Socioemotional and Psychological Outcomes of Hypoxic-Ischemic Encephalopathy: A Systematic Review.

BACKGROUND AND OBJECTIVES: Therapeutic hypothermia has reduced the risk of death or major disability following perinatal hypoxic-ischemic encephalopathy (HIE); however, many children who experience perinatal HIE still go on to develop personal and behavioral challenges, which can be difficult for caregivers and a public health burden for society. Our objective with this review is to systematically identify and synthesize studies that evaluate associations between perinatal HIE and socioemotional or psychological outcomes. METHODS: We screened all search-returned journal articles from Cochrane Library, Embase, Medline, PsycINFO, Scopus, and Web of Science from data inception through February 1, 2023. Keywords related to HIE (eg, neonatal encephalopathy, neonatal brain injury) and outcomes (eg, social*, emotion*, behav* problem, psycholog*, psychiatr*) were searched with a predefined search string. We included all observational human studies reporting socioemotional or psychological sequelae of term HIE. Study data were recorded on standardized sheets, and the Newcastle-Ottawa Scale was adapted to assess study quality. RESULTS: We included 43 studies documenting 3244 HIE participants and 2132 comparison participants. We found statistically significant associations between HIE and social and emotional, behavioral, and psychological and psychiatric deficits throughout infancy, childhood, and adolescence (19 studies). The authors of the included studies also report nonsignificant findings (11 studies) and outcomes without statistical comparison (25 studies). CONCLUSIONS: Perinatal HIE may be a risk factor for a range of socioemotional and psychological challenges in the short- and long-term. Routine screening, early intervention, and follow-up support may be particularly beneficial to this population.

Association between maternal hemoglobin concentration and educational attainment in mid-childhood in a high-resource obstetric setting: a prospective cohort study.

BACKGROUND: Although maternal hemoglobin levels during pregnancy are commonly associated with perinatal outcomes, their link to childhood neurodevelopment remains uncertain. OBJECTIVE: This study aimed to examine the associations between maternal hemoglobin in early and late pregnancy and the educational attainment of offspring mid-childhood in a high-resource obstetric setting. STUDY DESIGN: Pregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, United Kingdom, 2008-2012, N=3285) were linked to mid-childhood educational outcomes (Department for Education, United Kingdom). Regression models adjusted for maternal, child, and socioeconomic factors were used to determine associations between maternal hemoglobin, pregnancy complications, and offspring educational outcomes (aged 5-7 years). RESULTS: No association was observed between maternal hemoglobin at 12 weeks and the likelihood of either adverse pregnancy outcomes or children meeting expected educational standards between ages 5-7 years. Higher maternal hemoglobin at 28 weeks was associated with an increased risk of small-for-gestational-age infants (adjusted odds ratio, 1.26 [95% confidence interval, 1.11-1.59]; P=.002) and preterm birth (adjusted odds ratio, 1.38 [95% confidence interval, 1.11-1.81]; P=.005). There were no adverse birth outcomes associated with anemia. However, children of mothers who were anemic at 28 weeks had ∼40% increased risk of not attaining expected educational standards at age 5 (adjusted odds ratio, 1.42 [95% confidence interval, 1.03-1.95]; P=.03). There was no association between maternal anemia at 28 weeks and educational performance at ages 6-7. No associations were found between high maternal hemoglobin concentrations (top decile) or change in hemoglobin concentrations between 12 and 28 weeks and childhood educational attainment. CONCLUSION: Maternal anemia at 28 weeks of pregnancy is associated with reduced educational attainment at 5 years old but not at older ages (6-7 years old). A proactive approach to increasing maternal hemoglobin in high-resource settings is unlikely to impact long-term childhood educational attainment.

Maternal high body mass index, but not gestational diabetes, is associated with poorer educational attainment in mid-childhood.

BACKGROUND: Previous studies suggest that gestational diabetes mellitus is associated with poorer cognitive outcomes in children. However, confounding factors, especially maternal body mass index, have been poorly accounted for. OBJECTIVE: This study aimed to examine the independent associations between maternal body mass index, gestational diabetes mellitus status, and educational outcomes. STUDY DESIGN: Antenatal data from a prospective birth cohort (Pregnancy Outcome Prediction Study, 2008-2012, Cambridge, United Kingdom) were linked to mid-childhood educational outcomes (Department for Education, United Kingdom). A total of 3249 children born at term were stratified by maternal gestational diabetes mellitus status and body mass index at booking (<25 vs ≥25 kg/m2). Regression models adjusted for relevant maternal, child, and socioeconomic factors were used to determine associations with academic outcomes at ages of 5 to 7 years. RESULTS: No differences in educational attainment were found between children exposed to gestational diabetes mellitus and nonexposed children. Neither maternal glucose levels measured at 11 to 14 or 24 to 28 weeks, nor acceleration of the fetal abdominal circumference growth velocity were related to educational attainment at ages of 5 to 7 years. Children of mothers with booking body mass index ≥25 kg/m2 (vs <25 kg/m2) were ∼50% more likely to not meet expected educational standards regardless of gestational diabetes mellitus status (age 5: adjusted odds ratio, 1.44; 95% confidence interval, 1.19-1.74; P<.001; age 6: adjusted odds ratio, 1.61; 95% confidence interval, 1.28-2.02; P<.001). The association between maternal body mass index and offspring educational attainment is dose-dependent and robust to stratification by gestational diabetes mellitus status and adjustment for socioeconomic factors. CONCLUSION: Mid-childhood educational attainment is not associated with maternal glucose status. This may provide important reassurance for pregnant women and clinicians. However, maternal body mass index is associated with lower childhood educational attainment and may be modifiable with intervention before or during pregnancy.

Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants.

Streptococcus agalactiae (Group B Streptococcus; GBS) is a common cause of sepsis in neonates. Previous work detected GBS DNA in the placenta in ~5% of women before the onset of labour, but the clinical significance of this finding is unknown. Here we re-analysed this dataset as a case control study of neonatal unit (NNU) admission. Of 436 infants born at term (≥37 weeks of gestation), 7/30 with placental GBS and 34/406 without placental GBS were admitted to the NNU (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.3-7.8). We then performed a validation study using non-overlapping subjects from the same cohort. This included a further 239 cases of term NNU admission and 686 term controls: 16/36 with placental GBS and 223/889 without GBS were admitted to the NNU (OR 2.4, 95% CI 1.2-4.6). Of the 36 infants with placental GBS, 10 were admitted to the NNU with evidence of probable but culture-negative sepsis (OR 4.8, 95% CI 2.2-10.3), 2 were admitted with proven GBS sepsis (OR 66.6, 95% CI 7.3-963.7), 6 were admitted and had chorioamnionitis (inflammation of the foetal membranes) (OR 5.3, 95% CI 2.0-13.4), and 5 were admitted and had funisitis (inflammation of the umbilical cord) (OR 6.7, 95% CI 12.5-17.7). Foetal cytokine storm (two or more pro-inflammatory cytokines >10 times median control levels in umbilical cord blood) was present in 36% of infants with placental GBS DNA and 4% of cases where the placenta was negative (OR 14.2, 95% CI 3.6-60.8). Overall, ~1 in 200 term births had GBS detected in the placenta, which was associated with infant NNU admission and morbidity.

Association between antenatal diagnosis of late fetal growth restriction and educational outcomes in mid-childhood: A UK prospective cohort study with long-term data linkage study.

BACKGROUND: Fetal growth restriction (FGR) is associated with a suboptimal intrauterine environment, which may adversely impact fetal neurodevelopment. However, analysing neurodevelopmental outcomes by observed birthweight fails to differentiate between true FGR and constitutionally small infants and cannot account for iatrogenic intervention. This study aimed to determine the relationship between antenatal FGR and mid-childhood (age 5 to 7 years) educational outcomes. METHODS AND FINDINGS: The Pregnancy Outcome Prediction Study (2008-2012) was a prospective birth cohort conducted in a single maternity hospital in Cambridge, United Kingdom. Clinicians were blinded to the antenatal diagnosis of FGR. FGR was defined as estimated fetal weight (EFW) <10th percentile at approximately 36 weeks of gestation, plus one or more indicators of placental dysfunction, including ultrasonic markers and maternal serum levels of placental biomarkers. A total of 2,754 children delivered at term were divided into 4 groups: FGR, appropriate-for-gestational age (AGA) with markers of placental dysfunction, healthy small-for-gestational age (SGA), and healthy AGA (referent). Educational outcomes (assessed at 5 to 7 years using UK national standards) were assessed with respect to FGR status using regression models adjusted for relevant covariates, including maternal, pregnancy, and socioeconomic factors. Compared to healthy AGA (N = 1,429), children with FGR (N = 250) were at higher risk of "below national standard" educational performance at 6 years (18% versus 11%; aOR 1.68; 95% CI 1.12 to 2.48, p = 0.01). By age 7, children with FGR were more likely to perform below standard in reading (21% versus 15%; aOR 1.46; 95% CI 0.99 to 2.13, p = 0.05), writing (28% versus 23%; aOR 1.46; 95% CI 1.02 to 2.07, p = 0.04), and mathematics (24% versus 16%; aOR 1.49; 95% CI 1.02 to 2.15, p = 0.03). This was consistent whether FGR was defined by ultrasound or biochemical markers. The educational attainment of healthy SGA children (N = 126) was comparable to healthy AGA, although this comparison may be underpowered. Our study design relied on linkage of routinely collected educational data according to nationally standardised metrics; this design allowed a high percentage of eligible participants to be included in the analysis (75%) but excludes those children educated outside of government-funded schools in the UK. Our focus on pragmatic and validated measures of educational attainment does not exclude more subtle effects of the intrauterine environment on specific aspects of neurodevelopment. CONCLUSIONS: Compared to children with normal fetal growth and no markers of placental dysfunction, FGR is associated with poorer educational attainment in mid-childhood.

Asymmetric Maxillary Expansion Introduced by Surgically Assisted Rapid Palatal Expansion: A Systematic Review.

PURPOSE: A commonly reported complication of surgically assisted rapid palatal expansion (SARPE) that has not been explored extensively is uneven expansion between left and right sides, which requires secondary surgery for correction. This systematic review aims to analyze the prevalence and potential causes of asymmetric expansion in the transverse dimension after SARPE to guide the clinical practice. METHODS: Electronic databases and manual search were used to search for original articles published on SARPE on March 11, 2022. Original human studies that recorded the number and percentage of asymmetric expansion after two-piece SARPE were included. The 2020 Preferred Reporting Items for Systemic Reviews and Meta-Analyses guideline was implemented for the quality assessment and data analysis of the included articles. The study was registered at the International Prospective Register of Systematic Reviews under the number CRD42022300782. RESULTS: After applying inclusion and exclusion criteria, 13 articles were included in the final review. The risk of bias was high in 8 studies and medium in the other 5 studies. Overall, the prevalence of asymmetric expansion in the transverse dimension (different amount of expansion between left and right sides) was 7.52%, with 12.90% of patients involved receiving a second surgery for correction. Expander design did not significantly affect the rate of asymmetry expansion. Pterygomaxillary fissure release significantly increased the rate of asymmetry expansion (11.02% vs 5.08%, P < .001). In comparison, lateral nasal wall osteotomy (4.26% vs 14.77%, P < .001) and release of the nasal septum (5.22% vs 17.15%, P < .001) significantly lowered the rate of asymmetry expansion, respectively. CONCLUSIONS: Asymmetric dentoskeletal expansion between left and right sides is a common complication of SARPE procedures, mostly caused by variations in surgical cuts. However, the risk of bias in currently available publications is high. Further studies are warranted to fully understand the causes of asymmetric expansion.

Lung injury in axolotl salamanders induces an organ-wide proliferation response.

BACKGROUND: Ambystoma mexicanum, the axolotl salamander, is a classic model organism used to study vertebrate regeneration. It is assumed that axolotls regenerate most tissues, but the exploration of lung regeneration has not been performed until now. RESULTS: Unlike the blastema-based response used during appendage regeneration, lung amputation led to organ-wide proliferation. Pneumocytes and mesenchymal cells responded to injury by increased proliferation throughout the injured lung, which led to a recovery in lung mass and morphology by 56 days post-amputation. Receptors associated with the Neuregulin signaling pathway were upregulated at one and 3 weeks post lung amputation. We show expression of the ligand, neuregulin, in the I/X cranial nerve that innervates the lung and cells within the lung. Supplemental administration of Neuregulin peptide induced widespread proliferation in the lung similar to an injury response, suggesting that neuregulin signaling may play a significant role during lung regeneration. CONCLUSION: Our study characterizes axolotl lung regeneration. We show that the lung responds to injury by an organ-wide proliferative response of multiple cell types, including pneumocytes, to recover lung mass.

Generation COVID-19 - Should the foetus be worried?

AIM: The aim of this narrative review was to evaluate the risks, both direct and indirect, to the foetus from the COVID-19 pandemic. METHODS: Direct and indirect risks were defined as (a) vertical infection (congenital or intrapartum), (b) maternal infection and its sequelae, and (c) sources of maternal stress during lockdown, including social isolation and altered healthcare provision. RESULTS: Early studies suggest that vertical viral transmission is low; however, there may be an important effect of maternal infection on foetal growth and development. The impact of various degrees of lockdown on prospective mothers' health, habits and healthcare provision is of concern. In particular, increased maternal stress has been shown to have a significant effect on foetal brain development increasing the risk of mental health, and cognitive and behavioural disorders in later life. CONCLUSION: From the evidence available to date, direct risks to the foetus from the SARS-CoV-2 virus are low. Indirect effects of the pandemic, particularly resulting from the effect of maternal stress on the developing brain, can have lifelong detrimental impacts for this generation of children.

Pilot study to establish a prospective neonatal cohort: Study of Preterm Infants and Neurodevelopmental Genes (SPRING).

BACKGROUND: Genetic risk variants and preterm birth are early and potent risk factors for later neuropsychiatric disorders. To understand the interrelationships between these factors, a large-scale genetic study of very preterm (VPT, <32 weeks gestation) infants with prospective follow-up is required. In this paper, we describe a streamlined study approach, using efficient processes for biological and clinical data collection, to feasibly establish such a cohort. METHODS: We sought to recruit 500 VPT families within a 1 year period from neonatal units. Treating clinical teams recruited eligible participants, obtained parent consent, collected blood samples and posted specimens to the research laboratory. We extracted all clinical data from the National Neonatal Research Database, an existing UK resource that captures daily patient-level data on all VPT infants. RESULTS: Between May 2017 and June 2018, we established a cohort of 848 VPT infants and their parents from 60 English neonatal units. The study population (median (IQR), gestation: 28.9 (26-30) weeks; birth weight: 1120 (886-1420) g) represented 18.9% of eligible infants born at the study sites during the recruitment period (n=4491). From the subset of 521 complete family trios, we successfully completed genotyping for 510 (97.9%) trios. Of the original 883 infants whose parents consented to participate, the parents of 796 (90.1%) infants agreed to future data linkage and 794 (89.9%) agreed to be recalled. CONCLUSION: We demonstrate the feasibility and acceptability of streamlined strategies for genetic, neonatal and longitudinal data collection and provide a template for future cost-effective and efficient cohort development.

Developmental trajectories of infants born at less than 30 weeks' gestation on the Bayley-III Scales.

OBJECTIVE: To describe the cognitive, language and motor developmental trajectories of children born very preterm and to identify perinatal factors that predict the trajectories. DESIGN: Data from a cohort of 1142 infants born at <30 weeks' gestation who were prospectively assessed on the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III) at 3, 6, 12 and 24 months corrected age, were analysed using the Super Imposition by Translation and Rotation (SITAR) growth curve analysis model. MAIN OUTCOME MEASURES: Developmental trajectory SITAR models for Bayley-III cognitive, language (receptive and expressive communication subscales) and motor (fine and gross motor subscales) scores. RESULTS: The successfully fitted SITAR models explained 62% of variance in cognitive development, 68% in receptive communication, 53% in fine motor and 68% in the gross motor development. There was too much variation in the expressive communication subscale to fit a SITAR model. The rate of development (gradient of the curve) best explains the variation in trajectories of development in all domains. Lower gestational age, lower birth weight and male sex significantly predicted a slower rate of development. CONCLUSION: The rate of development, rather than single time point developmental assessment, best predicts the very preterm infant's developmental trajectory and should be the focus for monitoring and early intervention.

Contribution of de novo and inherited rare CNVs to very preterm birth.

BACKGROUND: The genomic contribution to adverse health sequelae in babies born very preterm (<32 weeks' gestation) is unknown. We conducted an investigation of rare CNVs in infants born very preterm as part of a study to determine the feasibility and acceptability of a larger, well-powered genome-wide investigation in the UK, with follow-up using linked National Health Service records and DNA storage for additional research. METHODS: We studied 488 parent-offspring trios. We performed genotyping using Illumina Infinium OmniExpress Arrays. CNV calling and quality control (QC) were undertaken using published protocols. We examined de novo CNVs in infants and the rate of known pathogenic variants in infants, mothers and fathers and compared these with published comparator data. We defined rare pathogenic CNVs as those consistently reported to be associated with clinical phenotypes. RESULTS: We identified 14 de novo CNVs, representing a mutation rate of 2.9%, compared with 2.1% reported in control populations. The median size of these CNV was much higher than in comparator data (717 kb vs 255 kb). The rate of pathogenic CNVs was 4.3% in infants, 2.7% in mothers and 2% in fathers, compared with 2.3% in UK Biobank participants. CONCLUSION: Our findings suggest that the rate of de novo CNVs, especially rare pathogenic CNVs, could be elevated in those born very preterm. However, we will need to conduct a much larger study to corroborate this conclusion.

Recent advances in the genetics of preterm birth.

Preterm birth is associated with short- and long-term impairments affecting physical, cognitive, and neuropsychiatric health. These sequelae, together with a rising preterm birth rate and increased survival, make prematurity a growing public health issue because of the increased number of individuals with impaired health throughout the life span. Although a major contribution to preterm birth comes from environmental factors, it is also modestly heritable. Little is known about the architecture of this genetic contribution. Studies of common and of rare genetic variation have had limited power, but recent findings implicate variation in both the maternal and fetal genome. There is some evidence risk alleles in mothers may be enriched for processes related to immunity and inflammation, and in the preterm infant, processes related to brain development. Overall genomic discoveries for preterm birth lag behind progress for many other multifactorial diseases and traits. Investigations focusing on gene-environment interactions may also provide insights, but these studies still have a number of limitations. Adequately sized genetic studies of preterm birth are a priority for the future especially given the breadth of its negative health impacts across the life span and the current interest in newborn genome sequencing.

The Tumor Suppressor FBW7 and the Vitamin D Receptor Are Mutual Cofactors in Protein Turnover and Transcriptional Regulation.

The E3 ligase and tumor suppressor FBW7 targets drivers of cell-cycle progression such as the oncogenic transcription factor c-MYC, for proteasomal degradation. Vitamin D signaling regulates c-MYC expression and turnover in vitro and in vivo, which is highly significant as epidemiologic data link vitamin D deficiency to increased cancer incidence. We hypothesized that FBW7 and the vitamin D receptor (VDR) controlled each other's function as regulators of protein turnover and gene transcription, respectively. We found that hormonal 1,25-dihydroxyvitamin D3 (1,25D) rapidly enhanced the interaction of FBW7 with VDR and with c-MYC, whereas it blocked FBW7 binding to c-MYC antagonist MXD1. 1,25D stimulated the recruitment of FBW7, SCF complex subunits, and ubiquitin to DNA-bound c-MYC, consistent with 1,25D-regulated c-MYC degradation on DNA. 1,25D also accelerated the turnover of other FBW7 target proteins such as Cyclin E, c-JUN, MCL1, and AIB1, and, importantly, FBW7 depletion attenuated the 1,25D-induced cell-cycle arrest. Although the VDR contains a consensus FBW7 recognition motif in a VDR-specific insertion domain, its mutation did not affect FBW7-VDR interactions, and FBW7 ablation did not stabilize the VDR. Remarkably, however, FBW7 is essential for optimal VDR gene expression. In addition, the FBW7 and SCF complex subunits are recruited to 1,25D-induced genes and FBW7 depletion inhibited the 1,25D-dependent transactivation. Collectively, these data show that the VDR and FBW7 are mutual cofactors, and provide a mechanistic basis for the cancer-preventive actions of vitamin D. IMPLICATIONS: The key findings show that the VDR and the E3 ligase FBW7 regulate each other's functions in transcriptional regulation and control of protein turnover, respectively, and provide a molecular basis for cancer-preventive actions of vitamin D.Visual Overview: http://mcr.aacrjournals.org/content/17/3/709/F1.large.jpg.

Validity of neurodevelopmental outcomes of children born very preterm assessed during routine clinical follow-up in England.

OBJECTIVE: To determine the validity of assessing and recording the neurodevelopmental outcome of very preterm infants during routine clinical follow-up in England. DESIGN: Children born <30 weeks gestation, attending routine clinical follow-up at post-term ages 20-28 months, were recruited. Data on neurodevelopmental outcomes were recorded by the reviewing clinician in a standardised format in the child's electronic patient record, based on a set of key questions designed to be used without formal training or developmental testing. Using a predefined algorithm, each participant was classified as having 'no', 'mild/moderate' or 'severe' impairment in cognitive, communication and motor domains. All participants also received a research assessment by a single assessor using the Bayley Scales of Infant Development, third edition (Bayley-III). The sensitivity and specificity of routine data in capturing impairment (any Bayley-III score <85) or severe impairment (any Bayley-III score <70) was calculated. RESULTS: 190 children participated. The validity of routine assessments in identifying children with no impairment and no severe impairment was high across all domains (specificities 83.9%-100.0% and 96.6%-100.0%, respectively). However, identification of impairments, particularly in the cognitive (sensitivity 69.7% (55.1%-84.3%)) and communication (sensitivity (53.2% (42.0%-64.5%)) domains, was poor. CONCLUSIONS: Neurodevelopmental status determined during routine clinical assessment lacks adequate sensitivity in cognitive and communication domains. It is uncertain whether this reflects the assessment or/and the recording of findings. As early intervention may improve education and social outcomes, this is an important area for healthcare quality improvement research.

Developmental Assessments in Preterm Children: A Meta-analysis.

CONTEXT: Developmental outcomes of very preterm (gestational age ≤32 weeks) or very low birth weight (<1500 g) children are commonly reported before age 3 years although the predictive validity for later outcomes are uncertain. OBJECTIVE: To determine the validity of early developmental assessments in predicting school-age cognitive deficits. DATA SOURCES: PubMed. STUDY SELECTION: English-language studies reporting at least 2 serial developmental/cognitive assessments on the same population, 1 between ages 1 and 3 years and 1 at ≥5 years. DATA EXTRACTION: For each study, we calculated the sensitivity, specificity, and positive and negative predictive values of early assessment for cognitive deficit (defined as test scores 1 SD below the population mean). Pooled meta-analytic sensitivity and specificity were estimated by using a hierarchical summary receiver operator characteristic curve. RESULTS: We included 24 studies (n = 3133 children). Early assessments were conducted at 18 to 40 months and generally involved the Bayley Scales of Infant Development or the Griffiths Mental Development Scales; 11 different cognitive tests were used at school-age assessments at 5 to 18 years. Positive predictive values ranged from 20.0% to 88.9%, and negative predictive vales ranged from 47.8% to 95.5%. The pooled sensitivity (95% confidence interval) of early assessment for identifying school-age cognitive deficit was 55.0% (45.7%-63.9%) and specificity was 84.1% (77.5%-89.1%). Gestational age, birth weight, age at assessment, and time between assessments did not explain between-study heterogeneity. LIMITATIONS: The accuracy of aggregated data could not be verified. Many assessment tools have been superseded by newer editions. CONCLUSIONS: Early developmental assessment has poor sensitivity but good specificity and negative predictive value for school-age cognitive deficit.

Retinopathy of prematurity in English neonatal units: a national population-based analysis using NHS operational data.

OBJECTIVES: To report on retinopathy of prematurity (ROP) screening compliance against a national guideline, factors associated with non-compliance and effect on ROP treatment. DESIGN: National cohort study using operational NHS data from the National Neonatal Research Database (NNRD) for the period 2009-2011. SETTING: 161 (94%) neonatal units in England. POPULATION: Infants born below 32 weeks' gestation and/or with a birth weight below 1501 g. MAIN OUTCOME MEASURES: ROP screening status ('on-time', 'early', 'late', 'unknown') and associated infant and neonatal unit characteristics, ROP treatment. RESULTS: The proportion of infants screened on-time increased over the study period (p<0.001). Of 19 821 eligible infants, 7602 (38.4%) were recorded to have received ROP screening in accordance with the national guideline; 7474 (37.8%) received screening outside the recommended time period; data were missing for 4745 (16.7%) infants. For 16 411 infants in neonatal care during the recommended screening period, late screening was significantly associated with lower gestational age (relative risk ratio (RRR) (95% credible interval) for late versus on-time screening 0.83 (0.80 to 0.86) for each increased week of gestation) and care in a neonatal unit providing less than 500 days of intensive care per annum (2.48 (0.99 to 4.99)). Infants screened late were almost 40% more likely to receive ROP treatment (OR (95% CI) 1.36 (1.05 to 1.76)). CONCLUSIONS: Understanding organisational differences between neonatal units may help improve ROP screening. Patient-level electronic NHS clinical data offer opportunity for future rapid, low cost, population-based evaluations but require improved data entry.

Evaluation of early childhood social-communication difficulties in children born preterm using the Quantitative Checklist for Autism in Toddlers.

OBJECTIVES: To characterize early childhood social-communication skills and autistic traits in children born very preterm using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) and explore neonatal and sociodemographic factors associated with Q-CHAT scores. STUDY DESIGN: Parents of children born before 30 weeks gestation and enrolled in a study evaluating routinely collected neurodevelopmental data between the post-menstrual ages of 20 and 28 months were invited to complete the Q-CHAT questionnaire. Children with severe neurosensory disabilities and cerebral palsy were excluded. Participants received neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III). Q-CHAT scores of this preterm cohort were compared with published general population scores. The association between Bayley-III cognitive and language scores and neonatal and sociodemographic factors with Q-CHAT scores were examined. RESULTS: Q-CHAT questionnaires were completed from 141 participants. At a mean post-menstrual age of 24 months, the Q-CHAT scores of the preterm cohort (mean 33.7, SD 8.3) were significantly higher than published general population scores (mean 26.7; SD 7.8), indicating greater social-communication difficulty and autistic behavior. Preterm children received higher scores, particularly in the categories of restricted, repetitive, stereotyped behavior, communication, and sensory abnormalities. Lower Bayley-III language scores and non-white ethnicity were associated with higher Q-CHAT scores. CONCLUSIONS: Preterm children display greater social-communication difficulty and autistic behavior than the general population in early childhood as assessed by the Q-CHAT. The implications for longer-term outcome will be important to assess.

Nature or nurture: a systematic review of the effect of socio-economic status on the developmental and cognitive outcomes of children born preterm.

The effect of socio-economic status (SES) on the cognitive outcome of preterm-born children is unknown. The objectives of this study were to systematically review the published literature and to report the strength and consistency of the effect of SES on the cognitive outcomes of preterm children, across different SES indicators. We conducted a literature search on MEDLINE, EMBASE, PsycINFO and Social Science Citation Index to identify English-language cohort or case-control studies published after 1990 that had reported the effect of at least one SES indicator on cognitive outcome in children born <37 weeks gestation. Fifteen studies (from a total 4,162 identified) were included. Thirteen SES indicators were evaluated [categorized as: "individual-level" (6 indicators), "family-structure" (3), "contextual" (2) and "composite" (2)]. Maternal educational level was the most frequently evaluated SES indicator (by 11/15 studies) and was most consistently associated with cognitive outcome. Maternal education below high school level was associated with severe cognitive deficiency [reported odds ratios (95 % CI) range: OR = 1.4 (1.0-1.9) to OR = 2.3 (1.2-4.5)]. A meta-analytic measure of the effect of SES was not calculated due to heterogeneity in studies. SES appears to confound the association between preterm birth and cognitive deficit and should be adjusted for in studies reporting cognitive outcome.