Optimising homeothermy in neonates: a systematic review and clinical guidelines from the French Neonatal Society.

AIM: Thermal instability is harmful on the newborn infant. We sought to draw up practical guidelines on maintaining homeothermy alongside skin-to-skin contact. METHODS: A systematic analysis of the literature identified relevant studies between 2000 and 2021 in the PubMed database. Selected publications were evaluated, and their level of evidence were graded, in order to underpin the development of clinical guidelines. RESULTS: We identified 7 meta-analyses and 64 clinical studies with a focus on newborn infants homeothermy. Skin-to-skin contact is the easiest and most rapidly implementable method to prevent body heat loss. Alongside skin-to-skin contact, monitoring the newborn infant's body temperature with a target of 37.0°C is essential. For newborn infants <32 weeks of gestation, a skullcap and a polyethylene bag should be used in the delivery room or during transport. To limit water loss, inhaled gases humidification and warming is recommended, and preterm infants weighing less than 1600 g should be nursed in a closed, convective incubator. With regard to incubators, there are no clear benefits for single vs. double-wall incubators as well as for air vs. skin servo control. CONCLUSION: Alongside skin-to-skin contact, a bundle of practical guidelines could improve the maintenance of homeothermy in the newborn infant.

Altered autonomic control in preterm newborns with impaired neurological outcomes.

PURPOSE: Very preterm newborns are at high risk of neurological injury. The objective of this work was to study the impact of neurological aggression on the autonomic nervous system. METHODS: We studied polysomnography recordings, at term corrected gestational age, for 38 preterm infants born at less than 28 weeks or weighing less than 1 kg. These infants were seen by a neuropediatrician, average age at follow up was 54.4 months. We created two groups: one with children who did not have any neurological disorder, including cerebral palsy (CP), language or mental retardation, visual or hearing disability, and attention disorder; the second group contained children with at least one of these impairments. From the polysomnography recordings, using coarse-graining spectral analysis, we compared heart rate variability indices between preterm infants with normal and abnormal neurological outcomes. RESULTS: Twenty infants had an impaired neurological outcome. Regarding the clinical characteristics, there were more babies born from smoking mothers (p = 0.025), with early-onset neonatal sepsis (p = 0.04), and abnormal results on cerebral magnetic resonance imaging (p = 0.014) in the group with impaired neurological outcomes. Spectral parameters were significantly different between active and quiet sleep. Total powers, harmonic and non-harmonic powers, high frequency and low frequency powers were higher in active sleep compared with those in quiet sleep. Preterm babies with impaired neurological development, in particular those with CP, had lower total power and non-harmonic power especially in active sleep than those with normal neurological outcome. CONCLUSION: These findings suggest that, in very preterm infants, perinatal neurological injuries could be associated with abnormal maturation of the autonomic nervous system.

Transfontanellar contrast enhanced ultrasound in infants: initial experience.

BACKGROUND AND PURPOSE: Transfontanellar contrast enhanced ultrasound (TCEUS) in infants with neurological diseases has not been previously reported. Thus, the objective of our study was to describe the imaging findings of transfontanellar contrast enhanced ultrasound (TCEUS) performed in various neurological conditions in infants and to compare the findings with non-enhanced transfontanellar ultrasound (TFUS) and MRI. METHODS: Local institutional review board approval was obtained and, because of the need to catheterize children for contrast media administration, written informed consent of parents was obtained prior to all performed TCEUS. Twelve infants who underwent 12 TCEUS were included in this study from June 2009 to June 2012. Second generation contrast material was used (Bracco). TCEUS imaging findings were compared with those of conventional transfontanellar ultrasound in each case and with MRI. RESULTS: In 10 out of the 12 performed examinations, TCEUS showed abnormalities which were not depicted on non-enhanced TFUS. Accurate diagnosis of TCEUS compared with MRI was found in 10 out of 12 initial TCEUS. No adverse events during or immediately after contrast media injection occurred. CONCLUSION: TCEUS appears to be a potential bedside accessible non-ionizing alternative imaging modality in the assessment of neonatal brain injury. It provides additional information when compared to non-enhanced transfontanellar US, especially in the field of brain perfusion assessment. Moreover, the information provided seems to be accurate when compared with those of MRI.

Cognitive impairment at age 5 years in very preterm infants born following premature rupture of membranes.

OBJECTIVE: To evaluate the relationship between preterm premature rupture of membranes (PPROM) and cognitive impairment in 5-year-old children born very preterm. STUDY DESIGN: The Etude Epidémiologique sur les Petits Ages Gestationnels Study is a population-based cohort of children followed up from birth to age 5 years recruited in 9 French regions in 1997. We analyzed data from singletons born between 24 and 32 weeks gestation categorized into 4 groups according to etiology of prematurity: infants born after PPROM, after idiopathic preterm labor, in a vascular context (Vasc), and to women with other complications (Other). Cognitive development at age 5 years was assessed using the Mental Processing Composite score of the Kaufman-Assessment Battery for Children. RESULTS: Among the 1051 children followed up to age 5 years, the mean Mental Processing Composite score was 93.6 ± 19.7, and 13.3% of the children (140 of 1051) had cognitive impairment. After adjustment for potential confounders, the risk of cognitive impairment among infants in the PPROM group was not significantly different than that in the idiopathic preterm labor group (OR, 1.09; 95% CI, 0.62-1.92) and the Other group (OR, 1.36; 95% CI, 0.75-2.47), but was lower than that in the Vasc group (OR, 1.86; 95% CI, 1.16-2.97). In the PPROM group, the risk of cognitive impairment was greater when the latency period (ie, time from rupture to delivery) was <3 days (OR, 2.32; 95% CI, 1.07-5.02). CONCLUSION: Preterm infants born after PPROM are not at increased risk for cognitive impairment in childhood, but the time between PPROM and birth may influence that risk.

Decreased spontaneous arousability in preterm newborns with impaired neurological outcome.

Preterm newborns are at high risk of neurological injury. In this population, we investigated the link between neurological complications and sleep architecture. At term-corrected gestational age, we studied retrospectively the polysomnography of 45 preterm infants born at < 28 weeks or weighting < 1 kg. These infants were followed-up by a neuropaediatrician (median age at last follow-up 50.4 months). Two groups of children were constituted: a group without neurological disorder and a second group with at least one of the following: cerebral palsy, language or mental retardation, visual or hearing disability or attention disorder. A Multiple Indicators and Multiple Causes model assessed the relationship between the neurological outcome and two sleep components: spontaneous arousability [number of awakenings and movements per hour of quiet sleep (QS) and active sleep] and QS characteristics (median duration of QS cycles and percentage of QS over total sleep time). Twenty-six infants had an impaired neurological outcome. There were no statistical differences between the two groups regarding clinical characteristics. Compared to preterm neonates with normal neurological outcome, those with impaired outcomes had a lower spontaneous arousability; i.e. 0.7 (0.5­1) times less awakenings and movements per hour of QS and 0.9 (0.8­1) times less per hour of active sleep than infants with normal outcomes (P = 0.05). The differences in QS characteristics did not reach statistical significance. These findings suggested that, in preterm infants, perinatal neurological injuries could be associated with an abnormal sleep architecture characterized by altered spontaneous arousability.

Predictors of the risk of cognitive deficiency in very preterm infants: the EPIPAGE prospective cohort.

AIM: To assess cerebral lesions and other medical as well as social characteristics as predictors of risk of mild and severe cognitive deficiencies in very preterm infants. METHODS: As part of the EPIPAGE population-based prospective cohort study, perinatal data and cognitive outcome at 5 years of age were recorded for 1503 infants born before 33 weeks of gestation in nine regions of France in 1997. Mild cognitive deficiency was defined as a Mental Processing Composite score on the Kaufman Assessment Battery for Children test of between 70 and 84, and severe cognitive deficiency as a score of <70. RESULTS: After controlling for cerebral lesions and other medical as well as social factors, low parental socio-economic status and lack of breastfeeding were significant predictors of mild and severe cognitive deficiencies, whereas presence of cerebral lesions, being small for gestational age and having a large number of siblings were predictors of severe cognitive deficiency. CONCLUSION: Predictors of poor cognitive outcome in very preterm infants are low social status, lack of breastfeeding, presence of cerebral lesions on ultrasound scan, being born small for gestational age and having a high number of siblings. Social factors predicted both mild and severe cognitive deficiencies, whereas medical factors predicted mostly severe cognitive deficiencies.

Studying Clinical, Biologic and Echocardiography Criteria to Predict a Resistant Kawasaki Disease in Children.

BACKGROUND: Resistant Kawasaki disease (KD) represents 10%-15% of KD patients and increases risk of coronary artery abnormalities (CAAs). Different scores exist to predict resistant KD but only in Japanese population, although a French team has recently proposed a new scoring system. The principal objective of this study is to establish criteria to predict resistant KD in our representative French population. The second objective is an attempt to develop a predictive score of resistant KD. METHODS: We conducted a retrospective multicenter study including 2 universities and five secondary hospitals in Eastern France. Patients were included over a period from January 1, 2010 through December 31, 2019. Diagnosis of KD was recorded to the European Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative criteria. RESULTS: Two hundred two eligible patients had KD and 194 patients were analyzed: 160 sensitive KD and 34 (17.5%) resistant KD. In univariate model, serum sodium <133 mmol/L (odds ratio [OR] 2.97 [1.40-6.45]), hemoglobin level <110 g/L (OR 3.17 [1.46-7.34]), neutrophils >80% (OR 2.36 [1.03-5.25]), C reactive protein level >150 mg/L (OR 4.47 [2.07-10.19]), CAA (OR 3.85 [1.67-8.79]) or myocarditis (OR 6.98 [1.47-36.95]) at the diagnosis were statistically significant, but only serum sodium was an independent factor of resistant KD. CONCLUSION: This study shows an association between resistant KD and biologic and echocardiography criteria, but only serum sodium is an independent predictive factor. A score to predict resistant KD could not yet be established.

Association between moderated level of air pollution and fetal growth: the potential role of noise exposure.

This study aims to analyze, in a population of singletons, the potential confounding or modifying effect of noise on the relationship between fetal growth restriction (FGR) or small for gestational age (SGA) and environmental exposure to air pollution. All women with single pregnancies living in one of two medium-sized cities (Besançon, Dijon) and who delivered at a university hospital between 2005 and 2009 were included. FGR and SGA were obtained from medical records. Outdoor residential exposure to nitrogen dioxide (NO2) and particulate matter (PM10) was quantified at the mother's address at delivery over defined pregnancy periods; outdoor noise exposure was considered to be the annual average daily noise levels in the façade of building (LAeq,24 h). Adjusted odds ratios (ORa) were estimated by multivariable logistic regressions. Among the 8994 included pregnancies, 587 presented FGR and 918 presented SGA. In the two-exposure models, for SGA, the ORa for a 10-µg/m3 increase of PM10 during the two last months before delivery was 1.18, 95%CI 1.00-1.41 and for FGR, these ORa were for the first and the third trimesters, and the two last months before delivery: 0.77 (0.61-0.97), 1.38 (1.12-1.70), and 1.35 (1.11-1.66), respectively. Noise was not associated with SGA or FGR and did not confound the relationship between air pollution and SGA or FGR. These results are in favor of an association between PM10 exposure and fetal growth, independent of noise, particularly towards the end of pregnancy, and of a lack of association between noise and fetal growth.

Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-ß and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

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.

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.

Heart rate variability in preterm infants and maternal smoking during pregnancy.

OBJECTIVE: Tobacco smoke exposure increases the risk of premature birth and of dying of sudden infant death syndrome (SIDS). Prematurity significantly increases the risk of dying of SIDS, but mechanisms underlying this epidemiological finding are unclear. The cumulated effect of both prematurity and prenatal exposure to nicotine on autonomic heart rate control has not been studied. METHODS: Using coarse-graining spectral analysis, we compared heart rate variability (HRV) indices of preterm newborns at 33-34 weeks post-conceptional age from smoking (n = 19) and non-smoking (n = 21) mothers. Assessment of tobacco exposure relied on maternal reports and newborns cotinine analysis. We observed how indicators of HRV depended on gestational age at birth. RESULTS: At 33-34 weeks postconceptional age, the newborns from smoking mothers had lower HRV low frequency power normalised to the total spectral power (LF/TP) than the control group (median values: 8% vs. 15% respectively, p < 0.02). In the non-smoking group, RR-interval values and total HRV power were correlated with gestational age at birth, with a shorter RR and a lower total HRV power in lesser gestational ages (rho = 0.67, p = 0.03, rho = 0.71, p = 0.003 respectively). This correlation was not observed for RR values in the group with smoking mothers.

Pregnancy vulnerability in urban areas: a pragmatic approach combining behavioral, medico-obstetrical, socio-economic and environmental factors.

Multiple risk factors are associated with adverse pregnancy outcomes (APO), but how all these different factors combine and accumulate remains unknown. The objective of this observational retrospective study was to describe the accumulation of multiple vulnerability markers in pregnant women living in an urban area. Women living in Besançon (France) who delivered between 2005 and 2009 were included. Individual data were collected from the obstetrical records while environmental exposures were collected using environmental prediction models. The accumulation of 15 vulnerability markers, grouped into six dimensions (maternal age, smoking, body mass index (BMI), socio-economic, medico-obstetrical and environmental vulnerabilities) was described and analyzed in comparison with four APO. Among the 3686 included women, 20.8% were aged under 20 or over 34 and 21.9% had an extreme pre-pregnancy BMI. 18.8% declared smoking during pregnancy. Women exposed to socio-economic, medico-obstetrical or environmental vulnerability were 14.2%, 31.6% and 42.4% respectively. While 20.6% were not exposed to any marker, 18.8% accumulated three or more dimensions. The risk of APO increased significantly with the cumulative number of vulnerabilities. Define and validate a vulnerability score could be useful to identify vulnerable women, adapt their pregnancy monitoring and help policy makers to implement appropriate education or health promotion programs.

Maturation of spontaneous arousals in healthy infants.

OBJECTIVE: The propensity to arouse from sleep is an integrative part of the sleep structure and can have direct implications in various clinical conditions. This study was conducted to evaluate the maturation of spontaneous arousals during the first year of life in healthy infants. DESIGN: Nineteen infants were studied with nighttime polysomnography on 3 occasions: aged 2 to 3 months, 5 to 6 months, and 8 to 9 months. Ten infants with a median age of 3 weeks were added to the main study to assess the maturation of arousals from birth. The infants were born full-term, were healthy at the time of study, and had no history of apnea. Sleep-state and cardiorespiratory parameters were scored according to recommended criteria. Arousals were differentiated into subcortical activations or cortical arousals, according to the presence of autonomic and/or electroencephalographic changes. Frequencies of subcortical activations and cortical arousals were studied at different ages in both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. RESULTS: During sleep time, the frequency of total arousals, cortical arousals, and subcortical activations decreased with age. The maturation of the arousal events differed according to sleep states and types of arousals. With age, cortical arousals increased in REM sleep (P = 0.006) and decreased in NREM sleep (P = 0.01). Subcortical activations decreased with age in REM (P < 0.001) and NREM sleep (P < 0.001). CONCLUSIONS: During total sleep time, the frequency of cortical arousals and subcortical activations decreased with maturation. However, the maturation process was different between cortical arousals and subcortical activations. This finding suggests a difference in the maturational sequence of the different brain centers regulating arousals.

Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial.

OBJECTIVE: To compare the effectiveness of sedation by intranasal administration of midazolam (nMDZ) or ketamine (nKTM) for neonatal intubation. DESIGN: A multicentre, prospective, randomised, double-blind study. SETTING: Delivery rooms at four tertiary perinatal centres in France. PATIENTS: Preterm neonates with respiratory distress requiring non-emergent endotracheal intubation for surfactant instillation. INTERVENTIONS: Treatment was randomly allocated, with each neonate receiving a bolus of 0.1 mL/kg in each nostril, corresponding to 0.2 mg/kg for nMDZ and 2 mg/kg for nKTM. The drug was repeated once 7 min later at the same dose if adequate sedation was not obtained. MAIN OUTCOME MEASURES: Success was defined by adequate sedation before intubation and adequate comfort during the procedure. Intubation features, respiratory and cardiovascular events were recorded. RESULTS: Sixty newborns, with mean (SD) gestational age and birth weight of 28 (3) weeks and 1100 (350) g, were included within the first 20 min of life. nMDZ was associated with a higher success rate (89% vs 58%; RR: 1.54, 95% CI 1.12 to 2.12, p<0.01) and shorter delays between the first dose and intubation (10 (6) vs 16 (8) min, p<0.01).Number of attempts, time to intubation, mean arterial blood pressure measures over the first 12 hours after birth and length of invasive ventilation were not different. CONCLUSIONS: nMDZ was more efficient than nKTM to adequately sedate neonates requiring intubation in the delivery room. The haemodynamic and respiratory effects of both drugs were comparable. CLINICAL TRIAL: This clinical trial was recorded on the National Library of Medicine registry (NCT01517828).

Multiple pregnancies and air pollution in moderately polluted cities: Is there an association between air pollution and fetal growth?

BACKGROUND: Multiple pregnancies (where more than one fetus develops simultaneously in the womb) are systematically excluded from studies of the impact of air pollution on pregnancy outcomes. This study aims to analyze, in a population of multiple pregnancies, the relationship between fetal growth restriction (FGR), small for gestational age (SGA) and exposure to air pollution in moderately polluted cities. METHODS: All women with multiple pregnancies living in the city of Besançon or in the urban area of Dijon and who delivered at a university hospital between 2005 and 2009 were included. FGR and SGA were obtained from medical records. Outdoor residential nitrogen dioxide (NO2) exposure was assessed using the mother's address, considering a 50 m radius buffer over the following defined pregnancy periods: each trimester, entire pregnancy and two months before delivery. Logistic regression analyses were performed. RESULTS: This study included 249 multiple pregnancies with 506 newborns. The median of NO2 concentration considering a 50 m radius buffer during entire pregnancy was 23.1 µg/m3 (minimum at 10.1 µg/m3 and maximum at 46.7 µg/m3). No association was observed between NO2 and SGA whatever the pregnancy period (the odds ratio (OR) range 0.78 to 0.88). Regarding FGR, the OR associated with an increase of 10 µg/m3 of NO2 exposure during entire pregnancy was 1.52 (95% Confidence Interval (CI): 1.02-2.26). Similar results were observed for NO2 exposure during the various pregnancy periods. CONCLUSIONS: These results are in line with an association between NO2 and fetal growth in multiple pregnancies for an exposure mostly below the threshold set out in European legislation.

Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation.

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.

Does low to moderate environmental exposure to noise and air pollution influence preterm delivery in medium-sized cities?

Background: Preterm birth (PB) is an important predictor of childhood morbidity and educational performance. Beyond the known risk factors, environmental factors, such as air pollution and noise, have been implicated in PB. In urban areas, these pollutants coexist. Very few studies have examined the effects of multi-exposure on the pregnancy duration. The objective of this study was to analyse the relationship between PB and environmental chronic multi-exposure to noise and air pollution in medium-sized cities. Methods: A case-control study was conducted among women living in the city of Besançon (121 671 inhabitants) or in the urban unit of Dijon (243 936 inhabitants) and who delivered in a university hospital between 2005 and 2009. Only singleton pregnancies without associated pathologies were considered. Four controls were matched to each case in terms of the mother's age and delivery location. Residential noise and nitrogen dioxide (NO2) exposures were calculated at the mother's address. Conditional logistic regression models were applied, and sensitivity analyses were performed. Results: This study included 302 cases and 1204 controls. The correlation between noise and NO2 indices ranged from 0.41 to 0.59. No significant differences were found in pollutant exposure levels between cases and controls. The adjusted odds ratios ranged between 0.96 and 1.08. Sensitivity analysis conducted using different temporal and spatial exposure windows demonstrated the same results. Conclusions: The results are in favour of a lack of connection between preterm delivery and multi-exposure to noise and air pollution in medium-sized cities for pregnant women without underlying disease.

Prenatal risk factors for cerebral palsy in very preterm singletons and twins.

OBJECTIVE: To identify the main prenatal risk factors for cerebral palsy in very preterm singletons and twins. METHODS: The data were from the Epipage study, which included all very preterm children (< 33 weeks) born in 1997 in 9 regions of France. The analysis included 1,954 children for whom a medical questionnaire was completed at the age of 2 years (83% of the surviving children). The risk factors studied were pregnancy complications and specific factors in twins (type of placenta and death of cotwin). Logistic regression analysis was carried out for singletons and generalized estimating equation models used for twins. RESULTS: The proportion of cerebral palsy was 8% in singletons and 9% in twins. For singletons, spontaneous preterm labor (adjusted odds ratio [OR] 3.4, 95% confidence interval [CI] 1.7-6.7), preterm premature rupture of membranes (PPROM) with short latency (adjusted OR 4.9, 95% CI 2.0-11.8), and prolonged PPROM (adjusted OR 2.7, 95% CI 1.4-5.3) were associated with a higher risk of cerebral palsy than was hypertension. No such link was found between these pregnancy complications and cerebral palsy in twins. For twins, a monochorionic placenta (OR 1.9, 95% CI 1.0-3.6) increased the risk of cerebral palsy, but the OR became nonsignificant after adjustment (OR 1.7, 95% CI 0.8-3.4). CONCLUSION: In very preterm singletons, spontaneous preterm labor and PPROM increased the risk of cerebral palsy compared with hypertension.