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BACKGROUND: Very preterm infants are at high risk for neurodevelopmental impairments. We used a child-centered approach (latent profile analysis [LPA]) to describe 2-year neurobehavioral profiles for very preterm infants based on cognitive, motor, and behavioral outcomes. We hypothesized that distinct outcome profiles would differ in the severity and co-occurrence of neurodevelopmental and behavioral impairment. METHODS: We studied children born <33 weeks' gestation from the Environmental influences on Child Health Outcomes Program with at least one neurobehavioral assessment at age 2 (Bayley Scales of Infant and Toddler Development, Child Behavior Checklist, Modified Checklist for Autism in Toddlers, cerebral palsy diagnosis). We applied LPA to identify subgroups of children with different patterns of outcomes. RESULTS: In 2036 children (52% male; 48% female), we found four distinct neurobehavioral profiles. Most children (~85%) were categorized into one of two profiles characterized by no/mild neurodevelopmental delay and a low prevalence of behavioral problems. Fewer children (~15%) fell into one of two profiles characterized by severe neurodevelopmental impairments. One profile consisted of children (5%) with co-occurring neurodevelopmental impairment and behavioral problems. CONCLUSION: Child-centered approaches provide a comprehensive, parsimonious description of neurodevelopment following preterm birth and can be useful for clinical and research purposes. IMPACT: Most research on outcomes for children born very preterm have reported rates of impairment in single domains. Child-centered approaches describe profiles of children with unique combinations of cognitive, motor, and behavioral strengths and weaknesses. We capitalized on data from the nationwide Environmental influences on Child Health Outcomes Program to examine these profiles in a large sample of children born <33 weeks gestational age. We found four distinct neurobehavioral profiles consisting of different combinations of cognitive, motor, and behavioral characteristics. This information could aid in the development of clinical interventions that target different profiles of children with unique developmental needs.
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Recien Nacido Prematuro , Nacimiento Prematuro , Lactante , Humanos , Recién Nacido , Masculino , Femenino , Preescolar , Estudios Prospectivos , Edad Gestacional , Retardo del Crecimiento Fetal , Evaluación de Resultado en la Atención de Salud , Desarrollo InfantilRESUMEN
BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.
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PURPOSE: This study aimed to longitudinally investigate the preterm infant feeding regimens, feeding behaviors, effect on infant growth, and caregiver perceptions and experiences with feeding in the first 4 weeks following hospital discharge. BACKGROUND: Preterm infants face high nutritional risk due to their underdeveloped gastrointestinal systems and feeding coordination. METHODS: Caregivers of preterm infants were recruited to participate in a weekly telephone survey for the first 4 weeks following the infant's hospital discharge. Responses for infant feeding behaviors and caregiver experiences were scored on a 3-point Likert scale. Growth and feeding data were collected from the infant's first neonatal intensive care unit (NICU) developmental follow-up visit. RESULTS: Twenty-four caregivers completed the study. Changes in feeding regimens were common (8/24 infants; 33%), with the percentage of infants receiving any human milk feedings decreasing from 70% at hospital discharge to 54% at 4 weeks post-discharge. Poor infant feeding skills were weakly associated with poor caregiver feeding experiences, and 46% of caregivers reported contacting their healthcare provider with feeding-related questions. Thirty-eight percent of infants required nutritional intervention at NICU developmental follow-up visit. Infants who received fortified feedings during the first 4 weeks after hospital discharge grew an average of 2.5 g/day faster than infants who did not receive fortified feedings. CONCLUSION: The postdischarge period for preterm infants is characterized by feeding regimen changes, a decrease in human milk use, and caregiver questions about feeding. IMPLICATIONS FOR PRACTICE AND RESEARCH: Future studies should further investigate the period after hospital discharge to enable better feeding support for preterm infants and their caregivers.
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Cuidadores , Conducta Alimentaria , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Alta del Paciente , Humanos , Recién Nacido , Femenino , Masculino , Cuidadores/psicología , Conducta Alimentaria/psicología , Fenómenos Fisiológicos Nutricionales del Lactante , Desarrollo Infantil/fisiología , Estudios Longitudinales , Lactante , Lactancia Materna/psicologíaRESUMEN
OBJECTIVE: To assess whether prenatal risk phenotypes are associated with neurobehavioral impairment for children born <30 weeks of gestation at discharge from the neonatal intensive care unit (NICU) and at 24-month follow-up. STUDY DESIGN: We studied infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, a multisite investigation of infants born <30 weeks of gestation. There were 704 newborns enrolled in the NOVI study; of these, 679 (96%) had neonatal neurobehavioral data and 556 (79%) had 24-month follow-up data. Maternal prenatal phenotypes (physical and psychological risk groups) were characterized from 24 physical and psychological health risk factors. Neurobehavior was assessed at NICU discharge using the NICU Network Neurobehavioral Scales and at 2-year follow-up using the Bayley Scales of Infant and Toddler Development and the Child Behavior Checklist. RESULTS: Children born to mothers in the psychological risk group were at increased risk for dysregulated neonatal neurobehavior (OR, 2.04; 95% CI, 1.08-3.87) at NICU discharge, and for severe motor delay (OR, 3.80; 95% CI, 1.48-9.75), and clinically significant externalizing problems (OR, 2.54; 95% CI, 1.15-5.56) at age 24 months, compared with children born to mothers in the low-risk group. Children born to mothers in the physical risk group were more likely to have severe motor delay (OR, 2.70; 95% CI, 1.07-6.85) compared with the low-risk group. CONCLUSIONS: High-risk maternal prenatal phenotypes were associated with neurobehavioral impairment for children born very preterm. This information could identify newborns at risk for adverse neurodevelopmental outcomes.
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Recien Nacido Extremadamente Prematuro , Madres , Recién Nacido , Humanos , Embarazo , Femenino , Unidades de Cuidado Intensivo Neonatal , Alta del Paciente , FenotipoRESUMEN
OBJECTIVE: To identify neonatal characteristics and 2-year neurodevelopmental outcomes associated with positive screening for risk of autism. STUDY DESIGN: Nine university-affiliated neonatal intensive care units (NICUs) enrolled infants born at <30 weeks of gestation. Infants underwent the NICU Network Neurobehavioral Scale examination before discharge and the Bayley Scales of Infant and Toddler Development, Third Edition, the Child Behavior Checklist, and the Modified Checklist for Autism in Toddlers, revised with follow-up (M-CHAT-R/F) at 2 years of corrected age. Generalized estimating equations examined associations between M-CHAT-R/F, neurobehavioral test results, and neonatal medical morbidities. RESULTS: At 2 years of corrected age, data were available for 466 of 744 enrolled infants without cerebral palsy. Infants with hypoaroused NICU Network Neurobehavioral Scale profiles were more likely to screen M-CHAT-R/F-positive (OR 2.76, 95% CI 1.38-5.54). Infants with ≥2 medical morbidities also were more likely to screen positive (OR 2.65, 95% CI 1.27-5.54). Children with positive M-CHAT-R/F scores had lower Bayley Scales of Infant and Toddler Development, Third Edition, Cognitive (t [451] = 5.43, P < .001, d = 0.82), Language (t [53.49] = 7.82, P < .001, d = 1.18), and Motor (t [451] = 7.98, P < .001, d = 1.21) composite scores and significantly greater Child Behavior Checklist Internalizing (t [457] -6.19, P < .001, d = -0.93) and Externalizing (t [57.87] = -5.62, P < .001, d = -0.84) scores. CONCLUSIONS: Positive M-CHAT-R/F screens at 2 years of corrected age were associated with neonatal medical morbidities and neurobehavioral examinations as well as toddler developmental and behavioral outcomes. These findings demonstrate the potential utility of the M-CHAT-R/F as a global developmental screener in infants born very preterm, regardless of whether there is a later autism diagnosis.
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Trastorno Autístico , Recién Nacido , Lactante , Humanos , Trastorno Autístico/diagnóstico , Recien Nacido Extremadamente PrematuroRESUMEN
Early Check is a voluntary, large-scale expanded newborn screening study in North Carolina that uses a self-directed web-based portal for return of normal individual research results (IRR). Little is known about participant perspectives in using web-based portals to receive IRR. This study explored user attitudes and behaviors within the Early Check portal using three methods: (1) a feedback survey available to the consenting parent of participating infants (typically mothers), (2) semi-structured interviews conducted with a subset of parents, and (3) Google Analytics. During an approximate 3-year period, 17 936 newborns received normal IRR and there were 27 812 visits to the portal. Most surveyed parents reported viewing their baby's results (86%, 1410/1639). Parents largely found the portal easy to use to get results, and helpful in understanding the results. However, 10% of parents said it was difficult to find enough information to understand their baby's results. In Early Check, providing normal IRR via the portal made a large-scale study practical, and was highly rated by most users. Return of normal IRR may be particularly amenable to web-based portals, as the consequences to participants from not viewing results are modest, and the interpretation of a normal result is relatively straightforward.
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Madres , Padres , Lactante , Femenino , Humanos , Recién Nacido , Encuestas y Cuestionarios , Tamizaje Neonatal , InternetRESUMEN
BACKGROUND: Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures. METHODS: We studied 1112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium. We used latent profile analysis to characterize infant neurobehavioral profiles and generalized estimating equations to determine predictors of NNNS profiles. RESULTS: Six distinct neonatal neurobehavioral profiles were identified, including two dysregulated profiles: a hypo-aroused profile (16%) characterized by lethargy, hypotonicity, and nonoptimal reflexes; and a hyper-aroused profile (6%) characterized by high arousal, excitability, and stress, with low regulation and poor movement quality. Infants in the hypo-aroused profile were more likely to be male, have younger mothers, and have mothers who were depressed prenatally. Infants in the hyper-aroused profile were more likely to be Hispanic/Latino and have mothers who were depressed or used tobacco prenatally. CONCLUSIONS: We identified two dysregulated neurobehavioral profiles with distinct perinatal antecedents. Further understanding of their etiology could inform targeted interventions to promote positive developmental outcomes. IMPACT: Prior research on predictors of neonatal neurobehavior have included single-cohort studies, which limits generalizability of findings. In a multi-cohort study of preterm and term-born infants, we found six distinct neonatal neurobehavioral profiles, with two profiles being identified as dysregulated. Hypo- and hyper-aroused neurobehavioral profiles had distinct perinatal antecedents. Understanding perinatal factors associated with dysregulated neurobehavior could help promote positive developmental outcomes.
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Trastornos Mentales , Parto , Recién Nacido , Lactante , Niño , Embarazo , Femenino , Humanos , Masculino , Estudios de Cohortes , Vigilia , Madres , Conducta del LactanteRESUMEN
BACKGROUND: Utility of total parenteral nutrition (TPN) with an intravenous lipid emulsion (IVLE) component is common in the neonatal intensive care unit; however, there are inherent risks to TPN use. With IVLE administered separate from other TPN components, opportunities exist for additional error and subsequent potential harm. CLINICAL FINDINGS: We present 2 cases in term infants where IVLE infusions were noted to be inadvertently administered at higher than prescribed rates, prompting concern for lipemia and end-organ damage due to hyperviscosity. PRIMARY DIAGNOSIS: Both infants developed iatrogenic hypertriglyceridemia and hyponatremia. INTERVENTION: Upon recognition of the error, IVLE was immediately discontinued in each case. Triglyceride levels were serially monitored until they reached a normal level. Electrolyte panels and hepatic function panels were also drawn to assess for electrolyte derangements and function. Radiologic studies were performed for evaluation of end-organ effects of hyperviscosity. OUTCOMES: Triglyceride levels for both infants normalized within 7 hours. Both infants survived to discharge without any known effects related to the inadvertent excessive lipid infusion. CONCLUSION: It is helpful to perform a root-cause analysis for these types of events; have the exact amount of lipids in the bag needed and no overfill; consider having lipids in 4-hour dosage aliquots; require 2 nurses to verify infusion rates hourly; and educational sessions and unit protocols for any infusion may reduce the risk of administration error.
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Emulsiones Grasas Intravenosas , Nutrición Parenteral , Recién Nacido , Humanos , Emulsiones Grasas Intravenosas/efectos adversos , Nutrición Parenteral/efectos adversos , Lípidos , TriglicéridosRESUMEN
BACKGROUND: Infants born <30 weeks postmenstrual age (PMA) are at increased risk for neurodevelopmental impairment by age 2. Prior studies report rates of impairment for individual outcomes separately. Our objective was to describe neurodevelopmental profiles of children born <30 weeks PMA, using cognitive, language, motor, and behavioral characteristics. METHODS: We studied 587 children from a multi-center study of infants born <30 weeks PMA. Age 2 outcomes included Bayley-III subscale scores, Child Behavior Checklist syndrome scores, diagnosis of cerebral palsy (CP), and positive screen for autism spectrum disorder (ASD) risk. We used latent profile analysis (LPA) to group children into mutually exclusive profiles. RESULTS: We found four discrete neurodevelopmental profiles indicating distinct combinations of developmental and behavioral outcomes. Two of the profiles included 72.7% of the sample with most having Bayley scores within the normal range. The other two profiles included the remaining 27.3% of the sample with most having Bayley scores outside of the normal range. Only one profile (11% of sample) was comprised of children with elevated behavioral problems. CONCLUSION: Child-centered analysis techniques could facilitate the development of targeted intervention strategies and provide caregivers and practitioners with an integrative understanding of child behavior. IMPACT: Most studies examining neurodevelopmental outcomes in very preterm children report rates of impairment for individual outcomes separately. Comprehensive, "child-centered" approaches that integrate across multiple domains can be used to identify subgroups of children who experience different types of neurodevelopmental impairments. We identified four discrete neurodevelopmental profiles indicating distinct combinations of developmental and behavioral outcomes in very preterm children at 24 months. "Child-centered" analysis techniques may provide clinically useful information and could facilitate the development of targeted intervention strategies for high-risk children.
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Trastorno del Espectro Autista , Parálisis Cerebral , Trastornos del Neurodesarrollo , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/diagnóstico , Niño , Desarrollo Infantil , Preescolar , Discapacidades del Desarrollo/complicaciones , Discapacidades del Desarrollo/diagnóstico , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/etiología , Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND/OBJECTIVES: Propranolol is used to treat problematic infantile hemangiomas (IHs), but its safety in infants <5 weeks corrected age has not been established. The objective of this study was to assess the safety and efficacy of propranolol for treatment of IH in infants <5 weeks corrected age, or 45 weeks corrected gestational age (CGA). METHODS: We performed a single institution, retrospective review of patients treated with propranolol prior to the age of 6 months between 2017 and 2021. Patient characteristics, location of hemangioma(s), weight at initiation of treatment, dosing information, side effects, response, and duration of treatment were documented. RESULTS: Of 200 patients with IH treated with propranolol, 24 started treatment prior to 45 weeks CGA. Mean CGA at initiation of treatment was 42 weeks. Sixty-seven percent were female and 75% were white, non-Hispanic. Mean duration of treatment was 255 days. Twenty-two patients (92%) had clear benefit from treatment at a dose of 1-3 mg/kg/day. The most common side effects were sleep disturbance (21%), irritability (17%), and cool hands/feet (13%). There were no serious adverse events. CONCLUSIONS: In this cohort of 24 patients with corrected age <5 weeks (CGA <45 weeks), propranolol was safe and effective for the treatment of infantile hemangiomas. Larger, prospective studies are indicated to investigate propranolol in this age group.
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Hemangioma Capilar , Hemangioma , Neoplasias Cutáneas , Administración Oral , Antagonistas Adrenérgicos beta/efectos adversos , Preescolar , Femenino , Hemangioma/tratamiento farmacológico , Hemangioma Capilar/tratamiento farmacológico , Humanos , Lactante , Masculino , Propranolol/efectos adversos , Estudios Prospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
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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Hemorragia Cerebral Intraventricular/complicaciones , Hemorragia Cerebral Intraventricular/diagnóstico por imagen , Enfermedades del Prematuro/diagnóstico por imagen , Leucoencefalopatías/complicaciones , Leucoencefalopatías/diagnóstico por imagen , Trastornos del Neurodesarrollo/epidemiología , Factores de Edad , Hemorragia Cerebral Intraventricular/terapia , Niño , Estudios de Cohortes , Cuidados Críticos , Ecoencefalografía , Femenino , Hospitalización , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido , Enfermedades del Prematuro/terapia , Leucoencefalopatías/terapia , Masculino , Trastornos del Neurodesarrollo/diagnóstico , Estados UnidosRESUMEN
BACKGROUND: To assess the growth outcomes at 18 months corrected age in very low birth weight (VLBW) infants compared to standardized norms, and in VLBW infants with and without bronchopulmonary dysplasia (BPD) or fetal growth restriction (FGR). METHODS: In all, 1149 VLBW infants completed anthropometrics at 18 months corrected age. To derive weight, height, and body mass index (BMI) percentiles and z-scores at 18 months, we used the SAS macro from the Centers for Disease Control and Prevention (CDC). z-scores for a child's sex and age are based on the World Health Organization's growth charts for children <24 months of age. RESULTS: Female and male VLBW infants had higher body-mass-index (BMI)-for-age z-scores compared to normative data (0.82 and 1.77 respectively). No significant difference was found in BMI-for-age z-scores in BPD and non-BPD (1.76 vs. 2.3; p = 0.4), nor in FGR and non-FGR (1.24 vs. 2.16; p = 0.2). CONCLUSIONS: At 18 months corrected age, VLBW infants, including those with BPD or FGR, had BMI-for-age z-scores higher than reference standards. No significant difference was seen comparing BMI-for-age z-scores in the BPD/non-BPD and FGR/non-FGR groups.
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Displasia Broncopulmonar/terapia , Retardo del Crecimiento Fetal/terapia , Recien Nacido Prematuro/crecimiento & desarrollo , Antropometría , Peso al Nacer , Índice de Masa Corporal , Desarrollo Infantil , Bases de Datos Factuales , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Recién Nacido de muy Bajo Peso , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Background Parents of overweight children frequently under-recognize their child's overweight status. We hypothesized that parents of preterm children would be more likely than parents of term children to incorrectly perceive their child's weight. Methods We recruited parents of term and preterm when children were 2 months to 2 years of age. Small for gestational age infants were excluded. We compared parents' perceived weight category with child's actual weight category, based on normative data (underweight, normal weight, or overweight). We based analyses on encounters and adjusted for within-child clustering across repeated measures. Results In the preterm (n = 94) and term (n = 1,263) cohorts, 12 and 13% of children, respectively, were overweight (weight-for-length ≥ 95th percentile). Among parents of overweight children, 91% in the preterm cohort and 90% in the term cohort reported their child as healthy weight. Among healthy weight children (weight-for-length 6th-94th percentile), parents in the preterm cohort were more likely to report their child as underweight compared with parents in the term cohort (24 vs. 7%; p < 0.001). Conclusion Parental perception of weight status was impaired among parents of overweight children regardless of gestational age. However, parents were more likely to perceive their healthy weight child as underweight if their child was preterm.
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Sobrepeso/epidemiología , Padres/psicología , Delgadez/epidemiología , Percepción del Peso , Índice de Masa Corporal , Femenino , Humanos , Lactante , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Masculino , North Carolina , Encuestas y Cuestionarios , Nacimiento a TérminoRESUMEN
Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.
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Metilación de ADN , Nacimiento Prematuro , Lactante , Niño , Embarazo , Femenino , Humanos , Recién Nacido , Preescolar , Epigenoma , Estudio de Asociación del Genoma Completo , Recien Nacido Extremadamente Prematuro , Islas de CpG , Epigénesis Genética , AtenciónRESUMEN
Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability. We studied 379 neonates (54% male) born less than 30 weeks GA who had DNA methylation measured at neonatal intensive care unit discharge along with 3-year follow-up data. Cumulative prenatal risk was calculated from 24 risk factors obtained from maternal report and medical record and epigenome-wide neonatal DNA methylation was assayed from buccal swabs. At 3-year follow-up, child cognitive ability was assessed using the Bayley Scales of Infant and Toddler Development (third edition). Cumulative prenatal risk and DNA methylation at two cytosine-phosphate-guanines (CpGs) were uniquely associated with child cognitive ability. Using high-dimensional mediation analysis, we also identified differential methylation of 309 CpGs that mediated the association between cumulative prenatal risk and child cognitive ability. Many of the associated CpGs were located in genes (TNS3, TRAPPC4, MAD1L1, APBB2, DIP2C, TRAPPC9, DRD2) that have previously been associated with prenatal exposures and/or neurodevelopmental phenotypes. Our findings suggest a role for both prenatal risk factors and DNA methylation in explaining outcomes for children born preterm and suggest we should further study DNA methylation as a potential mechanism underlying the association between prenatal risk and child neurodevelopment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Metilación de ADN , Epigénesis Genética , Recien Nacido Extremadamente Prematuro , Humanos , Femenino , Masculino , Factores de Riesgo , Preescolar , Recién Nacido , Embarazo , Cognición/fisiología , Desarrollo Infantil/fisiología , Estudios de Seguimiento , Efectos Tardíos de la Exposición PrenatalRESUMEN
Importance: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. Objective: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. Design, Setting, and Participants: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Exposure: Maternal preeclampsia and FGR in very preterm infants. Main Outcomes and Measures: The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Results: Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. Conclusions and Relevance: In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.
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Retardo del Crecimiento Fetal , Preeclampsia , Humanos , Femenino , Preeclampsia/epidemiología , Embarazo , Retardo del Crecimiento Fetal/epidemiología , Masculino , Recién Nacido , Estudios Prospectivos , Adulto , Desarrollo Infantil/fisiología , Preescolar , Recien Nacido Extremadamente Prematuro , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/etiología , Lactante , Recien Nacido Prematuro , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/etiología , Estudios de CohortesRESUMEN
OBJECTIVE: Understand how high-risk infants' development changes over time. Examine whether NICU Network Neurobehavioral Scale (NNNS) profiles are associated with decrements in developmental outcomes between ages 2 and 3 years in infants born very preterm. STUDY DESIGN: The Neonatal Outcomes for Very preterm Infants (NOVI) cohort is a multisite prospective study of 704 preterm infants born <30 weeks' gestation across nine university and VON affiliated NICUs. Data included infant neurobehavior measured by NNNS profiles at NICU discharge and the Bayley Scales of Infant and Toddler Development (BSID-III) at ages 2 and 3 years. Generalized estimating equations tested associations between NNNS profiles and BSID-III composite score changes between ages 2 and 3 years. RESULTS: The final study sample included 433 infants with mean gestational age of 27 weeks at birth. Infants with dysregulated NNNS profiles were more likely to have decreases in BSID-III Cognitive (OR = 2.66) and Language scores (OR = 2.53) from age 2 to 3 years compared to infants with more well-regulated neurobehavioral NNNS profiles. Further, infants with more well-regulated NNNS profiles were more likely to have increases in BSID-III Cognitive scores (OR = 2.03), rather than no change, compared to infants with dysregulated NNNS profiles. CONCLUSIONS AND RELEVANCE: Prior to NICU discharge, NNNS neurobehavioral profiles identified infants at increased risk for developing later language and cognitive challenges. Findings suggests that neonatal neurobehavior provides a unique, clinically significant contribution to the evaluation of very preterm infants to inform treatment planning for the most vulnerable.
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Desarrollo Infantil , Recien Nacido Extremadamente Prematuro , Humanos , Masculino , Femenino , Preescolar , Recién Nacido , Desarrollo Infantil/fisiología , Recien Nacido Extremadamente Prematuro/crecimiento & desarrollo , Recien Nacido Extremadamente Prematuro/fisiología , Conducta del Lactante/fisiología , Recien Nacido Prematuro/crecimiento & desarrollo , Recien Nacido Prematuro/fisiología , Discapacidades del Desarrollo/epidemiologíaRESUMEN
OBJECTIVE: Broadband parent rating scales are commonly used to assess behavioral problems in children. Multiple rating scales are available, yet agreement between them is not well-understood. The objective of this study was to evaluate agreement between the Behavior Assessment System for Children, Third Edition (BASC-3), and Child Behavior Checklist 1.5 to 5 years (CBCL) in a sample of children born very preterm. METHOD: We assessed 73 children born < 30 weeks' gestational age whose caregivers completed the BASC-3 and CBCL at age 4. We examined correlations, within-person differences, and agreement in clinical categorization for all corresponding subscales and composites. RESULTS: Comparable subscales on the BASC-3 and CBCL were significantly correlated, albeit to differing magnitudes. Subscales indexing hyperactivity and attention problems were the most comparable across the 2 measures, evidenced by strong correlations and few to no differences in mean T-scores. Composite scores indexing internalizing, externalizing, and total problems were also strongly correlated, and there were no differences in the mean T-scores for externalizing or total problems across measures. Agreement in clinical classifications were weak to moderate, though again, the highest agreement was found for hyperactivity, attention, externalizing, and total problems. CONCLUSION: Agreement between BASC-3 and CBCL subscales was weak to moderate, with the exception of subscales related to attention and hyperactivity, as well as composite scores indicating overall behavior problems. Researchers and clinicians should consider these discrepancies when interpreting the results of behavior rating scales with preschool children because conclusions could differ based on the assessment that is used.
Asunto(s)
Trastornos de la Conducta Infantil , Problema de Conducta , Recién Nacido , Preescolar , Niño , Humanos , Escala de Evaluación de la Conducta , Trastornos de la Conducta Infantil/diagnóstico , Trastornos de la Conducta Infantil/etiología , Recien Nacido Extremadamente PrematuroRESUMEN
Importance: Use of the Modified Checklist for Autism in Toddlers, Revised With Follow-Up, a 2-stage parent-report autism risk screening tool, has been questioned due to reports of poor sensitivity and specificity. How this measure captures developmental delays for very preterm infants may provide support for continued use in pediatric care settings. Objective: To determine whether autism risk screening with the 2-stage parent-report autism risk screening tool at age 2 years is associated with behavioral and developmental outcomes at age 3 in very preterm infants. Design, Setting, and Participants: Neonatal Neurobehavior and Outcomes for Very Preterm Infants was a longitudinal, multisite cohort study. Enrollment occurred April 2014 to June 2016, and analyses were conducted from November 2022 to May 2023. Data were collected across 9 university-affiliated neonatal intensive care units (NICUs). Inclusion criteria were infants born less than 30 weeks' gestational age, a parent who could read and speak English and/or Spanish, and residence within 3 hours of the NICU and follow-up clinic. Exposures: Prematurity and use of the 2-stage parent-report autism risk screening tool at age 2 years. Main Outcomes and Measures: Outcomes include cognitive, language, motor composites on Bayley Scales for Infant and Toddler Development, third edition (Bayley-III) and internalizing, externalizing, total problems, and pervasive developmental disorder (PDD) subscale on the Child Behavior Checklist (CBCL) at age 3 years. Generalized estimating equations tested associations between the 2-stage parent-report autism risk screening tool and outcomes, adjusting for covariates. Results: A total of 467 children (mean [SD] gestational age, 27.1 [1.8] weeks; 243 male [52%]) were screened with the 2-stage parent-report autism risk screening tool at age 2 years, and outcome data at age 3 years were included in analyses. Mean (SD) maternal age at birth was 29 (6) years. A total of 51 children (10.9%) screened positive on the 2-stage parent-report autism risk screening tool at age 2 years. Children with positive screening results were more likely to have Bayley-III composites of 84 or less on cognitive (adjusted odds ratio [aOR], 4.03; 95% CI, 1.65-9.81), language (aOR, 5.38; 95% CI, 2.43-11.93), and motor (aOR, 4.74; 95% CI, 2.19-10.25) composites and more likely to have CBCL scores of 64 or higher on internalizing (aOR, 4.83; 95% CI, 1.88-12.44), externalizing (aOR, 2.69; 95% CI, 1.09-6.61), and PDD (aOR, 3.77; 95% CI, 1.72-8.28) scales. Conclusions and Relevance: Results suggest that the 2-stage parent-report autism risk screening tool administered at age 2 years was a meaningful screen for developmental delays in very preterm infants, with serious delays detected at age 3 years.
Asunto(s)
Trastorno Autístico , Enfermedades del Prematuro , Lactante , Recién Nacido , Humanos , Masculino , Preescolar , Adulto , Recien Nacido Prematuro , Estudios de Cohortes , Recién Nacido de muy Bajo Peso , Edad GestacionalRESUMEN
The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (< 30 weeks gestation; VPT), as they experience a significant disruption in the normal developmental trajectories and are at heightened risk of experiencing developmental impairments and delays. Variations in the epigenetic landscape during this period may reflect this disruption and shed light on the interrelationships between aging, maturation, and the epigenome. We evaluated how gestational age (GA) and age since conception in neonates [post-menstrual age (PMA)], were related to DNA methylation in buccal cells collected at NICU discharge from VPT infants (n = 538). After adjusting for confounders and applying Bonferroni correction, we identified 2,366 individual CpGs associated with GA and 14,979 individual CpGs associated with PMA, as well as multiple differentially methylated regions. Pathway enrichment analysis identified pathways involved in axonogenesis and regulation of neuron projection development, among many other growth and developmental pathways (FDR q < 0.001). Our findings align with prior work, and also identify numerous novel associations, suggesting that genes important in growth and development, particularly neurodevelopment, are subject to substantial epigenetic changes during early development among children born VPT.