Perceived maternal information on premature infant's pain during hospitalization: the French EPIPAGE-2 national cohort study.

BACKGROUND: Parents of preterm neonates wish greater involvement in pain management; little is known about factors associated with this involvement. We aim to describe perceived maternal information on infants' pain during hospitalization (PMIP), to study associations between PMIP and mothers' attitudes during painful procedures, and to identify individual and contextual factors associated with PMIP. METHODS: Analyses of questionnaires from the French national cohort study of preterm neonates, EPIPAGE-2. PMIP was derived from mothers' answers to questions about information perceived on both pain assessment and management. RESULTS: Among 3056 eligible neonates born before 32 weeks, 1974, with available maternal reports, were included in the study. PMIP was classified as "sufficient," "little, not sufficient," or "insufficient, or none" for 22.7, 45.9, and 31.3% of neonates, respectively. Mothers reporting PMIP as "sufficient" were more frequently present and more likely comforting their child during painful procedures. Factors independently associated with "sufficient" PMIP were high maternal education, gestational age <29 weeks, daily maternal visits, perception of high team support, and implementation of the neonatal and individualized developmental care and assessment program. CONCLUSION: Perceived maternal information on premature infants' pain reported as sufficient increased maternal involvement during painful procedures and was associated with some units' policies.

Maternal employment and socio-economic status of families raising children born very preterm with motor or cognitive impairments: the EPIPAGE cohort study.

AIM: To describe maternal employment and the socio-economic status of the household up to 8 years after the very preterm birth of a child, according to the presence and type of motor or cognitive impairment. METHOD: A total of 1885 families from the French EPIPAGE cohort of children who were born very preterm between 1997 and 1998 were included. Motor and cognitive impairments were identified in children between the ages of 2 and 8 years in 770 families and were classified according to type. The 1115 families with children born very preterm without these impairments were considered the reference group. RESULTS: Mothers of children with severe motor or cognitive impairments were less often working at 5 years after the birth than the reference mothers (21% and 30% vs 57%; p<0.001). Those working before birth returned to work less often and those not working started to work less often after the birth than did reference mothers. At 8 years, mothers of children with severe impairments reported financial difficulties more often than mothers of children without impairments. INTERPRETATION: Despite a fairly protective regulatory framework in France, families of infants born very preterm with severe motor or cognitive impairments are socially underprivileged. Measures to maintain an acceptable standard of living for these families and their children are needed.

Volume of Neonatal Care and Survival without Disability at 2 Years in Very Preterm Infants: Results of a French National Cohort Study.

OBJECTIVES: To investigate the relation between neonatal intensive care unit (NICU) volume and survival, and neuromotor and sensory disabilities at 2 years in very preterm infants. STUDY DESIGN: The EPIPAGE-2 (Etude Epidémiologique sur les Petits Âges Gestationnels-2) national prospective population-based cohort study was used to include 2447 babies born alive in 66 level III hospitals between 24 and 30 completed weeks of gestation in 2011. The outcome was survival without disabilities (levels 2-5 of the Gross Motor Function Classification System for cerebral palsy with or without unilateral or bilateral blindness or deafness). Units were grouped in quartiles according to volume, defined as the annual admissions of very preterm babies. Multivariate logistic regression analyses with population average models were used. RESULTS: Survival at discharge was lower in hospitals with lower volumes of neonatal activity (aOR 0.55, 95% CI 0.33-0.91). Survival without neuromotor and sensory disabilities at 2 years increased with hospital volume, from 75% to 80.7% in the highest volume units. After adjustment for gestational age, small for gestational age, sex, maternal age, infertility treatment, multiple pregnancy, principal cause of prematurity, parental socioeconomic status, and mother's country of birth, survival without neuromotor or sensory disabilities was significantly lower in hospitals with a lower volume of neonatal activity (aOR 0.60, 95% CI 0.38-0.95) than in the highest quartile hospitals. CONCLUSIONS: These results suggest that lower neonatal intensive care unit volume is associated with lower survival without an increase in disabilities at 2 years. These results could be useful to generate improvements of perinatal regionalization.

Unit policies and breast milk feeding at discharge of very preterm infants: The EPIPAGE-2 cohort study.

BACKGROUND: Facilitating factors and barriers to breast milk feeding (BMF) very preterm (VP) infants have been widely studied at the individual level. We aimed to describe and analyse factors associated with BMF at discharge for VP infants, with a special focus on unit policies aiming to support BMF. METHODS: We described BMF at discharge in 3108 VP infants enrolled in EPIPAGE-2, a French national cohort. Variables of interest were kangaroo care during the 1st week of life (KC); unit's policies supporting BMF initiation (BMF information systematically given to mothers hospitalised for threatened preterm delivery and breast milk expression proposed within 6 hours after birth) and BMF maintenance (availability of protocols for BMF and a special room for mothers to pump milk); the presence in units of a professional trained in human lactation and regional BMF initiation rates in the general population. Associations were investigated by multilevel logistic regression analysis, with adjustment on individual factors. RESULTS: In total, 47.2% of VP infants received BMF at discharge (range among units 21.1%-84.0%). Unit policies partly explained this variation, regardless of individual factors. BMF at discharge was associated with KC (adjusted odds ratio (aOR) 2.26 (95% confidence interval (CI) 1.40, 3.65)), with policies supporting BMF initiation (aOR 2.19 (95% CI 1.27, 3.77)) and maintenance (aOR 2.03 (95% CI 1.17, 3.55)), but not with BMF initiation rates in the general population. CONCLUSION: Adopting policies of higher performing units could be an effective strategy for increasing BMF rates at discharge among VP infants.

The impact of neonatal unit policies on breast milk feeding at discharge of moderate preterm infants: The EPIPAGE-2 cohort study.

Facilitating factors and barriers to breast milk feeding (BMF) for preterm infants have been mainly studied in very preterm populations, but little is known about moderate preterm infants. We aimed to analyze hospital unit characteristics and BMF policies associated with BMF at discharge for infants born at 32 to 34 weeks' gestation. EPIPAGE-2, a French national cohort of preterm births, included 883 infants born at 32 to 34 weeks' gestation. We investigated kangaroo care in the first 24 hr, early involvement of parents in feeding support, volume of the unit, BMF information given to mothers hospitalized for threatened preterm delivery, protocols for BMF, presence of a professional trained in human lactation, unit training in neurodevelopmental care, and regional BMF initiation rates in the general population. Multilevel logistic regression analysis was used to investigate associations between unit policies and BMF at discharge, adjusted for individual characteristics and estimating odds ratios (ORs) and 95% confidence intervals (CIs). Overall, 59% (490/828) of infants received BMF at discharge (27% to 87% between units). Rates of BMF at discharge were higher with kangaroo care (adjusted OR 2.03 [95% CI 1.01, 4.10]), early involvement of parents in feeding support (1.94 [1.23, 3.04]), unit training in a neurodevelopmental care programme (2.57 [1.18, 5.60]), and in regions with a high level of BMF initiation in the general population (1.85 [1.05, 3.28]). Creating synergies by interventions at the unit and population level may reduce the variability in BMF rates at discharge for moderate preterm infants.

Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing.

Autosomal dominant genetic diseases can occur de novo and in the form of somatic mosaicism, which can give rise to a less severe phenotype, and make diagnosis more difficult given the sensitivity limits of the methods used. We report the case of female child with a history of surgery for syndactyly of the hands and feet, who was admitted at 6 years of age to a pediatric intensive care unit following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval that on occasions reached 500 ms. Despite the absence of facial dysmorphism and the presence of normal psychomotor development, a diagnosis of Timothy syndrome was made given the association of syndactyly and the ECG features. Sanger sequencing of the CACNA1C gene, followed by sequencing of the genes KCNQ1, KCNH2, KCNE1, KCNE2, were negative. The subsequent analysis of a panel of genes responsible for hereditary cardiac rhythm disorders using Haloplex technology revealed a recurrent mosaic p.Gly406Arg missense mutation of the CACNA1C gene in 18% of the cells. This mosaicism can explain the negative Sanger analysis and the less complete phenotype in this patient. Given the other cases in the literature, mosaic mutations in Timothy syndrome appear more common than previously thought. This case demonstrates the importance of using next-generation sequencing to identify mosaic mutations when the clinical picture supports a specific mutation that is not identified using conventional testing. © 2016 Wiley Periodicals, Inc.

Clinical and molecular spectrum of renal malformations in Kabuki syndrome.

OBJECTIVE: To determine the frequency and types of renal malformations, and to evaluate renal function in a cohort of patients with Kabuki syndrome (KS). STUDY DESIGN: Renal ultrasound scans and plasma creatinine measurements were collected from a French cohort of 94 patients with genotyped KS. Renal function was evaluated based on the estimated glomerular filtration rate. A genotype-phenotype study was conducted for renal and urinary tract malformations. RESULTS: Renal malformations were present in 22% of cases, and urinary tract anomalies were present in 15%. Renal malformations were observed in 28% of the MLL2 mutation-positive group and in 0% of the MLL2 mutation-negative group (P = .015). No correlation was found between the presence or absence of renal or urinary tract malformations and the location or type of MLL2 mutation. Renal function was normal except for 1 patient with a MLL2 mutation diagnosed in the first days of life and severe renal disease due to unilateral renal agenesia and controlateral severe hypoplasia that progressed to the terminal stage at age 2 years. CONCLUSION: Our study emphasizes the need for ultrasound and renal function screening in children diagnosed with KS.

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.

The influence of fetal growth reference standards on assessment of cognitive and academic outcomes of very preterm children.

OBJECTIVE: To compare 3 methods of identifying small-for-gestational-age (SGA) status in very preterm children as related to cognitive function and academic outcome. STUDY DESIGN: There were 1038 singletons in the Epipage Study, born before 33 weeks in 1997 without severe neurosensory impairment, who were classified as SGA when birth weight was below the 10th percentile according to: (1) birth weight (bw) reference: SGA(bw)/appropriate for gestational age (AGA)(bw); (2) intrauterine (intraut) reference: SGA(intraut)/AGA(intraut); and (3) intrauterine reference customized (cust) according to individual characteristics: SGA(cust)/AGA(cust). Cognitive function was assessed by the mental processing composite (MPC) score of the Kaufman Assessment Battery for Children at age 5 and academic achievement by a parental questionnaire at age 8. RESULTS: Of the children, 15% were SGA(bw), 38% were SGA(intraut), and 39% were SGA(cust). All children SGA(bw) were also SGA(intraut) and SGA(cust). MPC was <85 in 32% of children and 27% had low academic achievement. AGA(bw)/SGA(intraut) children had a significantly increased risk of MPC <85 (adjusted OR 1.74, 95% CI 1.22-2.28) or low academic achievement (adjusted OR 1.64, 95% CI 1.05-2.55) compared with AGA(bw)/AGA(intraut) children. The SGA(cust) group was only slightly different from the SGA(intraut) group. CONCLUSIONS: An intrauterine reference identified very preterm infants at risk of poor cognitive or academic outcomes better than a birth weight reference. Customization resulted in only slight modifications of the SGA group.

Very preterm birth: who has access to antenatal corticosteroid therapy?

We describe the administration of antenatal corticosteroid therapy (ACT) for liveborn very preterm neonates in a population-based study. A total of 790 very preterm neonates (between 24 and 31 full weeks of gestation) were included in this regionally defined population of very preterm neonates in France. The main outcome measure was non-access to ACT. Data were analysed using logistic and polytomous models to control for neonatal and sociodemographic characteristics, mechanisms of very preterm birth and neonatal network organisation. As compared with level III, births in levels I-II maternity units were closely related to non-access to ACT (60.1% vs. 8.8%), but not to pregnancy follow-up (19.7% vs. 17.8%). Only 6.3% of very preterm neonates that benefited from antepartum referral did nor receive ACT. Births associated with rupture of membranes and gestational hypertension were significantly more often transferred to level-III units (73.8% and 68.3% respectively) than those due to maternal bleeding and spontaneous labour (57.0% and 50.7% respectively), and the neonates had a lower probability of not receiving ACT (8.5%, 11.5%, 23.0%, 31.2% respectively). Very preterm neonates referred in utero to a level-III unit came from a more favourable socio-economic environment. Non-access to ACT was more often observed in neonates born to 14- to 24-year-old mothers, smokers, of low socio-economic status, and preterm birth resulting from maternal bleeding or spontaneous labour. These data from a French regional study show that access to ACT is not only explained by practitioners' support of recommendations. In our population-based study, ACT access was related to socio-economic factors and to the mechanisms of very preterm birth. Improving the rate of access to ACT should take these organisational, medical and socio-economic dimensions into account.

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study.

AIM: The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population-based cohort of very preterm infants. METHOD: As part of EPIPAGE, a population-based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. RESULTS: The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1367 g (SD 393 g; range 450-2645 g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7-10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1305 g (SD 386 g; range 500-2480 g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03-2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95-3.14) were predictors of the development of CP in very preterm infants. INTERPRETATION: Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.

Variations in patterns of care across neonatal units and their associations with outcomes in very preterm infants: the French EPIPAGE-2 cohort study.

OBJECTIVES: To describe patterns of care for very preterm (VP) babies across neonatal intensive care units (NICUs) and associations with outcomes. DESIGN: Prospective cohort study, EPIPAGE-2. SETTING: France, 2011. PARTICIPANTS: 53 (NICUs); 2135 VP neonates born at 27 to 31 weeks. OUTCOME MEASURES: Clusters of units, defined by the association of practices in five neonatal care domains - respiratory, cardiovascular, nutrition, pain management and neurodevelopmental care. Mortality at 2 years corrected age (CA) or severe/moderate neuro-motor or sensory disabilities and proportion of children with scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ). METHODS: Hierarchical cluster analysis to identify clusters of units. Comparison of outcomes between clusters, after adjustment for potential cofounders. RESULTS: Three clusters were identified: Cluster 1 with higher proportions of neonates free of mechanical ventilation at 24 hours of life, receiving early enteral feeding, and neurodevelopmental care practices (26 units; n=1118 babies); Cluster 2 with higher levels of patent ductus arteriosus and pain screening (11 units; n=398 babies); Cluster 3 with higher use of respiratory, cardiovascular and pain treatments (16 units; n=619 babies). No difference was observed between clusters for the baseline maternal and babies' characteristics. No differences in outcomes were observed between Clusters 1 and 3. Compared with Cluster 1, mortality at 2 years CA or severe/moderate neuro-motor or sensory disabilities was lower in Cluster 2 (adjusted OR 0.46, 95% CI 0.25 to 0.84) but with higher proportion of children with an ASQ below threshold (adjusted OR 1.49, 95% CI 1.07 to 2.08). CONCLUSION: In French NICUs, care practices for VP babies were non-randomly associated. Differences between clusters were poorly explained by unit or population differences, but were associated with mortality and development at 2 years. Better understanding these variations may help to improve outcomes for VPT babies, as it is likely that some of these discrepancies are unwarranted.

Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study.

BACKGROUND: The increasing survival rates of children who are born very preterm raise issues about the risks of neurological disabilities and cognitive dysfunction. We aimed to investigate neurodevelopmental outcome and use of special health care at 5 years of age in a population-based cohort of very preterm children. METHODS: We included all 2901 livebirths between 22 and 32 completed weeks of gestation from nine regions in France in Jan 1-Dec 31, 1997, and a reference group of 667 children from the same regions born at 39-40 weeks of gestation. At 5 years of age, children had a medical examination and a cognitive assessment with the Kaufman assessment battery for children (K-ABC), with scores on the mental processing composite (MPC) scale recorded. Data for health-care use were collected from parents. Severe disability was defined as non-ambulatory cerebral palsy, MPC score less than 55, or severe visual or hearing deficiency; moderate deficiency as cerebral palsy walking with aid or MPC score of 55-69; and minor disability as cerebral palsy walking without aid, MPC score of 70-84, or visual deficit (<3/10 for one eye). FINDINGS: In total, 1817 (77%) of the 2357 surviving children born very preterm had a medical assessment at 5 years and 396 (60%) of 664 in the reference group. Cerebral palsy was diagnosed in 159 (9%) of children born very preterm. Scores for MPC were available for 1534 children born very preterm: 503 (32%) had an MPC score less than 85 and 182 (12%) had an MPC score less than 70. Of the 320 children in the reference group, the corresponding values were 37 (12%) and 11 (3%), respectively. In the very preterm group, 83 (5%) had severe disability, 155 (9%) moderate disability, and 398 (25%) minor disability. Disability was highest in children born at 24-28 completed weeks of gestation (195 children [49%]), but the absolute number of children with disabilities was higher for children born at 29-32 weeks (441 children [36%]). Special health-care resources were used by 188 (42%) of children born at 24-28 weeks and 424 (31%) born at 29-32 weeks, compared with only 63 (16%) of those born at 39-40 weeks. INTERPRETATION: In children who are born very preterm, cognitive and neuromotor impairments at 5 years of age increase with decreasing gestational age. Many of these children need a high level of specialised care. Prevention of the learning disabilities associated with cognitive deficiencies in this group is an important goal for modern perinatal care for children who are born very preterm and for their families.

Correction: Maternal Haemoglobin and Short-Term Neonatal Outcome in Preterm Neonates.

[This corrects the article DOI: 10.1371/journal.pone.0089530.].

Does Embryo Culture Medium Influence the Health and Development of Children Born after In Vitro Fertilization?

In animal studies, extensive data revealed the influence of culture medium on embryonic development, foetal growth and the behaviour of offspring. However, this impact has never been investigated in humans. For the first time, we investigated in depth the effects of embryo culture media on health, growth and development of infants conceived by In Vitro Fertilization until the age of 5 years old. This single-centre cohort study was based on an earlier randomized study. During six months, in vitro fertilization attempts (No. 371) were randomized according to two media (Single Step Medium--SSM group) or Global medium (Global group). This randomized study was stopped prematurely as significantly lower pregnancy and implantation rates were observed in the SSM group. Singletons (No. 73) conceived in the randomized study were included (42 for Global and 31 for SSM). The medical data for gestational, neonatal and early childhood periods were extracted from medical records and parental interviews (256 variables recorded). The developmental profiles of the children in eight domains (social, self-help, gross motor, fine motor, expressive language, language comprehension, letter knowledge and number knowledge--270 items) were compared in relation to the culture medium. The delivery rate was significantly lower in the SSM group than in the Global group (p<0.05). The culture medium had no significant effect on birthweight, risk of malformation (minor and major), growth and the frequency of medical concerns. However, the children of the Global group were less likely than those of the SSM group to show developmental problems (p = 0.002), irrespective of the different domains. In conclusion, our findings showed that the embryo culture medium may have an impact on further development.

Temperament at 9 months of very preterm infants born at less than 29 weeks' gestation: the Epipage study.

The objective was to determine whether the temperament of very preterm singleton infants born before 29 weeks' gestation differs from their full-term counterparts at 9 months and to examine the influence of neurological sequelae on temperament in very preterm infants. The parents of very preterm infants from nine French regions and a group of full-term infants were sent the Infant Characteristics Questionnaire when the infants were 9 months old. The analysis included 266 singleton very preterm infants from the same regions born before 29 weeks' gestation and 546 full-term singleton infants. There were no significant differences for the Difficult, Unadaptable, and Unpredictable scales between very premature and term infants. Very preterm infants had a slightly higher Dull scale score than term infants. After taking into account mother's age, duration of hospitalization, and cerebral lesions found on neonatal ultrasound scans, this difference was no longer significant. Among very premature infants, those with cerebral lesions as diagnosed by neonatal ultrasound scan were rated higher on the Dull and Unadaptable scales. Delays in development at 9 months were also related to higher Dull and Unpredictable scales. These data suggest that prematurity does not affect temperament ratings at 9 months as assessed by the mother. However, very preterm infants with neurological insults, documented by the neonatal cerebral ultrasound or by a delay in development, are rated higher by their mothers on the Dull, Unadaptable, and Unpredictable scales.

[Gestational diabetes and urinary tract malformations: a hospital case-control study]. / Diabète gestationnel et malformations de l'appareil urinaire: une étude cas témoins en milieu hospitalier.

INTRODUCTION: Urinary tract malformations represent the leading cause of renal failure in children. Gestational diabetes plays a controversial role in the development of urinary tract malformations. The purpose of this study was to assess the role of insulin-requiring gestational diabetes on the development of ureteric malformations in children. MATERIAL AND METHODS: The authors report the results of a prospective case-control survey (102 cases, 104 controls) conducted in a teaching hospital. The role of insulin-requiring gestational diabetes on the development of urinary tract malformations was tested by logistic regression after adjustment for risk factors for urinary tract malformations 'family history of urinary tract malformations, parity, smoking, substance abuse during pregnancy). RESULTS: Gestational diabetes is a risk factor for urinary tract malfornations after adjustment (aOR=5.1; 95%CI: 1.1-24.5), and for ureteropelvic junction syndrome (aOR=6.5; 95%CI: 1.1-39.4) and vesicoureteric reflux (aOR=5.9; 95%CI: 1.1-32.1). CONCLUSION: All perinatal healthcare professionals must be familiar with the concept of insulin-requiring gestational diabetes as an uncommon, but fairly powerful risk factor for ureteric malformations.

Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study.

IMPORTANCE: Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. OBJECTIVES: To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. DESIGN, SETTING, AND PARTICIPANTS: The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. MAIN OUTCOMES AND MEASURES: Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). RESULTS: A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. CONCLUSIONS AND RELEVANCE: The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.

Maternal haemoglobin and short-term neonatal outcome in preterm neonates.

OBJECTIVE: To determine whether there is a significant association between maternal haemoglobin measured before delivery and short-term neonatal outcome in very preterm neonates. STUDY DESIGN: We included prospectively all live births occurring from 25 to 32+6 weeks of gestation in a tertiary care centre between January 1(st) 2009 and December 31(st) 2011. Outborn infants and infants presenting with lethal malformations were excluded. Three hundred and thirty-nine mothers and 409 infants met the inclusion criteria. For each mother-infant pair a prospective record of epidemiologic data was performed and maternal haemoglobin concentration recorded within 24 hours before delivery was retrospectively researched. Maternal haemoglobin was divided into quartiles with the second and the third one regarded as reference as they were composed of normal haemoglobin values. Short-term outcome was defined as poor in case of death during hospital stay and/or grades III/IV intraventricular haemorrhage and/or periventricular leukomalacia and/or necessity of ventriculoperitoneal shunt. RESULTS: The global rate of poor short-term neonatal outcome was 11.4% and was significantly associated with low maternal haemoglobin values. This association remained significant after adjustment for antenatal corticosteroids therapy, gestational age, parity, mechanism of preterm birth, mode of delivery and birth weight (aOR = 2.97 CI 95% [1.36-6.47]). There was no relation between short-term neonatal outcome and high maternal haemoglobin concentration values. CONCLUSION: We show that low maternal haemoglobin concentration at delivery is an independent risk factor for poor short-term neonatal outcome in very preterm neonates. This study is one of the first to show such an association within the preterm population.