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The BEAM Trial. [ABSTRACT FROM AUTHOR]

Objective To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. Study Design This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. Results Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67–0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1–13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6–104.6), and male gender (OR: 2.5, CI: 1.4–4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78–0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. Conclusion IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. Key Points Factors known at hospital discharge are identified which are independently associated with death or CP by age 2. A model was created and validated using these findings to counsel parents. The risk of death or CP can be calculated at the time of hospital discharge. [ABSTRACT FROM AUTHOR]

The prevalence of cerebral palsy (CP) varies globally, with higher rates and burden of disease in low- and middle-income countries. CP is a lifelong condition with no cure, presenting diverse challenges such as motor impairment, epilepsy, and mental health disorders. Research progress has been made but more is needed, especially given consumer demands for faster advancements and improvements in the scientific evidence base for interventions. This paper explores three strategies to accelerate CP research: consumer engagement, global clinical trial networks, and adaptive designs. Consumer engagement involving individuals with lived experience enhances research outcomes. Global clinical trial networks provide efficiency through larger and more diverse participant pools. Adaptive designs, unlike traditional randomized controlled trials, allow real-time modifications based on interim analyses, potentially answering complex questions more efficiently. The establishment of a CP Global Clinical Trials Network, integrating consumer engagement, global collaboration, and adaptive designs, marks a paradigm shift. The Network aims to address consumer-set research priorities. While challenges like ethical considerations and capacity building exist, the potential benefits for consumers, clinicians, researchers, and funding bodies are substantial. This paper underscores the urgency of transforming CP research methodologies for quicker translation of novel treatments into clinical practice to improve quality of life for those with CP. [ABSTRACT FROM AUTHOR]

The article presents findings from the MAGENTA randomized clinical trial, indicating that the administration of magnesium sulfate to pregnant women at risk of imminent preterm birth between 30 and 34 weeks of gestation did not lead to improved neurological function or child survival at 2 years of age. Despite the established neuroprotective effects of magnesium sulfate in previous trials, the MAGENTA trial's results suggest a lack of significant benefit in the specified gestational age range.

Neonatal hypoxic–ischemic encephalopathy (HIE) causes permanent motor deficit "cerebral palsy (CP)," and may result in significant disability and death. Therapeutic hypothermia (TH) had been established as the first effective therapy for neonates with HIE; however, TH must be initiated within the first 6 hours after birth, and the number needed to treat is from 9 to 11 to prevent brain damage from HIE. Therefore, additional therapies for HIE are highly needed. In this review, we provide an introduction on the mechanisms of HIE cascade and how TH and cell therapies such as umbilical cord blood cells and mesenchymal stromal cells (MSCs), especially umbilical cord-derived MSCs (UC-MSCs), may protect the brain in newborns, and discuss recent progress in regenerative therapies using UC-MSCs for neurological disorders. The brain damage process "HIE cascade" was divided into six stages: (1) energy depletion, (2) impairment of microglia, (3) inflammation, (4) excitotoxity, (5) oxidative stress, and (6) apoptosis in capillary, glia, synapse and/or neuron. The authors showed recent 13 clinical trials using UC-MSCs for neurological disorders. The authors suggest that the next step will include reaching a consensus on cell therapies for HIE and establishment of effective protocols for cell therapy for HIE. Key Points This study includes new insights about cell therapy for neonatal HIE and CP in schema. This study shows precise mechanism of neonatal HIE cascade. The mechanism of cell therapy by comparing umbilical cord blood stem cell with MSC is shown. The review of recent clinical trials of UC-MSC is shown. [ABSTRACT FROM AUTHOR]

Context Nutritional interventions for newborns with brain injury are scarce, and there are gaps in the knowledge of their mechanisms of action in preventing the occurrence of cerebral palsy (CP) or the incidence of other developmental disabilities. Objective The objective of this review was to assess the effect of nutritional interventions in preventing nonprogressive congenital or perinatal brain injuries, or in improving outcomes related to neurological development. Data Sources Randomized trials on any nutritional intervention for pregnant women at risk of preterm delivery, or for children with low birth weight, preterm, or with confirmed or suspected microcephaly, CP, or fetal alcohol syndrome disorders (FASDs) were retrieved from MEDLINE, Embase, Scopus, Web of Science, LILACS, and CENTRAL databases from inception to September 17, 2020. Data Extraction Data extraction, risk of bias (Cochrane Risk of Bias tool 2), and quality of evidence (GRADE approach) were assessed by 2 authors. Data Analysis Pooled risk ratios (RRs) with 95% confidence intervals were calculated using a random-effects meta-analysis. Seventeen studies were included on intravenous interventions (magnesium sulfate [n = 5], amino acids [n = 4], vitamin A [n = 1], and N-acetylcysteine [n = 1]); enteral interventions (vitamin D [n = 1], prebiotic [n = 1], nutrient-enriched formula [n = 1], and speed of increasing milk feeds [n = 1]); and oral interventions (choline [n = 1] and docosahexaenoic acid, choline, and uridine monophosphate [n = 1]). All studies assessed CP, except 1 on FASDs. Eight studies were judged as having high risk of bias. Five studies (7413 babies) with high-quality evidence demonstrated decreased risk of childhood CP (RR = 0.68, 95% CI: 0.52–0.88) with magnesium sulfate. Interventions with amino acids had no effect on CP prevention or other outcomes. Except for 1 study, no other intervention decreased the risk of CP or FASDs. Conclusion Although different types of nutritional interventions were found, only those with antenatal magnesium sulfate were effective in decreasing CP risk in preterm infants. Well-designed, adequately powered randomized clinical trials are required. [ABSTRACT FROM AUTHOR]

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 interven)tions mainly focus on preventing hypoxia, oxidative stress, inflammation, and growth restric)tion. 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, reduc)ing, 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. [ABSTRACT FROM AUTHOR]

Magnesium sulfate given to women before birth at <30 weeks' gestation reduces the risk of cerebral palsy in their children. Our study aimed to assess the impact of a local quality improvement programme, primarily using plan-do-study-act cycles, to increase the use of antenatal magnesium sulfate. After implementing our quality improvement programme, an average of 86% of babies delivered at <30 weeks' gestation were exposed to antenatal magnesium sulfate compared with a historical baseline rate of 63%. Our study strengthens the case for embedding quality improvement programmes in maternal perinatal care to reduce the impact of cerebral palsy on families and society. [ABSTRACT FROM AUTHOR]

Previous work demonstrated that implementing a quality improvement (QI) program improves the uptake of guideline‐recommended antenatal magnesium sulphate, a critical intervention known to reduce cerebral palsy risk. Here we estimate potential cost savings attributable to the improved uptake. By expanding coverage from 63 to 83% of eligible women, we estimated that five children potentially would not have received a diagnosis of cerebral palsy, a potential cost saving of $AU4.8 million in lifetime healthcare costs. Our findings strengthen the case for embedding QI approaches in perinatal care to reduce the incidence of cerebral palsy. [ABSTRACT FROM AUTHOR]

Advances in perinatal care have improved the prognoses of both mothers and neonates; however, cerebral palsy continues to occur. In this study, we examined methods for the intragestational evaluation of the health of infants who later developed cerebral palsy. A retrospective review was conducted on light‐for‐dates cases among the 2113 cause analysis reports issued by the Japan Obstetric Compensation System between January 2009 and September 2018. In our examination, we determined that non‐stress tests and ultrasonic Doppler tests were used to evaluate fetal well‐being. Moreover, we observed cases in which additional testing was not performed even when fetal growth restriction (FGR) was identified. Appropriate management of FGR may help reduce the incidence of cerebral palsy. [ABSTRACT FROM AUTHOR]

PURPOSE: Recognizing health disparities among children with cerebral palsy (CP) is necessary for understanding potential risk factors for CP and for implementing early and effective preventative and intervention treatments. However, there is currently little and conflicting evidence regarding the direct impact of contextual factors such as socioeconomic status (SES) for children with CP in the United States. These contextual factors include the complex social determinants of health on prematurity, comprehensive informed obstetric management for minority and vulnerable populations, and cumulative adversity disproportionately experienced by children, by gender, minority status, immigration, poverty, and structural racism. METHODS: This study presents results from a review of health disparities among children with CP, using registry and population surveillance data from Australia, Canada, Scandinavia, the United Kingdom, Ireland, Turkey, and the United States. RESULTS: The review confirmed that there are significant health disparities among children with CP, both in terms of prevalence and severity, based on factors such as SES, neighborhood disadvantage, maternal education, gender, and minority status. CONCLUSION: Strategies need to be implemented in the United States to promote enablement and functioning among children with CP who face additional health disparities. This requires a greater understanding of population groups at increased risk, comprehensive assessment and care for young children with motor delays, and systematic population counts of children and adults with CP using registries and systems of neurodevelopmental surveillance across health, education, and community rehabilitation. These efforts also require sensitivity to structural and persistent racism, stigma, trauma-informed care, and culturally sensitive community engagement. Additional efforts are also required to improve outcomes over the life course for individuals living a life with CP from a framework of enablement, self-direction, equity and social justice. [ABSTRACT FROM AUTHOR]

Purpose: Guidelines for the management of people with cerebral palsy are available from many countries. However, these cannot be adopted in their entirety in other countries due to socio-cultural differences and varied health systems. This study set out to develop guidelines for the management of people with cerebral palsy, throughout their lifetime, in India. Methods: A mixed methodology with a multiphasic approach was used. The first phase involved an extensive literature review to compile current evidence about the management of people with cerebral palsy. In the second phase, a questionnaire was given to stakeholders in order to explore current practices. The third phase consisted of consensus-building meetings with stakeholders, to develop resolutions that incorporate global best-practice recommendations for India. Results: Responses from the second phase were compiled and categorised based on discipline. Proceedings of the consensus meetings were transcribed verbatim and best evidence was synthesised to understand current global practice guidelines. Resolutions were formed within the framework of the results of phases I and II. These were ratified by experts and then formalised. Conclusion: Sixty-four resolutions were formed, detailing a framework for multidisciplinary management of persons with cerebral palsy throughout their lifetime. A card with guidelines was developed to document all aspects of rehabilitation, development and care. However, the utilisation and application of these guidelines have not been explored as yet. [ABSTRACT FROM AUTHOR]

Aim: To link data from a large maternal perinatal trial with the Australian Cerebral Palsy Register (ACPR) to identify children with cerebral palsy (CP).Method: Deidentified data from the Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4 ) and the ACPR were linked. Children born from 1996 to 2000 at Australian hospitals who survived and had 2-year paediatric assessments were included. Children identified with CP in: (1) both the ACTOMgSO4 (2y) and the ACPR (5y), (2) the ACTOMgSO4 only, and (3) the ACPR only were compared.Results: We included 913 children (492 males, 421 females; mean gestational age at birth 27.8wks [standard deviation 2.1wks]; range 23.0-40.0wks). Eighty-four children received a CP diagnosis: 35 by the ACTOMgSO4 and the ACPR, 29 by the ACTOMgSO4 only, and 20 by the ACPR only. The ACTOMgSO4 diagnosed 76.2% (95% confidence interval [CI] 65.9-84.1) and the ACPR identified 65.5% (95% CI 54.7-74.9). Children born in states/territories with long-standing versus more recently established registers were more likely to be included on the ACPR (p<0.05).Interpretation: Linking deidentified perinatal trial data with the ACPR was achieved. Limitations of both strategies for identifying children with CP in this era (late 1990s and early 2000s) probably explain many of the differences observed, and inform future linkage studies and evaluations of CP-preventive interventions.What This Paper Adds: Randomized trial data were linked with the Australian Cerebral Palsy Register. Trial (2y) and register (up to 5y) diagnoses of cerebral palsy (CP) differed. States with long-standing registers were more likely to include children with CP. [ABSTRACT FROM AUTHOR]

Background: Ordinary meta-analyses indicate that magnesium sulphate (MgSO4 ) treatment in women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy (CP). However, repetitive testing of cumulative data calls for statistical caution, e.g. by trial sequential analysis (TSA), for which there are previously insufficient samples to draw a firm conclusion. Recently, a randomised controlled trial (RCT) provided additional data that potentially increased the sample size such that a new TSA might detect a statistically significant effect.Objectives: To assess the possible fetal neuroprotective effect of MgSO4 for women at imminent risk for preterm delivery in an updated systematic review with meta-analysis and TSA.Search Strategy: We searched MEDLINE, Embase, Cochrane and ClinicalTrials.gov on 8 October 2019. The search strategy clustered terms describing the MgSO4 intervention and preterm delivery.Selection Criteria: RCTs.Data Collection and Analysis: Two reviewers extracted the data. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models. A TSA was applied to the primary outcome, CP. The quality of the evidence was assessed using GRADE. The protocol was registered in PROSPERO (registration: CRD42019151441).Main Results: We identified six eligible trials (5917 women). MgSO4 intervention in women at imminent risk for preterm birth decreased the offspring's CP risk (meta-analysis RR 0.68, 95% CI 0.54-0.85; TSA RR 0.69, 95% CI 0.48-0.97).Conclusions: This systematic review with meta-analysis and TSA shows conclusively that MgSO4 , when given to women at imminent risk for preterm delivery, decreases the offspring's CP risk.Tweetable Abstract: Antenatal magnesium sulphate decreases the risk of cerebral palsy in children born preterm. [ABSTRACT FROM AUTHOR]

To compare the outcomes and cost effectiveness of two alternate policy strategies for prenatal care among low-income, immigrant women: coverage for delivery only (the federal standard) and prenatal care with delivery coverage (state option under the Children's Health Insurance Program). A decision-analytic model was developed to determine the cost effectiveness of two alternate policies for pregnancy coverage. All states currently provide coverage for delivery, and 19 states also provide coverage for prenatal care. An estimated 84,000 unauthorized immigrant women have pregnancies where no prenatal care is covered. Our outcomes were costs, quality-adjusted life-years, and cases of cerebral palsy and infant death before age 1. Model inputs were obtained from a database of Oregon Medicaid claims and the literature. Univariate and bivariate sensitivity analyses, as well as a Monte Carlo simulation, were performed. Extending prenatal coverage is a cost-effective strategy. Providing prenatal care for the 84,000 women annually who are currently uninsured could prevent 117 infant deaths and 34 cases of cerebral palsy. Prenatal care coverage costs $380 more per woman than covering the delivery only. For every 865 additional women receiving prenatal care, one infant death would be averted, at an average cost of $328,700. Cost-effectiveness acceptability curve analyses suggest a 99% probability that providing prenatal care is more cost effective at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. Extending prenatal care to low-income, immigrant women, regardless of citizenship status, is a cost-effective strategy. [ABSTRACT FROM AUTHOR]

Objective: To estimate whether improvement in outcomes from antenatal corticosteroid treatment in extremely and very preterm twins is similar to that observed in singletons, and to investigate whether antenatal corticosteroid treatment has different effects according to chorionicity or birth order.Methods: This population-based study was based on an analysis of data collected by the Neonatal Research Network of Japan from 2003 to 2015 of neonates weighing 1,500 g or less at birth, from gestational ages of 24 0/7 to 31 6/7 weeks of gestation. After propensity score matching, univariate logistic and interaction analyses were performed to compare short-term (neonatal period) and medium-term (3 years of age) outcomes of the children of mothers who received antenatal corticosteroids with those of children of mothers who did not receive antenatal corticosteroids. We focused on differences between singletons and twins, between monochorionic and dichorionic twins and between the first and second twin.Results: The study comprised 23,502 singletons and 6,546 twins. Antenatal corticosteroid treatment was associated with significant decreased short-term neurologic outcomes in both singletons and twins. However, antenatal corticosteroid treatment was associated with significantly decreased mortality (odds ratio [OR] 0.61; 95% CI 0.53-0.70), respiratory distress syndrome (OR 0.71, 95% CI 0.67-0.76), and cerebral palsy (OR 0.85, 95% CI 0.72-0.99) in singletons but not in twins (OR 0.89, 95% CI 0.68-1.17; OR 0.99, 95% CI 0.87-1.12; and OR 0.82, 95% CI 0.61-1.11, respectively). No association was found between chorionicity and the efficacy of antenatal corticosteroid treatment on outcomes. Further, no association was found between birth order and the efficacy of antenatal corticosteroid treatment on outcomes, except for periventricular leukomalacia and necrotizing enterocolitis (interaction: P=.02 and P=.04, respectively).Conclusion: Antenatal corticosteroid treatment in twins was associated with a beneficial effect on short-term neurologic outcomes only, without improvement in other short-term and medium-term outcomes. There was no difference related to chorionicity. [ABSTRACT FROM AUTHOR]

Objective  To evaluate sex-specific genetic susceptibility to adverse neurodevelopmental outcome (ANO, defined as cerebral palsy [CP], mental, or psychomotor delay) at risk for early preterm birth (EPTB, < 32 weeks). Study Design  Secondary case–control analysis of a trial of magnesium sulfate (MgSO 4) before anticipated EPTB for CP prevention. Cases are infants who died by the age of 1 year or developed ANO. Controls, matched by maternal race and infant sex, were neurodevelopmentally normal survivors. Neonatal DNA was evaluated for 80 polymorphisms in inflammation, coagulation, vasoregulation, excitotoxicity, and oxidative stress pathways using Taqman assays. The primary outcome for this analysis was sex-specific ANO susceptibility. Conditional logistic regression estimated each polymorphism's odds ratio (OR) by sex stratum, adjusting for gestational age, maternal education, and MgSO 4 -corticosteroid exposures. Holm–Bonferroni corrections, adjusting for multiple comparisons (p  < 7.3 × 10 −4), accounted for linkage disequilibrium between markers. Results  Analysis included 211 cases (134 males; 77 females) and 213 controls (130 males; 83 females). An interleukin-6 (IL6) polymorphism (rs2069840) was associated with ANO in females (OR: 2.6, 95% confidence interval [CI]: 1.5–4.7; p  = 0.001), but not in males (OR: 0.8, 95% CI: 0.5–1.2; p  = 0.33). The sex-specific effect difference was significant (p  = 7.0 × 10 −4) and was unaffected by MgSO 4 exposure. No other gene–sex associations were significant. Conclusion  An IL6 gene locus may confer susceptibility to ANO in females, but not males, after EPTB. [ABSTRACT FROM AUTHOR]

Background: Erythropoietin (EPO) appears to confer neuroprotection to the injured brain. Randomized clinical trials (RCTs) have demonstrated its safety in neonates with hypoxic-ischemic encephalopathy (HIE); however, the evidence is unclear. The objective of this study was to examine the role of EPO in perinatal HIE by a systematic review and meta-analysis. Methods: Database search included Embase, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). RCTs reporting a death, neurodevelopmental outcomes or brain injury were included. Two authors extracted the data independently from included studies and assessed the level of evidence (LOE). Results: Six RCTs (EPO = 5 and darbepoetin α = 1) involving 454 neonates were included. A trend toward a lower risk of death was identified in infants treated with EPO [EPO with or without hypothermia: five RCTs, 368 participants, relative risk (RR) 0.74, 95% confidence interval (CI) 0.47-1.19, LOE - low; EPO without hypothermia: four RCTs, 318 participants, RR 0.89, 95% CI 0.49-1.32, LOE - low]. EPO treatment without hypothermia compared to placebo resulted in a reduced risk of cerebral palsy (two RCTs, 230 participants, RR 0.47, 95% CI 0.27-0.80, LOE - moderate) and moderate to severe cognitive impairment (two RCTs, 226 participants, RR 0.49, 95% CI 0.28-0.85, LOE - moderate). A reduced risk of brain injury was identified in EPO treated infants (EPO with or without hypothermia, two RCTs, 148 participants, RR 0.70, 95% CI 0.53-0.92, LOE - moderate). Conclusion: EPO administration in neonates with perinatal HIE reduces the risk of brain injury, cerebral palsy and cognitive impairment. The evidence is limited to suggest its role as an adjuvant to hypothermia. Larger powered trials are underway to overcome this limitation. [ABSTRACT FROM AUTHOR]

The Japan Obstetric Compensation System for Cerebral Palsy (JOCS‐CP), which investigates, develops preventive mechanisms and awards monetary compensation, to cases of cerebral palsy was urgently introduced in 2009 in response to growing concern about Japan's deteriorating perinatal care and low birthrate. Under the political leadership, the Japan Council for Quality Health Care launched the JOCS‐CP with support of various stakeholders. The JOCS‐CP features of no‐fault‐based compensation which was discussed decades ago in the Japan Medical Association aiming at financial aid to patient and family and early settlement of dispute. As of 2017, 2233 petitions had been approved by the Review Committee for compensation. All the approved cases were consecutively put on analysis in the Investigation Committee which has compiled more than 1000 Investigative Reports. The reports were delivered not only to the childbirth facility but to the guardians/families. Survey revealed that most of childbirth facility and the guardians/families responded in favor of the reports. With regard to amelioration of profound cerebral palsy, the Prevention Report has been published on annual basis through analysis of all the Investigative Reports. The Prevention Reports and other educational materials were produced and distributed not only among medical professionals but among pregnant women. It is notable that the number of lawsuit filing related to obstetrics demonstrated rapid decrease compared to that of other medical specialties. The JOCS‐CP could be described as a social experiment. It was overhauled in 2015 but deserves further discussion on reform for evolving into better system. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) remains the most significant neurological disorder associated with preterm birth. It disrupts quality of life and places huge cost burdens on society. Antenatal magnesium sulphate administration to females before 32 weeks' gestation has proven to be an effective intervention to reduce the rate of CP. In models of hypoxia, hypoxia-ischemia, inflammation, and excitotoxicity in various animal species, magnesium sulphate preconditioning decreased the resulting lesion sizes and inflammatory cytokine levels, prevented cell death, and improved long-term cognitive and motor behaviours. In humans, meta-analyses of five randomized controlled trials using magnesium sulphate as a neuroprotectant showed prevention of CP at 2 years. The benefit remained consistent regardless of gestational age, cause of preterm birth, and total dose received. Antenatal magnesium sulphate treatment is now recommended by the World Health Organization and by many obstetric societies. Its cost-effectiveness further justifies its widespread implementation. WHAT THIS PAPER ADDS: Neuroprotective effect of magnesium sulphate to reduce cerebral palsy in infants born preterm when administered to females at risk of imminent preterm birth. Neuroprotection regardless of gestational age, cause of preterm birth, and total dose. Antenatal magnesium sulphate treatment has good cost-effectiveness. [ABSTRACT FROM AUTHOR]

Objective  To quantify the potential cost savings if azithromycin is substituted for erythromycin in women with preterm premature rupture of membranes (PPROM). Study Design  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. Results  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. Conclusion  The use of azithromycin substituted for erythromycin in the standard antibiotic regimen of women with PPROM represents a potential for substantial cost reduction. [ABSTRACT FROM AUTHOR]

Objective: To determine whether early hydrocortisone treatment in extremely preterm infants affects neurodevelopmental outcomes at 2 years of age according to gestational age at birth.Patients and Methods: This is an exploratory analysis of neurodevelopmental outcomes by gestational age strata from the PREMILOC trial, in which patients were randomly assigned to receive either placebo or low-dose hydrocortisone and randomisation was stratified by gestational age groups (24-25 and 26-27 weeks of gestation). Neurodevelopmental impairment (NDI) was assessed using a standardised neurological examination and the revised Brunet-Lézine scale at 22 months of corrected age.Results: A total of 379 of 406 survivors were evaluated, 96/98 in the gestational age group of 24-25 weeks and 283/308 in the gestational age group of 26-27 weeks. Among surviving infants born at 24-25 weeks, significant improvement in global neurological assessment was observed in the hydrocortisone group compared with the placebo group (P=0.02) with a risk of moderate-to-severe NDI of 2% and 18%, respectively (risk difference 16 (95% CI -28% to -5%)). In contrast, no statistically significant difference between treatment groups was observed in infants born at 26-27 weeks (P=0.95) with a similar risk of moderate-to-severe NDI of 9% in both groups. The incidence of cerebral palsy or other major neurological impairments were found similar between treatment groups in each gestational group.Conclusions: In an exploratory analysis of neurodevelopmental outcomes from the PREMILOC trial, early low-dose hydrocortisone was associated with a statistically significant improvement in neurodevelopmental outcomes in infants born at 24 and 25 weeks of gestation. [ABSTRACT FROM AUTHOR]

Aim: To investigate the role of the severity of manual impairment and of hand dominance on postural sway during anticipatory [APA] and compensatory [CPA] postural adjustments in a seated manual reaching task performed by children with cerebral palsy (CP) and typical children (TC).Methods: We tested 26 TC (mean age 9.5 ± 2.1 years) and 29 children with CP (age 9.6 ± 3 years) classified based on manual impairment levels as mild (Manual Ability Classification System [MACS] I; n = 18) or moderate-to-severe (MACS II-III, n = 11). Participants were instructed to reach towards a target using their dominant vs. non-dominant arm while sitting on a force-plate. Center of pressure (CoP) sway was analyzed during APA and CPA.Results: For all groups, using the non-dominant arm determined greater amplitude and velocity of CoP sway in CPA. Children with moderate-to-severe manual impairment showed greater sway during APA and CPA compared to mild impairment and TC groups.Conclusion: More severe manual impairment resulted in higher sway during the anticipatory and compensatory phases of the reaching task. Using the non-dominant arm resulted in greater compensatory adjustments during reaching. [ABSTRACT FROM AUTHOR]

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. Preventing perinatal brain damage. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is the most prevalent, severe and costly motor disability of childhood. Consequently, CP is a public health priority for prevention, but its aetiology has proved complex. In this Review, we summarize the evidence for a decline in the birth prevalence of CP in some high-income nations, describe the epidemiological evidence for risk factors, such as preterm delivery and fetal growth restriction, genetics, pregnancy infection and other exposures, and discuss the success achieved so far in prevention through the use of magnesium sulfate in preterm labour and therapeutic hypothermia for birth-asphyxiated infants. We also consider the complexities of disentangling prenatal and perinatal influences, and of establishing subtypes of the disorder, with a view to accelerating the translation of evidence into the development of strategies for the prevention of CP. [ABSTRACT FROM AUTHOR]

The article discusses a research which differentiates between mothers of preterm versus term infants or identifies the number of weeks that women should stop breastfeeding or pumping breast milk. According to the organization American Academy of Pediatrics (AAP), breastfeeding is required for all infants regardless of birthweight. Also emphasized is the health benefits of breastfeeding to reduce intellectual disability, cerebral palsy and growth restriction.

Objective To evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. Study Design We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. Results Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). Conclusion Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci. [ABSTRACT FROM AUTHOR]

Purpose: We examined the effects of magnesium on premature neonatal outcomes complicated by chorioamnionitis.Materials and Methods: We conducted a secondary analysis of data from the BEAM Trial, an RCT to determine if antenatal magnesium decreases the incidence of CP in preterm birth. We compared the effect of magnesium sulfate by the presence or absence of chorioamnionitis. Outcomes examined include CP, IVH, NEC, BPD, and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios of each outcome.Results: About 1944 women were included in this analysis of which 228 were diagnosed with chorioamnionitis. Demographic characteristics were similar between women randomized to receive magnesium or placebo. Magnesium therapy demonstrated no significant reduction in CP in the presence of chorioamnionitis (OR 0.76, CI: 0.19-2.76) but does demonstrate benefit in the absence of chorioamnionitis (OR 0.52, CI: 0.31-0.86).Conclusions: Antenatal magnesium did not show a clear neuroprotective effect in the setting of chorioamnionitis. [ABSTRACT FROM AUTHOR]

Objective: Evidence supports the need of dose-adjustment of several drugs according to body mass index (BMI) to prevent toxicity in the underweight, and ensure efficacy in obese women. However, for MgSO4 neuroprotection, the effect of BMI on maternal toxicity and fetal neuroprotection is understudied. We analyze the effect of BMI on maternal/infant outcomes after MgSO4.Methods: Secondary analysis of a clinical trial that studied MgSO4 neuroprotection. Maternal side effects, magnesium cord levels, and offspring cerebral palsy/death were analyzed along BMI strata using ANOVA and chi-square test. Logistic regression was used to calculate adjusted odds ratios according to the treatment and BMI, using nonobese that received placebo as reference. Interaction analyses were performed to validate differential efficacy of BMI.Results: From 2241 women, more side effects and higher magnesium cord levels were seen in underweight women (p = 0.05). MgSO4 neuroprotection was effective in the non-obese (p = 0.02), but not in obese women (p = 1.00). In multivariate analyses, MgSO4 significantly reduced cerebral palsy only in nonobese women. Interaction analyses showed the moderator effect of BMI (p = 0.169). Increasing MgSO4 dose in obese mothers may ensure neuroprotective efficacy without representing increased maternal risks. Considering costs of studying this association, current analysis may form the basis for reasonable practice. [ABSTRACT FROM AUTHOR]

Background: Evidence supports magnesium sulphate (MgSO4) for women at risk of imminent birth at < 32-34 weeks to reduce the likelihood of cerebral palsy in the child. MAGnesium sulphate for fetal neuroprotection to prevent Cerebral Palsy (MAG-CP) was a multifaceted knowledge translation (KT) strategy for this practice.Methods: The KT strategy included national clinical practice guidelines, a national online e-learning module and, at MAG-CP sites, educational rounds, focus group discussions and surveys of barriers and facilitators. Participating sites contributed data on pregnancies with threatened very preterm birth. In an interrupted time-series study design, MgSO4 use for fetal neuroprotection (NP) was tracked prior to (Aug 2005-May 2011) and during (Jun 2011-Sept 2015) the KT intervention. Effectiveness of the strategy was measured by optimal MgSO4 use (i.e. administration when and only when indicated) over time, evaluated by a segmented generalised estimating equations logistic regression (p < 0.05 significant). Secondary outcomes included maternal effects and, using the Canadian Neonatal Network (CNN) database, national trends in MgSO4 use for fetal NP and associated neonatal resuscitation. With an anticipated recruitment of 3752 mothers over 4 years at Canadian Perinatal Network sites, we anticipated > 95% power to detect an increase in optimal MgSO4 use for fetal NP from < 5 to 80% (2-sided, alpha 0.05) and at least 80% power to detect any increases observed in maternal side effects from RCTs.Results: Seven thousand eight hundred eighty-eight women with imminent preterm birth were eligible for MgSO4 for fetal NP: 4745 pre-KT (18 centres) and 3143 during KT (11 centres). The KT intervention was associated with an 84% increase in the odds of optimal use (OR 1.00 to 1.84, p < 0.001), a reduction in the odds of underuse (OR 1.00 to 0.47, p < 0.001) and an increase in suboptimal use (too early or at ≥ 32 weeks; OR 1.18 to 2.18, p < 0.001) of MgSO4 for fetal NP. Maternal hypotension was uncommon (7/1512, 0.5%). Nationally, intensive neonatal resuscitation decreased (p = 0.024) despite rising MgSO4 use for fetal NP (p < 0.001).Conclusion: Multifaceted KT was associated with significant increases in use of MgSO4 for fetal NP, with neither important maternal nor neonatal risks. [ABSTRACT FROM AUTHOR]

Background: Limited data exist regarding the neonatal and neurodevelopmental outcomes of infants exposed to marijuana (MJ) in-utero, particularly among preterm infants. We hypothesized that MJ-exposed preterm infants would have worse neonatal and childhood developmental outcomes compared to MJ-unexposed infants.Methods: Secondary analysis of multicenter randomized-controlled trial of antenatal magnesium sulfate for the prevention of cerebral palsy was conducted. Singleton nonanomalous infants delivered <35 weeks exposed to MJ in-utero were compared to MJ-unexposed. Primary neonatal outcome was death, grade 3/4 intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, and/or stage II/III necrotizing enterocolitis before discharge. Primary childhood outcome was death, moderate/severe cerebral palsy, or/and Bayley II Scales <70 at age 2. Backward-stepwise regression used to estimate odds of primary outcomes.Results: 1867 infants met inclusion criteria; 135(7.2%) were MJ-exposed. There were no differences in neonatal (20% vs. 26%, p = 0.14) or childhood (26% vs. 21%, p = 0.21) outcomes in MJ-exposed infants compared to MJ-unexposed infants. In adjusted models, MJ-exposure was not associated with adverse neonatal outcomes (aOR 0.83 95% CI 0.47,1.44) or early childhood outcomes (aOR 1.47, 95% CI 0.97,2.23).Conclusions: Among infants born <35 weeks of gestation, MJ-exposure was not associated with adverse neonatal or childhood outcomes. Long-term follow-up studies are needed to assess later childhood neurodevelopmental outcomes following MJ-exposure. [ABSTRACT FROM AUTHOR]

The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population-based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy. Among 1905 women who met inclusion criteria, the incidence of cerebral palsy in the cohort was 3.6% for women who had received magnesium sulfate and 6.4% for controls. The simulated maternal serum concentration at delivery associated with the lowest probability of delivering an infant with cerebral palsy was 4.1 mg/dL (95%CI 3.7 to 4.4). Our population-based estimates of magnesium disposition suggest that to optimize fetal neuroprotection and prevent cerebral palsy, magnesium sulfate administration should target a maternal serum magnesium level between 3.7 and 4.4 mg/dL at delivery. [ABSTRACT FROM AUTHOR]

Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate.Methods and Findings: Trials in which women considered at risk of preterm birth (<37 weeks' gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited.Conclusions: Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to investigate the use of fetal cerebroplacental ratio (CPR) to identify fetuses at high risk before labor due to the brain sparing phenomenon.Materials and Methods: Four hundred and seventy-six singleton pregnancies were enrolled in this study. The CPR was recorded within 1 week of delivery and labor was managed according to local protocols and guidelines. Intrapartum and neonatal outcome details were recorded.Results: The CPR values of fetuses subsequently presenting category III intrapartum electronic fetal monitoring (EFM) or category II EFM without improvement (category IIB EFM) or with progression to category III (category IIC EFM) were significantly lower. On multivariate logistic regression, CPR was independently associated with the risk of categories III EFM, IIB EFM and IIC EFM. CPR was also a predictor of categories III EFM, IIB EFM and IIC EFM.Conclusions: Fetal CPR could be used to identify fetuses at high risk before labor and to help guide intrapartum management decisions. [ABSTRACT FROM AUTHOR]

This article provides a narrative review of lung-protective ventilatory strategies (LPVS) in intubated preterm infants with RDS. A description of strategies is followed by results on short-and long-term respiratory and neurodevelopmental outcomes. Strategies will include patient-triggered or synchronized ventilation, volume targeted ventilation, the technique of intubation, surfactant administration and rapid extubation to NCPAP (INSURE), the open lung concept, strategies of high-frequency ventilation, and permissive hypercapnia. Based on this review single recommendations on optimal LPVS cannot be made. Combinations of several strategies, individually applied, most probably minimize or avoid potential serious respiratory and cerebral complications like bronchopulmonary dysplasia and cerebral palsy. [ABSTRACT FROM AUTHOR]

A 3-year-old boy diagnosed with diplegic cerebral palsy had received Botulinum toxin injection to reduce severe spasticity. There was an improvement of muscles tone and motor function including better ability of limb flexion of the knees and hip, adduction of the hip, flexion of the toes, and plantar flexion of the foot. No side effect was observed after the procedure. [ABSTRACT FROM AUTHOR]

Electronic fetal monitoring (EFM) was predicted by its inventors to be the long-sought cerebral palsy (CP) nemesis. Rather than prevent CP or any other birth problems, 40 years of EFM use has done substantial harm to mothers and babies and created a worldwide CP-EFM litigation industry that enriches only trial lawyers. Physicians, frightened by the ever-expanding and costly CP-EFM litigation crisis, and focused on avoiding lawsuits at all costs, embraced ethical relativism—charitably called defensive medicine—and continued EFM use even in the face of overwhelming evidence that EFM is merely junk science. In doing so, physicians completely abandoned the bedrock bioethics principles of autonomy, beneficence, and nonmaleficence. This daily ethical drama has played itself out for the past almost half century with little protest from obstetricians and no protest from ethicists. This article reviews EFM harms, the CP-EFM litigation crisis, and the resulting abandonment of bioethics principles and explores why the CP-EFM paradigm has failed utterly to follow the Kuhnian model of the scientific, technology, medical paradigm shift. [ABSTRACT FROM AUTHOR]

Electronic fetal monitoring (EFM) was predicted by its inventors to be the long-sought cerebral palsy (CP) nemesis. Rather than prevent CP or any other birth problems, 40 years of EFM use has done substantial harm to mothers and babies and created a worldwide CP-EFM litigation industry that enriches only trial lawyers. Physicians, frightened by the ever-expanding and costly CP-EFM litigation crisis, and focused on avoiding lawsuits at all costs, embraced ethical relativism—charitably called defensive medicine—and continued EFM use even in the face of overwhelming evidence that EFM is merely junk science. In doing so, physicians completely abandoned the bedrock bioethics principles of autonomy, beneficence, and nonmaleficence. This daily ethical drama has played itself out for the past almost half century with little protest from obstetricians and no protest from ethicists. This article reviews EFM harms, the CP-EFM litigation crisis, and the resulting abandonment of bioethics principles and explores why the CP-EFM paradigm has failed utterly to follow the Kuhnian model of the scientific, technology, medical paradigm shift. [ABSTRACT FROM AUTHOR]

The article focuses on a study by Duke Health researchers who have identified a fatty molecule in breast milk that, in experiments with neonatal mice, triggers a process in which brain stem cells produce cells creating new white matter, potentially reversing brain injuries.

Translating risk estimates derived from epidemiologic study into evidence of causality for a particular patient is problematic. The difficulty of this process is not unique to the medical context; rather, courts are also challenged with the task of using risk estimates to infer evidence of cause in particular cases. Thus, an examination of how this is done in a legal context might provide insight into when and how it is appropriate to use risk information as evidence of cause in a medical context. A careful study of the case of Goodman v. Viljoen, a medical malpractice suit litigated in the Ontario Superior Court of Justice in 2011, reveals different approaches to how risk information is used as or might be considered a substitute for evidence of causation, and the pitfalls associated with these approaches. Achieving statistical thresholds, specifically minimizing the probability of falsely rejecting the null hypothesis, and exceeding a relative risk of 2, plays a significant role in establishing causality of the particular in the legal setting. However, providing a reasonable explanation or establishing 'biological plausibility' of the causal association also seems important, and (to some) may even take precedent over statistical thresholds for a given context. [ABSTRACT FROM AUTHOR]

Background The presence of a fetal inflammatory response is linked to cerebral palsy. Unfortunately no preventive therapies are available. In this study, we determined whether dietary supplementation with broccoli sprouts (BrSp), a phase-II enzyme inducer, would be effective in preventing the behavioural and pathologic manifestations in a rodent model of inflammation during late pregnancy. Methods Pregnant Long-Evans rats were administered i.p. Injections of saline (100 μl) or lipopolysaccharide (LPS, 200 μg/kg), every 12 h on embryonic day (E) 19 and 20. In the treatment groups, dams were supplemented with 200 mg/day of dried BrSp from E14 until postnatal day 21. Pups underwent a series of neurodevelopmental reflex tests from postnatal day 3–21 followed by neuropathological analyses. Results Pups born from the LPS group were significantly growth restricted (p < 0.001) and delayed in hindlimb placing (p < 0.05), cliff avoidance (p < 0.05), and gait (p < 0.001) compared to controls. In the open field behaviour analyses, LPS pups had an increase in grooming behaviour (p < 0.05) and a decreased amount of time spent in the center of the box compared to controls. Dietary supplementation with BrSp to offspring exposed to LPS had increased birth weights (p < 0.001), were no longer delayed in acquiring hindlimb placing, cliff avoidance, gait, and posture, and groomed less compared to LPS alone pups (p < 0.01). Histological analyses revealed that LPS pups had reduced myelin basic protein compared to controls. Conclusions Our data suggest that BrSp dietary supplementation during pregnancy may be effective in preventing growth restriction and neurodevelopmental delays. [ABSTRACT FROM AUTHOR]

Objective: To assess the neuroprotective effect of magnesium sulfate (MgSO4 ) in preterm children exposed to chorioamnionitis.Design: A secondary analysis of a multicentre randomised controlled trial of antenatal MgSO4 administered to women at risk of preterm birth for the prevention of cerebral palsy (CP). Singleton, non-anomalous pregnancies with clinical chorioamnionitis, delivering at ≥24 weeks of gestation, were selected. Cases were exposed to antepartum MgSO4 ; controls received placebo.Setting: Multicentre randomised controlled trial.Population: Singleton, non-anomalous pregnancies with clinical chorioamnionitis, delivering at ≥24 weeks of gestation.Methods: All data were analysed by intention to treat. Univariate and multivariate analyses were performed.Main Outcome Measures: Primary outcome was a composite of stillbirth, death by the age of 1 year, or moderate or severe CP by the age of 2 years. Secondary outcomes included a composite neonatal outcome as well as neurodevelopmental delay, defined as Bayley II mental and psychomotor developmental indices <70 at the age of 2 years. Subgroup analysis assessed these outcomes in children born at <28 weeks of gestation.Results: A total of 396 children were included, with 192 (48.5%) randomised to MgSO4 . Maternal and delivery characteristics were similar between the groups. The primary outcome occurred in 14.1% of children exposed to MgSO4 and 12.7% of children exposed to placebo (relative risk, RR 1.29; 95% CI 0.70-2.38). Rates of stillbirth, death, moderate-severe CP, and neurodevelopmental delay did not differ between groups. In the subgroup analysis of children born at <28 weeks of gestation, there was no difference in the rates of the primary outcome, nor in the secondary outcomes assessed. [Correction added on 02 March 2016 after online publication: There were errors in statistical data analysis and these have been corrected throughout the article.]Conclusions: Among children at risk for early preterm delivery exposed to chorioamnionitis, antenatal administration of MgSO4 was not associated with improved neurodevelopmental outcome. We do not recommend any change in the guidelines on the administration of MgSO4 for neuroprotection based on this study.Tweetable Abstract: MgSO4 was not associated with improved neurodevelopmental outcome in setting of chorioamnionitis. [ABSTRACT FROM AUTHOR]

Objective: Maternal exposure to magnesium sulphate has a neuroprotective effect in premature infants. This study aimed to examine this neuroprotective effect and the dose-response relationship in very-low-birthweight infants born between 24 and 32 weeks of gestation.Study Design: A retrospective cohort study compared the rates of mortality and brain damage between three groups: no magnesium sulphate, low-dose (<50g) magnesium sulphate and high-dose (≥50g) magnesium sulphate.Results: Japanese maternal and neonatal databases were linked using six key parameters from 2003 to 2007. Of 298,514 deliveries, 9101 were very-low-birthweight infants. Among these, full matching was possible for 5562 infants. Of the fully-matched infants, 3763 were born between 24 and 32 weeks of gestation, and 1813 (48%) were followed-up beyond 18 months. A multivariate analysis of the data, including gestational age, sex, fetal growth restriction, antenatal steroids and low pH (<7.1), showed that the low-dose group had no beneficial effects in terms of a reduction in mortality or incidence of brain damage (cerebral palsy or mental retardation). The high-dose group showed a significantly higher mortality rate [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.2-2.9]. A stratified subgroup analysis of infants born between 28 and 32 weeks of gestation showed that survivors in the low-dose group had significantly lower rates of cerebral palsy (OR 0.4, 95% CI 0.2-0.98) and brain damage (OR 0.2, 95% CI 0.1-0.9), while the high-dose group did not show any significant changes.Conclusion: This study found that antepartum exposure to magnesium sulphate did not reduce the infant mortality rate or influence neurological outcomes. However, among infants born between 28 and 32 weeks of gestation, rates of cerebral palsy and brain damage were found to be significantly lower among survivors in the low-dose group. [ABSTRACT FROM AUTHOR]

Background: Administration of magnesium sulphate (MgSO4) to women with imminent preterm birth at <34 weeks is an evidence-based antenatal neuroprotective strategy to prevent cerebral palsy. Although a Society of Obstetricians and Gynaecologists of Canada (SOGC) national guideline with practice recommendations based on relevant clinical evidence exists, ongoing controversies about aspects of this treatment remain. Given this, we anticipated managed knowledge translation (KT) would be needed to facilitate uptake of the guidelines into practice. As part of the Canadian Institutes of Health Research (CIHR)-funded MAG-CP (MAGnesium sulphate to prevent Cerebral Palsy) project, we aimed to compare three KT methods designed to impact both individual health care providers and the organizational systems in which they work.Methods: The KT methods undertaken were an interactive online e-learning module available to all SOGC members, and at MAG-CP participating sites, on-site educational rounds and focus group discussions, and circulation of an anonymous 'Barriers and Facilitators' survey for the systematic identification of facilitators and barriers for uptake of practice change. We compared these strategies according to: (i) breadth of respondents reached; (ii) rates and richness of identified barriers, facilitators, and knowledge needed; and (iii) cost.Results: No individual KT method was superior to the others by all criteria, and in combination, they provided richer information than any individual method. The e-learning module reached the most diverse audience of health care providers, the site visits provided opportunity for iterative dialogue, and the survey was the least expensive. Although the site visits provided the most detailed information around individual and organizational barriers, the 'Barriers and Facilitators' survey provided more detail regarding social-level barriers. The facilitators identified varied by KT method. The type of knowledge needed was further defined by the e-learning module and surveys.Conclusions: Our findings suggest that a multifaceted approach to KT is optimal for translating national obstetric guidelines into clinical practice. As audit and feedback are essential parts of the process by which evidence to practice gaps are closed, MAG-CP is continuing the iterative KT process described in this paper concurrent with tracking of MgSO4 use for fetal neuroprotection and maternal and child outcomes until September 2015; results are anticipated in 2016. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to determine the morbidity of preterm small for gestational age (SGA) infants compared with appropriate for GA (AGA). Study Design This is a secondary analysis of the randomized trial evaluating magnesium sulfate for the prevention of cerebral palsy (CP). We compared outcomes of preterm (< 37 weeks) nonanomalous infants who were SGA (birth weight < 10% for GA) versus AGA (birth weight 10-89% for GA). We compared (1) the parent trial primary outcome, a composite of stillbirth, infant death by 1 year of age, or moderate to severe CP at 2 years of age and (2) composite neonatal morbidity (CNM). Results Of the 1,948 infants who met inclusion criteria, 95% were AGA and 5% were SGA. The primary outcome was similar (10 and 15%, p = 0.08), as was the CNM (24 and 25%, p = 0.89). Sample size calculations indicate that detection of a one-third higher rate of CNM among SGA compared with AGA infants requires more than 93,900 preterm births; fora one-third difference in moderate to severe CP, more than 1.4 million infants. Conclusion Owing to the prohibitive sample size required, ascertaining a difference in sequela between preterm SGA and AGA infants is possibly unverifiable. [ABSTRACT FROM AUTHOR]

The neuro-protective effect of antenatal magnesium sulfate on very preterm infants has been demonstrated in good-quality randomised controlled trials and meta-analyses. Magnesium administered prior to preterm delivery crosses over to the foetal circulation and acts via several pathways to reduce perinatal neuronal damage. Meta-analysis of the trial data indicates that antenatal magnesium sulfate reduces the risk of cerebral palsy by one-third, and results in one fewer case in every 50 women treated. Treatment is associated with discomfort and flushing in some women, but maternal side-effects are mostly transient and manageable. Magnesium sulfate has also been found to be without any serious adverse consequences in newborn infants. Consensus recommendations and guidelines have been developed and implemented internationally, and endorsed by the UK Royal College of Obstetricians and Gynaecologists. However, magnesium sulfate for neuro-protection of very preterm infants has not yet become established widely in UK practice. Paediatricians, neonatologists and advocacy groups for preterm infants and their families could contribute to raising awareness and engage in dissemination activities and implementation initiatives to develop local protocols for adoption of this safe, effective and cost-effective intervention to reduce the burden of cerebral palsy in children born very preterm. [ABSTRACT FROM AUTHOR]

Objective: To systematically review meta-analyses (MAs) and randomised controlled trials (RCTs) of interventions for infants at risk of cerebral palsy (CP), to determine if consensus exists in study end-points.Methods: MAs within the "Neonatal" and "Pregnancy and Childbirth" Review Groups in Cochrane Database of Systematic Reviews (to June 2011) were included if they contained risk factors for CP as a study end-point, and were either published in 2010 or 2011 or cited >20 times in Sciverse Scopus. Up to 20 RCTs from each MA were included. Outcome measures, definitions and cut-points for ordinal groupings were extracted from MAs and RCTs and frequencies calculated.Results: Twenty-two MAs and 165 RCTs were appraised. High consistency existed in types of outcome domains listed as important in MAs. For 10/16 most frequently cited outcome domains, <50% of RCTs contributed data for meta-analyses. Low consistency in outcome definitions, measures, cut-points in RCTs and long-term follow-up prohibited data aggregation.Conclusions: Variation in outcome measurement and long-term follow up has hampered the ability of RCTs to contribute data on important outcomes for CP, resulting in lost opportunities to measure the impact of maternal and neonatal interventions. There is an urgent need for and long-term follow up of these interventions and an agreed set of standardised and clinically relevant common data elements for study end-points. [ABSTRACT FROM AUTHOR]

Background: Strong evidence supports administration of magnesium sulphate prior to birth at less than 30 weeks' gestation to prevent very preterm babies dying or developing cerebral palsy. This study was undertaken as part of The WISH (Working to Improve Survival and Health for babies born very preterm) Project, to assess health professionals' self-reported use of antenatal magnesium sulphate, and barriers and enablers to implementation of 2010 Australian and New Zealand clinical practice guidelines. Methods: Semi-structured, one-to-one interviews were conducted with obstetric and neonatal consultants and trainees, and midwives in 2011 (n = 24) and 2012–2013 (n = 21) at the Women's and Children's Hospital, South Australia. Transcribed interview data were coded using the Theoretical Domains Framework (describing 14 domains related to behaviour change) for analysis of barriers and enablers. Results: In 2012–13, health professionals more often reported 'routinely' or 'sometimes' administering or advising their colleagues to administer magnesium sulphate for fetal neuroprotection (86 % in 2012–13 vs. 46 % in 2011). 'Knowledge and skills', 'memory, attention and decision processes', 'environmental context and resources', 'beliefs about consequences' and 'social influences' were key domains identified in the barrier and enabler analysis. Perceived barriers were the complex administration processes, time pressures, and the unpredictability of preterm birth. Enablers included education for staff and women at risk of very preterm birth, reminders and 'prompts', simplified processes for administration, and influential colleagues. Conclusions: This study has provided valuable data on barriers and enablers to implementing magnesium sulphate for fetal neuroprotection, with implications for designing and modifying future behaviour change strategies, to ensure optimal uptake of this neuroprotective therapy for very preterm infants. [ABSTRACT FROM AUTHOR]

Objective This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 316/7 weeks' gestation. Study Design This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 316/7 weeks' gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysiswere delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. Results A total of 1,259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p ј 0.51). Delivery < 7 days was similar between groups (55.4 and 51.4%, p ј 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p ј 0.29). Composite neonatal outcomes did not differ between groups. Conclusion Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency. [ABSTRACT FROM AUTHOR]

Antenatal magnesium sulphate reduces the risk of cerebral palsy in babies born <30 weeks' gestation. A guideline for its use in women at imminent risk of preterm birth was implemented at National Women's Health, Auckland City Hospital in 2012. This prospective audit assessed adherence to the guideline in women delivering at <30 weeks in the first year after its implementation. Magnesium sulphate was safely administered to 58 of 71 (82%) eligible women and 58 of 61 (95%) of women where it was clinically appropriate and practically achievable. [ABSTRACT FROM AUTHOR]