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Background: The increasing complexity of congenital cardiac surgery has led to greater utilization of extracorporeal membrane oxygenation (ECMO) support for children post‐surgery. This study aims to identify risk factors for mortality and brain injury in pediatric patients requiring post‐cardiotomy ECMO and to evaluate their neurological outcomes. Methods: This retrospective study includes pediatric patients with congenital heart diseases who required ECMO after surgery. Risk factors for in‐hospital mortality and brain injury were assessed. Neurodevelopmental status was determined using the Pediatric Cerebral Performance Category (PCPC) Scale at discharge and during follow‐up. Results: Between October 2014 and May 2021, 2651 pediatric patients underwent cardiac surgery, with 90 (3.4%) requiring ECMO. The mean age was 0.6 years, ranging from 1 day to 13 years and 7 months. ECMO was implemented for 45 patients due to CPB weaning failure (NW‐CPB), 24 due to postoperative low‐cardiac output syndrome (LCOS), and 21 for extracorporeal cardiopulmonary resuscitation (E‐CPR). ECMO weaning was achieved in 73 patients (81%), with an overall mortality rate of 36%. Pre‐implant lactate levels (OR: 1.13, 95% CI: 1.03–1.25; p = 0.009) and peak bilirubin levels (OR: 1.04, 95% CI: 0.87–1.24; p = 0.69) were risk factors for in‐hospital mortality. Survival rates were 79% for LCOS, 60% for NW‐CPB, and 48% for E‐CPR. Brain injury incidence was 33%, with E‐CPR being a significant risk factor (p = 0.006) and NW‐CPB being protective (p = 0.001). Follow‐up in November 2023 showed significant improvement in neurodevelopmental status (p < 0.001). Conclusion: Elevated pre‐implant lactate and elevated bilirubin levels during ECMO are major risk factors for mortality. E‐CPR is the primary risk factor for brain injury. Follow‐up revealed significant improvements in neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Aim: Intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL) in preterm infants are associated with an increased risk of long‐term neurodevelopmental impairments (NDI) and cerebral palsy (CP). However, little is known about their impact on early neurodevelopmental outcomes despite increasing evidence highlighting the feasibility and importance of early NDI/CP diagnosis. We aimed to determine the early neurodevelopmental outcomes of preterm infants with IVH and PVL. Methods: This was a retrospective single‐centre cohort study of preterm infants born at <29 weeks gestation or <1000 g birth weight who attended an Early Neurodevelopment Clinic at 3 to 4 months of corrected age. Primary outcomes of early NDI and CP/high‐risk CP diagnoses based on Prechtl's General Movements Assessment and the Hammersmith Infant Neurological Examination were compared between infants without IVH and infants with mild IVH (grades I‐II), severe IVH (grades III‐IV), and severe brain injury (SBI; severe IVH or cystic PVL). Results: Of 313 infants, 52.1% (n = 163), 41.2% (n = 129), 6.7% (n = 21) and 8.6% (n = 27) had no IVH, mild IVH, severe IVH and SBI, respectively. The adjusted odds of early CP/high‐risk CP diagnosis were significantly higher in infants with severe IVH (aOR 6.07, 95% CI 1.50–24.50) and SBI (aOR 15.28, 95% CI 3.70–63), but not in those with mild IVH (aOR 1.24, 95% CI 0.49–3.10). However, the adjusted odds of any early NDI were similar across groups. Conclusion: Preterm infants with severe IVH and SBI are at increased risk of early CP/high‐risk of CP diagnosis at 3 to 4 months of corrected age. [ABSTRACT FROM AUTHOR]

Twin-twin transfusion syndrome (TTTS) is a serious complication in monochorionic (MC) pregnancies. Fetoscopic laser surgery (FLS) is the primary treatment for advanced TTTS, but managing Quintero stage I TTTS is still controversial. We conducted an observational study evaluating the 2-year neurodevelopment of fetuses, which underwent FLS for stage I TTTS, compared with advanced TTTS and uncomplicated monochorionic diamniotic twins (MCDTs). The study included 156 children: 14 in stage I TTTS group, 28 in advanced TTTS group, and 114 in uncomplicated twin group. In stage I TTTS, 92.9% showed normal neurodevelopment, with no severe neurological impairments observed. These results were comparable with uncomplicated twins (92.1% normal neurodevelopment, P =.921, adjusted odds ratio [aOR] = 1.56, 95% confidence interval [CI] = 0.42-5.79; 1.8% severe impairment, P =.617). Advanced TTTS had a non-significant lower rate of normal neurodevelopment (89.3%, P =.710, aOR = 1.31, 95% CI = 0.12-14.87). In conclusion, FLS for stage I TTTS shows favorable long-term neurodevelopmental outcomes, similar to uncomplicated MC pregnancies. [ABSTRACT FROM AUTHOR]

Background: Brain magnetic resonance imaging (MRI) of infants with congenital heart disease (CHD) shows brain immaturity assessed via a cortical-based semi-quantitative score. Our primary aim was to develop an infant paralimbic-related subcortical-based semi-quantitative dysmaturation score, termed brain dysplasia score (BDS), to detect abnormalities in CHD infants compared to healthy controls and secondarily to predict clinical outcomes. We also validated our BDS in a preclinical mouse model of hypoplastic left heart syndrome. Methods: A paralimbic-related subcortical BDS, derived from structural MRIs of infants with CHD, was compared to healthy controls and correlated with clinical risk factors, regional cerebral volumes, feeding, and 18-month neurodevelopmental outcomes. The BDS was validated in a known CHD mouse model named Ohia with two disease-causing genes, Sap130 and Pchda9. To relate clinical findings, RNA-Seq was completed on Ohia animals. Findings: BDS showed high incidence of paralimbic-related subcortical abnormalities (including olfactory, cerebellar, and hippocampal abnormalities) in CHD infants (n = 215) compared to healthy controls (n = 92). BDS correlated with reduced cortical maturation, developmental delay, poor language and feeding outcomes, and increased length of stay. Ohia animals (n = 63) showed similar BDS findings, and RNA-Seq analysis showed altered neurodevelopmental and feeding pathways. Sap130 mutants correlated with a more severe BDS, whereas Pcdha9 correlated with a milder phenotype. Conclusions: Our BDS is sensitive to dysmaturational differences between CHD and healthy controls and predictive of poor outcomes. A similar spectrum of paralimbic and subcortical abnormalities exists between human and Ohia mutants, suggesting a common genetic mechanistic etiology. [ABSTRACT FROM AUTHOR]

Abstract Human Milk is the best option for infant feeding; and for this reason, it should be promoted, protected, and supported. HM is an individual-specific-dynamic biofluid, characterized by an extreme variability in its composition. A wealth of literature has investigated how HM is related to healthy development. An association between HM composition, including nutrients and growth-related hormones as well as other bioactive components, and short-term and long-term infant outcomes could support this statement; however, the evidence is limited. In fact, HM composition is difficult to examine as it is dynamic and changes within a single feed, diurnally, according to stage of lactation and between and within populations. The aim of this review is summarizing only the innovative knowledge on the association between HM composition and long-term outcomes: infant growth and neurodevelopment. In this specific contest, macronutrients and historical biological component with well recognized effect were excluded (i.e. LCPUFA, DHA, iodine). Revised articles have been found in MEDLINE using breast milk-related outcomes, neurodevelopment, infant growth, breast milk-related biological factors, biomarkers, biological active components, and constituents as keywords. Moreover, we focus our search on the latest research results.

Background: To evaluate whether thyroid-stimulating hormone (TSH) measured during newborn screening (NBS) at birth and at discharge can be surrogate markers for neurodevelopmental impairment (NDI) in extremely preterm infants. Methods: The population cohort enrolled infants born

Introduction: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns. Methods: Retrospective multicenter study included infants with gestational age (GA) 24.0–36.0 weeks and PA, defined as ≥2 of the following: (1) umbilical cord pH ≤7.0, (2) 5-min Apgar score ≤5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA <28.0 (group 1), 28.0–31.9 (group 2), and 32.0–36.0 weeks (group 3). Early MRI (<36 weeks postmenstrual age or <10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0–44.0 weeks and ≥10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment <-1 SD at 18–24 months corrected age. Results: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8–58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3–4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0–1.6) and DGM sub-scores (aOR 4.8, 95% CI: 1.1–21.7) around TEA were associated with adverse neurodevelopmental outcomes. Conclusion: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Levothyroxine (L-T4) is available for use in congenital hypothyroidism (CH) in three formulations: tablets, drops, and oral solution. This study aims to compare the efficacy and safety of all three L-T4 formulations. Methods: We enrolled 63 children born between January 2019 and April 2023 in the Emilia-Romagna Region (Italy) and diagnosed with CH by newborn screening. They were divided according to the L-T4 formulation used: drops (Group D), oral solution (Group S), and tablets (Group T). Clinical and laboratory data were collected up to 3 years after the start of replacement therapy. Results: Serum-free thyroxine (sFT4) and thyroid stimulating hormone (sTSH) normalization occurred within the first month of treatment in most patients of all groups. No negative effects on growth and cognitive development were observed. At 7–15 days we found higher median sTSH levels (p = 0.031) and a greater percentage of patients with sTSH > 5 µU/mL (p = 0.011) in Group S than in Group T, but comparable sFT4 levels. At 12 months, a greater percentage of patients of Group D showed sFT4 values below the normal range than Group S (p = 0.011) and Group T (p = 0.038); Conclusions: Overall, our study reported an equal efficacy of the L-T4 oral solution compared to drops and tablets in CH treatment. A larger series of patients and a long-term follow-up are needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine genetic variations underlying the early neurodevelopmental outcome of developmental disabilities (DDs). The study cohort consisted of 191 children with DDs. Diagnosis was assessed at baseline and at the index age (72–84 months). Exome sequencing was conducted and putative risk variants were identified. According to the diagnostic improvement, children were categorized into the improvement group (n = 19) and the non-improvement group (n = 172). Compared to the non-improvement group, the improvement group had lower number of risk variants in known DD genes and haploinsufficient genes, and lower number of overall putative risk variants. Our results may serve as a preliminary basis for developing a model that informs clinical outcome by sequencing analysis. [ABSTRACT FROM AUTHOR]

Home oxygen therapy (HOT) is frequently used as a therapeutic strategy for children experiencing chronic oxygen dependency associated with bronchopulmonary dysplasia (BPD). Recent studies have highlighted substantial variations in the characteristics and outcomes of infants requiring oxygen, primarily due to the absence of a consensus on the management of HOT in infants with BPD. We conducted this retrospective study and reviewed the medical records of extremely and very preterm infants who were diagnosed with BPD in a tertiary center in northern Taiwan from January 2020 to September 2021. Their neurodevelopmental outcomes were evaluated at 18 to 24 months of corrected age. A total of 134 patients diagnosed with BPD were divided into a HOT group (n = 39) and a room air group (n = 95). The children in the HOT group had a higher incidence of hemodynamic significant patent ductus arteriosus (PDA) (p = 0.005) and PDA ligation (p = 0.004), high-frequency oscillatory ventilation (p < 0.001), nitrogen oxide inhalation (p < 0.001), pulmonary hypertension (p = 0.01), and longer invasive ventilation (p < 0.001), as well as longer hospitalization (p < 0.001). A multivariate logistic regression model demonstrated that prolonged invasive ventilation (OR = 1.032, 95% CI 0.984–1.020, p = 0.001) was correlated with oxygen dependency in children. Infants with BPD born at advanced gestational age (OR = 0.760, 95%CI 0.582–0.992, p = 0.044) had a decreasing risk of requiring HOT. The children in the HOT group had a higher incidence of emergency room visits (p < 0.001) and re-hospitalization (p = 0.007) within one year of corrected age. The neurodevelopmental outcomes revealed the HOT group had an increasing portion of moderate to severe cognitive delay (18.2% vs. 3.7%, p = 0.009) and moderate to severe language delay (24.2% vs. 6.1%, p = 0.006) at 18 to 24 months of corrected age. In conclusion, infants with BPD necessitating HOT required prolonged invasive ventilation during hospitalization and exhibited a greater prevalence of unfavorable neurodevelopmental outcomes at 18 to 24 months of corrected age as well. [ABSTRACT FROM AUTHOR]

BackgroundPersistent pulmonary hypertension of the newborn (PPHN) is a serious condition that affects 1–2 per 1,000 newborns. Scientific data report the existence of neurological developmental abnormalities between 10 and 30%, but the description of these disorders linked with this situation of cerebral hypoxia and haemodynamic failure remains poorly documented.ObjectiveThe main goal of this study was to describe the prevalence of neuro-psychomotor developmental disorders in children aged between one and five years old who have been hospitalised at birth in a neonatal intensive care unit for the management of PPHN.MethodsAll of the newborns ≥34 weeks of gestational age (WGA) with PPHN, treated with inhaled nitric oxide in our neonatal intensive care unit between January 2015 and December 2019 were retrospectively enrolled. An ASQ-3 standardised questionnaire, adapted to the appropriate age (12, 24, 36, 48 and 60 months) was performed by the parents.ResultsFifty-five children (81% of answers) with a median age of 36 months (11–68), whose real age was close to the one of the questionnaire (12, 24, 36, 48 and 60 months), have been included in this study. There was 47% of pathological score [borderline: less than 1 standard deviation (SD) or suspect: less than 2SD] in at least one of the five studied domains, mainly in communication (25%) and individual and social skills (22%), despite a high overall score of 250 [220; 285] out of 300 that improved with age.ConclusionThis study showed a significant prevalence of neuro-psychomotor developmental disorders which justifies making more accessible a prolonged and adapted follow-up for early and multidisciplinary screening and management of these children with PPHN history. Larger cohorts are needed to better explore long term outcome of these vulnerable term neonates.

Introduction: Blood lactate levels in neonates with hypoxic-ischemic encephalopathy (HIE) vary, and their impact on neurodevelopmental outcome is unclear. We assessed blood lactate course over time in neonates with HIE during therapeutic hypothermia (TH) and investigated if blood lactate values were associated with neurodevelopmental outcome at 2 years of age. Methods: This is a retrospective cohort study of neonates with HIE born between 2013 and 2019, treated at the University Children’s Hospital Zurich. We recorded blood lactate values over time and calculated time until lactate was ≤2 mmol/L. Neurodevelopmental outcome was assessed at 18–24 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and categorized as favorable or unfavorable. We investigated associations between blood lactate values and outcome using logistic regression and adjusted for Sarnat stage. Results: 33/45 neonates (69%) had a favorable and 14 (31%) an unfavorable neurodevelopmental outcome. Mean initial lactate values were lower in the favorable (13.9 mmol/L, standard deviation [SD]: 2.9) versus unfavorable group (17.1 mmol/L, SD 3.2; p = 0.002). Higher initial and maximal blood lactate levels were associated with unfavorable outcome, also when adjusted for Sarnat stage (adjusted odds ratio [aOR]: 1.37, 95% CI: 1.01–1.88, p = 0.046, and aOR: 1.35, 95% CI: 1.01–1.81, p = 0.041, respectively). Conclusion: In neonates with HIE receiving TH, initial and maximal blood lactate levels were associated with neurodevelopmental outcome at 18–24 months of age, also when adjusted for Sarnat stage. Further investigations to analyze blood lactate as a biomarker for prognostic value are needed. [ABSTRACT FROM AUTHOR]

There are no evidence-based recommendations regarding the introduction of solid foods in preterm infants. The objective of this study was to investigate whether age at the introduction of solid foods affects neurodevelopmental outcomes. This study focuses on analyzing secondary outcomes from a prospective trial involving very low birth weight infants who were randomly assigned to either an early (10–12th week corrected age) or a late (16–18th week corrected age) complementary feeding group. The study evaluated neurodevelopmental outcomes at one and two years of corrected age, as well as at three years and four months of uncorrected age by utilizing Bayley scales. In total, 89 infants were assigned to the early and 88 infants to the late group, all with a mean gestational age of 27 + 1 weeks. A linear mixed-effects model was used to compare neurodevelopmental outcomes across the study groups, taking into account variables such as gestational age at birth, sex, nutrition at discharge, parents' highest education level, and high-grade intraventricular hemorrhage. The analysis did not reveal any significant differences between the groups. The timepoint of the introduction of solid foods had no impact on neurodevelopmental outcomes at one and two years of corrected age, and at three years and four months of uncorrected age. [ABSTRACT FROM AUTHOR]

Objective We describe the survival and neurodevelopmental outcomes of congenital diaphragmatic hernia (CDH) patients who received single and repeat extracorporeal membrane oxygenation (ECMO). Study Design This is a retrospective single-center study comparing neurodevelopmental outcomes in CDH patients who were managed without ECMO, who received one ECMO run, and those who received two ECMO runs. Neurodevelopmental testing was performed utilizing the Bayley Scales of Infant Development-III. Results There were 68 neonates identified with CDH from January 2011 to June 2019: 30 did not receive ECMO, 29 received single ECMO run, and 9 received two ECMO runs. Survival of ECMO patients was 50%, with 48% of single run and 57% of repeat run patients surviving to discharge. Second-run ECMO patients had increased median ventilator days (60 vs. 33, p = 0.04) and increased median length of hospital stay (159 vs. 89, p = 0.01). Neurodevelopmental testing via Bayley Scales of Infant Development-III was performed on 74% of survivors at the mean age of 24 months. CDH neonates who underwent ECMO (single or repeat runs) were more likely to have lower cognitive, language, and motor composite scores as compared with CDH neonates who had not required ECMO. Motor composite scores were significantly lower in repeat ECMO run neonates as compared with single ECMO run (72 + 6 vs. 85 + 4, p = 0.0003), but there were no further deficits noted in language or cognitive domains. Conclusion Survival after a second ECMO run in CDH is possible, although with increased ventilator days and increased length of hospitalization. We also find further deficits in motor outcomes in the second-run ECMO group compared with single-run ECMO. Our findings do not preclude a second ECMO run, but rather inform our counseling to families and reinforce the need for close neurodevelopmental follow-up for these patients. Key Points A repeat ECMO run is associated with further neurodevelopmental deficits in the motor domain. Survival is possible after repeat ECMO and is associated with increased length of hospital stay. Neurodevelopmental follow-up is critical for all CDH ECMO patients. [ABSTRACT FROM AUTHOR]

We estimated the incidence of intraventricular hemorrhage (IVH) and/or periventricular leukomalacia/echogenicity (PVL/E) in Rhesus isoimmunized infants. Seventy-one infants underwent cranial ultrasound within the first 3 days of life or discharge, whichever was earlier. Of these, 27 (38%) infants had IVH/ PVL/E. On multivariate analysis, lower gestational age (P = 0.035), small for gestational age [aOR (95% CI) 10.6 (1.9, 58.9)], and sepsis [aOR (95% CI) 4.5 (1.1, 18.4)] were independently associated with IVH/PVL. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to analyze neurodevelopmental outcome of very and extremely preterm infants in Vorarlberg, Austria, accessed with neurodevelopmental testing, at the corrected age of 24 months. This article also compared these results with (inter)national data and analyzed the impact of perinatal parameters. Methods Population-based, retrospective multicenter study with data on very and extremely preterm infants born in Vorarlberg from 2007 to 2019 assessed with Bayley Scales of Infant Development (BSID-II/Bayley-III). Results Included were 264 infants with a mean age of 29.0 (± 2.1) weeks of gestational age and a mean birth weight of 1177 (± 328.26) g; 172 infants underwent a BSID-II, 92 a Bayley-III assessment. The psychomotor developmental index (PDI) and mental developmental index (MDI) showed mean scores of 99.6 (± 14.4) and 91 (± 20.4), respectively. Adverse outcomes (scores <70) were assessed in 4.2% for PDI and 15.5% for MDI. In the extremely preterm group (n = 79), results for mean PDI were 100.1 (± 16.8) and for mean MDI 88.4 (± 22.4). Accordingly, adverse outcomes were assessed in 5.1% for PDI and in 20.3% for MDI. In addition to bronchopulmonary dysplasia and intraventricular hemorrhage Grade 3-4, head circumference at birth and patent ductus arteriosus were also identified as risk factors for poor outcome. Conclusion This study showed a remarkably good neurodevelopmental outcome in preterm infants with low rates of adverse outcome, similar to (inter)national reports, especially in the group of extremely preterm infants. Research is needed to explore the role of social factors and infants' environment, especially cognitive outcome and language skills. [ABSTRACT FROM AUTHOR]

To determine the association between optimality score at term age and age three to five months and neurodevelopmental outcome among neonates with hyperbilirubinemia. Fifty infants with and without hyperbilirubinemia were enrolled. The motor repertoires of the infants were evaluated through general movement assessment (GMA) at term age and three to five months post-term. The association between the General Movement Optimality Score (GMOS), Motor Optimality Score (MOS), and Development Assessment Scale for Indian Infants (DASII) at age 12 to 15 months was also assessed. During term age, the median GMOS was significantly lower among infants in the study group when compared with the control group (40 [29 to 42] vs 42 [42 to 42], P < 0.001). However, at age three to five months, there was no significant difference between the groups. Significantly higher number of neonates had abnormal motor repertoire at term age and age three to five months in the study group when compared with the control group (18 [36%] vs 2 [4%], P = 0.001, at term age and 6 [12.2%] vs 1 [2%], P = 0.04, at age three to five months). Among neonates with hyperbilirubinemia, the median GMOS and MOS were significantly lower at term age and age three to five months in infants with motor and mental developmental quotient scores <85 when compared with ≥85. GMA including GMOS and MOS performed in neonates with hyperbilirubinemia during the neonatal period and early infancy is associated with neurodevelopmental outcomes in the first year of life. GMA can help initiate early intervention in such neonates. [ABSTRACT FROM AUTHOR]

Objective This study aimed to compare inborn infants aged 22 and 23 gestational weeks at our hospital to assess for differences in survival and long-term prognosis. Study Design We retrospectively analyzed 22- and 23-gestational-weeks-old infants born in our hospital between January 2011 and December 2018. The prognosis of inborn infants in Japan was also calculated using the Neonatal Research Network of Japan (NRNJ) data during the same period. Results The survival rates at our institution's neonatal intensive care unit discharge, including stillbirth, were 72 and 89% at 22 and 23 gestational weeks, respectively. The mortality rate and neurodevelopmental impairment (NDI) rate at 3 years of age, including stillbirth, were 58 and 32% at 22 and 23 weeks, respectively. Cerebral palsy, mental developmental retardation, visual impairment, and hearing impairment defined NDI. The prognosis at our hospital was better than the average calculated using NRNJ data. Survival rates varied among facilities, and some facilities had survival rates similar to that of our hospital. Conclusion The prognosis of 22-gestational-week-old inborn infants was inferior to that of 23 gestational weeks in our institution but was better than previously reported. If aggressive treatment is provided, survival without sequelae can be fully expected even for 22-gestational-week-old infants. Key Points We examined babies of gestation ages 22 and 23 weeks. We examined the survival and neurological prognoses. We compared our facility with that in entire Japan. [ABSTRACT FROM AUTHOR]

IntroductionChildren who have experienced the coronavirus disease 2019 (COVID-19) pandemic are at an increased risk of adverse neurologic developmental outcomes. Limited data exist on the environmental influences of during the COVID-19 pandemic on preterm infant development. This study aimed to investigate whether COVID-19 exposure affects the neurodevelopmental outcomes in preterm children up to 3 years of age.MethodsThis prospective cohort study included all very low birth weight (VLBW) infants from the Korean Neonatal Network who had undergone a neurodevelopmental assessment between January 2015, and May 2022. The neurodevelopmental outcomes along with the scores on the Bayley Scales of Infant and Toddler Development (BSID) and the Korean Developmental Screening Test for Infants and Children of pediatric patients aged 18–24 and 33–39 months who were exposed to COVID-19 were compared with those of VLBW children born and tested before the pandemic.ResultsThe cohort included 1,683 VLBW infants. The pandemic group had significantly lower language scores on the BSID-III at ages 18–24 months (p = 0.021) and 33–39 months (p = 0.023) than the pre-pandemic group after adjusting for gestational age, morbidity, and environmental factors. At 2nd follow-up period, the pandemic group showed significantly lower scores in the cognitive (p = 0.026) domains with a mean difference of 7 points and had a significantly higher percentage of ≤−1SD in the gross motor domain (p

Introduction: Infants with congenital CMV (cCMV) infection may show manifestations at birth and develop symptomatic disease, although the majority have no apparent clinical signs and should be considered asymptomatic (acCMV). Studies about neurodevelopmental and neurological sequelae in acCMV patients during childhood are few and contradictory, thus, the purpose of this study is to evaluate the neurological and neurodevelopmental outcomes in 1-year-old children with acCMV infections. Method: Thirty-five infants with acCMV infections were followed-up for 12 months and were compared to healthy children matched for age and gender. The Bayley Scales of Infant Development III (BSID-III) were administered, and neurological examinations were performed. Results: Children with acCMV infection showed minimal to mild neurological signs and the score obtained from the Motor Scale was significantly lower than that of the control group. No significant differences between the two groups were found regarding the Cognitive and Language Scales. Discussion: Asymptomatic congenital infection of CMV may be associated with a decrease in motor skills that may become evident during the first year of life. Close monitoring is essential to determine if rehabilitative treatment is required for children with asymptomatic congenital cytomegalovirus (acCMV). Longer follow-up is necessary to provide further details about their neurodevelopmental outcomes.

ObjectivesWe analyzed the impact of postoperative necrotizing enterocolitis (NEC) after cardiac surgery in neonatal age on neurodevelopmental (ND) outcome at 1 year of age.MethodsUsing data from the Swiss Neurodevelopmental Outcome Registry for Children with Congenital Heart Disease (ORCHID), we analyzed perioperative variables including postoperative NEC (Bell's stage ≥2) and 1-year ND outcome (Bayley III).ResultsThe included patients (n = 101) had congenital heart disease (CHD), categorized as follows: 77 underwent biventricular repair for CHD with two functional chambers, 22 underwent staged palliation until the Fontan procedure for CHD with single ventricle physiology (n = 22), or 4 underwent single ventricle palliation or biventricular repair for borderline CHD (n = 4). Neonatal cardiopulmonary bypass (CBP) surgery was performed at a median age (IQR) of 8 (6) days. NEC occurred in 16 patients. Intensive care unit (ICU) length of stay (LOS) and the total duration of the hospitalization were longer in children with NEC than those in others (14 with vs. 8 days without NEC, p

INTRODUCTION: The aim of this study was to evaluate neurological development of infants with transient premature hypothyroxinemia (THOP). METHODS: This prospective study included newborns who were born between 28-36 weeks of gestation (GW) and were admitted to the neonatal intensive care unit. Newborns exposed to maternal thyroid disease, or with severe intracranial problems, and congenital anomalies were excluded. Infants with THOP were the study group and those without THOP formed the control group. The study group was subdivided into those receiving levothyroxine replacement (5 μg/kg/day) and those who were untreated. Neonatal demographics, and morbidities, including respiratory distress syndrome, bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) were evaluated. The Ages and Stages Questionnaire (ASQ) and ASQ: Social-Emotional (ASQ: SE) developmental screening tests were administered to the entire study population at the corrected age of two years. RESULTS: Seventy infants were included in this study, 40 of whom had THOP. The mean GW was 34.4+-3.8 weeks in the study group and 37.2+-2.3 weeks in controls (p=0.69). Mean overall birth weight was 1640+-428 g. Levothyroxine replacement was started in 12/40 infants (30%). The groups were similar in terms of demographic characteristics. Rates of BPD and ROP were higher in the treated group (p=0.01). ASQ and ASQ: SE results did not differ between groups (p=0.75), nor did these scores differ between infants with THOP who did or did not receive levothyroxine (p=0.14). DISCUSSION AND CONCLUSION: Although levothyroxine replacement therapy was associated with increased rates of BPD and ROP, this treatment did not appear to improve long-term neurological outcomes in this small group of infants with THOP. Prospective controlled studies with much larger sample sizes are needed to clarify the role of levothyroxine replacement in THOP.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disorder characterized by peripheral thyrotoxicosis and severe cognitive and motor disability due to cerebral hypothyroidism. 3,3',5-triiodothyroacetic acid (Triac) was shown to improve peripheral thyrotoxicosis but data on neurodevelopmental outcome are scarce. We present a case of MCT8 deficiency and the experience with Triac focusing on change in neurodevelopmental and peripheral features. A five-month-old boy was referred because of feeding difficulty, central hypotonia and global developmental delay. Despite six months of physiotherapy, physical developmental milestones did not improve, and distal muscle tone was increased. A hemizygous pathogenic variant in SLC16A2 was found and MCT8 deficiency was confirmed at 19-months. Thyroid stimulating hormone was 2.83 mIU/mL, free thyroxine 6.24 pmol/L (N=12-22) and free triiodothyronine (FT3) 15.65pmol/L (N=3.1-6.8). He had tachycardia, blood pressure and transaminases were elevated. Triac was started at 21-months. Two weeks after treatment, FT3 dramatically decreased, steady normal serum FT3 was achieved at 28-months. Assessment of neurodevelopmental milestones and signs of hyperthyroidism were evaluated at baseline, 6 months and 12 months after treatment. Signs of hyperthyroidism were improved by 6 months. Developmental composite scores of Bayley Scales of Infant Developmental 3rd Edition remained the same but important developmental milestones (head control, recognition of caregiver, response to his name) were attained, regression in the attained milestones were not observed. Initial dose, management protocol for Triac and research into its efficacy on neurodevelopmental signs in MCT8 deficiency are progressing. This case presents evidence that Triac may resolve peripheral thyrotoxicosis successfully and may slow neurodevelopmental regression, while some developmental milestones were achieved after one year of treatment.

Abstract Background Follow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability. Methods We developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score

Objectives: Brain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. Methods: Term newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included. Those with underlying genetic conditions were excluded. Brain injury was characterized using an magnetic resonance imaging scoring system. Neurodevelopmental outcomes were assigned using the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Independent risk factors for poor neurodevelopmental outcomes were determined by multivariable Cox regression. Results: A total of 122 patients were included. New or progressive postoperative brain injury was noted in 69 patients (57%). A total of 101 patients (83%) had at least 1 neurodevelopmental assessment (median age 36 months) with an early assessment (5-24 months) performed in 95 children. Multivariable Cox regression analysis of early neurodevelopmental outcomes identified new stroke on postoperative magnetic resonance imaging to be an independent predictor of poor neurodevelopmental outcome. Postoperative peak lactate was an independent predictor of poor outcome assessed by the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Conclusions: Our study reveals that evidence of new stroke on magnetic resonance imaging after infant congenital heart surgery is a predictor of poor neurodevelopmental outcomes in early childhood. Postoperative lactic acidosis is associated with poor neurodevelopmental outcome and may be a surrogate biomarker for ischemic brain injury.

Objectives: To determine the effects of in-utero exposure to maternal SARS-CoV-2 infection on offspring's neurodevelopment during the first year of life. Methods: We performed a prospective cohort of babies exposed to SARS-CoV-2 during pregnancy, and a control group (CG) of unexposed babies in a low-income area in Brazil. Children's neurodevelopment was assessed using the guide for Monitoring Child Development in the Integrated Management of Childhood Illness context for both groups (at 1,2,3,4,5,6, 9, and 12 months), and the Ages & Stages Questionnaire (ASQ-3) for the exposed group (EG) (at 4, 6 and 12 months). Results: We followed 137 children for 1 year, 69 in the COVID-19-EG, and 68 in the CG. All mothers were unvaccinated at the time of cohort inclusion, and maternal demographics were similar in the two groups. 20.3% of EG children and 5.9% of the CG received a diagnosis of neurodevelopmental delay within 12 months of life (P = 0.013, relative risk = 3.44; 95% confidence interval, 1.19- 9.95). For the EG, the prevalence of neurodevelopment impairment using Ages & Stages Questionnaire was 35.7% at 4 months, 7% at 6 months, and 32.1% at 12 months. Conclusion: SARS-CoV-2 exposure was associated with neurodevelopmental impairment, and specific guidelines are needed for the follow-up of these high-risk children to mitigate the long-term effects on children's health.

Objective We aimed to investigate the feasibility of evaluating overall preterm brain growth using a gathered set of measurements of brain structures in standard cranial ultrasound planes. We called this method of assessment Brain Growth Evaluation Assessed with Transfontanellar ultrasound (B-GREAT). Study design In this prospective observational cohort study, cranial ultrasound was regularly performed (on day 1, 2, 3, and 7 of life, and then weekly until discharge, and at term) in preterm infants born with gestational age (GA) less than 32 weeks. We evaluated corpus callosum length, corpus callosum–fastigium length, anterior horn width, frontal white matter height, total brain surface, deep grey matter height, hemisphere height, transverse cerebellar diameter in the axial view, and transverse cerebellar diameter coronal view. Measurements obtained were used to develop growth charts for B-GREAT markers as a function of postmenstrual age. Reproducibility of B-GREAT markers was studied. Results A total of 528 cranial ultrasounds were performed in 80 neonates (median birth GA: 28 +5 weeks and interquartile range: 27 +3 –30 +5). The intraclass correlation coefficients for intra-observer and inter-observer analyses showed substantial agreement for all B-GREAT markers. Growth curves for B-GREAT markers were developed. Conclusion B-GREAT is a feasible and reproducible method for bedside monitoring of the growth of the main brain structures in preterm neonates. Key Points Overall neonatal brain growth is not routinely monitored using ultrasound. Old and new markers were used to build a standardized and non-invasive tool to monitor brain growth. All B-GREAT measurements had a good intra-observer and inter-observer agreement. [ABSTRACT FROM AUTHOR]

Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disorder characterized by peripheral thyrotoxicosis and severe cognitive and motor disability due to cerebral hypothyroidism. 3,3',5-triiodothyroacetic acid (Triac) was shown to improve peripheral thyrotoxicosis but data on neurodevelopmental outcome are scarce. We present a case of MCT8 deficiency and the experience with Triac focusing on change in neurodevelopmental and peripheral features. A five-month-old boy was referred because of feeding difficulty, central hypotonia and global developmental delay. Despite six months of physiotherapy, physical developmental milestones did not improve, and distal muscle tone was increased. A hemizygous pathogenic variant in SLC16A2 was found and MCT8 deficiency was confirmed at 19-months. Thyroid stimulating hormone was 2.83 mIU/mL, free thyroxine 6.24 pmol/L (N=12-22) and free triiodothyronine (FT3) 15.65pmol/L (N=3.1-6.8). He had tachycardia, blood pressure and transaminases were elevated. Triac was started at 21-months. Two weeks after treatment, FT3 dramatically decreased, steady normal serum FT3 was achieved at 28-months. Assessment of neurodevelopmental milestones and signs of hyperthyroidism were evaluated at baseline, 6 months and 12 months after treatment. Signs of hyperthyroidism were improved by 6 months. Developmental composite scores of Bayley Scales of Infant Developmental 3rd Edition remained the same but important developmental milestones (head control, recognition of caregiver, response to his name) were attained, regression in the attained milestones were not observed. Initial dose, management protocol for Triac and research into its efficacy on neurodevelopmental signs in MCT8 deficiency are progressing. This case presents evidence that Triac may resolve peripheral thyrotoxicosis successfully and may slow neurodevelopmental regression, while some developmental milestones were achieved after one year of treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate neurological development of infants with transient premature hypothyroxinemia (THOP). Methods: This prospective study included newborns who were born between 28-36 weeks of gestation (GW) and were admitted to the neonatal intensive care unit. Newborns exposed to maternal thyroid disease, or with severe intracranial problems, and congenital anomalies were excluded. Infants with THOP were the study group and those without THOP formed the control group. The study group was subdivided into those receiving levothyroxine replacement (5 μg/kg/day) and those who were untreated. Neonatal demographics, and morbidities, including respiratory distress syndrome, bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) were evaluated. The Ages and Stages Questionnaire (ASQ) and ASQ:Social-Emotional (ASQ:SE) developmental screening tests were administered to the entire study population at the corrected age of two years. Results: Seventy infants were included in this study, 40 of whom had THOP. The mean GW was 34.4±3.8 weeks in the study group and 37.2±2.3 weeks in controls (p=0.69). Mean overall birth weight was 1640±428 g. Levothyroxine replacement was started in 12/40 infants (30%). The groups were similar in terms of demographic characteristics. Rates of BPD and ROP were higher in the treated group (p=0.01). ASQ and ASQ:SE results did not differ between groups (p=0.75), nor did these scores differ between infants with THOP who did or did not receive levothyroxine (p=0.14). Conclusion: Although levothyroxine replacement therapy was associated with increased rates of BPD and ROP, this treatment did not appear to improve long-term neurological outcomes in this small group of infants with THOP. Prospective controlled studies with much larger sample sizes are needed to clarify the role of levothyroxine replacement in THOP. [ABSTRACT FROM AUTHOR]

Neonatal seizures (NS) are the most common neurological emergency in the neonatal period. The International League Against Epilepsy (ILAE) proposed a new classification of NS based on semiology and highlighted the correlation between semiology and aetiology. However, neurodevelopmental outcomes have not been comprehensively evaluated based on this new classification. To evaluate neurodevelopmental outcomes and potential risk factors for severe outcomes in NS. Patients with video electroencephalogram confirmed NS were evaluated. Seizure aetiology, cerebral magnetic resonance imaging (MRI) data, background electroencephalograms data, general movements, and neurodevelopmental outcomes were analysed. Severe outcomes were one of the following: death, cerebral palsy, Griffiths developmental quotient <70, epilepsy, deafness, or blindness. A total of 74 neonates were evaluated: 62 (83.8 %) with acute provoked NS (primarily hypoxic-ischaemic encephalopathy), and 12 (16.2 %) with neonatal-onset epilepsies (self-limited neonatal epilepsy, developmental and epileptic encephalopathy, cerebral malformations). Of these, 32 (43.2 %) had electrographic seizures, while 42 (56.7 %) had electroclinical seizures – 38 (90.5 %) were motor (42.1 % clonic) and 4 (9.5 %) were non-motor phenomena. Severe outcomes occurred in 33 of the 74 (44.6 %) participants. In multivariate analysis, neonatal-onset epilepsies (odds ratio [OR]: 1.3; 95 % confidence interval [CI]: 1.1–1.6), status epilepticus (OR: 5.4; 95 % CI: 1.5–19.9), and abnormal general movements (OR: 3.4; 95 % CI: 1.9–7.6) were associated with severe outcomes. At present, hypoxic-ischaemic encephalopathy remains the most frequent aetiology of NS. The prognosis of neonatal-onset epilepsies was worse than that of acute provoked NS, and status epilepticus was the most predictive factor for adverse outcomes. • The new International League Against Epilepsy (ILAE) classification of neonatal seizures (NS) highlighted a correlation between seizure semiology and aetiology. • In the framework of this classification, we evaluated the neurodevelopmental outcomes in patients with video electroencephalogram (EEG)-confirmed NS. • Hypoxic ischaemic encephalopathy (HIE) remains the most frequent aetiology of NS, often associated with exclusively electrographic seizures and favourable outcomes. Acute provoked NS predominantly manifest with clonic phenomena, whereas neonatal-onset epilepsy presents with spasms, tonic or sequential seizures. • Neonatal-onset epilepsy and status epilepticus were associated with severe outcomes. [ABSTRACT FROM AUTHOR]

• An adverse outcome was in 41.5% of infants with NE. • An unfavorable functional outcome was 15.3% at 12 months. • No difference in outcomes between infants with NE for clinical seizure presence. • This study documents an assertive role for etiology than clinical seizures. To assess the impact of clinical neonatal seizures on outcome characteristics of preterm and term newborns with neonatal encephalopathy (NE). We designed a prospective comparative study with 53 babies (preterm neonates: 26 and term neonates: 27) with NE: group 1 (preterm neonates with seizures, n = 13), group 2 (preterm neonates without seizures, n = 13), group 3 (term neonates with seizures, n = 13) and group 4 (term neonates without seizures, n = 14). The functional outcome characteristics of the survivors were assessed by the Ankara Developmental Screening Inventory (ADSI) and the Guide for Monitoring Child Development (GMCD) at 12 months of age. Clinically defined acute symptomatic seizures were diagnosed with prompt conventional EEG / amplitude-integrated EEG in preterm (92.3%) and term neonates (81.4%) with etiology-specific diagnoses of NE. There were no differences between the study groups regarding seizure semiology and EEG characteristics. A primary adverse outcome was defined in 22 (41.5%) of the cohort. However, only 15.3% of infants had an unfavorable functional outcome with ADSI at 12 months. Among the survivors, there was no significant difference between the study groups regarding ADSI scores. The GMDC test revealed normal development in 50% of survivors with seizures in the preterm group and 83% in the term group. There was no significant difference between the characteristics of functional outcomes at 12 months in preterm and term neonates with NE for clinical seizures. [ABSTRACT FROM AUTHOR]

Gut microbiota are associated with adverse neurodevelopmental outcomes in preterm infants; however, the precise causal relationship remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to comprehensively study the relationship between gut microbiota and adverse neurodevelopmental outcomes in preterm infants and identify specific causal bacteria that may be associated with the occurrence and development of adverse neurodevelopmental outcomes in preterm infants. The genome-wide association analysis (GWAS) of the MiBioGen biogroup was used as the exposure data. The GWAS of six common adverse neurodevelopmental outcomes in premature infants from the FinnGen consortium R9 was used as the outcome data. Genetic variations, namely, single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5 ) and genome-wide statistical significance threshold (5 × 10-8 ) were selected as instrumental variables (IVs). MR studies use inverse variance weighting (IVW) as the main method. To supplement this, we also applied three additional MR methods: MR-Egger, weighted median, and weighted mode. In addition, the Cochrane’s Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods were used for sensitivity analysis. Our study shows a causal relationship between specific gut microbiota and neurodevelopmental outcomes in preterm infants. These findings provide new insights into the mechanism by which gut microbiota may mediate adverse neurodevelopmental outcomes in preterm infants. [ABSTRACT FROM AUTHOR]

(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case–control study included infants with birth weight < 1500 g and/or gestational age ≤ 30 weeks. Short-term outcomes, brain MRI findings, and severe functional disability (SFD) at age 24 months were compared between infants with culture-proven or culture-negative sepsis or without sepsis. A chi-squared test or Mann–Whitney U test was used to compare the clinical and instrumental characteristics and the outcomes between cases and controls. (3) Results: Infants with sepsis (all sepsis n = 76; of which culture-proven n = 33 and culture-negative n = 43) were matched with infants without sepsis (n = 76). Compared with infants without sepsis, both all sepsis and culture-proven sepsis were associated with SFD. In multivariate logistic regression analysis, SFD was associated with intraventricular hemorrhage (OR 4.7, CI 1.7–13.1, p = 0.002) and all sepsis (OR 3.68, CI 1.2–11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority. [ABSTRACT FROM AUTHOR]

• A prospective cohort of infants exposed to maternal SARS-CoV-2 intra uterus. • SARS-CoV-2-exposed infants had an increased risk of neurodevelopmental impairment. • Fine motor and personal-social were the subdomains most at risk of delay. • A total of 10% of exposed infants had an abnormal result at cranial sonography. To determine the effects of in-utero exposure to maternal SARS-CoV-2 infection on offspring's neurodevelopment during the first year of life. We performed a prospective cohort of babies exposed to SARS-CoV-2 during pregnancy, and a control group (CG) of unexposed babies in a low-income area in Brazil. Children's neurodevelopment was assessed using the guide for Monitoring Child Development in the Integrated Management of Childhood Illness context for both groups (at 1,2,3,4,5,6, 9, and 12 months), and the Ages & Stages Questionnaire (ASQ-3) for the exposed group (EG) (at 4, 6 and 12 months). We followed 137 children for 1 year, 69 in the COVID-19-EG, and 68 in the CG. All mothers were unvaccinated at the time of cohort inclusion, and maternal demographics were similar in the two groups. 20.3% of EG children and 5.9% of the CG received a diagnosis of neurodevelopmental delay within 12 months of life (P = 0.013, relative risk = 3.44; 95% confidence interval, 1.19- 9.95). For the EG, the prevalence of neurodevelopment impairment using Ages & Stages Questionnaire was 35.7% at 4 months, 7% at 6 months, and 32.1% at 12 months. SARS-CoV-2 exposure was associated with neurodevelopmental impairment, and specific guidelines are needed for the follow-up of these high-risk children to mitigate the long-term effects on children's health. [ABSTRACT FROM AUTHOR]

Objective: Twin pregnancy is associated with increased perinatal mortality and morbidity, but long‐term neurodevelopmental outcome remains underinvestigated. The primary objective of this study was to investigate the incidence of adverse neurodevelopment after 1 year of age in complicated monochorionic diamniotic (MCDA) twin pregnancies compared with uncomplicated twin pregnancies. Methods: This was a prospective cohort study conducted at St George's University Hospital NHS Foundation Trust, London, UK. Women with a twin pregnancy culminating in at least one surviving child, aged between 12 and 60 months (corrected for prematurity) at the time of assessment, were invited to complete the relevant Ages and Stages Questionnaire® version 3 (ASQ‐3) test. The two study groups were: (1) complicated MCDA twin pregnancies, including those with twin–twin transfusion syndrome, twin anemia–polycythemia sequence, selective fetal growth restriction, twin reversed arterial perfusion sequence and/or single intrauterine demise; and (2) uncomplicated MCDA and dichorionic diamniotic twin pregnancies. The primary outcome measure was an abnormal ASQ‐3 score, defined as a score of more than 2 SD below the mean in any one of the five domains. Mixed‐effects multivariable logistic regression analysis was performed to determine whether a complicated MCDA twin pregnancy was associated independently with an abnormal ASQ‐3 score. Results: The study included 174 parents who completed the questionnaire for one or both twins; therefore, 327 ASQ‐3 questionnaires were available for analysis. Of those, 117 (35.8%) were complicated MCDA twin pregnancies and 210 (64.2%) were controls. The overall rate of an abnormal ASQ‐3 score in children born of a complicated MCDA twin pregnancy was nearly double that of those from uncomplicated twin pregnancies (14.5% vs 7.6%; P = 0.056). Children born of a complicated MCDA twin pregnancy had a significantly higher rate of impairment in the gross‐motor domain compared with the control group (8.5% vs 2.9%; P = 0.031). Complicated MCDA twin pregnancies that underwent prenatal intervention had a significantly higher rate of abnormal ASQ‐3 score compared with those that did not undergo prenatal intervention (28.1% vs 1.7%; P < 0.001). On multilevel logistic regression analysis, complicated MCDA twin pregnancy was an independent predictor of abnormal ASQ‐3 score (adjusted odds ratio, 3.28 (95% CI, 3.27–3.29); P < 0.001). Conclusions: This study demonstrates that survivors of complicated MCDA twin pregnancies have a higher rate of adverse neurodevelopmental outcome, independently of prematurity. Long‐term neurodevelopmental follow‐up in these pregnancies can ensure timely and optimal management of those affected. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Brain development is a complex process that begins during pregnancy, and the events occurring during this sensitive period can affect the offspring's neurodevelopmental outcomes. Respiratory viral infections are frequently reported in pregnant women, and, in the last few decades, they have been related to numerous neuropsychiatric sequelae. Respiratory viruses can disrupt brain development by directly invading the fetal circulation through vertical transmission or inducing neuroinflammation through the maternal immune activation and production of inflammatory cytokines. Influenza virus gestational infection has been consistently associated with psychotic disorders, such as schizophrenia and autism spectrum disorder, while the recent pandemic raised some concerns regarding the effects of severe acute respiratory syndrome coronavirus 2 on neurodevelopmental outcomes of children born to affected mothers. In addition, emerging evidence supports the possible role of respiratory syncytial virus infection as a risk factor for adverse neuropsychiatric consequences. Understanding the mechanisms underlying developmental dysfunction allows for improving preventive strategies, early diagnosis, and prompt interventions. [ABSTRACT FROM AUTHOR]

(1) Background: Breast milk is the only source of nutrition for breastfed infants, but few studies have examined the relationship between breast milk micronutrients and infant neurodevelopmental outcome in exclusively breastfed infants. The aim of this study was to characterize the association between nicotinamide adenine dinucleotide (NAD)-related compounds in the breast milk of Japanese subjects and infant neurodevelopmental outcome. (2) Methods: A total of 150 mother–child pairs were randomly selected from the three-generation cohort of the Tohoku Medical Megabank in Japan. Infants were exclusively breastfed for up to 6 months. Breast milk was collected at 1 month postpartum, and the quantity of NAD-related substances in the breast milk was quantified. The mothers also completed developmental questionnaires at 6, 12, and 24 months. The relationship between the concentration of NAD-related substances in breast milk and developmental indicators was evaluated via ordinal logistic regression analysis. (3) Results: Nicotinamide mononucleotide (NMN) was quantified as the major NAD precursor in breast milk. The median amount of NMN in the breast milk was 9.2 μM. The NMN concentration in breast milk was the only NAD-related substance in breast milk that showed a significant positive correlation with neurodevelopmental outcome in infants at 24 months. (4) Conclusions: The results suggest that NMN in human milk may be an important nutrient for early childhood development. [ABSTRACT FROM AUTHOR]

BackgroundThe risks of invasive prenatal tests are reported in previous studies such as miscarriage, fetal anomalies, and bleeding. However, few compare short-term and long-term outcomes between invasive tests. This study aims to investigate obstetric, perinatal, and children’s neurodevelopmental outcomes following chorionic villus sampling (CVS) or amniocentesis in singleton pregnancy.MethodsThis retrospective cohort study included healthy singleton pregnancies underwent transabdominal CVS (gestational age [GA] at 10–13 weeks) or amniocentesis (GA at 15–21 weeks) at a single medical center between 2012 and 2022. Only cases with normal genetic results were eligible. Short-term and long-term neurodevelopmental outcomes were evaluated.ResultsThe study included 200 CVS cases and 498 amniocentesis cases. No significant differences were found in body mass index, parities, previous preterm birth, conception method, and cervical length (CL) before an invasive test between the groups. Rates of preterm labor, preterm premature rupture of the membranes, preterm birth, neonatal survival, neonatal short-term morbidities, and long-term neurodevelopmental delay were similar. However, the CVS group had a higher rate of cervical cerclage due to short CL before 24 weeks (7.0%) compared to the amniocentesis group (2.4%). CVS markedly increased the risk of cervical cerclage due to short CL (adjusted odd ratio [aOR] = 3.17, 95%CI [1.23–8.12], p = 0.016), after considering maternal characteristics.ConclusionPerforming CVS resulted in a higher incidence of cerclage due to short cervix or cervical dilatation compared to amniocentesis in singleton pregnancies. This highlights the importance of cautious selection for CVS and the necessity of informing women about the associated risks beforehand.

Background/Objectives: Levothyroxine (L-T4) is available for use in congenital hypothyroidism (CH) in three formulations: tablets, drops, and oral solution. This study aims to compare the efficacy and safety of all three L-T4 formulations. Methods: We enrolled 63 children born between January 2019 and April 2023 in the Emilia-Romagna Region (Italy) and diagnosed with CH by newborn screening. They were divided according to the L-T4 formulation used: drops (Group D), oral solution (Group S), and tablets (Group T). Clinical and laboratory data were collected up to 3 years after the start of replacement therapy. Results: Serum-free thyroxine (sFT4) and thyroid stimulating hormone (sTSH) normalization occurred within the first month of treatment in most patients of all groups. No negative effects on growth and cognitive development were observed. At 7–15 days we found higher median sTSH levels (p = 0.031) and a greater percentage of patients with sTSH > 5 µU/mL (p = 0.011) in Group S than in Group T, but comparable sFT4 levels. At 12 months, a greater percentage of patients of Group D showed sFT4 values below the normal range than Group S (p = 0.011) and Group T (p = 0.038); Conclusions: Overall, our study reported an equal efficacy of the L-T4 oral solution compared to drops and tablets in CH treatment. A larger series of patients and a long-term follow-up are needed.

Home oxygen therapy (HOT) is frequently used as a therapeutic strategy for children experiencing chronic oxygen dependency associated with bronchopulmonary dysplasia (BPD). Recent studies have highlighted substantial variations in the characteristics and outcomes of infants requiring oxygen, primarily due to the absence of a consensus on the management of HOT in infants with BPD. We conducted this retrospective study and reviewed the medical records of extremely and very preterm infants who were diagnosed with BPD in a tertiary center in northern Taiwan from January 2020 to September 2021. Their neurodevelopmental outcomes were evaluated at 18 to 24 months of corrected age. A total of 134 patients diagnosed with BPD were divided into a HOT group (n = 39) and a room air group (n = 95). The children in the HOT group had a higher incidence of hemodynamic significant patent ductus arteriosus (PDA) (p = 0.005) and PDA ligation (p = 0.004), high-frequency oscillatory ventilation (p < 0.001), nitrogen oxide inhalation (p < 0.001), pulmonary hypertension (p = 0.01), and longer invasive ventilation (p < 0.001), as well as longer hospitalization (p < 0.001). A multivariate logistic regression model demonstrated that prolonged invasive ventilation (OR = 1.032, 95% CI 0.984–1.020, p = 0.001) was correlated with oxygen dependency in children. Infants with BPD born at advanced gestational age (OR = 0.760, 95%CI 0.582–0.992, p = 0.044) had a decreasing risk of requiring HOT. The children in the HOT group had a higher incidence of emergency room visits (p < 0.001) and re-hospitalization (p = 0.007) within one year of corrected age. The neurodevelopmental outcomes revealed the HOT group had an increasing portion of moderate to severe cognitive delay (18.2% vs. 3.7%, p = 0.009) and moderate to severe language delay (24.2% vs. 6.1%, p = 0.006) at 18 to 24 months of corrected age. In conclusion, infants with BPD necessitating HOT required prolonged invasive ventilation during hospitalization and exhibited a greater prevalence of unfavorable neurodevelopmental outcomes at 18 to 24 months of corrected age as well.

ObjectiveTo evaluate the association of therapeutic hypothermia with magnetic resonance imaging (MRI) findings and 30-month neurodevelopment in term neonatal encephalopathy.Study designCross-sectional analysis of 30-month neurodevelopment (IQR 19.0-31.4) in a prospective cohort of mild-to-severe neonatal encephalopathy imaged on day 4 (1993-2017 with institutional implementation of therapeutic hypothermia in 2007). MRI injury was classified as normal, watershed, or basal ganglia/thalamus. Abnormal motor outcome was defined as Bayley-II psychomotor developmental index

We studied the effect of microstructural abnormalities in the corpus callosum on language development in 348 infants born very prematurely. We discovered that the fractional anisotropy of the corpus callosum anterior midbody was a significant predictor of standardized language scores at 2 years, independent of clinical and social risk factors.

Brain development is a complex process that begins during pregnancy, and the events occurring during this sensitive period can affect the offspring’s neurodevelopmental outcomes. Respiratory viral infections are frequently reported in pregnant women, and, in the last few decades, they have been related to numerous neuropsychiatric sequelae. Respiratory viruses can disrupt brain development by directly invading the fetal circulation through vertical transmission or inducing neuroinflammation through the maternal immune activation and production of inflammatory cytokines. Influenza virus gestational infection has been consistently associated with psychotic disorders, such as schizophrenia and autism spectrum disorder, while the recent pandemic raised some concerns regarding the effects of severe acute respiratory syndrome coronavirus 2 on neurodevelopmental outcomes of children born to affected mothers. In addition, emerging evidence supports the possible role of respiratory syncytial virus infection as a risk factor for adverse neuropsychiatric consequences. Understanding the mechanisms underlying developmental dysfunction allows for improving preventive strategies, early diagnosis, and prompt interventions.

Introduction: There are data linking gestational diabetes mellitus (GDM) with adverse neurodevelopmental outcome in the offspring. We investigated the effect of GDM on microstructural brain development and neurodevelopmental outcome of very preterm infants. Materials and Methods: Preterm infants <32 gestational weeks of mothers with GDM obtained cerebral magnetic resonance imaging (MRI) including diffusion-tensor imaging at term-equivalent age. For every infant, two gestational age-, sex-, and MRI scanner type-matched controls were included. Brain injury was assessed and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measured in 14 defined cerebral regions. Neurodevelopmental outcome was quantified at the corrected age of 24 months using the Bayley Scales of Infant Development. Results: We included 47 infants of mothers with GDM and 94 controls. There were no differences in neonatal morbidity between the groups, nor in any type of brain injury. The GDM group showed significantly higher FA values in the centrum semiovale, the posterior limb of the internal capsule and the pons bilaterally, in the corpus callosum and the right occipital white matter, as well as lower ADC values in the right centrum semiovale, the right occipital white matter and the corpus callosum. Neurodevelopmental outcome did not differ between the groups. Conclusion: We found no impairment of brain development in GDM-exposed infants compared to matched controls, but differences in white matter microstructure in specific regions indicating an enhanced maturation. However, neurodevelopmental outcome was equal in both groups. Further studies are needed to better understand brain maturation in preterm infants exposed to GDM. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) affects roughly 40,000 children annually. Despite advancements, children undergoing surgery for CHD are at an increased risk for adverse neurological outcomes. At present, there is no gold standard for the diagnosis of cerebral injury during the perioperative period. To determine the utility of brain injury biomarkers in children undergoing cardiac surgery. We searched PUBMED, EMBASE, LILACS, EBSCO, ClinicalTrials.gov , Cochrane Databases, and OVID interface to search MEDLINE through July 2021 and assessed the literature following the snowball method. The search terms used were "congenital heart disease," "cardiopulmonary bypass," "biomarkers," "diagnosis," "prognosis," and "children." No language or publication date restrictions were used. Papers studying inflammatory and imaging biomarkers were excluded. The risk of bias, strengths, and limitations of the study were reported. Study was registered in PROSPERO ID: CRD42021258385. A total of 1449 articles were retrieved, and 27 were included. Eight neurological biomarkers were examined. Outcomes assessed included prognosis of poor neurological outcome, mortality, readmission, and diagnosis of brain injury. Results from these studies support that significant perioperative elevations in brain injury biomarkers in cerebrospinal fluid and serum, including S100B, GFAP, NSE, and activin A, may be diagnostic of real-time brain injury and serve as an independent predictor of adverse neurological outcomes in patients with CHD undergoing cardiopulmonary bypass. There are limited homogeneous data in the field, limiting the generalizability and comparability of the results. Further large-scale longitudinal studies addressing neurological biomarkers in children undergoing CHD corrective surgery are required to support the routine use of neuronal biomarkers in this population. [ABSTRACT FROM AUTHOR]

Aim: Kangaroo mother care (KMC) has immense short‐term benefits, but data on long‐term outcomes are scarce. Hence, this study aimed to compare the neurodevelopmental outcomes at 12 months of corrected age (CA) in infants <2000 g receiving early and prolonged KMC to a control group. Methods: This was a cohort study that was conducted from January 2017 to November 2018. All neonates<2000 g were eligible for the study. Neonates that received early initiation (<72 h of life) and prolonged KMC comprised the intervention group and were compared to neonates without the intervention. Bayley Scales of Infant and Toddler Development, Third edition (BSID‐III) was done at 12 months of CA, and this was analysed using t‐test and multi‐linear regression analysis. Results: There were 75 neonates in the intervention and 69 in the control group. Baseline characteristics were comparable. We found higher composite scores for cognition (110.38 ± 9.89 vs. 105.44 ± 8.77, p value = 0.023), language (107.51 ± 10.72 vs. 101.05 ± 12.06, p value = 0.014) and adaptive behaviour (87.97 ± 9.97 vs. 80 ± 9.1, p value<0.001) in the early and prolonged KMC group in comparison to the control group. Conclusion: Infants with early and prolonged KMC have better neurodevelopmental outcomes in terms of cognition, language and adaptive behaviour at 12 months of CA. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate if adaptive responses of very preterm newborns to neonatal intensive care unit (NICU) daily nursing, specifically bathing and weighing procedures are associated with their neurodevelopment after 2 years. Study Design Twenty-six very preterm newborns, with a gestational age <32 weeks, were enrolled. Infants' adaptive responses to daily nursing were evaluated, at 30 to 32 to 35 postmenstrual age (PMA) weeks by an observational sheet. Neurodevelopment was assessed at 24 months of corrected age by the Bayley Scales of Infant and Toddler Development, third edition. Autonomic, motor, and self-regulatory responses to NICU nursing were analyzed by Spearman's correlation coefficient and multivariate linear regression with Bayley's cognitive, language, and motor scales. Results Significant (p < 0.05) positive correlations of self-regulatory and autonomic responses to nursing with all Bayley's scales were found at 30- and 32-week PMA. At 35-week PMA, only self-regulatory responses had significant positive correlations with all Bayley's scales. When adjusted for birth weight and sex, the significant associations were confirmed only at 30- and 32-week PMA. Conclusion Very preterm newborn adaptive responses to NICU daily nursing reveal to be positively related to forthcoming neurodevelopment 2 years later, as early as the 30-week PMA. Helping preterm babies to adapt to daily NICU nursing may promote their future neurobehavior. Key Points Preterm adaptation to nursing was studied. Adaptation positively relates to neurodevelopment. Such relation is detected since 30-week PMA. [ABSTRACT FROM AUTHOR]

Cannabinoid use in all populations is increasing as legalization across the United States continues. Concerningly, there is a lack of caution provided by medical providers to pregnant individuals as to the impact the use of cannabinoids could have on the developing fetus. Research continues in both the preclinical and clinical areas, and is severely needed, as the potency of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has increased dramatically since the initial studies were completed. Thus far, clinical studies raise compelling evidence for short term memory deficits, impulse control issues, and attention deficiencies following prenatal cannabinoid exposure (PCE). These changes may be mediated through epigenetic modifications that not only impact the current offspring but could carry forward to future generations. While additional studies are needed, a pregnancy pause from cannabinoid products should be strongly recommended by providers to ensure the optimal health and well-being of our future generations.

Introduction: Children born to mothers with gestational diabetes mellitus (GDM) are at risk of metabolic disturbances such as diabetes mellitus and overweight. However, few have examined the outcome of children whose mothers were at risk of GDM. The aim of the study was to investigate how mothers' risk of developing GDM affects physical health and neurodevelopment of the children at 7 years of age. Material and methods: This is a secondary analysis of a follow‐up study of a multicenter randomized controlled trial including 855 pregnant women, carried out at St. Olavs Hospital, Trondheim University Hospital, and Stavanger University Hospital in Norway from 2007 to 2009. Risk factors for developing GDM included age >40 years, diabetes in near family, previous child with birthweight ≥4500 g and pre‐pregnancy body mass index (BMI) ≥25 kg/m2. Data on GDM risk factors were available for 750 women, who were divided into a risk group if they had one or more risk factors for developing GDM (n = 238) and a no risk (n = 512) group. At 7 years of age, 72 children born to mothers in the risk group and 194 children born to mothers in the no risk group participated. The children's height, weight and physical activity were reported by their parents. Neurodevelopmental outcomes were assessed by using the Five‐to‐Fifteen questionnaire, which includes motor skills, executive functions, perception, memory, language, social skills, and emotional/behavioral problems. Results: Most women had only one risk factor for GDM, and pre‐pregnancy overweight was the most prevalent risk factor. Children of mothers in the risk group had higher birthweight and length. At the 7‐year follow‐up, they had a higher weight and BMI, and the odds ratio of being overweight was 3.0 (95% confidence interval 1.1–8.3). There was no group difference in the children's physical activity and their neurodevelopmental outcomes were similar. Conclusions: We found higher BMI and increased risk of overweight in children born to mothers with one or more risk factors for developing GDM. A focus on preventing pre‐pregnancy overweight should be encouraged. [ABSTRACT FROM AUTHOR]