Differences In Neurodevelopmental Outcomes Research Articles

Trends in sex differences in neurodevelopmental outcomes among extremely preterm infants

ObjectiveTo examine whether changes in survival without moderate or severe neurodevelopmental impairment (NDI) at 18–26 months’ corrected age from 1999 to 2018 differed between male and female infants.DesignThis retrospective cohort...

Preterm Sex Differences in Neurodevelopment and Brain Development from Early Life to 8 Years of Age

To examine sex differences in neurodevelopmental outcomes and brain development from early life to 8 years in males and females born preterm. This was a prospective cohort study of infants born very preterm (24-32 weeks' gestation) and followed to 8 years with standardized measures of neurodevelopment. Brain magnetic resonance imaging (MRI) scans were performed soon after birth, term-equivalent age, and 8 years. The relationship between sex, severe brain injury, early pain exposure, fractional anisotropy (FA), and neurodevelopmental outcomes were assessed using multivariable generalized estimating equations. Males (N=78) and females (N=66) were similar in clinical risk factors. Male sex was associated with lower cognitive scores (β=-3.8, P=0.02) and greater motor impairment (OR=1.8, P=0.04) across time. Male sex was associated with lower superior white matter FA across time (β=-0.01, P=0.04). Sex moderated the association between severe brain injury, early pain, and neurodevelopmental outcomes. With severe brain injury, males had lower cognitive scores at 3 years (P<0.001). With increasing pain, females had lower cognitive scores at 8 years (P=0.008), and males had greater motor impairment at 4.5 years (P=0.001) and 8 years (P=0.05). Males born preterm had lower cognitive scores and greater motor impairment compared with females, which were associated with differences in white matter maturation. The association between severe brain injury, early pain exposure, and neurodevelopmental outcomes was moderated by sex, indicating a differential response to early-life adversity in males and females born preterm.

Non-invasive Respiratory Support or Intubation during Stabilization after Birth and Neonatal and Neurodevelopmental Outcomes in Infants Born Preterm at 23-25 Weeks of Gestation

To examine the association between non-invasive respiratory support (NRS) or tracheal intubation (TI) during stabilization in infants born at 23-25 weeks of gestation and severe brain injury (sBI) or death, and significant neurodevelopmental impairment (sNDI). A retrospective cohort study of infants born at 230/7-256/7 weeks of gestation in Canada. We compared infants successfully managed with NRS or TI during 30 minutes after birth. The primary outcomes were sBI or death before discharge, and sNDI among survivors with follow-up data at 18-24 months corrected age. The associations between exposures and outcomes were assessed using logistic regression models, and propensity score matched (PSM) analyses. The mean (SD) of gestational age and birth weight were 24.6 (0.6), 24.3 (0.7) weeks [p <0.01], and 757 (173), 705 (130) grams [p <0.01] in the NRS, and TI groups, respectively, and 77% of infants in the NRS group were intubated by 7 days of age. sBI or death occurred in 25% (283/1118), and 36% (722/ 2012) of infants in the NRS and TI groups, respectively (adjusted odds ratio [aOR] and 95% confidence interval [CI] 0.74 [0.60, 0.91]). Among survivors with follow-up data, sNDI occurred in 17% (96/551), and 23% (218/937) of infants in the NRS and TI groups, respectively (aOR [95% CI] 0.77 [0.60, 0.99]). In the PSM analyses (NRS vs TI), results were consistent for sBI or death (OR [95% CI] 0.72 [0.60, 0.86]), but not for sNDI (OR [95% CI] 0.78 [0.58, 1.05]). Infants born at 23-25 weeks who were successfully managed with NRS, compared with TI, in the first 30 minutes after birth had lower odds of sBI or death before discharge, but had no significant differences in neurodevelopmental outcomes among survivors.

Morbidity and neurodevelopmental outcomes at 2 years in preterm infants undergoing percutaneous transcatheter closure vs. surgical ligation of the PDA.

Review a cohort of preterm infants ≤29 weeks of gestation at birth and compare morbidities and neurodevelopmental outcomes based on PDA status and type of PDA closure. Single center observational retrospective-prospective case control study of premature infants who had no hsPDA, underwent surgical ligation or percutaneous transcatheter closure of the PDA. Neurodevelopmental testing was done using the Bayley Scales of Infant Development 3rd ed. The percutaneous transcatheter closure group had an older post menstrual age and greater weight at the time of procedure, and started enteral feeds and achieved room air status at an earlier post procedure day. Infants in the surgical ligation group were more likely to experience vocal cord paralysis. There was no difference in neurodevelopmental outcomes between groups. Waiting for infants to achieve the appropriate size for percutaneous transcatheter closure of the PDA may lead to reduced short-term complications without increasing the risk of neurodevelopmental impairment.

C.6 Sex differences in neurodevelopmental outcomes and brain development from early-life to 8-years in preterm males and females

Background: Sex is associated with differences in early outcomes with preterm males at greater risk for mortality and morbidity. The objective of this study was to examine preterm sex differences in neurodevelopmental outcomes and brain development from early-life to 8-years. Methods: A prospective cohort of preterm infants born 24-32 weeks gestation were followed to 8-years with standardized measures. MRI scans were performed after birth, term-equivalent age and 8-years. Associations between sex, risk factors, brain volumes, white matter fractional anisotropy (FA) and outcomes were assessed using generalized estimating equations. Results: Preterm males (N=83) and females (N=72) had similar risk factors, brain injury and pain exposure. Sex was a predictor of cognitive scores (P=0.02) and motor impairment (P=0.03), with males having lower cognitive scores and higher motor impairment over time. There was a sex effect for FA (P=0.04), with males having lower FA over time. There were significant sex-brain injury and sex-pain interactions for cognitive and motor outcomes. Conclusions: In this longitudinal study, preterm males had lower cognitive scores and greater motor impairment, which may relate to differences in white matter maturation. Effects of brain injury and pain on outcomes is moderated by sex, indicating a differential response to early-life adversity in preterm males and females.

Association of Breastfeeding Duration with Neurodevelopmental Outcomes in an Enriched Familial Likelihood Cohort for Autism Spectrum Disorder.

This study aimed to compare the breastfeeding (BF) duration of the younger siblings of children with ASD in an enriched-likelihood cohort for autism spectrum disorder (ASD), and to determine whether longer BF duration was associated with differences in neurodevelopmental outcomes in this cohort. Information on BF practices was collected via surveys in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. Developmental evaluations, including the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, were conducted by expert clinicians. Participants' neurodevelopmental outcome was classified by an algorithm into three groups: typical development, ASD, and non-typical development. The median duration of BF was 10.70months (interquartile range of 12.07months). There were no significant differences in the distribution of duration of BF among the three neurodevelopmental outcome categories. Children in this enriched-likelihood cohort who were breastfed for > 12months had significantly higher scores on cognitive testing compared to those who were breastfed for 0-3months. There was no significant difference in ASD symptomatology or ASD risk based on BF duration.

Postnatal acetaminophen exposure and neurodevelopmental outcomes at 18-21 months corrected gestational age in preterm infants

Studies have reported prenatal acetaminophen exposure is associated with abnormal neurodevelopment. There is limited and conflicting data on neurodevelopmental outcomes following postnatal acetaminophen exposure. Our objective was to investigate the neurodevelopmental outcomes of preterm infants < 29 weeks gestation postnatally exposed to acetaminophen. Retrospective cohort study of infants born between 2008 and 2017 at a tertiary care perinatal center. Exclusion criteria included chromosomal disorders, major congenital abnormalities, and congenital infections. The primary outcome was a composite score of <85 on the cognitive, language, or motor components of the Bayley Scales of Infant and Toddler Development, 3rd edition, assessed at 18 to 21 months corrected gestational age. Multivariate logistic regression was used to assess confounders. Of the 945 infants included in the study, 120 were in the acetaminophen group. There was no difference in any of Bayley-III cognitive, language or motor composite scores of < 85 between the two groups for postnatal acetaminophen exposure, adjusted odds ratios (aORs) 1.03, 95% CI 0.60-1.78, or days of acetaminophen use, aORs 1.10, 95% CI 0.93-1.29. There was no difference in neurodevelopmental outcome between the acetaminophen exposed and non-exposed groups. Our results need validation in larger cohorts. Animal research and cohort studies have suggested that prenatal acetaminophen exposure may be associated with an elevated risk of neurobehavioral abnormalities. However, there is limited and conflicting research on the impact of postnatal acetaminophen on neurodevelopment. The results of this study suggest that postnatal acetaminophen does not negatively impact neurodevelopment at 18 to 21 months in preterm infants born at <29 weeks gestational age. While these results need validation in larger and more longitudinal studies, this study provides reassurance for the use of postnatal acetaminophen in extremely preterm infants.

KEAP1 polymorphisms and neurodevelopmental outcomes in children with exposure to prenatal MeHg from the Seychelles Child Development Study Nutrition Cohort 2

BackgroundHumans differ in the metabolism of the neurotoxicant methyl mercury (MeHg). This variation may be partially due to variation in genes encoding the transcription factor Nuclear factor E2-related factor 2 (NRF2) and its negative regulator Kelch-like ECH-Associated Protein 1 (KEAP1), which regulate glutathione and related transporter and antioxidant proteins that play a role in the metabolism and neurotoxicity of MeHg. AimTo elucidate a potential risk from genetic variation in NFE2L2 (encoding NRF2) and KEAP1 toward prenatal mercury exposure and child neurodevelopmental outcomes at 20 months and 7 years of age in a population with variable prenatal exposure to MeHg from maternal fish consumption. Material and MethodsNutrition Cohort 2 is a mother–child cohort in the Republic of Seychelles. Children were genotyped for NFE2L2 (rs2364723, rs13001694) and KEAP1 (rs8113472, rs9676881) polymorphisms (N = 1285 after removing siblings). Total mercury (Hg) was measured in cord blood as a biomarker for prenatal MeHg exposure. Child neurodevelopmental outcomes included the Bayley Scales of Infant Development II administered at 20 months of age, and outcomes across multiple neurodevelopmental domains from 14 tests administered in children and 3 instruments completed by parents when children were 7 years of age. ResultsThe mean cord blood MeHg concentration was 34 (95% CI 11, 75) µg/L. None of the four polymorphisms had a significant association (p < 0.05) with either cord MeHg or neurodevelopmental test results at 20 months. There were no significant associations between either NFE2L2 polymorphism and any developmental test scores. At 7 years, children carrying KEAP1 rs8113472 CA showed significantly worse performance on psychomotor function than children with the CC variant (finger tapping, dominant hand: β − 1.19, SE 0.34; finger tapping, non-dominant hand: β − 0.92, SE 0.31) and worse social communication (SCQ Total: β 0.65, SE 0.27). Children carrying rs8113472 AA, versus children with CC, showed significantly better performance on social communication (SRS Total: β − 8.88, SE 3.60). Children carrying KEAP1 rs9676881 AG, versus children with GG, showed significantly worse performance on psychomotor function (trailmaking A time: β 8.66, SE 3.37) and cognition (KBIT Matrices: β − 0.96, SE 0.36). ConclusionNo associations between NFE2L2 and KEAP1 polymorphisms and MeHg concentration were identified. However, at 7 years, KEAP1 polymorphisms were associated with differences in neurodevelopmental outcomes in children from a population with high fish intake.

Tocolysis after preterm prelabor rupture of membranes and 5-year outcomes: a population-based cohort study

The administration of tocolytics after preterm prelabor rupture of membranes remains a controversial practice. In theory, reducing uterine contractility should delay delivery and allow for optimal antenatal management, thereby reducing the risks for prematurity and adverse consequences over the life course. However, tocolysis may be associated with neonatal death or long-term adverse neurodevelopmental outcomes, mainly related to prolonged fetal exposure to intrauterine infection or inflammation. In a previous study, we showed that tocolysis administration was not associated with short-term benefits. There are currently no data available to evaluate the impact of tocolysis on neurodevelopmental outcomes in school-aged children born prematurely in this clinical setting. This study aimed to investigate whether tocolysis administered after preterm prelabor rupture of membranes is associated with neurodevelopmental outcomes at 5.5 years of age. We used data from a prospective, population-based cohort study of preterm births recruited in 2011 (referred to as the EPIPAGE-2 study) and for whom the results of a comprehensive medical and neurodevelopmental assessment of the infant at age 5.5 years were available. We included pregnant individuals with preterm prelabor rupture of membranes at 24 to 32 weeks' gestation in singleton pregnancies with a live fetus at the time of rupture, birth at 24 to 34 weeks' gestation, and participation of the infant in an assessment at 5.5 years of age. Exposure was the administration of any tocolytic treatment after preterm prelabor rupture of membranes. The main outcome was survival without moderate to severe neurodevelopmental disabilities at 5.5 years of age. Secondary outcomes included survival without any neurodevelopmental disabilities, cerebral palsy, full-scale intelligence quotient, developmental coordination disorders, and behavioral difficulties. A propensity-score analysis was used to minimize the indication bias in the estimation of the treatment effect on outcomes. Overall, 596 of 803 pregnant individuals (73.4%) received tocolytics after preterm prelabor rupture of membranes. At the 5.5-year follow-up, 82.7% and 82.5% of the children in the tocolysis and no tocolysis groups, respectively, were alive without moderate to severe neurodevelopmental disabilities; 52.7% and 51.1%, respectively, were alive without any neurodevelopmental disabilities. After applying multiple imputations and inverse probability of treatment weighting, we found no association between the exposure to tocolytics and survival without moderate to severe neurodevelopmental disabilities (odds ratio, 0.93; 95% confidence interval, 0.55-1.60), survival without any neurodevelopmental disabilities (odds ratio, 1.02; 95% confidence interval, 0.65-1.61), or any of the other outcomes. There was no difference in the neurodevelopmental outcomes at age 5.5 years among children with and without antenatal exposure to tocolysis after preterm prelabor rupture of membranes. To date, the health benefits of tocolytics remain unproven, both in the short- and long-term.

Outcomes at 7 Years of Age of Former Very Preterm Neonates with Repeated Surfactant Treatment for Prolonged Respiratory Distress in the Neonatal Period.

This study aimed at evaluating the 7-year outcomes of 118 very preterm newborns (VPNs, gestational age = 26 ± 1.4 w) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS), requiring ventilation for 14 ± 2 days post-natal age (PNA). A repeated instillation of 200 mg/kg poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but the SURF infants needed less re-hospitalization than the controls for respiratory problems at 1- and 2-year PNA. There was no growth difference at 7.1 ± 0.3 years between 41 SURF infants and 36 controls (80% of the eligible children), and 7.9% SURF infants vs. 28.6% controls presented asthma (p = 0.021). The children underwent cognitive assessment (WISC IV) and pulmonary function testing (PFT), measuring their spirometry, lung volume, and airway resistance. The spirometry measures showed differences (p < 0.05) between the SURF infants and the controls (mean ± standard deviation (median z-score)) for FEV1 (L/s) (1.188 ± 0.690(-0.803) vs. 1.080 ± 0.243 (-1.446)); FEV1 after betamimetics (1.244 ± 0.183(-0.525) vs. 1.091 ± 0.20(-1.342)); FVC (L) (1.402 ± 0.217 (-0.406) vs. 1.265 ± 0.267 (-1.141)), and FVC after betamimetics (1.452 ± 0.237 (-0.241) vs. 1.279 ± 0.264 (-1.020)). PFT showed no differences in the volumes or airway resistance. The global IQ median (interquartile range) was 89 (82:99) vs. 89 (76:98), with 61% of the children >85 in both groups. Repeated surfactant treatment in VPNs presenting severe RDS led to the attenuation of early lung injuries, with an impact on long-term pulmonary sequelae, without differences in neurodevelopmental outcomes.

62 Neurodevelopmental Outcomes Following Preterm Prelabour Rupture of Membranes Versus Spontaneous Preterm Birth among Infants Born at &amp;lt;29 Weeks of Gestation

Abstract Background Few studies examine differences in neurodevelopmental outcomes between spontaneous preterm birth (sPTB) and those additionally complicated by preterm prelabour rupture of membranes (PPROM). Objectives This prospective cohort study from the Canadian Neonatal Follow-Up Network compared mortality and neurodevelopmental outcomes (Bayley-III scores &amp;lt;70 and &amp;lt;85, hearing/vision loss and cerebral palsy) at 18-24 months corrected age following PPROM versus sPTB among infants &amp;lt;29 weeks of gestation born between 2010-2018. Secondarily, this study compared neurodevelopmental outcomes between those with PPROM lasting 1-7 days, &amp;gt;7days, and sPTB. Design/Methods Differences in maternal-infant characteristics and neonatal morbidities were assessed by Chi-square and Student t-tests. Raw and adjusted odds ratios (OR) with 95% CIs were calculated to compare outcomes. Results Study population included 4271 children, 1503 (35%) PPROM, 2768 (65%) sPTB. The sPTB group had younger mothers, and a higher proportion of maternal nulliparity, maternal hypertension, and outborn infants. In the neonatal period, PPROM neonates had lower rates of ROP and severe neurologic injury. Raw OR comparing PPROM vs. sPTB showed decreased mortality (OR: 0.75[0.65, 0.87]), and decreased total cerebral palsy rates (OR: 0.57 [0.41, 0.80]) (Table 1). Conclusion Among Canadian infants born at &amp;lt;29 weeks of gestation, PPROM lasting 1-7 days associated with decreased mortality and decreased rates of non-ambulatory cerebral palsy at 18-24 months corrected age when compared to sPTB. Such findings may be explained by heightened maternal/fetal care in PPROM cases. RESULTS Table1 Comparisons of the neurodevelopmental outcomes between exposure groups.

Neurodevelopmental Outcome of Very Low Birth Weight Infants in the Northern District of Israel: A Cross-Sectional Study.

Currently, no local database in Israel collects neurodevelopmental outcomes of very low birth weight (VLBW) preterm infants. We investigated neurodevelopmental outcomes in one district of the largest healthcare organization in Israel. A cross-sectional study including all VLBW (<1500 g) preterm infants born between 1 January 2006 and 31 December 2016 who were followed in any of seven child development centers in Israel's Northern District. Data were retrospectively collected from the computerized medical record database. Out of 436 participants, 55.1% had normal developmental outcomes. A total of 8.9% had cerebral palsy (CP), 12.2% had a global developmental delay (GDD), and 33.4% had a language delay. Out of the extremely preterm infants (n = 109), 20.2% had CP, 22.0% had GDD, and 44.9% had language delay. We found a statistically significant higher rate of abnormal neurodevelopment outcomes in non-Jews compared to Jews (57% vs. 37.8%, respectively, p < 0.0001). We found a relatively high overall rate of CP in our local population and a significant difference in neurodevelopmental outcomes between Jews and non-Jews. This study emphasizes the need for an expanded and detailed national database collecting post-discharge outcomes, as well as an assessment of national healthcare resource allocation and inequalities in preterm infants' post-discharge care.

Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study

The neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years. The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicentre cohort study at 20 specialty epilepsy centres in the USA. We have investigated pregnancy outcomes in women (aged 14-45 years) with and without epilepsy who were enrolled during pregnancy (≤20 weeks' gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing. Between Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n=284; adjusted least-square mean 102·7, 95% CI 101·4 to 103·9) versus those without epilepsy (n=87; 102·3, 99·8 to 104·7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child's sex, and child's ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n=258; adjusted parameter estimate -2·9, 95% CI -6·7 to 1·0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication. We found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasise the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects. National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute of Child Health and Development.

EBNEO commentary: Early amino acids in extremely preterm infants and neurodisability at 2 years.

Preterm infants require nutritional support immediately after birth to prevent catabolism and support normal growth, often in the setting of increased energy requirements due to postnatal environmental conditions and critical illness. Observational studies in preterm infants have shown that there is a positive association between protein intake in the first month of life, short-term growth outcomes at NICU discharge1 and long-term neurodevelopmental outcomes.2, 3 However, a meta-analysis of randomised controlled trials found that preterm infants with higher intake of parenteral amino acids demonstrated improved postnatal growth but did not show improvement in neurodevelopmental outcomes compared with infants who received lower intake of amino acids.4 Despite evidence for the benefit of early protein delivery on growth in the preterm infant, there are still many questions about the optimal dosing regimen of parenteral amino acids, including starting dose, maximal intake dose, timing and speed of increase in delivery. For example, there have been small, randomised controlled trials that have raised concerns for adverse effects from high-dose (>3 g/kg/day) parenteral amino acids advanced rapidly in the first week of life, including smaller head circumference at NICU discharge5, 6 and reduced growth through the first 2 years of life.7 In this multicenter, double-blind, randomised control trial, extremely low-birth-weight infants who received higher parenteral amino acid intake in the first 5 days of life (3.4 ± 0.6 vs 2.6 ± 0.6 g/kg/day) did not have improved survival without neurodevelopmental impairment at 2 years of corrected gestational age. In fact, higher amino acid intake was associated with higher rates of moderate-to-severe neurodisability than neonates who received lower amino acid intake. Although increased protein intake was associated with improved growth in the first month of life, there were no differences in growth at 2 years old. This study was adequately powered and is the largest study to date to test for differences in neurodevelopmental outcome as a result of amino acid dose in the first week of life. The investigators provided a difference of 0.8 g/kg per day of protein between groups, thus isolating its effect over other components of parenteral nutrition. Limitations included that additional amino acids were only administered for 5 days; it is unclear whether prolonged supplementation would change outcomes. Outcomes at 2 years old weakly predict outcomes in school-aged children. Plasma amino acid concentrations were not reported, but are critical to determine whether current paediatric amino acid solutions are adequate for preterm infants. In summary, increasing parenteral amino acid intake via the umbilical arterial catheter for 5 days after birth does not improve neurodevelopmental outcomes or growth at 2 years in preterm infants; higher protein intake may be associated with worse neurodevelopmental outcomes. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommends that preterm infants should not receive more than 3.5 g/kg/day of parenteral amino acids unless administered in a clinical trial.8 This study supports that recommendation; clinicians should be cautious of excessive parenteral protein administration to preterm infants especially in the first 5 days of life. URL LINK: https://ebneo.org/ebneo-commentary-early-amino-acids-and-nd-outcomes/ None. None.

Hydrocephalus and school-age neurodevelopmental outcomes in the management of myelomeningocele prenatal surgery trial: a secondary analysis.

The purpose of this secondary analysis was to assess the role of hydrocephalus on neurodevelopmental outcomes in a cohort of school-age children enrolled in the Management of Myelomeningocele Study (MOMS) clinical trial. The sample analyzed in this report consisted of 150 of 183 children aged 5-10 years (mean ± SD 7 years 8 months ± 1.2) who were randomly assigned between 20 and 26 weeks of gestational age to undergo either prenatal or postnatal surgery and were enrolled in the school-age follow-up study of MOMS. These 150 children (76 prenatal and 74 postnatal) were placed into three groups: no hydrocephalus (n = 22), unshunted hydrocephalus (n = 31), and shunted hydrocephalus (n = 97). Comparisons were made on the basis of measures of adaptive behavior, intelligence, reading and math skills, verbal and nonverbal memory, fine motor dexterity, and sensorimotor skills. Parent ratings of executive functions, inattention, and hyperactivity-impulsivity were also compared. There were no statistically significant differences in neurodevelopmental outcomes between the groups with no hydrocephalus and unshunted hydrocephalus, or between the prenatal and postnatal groups with shunted hydrocephalus, so these groups were combined (no/unshunted vs shunted hydrocephalus). The no/unshunted group showed significantly better performance (p < 0.05) than the shunted group in terms of adaptive behavior, intelligence, verbal and nonverbal memory, reading skills (but not math), fine motor dexterity, sensorimotor skills (but not visual-motor integration), and inattention (but not hyperactivity-impulsivity or executive function ratings). An assessment of the prenatal surgery group showed that the combined no/unshunted group performed better than the shunted group in terms of adaptive behavior and verbal memory skills. Both the prenatal and postnatal surgery subgroups with unshunted hydrocephalus performed as well as the group with no hydrocephalus despite significantly enlarged ventricles. Although the primary assessment of school-age outcomes in the MOMS clinical trial did not show better adaptive behavior and cognitive skills in the prenatal group, hydrocephalus and shunting were associated with poorer neurodevelopmental outcomes (both prenatal and postnatal groups). Disease severity and dynamic changes in hydrocephalus status may be the primary factors in the need for shunting and a major determinant of adaptive behavior and cognitive outcomes after prenatal surgery.

NEURODEVELOPMENTAL OUTCOMES AFTER ANTI-VEGF TREATMENT FOR RETINOPATHY OF PREMATURITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: The objective of this study was to assess the neurodevelopmental outcomes in preterm infants who have undergone intravitreal anti-vascular endothelial growth factor (anti-VEGF), either as monotherapy or in combination with laser therapy, for treatment of retinopathy of prematurity (ROP). Secondary, efficacy of anti-VEGF was also evaluated.&#x0D; Methods: Literature search was conducted using 7 online databases (CENTRAL, PubMed, ScienceDirect, SCOPUS, EBSCO, ProQuest, and JSTOR). Studies were selected based on the established inclusion and exclusion criteria. Primary outcomes were neurodevelopmental impairment (NDI), severe NDI (sNDI), neurodevelopmental scores, and cerebral palsy (CP) incidence. Secondary outcomes included impairment and severe impairment of each domain (motor, cognitive, and language) and retreatment of ROP.&#x0D; Result: Seventeen studies were included. Random-effects model meta-analysis showed no differences were observed between anti-VEGF compared to control group in NDI (unadjusted odds ratio (uOR) 1.28; 95% confidence interval (CI) 0.85 to 1.94), sNDI (uOR 1.33; 95% CI 0.92 to 1.93), and CP outcomes . Meta-analysis showed insignificant result with lower overall scores, motor, cognitive, and language domains associated with anti-VEGF treatment. Secondary outcomes showed inferior cognitive impairment (OR 1.41; 95% CI: 1.03 to 1.92) and higher retreatment rate (OR 47.55; 95% CI: 12.35 to 183.09) in anti-VEGF group.&#x0D; Conclusion: There were no differences in neurodevelopmental outcomes between anti-VEGF and control group. Despite not causing any adverse neurodevelopmental effect, clinicians should carefully weigh the benefits and risks of anti-VEGF injection for treating infants with ROP, since it has higher retreatment rate.

Effects of 1.5-T versus 3-T magnetic resonance imaging in fetuses: is there a difference in postnatal neurodevelopmental outcome? Evaluation in a fetal population with left-sided congenital diaphragmatic hernia.

The utilization of 3-T magnetic field strength in obstetric imaging is increasingly common. It is important to ensure that magnetic resonance (MR) imaging with higher magnetic field strength is safe for the fetus. Comparison of neurodevelopmental outcome in neonates undergoing prenatal MR imaging with 1.5-T versus 3-T is of interest but has not yet been examined. We hypothesized no clinically meaningful difference in neurodevelopmental outcome between fetuses undergoing 1.5-T versus 3-T fetal MR imaging. As imaging a normal fetus for research purposes is illegal in Pennsylvania, this study was conducted in a population of fetuses with left congenital diaphragmatic hernia (left-CDH). A retrospective review of neurodevelopmental outcome of fetuses with left-CDH scanned at 1.5-T (n=75) versus 3-T (n=25) magnetic field strength between July of 2012 and December of 2019 was performed. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development, 3rd Edition (BSID-III). There were no statistical differences in median age of assessment (1.5-T: 18 [12, 25] versus 3-T: 21 [11, 26], P=0.79), in mean BSID-III cognitive (1.5-T: 91 ± 14 versus 3-T: 90 ± 16, P=0.82), language (1.5-T: 92 ± 20 versus 3-T: 91 ± 20, P=0.91), and motor composite (1.5-T: 89 ± 15 versus 3-T: 87 ± 18, P=0.59) scores, subscales scores (for all, P>0.50), or in risk of abnormal neuromuscular exam (P=0.29) between neonates with left-CDH undergoing a 1.5-T versus 3-T MR imaging during fetal life. Additionally, the distribution of patients with average, mildly delayed, and severely delayed BSID-III scores was similar between the two groups (for all, P>0.50). The overall distribution of the composite scores in this CDH population was similar to the general population independent of exposure to 1.5-T or 3-T fetal MR imaging. Two 3-T patients (8%) and five 1.5-T patients (7%) scored within the significant delayed range for all BSID-III domains. Subjects with lower observed-to-expected fetal lung volume (O/E FLV) and postnatal need for ECMO had lower cognitive, language, motor, and subscales scores (for all, P<0.03) regardless of being imaged at 1.5-T versus 3-T. This preliminary study suggests that, compared to 1.5-T MR imaging, fetal exposure to 3-T MR imaging does not increase the risk of neurodevelopmental impairment in fetuses with left-CDH. Additional MR imaging studies in larger CDH cohorts and other fetal populations are needed to replicate and extend the present findings.

Automated oxygen control for very preterm infants and neurodevelopmental outcome at 2 years−a retrospective cohort study

Faster resolution of hypoxaemic or hyperoxaemic events in preterm infants may reduce long-term neurodevelopmental impairment. Automatic titration of inspiratory oxygen increases time within the oxygen saturation target range and may provide a more prompt response to hypoxic and hyperoxic events. We assessed routinely performed follow-up at 2 years of age after the implementation of automated oxygen control (AOC) as standard care and compared this with a historical cohort. Neurodevelopmental outcomes at 2 years of age were compared for infants born at 24–29 weeks gestational age before (2012–2015) and after (2015–2018) the implementation of AOC as standard of care. The primary outcome was a composite outcome of either mortality or severe neurodevelopmental impairment (NDI), and other outcomes assessed were mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and CBCL problem behaviour scores. A total of 289 infants were included in the pre-AOC epoch and 292 in the post-AOC epoch. Baseline characteristics were not significantly different. Fifty-one infants were lost to follow-up (pre-AOC 6.9% (20/289), post-implementation 10.6% (31/292). The composite outcome of mortality or severe NDI was observed in 17.9% pre-AOC (41/229) vs. 24.0% (47/196) post-AOC (p = 0.12). No significant differences were found for the secondary outcomes such as mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and problem behaviour scores, with the exception of parent-reported readmissions until the moment of follow-up which was less frequent post-AOC than pre-AOC.Conclusion: In this cohort study, the implementation of automated oxygen control in our NICU as standard of care for preterm infants led to no statistically significant difference in neurodevelopmental outcome at 2 years of age. What is Known:• Neurodevelopmental outcome is linked to hypoxemia, hyperoxaemia and choice of SpO2 target range.• Automated titration of inspired oxygen may provide a faster resolution of hypoxaemic and hyperoxaemic events.What is New: • This cohort study did not find a significant difference in neurodevelopmental outcome at two years of age after implementing automated oxygen control as standard of care.

Coronavirus Infection in Neonates: Neurodevelopmental Outcomes at 18 Months of Age.

Although most neonates with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection experience only mild disease, its impact on neurodevelopmental outcomes is unknown. This study aimed to assess the 18-month neurodevelopmental outcomes of infants who had SARS-CoV-2 infection as neonates. The authors conducted a prospective cohort study of neonates diagnosed with SARS-CoV-2 infection from June 2020 to December 2020 through nasopharyngeal coronavirus disease 2019 (COVID-19). A total of 58 neonates were identified from the Kuwait National COVID-19 Registry and enrolled. Historical controls were selected from the neonatal follow-up registry and matched in a 2 : 1 ratio based on sex and gestational age. When the subjects were 18 months of age, their neurodevelopmental outcomes were assessed by two trained assessors using the Bayley Scales of Infant and Toddler Development-3rd Edition (BSID-III). Forty children diagnosed with SARS-CoV-2 infection were included in the final analysis. The median age at infection was 18 days (range: 10-26 days). Eighteen (45%) patients were asymptomatic, 15 (37.5%) had a sepsis-like presentation, 5 (12.5%) exhibited respiratory distress, and 2 (5%) had a multisystem inflammatory syndrome in children (MIS-C)-like presentation. At the 18 months follow-up, only one child showed a severe developmental delay and one child had a language delay. BSID-III outcomes did not differ significantly between the SARS-CoV-2-infected and control groups. There was no difference in neurodevelopmental outcomes at 18 months in children infected with SARS-CoV-2 compared with controls, although longer neurodevelopmental follow-up studies are required.

Management of Anti-Seizure Medications during Pregnancy: Advancements in The Past Decade.

Management of seizures often involves continuous medication use throughout a patient's life, including when a patient is pregnant. The physiological changes during pregnancy can lead to altered drug exposure to anti-seizure medications, increasing patient response variability. In addition, subtherapeutic anti-seizure medication concentrations in the mother may increase seizure frequency, raising the risk of miscarriage and preterm labor. On the other hand, drug exposure increases can lead to differences in neurodevelopmental outcomes in the developing fetus. Established pregnancy registries provide insight into the teratogenicity potential of anti-seizure medication use. In addition, some anti-seizure medications are associated with an increased risk of major congenital malformations, and their use has declined over the last decade. Although newer anti-seizure medications are thought to have more favorable pharmacokinetics in general, they are not without risk, as they may undergo significant pharmacokinetic changes when an individual becomes pregnant. With known changes in metabolism and kidney function during pregnancy, therapeutic monitoring of drug concentrations helps to determine if and when doses should be changed to maintain similar seizure control as observed pre-pregnancy. This review concentrates on the results from research in the past decade (2010-2022) regarding risks of major congenital malformations, changes in prescribing patterns, and pharmacokinetics of the anti-seizure medications that are prescribed to pregnant patients with epilepsy.