Predicting mid-term hearing and developmental outcome in clinically inapparent congenital cytomegalovirus infection with hearing loss at birth.

Early language delay among infants with hypoxic-ischaemic encephalopathy after therapeutic hypothermia: A prospective cohort study.

Material and emotional hardship during pregnancy can shape early brain development and behavior in infants. This study used the COVID-19 pandemic as a natural context in which such hardships were widespread, particularly in low-resource settings. This cohort study examined associations between pandemic-related maternal emotional distress and material hardship during pregnancy and early neurodevelopmental outcomes in infants. A total of 235 mother-infant dyads from low-resource healthcare settings in Brazil were enrolled during the COVID-19 pandemic. Maternal hardships were assessed using a COVID-19-specific questionnaire, which included self-reported COVID-19 exposure/infection. Infant neurodevelopment was evaluated via MRI at 2-6 weeks of age and behavioral assessments at 14 months using the Bayley Scales of Infant Development. Material hardship was associated with reduced hippocampal volumes in the left (pfdr = .008) and right (pfdr = .025) hemispheres. Among female infants, material hardship was linked to lower functional connectivity between the right hippocampus and the right rostral anterior cingulate cortex (p = .004). Smaller hippocampal volumes correlated with weaker gross motor skills at 14 months (r = .23; p = .02). Maternal emotional distress and self-reported COVID-19 exposure/infection were not significantly associated with infant neurodevelopmental outcomes. Material hardship may adversely affect early neurodevelopment, particularly hippocampal structure and connectivity, with potential downstream effects on motor skills. These findings underscore the importance of addressing material hardship during the perinatal period to support infant brain health and development.

Background/Objectives: Overweight and obesity during pregnancy are metabolic risk factors that may compromise offspring brain development. The first 1000 days of life represent a critical window in which neurodevelopmental trajectories are shaped by intrauterine and early-life exposures. The 6- and 12-month milestones are key checkpoints where deviations may emerge, and interventions are most effective. This study evaluated the association between maternal pregestational weight status and infant neurodevelopment at 6 and 12 months of age. Methods: Mother and infant pairs from the OBESO perinatal cohort in Mexico City were included. Women in the first trimester of pregnancy were classified as normal weight and overweight/obesity according to their pregestational body mass index (pBMI), calculated from self-reported pre-pregnancy weight. Infant neurodevelopment was assessed at 6 and 12 months using the Bayley Scales of Infant Development III, Third Edition (BSID-III). Descriptive, bivariate and multiple linear regression analyses with mixed effects correction were conducted. Results: Among 97 mother–infant pairs, infants of mothers with overweight/obesity had lower language and socio-emotional scores at 12 months. Higher maternal pBMI was correlated with lower motor scores at 6 and 12 months, and with lower language scores at 12 months. Longitudinal analysis showed that maternal overweight/obesity was associated with a significant decline in language development from 6 to 12 months. (p = 0.002). Conclusions: Maternal pregestational overweight or obesity may negatively influence early neurodevelopment, particularly affecting language and cognitive domains during the first year of life. These early deficits could reflect alterations in intrauterine programming associated with maternal metabolic status.

ABSTRACTBackgroundThe Bayley Scales of Infant Development is used in many studies and clinical trials in children with developmental disabilities, including children with Angelman syndrome (AS).MethodWe assessed 142 children with AS in an international multicentre study with the Bayley Scales of Infant Development III, of which 52 children were tested more than once. We assessed criterion validity using proportion analysis, scalability using Mokken analyses and stability of scoring by counting pass‐to‐fail and fail‐to‐pass items.ResultsResults revealed good scalability in all scales but the expressive language scale, indicating that the items of these scales measured one underlying trait. In the expressive language scale, the AS‐related speech difficulties invalidated scoring. Scoring within children across assessments was unstable for all scales except the gross motor scale, as more than half of the children made one or more errors in previously correct items. Loss or regression of skills does not fully explain this finding. Alternative explanations including motivation, concentration, on‐task behaviour and anxiety should also be considered when scores decline.ConclusionsThis study shows that caution should be taken when interpreting single and successive scores of children with AS on the Bayley‐III and that other forms of assessment should complement assessment in children with AS.

ABSTRACTAldose reductase inhibitors (ARI) have been identified as a potential treatment for phosphomannomutase‐2 congenital disorder of glycosylation (PMM2‐CDG), a serious condition for which no treatments are approved. We treated a single patient for 36 months 30 months of age at enrollment, under a single‐patient investigational new drug expanded access request, with govorestat (AT‐007), a novel, highly selective, once daily, brain penetrant ARI at a starting dose of 1 mg/kg oral suspension, which was escalated to 30 mg/kg. The primary endpoint was safety. Secondary assessments included liver transaminases, factor XI, antithrombin III, and whole blood and urine sorbitol. Clinical outcomes were also assessed, including Nijmegen Pediatric CDG Rating Scale (NPCRS), Bayley Scales of Infant Development, and Vineland Adaptive Behavioral Scale. Govorestat was well tolerated; no adverse effects were noted. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels improved from a pre‐treatment 12‐month average of 205 and 268 U/L to 63 and 68 U/L, respectively, averaged over 36 months of govorestat treatment at 30 mg/kg. Antithrombin III and factor XI fluctuated with illness throughout the study period but overall increased by 60%–100%, approaching the normal range (> 83% activity) at the 5 mg/kg dose. Whole blood sorbitol decreased in a dose‐dependent fashion, normalizing at the 30 mg/kg dose. The NPCRS improved by 9 points (46%) over the course of treatment. In conclusion, our patient tolerated govorestat without safety concerns. Improvements in liver transaminases, clotting factors, and whole blood sorbitol were observed along with improvements in clinical measures. These findings support further study of govorestat as a potential treatment for PMM2‐CDG.

This study aimed to evaluate school-age neurodevelopmental outcomes among children with single ventricle heart disease who underwent neonatal Norwood operation with regional cerebral perfusion compared to deep hypothermic circulatory arrest. Additionally, we aimed to identify predictors of school-age development, including early developmental measures. Patients enrolled in a prospective randomised trial of infants with single ventricle heart disease undergoing the Norwood operation with either regional cerebral perfusion or deep hypothermic circulatory arrest were included. For the same cohort of patients, this study performed neurodevelopmental testing at 5 years and 10 years of age. At 5years, a comprehensive neuropsychological evaluation was performed. At 10 years, parent report instruments were used to measure participants' behaviour and executive function. Forty-one patients at 5 years of age and 33 patients at 10 years of age completed neurodevelopmental evaluation. There were no significant differences in neurodevelopmental scores between the regional cerebral perfusion and deep hypothermic circulatory arrest groups at either 5 or 10 years. At 5 years of age, the average full scale intelligence quotient (IQ) was 93.4 ± SD18.8. The Bayley Scale of Infant Development Psychomotor Developmental Index (r = 0.68, p < .0001) and mental developmental index (r = 0.64, p < .0001) at 1 year positively correlated with the full scale IQ at 5 years. Neurodevelopment is delayed in patients with single ventricle heart disease. Neurodevelopmental outcomes at school age did not differ based on the perfusion strategy for the Norwood operation. Mental and psychomotor developmental indices at 1 year are predictive of early school-age measures.

To determine the effects of empiric antibiotic therapy within the first 72 hours after birth, in cases of suspected early-onset sepsis without positive blood cultures, on the neurodevelopment of VLBW infants.Cohort study conducted from January 2014 to December 2021, included neonates from 24 to 32 weeks' gestation. They were categorized based on receiving early antibiotics. Outcomes measured included neonatal morbidities and scores on the Bayley Scales of Infant Development, Third Edition (BSID-III), at 12 to 36 months corrected age.Of 261 VLBW infants 52.9% (n = 138) received empiric antibiotics within the first 72 hours, while 47.1% (n = 123) did not. Multivariate analysis revealed no association between early antibiotics and neurodevelopmental delay. Severe intraventricular hemorrhage independently correlated with delays, while late-onset sepsis and bronchopulmonary dysplasia contributed to specific motor and cognitive delays. Propensity score matching (PSM) was conducted using various models that included gestational age, late-onset sepsis, severe intraventricular hemorrhage, bronchopulmonary dysplasia, and clinical chorioamnionitis. However, antibiotic use was not independently associated with an increased risk of developmental delay in the applied models.Although the use of antibiotics did not emerge as an independent factor contributing to developmental delay, VLBW infants who received antibiotics had more morbidities during their NICU stay.

Fetal Dehydroepiandrosterone from Hair Samples at Birth Predicts Language Development.

We determined whether white matter injury (WMI) severity and location on early-life vs term-equivalent age (TEA) brain MRI were more strongly associated with 36-month neurodevelopment. Very preterm infants were recruited across 3 tertiary NICUs and underwent early-life and TEA MRI. Moderate-severe WMI severity and anterior or posterior location were scored. 36-month neurodevelopmental assessments were completed with Bayley Scales of Infant Development, Third Edition; delay was defined as a composite score <85 points. Multivariable logistic regressions adjusting for birth gestational age, site, infection, retinopathy of prematurity, moderate-severe intraventricular hemorrhage, and antenatal magnesium sulfate were used to determine associations of WMI severity and location at each scan with neurodevelopment. A total of 393 neonates (postmenstrual age median 27.6, SD 2.3 weeks, 47% female) completed early-life and TEA MRI scans. Cognitive delay was associated with early-life moderate-severe (OR 3.82, 95% CI 1.17-9.14) and anterior (OR 5.47, 95% CI 1.72-17.29) WMI. Motor delay was associated with early-life anterior WMI (OR 3.02, 95% CI 1.12-8.2). These associations were not observed at TEA in multivariable logistic regressions. Moderate-severe and anterior WMI on early-life, but not TEA, MRI were associated with neurodevelopmental outcomes. Early-life MRI may represent a more optimal time point for assessing WMI in very preterm infants.

The relationship between maternal thyroid function and intellectual development of offspring is controversial. Iodine may be an important confounding factor. This study investigated whether maternal iodine status could affect the efficacy of levothyroxine (LT4) treatment during early pregnancy on the intellectual growth of progeny.This prospective study divided participants into two groups; the normal iodine group included 53 mother-child pairs and the low iodine group included 60 mother-child pairs (urinary iodine concentration (UIC) ≥ 150µg/L and UIC < 150µg/L). Each iodine status group was further subdivided according to specific maternal thyroid disorders. The two groups were categorized as follows: Control(N), hypothyroxinemia (IH) + LT4, subclinical hypothyroidism (SCH) + LT4, positive thyroid peroxidase antibodies (TPOAbs) + LT4. Finally, the study included eight groups. The Bayley Scales of Infant Development-II were employed to evaluate the neurodevelopment of children (age: 12 -30months). The main results were age-adjusted scores from the Mental Development Index (MDI) and Psychomotor Development Index (PDI).We found that: 1) Under the similar conditions of thyroid function and treatment, iodine deficiency during early pregnancy reduced the MDI value of the offspring (P < 0.001), while, the PDI value was not affected (P = 0.276). Linear regression demonstrated a substantial positive correlation between maternal UIC and MDI of offspring (B = 0.09 [CI 0.06-0.13]; P = 0.01). In the case of iodine deficiency during pregnancy, LT4 treatment on SCH and IH could not improve offspring MDI scores (P < 0.001, P = 0.037, respectively) in contrast to the normal group. However, under normal iodine status during pregnancy, LT4 treatment on SCH and IH could improve offspring MDI scores (P = 0.525, P = 0.650, respectively) compared with the normal group. Concurrently, the PDI of the aforementioned categories did not differ significantly (P > 0.05). 3) In comparison to the normal group, LT4 treatment on TPOAbs during pregnancy could not improve the MDI of the offspring, regardless of whether the iodine nutritional status was normal or not (P < 0.001, P = 0.047, respectively). These findings suggest that concurrent assessment and optimization of both thyroid function and iodine status during early pregnancy may be essential for maximizing offspring intellectual development.

IntroductionPreterm infants are at risk of developmental impairment, especially those born before 33 weeks gestational age. Many studies have shown a positive impact of early interventions on medical outcomes during hospitalisation, long-term cognitive development and parental anxiety. Infant Behavioral Assessment and Intervention Program (IBAIP) has shown positive effects on cognitive development but also on motor impairment in a Dutch cohort. We aim to confirm these results in a multicentric, cluster randomised controlled trial in a French setting.Methods and analysisEight French neonatal intensive care units (NICUs) will be randomised before study initiation to intervention or control group. We aim to include 240 infants born between 25 weeks and 33 weeks gestational age. IBAIP intervention comprises monthly home visits with a trained professional from hospital discharge until 6 months corrected age. Both groups receive standard care according to local organisation. The primary endpoint is composite cognitive score at 2 years corrected age using Bayley Scale of Infant Development Fourth Edition (BSID IV). Secondary endpoints include BSID IV subscores, Ages and Stages Questionnaire scores and parental stress. Analysis is in intention to treat. Univariate and multivariate analysis will be performed on primary and secondary endpoints.Ethics and disseminationInformed consent from one or both parents will be necessary for all patients. Study results will be published in peer-reviewed scientific journals. If our hypothesis is confirmed, IBAIP could be implemented on a nationwide scale. The study was registered with clinicaltrials.gov (ID: 29BRC17.0219).Trial registration numberNCT04685356.

Very low birth weight infants (VLBWIs) are vulnerable to growth restrictions and neurodevelopmental impairments. Congenital anomalies further complicate these risks; however, their long-term effects remain unclear. This study examined the impact of congenital anomalies on the growth and neurodevelopment of VLBWIs. This prospective cohort study analyzed data from the Korean Neonatal Network (2013-2017). A total of 172 VLBWIs with congenital anomalies were matched by gestational age to 516 without anomalies at 18-24 months corrected age, and 136 were matched to 408 at 3 years of age. Growth was assessed using WHO standards, and neurodevelopment was evaluated using the Bayley Scales of Infant Development (II/III) and Korean Developmental Screening Test. Logistic regression analyses were used to identify factors associated with adverse outcomes, with statistical significance set at P < 0.05. VLBWIs with congenital anomalies had significantly lower weight, height, and head circumference z-scores at both time points. Growth restriction persisted, and neurodevelopmental delays, particularly in motor function, were more prevalent. Infants with multiple congenital anomalies had the highest risk of severe growth restriction and developmental impairment. Congenital anomalies pose significant challenges to the growth and neurodevelopment of VLBWIs. Early and individualized interventions, structured neurodevelopmental follow-up, and multidisciplinary care are essential for improving long-term outcomes.

Prenatal exposure to arsenic, umbilical cord blood DNA methylation, and child neurodevelopment: A prospective birth cohort study.

Infantile spasms (IS) are associated with significant neurodevelopmental impairments, yet the underlying brain microstructural and functional alterations remain poorly understood. This study aimed to investigate gray and white matter abnormalities in IS patients and their correlations with neurological dysfunction using advanced neuroimaging techniques. Thirty-four IS patients (21 males, age = 2.8-64.4 months) and 32 age- and sex-matched healthy controls (HC) underwent high-resolution magnetic resonance imaging. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) were employed to analyze gray matter volume (GMV) and cortical thickness, respectively. Diffusion tensor imaging (DTI) assessed white matter integrity. Cognitive and motor functions were evaluated using the Bayley Scales of Infant Development-II. IS patients exhibited significantly lower Mental Development Index (MDI; 50 vs. 99, p < .001) and Physical Development Index (50 vs. 106, p < .001) compared to HC. VBM revealed reduced GMV in bilateral inferior temporal gyri (BA20/37), left middle occipital gyrus (BA19), right precentral gyrus (BA6), posterior cingulate gyrus, and parahippocampal regions (p < .001). Cortical thinning (by SBM) was observed in the right parahippocampal gyrus, supramarginal gyrus, and left middle temporal gyrus. DTI demonstrated decreased fractional anisotropy in corticospinal tracts and hippocampal-cingulum pathways (p < .05). GMV in the left middle occipital gyrus correlated positively with MDI scores (r = .42, p = .02). IS patients exhibit widespread microstructural abnormalities in brain regions critical for visual, auditory-language, motor, and limbic functions. These structural deficits, particularly in the occipital and temporal cortices, may underlie the neurodevelopmental impairments observed in IS. The findings highlight the importance of early neuroimaging to identify anatomical correlates of dysfunction and guide targeted interventions.

BackgroundMaternal oxidative stress during pregnancy plays a role as a hazardous factor of offspring neurodevelopment in animal models. However, epidemiological evidence remains limited. In this prospective cohort, we aimed to investigate the associations between maternal oxidative stress biomarkers (OSBs) across pregnancy and neurodevelopmental outcomes in different stages across early childhood.MethodsThis was a prospective cohort study conducted in 1791 mother–child pairs from Wuhan, China. Three OSBs, including DNA oxidative damage marker (8-hydroxy-2′-deoxyguanosine, 8-OHdG), RNA oxidative damage marker (8-hydroxyguanosine, 8-OHG) and lipid oxidative damage marker (4-hydroxy nonenal mercapturic acid, HNE-MA), were measured in repeatedly collected urine samples in three trimesters across pregnancy. We followed children at age 2, age 3, and age 6 years. At age 2 years, the Bayley Scales of Infant Development of China Revision (BSID-CR) was employed to assess children’s mental and psychomotor development. Brain-derived neurotrophic factor (BDNF) levels were measured in children’s plasma at age 3 years. The Wechsler Preschool and Primary Scale—Fourth Edition (WPPSI-IV) was used to assess children’s intelligence quotients at ages 6 years. Generalized estimating equation models were applied to estimate the associations between OSBs and neurodevelopmental outcomes.ResultsHigher maternal HNE-MA levels in late pregnancy were associated with lower mental development index at age 2 years (β = − 0.95, 95% confidence interval (CI): − 1.78, − 0.11). Elevated early pregnancy HNE-MA levels were associated with decreased BDNF levels at age 3 years (β = − 0.07, 95% CI: − 0.13, − 0.01). Each one-unit increase in natural log-transformed concentrations of 8-OHdG and 8-OHG in mid pregnancy was associated with a decrease in full-scale intelligence quotient at age 6 years by 1.55 points (95% CI: − 2.84, − 0.26) and 1.89 points (95% CI: − 3.30, − 0.49), respectively.ConclusionsThis study suggested that higher levels of OSBs in each trimester of pregnancy might be a risk factor of consistently suboptimal neurodevelopment across early childhood. This finding provides new epidemiological data on the linkages of oxidative stress across pregnancy to child neurodevelopment and gives clues to the possible sensitive windows.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04297-3.

Objective: Therapeutic hypothermia is the standard neuroprotective treatment for neonates with hypoxic-ischemic encephalopathy (HIE). However, neurodevelopmental outcomes may still vary depending on the severity of encephalopathy. This study aimed to evaluate two-year neurodevelopmental outcomes in infants with HIE treated with therapeutic hypothermia and compare outcomes between Stage 2 and Stage 3 cases classified according to the Sarnat &amp; Sarnat staging system. Material and Methods: We conducted a retrospective cross-sectional study including 138 infants born at ≥35 weeks of gestation who were diagnosed with HIE and received therapeutic hypothermia in a Level III NICU between January 2016 and December 2017. Neurodevelopment was assessed at 24 months using the Bayley Scales of Infant and Toddler Development-II (BSID-II), focusing on Mental Development Index (MDI) and Psychomotor Development Index (PDI) scores. Results: Infants in the Stage 3 group required significantly more respiratory support, had a higher frequency of aEEG abnormalities, and more often received anticonvulsant therapy (p=0.020, p&lt;0.001 and p&lt;0.001, respectively). The Stage 3 group had significantly lower mean MDI and PDI scores (84±10 and 71±11, respectively) than the Stage 2 group (89±17 and 94±18; p=0.049 and p=0.001). Neurodevelopmental impairment was more prevalent in Stage 3 patients (36.5% vs. 17.3%, p=0.012). Conclusion: Despite uniform application of therapeutic hypothermia, neurodevelopmental outcomes at 24 months differ significantly by HIE severity. These findings highlight the importance of timely intervention, individualized follow-up, and the need for additional strategies in managing severe HIE cases.

Alcohol use remains common in pregnancy with prenatal alcohol exposure (PAE) associated with a plethora of adverse outcomes, including impaired emotional regulation and stress reactivity. Prior preclinical studies and emerging clinical evidence indicate that PAE affects the fetal hypothalamic-pituitary-adrenal (HPA) axis via the maternal-fetal interface in the placenta; however, little is known about the effect of these alterations on neurodevelopmental outcomes. We earlier reported on the effect of PAE and maternal stress on HPA axis biomarkers in placenta and umbilical cord (UC) blood; in the current study, we examined the effect of HPA axis biomarkers on infant neurodevelopmental outcomes at 6-9 months of term-equivalent age. Participants in the Ethanol, Neurodevelopment, Infant and Child Health (ENRICH-2) prospective cohort were followed from the second trimester of pregnancy until infants were 6-9 months of term-equivalent age. Maternal alcohol use was assessed through prospective interviews and a battery of ethanol biomarkers; maternal stress, by a Perceived Stress Scale (PSS). Placenta and UC blood specimens were collected shortly after birth, flash frozen, and analyzed for mRNA and protein expression of placental corticotropin-releasing hormone (pCRH), hydroxysteroid 11-beta dehydrogenase types 1 and 2 (HSD11B1, HSD11B2) and corresponding proteins (11β-HSD1 and 11β-HSD2), and Nuclear receptor subfamily 3 Group C Member 1-alpha (NR3C1-α) and corresponding glucocorticoid receptor alpha. UC plasma cortisol and cortisone levels were measured with ELISA. Bayley Scales of Infant Development, fourth edition (BSID-4; Motor, Language, Cognitive scores) and Infant Behavior Questionnaire Revised (IBQ-R; Surgency, Orienting/Regulation, Negative Affect) assessed neurodevelopment at 6-9 months of term-equivalent age. Pearson correlation was used to examine associations between placental HPA axis biomarkers and neurodevelopmental outcomes overall and after stratification by group (Alcohol/Control). Multivariable linear regression assessed the independent effect of placental biomarkers and Alcohol * biomarker interactions on infant outcomes after adjusting for Alcohol and maternal stress. Participants (32 Alcohol and 68 Controls) were comparable in sociodemographic characteristics. Activation of the placental HPA axis was correlated with a decrease in BSID-4 scores among Controls and an increase in IBQ-R scores (Surgency and Negative Affect) among Alcohol participants. In multivariable analyses, the HSD11B2/HSD11B1 ratio was associated with a decrease in Cognitive scores, and the Alcohol * pCRH interaction was associated with a decrease in Orienting/Regulation and an increase in Surgency and Negative Affect (all p's < .05), after adjusting for Alcohol and PSS. A significant independent effect of PSS was also observed on infant motor skills, Orienting/Regulation, and Negative Affect. This is the first clinical study to characterize the role of placental HPA axis biomarkers and maternal psychosocial stress in PAE-induced changes on infant neurodevelopment, highlighting the importance of a "placenta-brain axis". We demonstrated that the effects of mild-to-moderate PAE on infant neurobehavior were observed in participants with the highest quartile of pCRH expression, emphasizing the role of placental biomarkers in PAE-induced effects.

Effects of prenatal vanadium exposure on neurodevelopment in early childhood and identification of critical window.

ABSTRACTObjectivePreterm infants frequently experience short apneas which can occur in isolation or in a repetitive pattern termed periodic breathing. We assessed the consequences of the amount of time spent with short apneas on developmental outcomes at 2 years of age.MethodsPreterm infants (N = 23) born between 28 and 32 weeks gestational age were studied during daytime sleep in the supine position at 32–36 weeks post menstrual age (PMA), 36‐40 weeks PMA, 3 months and 6 months corrected age. The percentage of total sleep time (TST) spent with apneas at each study was calculated. Infants were divided into those below and above the median cumulative time spent with apneas over the 4 studies (28.4% TST) and developmental assessments (Bayley Scales of Infant Development III, Early Childhood Behavior Questionnaire, Child Behavior Check List) at 2 years of age were compared with ANCOVA.ResultsThe above median group tended to have lower unadjusted scores for motor composite, social emotional composite and adaptive behavior composite on the Bayley's. After adjusting for confounders and %TST spent with apneas, the motor composite score was significantly lower in the above median group (p < 0.05). Perceptual Sensitivity was lower in the above median group (p < 0.05).ConclusionsIn clinically stable very preterm infants, who had been discharged home with no concerns of respiratory instability, those infants who spent more time with short apneas, particularly periodic breathing, had reduced motor outcomes at 2 years of age. Our findings add to a growing literature suggesting that short apneas and periodic breathing are not benign.