Observational study on the neonatal outcome during the COVID-19 pandemic in Germany.

AIM: We aimed to determine stillbirth, preterm birth, perinatal complications, and the developmental outcome of children born preterm during the COVID-19 pandemic in Germany. METHODS: National data from the perinatal survey of preterm and term infants born in 2017-2020 between 22 March and 31 December were evaluated. Neurodevelopment of preterm infants at 2 years corrected age was tested with the Parent Report of Children's Abilities-Revised questionnaire and by clinical testing with Bayley scales, either before or during the COVID-19 pandemic. Statistical significance was calculated using a Pearson's chi-square-independence test and a linear regression model. RESULTS: In 2020, there was an increase of stillbirths of 0.02% (p = 0.01) and a decrease in preterm births by 0.38% (p < 0.001). No changes were found in a representative subgroup of infants with regard to neurodevelopmental scores (mental developmental index and psychomotor developmental index) or in parent survey data (non-verbal cognition scale and language development scale). CONCLUSION: Increasing rates of stillbirths and decreasing preterm births in Germany were observed. Existing networks might stabilise neurodevelopment of preterm infants during the COVID-19 pandemic.

Comparing the Growth and Development of Six Months Infants between the Mothers With/Without Covid-19 during Their Pregnancy

Background: Viral infection during pregnancy induces pro-inflammatory cytokines and increases the level of IL-6, which as a measure of the inflammation of the mother's immune system is effective on the development of the brain of the fetus and increases the rate of mental disorders of the fetus. The possible effect of the mother's COVID-19 on children, if any, is still unknown. Therefore, this study was conducted with the aim of investigating and comparing the consequences of neurodevelopment and growth at the age of 6 months in infants among mothers with/without exposure to COVID-19 during pregnancy in Birjand, 2021.Methods: A total of 161 pregnant women with PCR-positive coronavirus and 181 pregnant women without infection were selected by simple random sampling. Demographic characteristics including age, occupation, education, gender, nationality, sex of babies, along with data related to the neurodevelopmental status of infants by the use of ASQ questionnaire were extracted and entered into SPSS 16 software. For descriptive statistics, Mean, standard deviation, and frequency distribution tables were used, and inferential analyses were conducted by the use of Chi-square, t-test, and analysis of variance at a significance level of less than 0.05. The disturbance was equal / lower than 1 SD in each of ASQ-3 score domains.Results: In this cohort study, demographic characteristics in the exposed and unexposed groups were not significantly different. There was no statistically significant difference between the average score of the ASQ_3 questionnaires as well as the average score in the areas of communication, gross motor, fine motor, problem-solving, and social personality among infants born from mothers with and without COVID-19. Also, there was no significant difference in the incidence of disorders in different fields of neurodevelopment, except for the field of establishing communication between the two groups of exposed and unexposed. On the other hand, cesarean delivery was significantly higher in pregnant mothers with COVID-19 during pregnancy. However, there was no significant relationship between the incidence of COVID-19 and the rate of premature delivery, and low birth weight neonates. In addition, the severity and time of the corona infection during pregnancy did not have any significant effect on the neurodevelopment of infants with intrauterine exposure to COVID-19.Conclusion: According to the results of the study, infection with COVID-19 does not increase the incidence of developmental disorders in 6-month-old infants. Furthermore, it does not increase low birth weight and premature delivery. Due to the limitations of the study, it is suggested to conduct a study with a larger number of pregnant mothers with a severe form of the disease, especially in the first trimester of pregnancy, and to follow up with the babies at an older age.

COVID-19 and the developing brain

As of June 2022, children represent 18.9% of total cumulated cases of COVID-19 in the United States. While most children have mild symptoms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the central and peripheral nervous system function. The most common neurological symptoms in children with COVID-19 are headache, fatigue, anosmia, dysgeusia, and myalgia. In hospitalized children, the most common symptoms are headache, encephalopathy, and seizures. Neurological symptoms are associated with a more severe disease course, and up to a third of hospitalized children with COVID-19 require intensive care intervention. A rare and feared complication is multisystem inflammatory syndrome (MIS-C), a serious condition that involves severe inflammation of different organs, including the brain. Treatment for MIS-C has not been validated and primarily consists of supportive care and immune modulation. Some children with a history of COVID-19 develop persistent symptoms, also known as long COVID. However, recent evidence suggests that long COVID symptoms appear as frequently as in children without a history of COVID-19. Similarly, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2, is associated with differences in neurodevelopmental milestones. Almost 3years into the pandemic, the evidence in children is limited. Large-scale studies with adequate pre- and post-pandemic control groups are needed to establish the associations between COVID-19 and short and long-term neurological complications. © 2023 Elsevier Inc. All rights reserved

Maternal respiratory viral infections during pregnancy and offspring's neurodevelopmental outcomes: A systematic review.

Maternal infections during pregnancy, as cytomegalovirus and zika, have been consistently associated with severe newborn neurodevelopmental conditions, mainly related to vertical transmission and congenital infection. However, little is known about the neurodevelopmental consequences of maternal respiratory viral infections, which are the most prevalent infections during pregnancy. The recent COVID-19 pandemic has increased the interest in understanding the consequences of infections in offspring's development. This systematic review explores whether maternal gestational viral respiratory infections are associated with neurodevelopmental deviations in children below 10 years-old. The search was conducted in Pubmed, PsychInfo and Web of Science databases. 13 articles were revised, including information about maternal infection (Influenza, SARS-CoV-2 and unspecified respiratory infections) and offspring's neurodevelopment (global development, specific functions, temperament and behavioral/emotional aspects). Controversial results were reported regarding maternal respiratory infections during pregnancy and infants' neurodevelopment. Maternal infections seem to be associated with subtle alterations in some offspring's developmental subdomains, as early motor development, and attentional, behavioral/emotional minor problems. Further studies are needed to determine the impact of other psychosocial confounding factors.

Smell and taste of milk during tube feeding of preterm infants: neurodevelopmental follow-up of the randomized TASTE trial, study protocol.

BACKGROUND: The Taste And Smell To Enhance nutrition (TASTE) trial investigated the effects of smell and taste of milk with tube feeding compared to routine care on the growth of preterm infants. There was no difference between groups in growth (weight, head circumference, length) z-scores at discharge from the hospital. Infants in the intervention group had higher head circumference and length z-scores at 36 weeks postmenstrual age, both secondary outcomes. The objective of this follow-up study is to assess 2-year neurodevelopmental and growth outcomes after exposure of preterm infants to the smell and taste of milk with tube feeding compared to routine care. METHODS: This is a neurodevelopmental follow-up study of a two-center, placebo-controlled randomized trial. Infants born before 29 weeks postmenstrual age and/or with a birth weight of less than 1250 g were randomized to smell and taste of milk with each tube feed or routine care. The current follow-up assessed the 2-year neurodevelopmental and growth outcomes of participants of the TASTE trial discharged from the hospital (n = 334). The primary outcome is survival free of any major neurodevelopmental impairment comprising any moderate/severe cerebral palsy (Gross Motor Function Classification System score II-V), Bayley Scales of Infant and Toddler Development, Third/Fourth Edition (Bayley-III/Bayley-4) motor, cognitive, or language scores < -2SD, blindness, or deafness at 2 years of age. Other outcomes include death, breastfeeding within the first year, and respiratory support, oral feeding, and anthropometric parameters at 2 years of age. The Human Research Ethics Committees of Mater Misericordiae Limited and the Royal Women's Hospital approved the TASTE trial including the neurodevelopmental follow-up described in this protocol. DISCUSSION: For patients and their families, the neurodevelopmental outcomes of preterm infants are of utmost importance. Consequently, they should be investigated following any interventional study performed during the newborn period. Furthermore, improved weight gain and head growth in the hospital are associated with better long-term neurodevelopmental outcomes. Smelling and tasting of milk is an uncomplicated and cost-effective intervention that may improve the growth and neurodevelopmental outcomes of preterm infants. Potential limitations affecting this follow-up study, caused by the COVID-19 pandemic, are anticipated and discussed in this protocol. TRIAL REGISTRATION: Name of the registry: Australian and New Zealand Clinical Trials Registry; Registration number: ACTRN12617000583347 ; Registration date: 26 April 2017.

Using Telemedicine to Overcome Barriers to Neurodevelopmental Care from the Neonatal Intensive Care Unit to School Entry.

Dedicated Neonatal Intensive Care Unit (NICU) follow-up programs are recommended for ongoing surveillance for infants at high-risk for future neurodevelopmental impairment (NDI). Systemic, socioeconomic, and psychosocial barriers remain for referrals and the continued neurodevelopmental follow-up of high-risk infants. Telemedicine can help overcome these barriers. Telemedicine allows standardization of evaluations, increased referral rates, and reduced time to follow-up as well as increased therapy engagement. Telemedicine can expand neurodevelopmental surveillance and support all NICU graduates, facilitating the early identification of NDI. However, with the recent expansion of telemedicine during the COVID-19 pandemic, new barriers related to access and technological support have arisen.

Systematic Review: Neurodevelopmental Benefits of Active/Passive School Exposure to Green and/or Blue Spaces in Children and Adolescents.

Today more than half of the world's population lives in urban areas. Children spend about 40 h a week in the school environment. Knowing the influence of school exposure to green/blue spaces could improve the children's health, creating healthier environments and preventing exposure to legal/illegal drugs. This systematic review summarized the main results of published studies on active or passive exposure to green or blue spaces in different domains of child neurodevelopment. In August 2022, five databases were searched and twenty-eight eligible studies were included in the analysis. Cognitive and/or academic performance was the most frequently studied (15/28). Most studies evaluate passive exposure to green/blue spaces (19/28) versus active exposure (9/28). Only three studies addressed the relationship between blue space and neurodevelopment. The main results point toward mixed evidence of a protective relationship between green/blue space exposure and neurodevelopment, especially in improving cognitive/academic performance, attention restoration, behavior, and impulsivity. Renaturalizing school spaces and promoting "greener" capacities for school environmental health could improve children's neurodevelopment. There was great heterogeneity in methodologies and adjustment for confounding factors across studies. Future research should seek a standardized approach to delivering school environmental health interventions beneficial to children's development.

Impact of perinatal COVID on fetal and neonatal brain and neurodevelopmental outcomes.

After three years of the COVID-19 pandemic, we have learned many aspects of the disease and the virus: its molecular structure, how it infects human cells, the clinical picture at different ages, potential therapies, and the effectiveness of prophylaxis. Research is currently focused on the short- and long-term consequences of COVID-19. We review the available information on the neurodevelopmental outcome of infants born during the pandemic from infected and non-infected mothers, as well as the neurological impact of neonatal SARS-CoV-2 infection. We also discuss the mechanisms that could potentially affect the fetal or neonatal brain including direct impact after vertical transmission, maternal immune activation with a proinflammatory cytokine storm, and finally the consequences of complications of pregnancy secondary to maternal infection that could affect the fetus. Several follow-up studies have noted a variety of neurodevelopmental sequelae among infants born during the pandemic. There is controversy as to the exact etiopathogenesis of these neurodevelopmental effects: from the infection itself or as a result of parental emotional stress during that period. We summarize case reports of acute neonatal SARS-CoV-2 infections associated with neurological signs and neuroimaging changes. Many infants born during previous pandemics caused by other respiratory viruses demonstrated serious neurodevelopmental and psychological sequelae that were only recognized after several years of follow-up. It is essential to warn health authorities about the need for very long-term continuous follow up of infants born during the SARS-CoV-2 pandemic for early detection and treatment that could help mitigate the neurodevelopmental consequences of perinatal COVID-19.

Prenatal exposure to opioids and neurodevelopment in infancy and childhood: A systematic review.

Aim: This systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies. Methods: We searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using "Covidence" systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment. Results: Data were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis. Conclusion: We explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.

The causal effect of being born extremely preterm or extremely low birthweight on neurodevelopment and social-emotional development at 2 years.

AIM: To assess the causal effect of being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g), compared with being born at term, on neurodevelopment and social-emotional development at 2 years' corrected age. METHODS: Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term-born controls. Children were assessed at 2 years' corrected age with the Bayley Scales of Infant and Toddler Development-3rd edition and the Infant-Toddler Social and Emotional Assessment. Delay was defined as <-1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. RESULTS: A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social-emotional competence (4.1 [1.6, 10.2]). CONCLUSION: Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social-emotional competence at 2 years' corrected age. Close developmental surveillance, including social-emotional development, is recommended.

Telehealth services for cardiac neurodevelopmental care during the COVID-19 pandemic: a site survey from the Cardiac Neurodevelopmental Outcome Collaborative.

OBJECTIVE: COVID-19 has markedly impacted the provision of neurodevelopmental care. In response, the Cardiac Neurodevelopmental Outcome Collaborative established a Task Force to assess the telehealth practices of cardiac neurodevelopmental programmes during COVID-19, including adaptation of services, test protocols and interventions, and perceived obstacles, disparities, successes, and training needs. STUDY DESIGN: A 47-item online survey was sent to 42 Cardiac Neurodevelopmental Outcome Collaborative member sites across North America within a 3-week timeframe (22 July to 11 August 2020) to collect cross-sectional data on practices. RESULTS: Of the 30 participating sites (71.4% response rate), all were providing at least some clinical services at the time of the survey and 24 sites (80%) reported using telehealth. All but one of these sites were offering new telehealth services in response to COVID-19, with the most striking change being the capacity to offer new intervention services for children and their caregivers. Only a third of sites were able to carry out standardised, performance-based, neurodevelopmental testing with children and adolescents using telehealth, and none had completed comparable testing with infants and toddlers. Barriers associated with language, child ability, and access to technology were identified as contributing to disparities in telehealth access. CONCLUSIONS: Telehealth has enabled continuation of at least some cardiac neurodevelopmental services during COVID-19, despite the challenges experienced by providers, children, families, and health systems. The Cardiac Neurodevelopmental Outcome Collaborative provides a unique platform for sharing challenges and successes across sites, as we continue to shape an evidence-based, efficient, and consistent approach to the care of individuals with CHD.

Effects of the COVID-19 Pandemic on Mental Health and Brain Maturation in Adolescents: Implications for Analyzing Longitudinal Data.

Background: The COVID-19 pandemic has caused significant stress and disruption for young people, likely leading to alterations in their mental health and neurodevelopment. In this context, it is not clear whether youth who lived through the pandemic and its shutdowns are comparable psychobiologically to their age- and sex-matched peers assessed before the pandemic. This question is particularly important for researchers who are analyzing longitudinal data that span the pandemic. Methods: In this study we compared carefully matched youth assessed before the pandemic (n=81) and after the pandemic-related shutdowns ended (n=82). Results: We found that youth assessed after the pandemic shutdowns had more severe internalizing mental health problems, reduced cortical thickness, larger hippocampal and amygdala volume, and more advanced brain age. Conclusions: Thus, not only does the COVID-19 pandemic appear to have led to poorer mental health and accelerated brain aging in adolescents, but it also poses significant challenges to researchers analyzing data from longitudinal studies of normative development that were interrupted by the pandemic.

Maternal SARS-CoV-2 exposure alters infant DNA methylation.

Background: Infection during pregnancy can increase the risk of neurodevelopmental disorders in offspring. The impact of maternal SARS-CoV-2 infection on infant neurodevelopment is poorly understood. The maternal immune response to infection may be mimicked in rodent models of maternal immune activation which recapitulate altered neurodevelopment and behavioural disturbances in the offspring. In these models, epigenetic mechanisms, in particular DNA methylation, are one pathway through which this risk is conferred in utero to offspring. We hypothesised that in utero exposure to SARS-CoV-2 in humans may alter infant DNA methylation, particularly in genes associated with neurodevelopment. We aimed to test this hypothesis in a pilot sample of children in Victoria, Australia, who were exposed in utero to SARS-CoV-2. Methods: DNA was extracted from buccal swab specimens from (n = 4) SARS-CoV-2 in utero exposed and (n = 4) non-exposed infants and methylation status assessed across 850,000 methylation sites using an Illumina EPIC BeadChip. We also conducted an exploratory enrichment analysis using Gene Ontology annotations. Results: 1962 hypermethylated CpG sites were identified with an unadjusted p-value of 0.05, where 1133 CpGs mapped to 959 unique protein coding genes, and 716 hypomethylated CpG sites mapped to 559 unique protein coding genes in SARS-CoV-2 exposed infants compared to non-exposed. One differentially methylated position (cg06758191), located in the gene body of AFAP1 that was hypomethylated in the SARS-CoV-2 exposed cohort was significant after correction for multiple testing (FDR-adjusted p-value <0.00083). Two significant differentially methylated regions were identified; a hypomethylated intergenic region located in chromosome 6p proximal to the genes ZP57 and HLA-F (fwer <0.004), and a hypomethylated region in the promoter and body of the gene GAREM2 (fwer <0.036). Gene network enrichment analysis revealed differential methylation in genes corresponding to pathways relevant to neurodevelopment, including the ERBB pathway. Conclusion: These pilot data suggest that exposure to SARS-CoV-2 in utero differentially alters methylation of genes in pathways that play a role in human neurodevelopment.

The Feasibility and Acceptability of Remote Videoconference Use of the Brief Developmental Assessment Tool for Young Children with Congenital Heart Disease.

Background: Young children with congenital heart disease (CHD) are at heightened risk of developmental delay. The outbreak of COVID-19 and the ensuing lockdowns presented an opportunity to test the feasibility of using a short neurodevelopmental assessment tool-the Brief Developmental Assessment (BDA)-remotely via new technologies. Methods: We tested the feasibility and acceptability of remote testing of the tool's 6 domains of development with 30 children younger than 5 years with CHD and 10 healthy controls. Results: Despite some technical issues, parents largely responded positively to the use of the remote assessment as opposed to traditional face-to-face appointments, citing the beneficial saving of time, money, and childcare. Conclusions: The acceptability of the remote use of the BDA for the developmental screening of children with CHD will allow for the possibility of increased screening for more children and earlier identification of developmental problems, both during and after COVID-19 restrictions.

A prospective, longitudinal, case-control study to evaluate the neurodevelopment of children from birth to adolescence exposed to COVID-19 in utero.

BACKGROUND: The Coronavirus disease (COVID-19) pandemic has created unprecedented acute global health challenges. However, it also presents a set of unquantified and poorly understood risks in the medium to long term, specifically, risks to children whose mothers were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Infections during pregnancy can increase the risk of atypical neurodevelopment in the offspring, but the long-term neurodevelopmental impact of in utero COVID-19 exposure is unknown. Prospective, longitudinal studies are needed to evaluate children exposed in utero to SARS-CoV2 to define this risk. METHODS: We have designed a prospective, case-controlled study to investigate the long-term impacts of SARS-CoV2 exposure on children exposed in utero. Women infected with SARS-CoV-2 during pregnancy will be recruited from Monash Health, the Royal Women's Hospital and Western Health (Melbourne, Australia) and Londrina Municipal Maternity Hospital Lucilla Ballalai and PUCPR Medical Clinical (Londrina, Brazil). A control group in a 2:1 ratio (2 non-exposed: 1 exposed mother infant dyad) comprising women who gave birth in the same month of delivery, are of similar age but did not contract SARS-CoV-2 during their pregnancy will also be recruited. We aim to recruit 170 exposed and 340 non-exposed mother-infant dyads. Clinical and socio-demographic data will be collected directly from the mother and medical records. Biospecimens and clinical and epidemiological data will be collected from the mothers and offspring at multiple time points from birth through to 15 years of age using standardised sample collection, and neurological and behavioural measures. DISCUSSION: The mapped neurodevelopmental trajectories and comparisons between SARS-CoV-2 exposed and control children will indicate the potential for an increase in atypical neurodevelopment. This has significant implications for strategic planning in the mental health and paediatrics sectors and long-term monitoring of children globally.

COVID-19 and fetal brain: Affectation and sequelae

Introduction: Viral infections in pregnant mothers can result in neurological disorders. Because of this, it is important to establish that there is fetal brain affectation due to COVID-19. Objective: To establish a direct and indirect relationship between SARS-CoV-2 infection during pregnancy, and adverse results on perinatalneurologicaldevelopment, as much as psychological long-term results. Material and methods: A narrative review of available evidence linked to the placenta and SARS-CoV-2 relationship, fetal brain physiopathology, and neuropsychiatric affectation was performed using PubMed, LILACS, and Google Scholar databases, on the time lapse between January 1997 to June 2022. Results: 66 studies with methodology, qualitative representability, and citation impact, according to the present research´s objective, were reviewed. Evidence review over COVID-19 and fetal central nervous system (CNS), establishes that chronic histiocytic intervillositis and trophoblast necrosis are risk factors for placental infection by SARS-CoV-2, viral vertical transmission, and breach of the maternal barrier-fetal. Fetal brain expression of protein S receptors suggests fetal brain incursion of SARS-CoV-2 in infected pregnancies, especially during the second and third trimesters of pregnancy. Infections during critical periods of early fetal neurodevelopment have been shown to increase the likelihood of neurodegenerative and neurobehavioral disorders, including autism or autism spectrum disorders (ASDs), and psychiatric illnesses in offspring. Conclusion: Evidence supports the possibility to establish a direct and indirect relationship between SARS-CoV-2 infection during pregnancy, and adverse results on perinatalneurologicaldevelopment, as much as psychological long-term results. © 2022 Academia Nacional de Medicina. All rights reserved.

Adaptive behaviour in children exposed to topiramate in the womb: An observational cohort study.

OBJECTIVE: Many women with epilepsy need to continue anti-seizure medications (ASMs) throughout pregnancy. The current study investigated adaptive behaviour outcomes in children exposed to topiramate in the womb. METHOD: An observational, cross-sectional study was designed, recruiting mother-child-pairs from the UK Epilepsy and Pregnancy Register (UKEPR). Health, developmental histories and Vineland Adaptive Behaviour Scale-Third Edition (VABS-III) assessments were administered via telephone by a blinded researcher, supplemented with prospectively collected pregnancy and medication information. Topiramate monotherapy exposed children were compared to VABS-III normative data as recruitment was disrupted by the COVID-19 pandemic. RESULTS: Thirty-four women with epilepsy from 135 (25%) initially agreed to participate in the study, of whom 26 women completed telephone interviews about their children (n = 28). Children ranged from 2.5 to 17 years of age at the time of assessment. Six topiramate-exposed children were born small for gestational age, and there were significant associations between birthweight, dose and VABS-III scores. Significantly lower scores were observed in topiramate-exposed children (n = 21) with a significant dose-response relationship established after adjustment for parental educational level. Daily mean dosage was 280.21 mg, with high dosages of topiramate associated with a 12-point reduction in VABS-III scores. Additionally, four topiramate-exposed children (19.05%) had diagnoses of Autism Spectrum Disorder, which was significantly higher than UK prevalence rates (1.1%). CONCLUSIONS: The findings of poorer adaptive behaviour, higher incidence of ASD and associations with birth weight are of concern and require further validation and replication using larger prospectively-recruited samples and comparator cohorts. Implications for research and clinical practice are discussed.

Paternal De Novo Variant of TAOK1 in a Fetus With Structural Brain Abnormalities.

A dilated lateral ventricle is a relatively common finding on prenatal ultrasound, and the causes are complex. We aimed to explore the etiology of a fetus with a dilated lateral ventricle. Trio whole-exome sequencing was performed to detect causative variants. A de novo variant of TAOK1 (NM_020791.2: c.227A>G) was detected in the proband and evaluated for potential functional impacts using a variety of prediction tools. Droplet digital polymerase chain reaction was used to exclude the parental mosaicism and to verify the phasing of the de novo variant. Based on peripheral blood analysis, the parents did not exhibit mosaicism at this site, and the de novo variant was paternally derived. Here, we describe a fetus with a de novo likely pathogenic variant of TAOK1 who had a dilated lateral ventricle and a series of particular phenotypes. This case expands the clinical spectrum of TAOK1-associated disorders. We propose a method for solving genetic disorders in which the responsible genes have not yet gone through ClinGen curation, particularly for prenatal cases.

Neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections during pregnancy: a national prospective study in Kuwait.

BACKGROUND: An increasing proportion of women are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study was to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy. METHODS: In this prospective cohort study, the neurodevelopmental status of infants (N = 298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10-12 months post-discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff scores ≤ 2 standard deviations (SDs) below the population mean) and no delays (scores > 2 SDs above the population mean). RESULTS: The majority (90%) of the infants born to mothers with SARS-CoV-2 infections during pregnancy had favorable outcomes and only 10% showed developmental delays. Two of the 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infections during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P = 0.039) and second trimesters (P = 0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester. CONCLUSION: The neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections seem favorable. However, more studies with larger sample sizes and longer follow-up periods are required.