Poor Neurodevelopmental Outcomes Research Articles

PCO2 values in asphyxiated infants under therapeutic hypothermia after tailored respiratory management: a retrospective cohort study.

Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants. This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system. A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117). Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

Neurodevelopment Outcomes in Very-Low-Birth-Weight Infants with Metabolic Bone Disease at 2 Years of Age.

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing <1500 g. However, there are limited reports on MBD and neurodevelopmental outcomes. This study aimed to analyze the risk factors for MBD and understand its impact on neurodevelopmental outcomes at 2 years of corrected age. Overall, 749 VLBW infants weighing <1350 g at birth were enrolled. Exclusion criteria were major congenital abnormalities, chromosomal abnormalities, and loss of follow-up on the Bayley Scales of Infant Development, Third Edition (BSID-III) test at 24 months of corrected age. Infants were retrospectively assessed by a trained case manager using the BSID-III test at 6, 12, and 24 months old. Infants were categorized as with or without MBD according to radiographic signs. Of those enrolled, 97 VLBW infants were diagnosed with MBD, compared to 362 VLBW infants without MBD. The proportion of infants that completed three follow-ups was 86%. At the assessment at 2 years of age, infants with MBD had lower and more significant differences in motor, language, and cognitive composites. MBD is associated with poor neurodevelopmental outcomes in cognitive, motor, and language composites for VLBW infants at 24 months of corrected age.

Neonatal hypoglycemia and neurodevelopmental outcomes: Yesterday, today, tomorrow.

Neonatal hypoglycemia is a major source of concern for pediatricians since it has commonly been related to poor neurodevelopmental outcomes. Diagnosis is challenging, considering the different operational thresholds provided by each guideline. Screening of infants at risk plays a crucial role, considering that most hypoglycemic infants show no clinical signs. New opportunities for prevention and treatment are provided by the use of oral dextrose gel. Continuous glucose monitoring systems could be a feasible tool in the next future. Furthermore, there is still limited evidence to underpin the current clinical practice of administering, in case of hypoglycemia, an intravenous "mini-bolus" of 10% dextrose before starting a continuous dextrose infusion. This brief review provides an overview of the latest advances in this field and neurodevelopmental outcomes according to different approaches. Conclusion:To adequately define if a more permissive approach is risk-free for neurodevelopmental outcomes, more researchon continuous glucose monitoring and long-term follow-up is still needed. What is Known: •Neonatal hypoglycemia (NH) is a well-known cause of brain injury that could be prevented to avoidneurodevelopmental impairment. • Diagnosis is challenging, considering the different suggested operational thresholds for NH (<36, <40, <45, <47or <50 mg/dl). What is New: •A 36 mg/dl threshold seems to be not associated with a worse psychomotor development at 18 months of lifewhen compared to the "traditional" threshold (47 mg/dl). •Further studies on long-term neurodevelopmental outcomes are required before suggesting a more permissivemanagement of NH.

Neurodevelopmental outcomes in congenital heart disease: usefulness of biomarkers of brain injury

IntroductionAt present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. MethodsProspective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: 1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; 2) clinical and laboratory data from the immediate postnatal and perioperative periods; 3) treatments and complications; 4) neurodevelopment (Bayley-III scale) at age 2 years. Resultsthe study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. Conclusionschildren with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer followups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Predictors of poor neurodevelopmental outcomes in neonates with clinically observed seizures: A prospective observational study in a tertiary care hospital of Bangladesh

Neonatal seizures can lead to long-term neurodevelopmental problems. This study aims to identify predictors of poor developmental outcomes in neonates with seizures to aid in early intervention and referral for follow-up and rehabilitation.This observational study was conducted in the Department of Neonatology and Institute of Paediatric Neurodisorder and Autism, Bangabandhu Sheikh Mujib Medical University. Among 75 study cases of neonatal seizure, 23 died, and 46 were followed-up at 6 and 9 months after discharge. EEGs were performed on every patient. A comprehensive neurological examination and developmental evaluation were performed using Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III).Three-fourths of neonates were born at term (76.1 %), and over half were male (56.5 %). The majority were appropriate for gestational age (79.7 %) and had an average birth weight of 2607 ± 696 g (±SD). Over half of the neonates (52.2 %) had adverse neurodevelopmental outcomes, with global developmental delay being the most common. Recurrent seizures, the number of anticonvulsants needed to control seizures, and abnormal Electroencephalograms were identified as independent predictors of adverse neurodevelopmental outcomes.The study highlights the need for early referral for follow-up and rehabilitation of neonates with seizures having abnormal electroencephalograms, recurrent seizures and requiring more anticonvulsants to control seizures.

Maltodextrin Use in Persistent Neonatal Hypoglycemia; Audit Report of a Single Center Experience

Background: Neonatal hypoglycemia is known to cause significant neuronal damage and poor neurodevelopmental outcomes. Consensus guidelines are lacking for the management of persistent neonatal hypoglycemia and hyperinsulinism which often requires high concentrations of dextrose and medications. Although used in the pediatric population with persistent hypoglycemia, only a few case reports are published regarding the use of Maltodextrin supplementation in persistent neonatal hypoglycemia due to transient hyperinsulinism. Objective: To audit the use of Maltodextrins in the management of persistent neonatal hypoglycemia due to transient hyperinsulinism in neonates. Audit design: A retrospective chart review (CERNER electronic data) of all cases with persistent neonatal hypoglycemia who received Maltodextrin supplementation for a period of 3½ years between July 2018 and December 2021. Results: A total of 18 neonates received Maltodextrin supplementation for neonatal hypoglycemia during the audit period. 16/18 (89%) neonates who received Maltodextrin supplementation were weaned off from intravenous dextrose within 1 week without major side effects or severe rebound hypoglycemia. Two out of 18 babies who received Maltodextrin needed Diazoxide supplementation for persistent hypoglycemia. Conclusion: The results of our audit are promising, yet further research and randomized controlled studies are needed to systematically evaluate the findings of this audit regarding Maltodextrin supplementation for the management of neonatal hypoglycemia with transient hyperinsulinism.

A case series of agenesis of the corpus callosum in children - Clinical and neuroimaging correlation with aspects of neuropathophysiology

The corpus callosum is the largest connective fiber between two hemispheres and a crucial structure for the integrated cerebral function of the normal brain. The study of agenesis of the corpus callosum (ACC) develops insights into neurodevelopmental delays and autism in children. This is a case series of eight children with ACC confirmed by a neuroimaging in a teaching hospital. The clinico-neuroradiological profile of ACC were studied retrospectively and reviewed clinical correlation with neuroradioimaging in the light of neuropathophysiology knowledge.The study group was appeared as nonsyndromic. Every subject had a normal chromosomal study by karyotyping. These ACC patients neither had a specific recognizable syndrome nor the constellation of malformations are indicative of a disorder. The mean age of subjects was 21.3 months, and no predilection for gender. The global developmental delay was the most common presentation found in seven ACC (87.5%) children. The second commonest, four ACC (50%) patients, was seizure. Two ACC (25%) had colpocephaly. Five ACC children (62.5%) had somatic anomalies; four ACC (50%) patients had cardiac defects.ACC children present a poor neurodevelopmental outcome. The extracallosal brain anomaly determines a worse neurological prognosis in nonsyndromic ACC. Grey matter heterotopia in neuroimaging was associated with seizure in ACC children. However, colpocephaly along with ACC may present with normal neurodevelopment. Hence, ACC in neuroimaging may have not predicted the final neurological outcome.ACC children with normal karyotyping may have somatic malformations. Moreover, echocardiography can be considered an initial routine screening in nonsyndromic ACC children.

Examining the relationship of acetaminophen use during pregnancy with early language development in children

BackgroundAcetaminophen is the only analgesic considered safe for use throughout pregnancy. Recent studies suggest that use during pregnancy may be associated with poorer neurodevelopmental outcomes in children, but few have examined language development.MethodsThe Illinois Kids Development Study is a prospective birth cohort in east-central Illinois. Between December 2013 and March 2020, 532 newborns were enrolled and had exposure data available. Participants reported the number of times they took acetaminophen six times across pregnancy. Language data were collected at 26.5–28.5 months using the MacArthur-Bates Communicative Development Inventories (CDI; n = 298), and 36–38 months using the Speech and Language Assessment Scale (SLAS; n = 254).ResultsTaking more acetaminophen during the second or third trimester was associated with marginally smaller vocabularies and shorter utterance length (M3L) at 26.5–28.5 months. More acetaminophen use during the third trimester was also associated with increased odds of M3L scores ≤25th percentile in male children. More use during the second or third trimester was associated with lower SLAS scores at 36–38 months. Third trimester use was specifically related to lower SLAS scores in male children.ConclusionsHigher prenatal acetaminophen use during pregnancy may be associated with poorer early language development.ImpactTaking more acetaminophen during pregnancy, particularly during the second and third trimesters, was associated with poorer scores on measures of language development when children were 26.5–28.5 and 36–38 months of age.Only male children had lower scores in analyses stratified by child sex.To our knowledge, this is the first study that has used a standardized measure of language development to assess the potential impact of prenatal exposure to acetaminophen on language development.This study adds to the growing body of literature suggesting that the potential impact of acetaminophen use during pregnancy on fetal neurodevelopment should be carefully evaluated.

Neurodesarrollo a los 2 años en cardiopatía congénita: utilidad pronóstica de los marcadores de daño cerebral

IntroductionAt present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. MethodsProspective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. ResultsThe study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. ConclusionsChildren with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer followups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Brain injury and neurodevelopmental outcomes in children undergoing surgery for congenital heart disease

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

Postischemic Infusion of Apigenin Reduces Seizure Burden in Preterm Fetal Sheep

Seizures are common in preterm newborns and are associated with poor neurodevelopmental outcomes. Current anticonvulsants have poor efficacy, and many have been associated with upregulation of apoptosis in the developing brain. Apigenin, a natural bioactive flavonoid, is a potent inhibitor of hyaluronidase and reduces seizures in adult animal models. However, its impact on perinatal seizures is unclear. In the present study, we examined the effect of apigenin and S3, a synthetic, selective hyaluronidase inhibitor, on seizures after cerebral ischemia in preterm fetal sheep at 0.7 gestation (98–99 days, term ~147 days). Fetuses received sham ischemia (n = 9) or ischemia induced by bilateral carotid occlusion for 25 min. Immediately after ischemia, fetuses received either a continuous infusion of vehicle (0.036% dimethyl sulfoxide, n = 8) or apigenin (50 µM, n = 6). In a pilot study, we also tested infusion of S3 (2 µM, n = 3). Fetuses were monitored continuously for 72 h after ischemia. Infusion of apigenin or S3 were both associated with reduced numbers of animals with seizures, total seizure time, and mean seizure burden. S3 was also associated with a reduction in the total number of seizures over the 72 h recovery period. In animals that developed seizures, apigenin was associated with earlier cessation of seizures. However, apigenin or S3 treatment did not alter recovery of electroencephalographic power or spectral edge frequency. These data support that targeting brain hyaluronidase activity with apigenin or S3 may be an effective strategy to reduce perinatal seizures following ischemia. Further studies are required to determine their effects on neurohistological outcomes.

Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: statistical analysis plan for the international, multicenter, randomized PLUSS trial

BackgroundBronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks’ gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. The primary objective of the PLUSS trial is to determine whether intratracheal budesonide mixed with surfactant increases survival free of bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age (PMA) in extremely preterm infants born before 28 weeks’ gestation.MethodsAn international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks’ postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks’ PMA), and potential systemic side effects of corticosteroids. Longer-term outcomes will be published separately, and include cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity).Statistical analysis planA sample size of 1038 infants (519 in each group) is required to provide 90% power to detect a relative increase in survival free of BPD of 20% (an absolute increase of 10%), from the anticipated event rate of 50% in the control arm to 60% in the intervention (budesonide) arm, alpha error 0.05. To allow for up to 2% of study withdrawals or losses to follow-up, PLUSS aimed to enroll a total of 1060 infants (530 in each arm). The binary primary outcome will be reported as the number and percentage of infants who were alive without BPD at 36 weeks’ PMA for each randomization group. To estimate the difference in risk (with 95% CI), between the treatment and control arms, binary regression (a generalized linear multivariable model with an identity link function and binomial distribution) will be used. Along with the primary outcome, the individual components of the primary outcome (death, and physiological BPD at 36 weeks’ PMA), will be reported by randomization group and, again, binary regression will be used to estimate the risk difference between the two treatment groups for survival and physiological BPD at 36 weeks’ PMA.

Intrauterine Exposure to Antidepressants or Maternal Depressive Symptoms and Offspring Brain White Matter Trajectories From Late Childhood to Adolescence

BackgroundDuring pregnancy, both selective serotonin reuptake inhibitor (SSRI) exposure and maternal depression have been associated with poor offspring neurodevelopmental outcomes. In a population-based cohort, we investigated the association between intrauterine exposure to SSRIs and depressive symptoms and offspring white matter development from childhood to adolescence. MethodsSelf-reported SSRI use was verified by pharmacy records. In midpregnancy, women reported on depressive symptoms using the Brief Symptom Inventory. Using diffusion tensor imaging, offspring white matter microstructure, including whole-brain and tract-specific fractional anisotropy (FA) and mean diffusivity, was measured at 3 assessments between ages 7 to 15 years. The participants were divided into 4 groups: prenatal SSRI exposure (n = 37 with 60 scans), prenatal depression exposure (n = 229 with 367 scans), SSRI use before pregnancy (n = 72 with 95 scans), and reference (n = 2640 with 4030 scans). ResultsIntrauterine exposure to SSRIs and depressive symptoms were associated with lower FA in the whole-brain and the forceps minor at 7 years. Exposure to higher prenatal depressive symptom scores was associated with lower FA in the uncinate fasciculus, cingulum bundle, superior and inferior longitudinal fasciculi, and corticospinal tracts. From ages 7 to 15 years, children exposed to prenatal depressive symptoms showed a faster increase in FA in these white matter tracts. Prenatal SSRI exposure was not related to white matter microstructure growth over and above exposure to depressive symptoms. ConclusionsThese results suggest that prenatal exposure to maternal depressive symptoms was negatively associated with white matter microstructure in childhood, but these differences attenuated during development, suggesting catch-up growth.

Neurodevelopmental Outcomes in Preterm Babies: A 12-Month Observational Study.

Background Preterm births are a significant concern worldwide due to their association with both short- and long-term morbidity. Modern neonatal intensive care techniques have improved the survival of infants born at the brink of viability. However, there remain significant challenges concerning their neurodevelopment. A considerable proportion of very low birth weight infants exhibit significant motor deficits such as cerebral palsy or cognitive, behavioral, or attention disabilities. The consequences of these impairments, particularly given their life-long nature, can be severe for the affected individuals, families, and public health resources. Consequently, timely neurodevelopmental assessment is critical in recognizing delayed development and selecting infants for neurodevelopmental stimulation. This study aimed to estimate the neurodevelopment of preterm infants, identify influencing factors, detect at-risk groups, and refer/recommend early intervention when developmental delays are observed. Methodology This prospective, observational, hospital-based study done in the department of pediatrics, Gujarat Medical Education and Research Society (GMERS) Medical College and Hospital, Gotri, Vadodara, Gujrat, India included inborn and outborn preterm neonates admitted to the Neonatal Intensive Care Unit (NICU) or the Sick Newborn Care Unit from their first day of life. The study period was from October 2020 to January 2021, and only neonates with an uncomplicated clinical course were included. Newborns were enrolled in a high-risk clinic, and follow-up appointments were scheduled at three, six, nine, and 12 months of corrected gestational age (CGA). We used the Baroda Developmental Screening Tool (BDST) to calculate the developmental quotient (DQ) at each appointment. This assessment involved parental interviews, observation of developmental milestones, and simple test demonstrations. The gathered DQ data at different ages were analyzed and compared across groups. Results Of 100 preterms enrolled, 62 preterms were followed up until 12 months of CGA. Thirteen patients out of the 62(approximately one-fifth) preterm neonates exhibited developmental delays at one year of CGA, most of whom were early preterm infants. Twenty-six patients (approximatelytwo-fifths) were delayed at three months of CGA, and thus 13 patients (half) showed catch-up growth and development. There was no statistically significant difference between the neurodevelopment of female and male infants. However, infants born to mothers with better socioeconomic status and higher education showed improved neurodevelopment. Conclusions Our study findings suggest that preterm infants discharged from the NICU exhibit poor neurodevelopmental outcomes, especially those born early preterm. This pattern indicates an inverse relationship between neurodevelopmental delay and the maturity of the neonate. Maternal education and socioeconomic status positively impacted the neurodevelopment of preterm NICU graduates. Thus, regularfollow-up (at least once every three months), early detection by a screening scale like the BDSTand intervention significantly improved neurodevelopmental outcomes.

Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California

BackgroundFluoride is ubiquitous in the United States (US); however, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. We examined specific gravity adjusted maternal urinary fluoride (MUFsg) in relation to sociodemographic variables and metal co-exposures among pregnant women in Los Angeles, California.MethodsParticipants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. There were 293 and 490 women with MUFsg measured during first and third trimesters, respectively. An intra-class correlation coefficient examined consistency of MUFsg between trimesters. Kruskal–Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Covariate adjusted linear regression examined associations of MUFsg with blood metals and specific gravity adjusted urine metals among a subsample of participants within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons.ResultsMedian (IQR) MUFsg was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, during trimesters one and three respectively. During both trimesters, MUFsg was higher among older participants, those with higher income, and White, non-Hispanic participants than Hispanic participants. MUFsg was also higher for White, non-Hispanic participants than for Black, non-Hispanic participants in trimester three, and for those with graduate training in trimester one. MUFsg was negatively associated with blood mercury in trimester one and positively associated with blood lead in trimester three. MUFsg was positively associated with various urinary metals, including antimony, barium, cadmium, cobalt, copper, lead, nickel, tin, and zinc in trimesters one and/or three.ConclusionsMUFsg levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes.

Impact of early-onset fetal growth restriction on the neurodevelopmental outcome of very preterm infants at 24 months: a retrospective cohort study

BackgroundThe association between fetal growth restriction (FGR) and childhood neurodevelopmental delay is unclear and the evidence available to the present date shows conflicting results. Our aim was to analyse the impact of early-onset FGR on the neurodevelopmental outcome at 24 months of corrected age in very preterm infants.MethodsRetrospective cohort study of very preterm infants (≤ 32 weeks’ gestation) admitted to a neonatal intensive care unit between 1 January 2013–31 December 2019. The control group comprised appropriate for gestational age (AGA) newborns. Griffiths III Mental Development Scale was performed at 24 months of corrected age.Results132 infants were included: 44 FGR and 88 AGA. Mean Global Development Quotient (GDQ) was lower for FGR infants (p = 0.004) even after adjusting for maternal and perinatal factors (βadjusted -16.703; p = 0.009). The average scores for the neurodevelopmental domains were highest for personal-social-emotional skills (107.02 ± 16.34), followed by eye/hand coordination (105.61 ± 14.20) and foundation of learning skills (102.23 ± 13.74) and were lowest for gross motor (97.90 ± 11.88) and language/communication skills (96.39 ± 18.88). FGR had a significant negative impact on all domains except for gross motor skills. After adjustment, FGR continued to have a significant adverse impact on language/communication (βadjusted -21.924; p = 0.013), eye/hand coordination (βadjusted -15.446; p = 0.015) and foundation of learning skills (βadjusted -15.211; p = 0.013).ConclusionsIn very preterm infants, FGR was associated with a significantly increased risk of poor neurodevelopmental outcome at 24 months of corrected age compared to age-matched AGA infants.

Psychiatric illness and pregnancy: A literature review

BackgroundWomen of reproductive age frequently suffer from psychiatric disorders. The risk of developing anxiety, bipolar, and depressive disorders is especially significant during the perinatal period. ObjectivesThis article aims to identify and discuss the different psychiatric conditions that might affect pregnant women and update the mother's carers about the recent and updated bidirectional relationship between psychiatric disease and adverse pregnancy outcomes, As well as the most updates in diagnostic and management strategies. MethodsA thorough analysis of the literature was conducted using database searches in EMBASE, Science Direct, Google Scholar, Scopus, and PubMed to obtain the objectives and aim of the study. ResultsThe presence of maternal mental illness during pregnancy has been linked to preterm delivery, newborn hypoglycemia, poor neurodevelopmental outcomes, and disturbed attachment. Placental anomalies, small-for-gestational-age foetuses, foetal discomfort, and stillbirth are among more undesirable perinatal outcomes. ConclusionsPregnancy-related psychiatric disorders are frequent. The outcomes for pregnant women, infants, and women's health are all improved by proper diagnosis and treatment of psychiatric problems.

Treatment of electrographic seizures versus clinical seizures in neonates: A systematic review and meta-analysis

IntroductionElectrographic seizures in neonates are commonly associated with poor neurodevelopmental outcomes. However, there is conflict in evidence whether control of electrographic seizures translate into improved neurodevelopmental outcome. We aimed to evaluate whether treating all electrographic seizures compared with treating clinical seizures leads to a better neurodevelopmental outcome at 18–24 months in neonates. MethodsWe searched four electronic databases (Medline, Cochrane Library, Embase, and Web of Science) for randomized controlled trials (RCTs) published until October 31, 2022. We included RCTs comparing the treatment of electrographic seizures with clinical seizures in neonates with or at risk of seizures. The Risk of Bias version 2 tool was used to assess the risk of bias. The random-effects meta-analysis was performed using RevMan 5.4 software. ResultsOf the 2872 unique records identified by the database search, five trials involving 474 infants were eligible for the review. There was no significant difference in the incidence of neurodevelopmental disability at 18–24 months. Infants in the electrographic seizure group had lower scores in the cognitive domain (2 trials, 186 participants, MD: −5.4; 95% CI:−10.3 to −0.4, I2-0%). There were no significant differences in scores in the motor and language domains, mortality, seizure burden, brain injury scores, antiseizure medication use, and post-neonatal epilepsy. ConclusionsHaving limitations of small number of trials and heterogeneity, the systematic review does not identify evidence demonstrating improved neurodevelopmental outcomes or improved survival in neonates treated for electrographic seizures versus clinical seizures.

GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice

BackgroundNeonatal hyperoxia exposure is associated with brain injury and poor neurodevelopment outcomes in preterm infants. Our previous studies in neonatal rodent models have shown that hyperoxia stimulates the brain’s inflammasome pathway, leading to the activation of gasdermin D (GSDMD), a key executor of pyroptotic inflammatory cell death. Moreover, we found pharmacological inhibition of caspase-1, which blocks GSDMD activation, attenuates hyperoxia-induced brain injury in neonatal mice. We hypothesized that GSDMD plays a pathogenic role in hyperoxia-induced neonatal brain injury and that GSDMD gene knockout (KO) will alleviate hyperoxia-induced brain injury.MethodsNewborn GSDMD knockout mice and their wildtype (WT) littermates were randomized within 24 h after birth to be exposed to room air or hyperoxia (85% O2) from postnatal days 1 to 14. Hippocampal brain inflammatory injury was assessed in brain sections by immunohistology for allograft inflammatory factor 1 (AIF1) and CD68, markers of microglial activation. Cell proliferation was evaluated by Ki-67 staining, and cell death was determined by TUNEL assay. RNA sequencing of the hippocampus was performed to identify the transcriptional effects of hyperoxia and GSDMD-KO, and qRT-PCR was performed to confirm some of the significantly regulated genes.ResultsHyperoxia-exposed WT mice had increased microglia consistent with activation, which was associated with decreased cell proliferation and increased cell death in the hippocampal area. Conversely, hyperoxia-exposed GSDMD-KO mice exhibited considerable resistance to hyperoxia as O2 exposure did not increase AIF1 + , CD68 + , or TUNEL + cell numbers or decrease cell proliferation. Hyperoxia exposure differentially regulated 258 genes in WT and only 16 in GSDMD-KO mice compared to room air-exposed WT and GSDMD-KO, respectively. Gene set enrichment analysis showed that in the WT brain, hyperoxia differentially regulated genes associated with neuronal and vascular development and differentiation, axonogenesis, glial cell differentiation, hypoxia-induced factor 1 pathway, and neuronal growth factor pathways. These changes were prevented by GSDMD-KO.ConclusionsGSDMD-KO alleviates hyperoxia-induced inflammatory injury, cell survival and death, and alterations of transcriptional gene expression of pathways involved in neuronal growth, development, and differentiation in the hippocampus of neonatal mice. This suggests that GSDMD plays a pathogenic role in preterm brain injury, and targeting GSDMD may be beneficial in preventing and treating brain injury and poor neurodevelopmental outcomes in preterm infants.

Predictors of poor neurodevelopmental outcomes of very preterm and very low birth weight infants.

Despite recent improvements, premature infants remain at high risk for long-term morbidity and poorer neurodevelopment, particularly very preterm (VP) and very low birth weight (VLBW). The aim of this study was to describe neurodevelopmental outcomes at two years and identify potential predictors of worse performance. In a retrospective cohort, a two-years' neurodevelopmental evaluation was analyzed. Multivariable regressions were used to study the association of perinatal history with neurodevelopmental outcomes. Subjects included VP and/or VLBW born at a Portuguese III-level perinatal center between 2011-2017. Milestones outcomes were assessed using the Griffiths' Mental Development Scales. One hundred seventy-seven infants were included. Two-years milestones were not achieved in 18.6% in language domain and 7.3% in motor function, 4.5% wore glasses and 1.1% auditory prosthesis/cochlear implant. Almost 30% needed intervention, 18.6% occupational therapy, 16.4% physiotherapy and 13.6% speech therapy. Griffiths' Mental Development Scales was performed in 139, with a mean global quotient of 98.3 and hearing/speech as the least quoted scale. Global development delay (GDD) was present in 14.8% and cerebral palsy in 2.8%. Multivariate analysis by logistic regression adjusted to gestational age, birth weight and confounding variables, revealed a statistically significant association between GDD and hydrocephalus with shunt/reservoir (OR:19.01), retinopathy of prematurity stage ≥2 (OR:7.86) and neonatal sepsis (OR:3.34). Consistent with recent studies, preterm are at increased risk of neurodevelopmental impairment, mainly due to GDD and language delay, rather than cerebral palsy. In this population, hydrocephalus, retinopathy of prematurity and neonatal sepsis were strongly associated with poorer outcomes. Insight into these factors is essential to refer patients for specific early intervention programs.