Association of Continuous Opioids and/or Midazolam During Early Mechanical Ventilation with Survival and Sensorimotor Outcomes at Age 2 Years in Premature Infants: Results from the French Prospective National EPIPAGE 2 Cohort.

OBJECTIVE: To evaluate the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age 2 years in very premature infants who were ventilated. STUDY DESIGN: This national observational study included premature infants born before 32 weeks of gestation intubated within 1 hour after birth and still intubated at 24 hours from the French EPIPAGE 2 cohort. Infants only treated with bolus were excluded. Treated infants received continuous opioid and/or midazolam infusion started before 7 days of life and before the first extubation. Naive infants did not receive these treatments before the first extubation, or received them after the first week of life, or never received them. This study compared treated (n = 450) vs naive (n = 472) infants by using inverse probability of treatment weighting after multiple imputation in chained equations. The primary outcomes were survival and survival without moderate or severe neuromotor or sensory impairment at age 2 years. RESULTS: Survival at age 2 years was significantly higher in the treated group (92.5% vs 87.9%, risk difference, 4.7%; 95% CI, 0.3-9.1; P = .037), but treated and naive infants did not significantly differ for survival without moderate or severe neuromotor or sensory impairment (86.6% vs 81.3%; risk difference, 5.3%; 95% CI -0.3 to 11.0; P = .063). These results were confirmed by sensitivity analyses using 5 alternative models. CONCLUSIONS: Continuous opioid and/or midazolam infusions in very premature infants during initial mechanical ventilation that continued past 24 hours of life were associated with improved survival without any difference in moderate or severe sensorimotor impairments at age 2 years.

Risk factors for very preterm delivery out of a level III maternity unit: The EPIPAGE-2 cohort study.

BACKGROUND: Regionalisation programmes aim to ensure that very preterm infants are born in level III units (inborn) through antenatal referral or transfer. Despite widespread knowledge about better survival without disability for inborn babies, 10%-30% of women deliver outside these units (outborn). OBJECTIVE: To investigate risk factors associated with outborn deliveries and to estimate the proportion that were probably or possibly avoidable. METHODS: We used a national French population-based cohort including 2205 women who delivered between 24 and 30+6  weeks in 2011. We examined risk factors for outborn delivery related to medical complications, antenatal care, sociodemographic characteristics and living far from a level III unit using multivariable binomial regression. Avoidable outborn deliveries were defined by pregnancy risk (obstetric history, antenatal hospitalisation) and time available for transfer. RESULTS: 25.0% of women were initially booked in level III, 9.1% were referred, 49.8% were transferred, and 16.1% had outborn delivery. Risk factors for outborn delivery were gestational age <26 weeks (adjusted relative risk (aRR) 1.37, 95% confidence interval (CI) 1.13, 1.66), inadequate antenatal care (aRR 1.39, 95% CI 1.10, 1.81), placental abruption (aRR 1.66, 95% CI 1.27, 2.17), and increased distance to the closest level III unit ((aRR 2.79, 95% CI 2.00, 3.92) in the 4th versus 1st distance quartile). Among outborn deliveries, 16.7% were probably avoidable, and 25.6% possibly avoidable, which could increase the proportion of inborn deliveries between 85.9% and 92.9%. Avoidable outborn deliveries were mainly associated with gestational age, intrauterine growth restriction, preterm premature rupture of membranes, and haemorrhage, but not distance. CONCLUSIONS: Our study identified some modifiable risk factors for outborn delivery; however, when regionalised care relies heavily on antenatal transfer, as it does in France, only some outborn deliveries may be prevented. Earlier referral of high-risk women will be needed to achieve full access to tertiary care.

Repeat induced abortion and adverse childhood experiences in Aquitaine, France: a cross-sectional survey.

OBJECTIVE: The aim of the study was to analyse the relationship between adverse childhood experiences (ACEs) and repeat induced abortion, with regard to the potential effects of social deprivation and intimate partner violence. METHODS: An observational cross-sectional survey was conducted across each of the 25 abortion centres in Aquitaine, France, from 15 June to 15 September 2009. The sample comprised 806 women >18 years who had requested an induced abortion. Data were collected through a self-reported anonymous questionnaire on ACEs and experience of previous abortion. The main outcome measure was the percentage of repeat induced abortions. RESULTS: Among the participants, 473 (58.7%) were having their first induced abortion and 333 (41.3%) had already had a previous induced abortion. The abortion rank (first, second, third or more) was inversely related to the proportion of women with no ACE exposure (28%, 20% and 9%, respectively) and positively related to the proportion of women with a high ACE exposure (17%, 27% and 32%, respectively). Compared with women with no ACE exposure who were having a first induced abortion, in those with high ACE exposure, the odds of a third or more request for abortion was high: adjusted odds ratio 7.73 (95% confidence interval 3.56, 16.77). CONCLUSION: We found a strong graded link between the extent of ACE exposure and the occurrence of repeat induced abortion.

Nutritional strategies and gut microbiota composition as risk factors for necrotizing enterocolitis in very-preterm infants.

Background: The pathophysiology of necrotizing enterocolitis (NEC) remains poorly understood.Objective: We assessed the relation between feeding strategies, intestinal microbiota composition, and the development of NEC.Design: We performed a prospective nationwide population-based study, EPIPAGE 2 (Etude Epidémiologique sur les Petits Ages Gestationnels), including preterm infants born at <32 wk of gestation in France in 2011. From individual characteristics observed during the first week of life, we calculated a propensity score for the risk of NEC (Bell's stage 2 or 3) after day 7 of life. We analyzed the relation between neonatal intensive care unit (NICU) strategies concerning the rate of progression of enteral feeding, the direct-breastfeeding policy, and the onset of NEC using general linear mixed models to account for clustering by the NICU. An ancillary propensity-matched case-control study, EPIFLORE (Etude Epidémiologique de la flore), in 20 of the 64 NICUs, analyzed the intestinal microbiota by culture and 16S ribosomal RNA gene sequencing.Results: Among the 3161 enrolled preterm infants, 106 (3.4%; 95% CI: 2.8%, 4.0%) developed NEC. Individual characteristics were significantly associated with NEC. Slower and intermediate rates of progression of enteral feeding strategies were associated with a higher risk of NEC, with an adjusted OR of 2.3 (95% CI: 1.2, 4.5; P = 0.01) and 2.0 (95% CI: 1.1, 3.5; P = 0.02), respectively. Less favorable and intermediate direct-breastfeeding policies were associated with higher NEC risk as well, with an adjusted OR of 2.5 (95% CI: 1.1, 5.8; P = 0.03) and 2.3 (95% CI: 1.1, 4.8; P = 0.02), respectively. Microbiota analysis performed in 16 cases and 78 controls showed an association between Clostridium neonatale and Staphylococcus aureus with NEC (P = 0.001 and P = 0.002).Conclusions: A slow rate of progression of enteral feeding and a less favorable direct-breastfeeding policy are associated with an increased risk of developing NEC. For a given level of risk assessed by propensity score, colonization by C. neonatale and/or S. aureus is significantly associated with NEC. This trial (EPIFLORE study) was registered at clinicaltrials.gov as NCT01127698.

Early risk factors for posterior crossbite and anterior open bite in the primary dentition.

OBJECTIVE: To investigate risk factors specific to posterior crossbite and anterior open bite at the age of 3 years. MATERIALS AND METHODS: The study included 422 children of the French EDEN mother-child cohort. The main outcomes were the presence of posterior crossbite and anterior open bite assessed by dentists at 3 years. Social characteristics (collected during pregnancy), neonatal characteristics (collected at birth), duration of breast-feeding (collected prospectively), sucking habits at 3 years, and open lips (as a proxy for mouth breathing) were studied and two logistic regressions conducted. RESULTS: Preterm birth appears to be a risk factor specific for posterior crossbite (OR: 3.13; 95% CI: 1.13-8.68), whereas small for gestational age seems to be associated with a lower risk of posterior crossbite (OR: 0.32; 95% CI: 0.12-0.87). Ongoing pacifier or thumb sucking at 3 years is a risk factor for both posterior crossbite and anterior open bite. CONCLUSIONS: Children born preterm seem to be more at risk for posterior crossbite than those born at term. Different mechanisms may be involved in posterior crossbite and anterior open bite.