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Objective: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). Design: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. Setting: Ten‐year follow‐up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. Methods: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre‐pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non‐confounding variables. Main outcomes: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. Results: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45–1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. Conclusions: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. [ABSTRACT FROM AUTHOR]

We evaluated the relationship between blood levels of inflammatory and neurotrophic proteins during the first postnatal month in 692 children born before the 28th week of gestation and executive function limitations among those 10-year olds who had an IQ ≥ 70. The measures of dysfunction were Z-scores ≤ -1 on the Differential Ability Scales–II working memory (WM) assessment) (N = 164), the NEPSY-II (A Developmental NEuroPSYchological Assessment-II) Inhibition-Inhibition assessment) (N = 350), the NEPSY-II Inhibition-Switching assessment) (N = 345), as well as a Z-score ≤ -1 on all three assessments (identified as the executive dysfunction composite (N = 104). Increased risks of the executive dysfunction composite associated with high concentrations of inflammatory proteins (IL-8, TNF-α, and ICAM-1) were modulated by high concentrations of neurotrophic proteins. This pattern of modulation by neurotrophins of increased risk associated with inflammation was also seen for the working memory limitation, but only with high concentrations of IL-8 and TNF-α, and the switching limitation, but only with high concentrations of ICAM-1. We infer that among children born extremely preterm, risks of executive function limitations might be explained by perinatal systemic inflammation in the absence of adequate neurotrophic capability. [ABSTRACT FROM AUTHOR]

The main objective of this study was to evaluate the relationship between mother’s socioeconomic disadvantage and blood concentrations of inflammation-related proteins among extremely preterm newborns (<28 weeks gestation), a group at heightened risk of cognitive impairment when exposed to systemic inflammation. We measured the concentrations of 27 inflammatory and neurotrophic proteins in blood specimens collected a week apart during the first postnatal month from 857 extremely preterm newborns in the United States. We classified children according to 3 indicators/correlates of socioeconomic disadvantage, mother’s eligibility for government-provided medical care insurance (Medicaid), mother’s formal education level, and mother’s IQ approximated with the Kaufman Brief Intelligence Test– 2. The risks of a top-quartile concentration of each protein on each of 5 days a week apart, on two occasions during the first two postnatal weeks, and during the next two weeks were modeled as functions of each indicator of socioeconomic disadvantage. The risks of top quartile concentrations of multiple (2–5) inflammation-related proteins on multiple days during the first two weeks were increased for each of the 3 indicators of socioeconomic disadvantage, while the risks of top quartile concentrations of selected neurotrophic proteins were reduced. Adjustment for socioeconomic disadvantage did not alter the relationships between protein concentrations and both low IQ and low working memory 10 years later. Among extremely preterm newborns, indicators of socioeconomic disadvantage are associated with modestly increased risk of systemic inflammation in postnatal blood during the first postnatal month and with a slightly reduced risk of a neurotrophic signal, but do not confound relationships between protein concentrations and outcomes. [ABSTRACT FROM AUTHOR]

To find out why children born extremely preterm are at heightened risk of executive dysfunctions, the authors assessed 716 children who were 10 years old born extremely preterm whose IQ was ≥ 70. A working memory dysfunction (n = 169), an inhibition dysfunction (n = 360), a switching dysfunction (355), and all 3 (executive dysfunction; n = 107) were defined on the basis of Z-scores ≤ –1 on the Differential Ability Scales–II Working Memory composite, and/or on the NEPSY-II Inhibition-Inhibition and Inhibition-Switching subtests. All risk profiles include an indicator of socioeconomic disadvantage. The risk profile of each of the 3 individual dysfunctions includes an indicator of the newborn’s immaturity, and the risk profiles of the inhibition dysfunction and switching dysfunction also include an indicator of inflammation. Only the switching dysfunction was associated with fetal growth restriction. The risk factors for executive dysfunction can be subsumed under the 4 themes of socioeconomic disadvantage, immaturity/vulnerability, inflammation, and fetal growth restriction. [ABSTRACT FROM AUTHOR]