Developing a practical neurodevelopmental prediction model for targeting high-risk very preterm infants during visit after NICU: a retrospective national longitudinal cohort study.

BACKGROUND: Follow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability. METHODS: We developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score < 85 at 24 months CA. We used an evolutionary-derived machine learning method (EL-NDI) to develop models and compared them to those built by lasso regression, random forest, and support vector machine. RESULTS: One thousand two hundred forty-four VPI were in the developmental set and the two validation cohorts had 763 and 1347 VPI, respectively. EL-NDI used only 4-10 variables, while the others required 29 or more variables to achieve similar performance. For models at 6 months CA, the area under the receiver operating curve (AUC) of EL-NDI were 0.76-0.81(95% CI, 0.73-0.83) for cognitive regress with 4 variables and 0.79-0.83 (95% CI, 0.76-0.86) for motor regress with 4 variables. For models at 12 months CA, the AUC of EL-NDI were 0.75-0.78 (95% CI, 0.72-0.82) for cognitive delay with 10 variables and 0.73-0.82 (95% CI, 0.72-0.85) for motor delay with 4 variables. CONCLUSIONS: Our EL-NDI demonstrated good performance using simpler, transparent, explainable models for clinical purpose. Implementing these models for VPI during follow-up visits may facilitate more informed discussions between parents and physicians and identify high-risk infants more effectively for early intervention.

Neurodevelopmental outcome in complicated twin pregnancy: prospective observational study.

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

The Quartile Levels of Thyroid-Stimulating Hormone by Newborn Screening Stratified Risks of Neurodevelopmental Impairment in Extremely Preterm Infants - A Population Cohort Study.

BACKGROUND: To evaluate whether thyroid-stimulating hormone (TSH) by newborn screening (NBS) at birth and at discharge can be surrogate markers for neurodevelopmental impairment (NDI) in extremely preterm infants. METHODS: The population cohort enrolled infants born <29 weeks' gestation in 2008 - 2020 in southern Taiwan. Infants with a maternal history of thyroid disorders and infants who required thyroxine supplementation during hospitalization were excluded. TSH levels by NBS at birth and at term-equivalent age (TEA)/discharge were respectively categorized into the lowest quartile, the interquartile range, and the highest quartile, which were correlated to NDI outcomes. RESULTS: Among 392 patients with paired TSH data, 358 (91%) were prospectively followed until corrected age 24 months. At birth, infants with lowest-quartile TSH had higher NDI risks (OR 2.3, 95% CI 1.3 - 4.1, P = 0.004) compared to infants with interquartile-range TSH. Conversely, by TEA/discharge, infants with highest-quartile TSH had increased NDI (OR 1.9, 1.0 - 3.4, P = 0.03). By paired TSH categories, infants persistently in the lowest TSH quartile (48%, aOR 4.4, 1.4 - 14.5, P = 0.01) and those with a shift from interquartile range to the highest quartile (32%, aOR 2.7, 1.0 - 7.4, P = 0.046) had increased NDI risks compared with the reference with consistent interquartile-range TSH. CONCLUSIONS: Extremely preterm infants persistently in the lowest-quartile TSH level at birth and at discharge had the highest NDI risk. TSH quartile levels by NBS may serve as a population surrogate biomarker for assessing NDI risks in infants born extremely preterm.

Effects of Implementing a Standardized Surveillance Program on Cardiac Neurodevelopmental Program Referral Completion.

Differences in surveillance methods have resulted in significant variability in referral volumes and referral completion rates across cardiac neurodevelopmental programs, with frequent barriers to referral completion including high no-show rates, lack of education, and inaccessibility for underrepresented populations. The purpose of this study was to describe implementation of a standardized surveillance program and investigate impact on referral volume and completion over a two-year period. Between fiscal years 2021 and 2022, a surveillance program was implemented which standardized assessment of neurodevelopmental risk via a checklist as well as family education and referral procedures. All patients referred to the cardiac neurodevelopmental program during these two fiscal years were included in the analysis, and patient referrals were categorized as complete or incomplete (due to physician-related or patient-related factors). Referral completion rates between fiscal years were compared using two sample Z test of proportions, while associations between referral completion and demographic/anatomical variables were completed using chi-square tests of independence. Implementation of the formal surveillance program resulted in a 66.7% increase in referral volume. Proportions of both incomplete referrals (z = 2.00, p < 0.05) and incomplete referrals due to physician-related factors (z = 4.34, p < 0.01) were significantly lower after implementation. A significant association was found after implementation between referral completion and race/ethnicity (x2 = 14.08, p < 0.01) due to a significantly high proportion of completed referrals for patients identifying as Hispanic/Latino within the overall distribution of patients. This study describes the successful implementation of a standardized surveillance program, including improvements to referral volume and completion rate. Findings also support implementation of methods that emphasize physician surveillance methods and improve accessibility for historically marginalized groups at greatest risk for disparities in access and quality of care.

Early identification of autism spectrum disorder in children with CHD attending a Cardiac Developmental Outcomes Program.

OBJECTIVE: To determine the prevalence and timing of autism spectrum disorder diagnosis in a cohort of congenital heart disease (CHD) patients receiving neurodevelopmental follow-up and identify associated risk factors. METHOD: Retrospective single-centre observational study of 361 children undergoing surgery for CHD during the first 6 months of life. Data abstracted included age at autism spectrum disorder diagnosis, child and maternal demographics, and medical history. RESULTS: Autism spectrum disorder was present in 9.1% of children with CHD, with a median age at diagnosis of 34 months and 87.9% male. Prematurity, history of post-operative extracorporeal membrane oxygenation, and seizures were higher among those with autism (p = 0.013, p = 0.023, p = 0.001, respectively). Infants with autism spectrum disorder were older at the time of surgery (54 days vs 13.5 days, p = 0.002), and infants with surgery at ≥ 30 days of age had an increased risk of autism spectrum disorder (OR 2.31; 95% CI =1.12, 4.77, p = 0.023). On multivariate logistic regression analysis, being male (OR 4.85, p = 0.005), surgery ≥ 30 days (OR 2.46, p = 0.025), extracorporeal membrane oxygenation (OR 4.91, p = 0.024), and seizures (OR 4.32, p = 0.003) remained associated with increased odds for autism spectrum disorder. Maternal age, race, ethnicity, and surgical complexity were not associated. CONCLUSIONS: Children with CHD in our cohort had more than three times the risk of autism spectrum disorder and were diagnosed at a much earlier age compared to the general population. Several factors (male, surgery at ≥ 30 days, post-operative extracorporeal membrane oxygenation, and seizures) were associated with increased odds of autism. These findings support the importance of offering neurodevelopmental follow-up after cardiac surgery in infancy.

[Prevention of prematurity's complications]. / Prévention des complications de la prématurité.

Prematurity remains a leading cause of mortality and morbidity in neonates and children. Prevention of preterm birth and of its complications is a major public health issue. From before conception to long term follow up, many health actors are engaged in this preventive strategy with the same goal : to give the best quality of life for these vulnerable young patients. We will review different preventive aspects during antenatal and perinatal period, during NICU (Neonatal Intensive Care Unit) stay and after discharge. Prevention of prematurity's complications requires a global approach including respiratory, nutritional and infectious aspects among others. Neuroprotective strategies are a key point of this global approach.

La prématurité reste une cause majeure de mortalité et morbidité néonatales et infantiles. La prévention des naissances prématurées et de leurs complications est donc un enjeu majeur de santé publique. De la période pré-conceptionnelle au suivi à long terme de ces enfants, nombreux sont les acteurs impliqués dans un même objectif : offrir la meilleure qualité de vie à ces jeunes patients vulnérables. Nous reverrons ici différents aspects préventifs en période anténatale, périnatale, lors du séjour en néonatologie et lors du suivi après la sortie. La prévention des complications de la prématurité nécessite une prise en charge globale intégrée incluant, notamment, des aspects ventilatoires, nutritionnels, infectieux, néphrologiques et métaboliques. La neuroprotection est au centre des préoccupations et guide l'ensemble de l'approche.

A secondary Outcome Analysis of a Randomized Trial Using a Mixed Lipid Emulsion Containing Fish Oil in Infants with Extremely Low Birth Weight: Cognitive and Behavioral Outcome at Preschool Age.

OBJECTIVE: To evaluate the impact of a parenteral lipid emulsion containing fish oil compared with a soybean oil based-lipid emulsion on the cognitive outcome and behavior of preschool children with extremely low birth weight. STUDY DESIGN: This was a retrospective secondary outcome analysis of a randomized controlled trial performed between June 2012 and June 2015. Infants with extremely low birth weight received either a mixed (soybean oil, medium chain triglycerides, olive oil, fish oil) or a soybean oil-based lipid emulsion for parenteral nutrition. Data from the Kaufman Assessment Battery for Children II, the Child Behavior Checklist 1.5-5, and anthropometry were collected from medical charts at 5.6 years of age. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 5 years 6 months of age, data of 153 of 206 infants (74%) were available for analysis. There were no significant differences in Kaufman Assessment Battery for Children II scores for Sequential/Gsm, Simultaneous/Gv, Learning/Glr, and Mental Processing Index (mixed lipid: median, 97.5 [IQR, 23.5]; soybean oil: median, 96 [IQR, 19.5]; P = .43) or Child Behavior Checklist 1.5-5 scores for internalizing problems, externalizing problems, or total problems (mixed lipid: median, 37 [IQR, 12.3]; soybean oil: median, 37 [IQR, 13.5]; P = .54). CONCLUSIONS: A RandomForest machine learning regression analysis did not show an effect of type of lipid emulsion on cognitive and behavioral outcome. Parenteral nutrition using a mixed lipid emulsion containing fish oil did not affect neurodevelopment and had no impact on child behavior of infants with extremely low birth weights at preschool age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.

Additional Value of 3-Month Cranial Magnetic Resonance Imaging in Infants with Neonatal Encephalopathy following Perinatal Asphyxia.

OBJECTIVE: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia. METHODS: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy. RESULTS: Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59. CONCLUSIONS: In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI.

Assisted reproductive technology and neurodevelopmental outcomes in offspring: a prospective birth cohort study in East China.

RESEARCH QUESTION: Is ART associated with adverse neurodevelopmental outcome in 12-month-old offspring compared with those conceived through natural conception? DESIGN: In this prospective cohort study, 488 infertile women undergoing ART and 1397 women with natural conception were recruited and followed until their offspring were 12 months old. The primary outcome was the neurodevelopment in the offspring. The association between exposure to ART and Gesell developmental scale scores was investigated using multiple linear regression models after adjusting for confounders. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to verify the results. RESULTS: In total, 18 (3.7%) and 40 (2.9%) children in the ART and natural conception groups, respectively, had been diagnosed with neurodevelopmental delay at 12 months of age. It was found that gross motor, adaptive behaviour, language and total development quotient scores were comparable between the groups. Following multivariate linear regression and IPTW, social behaviour development quotient scores were found to be slightly higher in the ART group than the natural conception group. Higher social behaviour development quotient scores in the ART group were also observed in the male and the singleton subgroups. CONCLUSIONS: At 12 months, offspring born after ART appeared to have similar motor, language and adaptive behaviour skills, and total development quotient scores, to those born after natural conception. However, social behaviour development in 12-month-old infants was slightly higher in those conceived using ART than in naturally conceived offspring, especially in male or singleton infants. These findings may provide new information in evaluating the potential benefits and risks of ART.

Placental fetal vascular malperfusion, neonatal neurologic morbidity, and infant neurodevelopmental outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the association of placental fetal vascular malperfusion lesions with neonatal brain injury and adverse infant neurodevelopmental outcomes. DATA SOURCES: PubMed and Medline, Scopus, and Cochrane databases were searched from inception to July 2022. STUDY ELIGIBILITY CRITERIA: We included cohort and case-control studies reporting the associations of fetal vascular malperfusion lesions with neonatal encephalopathy, perinatal stroke, intracranial hemorrhage, periventricular leukomalacia, and infant neurodevelopmental and cognitive outcomes. METHODS: Data were analyzed by including fetal vascular malperfusion lesions as an exposure variable and brain injuries or neurodevelopmental impairment as outcomes using random-effects models. The effect of moderators, such as gestational age or study type, was assessed by subgroup analysis. Study quality and risk of bias were assessed by applying the Observational Study Quality Evaluation method. RESULTS: Out of the 1115 identified articles, 26 were selected for quantitative analysis. The rates of neonatal central nervous system injury (neonatal encephalopathy or perinatal stroke) in term or near-term infants were more common among fetal vascular malperfusion cases (n=145) than among controls (n=1623) (odds ratio, 4.00; 95% confidence interval, 2.72-5.90). In premature deliveries, fetal vascular malperfusion lesions did not influence the risk of intracranial hemorrhage or periventricular leukomalacia (odds ratio, 1.40; 95% confidence interval, 0.90-2.18). Fetal vascular malperfusion-associated risk of abnormal infant neurodevelopmental outcome (314 fetal vascular malperfusion cases and 1329 controls) was modulated by gestational age being higher in term infants (odds ratio, 5.02; 95% confidence interval, 1.59-15.91) than in preterm infants (odds ratio, 1.70; 95% confidence interval, 1.13-2.56). Abnormal infant cognitive development and mental development were more common among fetal vascular malperfusion cases (n=241) than among controls (n=2477) (odds ratio, 2.14; 95% confidence interval, 1.40-3.27). The type of study (cohort vs case-control) did not influence the association between fetal vascular malperfusion and subsequent infant brain injury or abnormal neurodevelopmental outcome. CONCLUSION: The findings of cohort and case-control studies indicate a considerable association between fetal vascular malperfusion placental lesions and increased risk of brain injury in term neonates, and neurodevelopmental impairment in both term and preterm infants. A diagnosis of placental fetal vascular malperfusion should be taken into consideration by both pediatricians and neurologists during the follow-up of infants at risk of adverse neurodevelopmental outcomes.

Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3-year follow-up of multicenter trial.

OBJECTIVES: Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia. METHODS: This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed. RESULTS: Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1-9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI. CONCLUSIONS: This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Impact on postoperative, neonatal and 2-year neurodevelopmental outcomes of UA-AREDF during and after fetal spina bifida repair.

OBJECTIVE: Absent or reversed end-diastolic flow (AREDF) in the umbilical artery (UA) on Doppler is a known phenomenon during fetal interventions, such as fetal open spina bifida (OSB) repair. We aimed to evaluate the clinical importance of these Doppler findings by investigating the impact of UA-AREDF on postoperative, neonatal and 2-year neurodevelopmental outcomes. METHODS: This was a prospective study of pregnancies undergoing fetal OSB repair at the Zurich Center for Fetal Diagnosis and Therapy between 2010 and 2019. The group with UA-AREDF during or immediately after the intervention was compared to the group with normal UA Doppler. Primary endpoint was the FIGO scores of cardiotocography (CTG) 1, 2 and 6 h postoperatively and on day 1 after surgery. Secondary endpoints were the neonatal parameters and 2-year neurodevelopmental outcome assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: Data of 130 patients were analyzed. None of the fetuses had UA-AREDF before OSB repair. Normal UA Doppler was observed in 107 (82%) patients and UA-AREDF was observed in 23 (18%) during or immediately after OSB surgery. UA-AREDF was more often observed after version of the fetus (P = 0.045). Seventeen (13%) cases had absent end-diastolic flow (UA-AEDF) and six (5%) cases had reversed end-diastolic flow (UA-REDF). UA-AREDF disappeared in all 23 cases within the first day after OSB surgery. One-third of all CTGs were restricted in oscillation after surgery, but no significant difference in CTG 1, 2 and 6 h postoperatively or on the first postoperative day was found between the UA-AREDF and normal-Doppler groups (P > 0.05). Gestational age at delivery, UA pH, 5-min Apgar score and birth weight were comparable between the two groups, and there was no difference in the 2-year neurodevelopmental outcome (P > 0.05). The neonatal and 2-year neurodevelopmental outcomes also did not differ significantly between the UA-REDF and UA-AEDF groups. CONCLUSIONS: Postoperative CTG abnormalities occur and recover at a similar rate in fetuses with transitory UA-AREDF and those with normal Doppler during fetal OSB repair. UA-AREDF during fetal OSB repair did not negatively influence postnatal or 2-year neurodevelopmental outcomes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

The role of early functional neuroimaging in predicting neurodevelopmental outcomes in neonatal encephalopathy.

Reliably assessing the early neurodevelopmental outcomes in infants with neonatal encephalopathy (NE) is of utmost importance to advise parents and implement early and personalized interventions. We aimed to evaluate the accuracy of neuroimaging modalities, including functional magnetic resonance imaging (fMRI) in predicting neurodevelopmental outcomes in NE. Eighteen newborns with NE due to presumed perinatal asphyxia (PA) were included in the study, 16 of whom underwent therapeutic hypothermia. Structural magnetic resonance imaging (MRI), and fMRI during passive visual, auditory, and sensorimotor stimulation were acquired between the 10th and 14th day of age. Clinical follow-up protocol included visual and auditory evoked potentials and a detailed neurodevelopmental evaluation at 12 and 18 months of age. Infants were divided according to sensory and neurodevelopmental outcome: severe, moderate disability, or normal. Structural MRI findings were the best predictor of severe disability with an AUC close to 1.0. There were no good predictors to discriminate between moderate disability versus normal outcome. Nevertheless, structural MRI measures showed a significant correlation with the scores of neurodevelopmental assessments. During sensorimotor stimulation, the fMRI signal in the right hemisphere had an AUC of 0.9 to predict absence of cerebral palsy (CP). fMRI measures during auditory and visual stimulation did not predict sensorineural hearing loss or cerebral visual impairment. CONCLUSION: In addition to structural MRI, fMRI with sensorimotor stimulation may open the gate to improve the knowledge of neurodevelopmental/motor prognosis if proven in a larger cohort of newborns with NE. WHAT IS KNOWN: • Establishing an early, accurate neurodevelopmental prognosis in neonatal encephalopathy remains challenging. • Although structural MRI has a central role in neonatal encephalopathy, advanced MRI modalities are gradually being explored to optimize neurodevelopmental outcome knowledge. WHAT IS NEW: • Newborns who later developed cerebral palsy had a trend towards lower fMRI measures in the right sensorimotor area during sensorimotor stimulation. • These preliminary fMRI results may improve future early delineation of motor prognosis in neonatal encephalopathy.

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance.

INTRODUCTION: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI). MATERIAL AND METHODS: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment. RESULTS: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other. CONCLUSIONS: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected.

Physical health and neurodevelopmental outcome in 7-year-old children whose mothers were at risk of gestational diabetes mellitus: a follow-up of a randomized controlled trial.

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

Growth and risk of adverse neuro-developmental outcome in infants with congenital heart disease: A systematic review.

AIM: Congenital heart disease (CHD) is one of the most common birth defects affecting around 1:100 infants. In this systematic review, we aimed to determine impact of growth on neurodevelopmental outcomes of infants with CHD. METHODS: Studies that reported association of growth with developmental outcomes in infants with CHD who had surgery, were included. The search strategy was prospectively registered. Relevant studies were identified by electronic searches. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched from their earliest date to February 2022. RESULTS: Twenty studies met inclusion criteria. Choice of growth measures, developmental assessment tools and timing of assessment varied widely precluding conduct of a meta-analysis. Seventeen studies reported on infants who had cardio-pulmonary bypass. Birth weight was reported in thirteen studies and was associated with adverse outcome in nine. Head circumference at birth and later predicted developmental outcomes in five. Impaired postnatal growth was associated with adverse developmental outcome in seven studies. CONCLUSION: Growth in infants with congenital heart disease, specifically single ventricle physiology can predict adverse neurodevelopmental outcome. Included studies showed significant clinical heterogeneity. Uniformity should be agreed by various data registries with routine prospective collection of growth and developmental data.

The beneficial effect of early and prolonged kangaroo mother care on long-term neuro-developmental outcomes in low birth neonates - A cohort study.

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

Prolonged requirements for mechanical ventilation and tube feeding support predicted 18-month outcomes for neonatal encephalopathy.

AIM: We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18-month composite outcomes in infants with hypoxic-ischaemic encephalopathy treated with hypothermia. METHODS: This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age. RESULTS: Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33-0.34) and 0.60 (95% CI 0.56-0.62), negative predictive value 0.97 (95% CI 0.91-0.99) and 0.93 (95% CI 0.90-0.95) and area under the curve 0.59 (95% CI 0.54-0.64) and 0.81 (95% CI 0.77-0.85). CONCLUSION: Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18-month outcomes in newborn infants who have received therapeutic hypothermia.

Prophylactic low-dose paracetamol for ductal closure and neurodevelopmental outcome in very preterm infants.

AIM: To investigate the direct effect of prophylactic low-dose paracetamol administration for ductal closure on neurodevelopmental outcome in very preterm infants who did not receive ibuprofen or surgical ligation for treatment of a patent ductus arteriosus. METHODS: Infants < 32 gestational weeks born 10/2014-12/2018 received prophylactic paracetamol (paracetamol group, n = 216); infants born 02/2011-09/2014 did not receive prophylactic paracetamol (control group, n = 129). Psychomotor (PDI) and mental (MDI) outcome were assessed using Bayley Scales of Infant Development at 12 and 24 months corrected age. RESULTS: Our analyses showed significant differences in PDI and MDI at age 12 months (B = 7.8 (95% CI 3.90-11.63), p < 0.001 and B = 4.2 (95% CI 0.81-7.63), p = 0.016). At age 12 months, the rate of psychomotor delay was lower in the paracetamol group (OR 2.22, 95% CI 1.28-3.94, p = 0.004). There was no significant difference between the rates of mental delay at any time-point. All group differences remained significant after adjustment for potential confounders (PDI 12 months B = 7.8 (95% CI 3.77-11.34), p < 0.001, MDI 12 months B = 4.3 (95% CI 0.79-7.45), p = 0.013, PDI < 85 12 months OR 2.65 (95% CI 1.44-4.87), p = 0.002). CONCLUSION: We found no impairment of psychomotor and mental outcome at age 12 and 24 months in very preterm infants after prophylactic low-dose paracetamol administration.

The risk of autism spectrum disorder and intellectual disability but not attention deficit/hyperactivity disorder is increased in individuals with esophageal atresia.

Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability (ID) in patients with esophageal atresia (EA) is scarce. The aims of this study were to investigate the prevalence and risk of ADHD, ASD and ID in individuals with EA. Data were obtained from four longitudinal population-based registries in Sweden and analyzed using Cox proportional hazards regression. Patients with EA born in Sweden in 1973-2018 were included together with five controls for each individual with the exposure matched on sex, gestational age at birth, birth year and birth county. Individuals with chromosomal aberrations and syndromes were excluded. In total, 735 individuals with EA and 3675 controls were included. Median age at time of the study was 20 years (3-48). ASD was found in 24 (3.9%), ADHD in 34 (5.5%) and ID in 28 (4.6%) individuals with EA. Patients with EA had a 1.66 times higher risk of ASD (95% confidence interval [CI], 1.05-2.64) and a 3.62 times higher risk of ID (95% CI, 2.23-5.89) compared with controls. The risk of ADHD was not significantly increased. ADHD medication had been prescribed to 88.2% of patients with EA and ADHD and to 84.5% of controls with ADHD. Individuals with EA have a higher risk of ASD and ID than individuals without the exposure. These results are important when establishing follow-up programs for children with EA to allow timely detection and consequentially an earlier treatment and support especially before school start.