Monique Kaminski

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

BACKGROUNDnThe 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.nnnMETHODSnWe 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).nnnFINDINGSnIn 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.nnnINTERPRETATIONnIn 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.

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

Aim:u2002 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.

Differential trends in breastfeeding according to maternal and hospital characteristics : results from the french National Perinatal Surveys

Aim: To assess breastfeeding trends in hospital, between 1998 and 2003, according to several characteristics of mothers and maternity units.

Do very preterm twins and singletons differ in their neurodevelopment at 5 years of age

Objective Twins have inconsistently shown poorer outcomes than singletons. Although a high proportion of twins are born very preterm, data are sparse on the long-term outcomes in very preterm twins. The objective of this study was to compare mortality and neurodevelopmental outcomes of very preterm singletons and twins and to study outcomes in relation to factors specific to twins. Design Birth cohort study Etude Epidemiologique sur les Petits Ages Gestationnels (EPIPAGE). Setting Nine regions in France. Patients All very preterm live births occurring from 22 to 32u2005weeks of gestation in all maternity wards of nine French regions in 1997 (n=2773). Main outcomes measures Neurodevelopmental status, including cerebral palsy, and a cognitive assessment with the Kaufman Assessment Battery for Children, with scores on the Mental Processing Composite (MPC) scale, was available for 1732 and 1473 children at 5u2005years of age, respectively. Results Among live births, twins had higher hospital mortality than singletons (adjusted (a)OR: 1.4 (95% CI 1.1 to 1.9)). Among survivors, there was no crude difference at 5u2005years between twins and singletons in the prevalence of cerebral palsy (8.0% vs 9.1%, respectively), MPC <70 (9.5% vs 11.1%) and mean MPC (94.6 vs 94.4). However, after adjustment for sex, gestational age, intrauterine growth restriction and social factors, twins were more likely to have lower MPC scores (mean difference: −2.4 (95% CI–4.8 to 0.01)). Live born twins had a higher risk of mortality when birth weight discordance was present (aOR:2.9 (95% CI 1.7 to 4.8)), but there were no differences in long-term outcomes. Conclusions Compared with very preterm singletons, twins had higher mortality, no difference with respect to severe deficiencies, but slightly lower MPC scores at 5u2005years.

Prenatal Maternal Depression Related to Allergic Rhinoconjunctivitis in the first 5 Years of Life in Children of the EDEN Mother-Child Cohort Study:

Backgroud Evidence about the relationship between prenatal maternal depression and the development of childhood asthma and allergies in early life is scarce. We aimed to examine this relationship by using data set of EDEN mother-child cohort study. A total of 1139 children were followed-up until the age of 5 years. Methods Prenatal maternal depression was self-reported by using the Centre for Epidemiological Studies-Depression scale (CES-D) questionnaire and was classified into binary variable (maternal depression [CES-D score of≥16] and no maternal depression [CES-D score of <16]). Asthma and allergies in the first 5 years were assessed by using the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC). Adjusted odds ratio (aOR) was estimated for the relationship between prenatal maternal depression and early life asthma and allergies by marginal models through the method of generalized estimating equation (GEE) when adjusting for the confounders. Results In our study population, 13.67 % of the mothers had clinical significant depression (the total scores for CES-D ≥16) during pregnancy. For children ages 5 years, the prevalence of wheezing, physician-diagnosed asthma, physician-diagnosed eczema and allergic rhinoconjunctivitis were 46.78, 20.99, 29.17, and 22.54%, respectively. Prenatal maternal depression was associated with ever allergic rhinoconjunctivitis (aOR 1.87 [95% confidence interval {CI}, 1.33–2.62]). No significant relationships were found between prenatal maternal depression and wheezing, physician-diagnosed asthma and physician-diagnosed eczema (aOR 1.12 [95% CI, 0.91–1.39], aOR 1.23 [95% CI, 0.81–1.85] and aOR 1.17 [95% CI, 0.86–1.61], respecitvely). Conclusion Prenatal maternal depression was related to ever allergic rhinoconjunctivitis in the first 5 years of life in children of EDEN mother-child cohort study.

207 Maternal Fatty Acids Intake During Pregnancy and Later Child Cognitive Development in the Eden Mother-Child Cohort Study

Background and aims Polyunsaturated Fatty Acids (PUFA) are needed for child brain development, especially n-3 PUFAs. Prenatal exposure depends on maternal lipids intake during pregnancy. We aimed to investigate associations between maternal PUFAs intake during pregnancy and later child cognitive development. Methods In 1066 children of the EDEN mother-child cohort, we assessed cognitive development at 3 years with the Ages and Stages Questionnaire (ASQ, score between 0 and 300). Maternal lipids intake during pregnancy was evaluated after delivery, using a food frequency questionnaire and a food-composition table. We investigated associations between PUFAs intake and ASQ score using multiple linear regressions adjusted for centre, child’s age, gender and gestational age, maternal tobacco and alcohol consumptions, parental education, siblings, caregivers and preschool attendance. Results Mean ASQ score was 270.1 (±29.4), n-6/n-3 ratio in food intake was 10.0 (±2.3) and total n-3 PUFAs intake was 0.47% (±0.09) of total energy intake. In crude analyzes, ASQ score was positively associated with each three n-3 PUFAs (α-linolenic, eicosapentaenoic and docosapentaenoic acids) and negatively with linoleic acid and n-6/n-3 ratio. After adjustment, ASQ score remained significantly associated with n-6/n-3 ratio (β= –1.16; SE=0.37; P=0.0015). Association with total n-3 PUFAs tended to persist (β=1834; SE=985; P=0.063). Conclusions After adjustment for confounders, especially maternal education, higher n-3 PUFAs intake and thus lower n-6/n-3 ratio in pregnancy food consumption were associated with better cognitive development in early childhood. We observed similar results with prepregnancy lipids intake. Our study suggests a role of prenatal nutrition on childhood cognitive development.

387 Polyunsaturated Fatty Acids in Colostrum and Cognitive Development in Breastfed Children of the Eden Mother-Child Cohort Study

Background and Aims Epidemiological studies suggest that breastfeeding could be beneficial for child cognitive development, but pathways involved remain to be elucidated. We aimed to investigate the potential role of breast milk content in polyunsaturated fatty acids (PUFAs), by studying their associations with later cognitive development. Methods We analyzed lipid contents of colostrum samples collected from 613 breastfeeding mothers of the EDEN mother-child cohort. Cognitive development at 3 years was assessed with the Ages and Stages Questionnaire (ASQ, score between 0 and 300). We investigated associations between colostrum PUFAs and ASQ score using multiple linear regressions adjusted for centre, child’s age, gender and gestational age, maternal tobacco and alcohol consumptions, parental education, siblings, caregivers, preschool attendance and exclusive breastfeeding duration. Results Mean ASQ score was 274.2 (±25.1). Total PUFAs and n-6 PUFAs means were respectively 14.3% (±2.0) and 12.1% (±1.9) of total lipids in colostrum. Mean n-6/n-3 ratio was 5.7 (±1.3). After adjustment, ASQ score was negatively associated with total PUFAs (β= –1.8 [–2.8; –0.8]), n-6 PUFAs (–1.95 [–3.0; –0.9]) and n-6/n-3 ratio (–1.7 [–3.3; –0.2]). No association was found with n-3 PUFAs. Associations did not differ according to breastfeeding duration (P interaction >0.57). Conclusions After adjustment for confounders, especially maternal education, colostrum content in n-6 PUFA was negatively associated with child cognitive development, independently of exclusive breastfeeding duration. These results suggest that n-6 PUFAs provided in excess might compete with n-3 PUFAs biosynthesis necessary for early brain maturation and impact negatively on later cognitive development.

White matter damage and neonatal sepsis: authors’ reply

Sir, With great interest we read the article by Beaino et al. (1) on risk factors for cognitive deficiency in the very preterm infant. As confirmed in this study periventricular leukomalacia (PVL) is currently known to be an important risk factor for severe cognitive impairment. Maternal-foetal infections were not associated with either mild or severe cognitive deficiency, but the role of early and ⁄ or late onset sepsis was not evaluated in the multivariate analysis. We retrospectively compared data of all preterm infants diagnosed as having cystic PVL hospitalized at our tertiary care neonatal intensive care unit from 2004 to 2008 with matched controls (each PVL case with four control infants) for gestational age, birth weight, year of birth, and sex. Cranial ultrasound scans are routinely obtained in all preterm infants on days 1, 3, 5, and thereafter once a week in cases with pathological findings using a commercially available unit (Advanced Technology Laboratories Inc., Bothell, WA, USA). Twenty-two infants with diagnosis of cystic PVL with a median gestational age of 29 weeks (range 24–32 weeks) were compared to 88 controls. Diagnosis of first cysts occurred at median day 13 (range 4–26 days) and 77% of the infants had diagnosis of bilateral cystic PVL. Antenatal risk factors (chorioamnionitis, fever during labour, and preterm rupture of the membranes) and antibiotic therapy of the mother were associated with the presence of PVL (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.07–8.54, p = 0.032 and OR 2.96, CI 95% 1–8.74, p = 0.044, respectively). Among the 22 cases of PVL eight infants had blood culture proven or clinical early onset sepsis (36%). Presence of early onset sepsis was significantly associated with PVL (OR 4, CI 95% 1.37–11.71, p < 0.01). When adjusted for presence of maternal risk factors and antibiotic therapy of the mother the association with sepsis was still significant (p = 0.035). Clinical factors associated with presence of white matter damage were cardiocirculatory symptoms (arterial hypotonia, tachyand bradycardia) (OR 2.74, CI 95% .98– 7.69, p < 0.05). Late onset sepsis was not associated with PVL (p = 0.25). The present analysis adds to a growing body of evidence suggesting a link between infection and white matter injury in the premature newborn. Several findings from human studies and animal models support the concept that a fetal exposure to inflammation triggers a prolonged neuroinflammatory response affecting the development of brain structure and function. Our results are limited by the small sample size but nevertheless confirm previous findings of bacterial infections in the early postnatal period being associated with a higher risk for white matter damage (2,3). Interestingly, Beaino et al. found no significant association of maternal-foetal infection with cognitive deficiency, but they did not link infection with white matter damage in their analysis. Further studies on the pathogenesis of white matter damage in the preterm infant are needed to evaluate the role of an either foetal or postnatal inflammatory response syndrome.