Showing papers by "Alan Leviton published in 2019"

Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm.

Abstract: 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

Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of Placental Insufficiency and with Systemic Inflammation.

Abstract: Objective To evaluate to what extent indicators of placenta insufficiency are associated with low concentrations of insulin-like growth factor 1 (IGF-1) and IGF-1–binding protein-1 (IGFBP-1) in neonatal blood, and to what extent the concentrations of these growth factors are associated with concentrations of proteins with inflammatory, neurotrophic, or angiogenic properties. Study Design Using multiplex immunoassays, we measured the concentrations of IGF-1 and IGFBP-1, as well as 25 other proteins in blood spots collected weekly from ≥ 880 infants born before the 28th week of gestation, and sought correlates of concentrations in the top and bottom quartiles for gestational age and day the specimen was collected. Results Medically indicated delivery and severe fetal growth restriction (sFGR) were associated with low concentrations of IGF-1 on the first postnatal day and with high concentrations of IGFBP-1 on almost all days. Elevated concentrations of IGF-1 and IGFBP-1 were accompanied by elevated concentrations of many other proteins with inflammatory, neurotrophic, or angiogenic properties. Conclusion Disorders associated with impaired placenta implantation and sFGR appear to account for a relative paucity of IGF-1 on the first postnatal day. Elevated concentrations of IGF-1 and especially IGFBP-1 were associated with same-day elevated concentrations of inflammatory, neurotrophic, and angiogenic proteins.

Socioeconomic status and early blood concentrations of inflammation-related and neurotrophic proteins among extremely preterm newborns.

Abstract: 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.

Neurocognitive function of 10-year-old multiples born less than 28 weeks of gestational age.

Abstract: Few studies have examined the relationship between birth plurality and neurocognitive function among children born extremely preterm. We compared rates of Z-scores ≤−2 on 18 tests of neurocognitive function and academic achievement at age 10 years in 245 children arising from twin pregnancies, 55 from triplet pregnancies, and 6 from a septuplet pregnancy to that of 568 singletons, all of whom were born before the 28th week of gestation. In total, 874 children were evaluated at the age of 10 years. After adjusting for confounders, children of multifetal pregnancies performed significantly better on one of six subtests of executive function than their singleton peers. Performance was similar on all other assessments of intelligence, language, academic achievement, processing speed, visual perception, and fine motor skills. We found no evidence that children born of multifetal pregnancies had worse scores than their singleton peers on assessments of neurocognitive and academic function.

Antecedents of epilepsy and seizures among children born at extremely low gestational age.

Abstract: Objective To identify specific risk factors for epilepsy for individuals born extremely preterm. Study design In a prospective cohort study, at 10-year follow-up, children were classified as having epilepsy or seizures not associated with epilepsy. We evaluated for association of perinatal factors using time-oriented, multinomial logistic regression models. Results Of the 888 children included in the study, 66 had epilepsy and 39 had seizures not associated with epilepsy. Epilepsy was associated with an indicator of low socioeconomic status, maternal gestational fever, early physiologic instability, postnatal exposure to hydrocortisone, cerebral white matter disease and severe bronchopulmonary dysplasia. Seizure without epilepsy was associated with indicators of placental infection and inflammation, and hypoxemia during the first 24 postnatal hours. Conclusions In children born extremely preterm, epilepsy and seizures not associated with epilepsy have different risk profiles. Though both profiles included indicators of infection and inflammation, the profile of risk factors for epilepsy included multiple indicators of endogenous vulnerability.