Childhood outcomes after maternal antenatal sildenafil treatment for severe early-onset fetal growth restriction: a randomized trial (STRIDER NZAus).

In this follow-up at 2.5 years of children from the STRIDER NZAus Trial (N = 112), in which women with singleton pregnancies affected by severe early fetal growth restriction were randomized to sildenafil citrate 75 mg daily or placebo until 32 weeks, there was no difference between groups in survival without neurosensory impairment, defined as any of cerebral palsy, deafness, blindness, cognitive delay (Bayley III cognition or language score >1 SD below mean) or motor delay: 30/56[54%] vs. 34/56[61%]; aOR = 0.74, 95%CI: 0.31, 1.77. However, children exposed to sildenafil appeared to be more likely to have cognitive delay (13/45[29%] vs. 4/40[10%]; aOR = 3.71, 95% CI: 1.01, 13.63) but less likely to have emotional-behavioural difficulties (2/43[5%] vs. 8/38[21%]; aOR = 0.19, 95%CI: 0.03, 1.00). Conclusion: maternal sildenafil treatment for severe early-onset FGR was not associated with altered survival free of neurosensory impairment at 2.5 years' corrected age.

SuPreme Study: a protocol to study the neuroprotective potential of sulfate among very/extremely preterm infants.

INTRODUCTION: Antenatal maternal magnesium sulfate (MgSO4) administration is a proven efficacious neuroprotective treatment reducing the risk of cerebral palsy (CP) among infants born preterm. Identification of the neuroprotective component with target plasma concentrations could lead to neonatal treatment with greater efficacy and accessibility. METHODS AND ANALYSIS: This is a prospective observational cohort study, in three tertiary Australian centres. Participants are preterm infants, irrespective of antenatal MgSO4 exposure, born in 2013-2020 at 24+0 to 31+6 weeks gestation, and followed up to 2 years corrected age (CA) (to September 2023). 1595 participants are required (allowing for 17% deaths/loss to follow-up) to detect a clinically significant reduction (30% relative risk reduction) in CP when sulfate concentration at 7 days of age is 1 SD above the mean.A blood sample is collected on day 7 of age for plasma sulfate and magnesium measurement. In a subset of participants multiple blood and urine samples are collected for pharmacokinetic studies, between days 1-28, and in a further subset mother/infant blood is screened for genetic variants of sulfate transporter genes.The primary outcome is CP. Surviving infants are assessed for high risk of CP at 12-14 weeks CA according to Prechtl's Method to assess General Movements. Follow-up at 2 years CA includes assessments for CP, cognitive, language and motor development, and social/behavioural difficulties.Multivariate analyses will examine the association between day 7 plasma sulfate/magnesium concentrations with adverse neurodevelopmental outcomes. A population pharmacokinetic model for sulfate in the preterm infant will be created using non-linear mixed-effects modelling. ETHICS AND DISSEMINATION: The study has been approved by Mater Misericordiae Ltd Human Research Ethics Committee (HREC/14/MHS/188). Results will be disseminated in peer-reviewed journal publications, and provided to the funding bodies. Using consumer input, a summary will be prepared for participants and consumer groups.

Robust and Interpretable General Movement Assessment Using Fidgety Movement Detection.

Fidgety movements occur in infants between the age of 9 to 20 weeks post-term, and their absence are a strong indicator that an infant has cerebral palsy. Prechtl's General Movement Assessment method evaluates whether an infant has fidgety movements, but requires a trained expert to conduct it. Timely evaluation facilitates early interventions, and thus computer-based methods have been developed to aid domain experts. However, current solutions rely on complex models or high-dimensional representations of the data, which hinder their interpretability and generalization ability. To address that we propose [Formula: see text], a method that detects fidgety movements and uses them towards an assessment of the quality of an infant's general movements. [Formula: see text] is true to the domain expert process, more accurate, and highly interpretable due to its fine-grained scoring system. The main idea behind [Formula: see text] is to specify signal properties of fidgety movements that are measurable and quantifiable. In particular, we measure the movement direction variability of joints of interest, for movements of small amplitude in short video segments. [Formula: see text] also comprises a strategy to reduce those measurements to a single score that quantifies the quality of an infant's general movements; the strategy is a direct translation of the qualitative procedure domain experts use to assess infants. This brings [Formula: see text] closer to the process a domain expert applies to decide whether an infant produced enough fidgety movements. We evaluated [Formula: see text] on the largest clinical dataset reported, where it showed to be interpretable and more accurate than many methods published to date.

'Low-normal' motor skills in infants at high risk for poor developmental outcomes: A prevalence and prognostic study.

AIM: To investigate the prevalence and prognostic value of 'low-normal' motor skills in infants at high-risk for poor developmental outcomes. METHOD: Infants born extremely low-birthweight and extremely preterm discharged from neonatal intensive care between 2015 and 2018 completed the Alberta Infant Motor Scale (AIMS), Neuro-Sensory Motor Developmental Assessment (NSMDA) at corrected age 4, 8, and 12 months, and Griffiths Mental Development Scale at corrected age 12 months. RESULTS: Participating infants (n = 191) with a mean gestational age (95% confidence interval [CI]) of 26.80 weeks (26.60, 27.1) and mean birthweight (95% CI) of 869 grams (843, 895) included 45 (23.80%) infants small for gestational age. AIMS rated 50.32%, 35.37%, and 14.86% of infants within the 'low-normal' motor skills range (1-2 SD below the mean for age) at 4, 8, and 12 months respectively. Of the infants within the AIMS 'low-normal' skills range, 55.70%, 88.46%, and 59.10% were classified as having impairment by NSMDA at 4, 8, and 12 months respectively. Griffiths assessment at 12 months identified only 7.33% of infants with 'low-normal' skills and 3.33% with motor disability. Minimal motor impairment rating on the NSMDA at 4 or 8 months significantly predicted general development at 12 months. INTERPRETATION: High-risk infants with 'low-normal' motor skills may warrant referral to early intervention as associated impairment represents increased risk for poorer general development outcomes. WHAT THIS PAPER ADDS: High prevalence of 'low-normal' motor skill exists in high-risk infants. Clinical motor assessment validly identifies infants with motor impairment. Minimal motor impairment in high-risk infants is prognostic of general development. High-risk infants with 'low-normal' motor skills may warrant early intervention. Griffiths Scales of Child Development, Third Edition assessment at 12-months age may under-identify motor difficulties.

QF2011: a protocol to study the effects of the Queensland flood on pregnant women, their pregnancies, and their children's early development.

BACKGROUND: Retrospective studies suggest that maternal exposure to a severe stressor during pregnancy increases the fetus' risk for a variety of disorders in adulthood. Animal studies testing the fetal programming hypothesis find that maternal glucocorticoids pass through the placenta and alter fetal brain development, particularly the hypothalamic-pituitary-adrenal axis. However, there are no prospective studies of pregnant women exposed to a sudden-onset independent stressor that elucidate the biopsychosocial mechanisms responsible for the wide variety of consequences of prenatal stress seen in human offspring. The aim of the QF2011 Queensland Flood Study is to fill this gap, and to test the buffering effects of Midwifery Group Practice, a form of continuity of maternity care. METHODS/DESIGN: In January 2011 Queensland, Australia had its worst flooding in 30 years. Simultaneously, researchers in Brisbane were collecting psychosocial data on pregnant women for a randomized control trial (the M@NGO Trial) comparing Midwifery Group Practice to standard care. We invited these and other pregnant women to participate in a prospective, longitudinal study of the effects of prenatal maternal stress from the floods on maternal, perinatal and early childhood outcomes. Data collection included assessment of objective hardship and subjective distress from the floods at recruitment and again 12 months post-flood. Biological samples included maternal bloods at 36 weeks pregnancy, umbilical cord, cord blood, and placental tissues at birth. Questionnaires assessing maternal and child outcomes were sent to women at 6 weeks and 6 months postpartum. The protocol includes assessments at 16 months, 2½ and 4 years. Outcomes include maternal psychopathology, and the child's cognitive, behavioral, motor and physical development. Additional biological samples include maternal and child DNA, as well as child testosterone, diurnal and reactive cortisol. DISCUSSION: This prenatal stress study is the first of its kind, and will fill important gaps in the literature. Analyses will determine the extent to which flood exposure influences the maternal biological stress response which may then affect the maternal-placental-fetal axis at the biological, biochemical, and molecular levels, altering fetal development and influencing outcomes in the offspring. The role of Midwifery Group Practice in moderating effects of maternal stress will be tested.