Preterm Children Research Articles

38 Disparities in health outcomes by the age of five among preterm children in rural versus urban communities in British Columbia

Abstract Background Health disparities exist between than urban and rural communities, as rates of preterm birth, severe maternal morbidity and severe neonatal morbidity are higher in rural areas. There are limited population-based studies on early childhood health outcomes among those born preterm by geographical area. Objectives To compare health service use, morbidity, and medication use for up to five years of age between preterm children in rural versus urban residences. Design/Methods The study included liveborn infants at 22-44 weeks’ gestational age (GA) in British Columbia (BC), Canada, 2004-2014. Follow-up data to December 2019 included linked health information from four provincial databases (perinatal database, outpatient visits, hospitalizations, and outpatient prescriptions). Urban-rural status was based on maternal residence at birth. Rate ratios (RR) of health service use, childhood morbidity and medication use were compared within GA categories (22-27, 28-33, 34-36, 37-44) by rural vs. urban region using Poisson regression. Results There were 49,555 (10.9%) rural and 406,149 (89.1%) urban children included in this study. 42,789 children were born at <37 weeks GA, and the preterm birth rate was 9.4%. Compared to urban areas, children in rural regions had more hospitalizations (28-33 weeks: RR 1.35, 95% CI: 1.19-1.51; 34-36 weeks: RR 1.35, 95% CI 1.27-1.44; 37-44 weeks: RR 1.32, 95% CI 1.29-1.34) by five years of age; and significantly fewer outpatient visits (22-27 weeks: RR 0.90, 95% CI: 0.87-0.93; 28-33 weeks: RR 0.81, 95% CI: 0.80-0.82; 34-36 weeks: RR 0.75, 95% CI 0.74-0.75; 37-44 weeks: RR 0.71, 95% CI 0.71-0.71). Rural children born at 34-36 weeks had significantly higher rates of bronchiolitis (RR: 1.35, 95% CI: 1.16-1.56) compared to urban children. They were prescribed more antibiotics and bronchodilators (RR: 1.15, 95% CI: 1.13-1.17, and RR: 1.12, 95% CI: 1.05-1.19, respectively). Conclusion Compared with urban areas, preterm children living in rural regions of BC had higher rates of hospitalization, higher rates of bronchiolitis and more frequent prescriptions of antibiotics and bronchodilators by five years of age. These disparities in health status and service use warrant further research and public health interventions.

86 Sociodemographic and family characteristics of children with and without neurodevelopmental impairment in a Canadian cohort of extreme preterm children

Abstract Background Despite improved survival of extreme preterm infants (<29 weeks’ gestation), neurodevelopmental impairment (NDI) remains high. Certain sociodemographic characteristics (SDC) and limited family resources are known to adversely affect children health and development, particularly those born preterm. There is a dearth of recent data from large cohorts examining the impact of social determinants of health on the neurodevelopment of preterm children. Objectives (1) to describe SDC and family composition in a population-based cohort of extreme preterm children using the Canadian Neonatal Follow Up Network (CNFUN) database; (2) to develop a logistic regression model examining the association of significant NDI (sNDI any of: CP ≥ GMFCS stage 3, Bayley III < 70 in any domain, deafness requiring aids, or bilateral blindness) with SDC using a unique family descriptor. Design/Methods A retrospective review of a national cohort of extreme preterm infants (230 -286 weeks) born between April 2009 and December 2018. We included children who had neurodevelopmental assessment at 18-24 month corrected age at a CNFUN participating Centre. We compared SDC of infants and caregivers and family descriptors (moderating variables) between children with no NDI and those with any NDI and sNDI. Multivariate logistic regression models were developed in two steps to evaluate the effect of SDC (Model 1) and family composition (Model 2) on the primary outcome of sNDI. GEE was used to account for clustering by multiples and within site. Results Out of 10833 eligible infants, 6219 (57%) were included. Of those, 3412 (55%) had no NDI and 2807 (45%) had any NDI. sNDI accounted for 17% of the cohort and 37% of those with NDI. Comparison of the SDC and family descriptors between the three groups are shown in Table 1. On multivariate analysis using SDC, infant’s gestational age and male sex, and primary caregiver’s ethnicity and level of education were independently associated with sNDI. Immigration and employment status were associated with sNDI when family descriptors were added to the first model (Table 2). Conclusion In this national cohort, half of extreme preterm children developed NDI and 1 in 7 had sNDI. There were differences in sociodemographic and family characteristics between those with and without sNDI. The degree of prematurity and caregiver’s education, employment and immigration status were independently associated with sNDI in those children. Future research is needed to determine what interventions and support to benefit those children at risk.

67 A population-based cohort study of endocrine outcomes within the first 5 years of life in children born preterm

Abstract Background Preterm birth (<37 weeks’ gestational age [GA]) occurs in 8% of live births in Canada. While advancements in neonatal medicine have led to increased survival in preterm births, infants born preterm continue to sustain short- and long-term health sequelae. There is paucity of large population studies evaluating childhood health care outcomes, including endocrine-related outcomes, in recent birth cohorts. Objectives To evaluate the rates of endocrine conditions during the first 5 years of life in children born preterm and term. Design/Methods The study cohort included liveborn infants at 22-44 weeks’ GA in British Columbia, Canada between 2004-2014. Follow-up data to December 2019 included linked health services use information from four BC provincial databases (perinatal database, hospitalizations, outpatient services, and outpatient prescriptions). Rates of outcomes were compared by GA at birth (37-44 weeks reference category) using robust Poisson regression. Results There were 455,960 children included in this study with 42,820 (9.4%) born at <37 weeks GA. Results are summarized in Table 1 and Table 2. Compared to children born at 37-44 weeks’ gestations, infants born at 36 weeks’ gestation or younger have an increased rate of thyroid disorders between 0 months and 5 years (rate ratio [RR]: 1.45, 95% confidence interval [CI]: 0.78-2.43; RR: 1.83, 95% CI 1.51-2.20; RR: 1.41 95% CI 1.26-1.57 for 22-27 weeks, 28-33 weeks and 34-36 weeks GA, respectively). Similarly, infants born at 36 weeks’ gestation or younger have a higher rate of conditions in growth and development (RR: 3.05, 95% CI: 0.76-7.96; RR: 3.20, 95% CI 2.04-4.76; RR: 1.42 95% CI 1.02-1.94 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively) and bone health conditions (RR: 1.38, 95% CI: 1.27-1.49; RR: 1.04, 95% CI 1.00-1.08; RR: 1.05 95% CI 1.03-1.07 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively). There was no difference in rates of conditions related to glucose metabolism such as diabetes mellitus or hypoglycemia. Conclusion Children born preterm have increased rates of endocrine conditions by age 5. Disorders of thyroid, growth and development are increased in infants born preterm. Children born preterm have an increase rate of bone-related disorders, including those born late-preterm. These results provide useful prognostic information for follow-up care for preterm children and for healthcare resource planning. Furthermore, these results highlight areas of future research in endocrine health among preterm infants.

Pulmonary function using impulse oscillometry system and clinical outcomes at age 4 years in children born extremely preterm with or without bronchopulmonary dysplasia

This study aimed to describe the early assessment of lung function and respiratory morbidity in children born extremely preterm with or without bronchopulmonary dysplasia (BPD). MethodsThis was a prospective study including all the children born at gestational age ≤28 weeks who received treatment in the NICU of the Centre Intercommunal de Créteil in France, from January 2006 to March 2012. Lung function, using the impulse oscillometry system, respiratory morbidity and growth were assessed at age 4 years. Lung function and clinical course of children were compared in children with and without BPD. ResultsWe included 136 extremely premature children; 26 (19 %) had BPD. Children with and without BPD did not significantly differ in resistance measurements at 5 Hz (R5) and 20 Hz (R20) and reactance (X5) measurements at age 4 years. A total of 104 (76 %) pre-term children had respiratory resistance R5 above the 95th percentile for the reference population (z-score >1.64), regardless of BPD status. The mean (SD) R5 z-score for all children was 2.1 (±0.7), whereas the mean (SD) R20 was in the normal range (z-score = 1.1 [±0.3]). After treatment with bronchodilators, all children showed no significant change in resistance. The prevalence of asthma symptoms at age 4 years was common and estimated at 30 % regardless of BPD status. ConclusionEarly assessment of lung function by the impulse oscillometry system revealed that most preschool children who were born extremely preterm had abnormal total airway resistance regardless of BPD status. The system is an essential tool for the early assessment of children born prematurely.

Effect of an early music intervention on emotional and neurodevelopmental outcomes of preterm infants at 12 and 24 months

BackgroundFew studies have found long-term effects of early musical environmental enrichment in the NICU on preterm infant’s development. This study examines how early music enrichment affects emotional development and effortful control abilities in 12- and 24-month-old very preterm (VPT) infants.MethodsOne hundred nineteen newborns were recruited, including 83 VPTs and 36 full-term (FT) infants. The VPT infants were randomly assigned to the music intervention (44 VPT-Music) or control (39 VPT-control) groups. VPT-Music infants listened specifically designed music intervention from the 33rd week of gestation until hospital discharge. At 12 and 24 months, children were clinically evaluated using the Bayley-III Scales of Infant and Toddler Development and the Laboratory Temperament Assessment Battery, and at 24 months, with 3 additional episodes of the Effortful Control Battery.Results and discussionOur analysis showed that during a fear eliciting task, the VPT-Music group expressed lower level of fear reactivity and higher positive motor actions than VPT-controls and FT infants. At 24 months, the VPT-music group had lower scores for negative motor actions in the joy task, compared to both VPT-control and FT groups. In addition, both FT and VPT-music had higher scores of sustained attention compared to VPT-controls, but the contrasts were not significant. No significant effects on mental, language and motor outcomes were identified and for all three dimensions of the ECBQ.ConclusionThe present study suggests that an early music intervention in the NICU might influence preterm children’s emotional processing at 12 and 24 months. Limitations and suggestions for future research are highlighted.

Association of different types of abortions with neonatal outcomes in subsequent pregnancy.

Abortion is an important issue that concerns all women. It holds great significance to investigate the correlation between various types of abortion histories and the neonatal outcomes of subsequent pregnancies. This retrospective cohort study included pregnant women who gave birth to singleton live-born in Shanghai First Maternity and Infant Hospital from 2016 to 2020 (n = 75 773). Women with a history of abortion, including spontaneous abortion (SAB) and induced abortion (IA), were included in the exposed group, and the remaining were included in the unexposed group. The main outcomes were birthweight and preterm birth in the subsequent pregnancy. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of maternal abortion history with birthweight and risk of preterm birth in subsequent pregnancy. Women who have experienced SAB history had an increased risk of delivering very low birth weight (VLBW) and preterm birth children, with (OR = 1.63, 95% CI = 1.15-2.32; OR = 1.38, 95% CI = 1.07-1.79). However, women with a history of IA were at greater risk of macrosomia (OR = 1.16; 95% CI = 1.06-1.27). We also observed that the likelihood of delivering a VLBW baby was heightened by the number of SAB occurrences (OR = 0.87, 95% CI = 0.54-1.38; OR = 1.84, 95% CI = 1.01-3.36, OR = 5.71, 95% CI = 3.21-10.15). Our study indicates that pregnant women with a history of SAB are at an increased risk of delivering VLBW infants and experiencing preterm labour. The risk is positively associated with the number of SABs. Conversely, women with a history of IA are more likely to deliver macrosomic infants.

Visual pathways functioning in healthy pre-term adolescents: Sex but not gestational age effect.

Visuo-spatial and visuo-perceptual functioning is widely studied in preterm child and is strongly sex-specific. However, little to no data is available regarding male-female differences in preterm children and adolescents and about the interaction effect between sex and preterm birth. We studied 30 adolescents born preterm with normal cognitive and clinical neurological outcomes and 34 age-matched controls to investigate the interaction between levels of prematurity and sex in predicting the outcome of visual pathways functioning and to explore the relation between psychophysiological perceptive processing and neuropsychological performance. In the presence of prematurity, a greater female vulnerability in central visuo-cognitive processing (Form Coherence Task), but not in neuropsychological accuracy (Street Completion Test and Visual Object and Space Perception battery), seems to be more evident. Moreover, the psychophysical threshold is correlated to neuropsychological accuracy only in preterm females and not in males. These results support the idea that the male vulnerability in cognitive functioning described in prematurity-related developmental conditions is negligible during school age in children-adolescents with normal cognitive and clinical neurological outcomes. Visuo-perceptual functioning is widely studied in prematurity. However, few data are available about the interaction effect between sex and preterm birth in predicting visuo-perceptual functioning. We evidenced that in females born preterm with preserved cognitive abilities, the efficiency of the psychophysical visuo-perceptual threshold is reduced, but not related to the neuropsychological performance. Females may implement compensation strategies to achieve good performance regardless of the perceptual threshold. The present study addresses an important gap in literature, suggesting possible sex-specific outcomes in visuo-perceptual ability among preterm children and adolescents with normal intelligence and neurological outcomes.

Finnish children born very preterm have good reading comprehension but weak reading fluency at age 11 years – a longitudinal cohort study

ABSTRACT Children born very preterm (<32 gestational weeks and/or birth weight ≤1500 g) are at elevated risk for reading difficulties. This study aimed to investigate reading fluency and reading comprehension at 11 and to analyze the associations between literacy skills at 7 and reading skills at 11 in 134 Finnish-speaking very preterm children. At 11, reading fluency and reading comprehension were evaluated. At 7, pre-reading skills, decoding, and writing were assessed. Results showed that there were more preterm children with weak skills in reading fluency compared to a normative test population. Reading comprehension was age appropriate. Additionally, 62% to 68% of the children with weak literacy skills at 7 had weak reading fluency at 11, compared to those with more advanced skills (43% to 33%, p < 0.001 to 0.026). Respectively, 30% to 50% of the children with weak literacy at 7 had weak reading comprehension at 11 compared to those with more advanced skills (13% to 17%, p < 0.001 to 0.005). Findings highlight the importance of screening reading fluency until 11 years and providing support for the continuum between literacy skills in the beginning of schooling and reading outcome at later school age.

Association between preterm birth and asthma and atopic dermatitis in preschool children: a nationwide population-based study.

Asthma and atopic dermatitis (AD) are representative chronic diseases in childhood. This study aimed to investigate the impact of preterm birth on the incidence and severity of asthma and AD in children, as well as to identify neonatal risk factors for asthma and AD. We used health claims data recorded between 2007 and 2014 in the Korean National Health Insurance Service database. We recruited 2,224,476 infants born between 2007 and 2014 and divided them into three groups: 3518 of extremely preterm (EP) infants (< 28weeks of gestational age (GA)), 82,579 of other preterm (OP) infants (28-36weeks of GA), and 2,138,379 of full-term (FT) infants (> 37weeks of GA). We defined asthma as > 3 episodes of clinical visits in a year before 6years of age, early asthma as onset at < 2years of age, and severe asthma as > 1 event of status asthmaticus or admission to a hospital via an emergency room. AD was defined as ≥ 3 diagnoses in a year before 6years of age, early AD as onset at < 2years of age, and severe AD as prescription of high-potency topical steroids or immunosuppressants. An association of preterm birth with asthma and AD was assessed using inverse probability of treatment-weighted multivariable Cox regression analysis. Cardiorespiratory conditions, such as respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, and pulmonary hypertension, significantly increased the risk of asthma. Specifically, bronchopulmonary dysplasia emerged as a significant risk factor for both severe and early-onset asthma (odds ratio (OR) 1.36, 95% CI 1.21-1.37 for severe asthma; OR 1.55, 95% CI 1.30-1.85 for early asthma), while it was associated with a decreased risk of AD (OR 0.86, 95% CI 0.80-0.92). Neonatal sepsis, jaundice, and retinopathy of prematurity were also identified as significant risk factors for later asthma. A stepwise increase in the risk of asthma with an increasing degree of prematurity was observed, with the OP group showing an adjusted hazard ratio (aHR) of 1.24 (95% CI: 1.22-1.26) and the EP group showing an aHR of 1.51 (95% CI: 1.41-1.63). Conversely, preterm birth was inversely associated with the risk of AD, with aHRs of 0.73 (95% CI: 0.67-0.79) for the OP group and 0.88 (95% CI: 0.87-0.89) for the EP group. Conclusion Preterm children have a significantly higher risk of asthma and lower risk of AD, with cardiorespiratory conditions significantly increasing the risk of asthma. Thus, we highlight the need for targeted respiratory management strategies for this high-risk population. What is Known: •Asthma and atopic dermatitis are prevalent chronic diseases in childhood, reducing the quality of life of children. •Preterm birth was associated with an increased risk of asthma, but few large nationwide studies. •Research on the relationship between preterm birth and pediatric atopic dermatitis is controversial, with few large nationwide studies. What is New: • Preterm children, especially born before 28weeks of gestational age, had a significantly higher risk of asthma and lower risk of atopic dermatitis. • Cardiorespiratory comorbidities such as RDS, BPD, PDA, and pulmonary hypertension in neonatal period are prominent risk factors for asthma. • Preterm children are vulnerable to both early-onset and severe asthma.

Maternal high-dose docosahexaenoic acid supplementation and neurodevelopment at 5 Years of preterm children

Background & AimsDocosahexaenoic acid (DHA) is the most abundant omega-3 fatty acid in the brain and is accumulated by the fetal brain during the last trimester of pregnancy. Our objective was to determine whether high-dose DHA supplementation during the neonatal period, vs. placebo, improves behavioral functioning at 5 years in children born very preterm. MethodsThis is a follow-up at 5 years corrected age of a subset of children who participated in a multicenter randomized controlled trial. The participants received a high-dose DHA supplementation, or a placebo, through maternal breast milk until 36 weeks’ postmenstrual age. Primary outcome was child behavioral functioning, assessed by the Total Difficulties Score from the Strengths and Difficulties Questionnaire (SDQ). Secondary outcomes included behavioral scores from the SDQ, executive functions assessment and global developmental performance. Neurodevelopmental outcomes were assessed through interviews with parents. Mean differences between DHA and placebo groups were estimated using mixed linear models. Subgroup analyses were conducted for sex and gestational age (GA) at birth. ResultsAmong 177 eligible children, 132 (74.6%) completed neurodevelopmental assessment at 5 years (DHA, N=64, placebo, N=68). Total Difficulties Score did not differ between the DHA and placebo groups (mean differences, -0.9 [95% confidence interval, -2.7 to 0.8], P=0.30), nor any of the secondary outcomes. There was no significant interaction between treatment groups and sex, nor GA, for the primary outcome. However, significant interactions between treatment groups and sex or GA were found for some secondary outcomes. ConclusionsIn very preterm infants, high-dose DHA supplementation did not improve behavioral functioning at 5 years. Clinical Trial RegistrationClinicalTrials.gov, NCT02371460, https://clinicaltrials.gov/study/NCT02371460

Health-related quality of life in children and adolescents born very preterm and its correlates: a cross-sectional study

ObjectiveWe aimed to assess health-related quality of life (HRQOL) in a cohort of very preterm born children and adolescents (aged 5–16), and to compare it with their fullterm born siblings...

Nonpharmaceutical Interventions and Neurodevelopmental Outcomes in School-Age Preterm Children and Adolescents: A Systematic Review

Abstract Objective: To systematically review nonpharmaceutical interventions aiming to enhance neurodevelopment in preterm children and adolescents (aged 4–18 years). Method: A systematic review of the literature was conducted for all studies published up to May 1, 2022, across Medline, Web of Science, and PsycINFO databases. Studies were evaluated for inclusion by 2 independent reviewers using predetermined inclusion criteria. The Risk of Bias In Non-randomized Studies of Interventions and the Cochrane risk-of-bias tool for randomized trials (RoB 2) tools were used to assess bias in the selected studies. Results: Of the 1778 articles identified, 23 were included. Quality assessment revealed moderate bias in 52.2%, low bias in 21.7%, and serious bias in 26.1%. The selected studies comprised 60.9% randomized controlled trials and 21.7% pre- versus postdesigns. Interventions included Cogmed Working Memory Training® (43.5%), BrainGame Brian (13%), physiotherapy (13%), and others (30.4%). Qualitative analysis showed the limited impact of interventions on neurodevelopmental outcomes in preterm children aged 4–18 years. Conclusion: Despite recent efforts to use more rigorous methodologies, current research on school-age interventions for preterm neurodevelopment exhibits methodological limitations. There is a pressing need for well-designed, large-scale clinical trials to evaluate the efficacy of nonpharmaceutical interventions in this vulnerable population.

Longitudinal transcriptional immune profiles and persistent wheezing in moderate-to-late preterm infants.

Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing. A convenience sample of a multicenter birth cohort (SAREPREM) of moderate-late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression. Seventy-six children were included in the study; 33 were classified as non-wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non-wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers. Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late-preterm infants.

Design and implementation of a multicenter protocol to obtain impulse oscillometry data in preterm children

ABSTRACTImportanceObjective measures of lung function are critical for assessing respiratory outcomes of prematurity. Among extremely low gestational age neonates (ELGANs) (&lt; 29 weeks gestational age), high rates of neurodevelopmental impairment may interfere with lung function testing. Impulse oscillometry (IOS) is a noninvasive test of respiratory system mechanics not requiring forced expiration.ObjectiveTo describe a multicenter study design for respiratory follow‐up testing in a cohort with a high rate of extreme prematurity.MethodsSchool‐age children enrolled in two prior trials of ELGANs and term controls were assessed by IOS at five centers. Groups consisted of children with prematurity with a high incidence of bronchopulmonary dysplasia, children with prematurity with no or minimal lung disease, and healthy term children. A rigorous centralized review process reviewed IOS studies for technical acceptability. Approach to design and implementation, rates of feasibility and success, and characteristics of participants are described.ResultsA total of 243 children were recruited, of whom 239 (98%) attempted oscillometry. There were high rates of technical acceptability across all three cohorts (85%–90% of attempted tests), and across all five centers (80%–94% of attempted tests). Respiratory and neuromotor clinical factors associated with testing failure included a higher number of days on ventilation during neonatal intensive care, a history of intraventricular hemorrhage grade 3 or 4, and gross motor functional impairment.InterpretationWe report high rates of feasibility and success of oscillometry in a large multicenter ELGAN population, in whom neurological and developmental comorbidities likely play a confounding role.

Health state at the age of 12 months in preterm children who have suffered intraventricular hemorrhages I and II degree during early neonatal period. Risk factors for the formation of cerebral palsy

Health state at the age of 12 months in preterm children who have suffered intraventricular hemorrhages I and II degree during early neonatal period. Risk factors for the formation of cerebral palsy

Is Temperament Associated with Academic School Readiness in Children Born Very Preterm?

ABSTRACT Research Findings: Temperament, which can be assessed as early as 3 months, is associated with school readiness and later academic achievement in children born full term. Although children born preterm demonstrate a dysregulated temperament and are at significant risk for lower school readiness, we found no studies investigating whether early temperament is associated with school readiness in this at-risk population. Investigating whether temperament is a precursor of academic risk in preterm children can facilitate early identification and possible intervention efforts. We explored the association of negative affect, surgency, and regulation/effortful control temperament ratings collected at 3-months and 3-years corrected ages with school readiness at 3-years corrected age in children born very preterm. Participants included 297 children born very preterm (53.9% male). After controlling for key covariates, Positive Affectivity/Surgency ratings at 3-months were significantly associated with the Bracken Basic Concept Scale – School Readiness composite score, and Effortful Control ratings at 3-years were associated with Adaptive Behavior Assessment System, Third Edition (ABAS-3) Functional Pre-Academics ratings. Practice or Policy: These findings may enhance the ability to identify premature children at risk for difficulties at school entry early.

Children born very preterm experience altered cortical expansion over the first decade of life.

The brain develops rapidly from the final trimester of gestation through childhood, with cortical surface area expanding greatly in the first decade of life. However, it is unclear exactly where and how cortical surface area changes after birth, or how prematurity affects these developmental trajectories. Fifty-two very preterm (gestational age at birth = 26 ± 1.6 weeks) and 41 full-term (gestational age at birth = 39 ± 1.2 weeks) infants were scanned using structural magnetic resonance imaging at term-equivalent age and again at 9/10 years of age. Individual cortical surface reconstructions were extracted for each scan. Infant and 9/10 cortical surfaces were aligned using anatomically constrained Multimodal Surface Matching (aMSM), a technique that allows calculation of local expansion gradients across the cortical surface for each individual subject. At the neonatal time point, very preterm infants had significantly smaller surface area than their full-term peers (P < 0.001), but at the age 9/10-year time point, very preterm and full-term children had comparable surface area (P > 0.05). Across all subjects, cortical expansion by age 9/10 years was most pronounced in frontal, temporal, and supramarginal/inferior parietal junction areas, which are key association cortices (P Spin < 0.001). Very preterm children showed greater cortical surface area expansion between term-equivalent age and age 9/10 compared to their full-term peers in the medial and lateral frontal areas, precuneus, and middle temporal/banks of the superior sulcus junction (P < 0.05). Furthermore, within the very preterm group, expansion was highly variable within the orbitofrontal cortex and posterior regions of the brain. By mapping these patterns across the cortex, we identify differences in association cortices that are known to be important for executive functioning, emotion processing, and social cognition. Additional longitudinal work will be needed to understand if increased expansion in very preterm children is adaptive, or if differences persist into adulthood.

Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions

Introduction: The innate branch of the immune system is important in early life, in particular for infants born preterm. Methods: We performed a longitudinal analysis of the peripheral monocyte compartment in extremely preterm children from a randomized, placebo-controlled study of probiotic supplementation. PBMCs and fecal samples were collected at several timepoints during the first months of life. Monocyte characteristics were analyzed by flow cytometry, and LPS-stimulated PBMC culture supernatants were analyzed by Luminex or ELISA. Plasma cytokines and gut microbiota composition were analyzed by ELISA and 16S rRNA-sequencing, respectively. Results: The extremely preterm infants had persistent alterations in their monocyte characteristics that were further aggravated in chorioamnionitis cases. They showed a markedly reduced TLR4 expression and hampered LPS-stimulated cytokine responses 14 days after birth. Notably, at later timepoints, TLR4 expression and LPS responses no longer correlated. Sepsis during the first weeks of life strongly associated with increased pro-inflammatory, and reduced IL-10, responses also at postmenstrual week 36. Further, we report a correlation between gut microbiota features and monocyte phenotype and responses, but also that probiotic supplementation associated with distinct monocyte phenotypic characteristics, without significantly influencing their responsiveness. Conclusion: Extremely preterm infants have monocyte characteristics and functional features that deviate from infants born full-term. Some of these differences persist until they reach an age corresponding to full-term, potentially making them more vulnerable to microbial exposures during the first months of life.

Gestational age, maternal smoking, neurological lesion and retinopathy predict strabismus at age 5.5 in preterm children.

Prematurity is a risk factor for strabismus, but the roles of intermediate factors like retinopathy of prematurity (ROP) and neurological lesions are less understood. We aimed to identify neonatal risk factors for strabismus at age 5.5 in preterm children. Data were extracted from the étude épidémiologique sur les petits âges gestationnels 2 cohort, a French prospective population-based study of preterm children born in 2011 with gestational age of 34 weeks or less. Strabismus was recorded during a medical interview at 5.5 years. Using a directed acyclic graph, intermediate and confounding factors were identified. Total and direct effects of gestational age on strabismus risk were analysed using generalised estimating equation. Among 2419 children assessed, 274 (52.6% male) presented strabismus at 5.5 years. The direct effect of gestational age remained significant after adjustment (p < 0.001). In the complete imputed model: maternal smoking during pregnancy (odds ratio, OR 1.8; 95% confident interval, 95% CI 1.3-2.6), neonatal severe cerebral lesions (OR 2.9, 95% CI 1.8-4.6) and severe ROP (OR 4.2, 95% CI 1.9-9.0) were independent risk factors. Special attention is needed regarding strabismus screening at age 5.5 in preterm children, even without severe cerebral lesions and ROP. Smoking cessation during pregnancy should be encouraged.

Local authority variation in special educational needs provision at the start of primary school: observational study of preterm children born in England, 2003-2013

Objective and ApproachWe explored variation in special educational needs (SEN) provision between local authorities (LAs) in England by focussing on children born preterm (24-&lt;37 weeks gestation). We used linked individual-level state-funded hospital and school records from the ECHILD database, alongside publicly available school-level records. LA of child’s residential address (n=150) and recording of SEN provision (split into SEN support and education, health and care plans, EHCPs) were captured at the January school census in year one, when pupils were five/six years old. We fitted multi-level logistic regression models to the child-level records that included a-priori selected child- and LA-level characteristics. ResultsOur population included 226,419 children (45.4% female ; 10.6% with a congenital anomaly) born between 2003-2013 and attending a state-funded primary school. Across LAs, the median prevalence of SEN support and EHCPs recorded in year one was 18.4% (interquartile range 16.4%-20.4%) and 4.2% (3.5%-4.8%), respectively. In the SEN support vs. no SEN provision model, there was very low correlation among children from the same LA (intraclass correlation coefficient (ICC)=0.006 )). There was higher correlation in the EHCP vs. no SEN provision model (ICC=0.032). Of the LA-level characteristics, the percentage of children eligible for free school meals had the greatest impact on the ICC values (reduction of 26.7% in the EHCP model). ConclusionsLess than 1% of the variation in SEN support and approximately 3% of the variation in EHCPs was explained at the LA level. We will extend these models to consider variation at the school level.