Neurodevelopmental Outcomes Research Articles

Comparing Parent Perception of Neurodevelopment after Primary versus Staged Repair of Neonatal Symptomatic Tetralogy of Fallot

To assess the association between primary (PR) and staged repair (SR) of neonatal symptomatic tetralogy of Fallot (sTOF) and neurodevelopmental outcomes in preschool through school-age children. Multi-center cohort (n=9 sites) study of sTOF patients who underwent neonatal intervention between 2005 and 2017. The neurodevelopmental outcomes measures included caregivers' ratings of executive function with the Behavior Rating Inventory of Executive Function (BRIEF), and psychosocial functioning with the Behavior Assessment System for Children - 3rd Edition (BASC-3). Results were compared with normative data and by treatment strategy (PR versus SR). A parent survey assessed history of disabilities and access to services related to neurodevelopment. Although the majority of patients (median age 8.3 years, interquartile range 5.7-11.2) had median BRIEF and BASC-3 scores within the normal range, a proportion had clinically elevated (abnormal) scores, especially in the school-age patient subgroup (BRIEF 24-30% and BASC 20-37%). There were no statistically significant differences based on treatment strategy for either the BRIEF or BASC-3. However, lower birth weight, genetic syndrome, and medical complexity were significantly associated with worse executive function, and lower maternal education was associated in school age children with lower executive and psychosocial functioning. Ongoing disabilities were relatively common (learning disability 35%, speech delay 33%, developmental delay 31%), although up to 50% of children were not receiving educational or developmental services. Elevated executive and psychosocial concerns are present in the sTOF patient population. Although initial treatment strategy appears unrelated to neurodevelopmental outcomes, lower birth weight, genetic syndrome, and medical complexity, and lower maternal education are risk factors. Early recognition of neurodevelopmental concerns can facilitate access to appropriate neuro-developmental services in this high-risk group.

Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. NCT05168228.

Maternal Nutrition during Pregnancy and Offspring Brain Development: Insights from Neuroimaging.

Maternal nutrition during pregnancy is known to be important for offspring growth and health and has also been increasingly recognized for shaping offspring brain development. On the other hand, recent advancements in brain imaging technology have provided unprecedented insights into fetal, neonatal, and pediatric brain morphometry and function. This review synthesizes the current literature regarding the impact of maternal nutrition on offspring brain development, with a specific focus on findings from neuroimaging studies. The diverse effects of maternal nutrients intake or status during pregnancy on neurodevelopmental outcomes in children are discussed. Neuroimaging evidence showed associations between maternal nutrition such as food categories, macronutrients, and micronutrients including vitamins and minerals during pregnancy and child brain imaging features measured using imaging techniques such as ultrasound, magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG). This review demonstrates the capability of neuroimaging in characterizing how maternal nutrition during pregnancy impacts structure and function of the developing brain that may further influence long-term neuropsychological, cognitive, and behavioral outcomes in children. It aims to inspire future research utilizing neuroimaging to deepen our understanding of the critical impacts of maternal nutrition during pregnancy on offspring brain development.

BMI in Pediatric Kidney Transplant Candidates: Association with Neurodevelopmental Outcomes

BMI in Pediatric Kidney Transplant Candidates: Association with Neurodevelopmental Outcomes

Deep Sequencing and Phenotyping in an Australian Tuberous Sclerosis Complex "No Mutations Identified" Cohort.

We describe the phenotypes in an Australian TSC NMI group (n = 18) and a molecular testing strategy implementable in a diagnostic laboratory. Massively parallel sequencing (MPS) of the whole genomic regions of TSC1 and TSC2 was performed using DNA extracted from multiple tissue samples per participant. Our study showed that the phenotype in TSC NMI individuals can be similar to those with heterozygous, particularly TSC1, variants. Although neurodevelopmental outcomes can be less severe, the number of organ systems involved was similar to the non-mosaic groups. A diagnostic yield of 72% (13/18) was achieved, with the majority (10/13) being mosaic variants and the remainder heterozygous variants missed on previous testing. Testing DNA from multiple tissue samples allowed for validation of otherwise discarded low-level mosaic variants and detection of mosaic variants by MPS without excessive cost or the need for specialised techniques. Implementing this approach in a diagnostic setting is viable and allows optimal clinical care of patients with NMI TSC.

Is an Exclusive Human Milk Diet at the Time of Neonatal Intensive Care Unit Discharge Adequate to Maintain Growth and Neurodevelopment among Very Preterm Infants?

Background: An exclusive human milk (EHM) diet has numerous benefits. Formula supplementation may be recommended for former preterm infants at the time of neonatal intensive care unit (NICU) discharge to meet perceived metabolic demands and caloric goals. Recommendations addressing postdischarge nutrition for very preterm infants (VPTIs) are controversial, as the benefits of human milk supplementation regarding long-term growth, neurodevelopment, and chronic conditions are mixed. Objective: To compare growth and neurodevelopment of former VPTI fed an EHM diet to a supplemented/formula diet at NICU discharge. Materials and Methods: A retrospective cohort study of VPTI was followed at the Regional Neonatal Follow-up Program. Patients were categorized by diet at NICU discharge: EHM diet; mixed diet (EHM and formula); and exclusive formula diet. Growth percentile ranks at the first neonatal follow-up visit and 3 years of age were compared by diet type at NICU discharge. Neurodevelopmental outcomes as measured by the Bayley Scales of Infant Development 3rd Edition at 3 years of age were also compared. Results: Among 835 VPTIs, weight percentiles at the first neonatal follow-up visit were similar between the three NICU discharge diet types. One hundred fifty-eight subjects received neurodevelopmental evaluations at 3 years of age; anthropometrics and neurodevelopment were similar irrespective of diet at NICU discharge. Conclusion: An EHM diet at NICU discharge is appropriate to support growth in infancy as well as growth and neurodevelopment through 3 years of age. Thus, this raises the question of whether routine nutritional supplementation is necessary for VPTIs at NICU discharge.

Efficacy and safety of ketogenic diet in infants with epilepsy: KIWE RCT

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with &gt; 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Implications of Prenatal Cannabis Exposure on Childhood Neurodevelopmental Outcomes: A Summary of the Clinical Evidence.

Cannabis is commonly used by pregnant patients for alleviation of pregnancy-associated symptoms. Multiple national medical associations have recommended against prenatal cannabis use, yet misinformation regarding its safety and efficacy remains prevalent in public discourse. Effective and evidence-based patient counseling on prenatal cannabis use requires a thorough understanding of the existing data on fetal neurodevelopment. The aim of this study was to summarize the existing clinical literature on the impacts of intrauterine cannabis exposure on offspring neurodevelopment. Articles were identified via literature search in PubMed and OVID; relevant articles were reviewed. Limited data have shown associations between intrauterine cannabis exposure and (1) increased startles and difficulty with consolation in the neonatal period, (2) memory challenges, verbal reasoning challenges, and diminished academic performance during early childhood, and (3) inattention, hyperactivity, and aggression during early childhood. Further research with large and diverse samples that use objective measures of cannabis use across multiple time points in pregnancy is required to assess causation, the true extent of impacts, and dose-dependent effects. The existing clinical data regarding the impacts of prenatal cannabis use on fetal neurodevelopment are limited by important confounders like genetic predisposition, concomitant tobacco and other substance use during pregnancy, and low socioeconomic status. However, the theoretical and demonstrated associations between prenatal cannabis use and adverse neurodevelopmental outcomes are compelling enough to warrant complete abstinence during pregnancy, pending further research. Providers can utilize this summary to offer data-driven guidance on prenatal cannabis use for pregnant patients.

A Scoping Review of Multimodal, Dyadic Early Relational Health Interventions in NICUs in the United States.

Early relational health (ERH) interventions can buffer toxic stress and improve the developmental trajectories of neonatal intensive care unit (NICU) infants. The purpose was to examine the current state of the science related to multimodal, dyadic ERH interventions implemented in the NICU setting in the United States and identify gaps in the current literature. PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycInfo were searched in November 2022 and November 2023 for original studies and conference proceedings from 1970 to present in the English language. Gray literature searches were performed in February 2023 and December 2023. English language, original research, with a focus on multimodal, dyadic ERH interventions that took place primarily in a NICU in the United States were included. Outcome measures could be related to implementation, relational health, or physical and/or mental health outcomes of parent and/or infant. Eighteen of 2021 reviewed articles met the inclusion criteria. Data were extracted for author, year, intervention, purpose, methods, sample, paternal inclusion, dyadic components, non-dyadic components, and major outcomes/results and distilled for study characteristics, multimodal, dyadic intervention characteristics, and outcome measures. Several multimodal dyadic interventions exist to aid ERH in the NICU, providing evidence of improved outcomes for infants and families. More research is required using higher sample sizes and replication studies. ERH interventions show promise in improving neurodevelopmental, behavioral, and maternal mental health outcomes and should be considered for implementation into NICU services.

Maternal Kidney Disease and Offspring Neurodevelopmental Outcomes: A Nationwide Population-Based Study

Maternal Kidney Disease and Offspring Neurodevelopmental Outcomes: A Nationwide Population-Based Study

Deep Learning Model for Predicting Neurodevelopmental Outcome in Very Preterm Infants Using Cerebral Ultrasound

ObjectiveTo develop deep learning (DL) models applied to neonatal cranial ultrasound (CUS) and clinical variables to predict neurodevelopmental impairment (NDI) in very preterm babies (VPI) at 3 years of corrected age. Patients and MethodsA retrospective study of a cohort of VPI (220-306 weeks' gestation) born between 2004 and 2016 in Nova Scotia, Canada. Clinical data at hospital discharge, and CUS images at three time points were used to develop DL models using elastic net (EN) and convolutional neural network (CNN). The models' performance was compared using Precision Recall Area Under the Curve (PR-AUC) and area under Receiver Operation Characteristic curve (ROC-AUC) with their 95% Confidence intervals. ResultsOf 665 eligible VPI, 619 (93%) infants with 4184 CUS images were included. The CNN model combining CUS, and clinical variables showed better performance (PR-AUC 0.75, C.I. 072 – 0.79 and ROC-AUC 0.71, CI 0.67 - 0.74) in the prediction of positive NDI outcome compared to the traditional models based solely on clinical predictors (PR AUC 0.60 (0.52-0.68), and ROC-AUC of 0.72 (0.68-0.75). When analyzed by the CUS plane and acquisition timepoint, the model utilizing the anterior coronal plane at 6 weeks of age provided the highest predictive accuracy: PR-AUC 0.81 (0.77-0.91) and ROC-AUC 0.78 (0.66-87). ConclusionWe developed and internally validated a DL prognostic model to predict NDI in VPI at 3 years utilizing CUS and clinical predictors. Early and accurate identification of infants at risk for NDI enables referral to targeted interventions which improves functional outcomes.

Neurodevelopmental outcomes of infants after in utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine compared with unexposed infants: a COVI-PREG prospective cohort study

ObjectivesData are lacking regarding the long-term consequences of SARS-CoV-2 and COVID-19 mRNA vaccine on infants exposed in utero. We aimed to evaluate the neurodevelopment of infants exposed prenatally to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy at 12 months after birth. MethodsInfants born to mothers exposed to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy, or unexposed to either the virus or the vaccine were enrolled from 2021 to 2023. Infants with prenatal exposure to the virus or vaccine were compared with infants without prenatal exposure to the virus and/or vaccine. Parents received a neurodevelopmental questionnaire (ages and stages questionnaire third edition) at 12 months after birth assessing five subdomains: communication, gross motor, fine motor, problem-solving, and personal social development. A low score was defined as <2 standard deviations below the normative mean in at least one of the subdomains. ResultsA total of 330 infants were included (76 in the SARS-CoV-2 group, 153 in the mRNA-COVID-19 vaccine group, and 101 in the reference group). In utero exposure to the SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one subdomain compared with the reference group. The crude ORs were 1.16 (95% CI, 0.59–2.28) and 1.04 (95% CI, 0.58–1.86), respectively. Results remained consistent in the multivariate analysis, showing no increased risk of a low score for at least one subdomain for infants exposed to the SARS-CoV-2 or mRNA-COVID-19 vaccine, compared with the reference group. The adjusted ORs were 1.74 (95% CI, 0.76–3.99) and 0.76 (95% CI, 0.39–1.49), respectively. DiscussionIn utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one ages and stages questionnaire third edition subdomain at 12 months after birth. Additional studies are needed to confirm our results, especially longer-term evaluation of infant development.

Maternal Prenatal Cannabis Use and Child Autism Spectrum Disorder

Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited. To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD). This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024. Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks' gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed. Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings. The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85). In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.

DNA methylation signatures of prenatal socioeconomic position associated with 36-month language outcomes

BackgroundSocioeconomic position (SEP), which reflects one’s position in society and access to resources, is strongly tied to neurodevelopment and is associated with epigenetic changes. AIM: This study examined whether DNA methylation signatures of prenatal SEP, measured in birth samples, are associated with child neurodevelopmental outcomes at 36 months of age. METHODS: Prenatal SEP DNA methylation scores were derived using 97 placenta and 127 cord blood biospecimens in the Early Autism Risk Longitudinal Investigation cohort. Participants completed the Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) at 36 months of age. Generalized regression analyses, adjusting for maternal age and race, were performed to test the association between SEP methylation score, for each birth biospecimen type, and MSEL and VABS scores. RESULTS: Significant associations were observed between placenta SEP methylation score and MSEL Expressive Language outcomes (beta = −2.7, p = 0.046, 95 % CI [- 5.43, −0.05]) and Receptive Language outcomes (beta = −2.5, p = 0.037, 95 % CI [-4.82, −0.16]). In cord blood, methylation-SEP scores were significantly associated with Receptive Language outcomes (beta = −2.0, p = 0.037, 95 % CI [-3.85, −0.12]). No significant associations were observed with VABS scores. CONCLUSION: Our results confirm associations between prenatal SEP and early childhood language development using a novel empiric DNA methylation measure of exposure

A study of sleep disorders in Indian children: Tip of the iceberg

BackgroundInsufficient quality and quantity of sleep has dangerous neurodevelopmental outcomes in the form of poor concentration, poor scholastic performance, hyperactivity and obstructive sleep apnea. There is no structured data on prevalence of various sleep behaviours and sleep related disorders in children in India. We aim to study sleep behaviour of children to know the common paediatric sleep related disorders. MethodsWe enrolled 270 children between the age of 1 to 18 years visiting pediatric OPDs for minor ailments between June 2022 to June 2023 using Children Sleep habit questionnaire – (NICHD SECCYD, Wisconsin). Children having clinical features suggestive of obstructive sleep apnoea were further subjected to overnight level 1 Polysomnography study. ResultsMost children had bed time consistency with average sleep duration of Mean ± 2SD (8.58 ± 1.35 h, N=270), which was shorter than global average. Allergic disorders were significantly high with prevalence of allergic rhinitis up to 30 % and asthma between 8-10 % in our study. Prevalence of obstructive sleep apnea on Polysomnography study was 5.6%, parent reported snoring 10 %, restless leg movements 30% and open mouth breathing in 35% Indian children. In our study, Asthma had statistically significant association with sleep disordered breathing and obstructive sleep apnea with p value < 0.01. ConclusionsAsthma has statistically significant association with obstructive sleep apnoea in our study. Proper asthma treatment may reduce the burden of obstructive sleep apnoea in children. There is a growing need to screen children regularly for sleep related issues on routine visits.

Postnatal weight loss and neurodevelopmental outcomes at age 3 years in extremely preterm infants: a cohort study

BackgroundPrevious research has suggested a correlation between postnatal maximum weight loss (MWL) and both neonatal mortality and morbidities in extremely preterm infants. However, the relationship between MWL and neurodevelopmental outcomes remains underexplored.MethodsIn a single-center, retrospective cohort study at Okayama Medical Center, we evaluated data from extremely preterm infants admitted to the neonatal intensive care unit from 2010 to 2020. Infants who died within the first 10 days of life were excluded. MWL in the first 10 days was the main exposure, categorized into three groups: >15%, 5–15%, and < 5%. The primary outcome evaluated was the occurrence of death or neurodevelopmental impairment (NDI) at age 3 years, defined as developmental impairments (developmental quotient [DQ] < 85), cerebral palsy, hearing impairments, or visual impairments. Data analysis involved robust Poisson regression, adjusted for perinatal confounders, with a restricted cubic spline function to examine the dose-response relationship. We also conducted a sensitivity analysis using a DQ of < 70 to define developmental impairment.ResultsAmong 135 infants assessed for neurodevelopmental outcomes, 40 were in the > 15% MWL group, 71 in the 5–15% group, and 24 in the < 5% group. Median gestational ages and birth weights were 25.9 weeks and 821 g for > 15% MWL; 26.1 weeks and 818 g for 5–15% MWL; and 26.0 weeks and 734 g for < 5% MWL. Compared with the 5–15% MWL group, the < 5% group exhibited a higher risk of death or NDI at age 3 years (62.8% vs. 80.8%, risk ratio [RR] 1.36, 95% confidence interval [CI] 1.04–1.79) and NDI alone (59.2% vs. 79.2%, RR 1.43, 95% CI 1.06–1.94). Furthermore, higher risks of developmental impairment were also noted in the > 15% (RR 1.32, 95% CI 1.00–1.75) and < 5% (RR 1.46, 95% CI 1.08–1.98) groups. These associations were confirmed by spline analyses. In contrast, the associations between MWL and neurodevelopmental outcomes using a DQ of < 70 were not apparent.ConclusionsMWL within the first 10 days of life may be associated with increased risks of NDI and developmental impairments by age 3 years in extremely preterm infants.

Neurodevelopmental outcome in preterm infants

Background and objectives. Preterm is defined as babies born alive before 37 weeks of pregnancy are completed. It is one of the world's critical health problems because it may be a significant cause of long-term neurodevelopmental disability. The purpose of this work was to evaluate the impact of premature birth and brain injuries on neurological development and to identify problems as soon as possible in order to prevent or minimize sequelae as much as possible. Materials and methods. Between June 2022 and July 2024, 374 infants were examined at “Prof. Dr. Panait Sarbu” Clinical Hospital of Obstetrics and Gynecology. Each baby's gross and fine motor development was assessed, cognitive acquisitions were evaluated using an adapted Denver Developmental Screening Test, and where needed, physical therapy, head ultrasound/MRI, EEG, or genetic tests were recommended. Results. From the 374 infants evaluated (M/F: 142/232), 72 were excluded considering the normal term of birth. Of the other 302, 23 did not present for follow-up checks after one or two appointments, and 54 completed all evaluations up to 21-24 months (the study is ongoing). 5/54 had poor neurodevelopmental outcomes, almost all due to very preterm birth. From the remaining 225 babies, with a few exceptions with variable neurological damage (13/225), no motor or cognitive development abnormalities have been observed in the evaluations carried out so far. Conclusions. In our cohort, almost all babies who completed or did not the follow-up program had normal development (261/279), but in some cases, prematurity, brain lesions, or genetic causes remain associated with a poor long-term outcome. Establishing a follow-up system for premature infants is necessary because early management during the period of higher brain plasticity may prevent neurological complications and improve the quality of life.

Long-term neurodevelopmental outcomes at three years in preterm infants born before 29 Weeks gestation following Preterm Premature Rupture of Membranes (PPROM).

To determine the association between preterm premature rupture of membranes (PPROM) and neurodevelopmental impairment (NDI) at 3 years corrected age (CA) in infants born before 29 weeks of gestational age (GA). Infants born before 29 weeks GA between 2005 and 2017 were included. The primary outcome was a composite of death or NDI (full-scale intelligence quotient<85, cerebral palsy, vision or hearing impairment) at 3 years of CA. Infants were stratified by maternal PPROM status. Associations were explored using multivariate models. Of 1231 participants, 481 were in the PPROM group, and 750 were in the No PPROM group. After adjusting for factors, the odds ratio of death or NDI for PPROM vs. No PPROM was 1.22 (95% Confidence Interval 0.93-1.59). Our study suggests that PPROM was not associated with an increased risk of a composite outcome of death or NDI at 3 years CA.

Home-ics: how experiences of the home impact biology and child neurodevelopmental outcomes.

Studies on the -omics of child neurodevelopmental outcomes, e.g. genome, epigenome, microbiome, metabolome, and brain connectome aim to enable data-driven precision health to improve these outcomes, or deliver the right intervention, to the right child, at the right time. However, evidence suggests that neurodevelopmental outcomes are shaped by modifiable socioenvironmental factors. Everyday exposures including family and neighbourhood-level socioeconomic status, housing conditions, and interactions with those living in the home, are strongly associated with child health and have been suggested to alter -omics. Our aim was to review and understand the biological pathways by which home factors contribute to child neurodevelopment outcomes. We review studies suggestive of the home factors contributing to neurodevelopmental outcomes that encompass the hypothalamic-pituitary-adrenal axis, the brain, the gut-brain-axis, and the immune system. We thus conceptualize home-ics as the study of how the multi-faceted living environment can impact neurodevelopmental outcomes through biology and highlight the importance of targeting the modifiable aspects of a child's home to optimize outcomes. We encourage clinicians and health care providers to routinely assess home factors in patient encounters, and counsel families on modifiable aspects of the home. We conclude by discussing clinical and policy implications and future research directions of home-ics. IMPACT: Home-ics can be conceptualized as the study of how home factors may shape child neurodevelopmental outcomes through altering biology. Targeting modifiable aspects of a child's home environment (e.g. parenting style, early intervention, enriched environment) may lead to improved neurodevelopmental outcomes. Clinicians should routinely assess home factors and counsel families on modifiable aspects of the home.

Polygenic scores stratify neurodevelopmental copy number variant carrier cognitive outcomes in the UK Biobank

Rare copy-number variants associated with neurodevelopmental conditions (ND-CNVs) exhibit variable expressivity of clinical, physical, behavioural outcomes. Findings from clinically ascertained cohorts suggest this variability may be partly due to additional genetic variation. Here, we assessed the impact of polygenic scores (PGS) and rare variants on ND-CNV carrier fluid intelligence (FI) scores in the UK Biobank. Greater PGS for cognition (PSCog) and educational attainment (PSEA) is associated with increased FI scores in all ND-CNVs (n = 1317), 15q11.2 del. (n = 543), and 16p13.11 dup. carriers (n = 275). No association of rare variants associated with intellectual disability, autism, or putatively loss-of-function, brain-expressed genes was found. Positive predictive values in the first deciles of PScog and PSEA showed a two- to five-fold increase in the rate of low FI scores compared to baseline rates. These findings demonstrate that PGS can stratify ND-CNV carrier cognitive outcomes in a population-based cohort.