White Matter Injury on Early-versus-Term-Equivalent Age Brain MRI in Infants Born Preterm.

BACKGROUND AND PURPOSE: White matter injury in infants born preterm is associated with adverse neurodevelopmental outcomes, depending on the extent and location. White matter injury can be visualized with MR imaging in the initial weeks following preterm birth but is more commonly defined at term-equivalent-age MR imaging. Our aim was to see how white matter injury detection in MR imaging compares between the 2 time points. MATERIALS AND METHODS: This study compared white matter injury on early brain MR imaging (30-34 weeks' postmenstrual age) with white matter injury assessment at term-equivalent (37-42 weeks) MR imaging, using 2 previously published and standardized scoring systems, in a cohort of 30 preterm infants born at <33 weeks' gestational age. RESULTS: There was a strong association between the systematic assessments of white matter injury at the 2 time points (P = .007) and the global injury severity (P < .001). CONCLUSIONS: Although the optimal timing to undertake neuroimaging in the preterm infant remains to be determined, both early (30-34 weeks) and term-equivalent MR imaging provide valuable information on white matter injury and the risk of associated sequelae.

Multisystem inflammatory syndrome in 1.2 million children: longitudinal cohort study of risk factors.

BACKGROUND: We identified patient characteristics associated with an increased risk of developing MIS-C. METHODS: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders. RESULTS: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development. CONCLUSIONS: Children with pre-existing morbidity have a considerably elevated risk of MIS-C. IMPACT: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication.

Hospitalization for child maltreatment and other types of injury during the COVID-19 pandemic.

BACKGROUND: The possibility that child maltreatment was misclassified as unintentional injury during the COVID-19 pandemic has not been evaluated. OBJECTIVE: We assessed if child maltreatment hospitalizations changed during the pandemic, and if the change was accompanied by an increase in unintentional injuries. PARTICIPANTS AND SETTING: This study included children aged 0-4 years who were admitted for maltreatment or unintentional injuries between April 2006 and March 2021 in hospitals of Quebec, Canada. METHODS: We used interrupted time series regression to estimate the effect of the pandemic on hospitalization rates for maltreatment, compared with unintentional transport accidents, falls, and mechanical force injuries. We assessed if the change in maltreatment hospitalization was accompanied by an increase in specific types of unintentional injury. RESULTS: Hospitalizations for child maltreatment decreased from 16.3 per 100,000 (95 % CI 9.1-23.4) the year before the pandemic to 13.2 per 100,000 (95 % CI 6.7-19.7) during the first lockdown. Hospitalizations for most types of unintentional injury also decreased, but injuries due to falls involving another person increased from 9.0 to 16.5 per 100,000. Hospitalization rates for maltreatment and unintentional injury remained low during the second lockdown, but mechanical force injuries involving another person increased from 3.8 to 8.1 per 100,000. CONCLUSIONS: Hospitalizations for child maltreatment may have been misclassified as unintentional injuries involving another person during the pandemic. Children admitted for these types of unintentional injuries may benefit from closer assessment to rule out maltreatment.

Associations between neurological examination at term-equivalent age and cerebral hemodynamics and oxygen metabolism in infants born preterm.

Background: Infants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA). Methods: Preterm infants (N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA. Results: Steeper increases in CBF i (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO2i from birth to TEA were not associated with neurological examination at TEA. Conclusion: In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.

Association of Maternal and Neonatal Birth Outcomes With Subsequent Pediatric Transplants.

BACKGROUND: We identified maternal and neonatal birth characteristics that were associated with organ or tissue transplants during childhood. METHODS: We designed a retrospective cohort study of the population of children born between 2006 and 2019 in Quebec, Canada. The exposure included birth complications such as congenital anomaly, neonatal blood transfusion, and oligohydramnios. The main outcome measure was organ or tissue transplantation before 14 y of age. We categorized transplants according to type (major organs versus superficial tissues). To determine the association of birth characteristics with risk of pediatric transplant, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards models adjusted for potential confounders. RESULTS: The cohort comprised 1 038 375 children with 7 712 678 person-years of follow-up, including 436 children who had transplants before 14 y of age. Birth complications were predominantly associated with major organ transplants. Congenital anomaly was associated with heart or lung (HR, 10.41; 95% CI, 5.33-20.33) and kidney transplants (HR, 13.69; 95% CI, 7.48-25.06), compared with no anomaly. Neonatal blood transfusion was associated with all major organ transplants, compared with no transfusion. Maternal complications were not as strongly associated with the risk of childhood transplant, although oligohydramnios was associated with 16.84 times (95% CI, 8.09-35.02) the risk of kidney transplant, compared with no oligohydramnios. CONCLUSIONS: Adverse birth outcomes such as congenital anomaly, neonatal blood transfusion, and maternal oligohydramnios are associated with a greater risk of transplantation before 14 y of age. Maternal and neonatal birth outcomes may be useful predictors of transplantation.

Longitudinal risk of maternal hospitalization for mental illness following preterm birth.

BACKGROUND: Preterm birth may affect maternal mental health, yet most studies focus on postpartum mental disorders only. We explored the relationship between preterm delivery and the long-term risk of maternal hospitalization for mental illness after pregnancy. METHODS: We performed a longitudinal cohort study of 1,381,300 women who delivered between 1989 and 2021 in Quebec, Canada, and had no prior history of mental illness. The exposure was preterm birth, including extreme (<28 weeks), very (28-31 weeks), and moderate to late (32-36 weeks). The outcome was subsequent maternal hospitalization for depression, bipolar, psychotic, stress and anxiety, personality disorders, and self-harm up to 32 years later. We used adjusted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between preterm birth and mental illness hospitalization. RESULTS: Compared with term, women who delivered preterm had a higher rate of mental illness hospitalization (3.81 vs. 3.01 per 1000 person-years). Preterm birth was associated with any mental illness (HR 1.38, 95% CI 1.35-1.41), including depression (HR 1.37, 95% CI 1.32-1.41), psychotic disorders (HR 1.35, 95% CI 1.25-1.44), and stress and anxiety disorders (HR 1.42, 95% CI 1.38-1.46). Delivery at any preterm gestational age was associated with the risk of mental hospitalization, but risks were greatest around 34 weeks of gestation. Preterm birth was strongly associated with mental illness hospitalization within 2 years of pregnancy, although associations persisted throughout follow-up. CONCLUSIONS: Women who deliver preterm may be at risk of mental disorders in the short and long term.

Varying Impact of Gestational Diabetes Mellitus on Incidence of Childhood Cancers: An Age-Stratified Retrospective Cohort Study.

OBJECTIVE: We studied the association between gestational diabetes mellitus and early versus late childhood cancer. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of 1 million children born between 2006 and 2019 in Quebec, Canada. We identified children who were exposed to gestational diabetes mellitus in utero and followed them from birth up to 14 years of age to identify new-onset cancers. We estimated hazard ratios (HRs) for the association between gestational diabetes mellitus and childhood cancer using Cox proportional regression models with adjustment for covariates through inverse propensity score weights. RESULTS: A total of 83,626 children (8.2%) were exposed to gestational diabetes mellitus, and 1,702 developed cancer during 7.6 million person-years of follow-up. Children exposed to gestational diabetes mellitus had a higher risk of any cancer (HR 1.19, 95% CI 1.01-1.40), with signals present for blood cancer (HR 1.27, 95% CI 0.92-1.76) and solid tumors (HR 1.14, 95% CI 0.94-1.40). The association between gestational diabetes mellitus and cancer was strongest early in life and decreased with age. Gestational diabetes mellitus was associated with 1.47 times the risk of any cancer (95% CI 1.21-1.79), 1.44 times the risk of solid cancer (95% CI 1.12-1.87), and 1.61 times the risk of blood cancer (95% CI 1.09-2.36) in children age <2 years. Gestational diabetes mellitus was not significantly associated with blood or solid cancers after 2 years of age, and all associations disappeared after 6 years. CONCLUSIONS: Hyperglycemia may be carcinogenic in utero and may be a novel risk factor for early childhood cancer.

Congenital Heart Disease and Neurodevelopment: Clinical Manifestations, Genetics, Mechanisms, and Implications.

Children with congenital heart disease (CHD) are at increased risk of neurodevelopmental disorders (NDDs) and psychiatric conditions. These include cognitive, adaptive, motor, speech, behavioural, and executive functioning deficits, as well as autism spectrum disorder and psychiatric conditions. Structural and functional neuroimaging have demonstrated brain abnormalities in young children with CHD before undergoing surgical repair, likely as a result of an in utero developmental insult. Surgical factors do not seem to play a significant role in neurodevelopmental outcomes. Specific genetic abnormalities, particularly copy number variants, have been increasingly implicated in both CHD and NDDs. Variations in genes involved in apolipoprotein E (APOE) production, the Wnt signalling pathway, and histone modification, as well as in the 1q21.1, 16p13.1-11, and 8p23.1 genetic loci, have been associated with CHD and NDDs and are important targets for future research. Understanding these associations is important for risk stratification, disease classification, improved screening, and pharmacologic management of individuals with CHD.

Apgar Scores Are Associated with Attention-Deficit/Hyperactivity Disorder Symptom Severity.

OBJECTIVE: Adverse events during pregnancy and delivery have been linked to attention-deficit/hyperactivity disorder (ADHD). Previous studies have investigated Apgar scores, which assess the physical condition of newborns, in relation to the risk of developing ADHD. We propose to go one step further and examine if Apgar scores are associated with ADHD symptom severity in children already diagnosed with ADHD. METHOD: ADHD symptoms severity, while off medication, was compared in 2 groups of children with ADHD: those with low (≤6, n = 52) and those with higher (≥7, n = 400) Apgar scores sequentially recruited from the ADHD clinic. RESULTS: Children with low Apgar at 1 minute after birth had more severe symptoms as assessed by the externalizing scale of the Child Behaviour Checklist, the Conners' Global Index for Parents, and the DSM-IV hyperactivity symptoms count (P = 0.02, <0.01, <0.01, respectively). CONCLUSION: Low 1-minute Apgar scores are associated with a significant increase in ADHD symptom severity. These findings underline the importance of appropriate pregnancy and perinatal care.