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

Objective: To examine sex differences in neurodevelopmental outcomes and brain development from early life to 8 years in males and females born preterm.

Study Design: This was a prospective cohort study of infants born very preterm (24-32 weeks of gestation) and followed to 8 years with standardized measures of neurodevelopment. Brain magnetic resonance imaging scans were performed soon after birth, term-equivalent age, and 8 years.

Socioeconomic status moderates associations between hippocampal development and cognition in preterms.

Objective: The hippocampus plays a critical role in cognitive networks. The anterior hippocampus is vulnerable to early-life stress and socioeconomic status (SES) with alterations persisting beyond childhood. How SES modifies the relationship between early hippocampal development and cognition remains poorly understood.

Change in Volumes and Location of Preterm White Matter Injury over a Period of 15 Years.

Objective: To evaluate whether white matter injury (WMI) volumes and spatial distribution, which are important predictors of neurodevelopmental outcomes in preterm infants, have changed over a period of 15 years.

Study Design: Five hundred and twenty-eight infants born <32 weeks' gestational age from 2 sequential prospective cohorts (cohort 1: 2006 through 2012; cohort 2: 2014 through 2019) underwent early-life (median 32.7 weeks postmenstrual age) and/or term-equivalent-age MRI (median 40.

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

Background And Objectives: We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants.

Methods: A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.

Pain Exposure and Brain Connectivity in Preterm Infants.

Importance: Early-life exposure to painful procedures has been associated with altered brain maturation and neurodevelopmental outcomes in preterm infants, although sex-specific differences are largely unknown.

Objective: To examine sex-specific associations among early-life pain exposure, alterations in neonatal structural connectivity, and 18-month neurodevelopment in preterm infants.

Design, Setting, And Participants: This prospective cohort study recruited 193 very preterm infants from April 1, 2015, to April 1, 2019, across 2 tertiary neonatal intensive care units in Toronto, Canada.

Relationships between cortisol levels across early childhood and processing speed at age 4.5 years in children born very preterm.

Children born very low gestational age (VLGA, 29-32 weeks gestational age [GA]) display slower processing speed and altered hypothalamic pituitary adrenal (HPA) axis function, with greater effects in those born extremely low gestational age (ELGA; 24-28 weeks GA). We investigated trajectories of HPA axis activity as indexed by cortisol output and patterns across cognitive assessment at ages 1.5, 3 and 4.

Neurodevelopmental outcomes at 18 months of children diagnosed with CHD compared to children born very preterm.

Objective: To compare neurodevelopmental outcomes and parent behaviour ratings of children born term with CHD to children born very preterm.

Methods: A clinical research sample of 181 children (CHD [n = 81]; very preterm [≤32 weeks; n = 100]) was assessed at 18 months.

Results: Children with CHD and born very preterm did not differ on Bayley-III cognitive, language, or motor composite scores, or on expressive or receptive language, or on fine motor scaled scores.

Prenatal serotonin reuptake inhibitor antidepressant exposure, SLC6A4 genetic variations, and cortisol activity in 6-year-old children of depressed mothers: A cohort study.

Prenatal exposure to maternal depression and serotonin reuptake inhibitor (SRI) antidepressants both affect the development of the hypothalamic-pituitary-adrenal (HPA) system, possibly via the neurotransmitter serotonin (5HT). In a community cohort, we investigated the impact of two factors that shape prenatal 5HT signaling (prenatal SRI [pSRI] exposure and child SLC6A4 genotype) on HPA activity at age 6 years. Generalized estimating equation (GEE) models were used to study associations between cortisol reactivity, pSRI exposure, and child SLC6A4 genotype, controlling for maternal depression, child age, and sex (48 pSRI exposed, 74 nonexposed).

Major Surgery, Brain Injury, and Neurodevelopmental Outcomes in Very Preterm Infants.

Objectives: We determined whether (1) major surgery is associated with an increased risk for brain injury and adverse neurodevelopment and (2) brain injury modifies associations between major surgery and neurodevelopment in very preterm infants.

Methods: Prospectively enrolled infants across 3 tertiary neonatal intensive care units underwent early-life and/or term-equivalent age MRI to detect moderate-severe brain injury. Eighteen-month neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development, third edition.

Association of Neonatal Midazolam Exposure With Hippocampal Growth and Working Memory Performance in Children Born Preterm.

Background And Objectives: Early exposure to analgesics and sedatives is a key concern for later learning disorders in children. The hippocampus, a key region for learning and memory, may be selectively affected by exposure to benzodiazepines that are commonly used for sedation, particularly in the neonatal period. In this prospective cohort study, the long-term association of neonatal midazolam exposure, a widely used benzodiazepine in neonatal intensive care, with school age hippocampal growth was examined.

Cortisol levels are related to neonatal pain exposure in children born very preterm at age 18 months in two independent cohorts.

Exposure to pain-related stress from frequent invasive procedures in the neonatal intensive care unit (NICU) has been associated with altered physiological stress regulation, neurodevelopment, and behavior in children born very preterm (≤32 weeks gestation). Previously, in a cohort born 2003-2006 (Cohort 1), we found that, at 18 months corrected age (CA), children born extremely low gestational age (ELGA; 24-28 weeks) and very low gestational age (VLGA; 29-32 weeks), had higher pre-test cortisol levels and a different pattern of cortisol output across a developmental assessment involving cognitive challenge compared to children born full-term (FT; 39-41 weeks). Also, greater neonatal pain-related stress exposure among the preterm children was related to higher pre-test cortisol levels.

Preterm Neurodevelopmental Trajectories from 18 Months to 4.5 Years.

Objective: To assess the longitudinal trajectory of cognitive, language, and motor outcomes from 18 months to 4.5 years of age in children born very preterm.

Study Design: This was a prospective cohort study of 163 infants born very preterm (born 24-32 weeks of gestation) followed longitudinally and assessed with neurodevelopmental scales and magnetic resonance imaging of the brain.

Early-life exposure to analgesia and 18-month neurodevelopmental outcomes in very preterm infants.

Background: We assessed variability of analgesic use across three tertiary neonatal intensive care units (NICUs) accounting for early-life pain, quantified as number of invasive procedures. We also determined whether analgesia exposure modifies associations between early-life pain and neurodevelopment.

Methods: Multicenter prospective study of 276 very preterm infants (born <24-32 weeks' gestational age [GA]).

Associations between maternal depressive symptoms and selective serotonin reuptake inhibitor antidepressant treatment on internalising and anxiety behaviours in children: 12-year longitudinal study.

Background: Prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure is associated with increased internalising and anxious behaviours in young children; whether this continues into early adolescence is unknown. Also, it is not well established whether it is the exposure to SSRIs or the underlying maternal mood that contributes more to these associations.

Aims: To examine associations between maternal depressive symptoms, prenatal SSRI antidepressant treatment and internalising and anxiety behaviours from childhood into pre-adolescence.

Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection.

Importance: Very preterm neonates (24-32 weeks' gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population.

Objectives: To characterize the pediatric buccal epigenetic (PedBE) clock-a recently developed tool to measure biological aging-among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age.

Association of Neonatal Pain-Related Stress and Parent Interaction With Internalizing Behaviors Across 1.5, 3.0, 4.5, and 8.0 Years in Children Born Very Preterm.

Importance: Internalizing (anxiety and/or depressive) behaviors are prevalent in children born very preterm (24-32 weeks' gestation). Procedural pain-related stress in the neonatal intensive care unit (NICU) is associated with long-term internalizing problems in this population; however, whether positive parenting during toddlerhood attenuates development of internalizing behaviors across childhood is unknown.

Objective: To investigate whether neonatal pain-related stress is associated with trajectories of internalizing behaviors across 1.

Impact of Differing Language Background Exposures on Bayley-III Language Assessment in a National Cohort of Children Born Less than 29 Weeks' Gestation.

Preterm infants are at risk for adverse neurodevelopmental outcomes, especially language delay. Preterm infants < 29 weeks’ gestational age, cared for in Canadian Neonatal Follow-Up Network affiliated hospitals, were assessed between 18 to 21 months corrected age using the Bayley-III. Bayley-III Language Composite Scores were compared using univariate and multivariate analyses for children in three primary language groups: English, French and other.

MRI based radiomics enhances prediction of neurodevelopmental outcome in very preterm neonates.

To predict adverse neurodevelopmental outcome of very preterm neonates. A total of 166 preterm neonates born between 24-32 weeks' gestation underwent brain MRI early in life. Radiomics features were extracted from T1- and T2- weighted images.

Neonatal pain, thalamic development and sensory processing behaviour in children born very preterm.

Background: Altered sensory processing is commonly reported in children born very preterm (≤32 weeks' gestational age [GA]). The immature nervous system, particularly the development of connections from the thalamus to the cortex, may show enhanced vulnerability to excessive sensory stimulation, and may contribute to altered sensory processing. Our objective was to determine whether sensory processing assessed at preschool-aged in children born very preterm was predicted by neonatal procedural pain and thalamic development.

Brain Development and Maternal Behavior in Relation to Cognitive and Language Outcomes in Preterm-Born Children.

Background: Children born very preterm (≤32 weeks gestational age) show poorer cognitive and language development compared with their term-born peers. The importance of supportive maternal responses to the child's cues for promoting neurodevelopment is well established. However, little is known about whether supportive maternal behavior can buffer the association of early brain dysmaturation with cognitive and language performance.

Ventricular Volume in Infants Born Very Preterm: Relationship with Brain Maturation and Neurodevelopment at Age 4.5 Years.

Objective: To evaluate the relationship of quantitative ventricular volume with brain maturation and neurodevelopmental outcomes at age 4.5 years in children born very preterm.

Study Design: T1-weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopy were performed shortly after birth (n = 212) and at term-equivalent age (TEA) (n = 194).

Pharmacologic Analgesia and Sedation in Neonates.

Chronic pain and agitation in neonatal life impact the developing brain. Oral sweet-tasting solutions should be used judiciously to mitigate behavioral responses to mild painful procedures, keeping in mind that the long-term impact is unknown. Rapidly acting opioids should be used as part of premedication cocktails for nonemergent endotracheal intubations.

Lower Maternal Chronic Physiological Stress and Better Child Behavior at 18 Months: Follow-Up of a Cluster Randomized Trial of Neonatal Intensive Care Unit Family Integrated Care.

Objective: To assess whether Family Integrated Care (FICare) in the neonatal intensive care unit improves maternal chronic physiological stress and child behavior at 18 months of corrected age for infants born preterm.

Study Design: Follow-up of a multicenter, prospective cluster-randomized controlled trial comparing FICare and standard care of children born at <33 weeks of gestation and parents, stratified by tertiary neonatal intensive care units, across Canada. Primary outcomes at 18 months of corrected age were maternal stress hormones (cortisol, ie, hair cumulative cortisol [HCC], dehydroepiandrosterone [DHEA]) assayed from hair samples.

Preterm infant heart rate is lowered after Family Nurture Intervention in the NICU: Evidence in support of autonomic conditioning.

Background: Cardiac complications after premature birth are associated with negative long-term consequences to health. The Family Nurture Intervention (FNI) has been designed to support mother-infant parasympathetic calming sessions in the neonatal intensive care unit (NICU). FNI has shown neurodevelopmental and autonomic benefit across infant development.