2 years old among twins born preterm: the EPIPAGE-2 cohort study.

OBJECTIVE: To compare the short- and mid-term outcomes of preterm twins by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: 546 maternity units in France, between March and December 2011. POPULATION: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: First, survival at 2-year corrected age with or without neurosensory impairment, and second, perinatal, short-, and mid-term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. RESULTS: In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2-year follow-up neurodevelopmental results were not significantly different between DC and MC twins. CONCLUSIONS: This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity. TWEETABLE ABSTRACT: Monochorionicity is associated with adverse perinatal outcomes, but outcomes for preterm twins are comparable irrespective of their chorionicity.

[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 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.

Infection néonatale bactérienne précoce (INBP) : quel algorithme de prise en charge en 2017 ?

In the era of intrapartum chemoprophylaxis to reduce GBS, rates of early onset bacterial infection have declined in term newborns. New guidelines have been written in order to adapt our current practices to this epidemiological evolution and limit excessive exams and antibiotic administrations. The main point of these new guidelines consists in a clinical systematic surveillance in maternity for well appearing newborns instead of the current empiric antibiotic treatment. Advised biological exams are also detailed.

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.

[Early-onset neonatal infection: assessment of professional practices in 14 maternity wards in the Île-de-France region in 2013]. / Infections néonatales bactériennes précoces : évaluation des pratiques professionnelles dans 14 maternités d'Île-de-France en 2013.

INTRODUCTION: Early-onset neonatal infection remains a major cause of morbidity and mortality in neonates. Both universal vaginal screening for group-B streptococcus (GBS) and intrapartum antibiotic prophylaxis have decreased the incidence of early-onset GBS disease. Almost 12 years after the implementation of the French recommendations, we assessed the practices around screening, diagnosis, and treatment of early-onset neonatal infection in the Île-de-France region. PATIENTS AND METHODS: We conducted a prospective, multicenter, observational study in 14 volunteer maternity wards from 18 to 31 March 2013. All live newborn infants delivered at 35 gestational weeks or more were eligible. Maternal, obstetrical, and neonatal characteristics were collected, as well as the management of suspected early-onset neonatal infections. RESULTS: A total of 1194 mothers and 1217 neonates were included. Among the latter, 54% had bacteriological samplings at birth, with at least a gastric aspirate. Bacteriological samples were collected at birth in 85% of cases based on major or minor anamnestic infection criteria defined by the French National Authority for Health in 2002. In addition, 26% of neonates had at least one blood sample taken. Antibiotic treatment was administered in 4% of the infants with cefotaxime administered in two thirds of cases. CONCLUSION: An update of the French guidelines for the management of early-onset neonatal infections is required in order to improve targeting of newborn infants suspected of having an infection and to optimize the antibiotics administered. Moreover, the role of bacteriological sampling at birth needs to be clarified.

Are children born after infertility treatment at increased risk of retinoblastoma?

BACKGROUND: Retinoblastoma (RB) is the most frequent eye tumour in children, with an incidence of 1 in 15-20,000 births. It accounts for 11% of all cancers in the first year of life. Except for the hereditary forms, its causes are not well-known. Studies have recently suggested an increased risk of RB among children born after IVF, but the relevant literature is sparse. We assessed the association between infertility treatment, subfertility and RB. METHODS: We included all children living in France diagnosed with RB between 1 January 2000 and 31 December 2006 at the Institut Curie, the national reference centre for RB diagnosis and treatment. We used multiple logistic regression to compare them with a national sample of births in France in 1998 and 2003 (n = 28 170). RESULTS: The study included 244 non-familial RB cases. The risk of RB increased with maternal age [adjusted odds ratio (adj OR) = 2.07, 95% confidence interval (CI) 1.33-3.22 at 35-39 years compared with younger than 25 years and adj OR = 2.42, 95% CI 1.22-4.81 at 40 years or older], but the associations with IVF (adj OR = 1.37, 95% CI 0.64-2.95) and ovarian stimulation or intrauterine insemination (adj OR = 1.35, 95% CI 0.77-2.38) were not statistically significant after adjustment for maternal age and tobacco use. Among women who had no infertility treatment, the risk of RB was significantly increased when time to pregnancy exceeded 24 months (adj OR = 2.02, 95% CI 1.17-3.48) compared with time to pregnancy ≤ 24 months. CONCLUSIONS: Our study did not observe a significantly increased risk of RB associated with infertility treatment, in particular with IVF. But we did find an increased risk for women for whom time to pregnancy exceeded 24 months.

[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.

[Factors associated to breastfeeding up to 6 months in the maternity of Antoine-Béclère Hospital, Clamart]. / Facteurs associés à l'allaitement maternel du nourrisson jusqu'à 6 mois à la maternité de l'hôpital Antoine-Béclère, Clamart.

OBJECTIVES: In order to improve the frequency and duration of breastfeeding, various public health initiatives have been established at local and national levels in France. In 2002, we conducted a study in the maternity center of the Antoine Beclere Hospital with the aim to describe breastfeeding practices and to identify factors associated with its duration. METHODS: This prospective study was conducted among newborns of immediate postpartum women admitted to the maternity center of the Antoine Beclere Hospital (Clamart, France). Extremely premature newborns were excluded (<31 weeks of amenorrhea). Mothers were interviewed at delivery, at one month and 6 months postpartum. Data were collected on maternal medical history, pregnancy and delivery, the newborn's health status, feeding practices, and the reasons for their choice in feeding practices. RESULTS: Between January 7 and April 7, 2002, 562 newborns were included in the study. At birth, 73% were breastfed, whereas 68% were breastfed at discharge from the maternity center. Among the latter, 89% of infants were still being breastfed at one month, and 37% at 6 months of age. Factors associated with breastfeeding at one month were as follows: a secondary level of education (OR(a): 2.4 [1.0-5.7] compared to primary level), multiparity (OR(a): 3.0 [1.2-8.0] compared to primiparity), full-term birth (OR(a): 6.6 [2.4-18.4] compared to premature birth), treatment during pregnancy (OR(a): 0.2 [0.04-0.6]), and medical history (OR(a): 0.4 [0.2-1.0]). Among women who were breastfeeding at one month, the continuation of breastfeeding at 6 months was associated with a secondary education level (OR(a): 2.2 [1.0-5.0]), the choice of feeding practice during pregnancy (OR(a): 2.5 [1.1-5.0] compared to those who did not choose), and to medically assisted reproduction (OR(a): 5.0 [1.2-14.3] compared to spontaneous procreation). DISCUSSION: The prevalence of breastfeeding observed in this study is higher than it was observed at the national level. Factors associated with continuation of breastfeeding at 6 months allow identifying women who should be encouraged to breastfeed by the maternity team involved during pregnancy. Interventions should therefore involve maternity healthcare professionals as a first step in breastfeeding promotion.

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.

Outcome of children born out of pregnancies complicated by unexplained polyhydramnios.

Our aim was to assess the long-term outcomes of infants born out of a pregnancy complicated by unexplained polyhydramnios. We retrospectively analysed a cohort of 173 singleton pregnancies with polyhydramnios. There were 24 singletons with unexplained polyhydramnios, defined as polyhydramnios where prenatal testing was negative. Infants were examined by a paediatrician at a median age of 12 months (range 12-64 months). Of the 24 infants, 19 (79%) had a normal outcome. West syndrome, polyuria and pulmonary stenosis were diagnosed in three children during follow up, while there were two perinatal deaths. Paediatric follow up of children born out of pregnancies complicated by unexplained polyhydramnios should be carried out systematically.

[Preimplantation genetic diagnosis (PGD): results from a Parisian center]. / Indications et résultats du diagnostic pré-implantatoire (DPI).

OBJECTIVE: To report the results of preimplantation genetic diagnosis (PGD) cycles performed in our unit from 2000 to 2004. Materials and methods. One hundred and seventy-one couples were enrolled in the PGD program over this period. The collected oocytes were inseminated by intracytoplasmic sperm injection (ICSI). The resulting embryos were biopsied on the third day of development and the genetic analysis was performed on the same day. Embryo transfers were carried out on the fourth day. RESULTS: The 416 stimulation cycles started yielded 280 oocyte pick-ups, 3506 oocytes retrieved, of which 2966 were suitable for ICSI. Among the 1982 embryos obtained, 1337 embryos were biopsied and genetic diagnosis was performed for 1083 (81%) of them. 381 embryos were transferred during the course of 189 transfer procedures. There were 51 clinical and 46 ongoing (35 single, 11 twin) pregnancies. In addition, 25 frozen embryo replacement cycles were initiated, leading to 6 embryo transfers and 1 ongoing pregnancy. A total of 58 unaffected children were born. CONCLUSION: PGD has gained a place among the choices offered to couples at risk of transmission of a serious and incurable genetic disease. It might be a realistic alternative to prenatal diagnosis for patients carrier of chromosomal rearrangements, single gene defects, X-linked disesases or mitochondrial DNA disorders.

Delay in diagnosis of imported Plasmodium falciparum malaria in children.

The study reported here prospectively evaluated the time-to-diagnosis of imported Plasmodium falciparum malaria in children in seven French pediatric emergency departments during a 1-week period. For the 29 patients included, the mean patient, doctor and total delays were 3.1, 1.5 and 4.7 days, respectively. The late medical diagnosis for 11 patients was mainly due to the treating physician's failure to consider malaria, despite having been informed that the child had been in an endemic area, and erroneously making a diagnosis of viral infection. The five patients who were diagnosed correctly without delay had higher mean platelet counts than the others (206,000 vs 118,541/mm(3); p=0.008). The results indicate that greater awareness of the risk of malaria in returning travelers may help reduce delays in diagnosis and its consequences.

[Factors predicting serious bacterial infections in febrile infants less than three months old: multivariate analysis]. / Facteurs prédictifs de la présence d'une infection bactérienne sévère chez les nourrissons fébriles âgés de moins de trois mois: analyse multivariée.

AIM: To identify predictive factors of the presence of a serious bacterial infection (SBI) in febrile infants less than three months old. METHODS: Retrospective analysis of the medical files of 315 consecutive consultations of febrile infants less than three months old in the pediatric emergency department of a French hospital, with logistic regression multivariate analysis of the different criteria routinely considered and C-reactive protein (CRP). RESULTS: SBI were diagnosed in 79 (25.1%) infants, primarily urinary tract infections (71; 22.5%). One of these 79 children had pneumococcal meningitis but met the classical criteria for low risk of SBI: he died because antibiotics were not prescribed sufficiently early. Factors significantly associated with SBI were: male sex; temperature >38.5 degrees C and lasting >24 hours; poor general condition; absence of ear, nose and throat symptoms; high white blood cell count with >50% neutrophils; and serum CRP concentration >20 mg/l. Multivariate analysis entering all these items retained only the latter two (respectively, OR: 13.5, 95% CI: [6.5-28.2] and OR: 2.9; 95% CI: [1.3-6.3]). CRP <20 mg/l and <50% neutrophils had a negative-predictive value of 93.1% for the absence of SBI. CONCLUSIONS: At present, no factor(s) is(are) able to predict with 100% accuracy the absence of SBI in febrile infants less than three months old. The risk of severe sequelae or death caused by untreated SBI would seem to justify the prescription of antibiotics until microbacterial culture results become available.

Benefit of antenatal glucocorticoids according to the cause of very premature birth.

In this observational study performed in a large cohort of very preterm singletons, respiratory outcome was found to be strongly dependent on the cause of premature delivery. Although less apparent in infants born to mothers with chorioamnionitis, exposure to antenatal glucocorticoids remained significantly associated with a decrease in the incidence of respiratory distress syndrome after adjustment for the main cause of premature birth.

Changes in risk factors of preterm delivery in France between 1981 and 1995.

Because of the important changes in medical care and the social context of pregnancy, the relevance of well-established risk factors of preterm delivery (< 37 weeks) needs to be re-assessed. The objective of this study was to determine whether the associations between maternal characteristics and preterm delivery in France in 1995 were similar to those in 1981. We used two national representative samples of births, 5577 newborns in 1981 and 13318 in 1995. Univariable and multivariable analyses were applied to identify variables associated with increased risk of preterm delivery. Some risk factors were similar in 1981 and 1995, including age > 34 years and previous adverse obstetric history. Other factors that were observed in 1981 but which were not linked to preterm delivery in 1995 included the mothers being very young, single or foreign. However, parity and previous induced abortion were associated with preterm delivery in 1995, but not in 1981. These results show that the definition of high-risk groups used in prevention programmes should be brought up to date regularly.

[Risk factors for prematurity in France and comparisons between spontaneous prematurity and induced labor: results from The National Perinatal Survey 1995]. / Facteurs de risque de prématurité en France et comparaisons entre prématurité spontanée et prématurité induite.

OBJECTIVE: To study risk factors of total preterm delivery, spontaneous preterm delivery and induced preterm delivery. POPULATION: Representative sample of births in 1995 in France, including 12869 single births. METHOD: Preterm deliveries included all births before 37 weeks. Risk factors were analyzed with logistic regression. Factors of spontaneous preterm delivery (after spontaneous onset of labor) and factors of induced preterm delivery (after induction or cesarean section before labor) were compared with polytomous logistic regression. RESULTS: The main risk factors of preterm delivery were history of adverse pregnancy outcome (ORa=4. 5), history of induced abortion (ORa=1.5), 35 year old or more (ORa=1.5) and inadequate antenatal care (ORa=2.1). Other factors such as age under 20 or being single were not significantly linked to preterm delivery. Risk factors differed slightly between spontaneous and induced preterm deliveries. CONCLUSION: The present risk factors do not always correspond with the well-known factors. Thus the assessment of risk factors would be necessary at regular interval. The small differences between the risk factors of spontaneous preterm delivery and induced preterm delivery may be explained by difficulties in defining those two types of preterm delivery or by difficulties in distinguishing specific causes for each of them.