Risk Factors For Cerebral Palsy Research Articles

Mendelian etiologies identified with whole exome sequencing in cerebral palsy.

ObjectivesCerebral palsy (CP) is the most common childhood motor disability, yet its link to single‐gene disorders is under‐characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP.MethodsWe performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non‐cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline.ResultsWe included 50 probands in this analysis (20 females, 30 males). Twenty‐four had cryptogenic CP, 20 had non‐cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic‐ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty‐six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST‐related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non‐cryptogenic CP (n = 3/20) had a Mendelian disorder on WES.InterpretationWES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors.

Sex Differences in Cardiovascular Markers and BDNF between Cerebral Palsy and Mild Cognitive Impairment

A diverse array of aging clocks, derived from a variety of omics data and clinical biomarkers, have been developed to describe aging and predict age-related disease. As such, these biomarkers are particularly applicable for use in observational studies, basic science and clinical trials focused on tackling biological aging. However, ongoing research suggests significant heterogeneity in aging, with deterioration and disease occurring in different organ systems or functional domains at various rates across individuals. Existing aging clocks only measure heterogeneity in the degree of aging, not in the manner of aging (e.g. different organ systems or functional domains). We hypothesize these unique trajectories exist and that they can be captured using a systems based approach. In our work, using clinical chemistry biomarkers from participants in the Health and Retirement Study (HRS), Framingham Heart study (FHS) and Women’s Health Initiative (WHI) , we modeled unique epigenetic aging trajectories from distinct groups of biological processes (such as Immune function, metabolic function, hepatic function, cardiac function, renal function and more). Interestingly, these biological system specific scores when combined gave an aging clock with superior mortality prediction than any published aging clock. We further validate the system aging scores and aging clock in different clinical studies to show the added advantage of such a measure, such as the fact that people with similar epigenetic age may have very different system scores. Overall, this method introduces the potential for quantitative and multi-dimensional, personalized aging scores that are indicative of an individual’s disease and disorder risk.

Analysis of Selected Risk Factors Depending on the Type of Cerebral Palsy.

Background: Cerebral palsy (CP) is not a defined, separate disease classification, but a set of etiologically diverse symptoms that change with the child’s age. According to the up-to-date definition, CP is a group of permanent but not unchanging disorders of movement and/or posture and motor function, which are due to a nonprogressive interference, lesion, or abnormality of the developing/immature brain. CP is one of the most frequent causes of motor disability in children. The aim of the present study was to analyze whether selected risk factors may vary depending on particular types of CP. Methods: 181 children with CP (aged 4–17 years), hospitalized at the Department of Pediatrics and Developmental Age Neurology in Katowice in the years 2008–2016 were retrospectively analyzed in the present study. The assumed risk factors of CP were divided into two groups: 1—pre-conception and prenatal (mother’s age, family history of epilepsy, burdened obstetric history, mother’s systemic diseases, pregnancy order, multiple pregnancy, duration of pregnancy, bleedings from the genital tract during gestation, arterial hypertension during pregnancy, infections during pregnancy, preterm contractions, maintained pregnancy, premature rupture of membranes, abruptio placentae, and others), 2—perinatal and postnatal (mode of delivery, birth weight, Apgar score at the first and fifth minute, neonatal convulsions, respiratory failure, infections in neonatal and infant period, and intraventricular bleeding). The division into particular CP types was based on Ingram’s classification. Results: The following risk factors were the most frequent in the total group: respiratory failure, infections, intraventricular bleeding, and prematurity. Among the analyzed preconception and prenatal factors, the duration of pregnancy and preterm contractions during pregnancy significantly differentiated the subgroups of patients depending on the type of CP. The prevalence of almost all analyzed perinatal, neonatal, and infant-related risk factors (i.e., birth weight, Apgar score at the first and fifth minute, neonatal convulsions, respiratory failure, infections in neonatal and infant period, and intraventricular bleeding) significantly differed between CP types, apart from the mode of delivery. However, in multivariate regression, only intraventricular bleeding was an independent predictor for tetraplegic CP type when compared to joined extrapyramidal and ataxic types (OR = 2.801, p = 0.028). Conclusions: As CP is a syndrome of multifactorial etiology, the identification of CP risk factors entails the need for careful observation and comprehensive care of children in the risk group. The presence of certain risk factors may be a prognostic indicator for particular types of CP. The knowledge about the association between the risk factor(s) and the CP type could be a very useful tool for pediatricians looking after the child at risk of developmental disorders.

Cerebral palsy biomarker

Cerebral palsy is a neurological disorder that is attributed to non-progressive injury or malformation that occurred in the developing fetal or infant brain. The motor disorders in cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, behaviour, and by epilepsy. Cerebral palsy is a complex disorder that is likely to be of multifactorial origin. Epidemiological studies have shown that the origins of most CP are prior to labor. A number of clinical risk factors for cerebral palsy have been described in the literature including preterm birth, low birth weight, inflammation, maternal infection during pregnancy and placenta pathology. Hypoxia at birth may be primary or secondary to preexisting pathology, but the currently known clinical risk factors do not explain the majority of cases. Many of these risk factors may have a genetic component. Several single nucleotide polymorphisms, DNA copy number variations and epigenetic patterns increase genetic susceptibility for cerebral palsy. Whole genome sequencing and gene expression studies may extend the percentage of cases with a genetic pathway. Clinical risk factors could act as triggers for CP where there is genetic susceptibility. These new findings should refocus research about the causes of these complex and varied neurodevelopmental disorders on the search for biomarkers of the risk of cerebral palsy. Genomics, proteomics and metabolomics have huge potential for deepening our understanding of many complex diseases by identifying diagnostic and prognostic panels of biomarkers, especially in various neurological disorders, including cerebral palsy.

Prenatal drug exposure as a risk factor for cerebral palsy and other developmental deficits.

This commentary is on the original article by Benninger et al. on pages 453–461 of this issue.

Intrauterine drug exposure as a risk factor for cerebral palsy.

To determine whether infants with intrauterine drug exposure (IUDE) are similarly at risk for cerebral palsy (CP) as other high-risk populations, whether CP classification differs based on IUDE status, and describe the association of CP with specific substances among exposed infants. This was a retrospective analysis of infants in a high-risk follow-up program (n=5578) between January 2014 and February 2018 with a history of IUDE or who received a CP diagnosis. CP rates were compared using two-sample z-tests. CP classification was assessed using Fisher's exact, Cochran-Armitage, and Wilcoxon rank-sum tests. Models for CP risk were assessed using multivariable logistic regression. Among all infants with IUDE (n=1086), 53.8% were male with a mean (SD) birth gestational age of 36.8 (3.6) weeks. Among unexposed infants with CP (n=259), 54.4% were male with a mean (SD) birth gestational age of 29.9 (5.7) weeks. Opioids were the most common exposure (93.7%) of all infants with IUDE. The CP rate in the IUDE (5.2%) and unexposed (5.7%) high-risk populations were not significantly different (p=0.168), nor were there differences in CP typology, topography, or severity between exposed (n=57) and unexposed (n=259) infants (all p>0.05). In patients with IUDE and after controlling for established CP risk factors, the observed odds of CP varied among substances. We suggest that IUDE should be considered a 'newborn-detectable risk' in the guidelines for the early detection of CP.

INCIDENCE OF CONSANGUINITY IN INDIAN CHILDREN WITH CEREBRAL PALSY: A SURVEY STUDY

Cerebral palsy is a non-progressive neurodevelopmental disorder. Cerebral palsy is 2.5 times higher in consanguineous marriage due to autosomal recessive transmission. In India, the estimated incidence is 3 per 1000 live births. The objective of this study is to evaluate the incidence of consanguinity in children with cerebral palsy and measures taken to create awareness. A survey study in the form of semi structured interview was conducted by eliciting the history from the parents of 50 cerebral palsy children in Hassan, Bangalore and Udupi within the period of 3 months using pretested questionnaires, where cerebral palsy patient’s cases were taken and symptoms, age of their parents, presence of consanguinity and its degree were noted and compared with other neurological and genetic conditions to exclude them. Thus obtained results were tabulated and analysis is done by statistical method. It was found that, the incidence rate of consanguinity in children with Cerebral palsy is 18%. And 22% of cases presented with dysmorphism, which suggests multiple genetic factors in the form of autosomal recessive gene mutation contributing for Cerebral palsy. Findings suggests that the incidence rate of consanguinity in children with Cerebral palsy is 18% those children also presented with dysmorphism, so when these two are taken into consideration we can conclude that consanguinity as a risk factor for cerebral palsy.

Maternal age as a risk factor for cerebral palsy

The relationship between maternal age and the occurrence of cerebral palsy is still highly controversial. The aim of the study was to examine the effect of maternal age on the risk of CP development, taking into account all significant risk factors and the division into single, twin, full-term, and pre-term pregnancies. The survey covered 278 children with CP attending selected educational institutions in Poland. The control group consisted of data collected from the medical records of 435 children born at Limanowa county hospital, Poland. The analyses included socio-economic factors, factors related to pregnancy and childbirth, and factors related to the presence of comorbidities and diseases in the child. Constructed logistic regression models were used for statistical analyses. For all age categories included in the estimated models (assessing the effect of demographic factors on the development of CP), only the category of ≤24 years of age (in the group of all children) was significant. It was estimated that in this mother’s age category, the risk of CP is lower (OR 0.6, 95% CI: 0.3–1.0) in comparison to mothers aged 25-29 (p = 0.03). However, estimation with the use of a complex logistic regression model did not show any significant effect of maternal age on the incidence of CP in groups from different pregnancies types. It became apparent that maternal age is a weak predictor of CP, insignificant in the final logistic regression model. It seems correct to assume that the studies conducted so far, showing a significant effect of maternal age in this respect, may be associated with bias in the estimators used to assess the risk of CP due to the fact that other important risk factors for CP development were not included in the research.

Risk Factors for Cerebral Palsy in Moldova.

Background and Objectives: This is the first study assessing risk factors for cerebral palsy (CP) among children born in Moldova. The aim of this study was to identify and describe risk factors for cerebral palsy (CP) among children born in Moldova, which is one of the low-middle income countries in Europe. Materials and Methods: We identified 351 children with CP born during 2009 and 2010 in Moldova. Detailed information on 417 children without CP served as a reference group. Logistic regression analyses were applied to the calculate crude and adjusted odds ratios (OR) for CP with 95% confidence intervals (CI) in addition to attributable fraction (AF). Results: Among children with CP (40.5% girls), 26% had spastic unilateral, 54% bilateral, 13% dyskinetic, 5% ataxic and 2% unclassified CP. Significant risk factors for CP included maternal alcohol consumption during pregnancy (OR 1.7, p = 0.002), maternal hypertension (OR 2.0, p < 0.001), children born to mothers from the rural areas (OR 1.6, p < 0.001), maternal age ≥35 years (OR 0.6, p = 0.018), maternal epilepsy (OR 4.3, p < 0.001), breech delivery (OR 3.1, p = 0.001), home births (OR 6.3, p = 0.001), umbilical cord around neck (OR 2.2, p < 0.001), AVD (OR 3.1, p < 0.001), male gender (OR 1.3, p < 0.001), SGA (OR 1.3, p = 0.027), multiple gestations (OR 1.7, p < 0.001) and hyperbilirubinemia (OR 4.5, p < 0.001). Multivariable analyses showed that the AF of CP was 64% for rural residence (OR 2.8, p = 0.002), 87% for home birth (7.6, p = 0.005), 79% for pre-labor rupture of membrane (OR 4.9, p = 0.001), 66% for breech delivery (OR 2.9, p = 0.002) and 81% for hyperbilirubinemia (OR 5.4, p < 0.001). Conclusions: A combination of factors related to the mother, the delivery and the child were risk factors for CP in Moldova, many of them possibly avoidable. Improved pregnancy and maternity care would potentially reduce the risk of CP. A national CP registry in Moldova is suggested as an opportunity to follow up on these findings.

Evaluation of risk factors for cerebral palsy

BackgroundCerebral palsy (CP) has been identified as one of the most important and common causes of childhood disabilities worldwide and is often accompanied by multiple comorbidities. CP is defined as a group of disorders of the development of movement and posture, causing activity limitation that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The objective of our study was to describe main clinical pattern and motor impairments of our patients, and to evaluate the presence of risk factors and if there is a relation to the type of cerebral palsy.MethodsChildren with cerebral palsy were retrospectively enrolled over 2 years from the neurology outpatient clinics. Cerebral palsy risk factors and motor impairments were determined through caregiver interviews, review of medical records, and direct physical examination.ResultsOne thousand children with cerebral palsy were enrolled. Subjects were 64.4% male, with a median age of 2.5 years. The risk factors for cerebral palsy in our study were antenatal (21%), natal and post-natal (30.5%), post-neonatal (17.1%), and unidentified (31.4%). Antenatal as CNS malformation (26.6%), maternal DM (17.6%), prolonged rupture of membrane (11.9%), maternal hemorrhage (10.4%), and pre-eclampsia (4.7%). Natal and post-natal as hypoxic ischemic encephalopathy (28.5%), infection (16.3%), hyperbilirubinemia (12.7%), cerebrovascular accidents (8.8%), meconium aspiration (6.2%), and intracranial hemorrhage. Post-neonatal as CNS infection (34.5%), cerebrovascular accidents (28.6%), sepsis (23.9%), and intracranial hemorrhage (8.7%).ConclusionsCerebral palsy has different etiologies and risk factors. Further studies are necessary to determine optimal preventative strategies in these patients.

Risk Factors for Cerebral Palsy in Brazilian Children: A Case-Control Study

Background: Cerebral palsy is the main cause of physical disability in childhood. Objectives: This study analyzed prenatal and perinatal risk factors that contribute to cerebral palsy in Brazilian children. Methods: A case-control study was conducted with 2- to 10-year-old children in the city of Aracaju, Sergipe, Brazil. The cases were population-based, selected from the Primary Health Care services. The controls were selected from the database of the Brazilian Live Births Information System. Controls were paired with cases by gender, year, and hospital of birth. Results: A total of 570 participants (114 cases and 456 controls) were studied. Most of the participants were male, with bilateral spastic cerebral palsy. Among the prenatal factors examined, the presence of congenital anomalies was significantly different between cases and controls (OR = 54.28, [95% CI 12.55, 234.86]). The analysis of perinatal factors revealed significant differences between cases and controls in low birth weight (OR = 3.8, [95% CI 2.34, 6.16]), preterm birth (OR = 2.31, [95% CI 1.41, 3.80]), and low Apgar scores (OR = 14.73, [95% CI 5.27, 41.15]). Conclusions: The main prenatal and perinatal factors associated with cerebral palsy in our population were congenital anomalies, low Apgar scores, low birth weight, and preterm birth. The perinatal period had more risk factors, demanding a deeper study of their causes and of possible preventive measures.

Neonatal risk factors for cerebral palsy

Neonatal risk factors for cerebral palsy

Genetic phenocopies of cerebral palsy: a review

Cerebral palsy (CP) represents a heterogeneous group of non-progressive disorders of motor development and posture control, leading to activity limitation due to disturbances in a fetal or infant’s developing brain. In CP, motor impairment is often accompanied by disturbances of sensation, cognition, communication, perception, and (or) behavior, and (or) by a seizure disorder. Despite profound knowledge of the CP risk factors, in many patients, the latter cannot be identified, and the neuroimaging features of the brain injury may also be absent. Those patients, at least in part, can include children with undiagnosed genetic phenocopies of the CP. Literature search was performed using Scopus, Web of Science, PubMed (MEDLINE), and eLibrary databases. In the review, we briefly touch upon the current understanding of CP’s risk factors and pathophysiology. Common neuroimaging findings typical for CP subtypes are presented. We then discuss the role of genetic factors that can lead to the development of CP phenocopies, briefly describing their phenotypic subtypes and some of the specific diseases. Clinical and neuroimaging «red flags» that can prompt a diagnostic search for genetic disorders are reviewed. The role of modern genetic testing techniques, including high-throughput sequencing, in diagnosing CP phenocopies is described. We present a general diagnostic approach to suspected genetic CP phenocopies. Early identification of the pediatric population’s genetic conditions can affect the individual and family prognosis and the patient’s management.

Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)

Preterm birth remains the leading identifiable risk factor for cerebral palsy (CP), a devastating form of motor impairment due to developmental brain injury occurring around the time of birth. We performed genome wide methylation and whole transcriptome analyses to elucidate the early pathogenesis of CP in extremely low gestational age neonates (ELGANs). We evaluated peripheral blood cell specimens collected during a randomized trial of erythropoietin for neuroprotection in the ELGAN (PENUT Trial, NCT# 01378273). DNA methylation data were generated from 94 PENUT subjects (n = 47 CP vs. n = 47 Control) on day 1 and 14 of life. Gene expression data were generated from a subset of 56 subjects. Only one differentially methylated region was identified for the day 1 to 14 change between CP versus no CP, without evidence for differential gene expression of the associated gene RNA Pseudouridine Synthase Domain Containing 2. iPathwayGuide meta-analyses identified a relevant upregulation of JAK1 expression in the setting of decreased methylation that was observed in control subjects but not CP subjects. Evaluation of whole transcriptome data identified several top pathways of potential clinical relevance including thermogenesis, ferroptossis, ribosomal activity and other neurodegenerative conditions that differentiated CP from controls.

Why the Hips Remain Stable When the Spine Strays: A Deeper Analysis of the Relationship Between Hip Displacement and Severe Scoliosis in Patients With Cerebral Palsy.

Many patients with spastic quadriplegic cerebral palsy (CP) and severe scoliosis develop hip displacement, whereas others do not. We investigated demographic characteristics, risk factors for CP, and imaging findings associated with nondisplaced hips in patients with CP and severe scoliosis. We retrospectively analyzed records of 229 patients with spastic quadriplegic CP and severe scoliosis who presented for treatment at our US academic tertiary care hospital between August 2005 and September 2015. Demographic characteristics, risk factors for CP, and brain magnetic resonance imaging (MRI) findings were documented. Patients were classified as Gross Motor Function Classification System (GMFCS) level 4 or higher, with 58% at GMFCS level 5.3. Displaced hips (n=181 patients) were defined as a migration percentage of ≥30% or previous surgery for hip displacement/adductor contractures. Patients who did not meet these criteria were classified as nondisplaced (n=48 patients). We used univariate analysis and multivariate logistic regression to determine associations between patient factors and hip displacement (alpha=0.05). Patients born at term (≥37 wk) had 2.5 times the odds [95% confidence interval (CI): 1.3-5.0] of having nondisplaced hips compared with patients born prematurely. Females had 2.0 times the odds (95% CI: 1.0-3.9) of having nondisplaced hips compared with males. Patients with normal brain MRI findings had 9.6 times the odds (95% CI: 2.3-41) of having nondisplaced hips compared with patients with abnormal findings. Hip displacement was not associated with race (P>0.05). Gestational age 37 weeks or above, female sex, and normal brain MRI findings are independently associated with nondisplaced hips in patients with spastic quadriplegic CP and severe scoliosis. These findings direct attention to characteristics that may place patients at greater risk of displacement. Future work may influence preventative screening practices and improve patient counseling regarding the risk of hip displacement. Level III-retrospective comparative study.

Cerebral palsy in twins and multiple births at Sindhudurg Arabian west coast of Maharashtra (Large cohort analysis of 206124 births from 1996 to 2014)

Introduction: This study aims at the prevalence of cerebral palsy in multiple births and also to determine the effects of birth weight and gestational age on the risk of cerebral palsy in a defined and contemporary Sindhudurg population. Material and Methods: Children born in 38 primary health centers, seven rural hospitals, three sub district hospitals and one civil hospital of this district between 1996 to 2014, inclusive comprised the cohort 2090 multiple birth deliveries with 4152 live births. Total number of deliveries from 1996 to 2014 was 2,06,124 observed in Sindhudurg district. Results: A moderate or severe congenital cerebral palsy had in 41 twins and three triplets, a prevalence of 10.8 and 13.6 per thousand twin and triplet children (95% CI 42, 9.8). The crude rate per 1000 survivors is 11.4 in multiple births. The cerebral palsy prevalence in male twins was three times more than female twins (RR =3.6, 95% CI 2.1, 6.2) and was higher in each birth weight group (below 1400 grams &amp; 1500 to 2000 grams). The twins born with birth weight less than 1600 grams had prevalence of 58 per thousand (95% CI 42, 106), risk three times higher than that of singletons in the same birth weight group (RR = 1.2, 95% CI 0.6,1.8). Multiple logistic regression analysis confirmed the importance of twins and triplets as a risk factor for cerebral palsy with regard to weight and gestational age. Conclusion: Twin pregnancies and triplets produced 12 and 14 times more often cerebral palsy than singleton pregnancies.

Cerebral palsy in twins and multiple births at Sindhudurg Arabian west coast of Maharashtra (Large cohort analysis of 206124 births from 1996 to 2014)

Introduction: This study aims at the prevalence of cerebral palsy in multiple births and also to determine the effects of birth weight and gestational age on the risk of cerebral palsy in a defined and contemporary Sindhudurg population. Material and Methods: Children born in 38 primary health centers, seven rural hospitals, three sub district hospitals and one civil hospital of this district between 1996 to 2014, inclusive comprised the cohort 2090 multiple birth deliveries with 4152 live births. Total number of deliveries from 1996 to 2014 was 2,06,124 observed in Sindhudurg district. Results: A moderate or severe congenital cerebral palsy had in 41 twins and three triplets, a prevalence of 10.8 and 13.6 per thousand twin and triplet children (95% CI 42, 9.8). The crude rate per 1000 survivors is 11.4 in multiple births. The cerebral palsy prevalence in male twins was three times more than female twins (RR =3.6, 95% CI 2.1, 6.2) and was higher in each birth weight group (below 1400 grams &amp; 1500 to 2000 grams). The twins born with birth weight less than 1600 grams had prevalence of 58 per thousand (95% CI 42, 106),risk three times higher than that of singletons in the same birth weight group (RR = 1.2, 95% CI 0.6,1.8). Multiple logistic regression analysis confirmed the importance of twins and triplets as a risk factor for cerebral palsy with regard to weight and gestational age. Conclusion: Twin pregnancies and triplets produced 12 and 14 times more often cerebral palsy than singleton pregnancies.

Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction.

Background and Objectives: Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Materials and Methods: Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. Results: HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Conclusions: Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.

Risk factors in early life for developmental coordination disorder: a scoping review.

AimTo perform a scoping literature review of associations between risk factors in early life and developmental coordination disorder (DCD).MethodPubMed, Embase, CINAHL, PsycINFO, and Web of Science (January 1994–March 2019) were searched to identify studies on early risk factors and motor impairment or DCD. The effect of single and multiple risk factors was assessed. Level of evidence was evaluated following the Centre for Evidence‐Based Medicine guidelines. Meta‐analysis on the effect of preterm birth was performed.ResultsThirty‐six studies fulfilled inclusion criteria; 35 had evidence level 3, one had level 4. Highest evidence was available that preterm birth and male sex in term‐born children were associated with DCD. The odds ratio of preterm birth was 2.02 (95% confidence interval: 1.43–2.85). Low to moderate evidence was available that parental subfertility, maternal smoking during pregnancy, postnatal corticosteroid treatment in infants born preterm, extra corporeal membrane oxygenation, retinopathy of prematurity, abnormalities on magnetic resonance imaging scans at term age, and accumulating perinatal or neonatal risk factors were associated with motor impairment.InterpretationLimited information on early risk factors of DCD is available. Only preterm birth and male sex were consistently associated with an increased risk of DCD.What this paper adds Preterm birth is a risk factor for developmental coordination disorder (DCD).In term‐born children, male sex was consistently associated with DCD.Risk factors for DCD are similar to risk factors for cerebral palsy.

Risk factors for cerebral palsy in neonates due to placental abruption

AimThis study aimed to identify risk factors for the onset of cerebral palsy (CP) in neonates due to placental abruption and investigate their characteristics.MethodsA retrospective case–control study was conducted using a nationwide registry from Japan. The study population included pregnant women (n = 122) who delivered an infant with CP between 2009 and 2015, where placental abruption was identified as the single cause of CP. The control group consisted of pregnant women with placental abruption, who delivered an infant without CP and were managed from 2013 to 2014. They were randomly identified from the prenatal database of the Japan Society of Obstetrics and Gynecology (JSOG‐DB; n = 1214). Risk factors were investigated using multivariate analysis.ResultsAlcohol consumption (3.38, 2.01–5.68) (odds ratio, 95% confidence interval), smoking during pregnancy (3.50, 1.32–9.25), number of deliveries (1.28, 1.05–1.56), polyhydramnios (5.60, 1.37–22.6), oral administration of ritodrine hydrochloride (2.09, 1.22–3.57) and hypertensive disorders in pregnancy (2.25, 1.27–4.07) were significant risk factors. In contrast, intravenous administration of oxytocin (odds ratio, 95% confidence interval: 0.22, 0.09–0.58) and magnesium sulfate (0.122, 0.02–0.89) attenuated risk.ConclusionAlcohol consumption, smoking during pregnancy, number of deliveries, polyhydramnios, oral administration of ritodrine hydrochloride and hypertensive disorders in pregnancy were identified as risk factors for CP following placental abruption. Regarding alcohol consumption and smoking during pregnancy, the results suggest the importance of educational activities targeting pregnant women to increase their awareness of placental abruption.