Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes

Preterm birth is a major risk factor for neurodevelopmental delays and disorders. This study aimed to identify genomic biomarkers of intrauterine inflammation in umbilical cord tissue in preterm neonates that predict cognitive impairment at 10 years of age

Antecedents of Obesity Among Children Born Extremely Preterm

BACKGROUND: Childhood obesity is a pervasive public health problem with risk factors such as maternal prepregnancy BMI and rapid infant weight gain. Although catch-up weight gain promotes more favorable neurodevelopment among infants born preterm, it is not clear whether faster weight gain early in life, or other correlates of preterm birth, are associated with later obesity in this population. METHODS: We used prospective data from the multicenter, observational Extremely Low Gestational Age Newborn Study. Among 1506 eligible individuals in the initial cohort, 1198 were eligible for follow-up at 10 years of age. We examined BMI in 871 children (58% of the cohort; 74% of survivors) and analyzed relationships between antecedents and overweight or obesity at 10 years of age. A time-oriented approach to multinomial multivariable regression enabled us to calculate odds of overweight and obesity associated with pre- and postnatal antecedents. RESULTS: Prepregnancy maternal BMI ≥25 and top quartile infant weight gain in the first year were associated with increased risk of both overweight and obesity at 10 years of age. Single marital status was a risk factor for later child obesity and exposure to tobacco smoke was a risk factor for later child overweight. CONCLUSIONS: The risk profiles for overweight and obesity at 10 years of age among children born extremely preterm appear to be similar to the risk profiles of overweight and obesity among children born at term

Neonatal systemic inflammation and the risk of low scores on measures of reading and mathematics achievement at age 10 years among children born extremely preterm

Background Difficulties with reading and math occur more commonly among children born extremely preterm than among children born at term. Reasons for this are unclear. Methods We measured the concentrations of 27 inflammatory-related and neurotrophic/angiogenic proteins (angio-neurotrophic proteins) in multiple blood specimens collected a week apart during the first postnatal month from 660 children born before the 28th week of gestation who at age 10 years had an IQ ≥ 70 and a Wechsler Individual Achievement Test 3rd edition (WIAT-III) assessment. We identified four groups of children, those who had a Z-score ≤ −1 on the Word Reading assessment only, on the Numerical Operations assessment only, on both of these assessments, and on neither, which served as the referent group. We then modeled the risk of each learning limitation associated with a top quartile concentration of each protein, and with high and lower concentrations of multiple proteins. Results The protein profile of low reading scores was confined to the third and fourth postnatal weeks when increased risks were associated with high concentrations of IL-8 and ICAM-1 in the presence of low concentrations of angio-neurotrophic proteins. The profile of low math scores was very similar, except it did not include ICAM-1. In contrast, the profile of low scores on both assessments was present in each of the first four postnatal weeks. The increased risks associated with high concentrations of TNF-α in the first two weeks and of IL-8 and ICAM-1 in the next two weeks were modulated down by high concentrations of angio-neurotrophic proteins. Conclusions High concentrations of angio-neurotrophic proteins appear to reduce/moderate the risk of each learning limitation associated with systemic inflammation. The three categories of limitations have protein profiles with some similarities, and yet some differences, too

Neurocognitive and Academic Outcomes at Age 10 Years of Extremely Preterm Newborns

Despite reductions in mortality and morbidity among children born extremely preterm, they remain at high risk of neurocognitive deficits, with up to 40% having significant cognitive deficits at school age. We assessed the rate of neurocognitive impairment in a contemporary US cohort of 873 children aged 10 years who were born <28 weeks’ gestation

Neurocognitive and Health Correlates of Overweight and Obesity among Ten-Year-Old Children Born Extremely Preterm

OBJECTIVE: To assess the relationship between overweight (body mass index [BMI] percentile ≥85 and &lt;95) and obesity (BMI ≥95 percentile) and developmental and health outcomes at 10 years of age in a cohort of individuals born extremely preterm. STUDY DESIGN: This was an observational cohort study of children born extremely preterm and then assessed at age 10 years for neurocognitive function and parent-reported behavior and health outcomes. Participants included 871 children aged 10 years. To describe the strength of association between overweight or obesity and outcomes, we used logistic regression models adjusting for confounders. Neurocognitive function, academic achievement, parent-reported health outcome surveys, and height and weight were measured. RESULTS: BMI category at 10 years of age was not associated with differences in intelligence, language, or academic achievement. Parents of children with obesity were more likely to report their child had asthma (OR 2.2; 95% CI 1.4-3.5), fair/poor general health (OR 3.2; 95% CI 1.4-7.5), and decreased physical function (OR 1.7; 95% CI 1.1-2.9) but less likely to have physician diagnosed attention-deficit/hyperactivity disorder (OR 0.5; 95% CI 0.3-0.97) or an individualized education plan (OR 0.6; 95% CI 0.4-0.99). CONCLUSION: Among children born extremely preterm, an elevated BMI, compared with normal or low BMI, is not associated with a difference in neurocognitive function. However, asthma, fair/poor general health, and decreased physical function were more prevalent among study participants with obesity, and attention-deficit/hyperactivity disorder and individualized education plan were less prevalent

Cognitive Development and Quality of Life Associated With BPD in 10-Year-Olds Born Preterm

OBJECTIVES: To compare neurocognitive, language, executive function, academic achievement, neurologic and behavioral outcomes, and quality of life at age 10 years in children born extremely preterm who developed bronchopulmonary dysplasia (BPD) to children who did not develop BPD. METHODS: The Extremely Low Gestational Age Newborns study population included 863 children born extremely preterm whose BPD status before discharge was known had an IQ (Differential Ability Scales II [DAS II]) assessment at 10 years. We evaluated the association of BPD with any cognitive (DAS II), executive function (NEuroPSYchological Assessment II), academic achievement (Wechsler Individual Achievement Test-III and Oral and Written Language Scales [OWLS]) as well as social dysfunctions (Social Responsiveness Scale). We used logistic regression models, adjusting for potential confounding factors, to assess the strength of association between the severity of BPD and each outcomes. RESULTS: Three hundred and seventy-two (43%) children were oxygen-dependent at 36 weeks postconception age, whereas an additional 78 (9%) were also oxygen- and ventilator-dependent. IQ scores 2 or more SDs below the expected mean (ie, z scores ≤-2) occurred twice as commonly among children who had BPD as among those who did not. Children with severe BPD consistently had the lowest scores on DAS II, OWLS, Wechsler Individual Achievement Test-III, NEuroPSYchological Assessment II, and Social Responsiveness Scale assessments. CONCLUSIONS: Among 10-year-old children born extremely preterm, those who had BPD were at increased risk of cognitive, language, and executive dysfunctions; academic achievement limitations; social skill deficits; and low scores on assessments of health-related quality of life

Socioemotional dysfunctions at age 10 years in extremely preterm newborns with late-onset bacteremia

Children born extremely preterm (EP) are at a higher risk of social impairment than those born at term. These difficulties emerge early and persist throughout childhood.” Among EP children, the “preterm behavioral phenotype,” a constellation of disorders and symptoms characterized by anxiety, inattention, and social and communication, problems has been described. Some of these mental health disorders might account for the lower parent-reported health-related quality of life among extremely preterm infants than in their peers born at term

Hand Preference and Cognitive, Motor, and Behavioral Functioning in 10-Year-Old Extremely Preterm Children

The association of hand preference (left, mixed, and right) with cognitive, academic, motor, and behavioral function was evaluated in 864 extremely preterm children at 10 years of age. Left-handed and right-handed children performed similarly but mixed-handed children had greater odds of functional deficits across domains than right-handed children

Antecedents of inflammation biomarkers in preterm newborns on days 21 and 28

Most studies of systemic inflammation in very preterm newborns focus on assessments made during the first two weeks. The purpose of this study was to identify some of the antecedents of systemic inflammation evident during postnatal weeks three and four

Changes in Neurodevelopmental Outcomes From Age 2 to 10 Years for Children Born Extremely Preterm

OBJECTIVES: Evidence-based care of extremely preterm infants (&lt;28 weeks' gestation) depends heavily on research in which a primary outcome is infant neurodevelopmental impairment (NDI), yet it is unclear how well NDI in infancy predicts long-term NDI. In this study, we aim to assess the relationship between 2- and 10-year neurodevelopment using a well-known 2-year definition and a 10-year definition developed by an expert panel. METHODS: Using data from the Extremely Low Gestational Age Newborn Study cohort, we classified 2-year NDI using definitions developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. We classified 10-year NDI using definitions developed by an expert panel, which added epilepsy and ASD at 10 years. RESULTS: Of 1506 infants, 80% survived. Data sufficient to classify severity of NDI at both 2 and 10 years were available for 67% of survivors (n = 802). Among children classified as having moderate to severe NDI at 2 years, 63% had none to mild NDI at 10 years; among children classified as having profound NDI at 2 years, 36% had none to mild NDI at 10 years. Cohen's κ statistic indicated minimal to fair agreement between NDI at 2 and 10 years (0.34, P &lt; .001). CONCLUSIONS: NDI in infancy, as defined in this study, only weakly predicts NDI in middle childhood. For the parents at risk for delivery of an extremely preterm infant, a hopeful message can be taken from our findings that one-third of surviving children classified as having profound NDI and nearly two-thirds of those classified as having moderate to severe NDI at 2 years had none to mild NDI at 10 years