Prevention Of Cerebral Palsy Research Articles

Review on Prevention of Cerebral Palsy from the Perspective of Social Pediatrics.

Cerebral palsy is a static encephalopathy with multiple etiologies. Several interventions toward perinatal risk factors, intrapartum asphyxia, and head injury or infection have been evaluated in order to deal with irreversible brain damage. Antenatal-intrapartum and neonatal interventions mainly focus on preventing hypoxia, oxidative stress, inflammation, and growth restriction. Among these preventive interventions, magnesium sulfate for neuroprotection of the fetus in women at risk of preterm birth and therapeutic hypothermia (cooling of body or just brain) for newborns with hypoxic-ischemic encephalopathy have effectively reduced cerebral palsy risk. There is still a lack of literature on the effectiveness of preventive interventions toward postnatally acquired brain injury. Social pediatricians are concerned with identifying, reducing, or eliminating risk factors of cerebral palsy and encourage a comprehensive approach to providing integrated and personalized care to children with cerebral palsy with the support of their families and communities.

Head Circumference within the Normal Range and Neurodevelopmental Outcomes in Preterm Infants.

We sought to determine if variation in head circumference (HC) within the range of normal (5th-10th and 90th-95th percentile) is associated with poor neurodevelopmental outcomes (NDO), which defined as mild or moderate delay by Bayley II psychometrics (BSID-II). This is a secondary analysis of a randomized controlled trial assessing the benefits of magnesium for the prevention of cerebral palsy. Fetuses with a normal HC at birth defined as within 5th to 95th percentile were included. NDO were assessed at age 2 with BSID-II. Moderate delay was defined as a score <70 and mild delay as <85. HC was classified as small normal (5th-10th percentile), normal (10th-90th percentile), and large normal (90th-95th percentile). Logistic regression models adjusted for confounding. Linear regression models estimated the impact for every 1 cm of change in HC. Of 1,236 included infants, 111 (8%) had small normal HC; 1,058 (85%) had normal HC; and 67 (5%) had large normal HC. Baseline characteristics were similar between groups. There was no association with changes in HC within the range of normal and developmental indices. When considered as a continuous variable, every 1 cm increase in HC was also not associated with a significant change in developmental indices. Within the normal range (5th-95th percentile), changes in HC did not correlate with changes in NDO at 2 years as measured by Bayley II scales. · It is unknown if variations in normal HC are associated with poor neurodevelopmental outcomes.. · Alterations in HC within the range of normal (5th-95th percentile) are not associated with adverse NDO.. · When considered as a continuous variable, a 1 cm increase in HC is not associated with adverse NDO.. · Changes in HC within the range of normal do not appear to be a pathologic change altering NDO..

Evaluating an enhanced quality improvement intervention in maternity units: PReCePT trial protocol

The UK’s National Institute for Health and Care Excellence Preterm labour and birth guideline recommends use of magnesium sulfate (MgSO4) in deliveries below 30 weeks’ gestation to prevent cerebral palsy...

Intrapartum opioid analgesia and childhood neurodevelopmental outcomes among infants born preterm

There are concerns regarding neurobehavioral changes in infants exposed to parenteral opioids during labor; however, long-term neurodevelopment remains unstudied. We aimed to examine the association between parenteral opioids used as labor analgesia and perinatal outcomes and childhood neurodevelopment until 2 years of age among infants born prematurely. We hypothesized that intrapartum exposure to parenteral opioids is associated with impaired neurodevelopment and adverse perinatal outcomes. This was a secondary analysis of a multicenter, randomized controlled trial assessing magnesium for the prevention of cerebral palsy in infants at risk for preterm birth. Women delivering a singleton, nonanomalous, live infant before 37 weeks' gestation were considered for inclusion. Women were excluded if they had missing exposure or primary outcome data, were exposed to general anesthesia, or reported use of heroin or unspecified illicit drugs. Women reporting use of nonopioid illicit drugs such as cocaine and marijuana were not excluded. Groups were compared based on exposure or nonexposure to parenteral opioids (intravenous or intramuscular) used as labor analgesia. The primary outcome was any psychomotor or mental developmental delay at 24 months according to the Bayley Scales of Infant Development II. Secondary outcomes were the Bayley Scales of Infant Development II subdomains and adverse perinatal outcomes. Multivariable logistic regression models were performed and adjusted odds ratios with 95% confidence intervals were estimated. Of the 1404 women included, 535 (38%) received parenteral opioids as labor analgesia. Women receiving parenteral opioids were more likely to be younger, Hispanic, and present with cervical dilation ≥4 cm. Parenteral opioid recipients had lower rates of illicit nonopioid drug or tobacco use, a lower rate of cesarean delivery, lower educational level and were less likely to be undergoing induction. Women receiving parenteral opioids who underwent cesarean delivery were less likely to do so because of a nonreassuring fetal status. In the unadjusted and adjusted analyses, there were no significant differences in the primary outcomes of psychomotor or mental developmental delay at 2 years of age (adjusted odds ratio, 0.96; confidence interval, 0.76-1.20). The only significant difference in secondary outcomes was a shorter O2 requirement duration in the parenteral opioid group (2 vs 4 days; P=.002). Among a population of preterm infants vulnerable to neurologic impairment, intrapartum exposure to parenteral opioids was not associated with an increased risk for neurodevelopmental delay up to 2 years of age, nor did these infants have worse perinatal outcomes.

Commentary on Fetal Movement in Actocardiogram and Prevention of Cerebral Palsy with Hypoxia Index

Commentary on Fetal Movement in Actocardiogram and Prevention of Cerebral Palsy with Hypoxia Index

Prevention of Cerebral Palsy and Fetal Demise with Hypoxia Index, FHR Score and Pathologic Sinusoidal FHR in Fetal Monitoring

Although fetal deaths was decreased by intrapartum Fetal Heart Rate (FHR) monitoring, infantile cerebral palsy was not decreased in Dublin trials of Electric Fetal Monitor (EFM), thus, an analysis to reduce cerebral palsy was studied, where cerebral palsy is prevented by setting the threshold of hypoxia index at 24 or less, in the analysis of FHR deceleration.

Prenatal Tobacco Exposure and Childhood Neurodevelopment among Infants Born Prematurely.

Nicotine is an established neuroteratogen, and prenatal tobacco exposure alters the structure of the developing nervous system. An association between prenatal tobacco exposure and impaired neurologic function is less well established. We examine the association between prenatal tobacco exposure and childhood neurodevelopment among infants born preterm. Secondary analysis of a multicenter randomized controlled trial assessing the benefits of magnesium sulfate for the prevention of cerebral palsy in preterm infants. Women were included if they delivered a singleton and nonanomalous infant before 37 weeks. Exposure was any self-reported prenatal tobacco use. Primary outcome was the original trial composite outcome of moderate or severe cerebral palsy at 2 years of age, or stillbirth, or infant death by 1 year of age. Secondary outcomes included components of the composite and mild cerebral palsy at 2 years, Bayley Scales of Infant Development II motor and mental scores, death before two years, and use of auditory aids or corrective lenses. Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals. Of 1,826 women included, 503 (27.5%) used tobacco. Tobacco users were more likely to be older, unmarried, and white; have a prior preterm birth; have received no prenatal care; and to use illicit drugs or alcohol. Gestational age at delivery, betamethasone exposure, and magnesium exposure were not different between groups. There were no differences in the composite primary outcome or in rates of cerebral palsy by tobacco use. Moderate developmental delay was more common among tobacco exposed in bivariate but not adjusted analysis (20.5 vs. 15.9%, p = 0.035). In adjusted analysis, tobacco exposure was associated with increased use of corrective lenses (5.0 vs. 2.9%, aOR: 2.28, 95% confidence interval: 1.28-4.07). Prenatal tobacco exposure is not associated with neurodevelopmental impairment in infants born preterm. However, tobacco exposure may be associated with impaired vision. · Tobacco exposure is not associated with impaired neurodevelopment in this preterm population.. · Prenatal tobacco exposure is associated with increased need for corrective lenses.. · Tobacco use in pregnancy may be a risk factor for poorer visual acuity in children..

General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial

BackgroundIn 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment. MethodsA secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders. ResultsOf 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010). ConclusionsGeneral anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.

Chorioamnionitis versus intraamniotic infection among preterm deliveries—is postpartum infectious morbidity different?

Chorioamnionitis can have a highly variable definition with substantial maternal and fetal morbidity, with higher frequencies in preterm births. With the recently updated intraamniotic infection diagnostic criteria by the American College of Obstetricians and Gynecologists, fewer women experiencing preterm delivery may qualify for intrapartum antibiotic treatment, potentially resulting in higher postpartum infectious morbidity. This study aimed to estimate whether the proportion of women delivering preterm who develop postpartum endometritis differs between subjects diagnosed as having clinical chorioamnionitis and those meeting the American College of Obstetricians and Gynecologists' criteria for intraamniotic infection. Secondary analysis was conducted using a randomized controlled trial of antenatal magnesium sulfate for the prevention of cerebral palsy. Subjects were included if they had a clinical diagnosis of chorioamnionitis and maternal temperature of ≥37.8°C and excluded if maternal temperature data were missing. The exposure group included women who met the criteria for intraamniotic infection, defined as a single maternal temperature of ≥39.0°C or maternal temperature of 38.0°C to 38.9°C plus 1 additional clinical risk factor (leukocytosis, purulent cervical drainage, or fetal tachycardia). The primary outcome was postpartum endometritis. The odds of postpartum endometritis were compared between women with intraamniotic infection and women with clinical chorioamnionitis, after adjusting for potential confounders using multivariate logistic regression. Of the original study population, 258 of 2241 (11.8%) subjects met the criteria for chorioamnionitis. Nearly all subjects (98.5%) received antibiotic treatment between randomization and delivery. A total of 144 subjects (55.8%) met the criteria for intraamniotic infection, whereas 114 (44%) only met the criteria for clinical chorioamnionitis. A total of 40 women (15.5%) experienced postpartum endometritis. Women with intraamniotic infection had higher parity (P=.02) and higher maximum maternal temperature (P<.001) and were more likely to have received antibiotic treatment (P=.04). Postpartum endometritis rates were similar between subjects with chorioamnionitis and intraamniotic infection (12% vs 18%; P=.50). After adjustment for potential confounders, the odds of developing postpartum endometritis did not differ between subjects who met the criteria for intraamniotic infection and those who did not (adjusted odds ratio, 1.28; 95% confidence interval, 0.62-2.62). Patients delivering preterm who receive a diagnosis of clinical chorioamnionitis in the intrapartum period seem to have similar odds of developing postpartum endometritis as those meeting the American College of Obstetricians and Gynecologists' criteria for intraamniotic infection, suggesting that this group remains at a high risk for postpartum infectious complications.

Authors' reply re: Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double‐blind, randomised, placebo‐controlled, multi‐centre trial

Authors' reply re: Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double‐blind, randomised, placebo‐controlled, multi‐centre trial

Re: Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double‐blind, randomised, placebo‐controlled, multi‐centre trial

Re: Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double‐blind, randomised, placebo‐controlled, multi‐centre trial

Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double-blind, randomised, placebo-controlled, multi-centre trial.

To study the effect of antenatal magnesium sulphate (MgSO4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis. Double-blind, randomised, placebo-controlled, multi-centre trial. Fourteen Danish obstetric departments. In total, 560 pregnant women at risk for preterm delivery before 32weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children. Women wererandomisedto receive either a loading dose of 5 g MgSO4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18months or older with a review of their medical charts and with the Ages and Stages Questionnaire. The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP. The crude rates of moderate to severe CP in the MgSO4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23-1.65). Antenatal MgSO4 before 32weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis. Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32weeks of gestation.

Prevention of cerebral palsy with hypoxia index in fetal monitoring

Although fetal deaths was decreased by intrapartum fetal heart rate (FHR) monitoring, infantile cerebral palsy was not decreased in Dublin trials of electric fetal monitor, thus, an analysis to prevent cerebral palsy was studied, where cerebral palsy is prevented by setting the threshold of hypoxia index at 24 or less, in the analysis of FHR deceleration.

610: Effect of general anesthesia at time of cesarean delivery on perinatal outcomes and childhood neurodevelopment

In 2016, the FDA expressed concern that general anesthesia or sedation exposure in pregnancy or before 3 years of age may impact pediatric neurodevelopment and called for further research examining the impact of anesthesia, including single, short exposures. We examine the impact of general anesthesia (GA) during cesarean delivery (CD) on neurodevelopment at two years of age among infants born preterm. Secondary analysis of a multicenter RCT assessing magnesium for prevention of cerebral palsy in preterm infants. Women were included if they delivered a singleton, non-anomalous infant < 37wks by CD. The exposure of interest was general anesthesia. The primary outcome was mild to moderate developmental delay at 24 mos by Bayley Scales of Infant Development II (BSID). Secondary outcomes were BSID subdomains, periventricular leukomalacia, seizures, abnormal tone, hypotension, ventilator need, duration of oxygen use, and use of visual aids. Chi square, Fisher Exact, student’s t-test, Wilcoxon Rank Sum tests, and multivariable logistic regression models were performed. Of 557 women, 119 (21%) received GA. Women receiving GA were more likely to be unmarried, non-white, delivering more preterm (28.6 vs 29.7 wks, p< 0.01), undergoing CD for fetal distress (49% vs 36%, p=0.01), and in preterm labor >4cm (11% vs 3%, p< 0.01). Betamethasone and magnesium exposure were similar between groups, as was substance use. Mild to moderate developmental delay was not increased in those exposed to GA (Table). When BSID subdomains were analyzed individually, nominal increases in mild and moderate mental delay among infants exposed to GA did not persist after controlling for significant variables, including gestational age at delivery. Secondary outcomes did not differ significantly between groups. General anesthesia at time of CD does not appear to increase the risk of neurodevelopmental delay at two years in infants born preterm. Future studies should evaluate the impact of longer or multiple anesthetic exposures on neurodevelopment among all infants.

669: Head circumference within the normal range and neurodevelopment in preterm infants

Head circumference (HC) is used as a surrogate marker of future neurodevelopmental outcomes (NDO). We sought to determine if variation in head circumference within the range of normal (within 2 standard deviations) is associated with neurodevelopmental outcomes. Secondary analysis of a randomized controlled trial assessing the benefits of magnesium for prevention of cerebral palsy. Women were included if HC at birth was within 2 standard deviations (SD) of the mean, specific for race and gestational age. Patients were excluded for fetal/neonatal death, infant lost to follow up, or race-specific HC was available. NDO were assessed at age 2 by trained psychologists or psychometrics. Moderate delay was defined as Bayley score < 70 and mild delay as < 85 on psychomotor and developmental indices. HC was classified as: 1-2 SD below, within 1 SD, and 1-2 SD above the mean. Logistic regression models were used to adjust for baseline confounding differences. Linear regression models were calculated to estimate the impact for every 1cm of change in HC, adjusted for gestational age and race. Of 1498 included, 253 (17%) were classified as HC 1-2 SD below, 1025 (68%) within 1 SD of the mean, and 220 (15%) 1-2SD above. Groups were similar regarding baseline characteristics. After adjusting for birthweight and race, HC 1-2SD below the mean was significantly associated with mild and moderate delay compared to HC within 1SD. HC 1-2 SD above the mean was not consistently associated with a difference in mild and moderate delay compared to HC within 1SD (Table 1). When considered as a continuous variable, every 1-cm increase in HC was associated with 1.03 point increase in psychomotor development index (p < 0.0001) and a 1.15 point increase in mental development index (p < 0.0001) (Figure 1). Within the normal range of head circumference (1-2SD above and 1-2SD below), changes in head circumference result in clinically significant differences in two-year neurodevelopmental outcomes as measured by Bayley II scales.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

A Cross-sectional Study of the Clinical Profile of Children With Cerebral Palsy in Benin, a West African Low-Income Country.

Cerebral palsy is a common cause of pediatric motor disability. Although there are increasing amounts of data on the clinical profile of children with cerebral palsy in high-income countries, corresponding information about low-income countries and developing countries is lacking. Therefore, we aimed to describe the clinical spectrum of cerebral palsy in children in Benin, a representative West African low-income country. Our cross-sectional observational study included 114 children with cerebral palsy recruited from community-based rehabilitation centers and teaching hospitals (median age: 7 years, range 2-17; sex: 66% male). Data were collected through review of medical records and interviews with children's mothers. Assessment included risk factors, clinical subtypes according to the Surveillance of CP in Europe criteria, severity of motor outcome scored by the Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System, comorbidities, and school attendance. We recorded a high prevalence of intrapartum adverse events. Seventeen percent of children had postneonatal cerebral palsy, with cerebral malaria being the most common cause. Most children were severely affected (67.5% as bilateral spastic; 54.4% as GMFCS IV or V), but severity declined substantially with age. Only 23% of the children with cerebral palsy had attended school. Poor motor outcomes and comorbidities were associated with school nonattendance. These results suggest that intrapartum risk factors and postnatal cerebral malaria in infants are opportune targets for prevention of cerebral palsy in Sub-Saharan low-income countries.

Prevention of Cerebral Palsy with Novel Hypoxia Index Composed of Fetal Heart Rate Deceleration

Fetal brain damage develops after the loss of FHR variability followed by infantile cerebral palsy due to severe hypoxia in frequently repeated fetal heart rate (FHR) decelerations (transient bradycardia) or prolonged fetal bradycardia, where novel hypxia index is 25 or more, and it is prevented if the hpoxia index is 24 or less. The hypoxia index (HI) is the sum of FHR deceleration durations (min) divided by the lowest FHR (bpm), and multiplied by 100 (Figure 1). The HI is calculated by visual measurement, while it is also suitably calculated by computerized FHR monitoring. Cerebral palsy is prevented when HI is 24 or less with almost zero error probability in the delivery. The cases whose HI was 25 or more will develop cerebral palsy, thus, it can receive early cerebral palsy trearments in neonatal stage. As late deceleration disappeared when the parturient woman changed her posture to lateral one from supine, a parturient woman is recommended to have lateral posture, when they notice the appearance of FHR deceleration during the delivery to disappear deceleration to prevent the increase of HI value. As the HI is adopted not only late deceleration, but also all decelerations and continuous bradycardia, fetal diagnosis will change to objective numeric FHR analysis from the monitoring with vague subjective FHR pattern classification.

The prevention of cerebral palsy in preterm infants – the potential role of magnesium sulfate

The prevention of cerebral palsy in preterm infants – the potential role of magnesium sulfate

Cost Analysis of Azithromycin versus Erythromycin in Pregnancies Complicated by Preterm Premature Rupture of Membranes.

To quantify the potential cost savings if azithromycin is substituted for erythromycin in women with preterm premature rupture of membranes (PPROM). Secondary analysis of a multicentered study investigating magnesium sulfate for the prevention of cerebral palsy in premature infants. All patients with PPROM who received antibiotics for prophylaxis were included in the analysis. The number of expected doses each patient would have received was calculated for erythromycin, multidose azithromycin, and single-dose azithromycin regimens accounting for latency from PPROM to delivery. The wholesale acquisition cost was used to calculate the expected cost of each regimen. There were 981 PPROM patients who received a penicillin class antibiotic and erythromycin. Patients would have received 7,528 intravenous doses and 10,194 oral doses of erythromycin at a combined cost of $357,169. In comparison, patients would have received 6,422 and 3,942 doses at a cost of $15,669 and $9,574 for the multidose and single-dose azithromycin regimens respectively, which represents a more than 95% cost reduction for either regimen compared with erythromycin. The use of azithromycin substituted for erythromycin in the standard antibiotic regimen of women with PPROM represents a potential for substantial cost reduction.

Antenatal prevention of cerebral palsy and childhood disability: is the impossible possible?

This review covers our current knowledge of the causes of perinatal brain injury leading to cerebral palsy-like outcomes, and argues that much of this brain damage is preventable. We review the experimental evidence that there are treatments that can be safely administered to women in late pregnancy that decrease the likelihood and extent of perinatal brain damage that occurs because of acute and severe hypoxia that arises during some births, and the additional impact of chronic fetal hypoxia, infection, inflammation, growth restriction and preterm birth. We discuss the types of interventions required to ameliorate or even prevent apoptotic and necrotic cell death, and the vulnerability of all the major cell types in the brain (neurons, astrocytes, oligodendrocytes, microglia, cerebral vasculature) to hypoxia/ischaemia, and whether a pan-protective treatment given to the mother before birth is a realistic prospect.