Risk Factors for Term-Born Spastic Diplegic Cerebral Palsy: A Case-Control Study.

BACKGROUND: To identify if a predetermined set of potential risk factors are associated with spastic diplegic cerebral palsy (SDCP) in term-born children. METHODS: This is a case-control study with cases (n = 134) extracted from the Canadian Cerebral Palsy Registry (CCPR) and controls (n = 1950) from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Our primary variable was the SDCP phenotype in term-born children. Possible risk factors were selected a priori and include extreme maternal age (<19 or >35 years), pregnancy complications, maternal disease, substance use, perinatal infection, mode of delivery, perinatal adversity (i.e., neonatal encephalopathy presumably on the basis of intrapartum hypoxia-ischemia), sex, and birth weight. Multivariable analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Multivariable analysis revealed associations between term-born SDCP and pregnancy complications (OR = 4.73; 95% CI = 1.91 to 10.56), maternal disease (OR = 2.52; 95% CI = 1.57 to 3.93), substance use (OR = 3.11; 95% CI = 2.10 to 4.55), perinatal infection (OR = 2.72; 95% CI 1.32 to 5.10), Caesarean section (OR = 2.35; 95% CI = 1.62 to 3.40), and perinatal adversity (OR = 2.91; 95% CI = 1.94 to 4.50). Multiple regression analysis revealed associations between SDCP and pregnancy complications (OR = 3.28; 95% CI 1.20 to 8.15), maternal disease (OR = 2.52; 95% CI 1.50 to 4.12), substance use (OR = 3.59; 95% CI 2.37 to 5.40), perinatal infection (OR = 3.78, 95% CI 1.71 to 7.72), Caesarean section (OR = 2.72; 95% CI 1.82 to 4.03), and perinatal adversity (OR = 4.16; 95% CI 2.67 to 6.70). INTERPRETATION: Antenatal (pregnancy complications, maternal disease, substance use) and perinatal (infections, Caesarean section, and perinatal adversity) risk factors are associated with an increased risk of SDCP in term-born children, suggesting variable interactions between risk factors to provide a clinicopathologic framework that is different from SDCP observed in preterm-born children.

Prevalence and Risk Factors for Cerebral Palsy in Children With Congenital Heart Disease Based on Risk of Surgical Mortality.

BACKGROUND: Children with congenital heart disease (CHD) have a higher prevalence of motor impairment secondary to brain injury, resulting in cerebral palsy (CP). The purpose of this study is to determine the prevalence of CP in CHD in a single-center cohort, stratify risk based on surgical mortality using Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) categories and identify risk factors. METHODS: Retrospective cohort study of pediatric patients registered in the University of Florida (UF) Society of Thoracic Surgeons Congenital Heart Surgery database from 2006 to 2017 with a diagnosis of CHD who continued follow-up for more than two years at UF. RESULTS: A total of 701 children with CHD met inclusion criteria. Children identified to have CP were 54 (7.7%). Most common presentation was spastic hemiplegic CP with a Gross Motor Function Classification System of level 2. Analysis of surgical and intensive care factors between the two groups showed that children with CHD and CP had longer time from admission to surgery (P = 0.003), higher STAT categories 4 and 5 (P = 0.038), and higher frequency of brain injury and seizures (P < 0.001). Developmental disabilities and rehabilitation needs were significantly greater for children with CHD and CP when compared with those with CHD alone (P < 0.001). CONCLUSIONS: In our cohort, 7.7% children with CHD develop CP; this is significantly higher than the 2010 US population estimate of 0.3%. Our study suggests higher STAT categories, brain injury, and seizures are associated with developing CP in children with CHD.

The Etiologic Risk Factors for Cerebral Palsy at an Orthopedic Surgery Clinic in South Africa.

BACKGROUND: Cerebral palsy (CP) is a group of disorders that affect movement and posture caused by injury to the developing brain. Although prematurity and low birth weight are common causes in developed countries, birth asphyxia, kernicterus, and infections have been identified as predominant etiologies in Africa. There is, however, very little information on the etiology of CP in South Africa. We aimed to determine the etiology, severity, and topographic distribution of CP in children undergoing orthopedic surgery at our tertiary pediatric unit. METHOD: A retrospective folder review was performed for patients with CP who underwent orthopedic surgery from July 2018 to June 2022. Data were collected on perinatal circumstances, etiologic risk factors for developing CP, severity of disability as classified by the Gross Motor Function Classification Scale (GMFCS), and topographic distribution. Descriptive analysis was performed. RESULTS: A total of 202 patients were included in the analysis. Prematurity (gestational age less than 37 weeks) was noted in 41.6% of the cohort and was the most common risk factor. Hypoxic-ischemic encephalopathy (30.7%), postnatal infections (13.4%), congenital brain malformations (10.4%), and cerebral infections were the next most common etiologic risk factors. Forty-eight percent of patients were classified as GMFCS IV or V. There was a predominance of bilateral (69.5%) compared with unilateral (21.3%) subtypes. CONCLUSION: Most patients undergoing orthopedic surgery for musculoskeletal sequelae of CP had GMFCS levels of IV or V and were bilateral subtypes, emphasizing the need for intervention at a primary care level to decrease the incidence of this frequently preventable condition.

Higher risk of cerebral palsy, seizures/epilepsy, visual- and hearing impairments, cancer, injury and child abuse in children with congenital anomalies: Data from the EUROlinkCAT study.

AIM: The aim is to examine the risk of cerebral palsy, seizures/epilepsy, visual- and hearing impairments, cancer, injury/poisoning and child abuse in children with and without a congenital anomaly up to age 5 and 10 years. METHODS: This is a population-based data linkage cohort study linking information from the European Surveillance of Congenital Anomalies network (EUROCAT) and birth registries to hospital discharge databases. We included 91 504 live born children with major congenital anomalies born from 1995 to 2014 from nine EUROCAT registries in five countries and 1 960 727 live born children without congenital anomalies (reference children). Prevalence and relative risk (RR) were estimated for each of the co-morbidities using Kaplan-Meier survival estimates. RESULTS: Children with congenital anomalies had higher risks of the co-morbidities than reference children. The prevalences in the reference children were generally very low. The RR was 13.8 (95% CI 12.5-15.1) for cerebral palsy, 2.5 (95% CI 2.4-2.6) for seizures/epilepsy, 40.8 (95% CI 33.2-50.2) for visual impairments, 10.0 (95% CI 9.2-10.9) for hearing loss, 3.6 (95% CI 3.2-4.2) for cancer, 1.5 (95% CI 1.4-1.5) for injuries/poisoning and 2.4 (95% CI 1.7-3.4) for child abuse. CONCLUSION: Children with congenital anomalies were more likely to be diagnosed with the specified co-morbidities compared to reference children.

Exposure to Paracetamol in Early Pregnancy and the Risk of Developing Cerebral Palsy: A Case-Control Study Using Serum Samples.

OBJECTIVE: To investigate whether maternal paracetamol use in early pregnancy is associated with cerebral palsy (CP) in offspring. STUDY DESIGN: We conducted a registry and biobank-based case-control study with mother-child pairs. We identified CP cases (n = 322) born between 1995 and 2014 from a nationwide CP-registry. Randomly selected controls (n = 343) and extra preterm controls (n = 258) were obtained from a birth registry. For each mother, a single serum sample from early pregnancy (gestation weeks 10-14) was retrieved from a biobank and analyzed for serum concentrations of paracetamol, categorized into unexposed (<1 ng/ml), mildly exposed (1-100 ng/ml), and highly exposed (>100 ng/ml), and in quartiles. Analyses were performed using logistic regression and adjusted for potential confounders. Separate analyses were conducted including only those children born preterm and only those born term. RESULTS: Of the 923 participants, 36.8% were unexposed, 53.2% mildly exposed, and 10% highly exposed to paracetamol. Overall, prenatal exposure to paracetamol was not associated with CP. Sensitivity and subgroup analyses showed no clear associations between paracetamol and CP across strata of term/preterm birth as well as subtypes of CP. CONCLUSIONS: The present study does not support an association between intrauterine exposure to paracetamol in early pregnancy and the risk of CP. However, it is important to stress that the exposure estimate is based on a single serum sample.

The aetiology of preterm birth and risks of cerebral palsy and cognitive impairment: A systematic review and meta-analysis.

AIM: The associations between the aetiology of preterm birth and later neurodevelopmental outcomes are unclear. A systematic review and meta-analysis examined the existing evidence. METHODS: The PubMed and Embase databases were searched for papers published in English from inception to 16 December 2020. We included original papers on the causes of preterm birth and the risks of cerebral palsy (CP) and suboptimal cognitive development. Two reviewers independently evaluated the studies and extracted the data. RESULTS: The literature search yielded 5472 papers and 13 were selected. The aetiology of preterm birth was classified under spontaneous or medically indicated delivery. A meta-analysis was performed, comprising 104 902 preterm infants from 11 papers on CP. Preterm infants born after a medically indicated delivery had a lower CP risk than infants born after spontaneous delivery, with a pooled odds ratio of 0.59 (95% confidence interval 0.40-0.86). This result was robust in the subgroup and sensitivity analyses. Cognitive development was reported in three papers, which suggested that worse outcomes were associated with medically indicated deliveries. CONCLUSION: The aetiology of preterm delivery may contribute to the risk of CP and cognitive delay. Further research is needed, using individual-level meta-analyses to adjust for possible confounders, notably gestational age.

Association Between Assisted Reproductive Technology and Cerebral Palsy: A Meta-Analysis.

BACKGROUND: Since 1978 many children are born thanks to assisted reproductive technology (ART). However, the long-term effects of these therapies are still not fully known. Our objective is to evaluate the risk of cerebral palsy (CP) after ART compared with that in those spontaneously conceived (SC) and to examine this risk in single, multiple, and preterm births and the evolution of the risk over the years. METHODS: PubMed, Embase, and Web of Science databases were searched until December 2022. Studies were included if they studied CP cases in children born through ART. 16 studies were finally selected. Quality of studies was assessed using Newcastle Ottawa Scale. Pooled OR was estimated by weighting individual OR/RR by the inverse of their variance. A random-effect model was applied. To assess the causes of heterogeneity, we performed meta-regression analyses. RESULTS: A significantly high risk of CP was found (OR = 1.27; 95% CI 1.12 to 1.43) in children born through ART compared with those SC. This risk increased in singletons (OR = 1.48; 95% CI 1.23 to 1.79) but disappeared in multiple (OR = 1.05; 95% CI 0.93 to 1.18) and preterm births (OR = 1.09; 95% CI 0.87 to 1.37). We found a higher risk of CP in children born before the year 2000 (OR = 3.40; 95% CI 2.49 to 4.63). CONCLUSIONS: ARTs slightly increase the risk of CP once the effect of multiple gestation is controlled. Further studies are needed to clarify whether the techniques themselves, fertility problems, or associated maternal comorbidities are responsible for this risk.

Classification of events contributing to postneonatal cerebral palsy: Development, reliability, and recommendations for use.

AIM: This paper introduces the Surveillance of Cerebral Palsy in Europe (SCPE) classification of events contributing to postneonatally acquired cerebral palsy, presents its interrater reliability, and describes the cases identified in the SCPE database. METHOD: The development of the classification, based on literature review and expert discussions, resulted in six main categories and 19 subcategories. The first chronological event designated as the primary event was mainly reported. Interrater reliability was assessed through online exercise providing 24 clinical vignettes representing single/complex pathways. Percent agreement and Gwet's AC1 index of reliability were estimated. Primary events were described using data of 221 children born between 2008 and 2012. RESULTS: Thirty-nine professionals (21 registries) participated in the reliability exercise. Substantial overall agreement was reached (0.75), with some contrast between complex (0.48, moderate agreement) and single events involved (0.89, almost perfect). The distribution of primary events showed that 32.1% were infections (category A), 23.1% head injuries (B), 15.4% related to surgery or medical interventions (C), 13.1% cerebrovascular accidents (D), 9.1% hypoxic brain damaging events of other origins (E), and 7.2% miscellaneous (F). INTERPRETATION: This classification allows all the events involved to be recorded while consistently reporting the primary event, and may be used in different settings. WHAT THIS PAPER ADDS: A standardized classification enables the description of the events contributing to postneonatal cerebral palsy (CP). The first chronological event in complex pathway leading to CP is coded. Category choice and coding of the primary event identify preventable situations. The detailed 2-level classification is easy to use in various settings. Substantial overall interrater reliability shows that main categories can be consistently differentiated.

Causation in cerebral palsy: Parental beliefs and associated emotions.

AIM: To better understand parents' beliefs about causation in cerebral palsy (CP) and the emotions related to those beliefs. METHOD: We surveyed 226 parents of children with CP aged 1 to 18 years, recruited from the Victorian Cerebral Palsy Register, to evaluate their beliefs about the causes of CP, including genetic causes, causes specific to their own child, and their attitudes and emotions in relation to these. RESULTS: Although 92% of participants reported that understanding the causes of their child's CP was important, uncertainty about the cause was expressed by 13%. The most frequently endorsed causal factors, in general and in their own child respectively, were intrapartum hypoxia (81%, 36%) or brain damage (69%, 22%), brain damage during pregnancy (73%, 28%), and preterm birth (66%, 28%). Genetic causes were deemed relevant by 13% of participants and hospital or professional error by 16%. Parents shared related feelings of anger (59%), sadness (80%), guilt (61%), and confusion (53%); parental anger was more likely when their child's CP was attributed to intrapartum events. INTERPRETATION: Substantial parental interest in understanding the causes of CP, together with uncertainty about the causes, parents' causal attributions, and significant emotional sequelae, highlight a strong need for provision of information and support for families of children recently diagnosed with CP. WHAT THIS PAPER ADDS: Understanding the causes of their child's cerebral palsy (CP) was important to parents. Parents most often endorsed intrapartum factors as a cause of CP. Parents reported experiencing strong emotions about the causes of their child's CP.

Associations between the aetiology of preterm birth and mortality and neurodevelopment up to 11 years.

AIM: To investigate how the aetiology of very preterm birth/very low birth weight is associated with mortality and later neurodevelopmental outcomes. METHODS: Very preterm/very low-birth weight singletons were categorised based on the aetiology of preterm birth: spontaneous preterm birth (n = 47, 28.1%), preterm premature rupture of membranes (n = 56, 33.5%) or placental vascular pathology (n = 64, 38.3%). Mortality, cerebral palsy, severe cognitive impairment by 11 years of age (<2SD) and mean full-scale intelligence quotient at 11 years were studied in association with birth aetiology. RESULTS: There was no difference in mortality or rate of cerebral palsy according to birth aetiologies. The rate of severe cognitive impairment was lower (4.9% vs. 15.3%) in the preterm premature rupture of the membrane group in comparison to the placental vascular pathology group (OR 0.2, 95% CI 0.03-0.9, adjusted for gestational age). At 11 years, there was no statistically significant difference in the mean full-scale intelligence quotient. CONCLUSION: Placental vascular pathology, as the aetiology of very preterm birth/very low birth weight, is associated with a higher rate of severe cognitive impairments in comparison to preterm premature rupture of membranes, although there was no difference in the mean full-scale intelligence quotient at 11 years. The aetiology of very preterm birth/very low birth weight was not associated with mortality or the rate of cerebral palsy.

Outcomes at 18-24 Months of Infants with Birth Weight under 500 g Born in Korea during 2013-2017: A Nationwide Cohort Study.

INTRODUCTION: This study aimed to investigate the outcomes of infants at 18-24 months born in the Korean Neonatal Network with a birth weight <500 g. METHODS: The anthropometric and neurodevelopmental data of infants with a birth weight <500 g at a gestational age of ≥22 weeks who were registered in the Korean Neonatal Network 2013-2017 and followed up at a corrected age of 18-24 months were reviewed. Neurodevelopmental impairment was defined as the presence of any of the following: (1) cerebral palsy; (2) severe visual impairment; (3) hearing impairment; or (4) cognitive impairment. Cognitive impairment was defined as (1) a Bayley Scales of Infant Development-II Mental Development Index score <70; and (2) Bayley Scales of Infant and Toddler Development-III Cognitive and Language Composite scores <85. Cognitive testing was performed for infants with suspected problems upon clinician's referral to developmental specialists. RESULTS: At a median corrected age of 20 months, 26/52 (50%) of included infants had neurodevelopmental impairment. Cerebral palsy, severe visual impairment, wearing of glasses, hearing impairment, and cognitive impairment occurred in 22%, 0%, 8%, 5%, and 57% of the included infants, respectively. The proportions of infants with <2 standard deviations of weight, length, and head circumference were 54%, 52%, and 56%, respectively. The majority (70%) of infants were rehospitalized, and the most common cause was respiratory problems. CONCLUSION: Half of infants with a birth weight <500 g in Korea may exhibit neurodevelopmental impairment and growth retardation at a corrected age of 18-24 months. Multidisciplinary follow-up along with continuous rehabilitation will be needed to improve neurological and physical development in this special population.

Maternal body mass index and cerebral palsy in children: A systematic review and dose-response meta-analysis.

BACKGROUND: Accumulating studies indicate that maternal obesity is associated with the risk of cerebral palsy (CP); however, their conclusions have been inconsistent. OBJECTIVES: To quantitatively estimate the association between maternal body mass index (BMI) and CP in offspring. DATA SOURCES: PubMed, Embase and Web of Science. STUDY SELECTION AND DATA EXTRACTION: Articles published up to 18 September 2022 were searched that reported the correlation between maternal BMI and CP in children. Two reviewers independently extracted data and critically assessed articles. SYNTHESIS: Pooled relative risks (RR) and 95% confidence intervals (CI) were estimated by the random-effects model. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. RESULTS: In total, 11 articles (8,407,668 participants) were identified for inclusion in our meta-analysis. For maternal underweight, no significant association was found with CP risk (RR 1.11, 95% CI 0.90, 1.38). The risk of CP was increased by 25% (RR 1.25, 95% CI 1.06, 1.47), 38% (RR 1.38, 95% CI 1.18, 1.61) and 127% (RR 2.27, 95% CI 1.82, 2.83) for maternal overweight, obesity and obesity grade 3, respectively. In addition, we observed a positive linear dose-response relationship, with the pooled risk of cerebral palsy in offspring increasing by 3% with each unit increase in maternal BMI. CONCLUSION: This meta-analysis indicates that the risk of CP in offspring grew with maternal overweight or obesity grades increasing, and was positively correlated with maternal BMI.

Neonatal well-being and timing of brain injury in persons with cerebral palsy born at term or late preterm.

AIM: To describe the distribution of neuroimaging patterns in a term/late preterm population-based cohort with cerebral palsy (CP), ascertain associations between neuroimaging patterns and neonatal well-being, estimate the proportion with antenatal or perinatal timing of neuropathology, and apply this information to the understanding of common mechanisms of brain injury and causal pathways. METHOD: The cohort for this observational study comprised 1348 persons born between 1999 and 2017 in Victoria, Australia. Using algorithms designed for the study, neonatal well-being and timing of brain injury were tabulated for the whole cohort and across neuroimaging patterns and birth epochs. RESULTS: Clinical and demographic profiles, neonatal well-being, and timing of brain injury differed across neuroimaging patterns. An estimated 57% of the cohort had a complicated neonatal period. Timing of brain injury was antenatal in 57% and perinatal in 41%. A decrease in the relative proportions of perinatal timing of brain injury was observed over a period when the rates of CP in live births at term decreased. INTERPRETATION: This study begins to bridge the knowledge gap about causation in CP, moving towards better description of the main mechanisms of brain injury and their contribution within CP cohorts, and facilitating the ability to monitor changes over time and the success of preventive measures. WHAT THIS PAPER ADDS: In a population-based, term/late preterm cohort with cerebral palsy, 57% had a complicated neonatal period. In the same cohort, 57% had presumed antenatal timing of brain injury. The relative proportion with perinatal injury decreased over time.

Etiology and Ontogeny of Cerebral Palsy: Implications for Practice and Research.

Cerebral palsy (CP) has been recognized as a group of neurologic disorders with varying etiologies and ontogenies. While a percentage of CP cases arises during labor, the expanded use of electronic fetal monitoring (EFM) to include prevention of CP has resulted in decades of vastly increased interventions that have not significantly reduced the incidence of CP for infants born at term in the USA. Litigation alleging that poor obstetrical practice caused CP in most of these affected children has led to contentious arguments regarding the actual etiologies of this condition and often resulted in substantial monetary awards for plaintiffs. Recent advances in genetic testing using whole exome sequencing have revealed that at least one-third of CP cases in term infants are genetic in origin and therefore not labor-related. Here, we will present and discuss previous attempts to sort out contributing etiologies and ontogenies of CP, and how these newer diagnostic techniques are rapidly improving our ability to better detect and understand such cases. In light of these developments, we present our vision for an overarching spectrum for proper categorization of CP cases into that the following groups: (1) those begun at conception from genetic causes (nonpreventable); (2) those stemming from adverse antenatal/pre-labor events (possibly preventable with heightened antepartum assessment); (3) Those arising from intrapartum events (potentially preventable by earlier interventions); (4) Those occurring shortly after birth (possibly preventable with closer neonatal monitoring); (5) Those that appear later in the postnatal period from non-labor-related causes such as untreated infections or postnatal intracranial hemorrhages.

Cerebral palsy and its medicolegal implications in low- resource settings - the need to establish causality and revise criteria to implicate intrapartum hypoxia: A narrative review.

The objective of this study was to establish scientific causality and to devise criteria to implicate intrapartum hypoxia in cerebral palsy (CP) in low-resource settings, where there is potential for an increase in damaging medicolegal claims against obstetric caregivers, as is currently the situation in South Africa. For the purposes of this narrative review, an extensive literature search was performed, including any research articles, randomised controlled trials, observational studies, case reports or expert or consensus statements pertaining to CP in low-resource settings, medicolegal implications, causality, and criteria implicating intrapartum hypoxia. In terms of causation, there are differences between high-income countries (HICs) and low-resource settings. While intrapartum hypoxia accounts for 10 - 14% of CP in HICs, the figure is higher in low-resource settings (20 - 46%), indicating a need for improved intrapartum care. Criteria implicating intrapartum hypoxia presented for HICs may not apply to low-resource settings, as cord blood pH testing, neonatal brain magnetic resonance imaging (MRI) and placental histology are frequently not available, compounded by incomplete clinical notes and missing cardiotocography tracings. Revised criteria in an algorithm for low-resource settings to implicate intrapartum hypoxia in neonatal encephalopathy (NE)/ CP are presented. The algorithm relies first on specialist neurological assessment of the child, determination of the occurrence of neonatal encephalopathy (by documented or verbal accounts) and findings on childhood MRI, and second on evidence of antepartum and intrapartum contributors to the apparent hypoxia-related CP. The review explores differences between low-resource settings and HICs in trying to establish causation in NE/CP and presents a revised scientific approach to causality in the context of low-resource settings for reaching appropriate legal judgments.

Season of Conception and Risk of Cerebral Palsy.

Importance: Cerebral palsy (CP) is the most prevalent neuromotor disability in childhood, but for most cases the etiology remains unexplained. Seasonal variation in the conception of CP may provide clues for their potential etiological risk factors that vary across seasons. Objective: To evaluate whether the month or season of conception is associated with CP occurrence. Design, Setting, and Participants: This statewide cohort study examined more than 4 million live births that were registered in the California birth records during 2007 to 2015 and were linked to CP diagnostic records (up to year 2021). Statistical analyses were conducted between March 2022 and January 2023. Exposures: The month and season of conception were estimated based on the child's date of birth and the length of gestation recorded in the California birth records. Main Outcomes and Measures: CP status was ascertained from the diagnostic records obtained from the Department of Developmental Services in California. Poisson regression was used to estimate the relative risk (RR) and 95% CI for CP according to the month or the season of conception, adjusting for maternal- and neighborhood-level factors. Stratified analyses were conducted by child's sex and neighborhood social vulnerability measures, and the mediating role of preterm birth was evaluated. Results: Records of 4 468 109 children (51.2% male; maternal age: 28.3% aged 19 to 25 years, 27.5% aged 26 to 30 years; maternal race and ethnicity: 5.6% African American or Black, 13.5% Asian, 49.8% Hispanic or Latinx of any race, and 28.3% non-Hispanic White) and 4697 with CP (55.1% male; maternal age: 28.3% aged 19 to 25 years, 26.0% aged 26 to 30 years; maternal race and ethnicity: 8.3% African American or Black, 8.6% Asian, 54.3% Hispanic or Latinx of any race, and 25.8% non-Hispanic White) were analyzed. Children conceived in winter (January to March) or spring (April to June) were associated with a 9% to 10% increased risk of CP (winter: RR, 1.09 [95% CI, 1.01-1.19]; spring: RR, 1.10 [95% CI, 1.02-1.20]) compared with summer (July to September) conceptions. Analyses for specific months showed similar results with children conceived in January, February, and May being at higher risk of CP. The associations were slightly stronger for mothers who lived in neighborhoods with a high social vulnerability index, but no child sex differences were observed. Only a small portion of the estimated association was mediated through preterm birth. Conclusions and Relevance: In this cohort study in California, children conceived in winter and spring had a small increase in CP risk. These findings suggest that seasonally varying environmental factors should be considered in the etiological research of CP.

Biological and environmental factors may affect children's executive function through motor and sensorimotor development: Preterm birth and cerebral palsy.

Disruptive biological and environmental factors may undermine the development of children's motor and sensorimotor skills. Since the development of cognitive skills, including executive function, is grounded in early motor and sensorimotor experiences, early delays or impairments in motor and sensorimotor processing often trigger dynamic developmental cascades that lead to suboptimal executive function outcomes. The purpose of this perspective paper is to link early differences in motor/sensorimotor processing to the development of executive function in children born preterm or with cerebral palsy. Uncovering such links in clinical populations would improve our understanding of developmental pathways and key motor and sensorimotor skills that are antecedent and foundational for the development of executive function. This knowledge will allow the refinement of early interventions targeting motor and sensorimotor skills with the goal of proactively improving executive function outcomes in at-risk populations.

Pre-pregnancy and pregnancy disorders, pre-term birth and the risk of cerebral palsy: a population-based study.

BACKGROUND: Cerebral palsy (CP) is the most common cause of childhood physical disability whose aetiology remains unclear in most cases. Maternal pre-existing and pregnancy complications are recognized risk factors of CP but the extent to which their effects are mediated by pre-term birth is unknown. METHODS: Population-based cohort study in Sweden including 2 055 378 singleton infants without congenital abnormalities, born between 1999 and 2019. Data on maternal and pregnancy characteristics and diagnoses of CP were obtained by individual record linkages of nationwide Swedish registries. Exposure was defined as maternal pre-pregnancy and pregnancy disorders. Inpatient and outpatient diagnoses were obtained for CP after 27 days of age. Adjusted rate ratios (aRRs) were calculated, along with 95% CIs. RESULTS: A total of 515 771 (25%) offspring were exposed to maternal pre-existing chronic disorders and 3472 children with CP were identified for a cumulative incidence of 1.7 per 1000 live births. After adjusting for potential confounders, maternal chronic cardiovascular or metabolic disorders, other chronic diseases, mental health disorders and early-pregnancy obesity were associated with 1.89-, 1.24-, 1.26- and 1.35-times higher risk (aRRs) of CP, respectively. Most notably, offspring exposed to maternal antepartum haemorrhage had a 6-fold elevated risk of CP (aRR 5.78, 95% CI, 5.00-6.68). Mediation analysis revealed that ∼50% of the effect of these associations was mediated by pre-term delivery; however, increased risks were also observed among term infants. CONCLUSIONS: Exposure to pre-existing maternal chronic disorders and pregnancy-related complications increases the risk of CP in offspring. Although most infants with CP were born at term, pre-term delivery explained 50% of the overall effect of pre-pregnancy and pregnancy disorders on CP.