Showing papers by "Alan Leviton published in 2016"
TL;DR: More than half of the extremely preterm cohort exhibited moderate or severe neurocognitive deficits at age 10 years, with the most extensive impairments found among those born at the lowest gestational age.
Abstract: BACKGROUND AND OBJECTIVE: 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 METHODS: The families of 889 of 966 (92%) children enrolled from 2002 to 2004 at 14 sites in 5 states returned at age 10 years for a comprehensive assessment of IQ, language, attention, executive function, processing speed, visual perception, visual-motor function, and academic achievement. RESULTS: A total of 873 children were assessed with well-validated tests of cognitive and academic function. Distributions of test scores were consistently and markedly shifted below normative expectation, with one-third to two-thirds of children performing >1 SD below age expectation. The most extreme downward shifts were on measures of executive control and processing speed. Multivariate analyses, adjusted for socioeconomic status, growth restriction, and other potential confounders, revealed that the risk of poor outcome was highest at the lowest gestational age across all 18 measures. CONCLUSIONS: More than half of our extremely preterm cohort exhibited moderate or severe neurocognitive deficits at age 10 years, with the most extensive impairments found among those born at the lowest gestational age. Children born extremely preterm continue to be at significant risk of persistent impairments in neurocognitive function and academic achievement, underscoring the need for monitoring and remediating such outcomes beginning in early childhood.
110 citations
TL;DR: This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children.
Abstract: Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations.
92 citations
TL;DR: In this contemporary cohort of children born extremely premature and evaluated at school age, boys had higher prevalence of cognitive, neurologic, and behavioral deficits than girls.
76 citations
TL;DR: Extremely preterm newborns who had systemic inflammation during the third and fourth postnatal weeks were at increased risk of ventriculomegaly during the months after birth, and of microcephaly, and low Bayley Scale scores at 2years old.
59 citations
TL;DR: Among extremely preterm children with ASD, almost one-half were not correctly screened by the M-CHAT at age 2 years, and sensorimotor and cognitive impairments, SES, and emotional/behavioral dysregulation contributed significantly to M-Chat misclassifications.
45 citations
TL;DR: ELGANs who have elevated systemic levels of IL-6R, TNF- α, or RANTES on their first postnatal day are approximately twice as likely to have elevated levels of these cytokines at the end of each of the first post prenatal month.
Abstract: Extremely low gestational age newborns (ELGANs, <28 completed weeks of gestation) that exhibit fetal and neonatal systemic inflammatory responses are at increased risk for developmental adversity, especially if the inflammatory process is sustained. We evaluated pro-inflammatory cytokine patterns in whole blood of 1220 ELGANs on one or more of postnatal days 1, 7, 14, 21, and 28. Protein concentrations were divided into quartiles within gestational week categories. We calculated odds ratios (OR) with 99% confidence intervals (CI) for having a concentration in the top quartile for each protein given that the infant had a protein concentration in the top quartile 1 week or more earlier compared to infants who did not. ELGANs who have elevated systemic levels of IL-6R, TNF-α, or RANTES on their first postnatal day are approximately twice as likely to have elevated levels of these cytokines at the end of each of the first postnatal month. In some, this twofold risk increase persisted for the entire first postnatal month. In extremely preterm newborns, inflammatory processes can be sustained over weeks.
34 citations
TL;DR: In this paper, the authors examined the extent to which weight gain and weight status in the first 2 years of life relate to the risk of neurodevelopmental impairment in extremely preterm infants.
20 citations
TL;DR: Newborns whose day-1 EPO was in the highest quartile were at increased risk for early and persistent respiratory dysfunction during the first 2 weeks of life, and NEC requiring surgery.
Abstract: Objective To explore the association between concentrations of endogenous erythropoietin (EPO) in blood the first 2 weeks of life and neonatal disorders in extremely low gestational age newborns (ELGANs). Design Prospective cohort study. Setting Neonatal care units at 14 participating hospitals in the USA. Patients 867 children born before the 28th week of gestation from the ELGAN study cohort. Main outcome measures EPO blood concentrations were measured on postnatal days 1, 7 and 14. The following neonatal characteristics and disorders were registered: blood gases, early and late respiratory dysfunction, pulmonary deterioration, retinopathy of prematurity (ROP), necrotising enterocolitis (NEC) and bronchopulmonary dysplasia (BPD). We calculated the gestational age-adjusted ORs for having each disorder associated with an EPO blood concentration in the highest or lowest quartile, compared with infants whose EPO concentration was in the middle two quartiles on the corresponding day. Results Newborns whose day-1 EPO was in the highest quartile were at increased risk for early and persistent respiratory dysfunction during the first 2 weeks of life, and NEC requiring surgery. The lowest EPO quartile on day 1 was associated with a decreased risk of moderate BPD. The association between low EPO and decreased risk of respiratory complications persisted on day 7. On day 14, being in the highest EPO quartile was associated with increased risk of ROP, and BPD not requiring ventilation assistance. Conclusions EPO blood concentrations in extremely preterm newborns during the first 2 weeks of life convey information about increased risks of bowel, lung and retinal diseases.
18 citations
TL;DR: In this high-risk sample, maternal gestational CVI, but not UTI, was associated with a higher risk of impaired motor development at 2 years of age, and the apparent protective effect of UTI might be spurious, reflect confounding due to untreated asymptomatic bacteriuria among women who were not given a diagnosis ofUTI, or reflect preconditioning.
Abstract: Gestational genitourinary infections, which have been associated with neurodevelopmental impairments among infants born near term, have not been studied among very preterm infants. The mothers of 989 infants born before 28 weeks of gestation were interviewed about urine, bladder, or kidney infections (UTIs) and cervical or vaginal infections (CVIs) during pregnancy, as well as other exposures and characteristics, and their charts were reviewed for the Extremely Low Gestational Age Newborns (ELGAN) Study (2002-2004). At 2 years of age, these infants underwent a neurodevelopmental assessment. Generalized estimating equation logistic regression models of developmental adversities were used to adjust for potential confounders. Infants born to women who reported a UTI were less likely than were others to have a very low Mental Development Index (adjusted odds ratio = 0.5; 95% confidence interval: 0.3, 0.8), whereas infants born to women who reported a CVI were more likely than others to have a low Psychomotor Development Index (adjusted odds ratio = 1.7; 95% confidence interval: 1.04, 2.7). In this high-risk sample, maternal gestational CVI, but not UTI, was associated with a higher risk of impaired motor development at 2 years of age. The apparent protective effect of UTI might be spurious, reflect confounding due to untreated asymptomatic bacteriuria among women who were not given a diagnosis of UTI, or reflect preconditioning.
15 citations
TL;DR: The purpose of this study was to identify some of the antecedents of systemic inflammation evident during postnatal weeks three and four.
Abstract: AIM 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. METHODS We measured the protein concentrations in blood spots collected on postnatal days 21 (N = 176) and 28 (N = 157) from infants born before the 28th week of gestation and sought correlates of measurements in the top quartile. Odds ratios of elevated concentrations were calculated for the most obvious correlates. RESULTS Infants born for maternal and foetal indications were more likely than their peers to have top quartile concentrations of IL-beta, IL-8, TNF-alpha and ICAM-1 on both days 21 and 28. Similarly, infants whose birthweight Z-score was <-2 or between -1 and -2 were also more likely than their peers to have elevated concentrations of these proteins. CONCLUSION Markers of systemic inflammation in the very preterm newborn during the third and fourth postnatal weeks are most strongly associated with maternal and foetal indications for (very preterm) delivery and their common correlate/consequence, foetal growth restriction.
14 citations
TL;DR: Maternal and neonatal characteristics might help identify at-risk ELGANs for NEC and SIP, who then may potentially benefit from targeted preventive strategies.
Abstract: Objective To identify antecedents of "medical" necrotizing enterocolitis (mNEC), "surgical" NEC (sNEC), and spontaneous intestinal perforation (SIP) in newborns delivered before 28 weeks gestation. Study design Prospective multicenter cohort study. During study period, 2002- 2004, women delivering before 28 weeks gestation at one of 14 participating institutions were enrolled. Well defined antenatal and postnatal variables were collected. Bivariate analyses were performed to identify candidates for developing multinomial multivariable time-oriented logistic regression models. Results Of the 1320 infants, 5% had mNEC, 6% had sNEC, and 4% had SIP. Antecedents of mNEC included mother's identification as Black, consumption of aspirin during the pregnancy, and vaginal bleeding after the 12th week of gestation. For sNEC the antecedents were maternal self- support, obesity and anemia during the pregnancy, birth before the 24th week, birth weight ≤750gm, and receipt of fresh frozen plasma (FFP) during the first postnatal week. An infant was at increased risk of SIP if the placenta had increased syncytial knots, birth occurred before the 24th week, and received FFP during the first week. Conclusions Maternal and neonatal characteristics might help identify at-risk ELGANs for NEC and SIP, who then may potentially benefit from targeted preventive strategies.
TL;DR: Among infants born before 28 weeks of gestational age, neither full, nor partial courses of antenatal glucocorticoids have a sustained anti-inflammatory effect.
TL;DR: Strabismus in very preterm populations is associated with a number of antenatal and postnatal antecedents as well as clinical and imaging correlates indicative of brain damage in these children, which can allow appropriate and timely interventions.
Abstract: Children born very preterm are at greater risk of ophthalmic morbidities, including strabismus, than children born at term. We evaluated perinatal factors associated with strabismus at age 2 years ...
TL;DR: To evaluate the relationship between placenta corticotropin‐releasing hormone (CRH) expression and brain structure and function abnormalities in extremely preterm newborns, a large number of newborns are diagnosed with severe brain abnormalities.
Abstract: Aim
To evaluate the relationship between placenta corticotropin-releasing hormone (CRH) expression and brain structure and function abnormalities in extremely preterm newborns.
Methods
In a sample of 1243 infants born before the 28th week of gestation, we evaluated the relationship between CRH expression in the placenta and the risk of brain ultrasound scan abnormalities identified while these infants were in the intensive care nursery, low scores on the Bayley Scales of Infant Development-II of 900 of these children at age two years and head circumference measurements then more than one and two standard deviations below the mean.
Results
Infants who had a low placenta CRH messenger ribonucleic acid (mRNA) concentration were at increased risk of ventriculomegaly on an ultrasound scan. An elevated placenta CRH mRNA concentration was associated with increased risk of an inability to walk at age two years, and a Bayley Motor Scale 3 standard deviations below the mean.
Conclusion
Placenta CRH mRNA concentration appears to convey information about the risk of brain damage in the infant born at an extremely low gestational age.
TL;DR: The omega-3 fatty acid docosahexaenoic acid (DHA) might play an explanatory role in the adverse neurodevelopmental outcomes found for two-year-old children of obese mothers, and several alternative possible mechanisms are offered.
Abstract: Dr. Strandvik suggests a possible explanation (1) for our finding some limitation of mental and motor development at age two years among children born preterm to obese mothers (2). She points out that the omega-3 fatty acid docosahexaenoic acid (DHA) might play an explanatory role in the adverse neurodevelopmental outcomes we found for two-year-old children of obese mothers. Low DHA levels at 44 weeks gestational age have been associated with low Bayley Scales of Infant Development at 6–18 months of age among infants born preterm. Obese mothers also show significantly lower DHA in their breastmilk than mothers with a normal BMI, indicating that the mother might already have had a low DHA status during pregnancy. Although Dr. Strandvik provides a possible plausible hypothesis, it is not one we could further explore in the ELGAN study. Delineating the possible role of fatty acids in the adverse developmental outcomes of children born to obese mothers would require measuring the fatty acid status of obese women during pregnancy, the fatty acid content of the milk they produce when nursing, and subsequently the developmental outcomes of the (pre)term children. As the ELGAN study did not assess the mothers diet during the pregnancy, we are unable to investigate the possible contribution of maternal DHA consumption to neurodevelopment. We offer several alternative possible mechanisms in a separate publication (3). Most postulate a role for inflammation; however, we do not specifically discuss the possible contributions of DHA. They are likely to be complex as DHA not only has the potential to be beneficial, but also fish oil supplementation has been reported to promote cytokine production and oxidative stress in mice. In addition, the balance of the potential beneficial and adverse effects of DHA appear to vary with the gestational age of the placenta (4). We hope others, like Dr. Strandvik, will further explore how maternal obesity interferes with normal development. We also encourage others to seek ways to minimise the adverse effects of obesity onmothers and their newborns.