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OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

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OBJECTIVE: To evaluate associations between changes in weight, length, and weight/length ratio during infancy and outcomes later in life among individuals born extremely preterm. STUDY DESIGN: Among participants in the Extremely Low Gestational Age Newborn (ELGAN) study, we measured weight and length at discharge from the neonatal intensive care unit (NICU) and at age 2 years and evaluated neurocognitive, psychiatric, and health outcomes at age 10 years and 15 years. Using multivariable logistic regression, we estimated associations between gains in weight, length, and weight/length ratio z-scores between discharge and 2 years and outcomes at 10 and 15 years. High gain was defined as the top quintile of change; low gain, as the bottom quintile of change. RESULTS: High gains in weight and weight/length were associated with greater odds of obesity at 10 years, but not at 15 years. These associations were found only for females. High gain in length z-score was associated with lower odds of obesity at 15 years. The only association found between high gains in growth measures and more favorable neurocognitive or psychiatric outcomes was between high gain in weight/length and lower odds of cognitive impairment at age 10 years. CONCLUSIONS: During the 2 years after NICU discharge, females born extremely preterm with high gains in weight/length or weight have greater odds of obesity at 10 years, but not at 15 years. Infants with high growth gains in the 2 years after NICU discharge have neurocognitive and psychiatric outcomes in middle childhood and adolescence similar to those of infants with lower gains in weight and weight/length.

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OBJECTIVE: To examine associations of systemic inflammation with growth outcomes at neonatal intensive care unit discharge or transfer among infants with extremely low gestational ages. STUDY DESIGN: We studied 850 infants at born at 23-27 weeks of gestation. We defined inflammatory protein elevation as the highest quartile of C-reactive protein (CRP), Interleukin (IL)-6, tumor necrosis factor-∝, or IL-8 on postnatal days 1, 7, and 14. We compared z-scores of weight, length, and head circumference at neonatal intensive care unit discharge or transfer between infants with vs without inflammatory protein elevation, adjusting in linear regression for birth size z-score, sex, gestational age, diet, comorbidities, medications, and length of hospitalization. RESULTS: The mean gestational age was 25 weeks (range, 23-27 weeks) and birth weight z-score 0.14 (range, -2.73 to 3.28). Infants with a high CRP on day 7 had lower weights at discharge or transfer (-0.17 z-score; 95% CI, -0.27 to -0.06) than infants without CRP elevation, with similar results on day 14. Infants with CRP elevation on day 14 were also shorter (-0.21 length z-scores; 95% CI, -0.38 to -0.04), and had smaller head circumferences (-0.18 z-scores; 95% CI, -0.33 to -0.04) at discharge or transfer. IL-6 elevation on day 14 was associated with lower weight (-0.12; 95% CI, -0.22 to -0.02); IL-6 elevation on day 7 was associated with shorter length (-0.27; 95% CI, -0.43 to -0.12). Tumor necrosis factor-∝ and IL-8 elevation on day 14 were associated with a lower weight at discharge or transfer. CONCLUSIONS: Postnatal systemic inflammation may contribute to impaired nutrient accretion during a critical period in development in infants with extremely low gestational ages.

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OBJECTIVE: To examine the association between neonatal cranial ultrasound (CUS) abnormalities among infants born extremely preterm and neurodevelopmental outcomes at 10 years of age. STUDY DESIGN: In a multicenter birth cohort of infants born at <28 weeks of gestation, 889 of 1198 survivors were evaluated for neurologic, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal CUS findings were classified as intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD. RESULTS: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes. CONCLUSIONS: Among children born extremely preterm, CUS abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy.

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OBJECTIVES: To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition. STUDY DESIGN: We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10 years of age (73 males; 93 females). Top quartile levels on ≥2 days for ≥3 inflammation-related proteins and for ≥4 neurotrophic proteins defined exposure. We examined associations among protein levels, brain Magnetic Resonance Imaging volumes, and cognition with multiple linear and logistic regressions. RESULTS: Analyses were adjusted for gestational age at birth and sex. Children with ≥3 elevated inflammation-related proteins had smaller grey matter, brain stem/cerebellar, and total brain volumes than those without elevated inflammation-related proteins, adjusted for neurotrophic proteins. When adjusted for inflammation-related proteins, children with ≥4 neurotrophic proteins, compared with children with no neurotrophic proteins, had larger grey matter and total brain volumes. Higher grey matter, white matter, and cerebellum and brainstem volumes were significantly correlated with higher IQ. Grey and white matter volumes were correlated with each other (r = -0.18; P = .021), and cerebellum and brainstem was highly correlated with grey matter (r = 0.55; P < .001) and white matter (r = 0.29; P < .001). Adjusting for other brain compartments, cerebellum and brainstem was associated with IQ (P = .016), but the association with white matter was marginally significant (P = .051). Grey matter was not associated with IQ. After adjusting for brain volumes, elevated inflammation-related proteins remained significantly associated with a lower IQ, and elevated neurotrophic proteins remained associated with a higher IQ. CONCLUSIONS: Newborn inflammatory and neurotrophin protein levels are associated with later brain volumes and cognition, but their effects on cognition are not entirely explained by altered brain volumes.

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OBJECTIVE: To assess the development of a Positive Child Health Index (PCHI) based on 11 adverse outcomes and evaluate the association of PCHI with quality of life (QoL) scores in a preterm cohort. STUDY DESIGN: A total of 889 children enrolled in the Extremely Low Gestational Age Newborn (ELGAN) study in 2002-2004 were followed up at 10 years of age. A parent/caregiver completed questionnaires for child QoL, asthma, visual or hearing impairment, gross motor function impairment, epilepsy, attention deficit/hyperactivity disorder, anxiety, and depression. The child was assessed for cognitive impairment, autism, and obesity. PCHI scores were computed and linear regression models were used to evaluate the relationship between QoL categories (psychosocial, physical, emotional, social, school, and total) and the PCHI (dichotomized and coded as a multilevel categorical predictor) and to assess sex differences. RESULTS: Among ELGAN children, higher PCHI scores were associated with higher reported QoL scores for all QoL categories. Children with no disorders and a PCHI of 100% had Pediatric Quality of Life Inventory total scores that were 11 points higher than children with 1 or more adverse outcomes (PCHI of <100%). Boys had lower QoL scores for the total, psychosocial, social, and school categories. CONCLUSIONS: Positive child health assessed using a quantitative PCHI was associated with QoL across the ELGAN cohort at school age. In the current study, the PCHI encompassed 11 outcomes assessed in ELGANs. Future research could include an enhanced panel of child health outcomes to support the use of PCHI as an indicator of positive child health.

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OBJECTIVES: To test the hypothesis that higher blood levels of neurotrophic proteins (proteins that support neuronal survival and function) in the first 2 weeks of life are associated with a lower risk of cognitive impairment at 10 years. STUDY DESIGN: We evaluated 812 10-year-old children with neonatal blood specimens enrolled in the multicenter prospective Extremely Low Gestational Age Newborn Study, assessing 22 blood proteins collected on 3 days over the first 2 weeks of life. Using latent profile analysis, we derived a cognitive function level based on standardized cognitive and executive function tests. We defined high exposure as the top quartile neurotrophic protein blood level on ≥2 days either for ≥4 proteins or for a specific cluster of neurotrophic proteins (defined by latent class analysis). Multinomial logistic regression analyzed associations between high exposures and cognitive impairment. RESULTS: Controlling for the effects of inflammatory proteins, persistently elevated blood levels of ≥4 neurotrophic proteins were associated with reduced risk of moderate (OR, 0.35; 95% CI, 0.18-0.67) and severe cognitive impairment (OR, 0.22; 95% CI, 0.09-0.53). Children with a cluster of elevated proteins including angiopoietin 1, brain-derived neurotrophic factor, and regulated upon activation, normal T-cell expressed, and secreted had a reduced risk of adverse cognitive outcomes (OR range, 0.31-0.6). The risk for moderate to severe cognitive impairment was least with 0-1 inflammatory and >4 neurotrophic proteins. CONCLUSIONS: Persisting elevations of circulating neurotrophic proteins during the first 2 weeks of life are associated with lowered risk of impaired cognition at 10 years of age, controlling for increases in inflammatory proteins.

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OBJECTIVE: To assess the relationship between overweight (body mass index [BMI] percentile ≥85 and <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.

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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.

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OBJECTIVE: To evaluate the difference in 10-year neurocognitive outcomes between extremely low gestational age newborns without bacteremia and those with suspected or confirmed late-onset bacteremia. STUDY DESIGN: Neurocognitive function was evaluated at 10 years of age in 889 children born at <28 weeks of gestation and followed from birth. Definite (culture-positive) late-onset bacteremia during postnatal weeks 2-4 was identified in 223 children, and 129 children had suspected bacteremia. RESULTS: Infants with the lowest gestational age and birth weight z-score had the highest prevalence of definite and suspected late-onset bacteremia. Compared with peers with no or suspected bacteremia, infants with definite bacteremia performed worse on tests of general cognitive ability, language, academic achievement, and executive function, even after adjustment for potential confounders. Adjustment for low IQ attenuated the associations between bacteremia and all dysfunctions at age 10 years. Children with suspected bacteremia did not differ appreciably from those with no evidence of bacteremia. The motor domain was unaffected. CONCLUSIONS: Extremely low gestational age newborns who had definite late bacteremia during postnatal weeks 2-4 are at heightened risk of neurocognitive limitations at age 10 years.

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OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy.

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OBJECTIVES: To evaluate whether in children born extremely preterm, indicators of sustained systemic inflammation in the first month of life are associated with cognitive impairment at school age. STUDY DESIGN: A total of 873 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborn Study from 2002 to 2004 were evaluated at age 10 years. We analyzed the relationship between elevated blood concentrations of inflammation-associated proteins in the first 2 weeks ("early elevations"; n = 812) and the third and fourth week ("late elevations"; n = 532) of life with neurocognition. RESULTS: Early elevations of C-reactive protein, tumor necrosis factor-α, interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, and erythropoietin were associated with IQ values >2 SD below the expected mean (ORs: 2.0-2.3) and with moderate to severe cognitive impairment on a composite measure of IQ and executive function (ORs: 2.1-3.6). Additionally, severe cognitive impairment was associated with late protein elevations of C-reactive protein (OR: 4.0; 95% CI 1.5, 10), IL-8 (OR: 5.0; 1.9, 13), ICAM-1 (OR: 6.5; 2.6, 16), vascular endothelial growth factor-receptor 2 (OR: 3.2; 1.2, 8.3), and thyroid-stimulating hormone (OR: 3.1; 1.3, 7.3). Moderate cognitive impairment was most strongly associated with elevations of IL-8, ICAM-1, and vascular endothelial growth factor-receptor 2. When 4 or more inflammatory proteins were elevated early, the risk of having an IQ <70 and having overall impaired cognitive ability was more than doubled (ORs: 2.1-2.4); the presence of 4 or more inflammatory protein elevated late was strongly linked to adverse cognitive outcomes (ORs: 2.9-4.8). CONCLUSIONS: Extremely preterm children who had sustained elevations of inflammation-related proteins in the first postnatal month are more likely than extremely preterm peers without such elevations to have cognitive impairment at 10 years.

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OBJECTIVE: To examine the predictive validity of the Modified Checklist for Autism in Toddlers (M-CHAT) administered at age 24 months for autism spectrum disorder (ASD) diagnosed at 10 years of age in a US cohort of 827 extremely low gestational age newborns (ELGANs) followed from birth. STUDY DESIGN: We examined the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the M-CHAT in predicting an ASD diagnosis at age 10 years based on gold standard diagnostic instruments. We then assessed how these predictive parameters were affected by sensorimotor and cognitive impairments, socioeconomic status (SES), and emotional/behavioral dysregulation at age 2 years. RESULTS: Using standard criteria, the M-CHAT had a sensitivity of 52%, a specificity of 84%, a PPV of 20%, and an NPV of 96%. False-positive and false-negative rates were high among children with hearing and vision impairments. High false-positive rates also were associated with lower SES, motor and cognitive impairments, and emotional/behavioral dysregulation at age 2 years. CONCLUSIONS: Among extremely preterm children with ASD, almost one-half were not correctly screened by the M-CHAT at age 2 years. Sensorimotor and cognitive impairments, SES, and emotional/behavioral dysregulation contributed significantly to M-CHAT misclassifications. Clinicians are advised to consider these factors when screening very preterm toddlers for ASD.

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OBJECTIVES: To compare the prevalence of cognitive, neurologic, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm. STUDY DESIGN: A total of 889 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborns Study from 2002-2004 were evaluated at 10 years of age. Children underwent a neuropsychological battery and testing for autism spectrum disorder (ASD), and parents reported on their child's behavior, development, and seizures. RESULTS: Of the children, 28% of boys and 21% of girls exhibited moderate to severe impairment on summary measures of cognitive abilities. Boys had a higher prevalence of impairment than girls in nearly all measures of cognition, were more than twice as likely to have microcephaly (15% in boys, 8% in girls), and require more often assistive devices to ambulate (6% in boys, 4% in girls). In contrast, boys and girls had comparable risk for a history of seizure (identified in 10% of the cohort) or epilepsy (identified in 7% of the cohort). The boy-to-girl ratio of ASD (9% in boys, 5% in girls) was lower than expected compared with the overall US autism population. CONCLUSIONS: 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. The ratio of boys to girls among those with ASD deserves further study as does the perinatal environmental-genetic interactions that might contribute to male preponderance of deficits in this high-risk sample.

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OBJECTIVE: To examine 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. STUDY DESIGN: In a cohort of 1070 infants born between 23 and 27 weeks' gestation, we examined weight gain from 7-28 days of life (in quartiles) and weight z-score at 12 and 24 months corrected age (in 4 categories: <-2; ≥-2, <-1; ≥1, <1; and ≥1) in relation to these adverse neurodevelopmental outcomes: Bayley-II mental development index <55, Bayley-II psychomotor development index <55, cerebral palsy, Gross Motor Function Classification System ≥1 (cannot walk without assistance), microcephaly. We adjusted for confounders in logistic regression, stratified by sex, and performed separate analyses including the entire sample, and excluding children unable to walk without assistance (motor impairment). RESULTS: Weight gain in the lowest quartile from 7-28 days was not associated with higher risk of adverse outcomes. Children with a 12-month weight z-score <-2 were at increased risk for all adverse outcomes in girls, and for microcephaly and Gross Motor Function Classification System ≥1 in boys. However, excluding children with motor impairment attenuated all associations except that of weight z-score <-2 with microcephaly in girls. Similarly, most associations of low weight z-score at 24 months with adverse outcomes were attenuated with exclusion of children with motor impairment. CONCLUSION: Excluding children who have gross motor impairment appears to eliminate the association of low weight status with neurodevelopmental impairments at 2 years in extremely preterm infants.

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OBJECTIVES: To assess antenatal and early postnatal antecedents of attention problems identified by the Child Behavior Checklist in extremely preterm children. STUDY DESIGN: In a cohort of 826 children born between 23 and 27 weeks' gestation, we collected demographic, birth, and postnatal information. We then identified behavior problems by using parent ratings from the Child Behavior Checklist at 2 years' adjusted age. We created time-oriented logistic regression risk models to identify significant risk factors for attention problems and Diagnostic and Statistical Manual of Mental Disorders-compatible attention deficit/hyperactivity problems (ADHP(DSM)). RESULTS: Children were at increased risk of both attention problems if they were born to a woman who had no formal education beyond high school and/or a woman who was exposed to secondhand smoke. Recovery of a single organism from the placenta was associated with increased risk of an attention problem, and fetal stem vessel thrombosis and recovery of Mycoplasma species were associated with increased risk of ADHP(DSM). Infants of multifetal gestations were at reduced risk of both attention problems. The only postnatal risk factor for an attention problem was recovery of bacteria from a tracheal aspirate. CONCLUSION: Among extremely preterm infants, several potentially modifiable antenatal and perinatal antecedents are associated with increased risk for attention problems and ADHP(DSM) at 2 years adjusted age.

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OBJECTIVE: To evaluate the hypothesis that elevated levels of inflammation-related proteins in early postnatal blood predict impaired mental and motor development in extremely preterm infants. STUDY DESIGN: We measured concentrations of 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14 from 939 infants born before 28 weeks gestation. An elevated level was defined as a concentration in the highest quartile for gestational age and day of blood collection. We identified impaired development at age 24 months using the Bayley Scales of Infant Development, Second Edition. The primary outcomes were scores on the Mental Scale or the Motor Scale of <55 (more than 3 SDs below the mean). RESULTS: For 17 of the 25 inflammation-related proteins, 1 or more statistically significant associations (P<.01) was found between an elevated blood level of the protein and a developmental impairment. Elevations on multiple days were more often associated with developmental impairment than were elevations present for only 1 day. The highest number of predictive elevations was found in day-14 blood. CONCLUSION: In extremely preterm infants, elevated levels of inflammation-related proteins in blood collected on postnatal days 7 and 14, especially when sustained, are associated with impaired mental and motor development at age 2 years.

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OBJECTIVE: To evaluate whether concentrations of inflammation-related proteins are elevated in the blood of preterm newborns who develop cerebral white matter damage. STUDY DESIGN: We measured 25 proteins in blood collected on days 1, 7, and 14 from 939 infants born before the 28th week of gestation. Brain ultrasound scans were read by at least two sonologists, who agreed on the presence or absence of lesions. A protein concentration was considered elevated if it was in the highest quartile for gestational age and the day on which the specimen was collected. RESULTS: In time-oriented models, elevated concentrations of vascular endothelial growth factor receptor 1, serum amyloid A, and macrophage inflammatory protein 1ß on day 1 and interleukin-8 on day 7 were associated with increased risk of ventriculomegaly. Elevated concentrations of macrophage inflammatory protein 1ß on day 1 and intercellular adhesion molecule 1 on day 7 were associated with increased risk of an echolucent lesion. Infants with elevated concentrations of inflammation-related proteins on two separate days were at significantly increased risk for ventriculomegaly, but at only modestly increased risk for an echolucent lesion. CONCLUSIONS: Concentrations of inflammation-related proteins in the circulation in the first days after preterm birth provide information about the risk of sonographic white matter damage. The inflammatory process might begin in utero.

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OBJECTIVE: To evaluate neurodevelopment after necrotizing enterocolitis (NEC) and late bacteremia, alone and together. STUDY DESIGN: Sample included 1155 infants born at 23 to 27 weeks' gestation. NEC was classified by the modified Bell's staging criteria and grouped as medical NEC or surgical NEC. Late bacteremia was defined as a positive blood culture result after the first postnatal week. Neurodevelopment was assessed at 24 months corrected age. Multivariable models estimated the risk of developmental dysfunction and microcephaly associated with medical or surgical NEC with and without late bacteremia. RESULTS: Children who had surgical NEC unaccompanied by late bacteremia were at increased risk of psychomotor developmental indexes <70 (OR = 2.7 [1.2, 6.4]), and children who had both surgical NEC and late bacteremia were at increased risk of diparetic cerebral palsy (OR = 8.4 [1.9, 39]) and microcephaly (OR = 9.3 [2.2, 40]). In contrast, children who had medical NEC with or without late bacteremia were not at increased risk of any developmental dysfunction. CONCLUSION: The risk of neurodevelopmental dysfunction and microcephaly is increased in children who had surgical NEC, especially if they also had late bacteremia. These observations support the hypothesis that bowel injury might initiate systemic inflammation potentially affecting the developing brain.

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