Identifying Newborns with Hypoxic-Ischemic Encephalopathy in Hospital Discharge Data: A Validation Study.

Hospital discharge databases (HDDs) are increasingly used for research on health of newborns. Linkage between a French population-based cohort of newborns with hypoxic-ischemic encephalopathy (HIE) and national HDD showed that the HIE ICD-10 code was not accurately reported. Our results suggest that HDD should not be used for research on neonatal HIE without prior validation of HIE ICD-10 codes.

Validity of a Delphi consensus definition of growth restriction in the newborn for identifying neonatal morbidity.

BACKGROUND: Small for gestational age is defined as a birthweight below a birthweight percentile threshold, usually the 10th percentile, with the third or fifth percentile used to identify severe small for gestational age. Small for gestational age is used as a proxy for growth restriction in the newborn, but small-for-gestational-age newborns can be physiologically small and healthy. In addition, this definition excludes growth-restricted newborns who have weights more than the 10th percentile. To address these limits, a Delphi study developed a new consensus definition of growth restriction in newborns on the basis of neonatal anthropometric and clinical parameters, but it has not been evaluated. OBJECTIVE: To assess the prevalence of growth restriction in the newborn according to the Delphi consensus definition and to investigate associated morbidity risks compared with definitions of Small for gestational age using birthweight percentile thresholds. STUDY DESIGN: Data come from the 2016 and 2021 French National Perinatal Surveys, which include all births ≥22 weeks and/or with birthweights ≥500 g in all maternity units in France over 1 week. Data are collected from medical records and interviews with mothers after the delivery. The study population included 23,897 liveborn singleton births. The Delphi consensus definition of growth restriction was birthweight less than third percentile or at least 3 of the following criteria: birthweight, head circumference or length <10th percentile, antenatal diagnosis of growth restriction, or maternal hypertension. A composite of neonatal morbidity at birth, defined as 5-minute Apgar score <7, cord arterial pH <7.10, resuscitation and/or neonatal admission, was compared using the Delphi definition and usual birthweight percentile thresholds for defining small for gestational age using the following birthweight percentile groups: less than a third, third to fourth, and fifth to ninth percentiles. Relative risks were adjusted for maternal characteristics (age, parity, body mass index, smoking, educational level, preexisting hypertension and diabetes, and study year) and then for the consensus definition and birthweight percentile groups. Multiple imputation by chained equations was used to impute missing data. Analyses were carried out in the overall sample and among term and preterm newborns separately. RESULTS: We identified that 4.9% (95% confidence intervals, 4.6-5.2) of newborns had growth restriction. Of these infants, 29.7% experienced morbidity, yielding an adjusted relative risk of 2.5 (95% confidence intervals, 2.2-2.7) compared with newborns without growth restriction. Compared with birthweight ≥10th percentile, morbidity risks were higher for low birthweight percentiles (less than third percentile: adjusted relative risk, 3.3 [95% confidence intervals, 3.0-3.7]; third to fourth percentile: relative risk, 1.4 [95% confidence intervals, 1.1-1.7]; fifth to ninth percentile: relative risk, 1.4 [95% confidence intervals, 1.2-1.6]). In adjusted models including the definition of growth restriction and birthweight percentile groups and excluding birthweights less than third percentile, which are included in both definitions, morbidity risks remained higher for birthweights at the third to fourth percentile (adjusted relative risk, 1.4 [95% confidence intervals, 1.1-1.7]) and fifth to ninth percentile (adjusted relative risk, 1.4 [95% confidence intervals, 1.2-1.6]), but not for the Delphi definition of growth restriction (adjusted relative risk, 0.9 [95% confidence intervals, 0.7-1.2]). Similar patterns were found for term and preterm newborns. CONCLUSION: The Delphi consensus definition of growth restriction did not identify more newborns with morbidity than definitions of small for gestational age on the basis of birthweight percentiles. These findings illustrate the importance of evaluating the results of Delphi consensus studies before their adoption in clinical practice.

Growth charts for use at birth and in the neonatal period: Recommendations of the French Neonatal Society.

INTRODUCTION: The use of different growth charts can lead to confusion in discussions between professionals. There are obstetric charts (of fetal growth) and neonatal charts (of measurements at birth and of postnatal growth). These charts can be descriptive (derived from an unselected population) or prescriptive (derived from of a population at low risk and with optimal conditions for growth). OBJECTIVES: (1) To describe available charts for infants at birth and in the neonatal period and compare them, and (2) to recommend one or more charts for use in neonatology in France. METHODS: Bibliographic research was conducted on MEDLINE and completed by the guidelines of professional societies. RESULTS: Antenatal information about fetal growth restriction (FGR) or fetuses identified as small-for-gestational-age using Intrauterine charts must be integrated into the identification of newborns at risk, but the use of Intrauterine charts to evaluate birthweight is not recommended to allow consistency with postnatal charts used in neonatal practice. Z-score variations using the updated Fenton postnatal charts are the most appropriate for the assessment of birthweight and postnatal growth for infants born preterm. These charts are sex-specific, include the three measurements (length, weight, and head circumference) and enable longitudinal follow-up of growth up to 50 weeks of corrected age and are linked to the WHO charts at term. The French Audipog charts, although are individualized, accessible online and can be used in maternity units to evaluate birthweight for term infants, but do not allow the follow-up of postnatal growth, while Fenton charts may be used to evaluate birthweight and postnatal growth in the first month for hospitalized term infants. CONCLUSION: The updated Fenton charts are the neonatal charts that best suit the objectives of pediatricians in France for monitoring the growth of preterm newborns. The use of the Audipog charts at term remains an alternative in maternity wards, while Fenton charts can be used for hospitalized term newborns.

Glycemia and Neonatal Encephalopathy: Outcomes in the LyTONEPAL (Long-Term Outcome of Neonatal Hypoxic EncePhALopathy in the Era of Neuroprotective Treatment With Hypothermia) Cohort.

OBJECTIVES: To assess in newborns with neonatal encephalopathy (NE), presumptively related to a peripartum hypoxic-ischemic event, the frequency of dysglycemia and its association with neonatal adverse outcomes. STUDY DESIGN: We conducted a secondary analysis of LyTONEPAL (Long-Term Outcome of Neonatal hypoxic EncePhALopathy in the era of neuroprotective treatment with hypothermia), a population-based cohort study including 545 patients with moderate-to-severe NE. Newborns were categorized by the glycemia values assessed by routine clinical care during the first 3 days of life: normoglycemic (all glycemia measurements ranged from 2.2 to 8.3 mmol/L), hyperglycemic (at least 1 measurement >8.3 mmol/L), hypoglycemic (at least 1 measurement <2.2 mmol/L), or with glycemic lability (measurements included at least 1 episode of hypoglycemia and 1 episode of hyperglycemia). The primary adverse outcome was a composite outcome defined by death and/or brain lesions on magnetic resonance imaging, regardless of severity or location. RESULTS: In total, 199 newborns were categorized as normoglycemic (36.5%), 74 hypoglycemic (13.6%), 213 hyperglycemic (39.1%), and 59 (10.8%) with glycemic lability, based on the 2593 glycemia measurements collected. The primary adverse outcome was observed in 77 (45.8%) normoglycemic newborns, 37 (59.7%) with hypoglycemia, 137 (67.5%) with hyperglycemia, and 40 (70.2%) with glycemic lability (P < .01). With the normoglycemic group as the reference, the aORs and 95% 95% CIs for the adverse outcome were significantly greater for the group with hyperglycemia (aOR 1.81; 95% CI 1.06-3.11). CONCLUSIONS: Dysglycemia affects nearly two-thirds of newborns with NE and is independently associated with a greater risk of mortality and/or brain lesions on magnetic resonance imaging. TRIAL REGISTRATION: NCT02676063.

Risk factors for unfavorable outcome at discharge of newborns with hypoxic-ischemic encephalopathy in the era of hypothermia.

OBJECTIVE: To re-visit short-term outcomes and associated risk factors of newborns with hypoxic-ischemic encephalopathy (HIE) in an era where hypothermia treatment (HT) is widespread. METHODS: This is a prospective population-based cohort in French neonatal intensive care units (NICU). Neonates born at or after 34 weeks of gestational age with HIE were included; main outcomes were in-hospital death and discharge with abnormal or normal MRI. Associations of early perinatal risk factors, present at birth or at admission to NICU, with these outcomes were studied. RESULTS: A total of 794 newborns were included and HT was administered to 670 (84.4%); 18.3% died and 28.5% and 53.2% survived with abnormal and normal MRI, respectively. Severe neurological status, Apgar score at 5 mn ≤5, lactate at birth ≥11 mMoles/l, and glycemia ≥100 mg/dL at admission were associated with an increased risk of death (relative risk ratios (aRRR) (95% CI) 19.93 (10.00-39.70), 2.89 (1.22-1.62), 3.06 (1.60-5.83), and 2.55 (1.38-4.71), respectively). Neurological status only was associated with survival with abnormal MRI (aRRR (95% CI) 1.76 (1.15-2.68)). CONCLUSION: Despite high use of HT in this cohort, 46.8% died or presented brain lesions. Early neurological and biological examinations were associated with unfavorable outcomes and these criteria could be used to target children who warrant further neuroprotective treatment. TRIAL REGISTRATION: Clinical trial registry, NCT02676063, ClinicalTrials.gov. IMPACT: In this population-based cohort of newborns with HIE where 84% received hypothermia, 46.8% still had an unfavorable evolution (death or survival with abnormal MRI). Risk factors for death were high lactate, low Apgar score, severe early neurological examination, and high glycaemia. While studies have established risk factors for HIE, few have focused on early perinatal factors associated with short-term prognosis. This French population-based cohort updates knowledge about early risk factors for adverse outcomes in the era of widespread cooling. In the future, criteria associated with an unfavorable evolution could be used to target children who would benefit from another neuroprotective strategy with hypothermia.

Serial plotting of symphysis-fundal height and estimated fetal weight to improve the antenatal detection of infants small for gestational age: A cluster randomised trial.

OBJECTIVE: To assess whether standardised longitudinal reporting of growth monitoring information improves antenatal detection of infants who are small for gestational age (SGA), compared with usual care. DESIGN: Cluster-randomised controlled trial. SETTING: Sixteen French level-3 units in 2018-2019. POPULATION: Singleton pregnancies. METHODS: The intervention consisted of the serial plotting of symphysis-fundal height (SFH) and estimated fetal weight (EFW) measurements on customised growth charts using a software program, compared with standard antenatal care. We estimated relative risks (RR) adjusted for known risk factors for fetal growth restriction (FGR). MAIN OUTCOME MEASURES: The primary outcome was antenatal detection of FGR among SGA births (with birthweights below the tenth centile of French customised curves), defined as the mention of suspected FGR in medical records and either referral ultrasounds for growth monitoring or indicated delivery for FGR. Secondary outcomes were false-positive rates, mode of delivery, perinatal morbidity and mortality, and number of antenatal visits and ultrasounds. RESULTS: In total, seven intervention clusters (n = 4349) and eight control clusters (n = 4943) were analysed, after the exclusion of one intervention centre for a major deviation in protocol. SGA births represented 613 (14.1%) and 626 (12.7%) of all births, respectively. The rates of antenatal detection of FGR among SGA births were 40.0% in the intervention arm versus 37.1% in the control arm (crude RR 1.08, 95% CI 0.87-1.34; adj RR 1.09, 95% CI 0.88-1.35). No benefits of the intervention were detected in the analyses of secondary outcomes. CONCLUSIONS: Serial plotting of SFH and EFW measurements on customised growth charts did not improve the antenatal detection of FGR among SGA births.

Healthcare organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort.

Initiation of therapeutic hypothermia (TH) within 6 h of life is a major concern for treating neonatal hypoxic ischemic encephalopathy (HIE). We aimed to determine clinical and healthcare organizational factors associated with delayed TH in a French population-based cohort of neonates with moderate/severe HIE. Time to reach a rectal temperature of 34 °C defines optimal and delayed (within and over 6 h, respectively) TH. Clinical and healthcare organizational factors associated with delayed TH were analysed among neonates born in cooling centres (CCs) and non-cooling centres (non-CCs). Among 629 neonates eligible for TH, 574 received treatment (91.3%). TH was delayed in 29.8% neonates and in 20.3% and 36.2% of those born in CCs and non-CCs, respectively. Neonates with moderate HIE were more exposed to delayed TH in both CCs and non-CCs. After adjustment for HIE severity, maternal and neonatal characteristics and circumstances of birth were not associated with increased risk of delayed TH. However, this risk was 2 to 5 times higher in maternities with < 1999 annual births, when the delay between birth and call for transfer (adjusted odds ratio [aOR] 2.47, 95% confidence interval [CI] [1.03 to 5.96]) or between call for transfer and admission (aOR 6.06, 95%CI [2.60 to 14.12]) was > 3 h and when an undesirable event occurred during transfer (aOR 2.66, 95%CI [1.11 to 6.37].  Conclusion: Increasing early identification of neonates who could benefit from TH and access to TH in non-CCs before transfer are modifiable factors that could improve care of neonates with HIE.  Trial registration: The trial was registered at ClinicalTrials.gov (NCT02676063). What is Known: • International recommendations are to initiate therapeutic hypothermia before 6 h of life in neonates with moderate or severe hypoxic ischemic encephalopathy. What is New: •In this French population-based cohort of infants with hypoxic ischemic encephalopathy, nearly one-third of neonates eligible for treatment did not have access to hypothermia in the therapeutic window of 6 h of life. . • Among infants born in non-cooling centres, healthcare organizational factors involved in delayed care were the small size of maternities (1999 annual births), a time interval of more than 3 h between birth and call for transfer and between call for transfer and admission in neonatology, and the occurrence of an undesirable event during transfer.

Cerebral injuries in neonatal encephalopathy treated with hypothermia: French LyTONEPAL cohort.

BACKGROUND: Hypothermia is widely used for infants with hypoxic-ischemic neonatal encephalopathy but its impact remains poorly described at a population level. We aimed to describe brain imaging in infants born at ≥36 weeks' gestation, with moderate/severe encephalopathy treated with hypothermia. METHODS: Descriptive analysis of brain MRI and discharge neurological examination for infants included in the French national multicentric prospective observational cohort LyTONEPAL. RESULTS: Among 575 eligible infants, 479 (83.3%) with MRI before 12 days of life were included. MRI was normal for 48.2% (95% CI 43.7-52.8). Among infants with brain injuries, 62.5% (95% CI 56.2-68.5) had damage to more than one structure, 19.8% (95% CI 15.0-25.3) showed a pattern-associating injuries of basal ganglia/thalami (BGT), white matter (WM) and cortex. Overall, 68.4% (95% CI 62.0-74.3) of infants with normal MRI survived with a normal neurological examination. The rate of death was 15.4% (95% CI 12.3-19.0), predominantly for infants with the combined BGT, cortex, and/or WM injuries. CONCLUSIONS: Among infants with neonatal encephalopathy treated with hypothermia, two-thirds of those with normal MRI survived with a normal neurological examination at discharge. When present, brain injuries often involved more than one structure. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT02676063). IMPACT: In this multicentric cohort of infants with neonatal encephalopathy (LYTONEPAL) two-thirds survived with normal MRI and neurological examination at discharge. In total, 10% of newborns showed a pattern associating injuries of the basal ganglia-thalami, white matter, and cortex, which was correlated with a high risk of death at discharge. The evolution of MRI techniques and sequences in the era of hypothermia calls for a revisiting of imaging protocol in neonatal encephalopathy, especially for the timing. The neurological examination did not give evidence of brain injuries, thus questioning the reproducibility of the clinical exam or the neonatal brain functionality.

Neurodevelopment at two years and appropriate schooling at five years in children born very preterm.

AIM: This single-centre French cohort study evaluated the relationship between standardised assessment at 2 years of corrected age and schooling level at 5 years of age in children born at ≤32 weeks' gestational age. METHODS: This was a single-centre retrospective study of children born preterm between 2010 and 2014 included in a follow-up network. At 5 years of age, the population was divided into 2 groups: (1) 'appropriate schooling', defined as age-appropriate schooling without support, and (2) 'schooling with support'. At 2 years of corrected age, the developmental quotient (DQ) was calculated using the revised Brunet-Lezine test. Neonatal variables and DQ categories were compared between the 2 groups on univariate and multivariate analyses. RESULTS: DQ was available for 251 of the 270 children included (93%), with a median score of 93.0 (IQR [87.0-100.0]), and 171 children (68%) were in the schooling without support group. On multivariate analysis, DQ ≥100 (n = 67) was the only variable that significantly associated with schooling without support (OR = 13.9; 95% CI: 5.5-35.4) at 5 years of age. CONCLUSION: This result may be useful for clinicians in their routine practice and for information given to parents in neonatal follow-up.

Propofol versus placebo (with rescue with ketamine) before less invasive surfactant administration: study protocol for a multicenter, double-blind, placebo controlled trial (PROLISA).

BACKGROUND: One major limitation for less invasive surfactant administration (LISA) is the difficulty in providing sedation before this procedure and the competitive risk of respiratory depression versus avoidance of intubation for most sedative or analgesic drugs used in this context. The objective of this study is to compare the need for mechanical ventilation within 72 h of life following premedication with propofol, versus placebo (rescue with ketamine), for the LISA procedure in preterm neonates born before 32 weeks gestational age (wGA). METHODS: ProLISA is a phase III, non-inferiority, multicenter, double blind, randomized, placebo controlled trial designed according to the SPIRIT Statement. Neonates born before 32 wGA in 12 geographically dispersed Neonatal Intensive Care Units in France needing surfactant will be included from September 2019 to September 2022. A sample of 542 patients is needed. The neonate is randomized to the intervention (propofol) or control placebo group. Open label rescue treatment with ketamine is possible in both groups if FANS (Faceless Acute Neonatal pain Scale) is ≥6. To guide drug administration, FANS is scored before attempting laryngoscopy. Once an adequate score has been obtained, LISA is performed according to a standardized protocol. The primary outcome is the need for mechanical ventilation within 72 h of life. Secondary outcomes are tolerance of the procedure, pain evaluation, hemodynamic and neurologic parameters after the intervention, morbidities before discharge and neurodevelopmental assessment at 2 years of age. DISCUSSION: This paper describes the first multicenter, double-blind, randomized, placebo-controlled trial on this topic and will provide crucial information to support implementation of the LISA procedure. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04016246. Registered 06 June 2019, N°EUDRACT: 2018-002876-41.

Nebulized hypertonic saline 3% for 1 versus 3 days in hospitalized bronchiolitis: a blinded non-inferiority randomized controlled trial.

BACKGROUND: The use and optimal duration of treatment with nebulized hypertonic saline (HS) in infants hospitalized for acute bronchiolitis is unclear. The objective was to compare the efficacy of 1 versus 3 days of nebulized 3% HS at 72 h of treatment. We conducted a blinded non-inferiority randomized controlled trial including infants aged less than 12 months old, hospitalized for a moderate bronchiolitis. METHODS: Nebulisations of 3% HS for 1 day were followed by either the continuation of 3% HS (HS3d group) or switched to 0.9% normal isotonic saline (HS1d group) for 2 days Randomization was performed according to a predefined list with a 1:1 ratio, obtained with a random generator number with blocks.. Main outcome was mean Wang clinical severity score (CSS) after 72 h of treatment. RESULTS: One hundred sixteen infants (HS1d n = 59 and HS3d n = 57), were included over two epidemic seasons from 2014 to 2016, but recruitement did not reach the planned sample size. The difference for the Wang CSS score in the HS3d vs HS1d group was 0.71 [IC 90% 0.1; 1.3], above the precluded value of 0.4 set in the protocol defining the non-inferiority of shorter treatment duration. Clinical remission was more rapidly obtained in the HS3d than in HS1d (2.3 ± 1.6 vs 2.9 ± 1.4 days, p = 0.04), with a non-significant tendency for less need of nutritional support and supplemental oxygen in HS3d group. Clinical worsening and treatment intolerance were similar in the 2 groups. CONCLUSIONS: Despite being underpowered, results seem not to be in favour of reducing the duration of nebulised HS treatment from 3 to 1 day in acute moderate bronchiolitis. TRIAL REGISTRATION: Clinical trials NCT02538458, October 2014.

Comparison of the Hadlock and INTERGROWTH formulas for calculating estimated fetal weight in a preterm population in France.

BACKGROUND: Accurate estimation of fetal weight is needed for growth monitoring and decision-making in obstetrics; the INTERGROWTH project developed an estimated fetal weight formula to construct new intrauterine growth standards. OBJECTIVE: We sought to compare the accuracy of the Hadlock and INTERGROWTH formulas for the estimation of fetal weight among preterm infants. STUDY DESIGN: Using the EPIPAGE 2 population-based study of births between 22-34 weeks of gestation, we included 578 nonanomalous singleton fetuses with an ultrasound-to-delivery interval <2 days. We used abdominal circumference, head circumference, and femur length to calculate estimated fetal weight with Hadlock formula and abdominal and head circumferences to calculate estimated fetal weight according to INTERGROWTH. The mean percentage errors and the proportions of estimated fetal weight measures within ±10% of birthweight were compared between the 2 methods. RESULTS: Mean (SD) gestational age and birthweight were 29.1 (SD 2.7) weeks and 1219 (SD 489) g. Mean (SD) percentage errors for Hadlock and INTERGROWTH were significantly different: -0.7 (SD 10.1) and -3.5 (SD 11.6), respectively (P < .001), and more infants were classified within ±10% of their birthweight with Hadlock compared to INTERGROWTH (68.7% vs 57.8%, P < .001). The INTERGROWTH formula overestimated birthweight at 22-23 weeks compared to Hadlock [mean errors of 18.8 (SD 13.6) vs 5.5 (SD 10.2)] and underestimated birthweight >28 weeks: at 29-31 weeks, mean errors were -5.8 (SD 10.9) for INTERGROWTH and -0.6 (SD 10.4) for Hadlock. CONCLUSION: Hadlock estimated fetal weight formula was more accurate than INTERGROWTH formula for fetuses delivered between 22-34 weeks of gestation. Our results support continued use of Hadlock formula in France and raise questions about the applicability of INTERGROWTH intrauterine growth standards.

LyTONEPAL: long term outcome of neonatal hypoxic encephalopathy in the era of neuroprotective treatment with hypothermia: a French population-based cohort.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a rare neonatal condition affecting about 1‰ births. Despite a significant improvement in the management of this condition in the last ten years, HIE remains associated with high rates of death and severe neurological disability. From September 2015 to March 2017, a French national cohort of HIE cases was conducted to estimate the extent of long-term moderate and severe neurodevelopmental disability at 3 years and its determinants. METHODS: This prospective population-based cohort includes all moderate or severe cases of HIE, occurring in newborns delivered between 34 and 42 completed weeks of gestation and admitted to a neonatal intensive care unit. Detailed data on the pregnancy, delivery, and newborn until hospital discharge was collected from the medical records in maternity and neonatology units. All clinical examinations including biomarkers, EEG, and imaging were recorded. To ensure the completeness of HIE registration, a registry of non-included eligible neonates was organized, and the exhaustiveness of the cohort is currently checked using the national hospital discharge database. Follow-up is organized by the regional perinatal network, and 3 medical visits are planned at 18, 24 and 36 months. One additional project focused on early predictors, in particular early biomarkers, involves a quarter of the cohort. DISCUSSION: This cohort study aims to improve and update our knowledge about the incidence, the prognosis and the etiology of HIE, and to assess medical care. Its final objective is to improve the definition of this condition and develop prevention and management strategies for high-risk infants. TRIAL REGISTRATION: NCT02676063 . Date of registration (Retrospectively Registered): February 8, 2016.

Fetal and neonatal outcomes of preterm infants born before 32 weeks of gestation according to antenatal vs postnatal assessments of restricted growth.

BACKGROUND: Fetal growth restriction is defined using ultrasound parameters during pregnancy or as a low birthweight for gestational age after birth, but these definitions are not always concordant. OBJECTIVE: The purpose of this study was to investigate fetal and neonatal outcomes based on antenatal vs postnatal assessments of growth restriction. STUDY DESIGN: From the EPIPAGE 2 population-based prospective study of very preterm births in France in 2011, we included 2919 singleton nonanomalous infants 24-31 weeks gestational age. We constituted 4 groups based on whether the infant was suspected with fetal growth restriction during pregnancy and/or was small for gestational age with a birthweight <10th percentile of intrauterine norms by sex: 1) suspected with fetal growth restriction/small for gestational age 2) not suspected with fetal growth restriction/small for gestational age 3) suspected with fetal growth restriction/not small for gestational age and 4) not suspected with fetal growth restriction/not small for gestational age. We estimated relative risks of perinatal mortality and morbidity for these groups adjusting for maternal and neonatal characteristics. RESULTS: We found that 22.2% of infants were suspected with fetal growth restriction/small for gestational age, that 11.4% infants were not suspected with fetal growth restriction/small for gestational age, that 3.0% infants were suspected with fetal growth restriction/not small for gestational age, and that 63.4% infants were not suspected with fetal growth restriction/not small for gestational age. Compared with infants who were not suspected with fetal growth restriction/not small-for-gestational-age infants, small-for-gestational-age infants suspected and not suspected with fetal growth restriction had higher risks of stillbirth or termination of pregnancy (adjusted relative risk, 2.0 [95% confidence interval, 1.6-2.5] and adjusted relative risk, 2.8 [95% confidence interval, 2.2-3.4], respectively), in-hospital death (adjusted relative risk, 2.8 [95% confidence interval, 2.0-3.7] and adjusted relative risk, 2.0 [95% confidence interval, 1.5-2.8], respectively), and bronchopulmonary dysplasia (adjusted relative risk, 1.3 [95% confidence interval, 1.2-1.4] and adjusted relative risk, 1.3 [95% confidence interval, 1.1-1.4], respectively), but not severe brain lesions. Risks were not increased for infants suspected with fetal growth restriction but not small-for-gestational-age. CONCLUSION: Antenatal and postnatal assessments of fetal growth restriction were not concordant for 14% of very preterm infants. In these cases, birthweight appears to be the more relevant parameter for the identification of infants with higher risks of adverse short-term outcomes.

Sound levels in a neonatal intensive care unit significantly exceeded recommendations, especially inside incubators.

AIM: This study measured sound levels in a 2008 built French neonatal intensive care unit (NICU) and compared them to the 2007 American Academy of Pediatrics (AAP) recommendations. The ultimate aim was to identify factors that could influence noise levels. METHODS: The study measured sound in 17 single or double rooms in the NICU. Two dosimeters were installed in each room, one inside and one outside the incubators, and these conducted measurements over a 24-hour period. The noise metrics measured were the equivalent continuous sound level (Leq ), the maximum noise level (Lmax ) and the noise level exceeded for 10% of the measurement period (L10 ). RESULTS: The mean Leq , L10 and Lmax were 60.4, 62.1 and 89.1 decibels (dBA), which exceeded the recommended levels of 45, 50 and 65 dBA (p < 0.001), respectively. The Leq inside the incubator was significantly higher than in the room (+8 dBA, p < 0.001). None of the newborns' characteristics, the environment or medical care was correlated to an increased noise level, except for a postconceptional age below 32 weeks. CONCLUSION: The sound levels significantly exceeded the AAP recommendations, particularly inside incubators. A multipronged strategy is required to improve the sound environment and protect the neonates' sensory development.

Prenatal and post-natal cost of small for gestational age infants: a national study.

BACKGROUND: Small for gestational age (SGA) infants are at increased risk for preterm birth morbidities as well as a range of adverse perinatal outcomes that result in part from associated premature birth. We sought to evaluate the costs of SGA versus appropriate for gestational age (AGA) infants in France from pregnancy through the first year of life and separate the contributions of prematurity from the contribution of foetal growth on costs. METHODS: This is a cross-sectional population-based study using national hospital discharge data from French public and private hospitals. SGA infants were defined as newborns with a birth weight below the 10th percentile of French intrauterine growth curves adjusted for foetal sex. AGA infants were defined as newborns with a birth weight between the 25th and the 75th. All births were selected between January 1st, 2011 and December 31st, 2011. Costs were calculated from the hospital perspective for both mothers and children using their diagnostic related group and the French national cost study. Hospital outcomes were extracted from the database and compared by gestational age and mode of delivery. RESULTS: Of 777,720 total births in 2011, 84,688 SGA births (10.9%) and 395,760 AGA births (50.8%) were identified. After adjustment for gestational age, the cost for an SGA infant was €2,783 higher than for an AGA infant. The total maternal and infant hospital cost of SGA in France was estimated at 23% the total cost for deliveries. The high cost is explained by higher complication rates, more frequent hospital readmissions and longer lengths of stay. CONCLUSIONS: Being small for gestational age is an independent contributor to 1-year hospital costs for both mothers and infants.

Does the Presence of Risk Factors for Fetal Growth Restriction Increase the Probability of Antenatal Detection? A French National Study.

BACKGROUND: Screening for fetal growth restriction (FGR) is a major component of prenatal care. We investigated whether the presence of maternal and pregnancy risk factors for FGR improves the antenatal suspicion of FGR for infants born small-for-gestational age (SGA) as well as their impact on screening specificity. METHODS: Data are from a representative sample of births from the 2010 French National Perinatal Survey (n = 14 100). Detection of FGR was determined by a suspicion of FGR noted in medical charts. Analyses were performed for singleton infants with birthweight under the 10th percentile (SGA), under the 3rd percentile (severely SGA), and above the 10th percentile (false positives) of French references. We studied risk factors for FGR (medical and obstetric conditions, advanced maternal age, nulliparity, body mass index and smoking) using multivariable Poisson regression to derive adjusted risk ratios (aRR). RESULTS: Of SGA infants, 21.7% were suspected of FGR. The presence of obstetric and medical risk factors for FGR was associated with higher suspicion among SGA infants [RR 2.1, 95% confidence interval (CI) 1.7, 2.7]. However, despite the presence of these factors, 60% and 40% of SGA and severely SGA infants, respectively, were not suspected of FGR. Two per cent of normal birthweight infants were suspected of FGR, increasing to 5% when obstetric and medical risk factors were present. Smoking and older maternal age were unrelated to suspicion while females were more likely to be suspected of FGR. CONCLUSION: Our results suggest that better risk assessment could improve antenatal identification of FGR. Sex-specific fetal growth references should be used to avoid systematic bias linked to sex.

Visual-perceptual impairment in children with cerebral palsy: a systematic review.

AIM: Visual perception is one of the cognitive functions often impaired in children with cerebral palsy (CP). The aim of this systematic literature review was to assess the frequency of visual-perceptual impairment (VPI) and its relationship with patient characteristics. METHOD: Eligible studies were relevant papers assessing visual perception with five common standardized assessment instruments in children with CP published from January 1990 to August 2011. RESULTS: Of the 84 studies selected, 15 were retained. In children with CP, the proportion of VPI ranged from 40% to 50% and the mean visual perception quotient from 70 to 90. None of the studies reported a significant influence of CP subtype, IQ level, side of motor impairment, neuro-ophthalmological outcomes, or seizures. The severity of neuroradiological lesions seemed associated with VPI. The influence of prematurity was controversial, but a lower gestational age was more often associated with lower visual motor skills than with decreased visual-perceptual abilities. INTERPRETATION: The impairment of visual perception in children with CP should be considered a core disorder within the CP syndrome. Further research, including a more systematic approach to neuropsychological testing, is needed to explore the specific impact of CP subgroups and of neuroradiological features on visual-perceptual development.

Effect of gestational age on cerebral lesions in neonatal encephalopathy.

OBJECTIVE: To determine the risk on brain lesions according to gestational age (GA) in neonates with neonatal encephalopathy. DESIGN: Secondary analysis of the prospective national French population-based cohort, Long-Term Outcome of NeonataL EncePhALopathy. SETTING: French neonatal intensive care units. PATIENTS: Neonates with moderate or severe neonatal encephalopathy (NE) born at ≥34 weeks' GA (wGA) between September 2015 and March 2017. MAIN OUTCOME MEASURES: The results of MRI performed within the first 12 days were classified in seven injured brain regions: basal ganglia and thalami, white matter (WM), cortex, posterior limb internal capsule, corpus callosum, brainstem and cerebellum. A given infant could have several brain structures affected. Risk of brain lesion according to GA was estimated by crude and adjusted ORs (aOR). RESULTS: MRI was available for 626 (78.8%) of the 794 included infants with NE. WM lesions predominated in preterm compared with term infants. Compared with 39-40 wGA neonates, those born at 34-35 wGA and 37-38 wGA had greater risk of WM lesions after adjusting for perinatal factors (aOR 4.0, 95% CI (1.5 to 10.7) and ORa 2.0, 95% CI (1.1 to 3.5), respectively). CONCLUSION: WM is the main brain structure affected in late-preterm and early-term infants with NE, with fewer WM lesions as GA increases. This finding could help clinicians to estimate prognosis and improve the understanding of the pathophysiology of NE. TRIAL REGISTRATION NUMBER: NCT02676063, ClinicalTrials.gov.

[Investigation of a French cohort of neonatal anoxo-ischemic encephalopathy in the era of therapeutic hypothermia: Questions and answers]. / Analyse d'une cohorte française d'encéphalopathies néonatales anoxo-ischémiques à l'ère de l'hypothermie thérapeutique : questions­réponses.

OBJECTIVE: To improve knowledge of neonatal hypoxic-ischemic encephalopathy, a prospective, nationwide, population-based cohort of affected children is being set up between September 2015 and March 2017. METHODS: During this period, 794 cases are collected, with information on pregnancy, delivery, neonatal stay and outcome at the end of hospitalization. Clinical and parental questionnaire follow-up is planned until the child is 4 years old. RESULTS: This article presents the clinical presentation of the newborns included, the analysis of factors associated with short-term outcome at hospital discharge and the organizational factors associated with treatment with therapeutic hypothermia. CONCLUSION: These data illustrate the value of a prospective cohort to analyze the management of anoxo-ischemic encephalopathy in France.