Ruth E Grunau
University of British Columbia, Pediatrics, Faculty Member
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... more
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. Given the adverse long‐term effects of neonatal pain in preterm infants and the ensuing rise in clinical concerns to appropriately manage pain in the NICU in recent years, we aimed to examine whether our findings from Cohort 1 would still be evident in an independent cohort (Cohort 2) born 2006–2011 and recruited from the same tertiary NICU in Vancouver, Canada. We also compared the cortisol patterns, clinical and socio‐demographic factors, and their interrelationships between the two cohorts. In Cohort 2, our findings using multi‐level modeling support and extend our earlier findings in Cohort 1, demonstrating that children born ELGA display higher pre‐test cortisol levels than FT. As well, greater cortisol output across assessment was related to more anxiety/depressive behaviors in children born VLGA. Importantly, children born ELGA were exposed to less neonatal pain/stress, mechanical ventilation, and morphine in Cohort 2 than Cohort 1. In both cohorts, however, cortisol levels and patterns were related to neonatal pain/stress and clinical factors (days on mechanical ventilation, overall morphine exposure). Despite less exposure to pain/stress and adverse clinical factors in Cohort 2 compared to Cohort 1, cortisol levels and patterns across cognitive challenge in preterm children at 18‐month CA were consistent across the two independent cohorts. These findings highlight that, despite improvements to neonatal care, children born extremely preterm continue to display altered HPA axis activity, which is associated with their poorer neurodevelopmental and behavioral outcomes.
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Research Interests: Endocrinology, Psychology, Cognitive Science, Depression, Medicine, and 15 moreAffect, Pregnancy, Humans, Internal Medicine, Antidepressant, Female, HPA axis, Infant, Clinical Sciences, Saliva, Adult, Selective serotonin reuptake inhibitor, Pregnancy complications, hydrocortisone, and Antidepressive agents
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Systematic ignoring of pain in the very young has given way to the measurement, treatment, and prevention of pain in all age groups. This profound shift has been supported by basic science research, leading to recognition of the... more
Systematic ignoring of pain in the very young has given way to the measurement, treatment, and prevention of pain in all age groups. This profound shift has been supported by basic science research, leading to recognition of the uniqueness of the developing pain system; mechanisms underlying the transmission, integration, and modulation of painful stimuli; and a distinct repertoire of behavioral and other responses associated with the pain experience at each developmental stage. The authors present an overview of the definition of pain in infants and the development of the pain system, explore pain's developmental plasticity, and review the acute and long-term effects of early painful experiences.
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Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may influence white matter (WM) development, as previous studies report widespread microstructural alterations and reduced interhemispheric connectivity in... more
Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may influence white matter (WM) development, as previous studies report widespread microstructural alterations and reduced interhemispheric connectivity in SSRI‐exposed infants. In rodents, perinatal SSRIs had sex‐specific disruptions in corpus callosum (CC) axon architecture and connectivity; yet it is unknown whether SSRI‐related brain outcomes in humans are sex specific. In this study, the neonate CC was selected as a region‐of‐interest to investigate whether prenatal SSRI exposure has sex‐specific effects on early WM microstructure. On postnatal day 7, diffusion tensor imaging was used to assess WM microstructure in SSRI‐exposed (n = 24; 12 male) and nonexposed (n = 48; 28 male) term‐born neonates. Fractional anisotropy was extracted from CC voxels and a multivariate discriminant analysis was used to identify latent patterns differing between neonates grouped by SSRI‐exposure and sex. Analysis revealed localized variations in CC fractional anisotropy that significantly discriminated neonate groups and correctly predicted group membership with an 82% accuracy. Such effects were identified across three dimensions, representing sex differences in SSRI‐exposed neonates (genu, splenium), SSRI‐related effects independent of sex (genu‐to‐rostral body), and sex differences in nonexposed neonates (isthmus‐splenium, posterior midbody). Our findings suggest that CC microstructure may have a sex‐specific, localized, developmental sensitivity to prenatal SSRI exposure.
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Background Maternal depressed mood during pregnancy may shape a child's adaptation to their environment and engagement in goal-directed behaviour such as executive functions. Whether everyday household context also alters executive... more
Background Maternal depressed mood during pregnancy may shape a child's adaptation to their environment and engagement in goal-directed behaviour such as executive functions. Whether everyday household context also alters executive functions in children with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure remains to be determined. Aims To examine the impact of prenatal depressed maternal mood and SSRI exposure on child executive functions and to determine whether these exposures shape a susceptibility to household chaos. Method A prospective cohort study of mothers and their children (118 mother–children dyads (47 SSRI-exposed, 71 non-exposed)) followed from the second trimester to 6 years. Regression models examined relationships between maternal depressed mood and household chaos on maternal report of child executive functions. Competitive-confirmatory regression models examined whether children were susceptible to household chaos or were positiv...
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Children born very preterm, even in the absence of overt brain injury or major impairment, are at risk of cognitive difficulties. This risk is associated with disruption of ongoing critical periods involving development of the... more
Children born very preterm, even in the absence of overt brain injury or major impairment, are at risk of cognitive difficulties. This risk is associated with disruption of ongoing critical periods involving development of the thalamocortical system while in the neonatal intensive care unit. The thalamus is an important structure that not only relays sensory information but acts as a hub integrating cortical activity, and through this integration, it regulates cortical power at different frequency bands. In this study, we investigate the association between atypical power at rest in children born very preterm at school age, neurocognitive function and structural alterations related to the thalamus. Our results indicate that children born extremely preterm have higher power at low frequencies and lower power at high frequencies, compared to controls born full-term. A similar pattern of spectral power was found to be associated with poorer neurocognitive outcomes. This pattern of spec...
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Oral sucrose is administered routinely to reduce pain of minor procedures in premature infants and is recommended as standard care in international guidelines. No human or animal studies on effects of early repeated sucrose exposure on... more
Oral sucrose is administered routinely to reduce pain of minor procedures in premature infants and is recommended as standard care in international guidelines. No human or animal studies on effects of early repeated sucrose exposure on long-term brain development have been done in the context of pain. We evaluated the effects of repeated neonatal sucrose treatment before an intervention on long-term brain structure in mouse pups. Neonatal C57Bl/6J mice (n = 109) were randomly assigned to one of 2 treatments (vehicle vs sucrose) and one of 3 interventions (handling, touch, or needle-prick). Mice received 10 interventions daily from postnatal day 1 to 6 (P1-6). A dose of vehicle or 24% sucrose was given orally 2 minutes before each intervention. At P85-95, brains were scanned using a multichannel 7.0 T MRI. Volumes of 159 independent brain regions were obtained. Early repetitive sucrose exposure in mice (after correcting for whole brain volume and multiple comparisons) lead to smaller...
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Early stress in the form of repetitive neonatal pain, in infants born very preterm, is associated with long-term dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and with poorer cognitive performance. Brain-derived... more
Early stress in the form of repetitive neonatal pain, in infants born very preterm, is associated with long-term dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and with poorer cognitive performance. Brain-derived neurotrophic factor (BDNF) which is important in synaptic plasticity and cognitive functions is reduced by stress. Therefore the BDNF Val66Met variant, which affects secretion of BDNF, may interact with early exposure to pain-related stress in children born very preterm, to differentially affect HPA regulation that in turn may be associated with altered cognitive performance. The aims of this study were to investigate whether in children born very preterm, the BDNF val66met variant modulates the association between neonatal pain-related stress and cortisol levels at age 7 years, and if cortisol levels were related to cognitive function. Furthermore, we examined whether these relationships were sex-specific. Using a longitudinal cohort design, N=90 children b...
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To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of... more
To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home-and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 ...
Research Interests: Pediatrics, Intelligence, Cognitive development, Cognition, Child Development, and 15 moreMedicine, Birth Weight, Humans, Female, Male, Infant, MDI, Retrospective Studies, Prognosis, Intelligence quotient, Medicine and Health Sciences, CAP, Child preschool, Paediatrics and reproductive medicine, and Infant Premature
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... more
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. AIMS We tested the hypothesis that heart rate (HR) will decrease after FNI over the course of the NICU stay, compared to matched controls. STUDY DESIGN We used a case-matched design. The intervention included on average four ~1-hour facilitated mother-infant 'calming' sessions per week. We collected 24/7 real time heart rate data from a central monitoring system and analyzed data from two time-periods. SUBJECTS The intervention group comprised 37 infants born ~30 weeks gestational age (GA) in a level IV NICU, treated with FNI. From the same NICU and time-period, we created a contemporaneous comparison group of 32 infants who were case-matched to each intervention infant for sex, age-at-birth, singleton or twin status, month of admission and length of stay. OUTCOME MEASURES Using generalized estimating equation (GEE) modeling, we analyzed 24/7 HR data during a 1-hour period between 4:30 and 5:30 am each day in the NICU, when all infants were least disturbed. Using repeated measures ANOVA, we analyzed 24/7 HR data during a 6-week period starting 1 week prior to the start of FNI and ending 5 weeks after start. RESULTS GEE modeling of the 1-hour data from all subjects showed significant lower HR in the FNI group, compared with controls. ANOVA modeling on a subset of subjects over the five-week period showed that FNI infant HR decreased in a dose-response manner relative to SC HR. CONCLUSION This study suggests FNI may condition lower infant HR in a dose-response manner during the NICU stay.
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ImportanceInternalizing (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... more
ImportanceInternalizing (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.ObjectiveTo investigate whether neonatal pain-related stress is associated with trajectories of internalizing behaviors across 1.5, 3.0, 4.5, and 8.0 years, and whether supportive parenting behaviors and lower parenting stress at 1.5 and 3.0 years attenuate this association.Design, Setting, and ParticipantsIn this prospective longitudinal cohort study, preterm neonates (born at 24-32 weeks’ gestation) were recruited from August 16, 2006, to September 9, 2013, with follow-up visits at ages 1.5, 3.0, 4.5, and 8.0 years. The study was conducted at BC Women’s Hospital, Vancouver, Can...
<p>R, right hemisphere; L, left hemisphere; Infection = number of culture proven infection; Pain = number of skin-breaking procedures exposure; Ventilation = number of days on mechanical ventilation; Morphine = cumulative daily dose... more
<p>R, right hemisphere; L, left hemisphere; Infection = number of culture proven infection; Pain = number of skin-breaking procedures exposure; Ventilation = number of days on mechanical ventilation; Morphine = cumulative daily dose in milligrams adjusted for daily body weight; SNAP-II = score for neonatal acute physiology; Surgery = number of surgeries; GA = gestational age.</p><p>B values are unstandardized. Number of days on mechanical ventilation was winsorized (replaced the outlier value with the closest value within the ±3 standard deviation range) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076702#pone.0076702-Tukey1" target="_blank">[84]</a>.</p>†<p>Bold text represents statistical significance; <i>p</i>-value threshold for significance adjusted for multiple comparisons with a false discovery rate (FDR) correction set at 5%.</p
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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... more
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. 6146 children were included. The primary language at home was English, French or another language for 3708 children (60%), 1312 children (21%) and 1126 children (18%), respectively, and overall, 44% were exposed to two or more languages at home. Univariate analysis showed that primary language was associated with lower Bayley-III Language scores; however, multivariate analyses demonstrated that neither primary language nor language of administration were significantly associated with lower language scores when adjusted for gestational...
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Children born preterm display altered sensory processing, which may manifest as hyper- and/or hypo-sensitivity to sensory information. In this vulnerable population, exposure to neonatal pain-related stress is associated with altered... more
Children born preterm display altered sensory processing, which may manifest as hyper- and/or hypo-sensitivity to sensory information. In this vulnerable population, exposure to neonatal pain-related stress is associated with altered stress regulation, as indexed by alterations in cortisol levels. It is unknown whether sensory processing behaviors are also affected by early life adversity, and whether dysregulated cortisol is related to sensory processing problems in preterm children. We examined relationships between neonatal pain-related stress, sensory processing profiles and cortisol levels at age 4 years, and whether pathways were sex-specific. In a longitudinal prospective cohort study, N = 146 infants born 24-32 weeks gestational age were recruited from BC Women's Hospital, Vancouver, BC, Canada; neonatal factors were collected from daily chart review. At age 4 years, saliva to assay cortisol was collected three times across cognitive assessment (pre-test, during, end) and parents completed the Short Sensory Profile questionnaire. Using generalized linear modeling, independent of other neonatal factors, higher number of invasive procedures (pain/stress) was associated with more sensory processing problems (total, hypo- and hyper-sensitivity) for girls only. After accounting for neonatal factors, greater cortisol output across the assessment was associated with more total sensory processing problems in girls only, and hypersensitivity to sensory input in both boys and girls. Findings suggest that in children born very preterm, how a child responds to sensory input and cortisol reactivity to stress are related but may have different precursors. Girls may be somewhat more susceptible to neonatal pain-related stress exposure in relation to sensory processing at preschool age.
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Towards a Cognitive Science of Social Inequality: Children’s Attention-related ERPs and Salivary Cortisol vary with their Socioeconomic Status Amedeo D’Angiulli ( amedeo@connect.carleton.ca ), Carleton University , Institute of... more
Towards a Cognitive Science of Social Inequality: Children’s Attention-related ERPs and Salivary Cortisol vary with their Socioeconomic Status Amedeo D’Angiulli ( amedeo@connect.carleton.ca ), Carleton University , Institute of Interdisciplinary Studies & Department of Psychology, 1125 Colonel By Drive Ottawa, ON K1S 5B6 Canada Joanne Weinberg ( joannew@interchange.ubc.ca ), The University of British Columbia, Department of Cellular and Physiological Sciences, 2350 Health Sciences Mall Vancouver, BC V6T 1Z3 Canada Ruth Grunau ( rgrunau@cw.bc.ca ), The University of British Columbia, Department of Pediatrics, 4480 Oak St. Vancouver, BC V6H 3V4 Canada Clyde Hertzman ( clyde.hertzman@ubc.ca ) The University of British Columbia , Department of Health Care & Epidemiology, 5804 Fairview Avenue Vancouver, BC V6T 1Z3 Canada Pavel Grebenkov ( pgrebenk@connect.carleton.ca ), Carleton University , Institute of Cognitive Science, 1125 Colonel By Drive Ottawa, ON K1S 5B6 Canada SES children gene...
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Prenatal exposure to maternal mood disturbances shapes children's cognitive development reflected in the critical construct of executive functions (EFs). Little is known, however, about underlying mechanisms. By examining cortisol... more
Prenatal exposure to maternal mood disturbances shapes children's cognitive development reflected in the critical construct of executive functions (EFs). Little is known, however, about underlying mechanisms. By examining cortisol responses in both everyday and lab challenge settings, we tested whether the child/offspring hypothalamic-pituitary-adrenal axis mediates effects of prenatal maternal mood on child EFs at age 6. In 107 Canadian children born to women with a wide range of anxious and depressive symptoms during pregnancy, we found that in boys but not girls, depressed and/or anxious prenatal maternal mood is associated with heightened diurnal cortisol levels in everyday settings, as well as heightened cortisol reactivity to a lab challenge and that this heightened reactivity was associated with poorer EFs. Among boys we also observed that cortisol reactivity but not diurnal cortisol mediated the association between depressed and/or anxious prenatal maternal mood and EFs....
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Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression during pregnancy. SSRIs cross the placenta, inhibit serotonin reuptake, and thereby are thought to alter central fetal serotonin signaling. Both... more
Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression during pregnancy. SSRIs cross the placenta, inhibit serotonin reuptake, and thereby are thought to alter central fetal serotonin signaling. Both prenatal maternal mood disturbances and in utero SSRI exposure have been associated with altered fetal and infant behavior. Resting-state functional magnetic resonance imaging has identified resting-state networks (RSNs) in newborns, reflecting functional capacity of auditory and visual networks and providing opportunities to examine early experiences effects on neurodevelopment. We sought to examine the effect of in utero SSRI exposure on neonatal RSN functional organization. We hypothesized that prenatal SSRI exposure would be associated with alterations in neonatal RSNs compared with healthy control infants and infants exposed to mothers with depression. Clinician-rated Hamilton Depression Rating Scale and self-reported Pregnancy Experiences Scale were ...
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Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate... more
Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate effects of neonatal caffeine therapy in very low birth weight (500-1250 g) infants on neurobehavioral outcomes in 11-year-old participants of the Caffeine for Apnea of Prematurity trial. Thirteen academic hospitals in Canada, Australia, Great Britain, and Sweden participated in this part of the 11-year follow-up of the double-blind, randomized, placebo-controlled trial. Measures of general intelligence, attention, executive function, visuomotor integration and perception, and behavior were obtained in up to 870 children. The effects of caffeine therapy were assessed by using regression models. Neurobehavioral outcomes were generally similar for both the caffeine and placebo group. The caffeine group performed better than the placebo group in fine mot...
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Understanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables... more
Understanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables affecting brain health and outcomes among children born preterm. To evaluate whether histologic chorioamnionitis among neonates born very preterm is associated with intraventricular hemorrhage (IVH) and punctate white matter injury (WMI) or with adverse neurodevelopmental outcomes during early childhood. Prospective cohort study conducted across 3 academic centers (from April 2006 to September 2013 in Canada, from March 2007 to March 2013 in the Netherlands, and from January 2004 to August 2011 in the United States). Children who were born preterm (24-32 weeks' gestation) and who had undergone a placental pathologic evaluation, magnetic resonance imaging as soon as clinically stable, and Bayley Scales of Infant and Toddler Development, Third Edit...
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Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, to date the link... more
Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, to date the link between pain and brain development has limited temporal and anatomic specificity. We hypothesized that early exposure to painful stimuli during a period of rapid brain development, before pain modulatory systems reach maturity, will predict pronounced changes in thalamic development, and thereby cognitive and motor function. In a prospective cohort study, 155 very preterm neonates (82 males, 73 females) born 24-32 weeks' gestation underwent two MRIs at median postmenstrual ages 32 and 40 weeks that included structural, metabolic, and diffusion imaging. Detailed day-by-day clinical data were collected. Cognitive and motor abilities were assessed at 3 years, corrected age. The association of early (skin breaks, birth-Scan 1) and late pain (skin b...
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To evaluate whether the number of postnatal infections is associated with abnormal white matter maturation and poorer motor neurodevelopmental outcomes at 36 months of corrected age. A prospective longitudinal cohort study was undertaken... more
To evaluate whether the number of postnatal infections is associated with abnormal white matter maturation and poorer motor neurodevelopmental outcomes at 36 months of corrected age. A prospective longitudinal cohort study was undertaken of 219 newborns born preterm at 24-32 weeks of gestational age recruited between 2006 and 2013 with magnetic resonance imaging of the brain both early in life and at term-equivalent age. Postnatal infection was defined as any clinical infection or positive culture ≥72 hours after birth. White matter maturation was assessed by magnetic resonance spectroscopic imaging, magnetic resonance diffusion tensor imaging, and tract-based spatial statistics. Neurodevelopmental outcomes were assessed in 175 (82% of survivors) infants with Bayley Scales of Infant and Toddler Development-III composite scores and Peabody Developmental Motor Scales at 35 months of corrected age (IQR 34-37 months). Infection groups were compared via the Fisher exact test, Kruskal-Wal...
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Our objectives were to determine whether procedural pain and glucose exposure are associated with altered structural and functional brain development differently in preterm males and females, and neurodevelopment at 18-months corrected... more
Our objectives were to determine whether procedural pain and glucose exposure are associated with altered structural and functional brain development differently in preterm males and females, and neurodevelopment at 18-months corrected age. Fifty-one very-preterm neonates (22 males; median[IQR] gestational age 27.6[2.0] weeks) underwent three serial scans including T1-weighted and resting-state functional magnetic resonance imaging (MRI) at median postmenstrual weeks: 29.4, 31.9, and 41.1. Thalamus, basal ganglia, and total brain volumes were segmented. Functional resting-state MRI data were extracted from the independent-components maps. Pain was operationalized as the total number of NICU-administered invasive procedures. Neurodevelopmental outcomes at 18-months corrected age were assessed with the Bayley Scales of Infant Development, second edition. Generalized estimating equations assessed the association of pain and glucose exposure with brain structural and functional developm...
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To examine associations between maternal pregnancy-specific stress and umbilical (UA PI) and middle cerebral artery pulsatility indices (MCA PI), cerebroplacental ratio, absent end diastolic flow (AEDF), birthweight, prematurity, neonatal... more
To examine associations between maternal pregnancy-specific stress and umbilical (UA PI) and middle cerebral artery pulsatility indices (MCA PI), cerebroplacental ratio, absent end diastolic flow (AEDF), birthweight, prematurity, neonatal intensive care unit admission and adverse obstetric outcomes in women with small for gestational age pregnancies. It was hypothesised that maternal pregnancy-specific stress would be associated with fetoplacental haemodynamics and neonatal outcomes. This is a secondary analysis of data collected for a large-scale prospective observational study. This study was conducted in the seven major obstetric hospitals in Ireland and Northern Ireland. Participants included 331 women who participated in the Prospective Observational Trial to Optimise Paediatric Health in Intrauterine Growth Restriction. Women with singleton pregnancies between 24 and 36 weeks gestation, estimated fetal weight <10th percentile and no major structural or chromosomal abnormali...
Research Interests: Body Image, Medicine, Birth Weight, Prospective studies, Pregnancy, and 14 moreHumans, Hemodynamics, Female, Young Adult, Adult, Internal medicine Doppler ultrasonography, Neonatal Intensive Care Unit, Parturition, Gestational Age, Psychological Stress, Premature Birth, Middle Cerebral Artery, Surveys and Questionnaires, and Fetal Growth Retardation
Objectives: To examine associations between maternal pregnancy-specific stress and umbilical (UA PI) and middle cerebral artery pulsatility indices (MCA PI), cerebroplacental ratio, absent end diastolic flow (AEDF), birthweight,... more
Objectives: To examine associations between maternal pregnancy-specific stress and umbilical (UA PI) and middle cerebral artery pulsatility indices (MCA PI), cerebroplacental ratio, absent end diastolic flow (AEDF), birthweight, prematurity, neonatal intensive care unit admission and adverse obstetric outcomes in women with small for gestational age pregnancies. It was hypothesised that maternal pregnancy-specific stress would be associated with fetoplacental haemodynamics and neonatal outcomes. Design: This is a secondary analysis of data collected for a large-scale prospective observational study. Setting: This study was conducted in the seven major obstetric hospitals in Ireland and Northern Ireland. Participants: Participants included 331 women who participated in the Prospective Observational Trial to Optimise Paediatric Health in Intrauterine Growth Restriction. Women with singleton pregnancies between 24 and 36 weeks gestation, estimated fetal weight <10th percentile and n...
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Objectives The objective of this study was to describe survival, short-term, and long-term morbidities of neonates with birth weight &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 500 g.... more
Objectives The objective of this study was to describe survival, short-term, and long-term morbidities of neonates with birth weight &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 500 g. Study Design Retrospective cohort studies to calculate survival, short-term, and long-term morbidity rates of neonates born weighing &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 500 g from 1993 to 2012 and neurodevelopmental impairment rates at 4.5 years for births 1993 to 2008 in one center. Results Of 549 inborn neonates with birth weight &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 500 g, 4% survived. For live births and neonatal intensive care unit (NICU) admissions, 10 and 55% survived, respectively. Of 28 NICU (inborn and outborn) survivors (median birth weight 460 g and gestation 25.9 weeks [range: 22.6–30.3 weeks]), 71% were inborn, 50% male, and 75% were small for gestational age. One in five neonates was a twin or multiple. Short-term morbidities noted were bronchopulmonary dysplasia (91%), culture proven sepsis (50%), retinopathy of prematurity (41%), and severe brain injury (22%); 27% had no long-term impairment, 23% one, 23% two, 18% three, and 9% four impairments in motor, cognitive, vision, and/or hearing domains. At 4.5 years, 29% had visual impairment, 10% wore hearing aids, 50% had IQ &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 70, 18% cerebral palsy, and 68% had low motor scores. Conclusion Only 4% of births &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 500 g survived. All survivors had short-term morbidities; 27% neonates survived without long-term major impairments.
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To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months' corrected age (CA) compared with neonates without severe ROP. We... more
To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months' corrected age (CA) compared with neonates without severe ROP. We conducted a prospective longitudinal cohort of extremely preterm neonates born 24-28 weeks' gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months' CA. Subjects were compared using Fisher's exact, Kruskal-Wallis and generalised estimating equations. Families were recruited from t...