Quality improvement interventions to increase the uptake of magnesium sulphate in preterm deliveries for the prevention of cerebral palsy (PReCePT study): a cluster randomised controlled trial.

OBJECTIVE: To compare two quality improvement (QI) interventions to improve antenatal magnesium sulphate (MgSO4 ) uptake in preterm births for the prevention of cerebral palsy. DESIGN: Unblinded cluster randomised controlled trial. SETTING: Academic Health Sciences Network, England, 2018. SAMPLE: Maternity units with ≥10 preterm deliveries annually and MgSO4 uptake of ≤70%; 40 (27 NPP, 13 enhanced support) were included (randomisation stratified by MgSO4 uptake). METHODS: The National PReCePT Programme (NPP) gave maternity units QI materials (clinical guidance, training), regional support, and midwife backfill funding. Enhanced support units received this plus extra backfill funding and unit-level QI coaching. MAIN OUTCOME MEASURES: MgSO4 uptake was compared using routine data and multivariable linear regression. Net monetary benefit was estimated, based on implementation costs, lifetime quality-adjusted life-years and societal costs. The implementation process was assessed through qualitative interviews. RESULTS: MgSO4 uptake increased in all units, with no evidence of any difference between groups (0.84 percentage points lower uptake in the enhanced group, 95% CI -5.03 to 3.35). The probability of enhanced support being cost-effective was <30%. NPP midwives gave more than their funded hours for implementation. Units varied in their support needs. Enhanced support units reported better understanding, engagement and perinatal teamwork. CONCLUSIONS: PReCePT improved MgSO4 uptake in all maternity units. Enhanced support did not further improve uptake but may improve teamwork, and more accurately represented the time needed for implementation. Targeted enhanced support, sustainability of improvements and the possible indirect benefits of stronger teamwork associated with enhanced support should be explored further.

Cerebral Palsy - Early Diagnosis and Intervention Trial: protocol for the prospective multicentre CP-EDIT study with focus on diagnosis, prognostic factors, and intervention.

BACKGROUND: Early diagnosis of cerebral palsy (CP) is important to enable intervention at a time when neuroplasticity is at its highest. Current mean age at diagnosis is 13 months in Denmark. Recent research has documented that an early-diagnosis set-up can lower diagnostic age in high-risk infants. The aim of the current study is to lower diagnostic age of CP regardless of neonatal risk factors. Additionally, we want to investigate if an early intervention program added to standard care is superior to standard care alone. METHODS: The current multicentre study CP-EDIT (Early Diagnosis and Intervention Trial) with the GO-PLAY intervention included (Goal Oriented ParentaL supported home ActivitY program), aims at testing the feasibility of an early diagnosis set-up and the GO-PLAY early intervention. CP-EDIT is a prospective cohort study, consecutively assessing approximately 500 infants at risk of CP. We will systematically collect data at inclusion (age 3-11 months) and follow a subset of participants (n = 300) with CP or at high risk of CP until the age of two years. The GO-PLAY early intervention will be tested in 80 infants with CP or high risk of CP. Focus is on eight areas related to implementation and perspectives of the families: early cerebral magnetic resonance imaging (MRI), early genetic testing, implementation of the General Movements Assessment method, analysis of the GO-PLAY early intervention, parental perspective of early intervention and early diagnosis, early prediction of CP, and comparative analysis of the Hand Assessment for Infants, Hammersmith Infant Neurological Examination, MRI, and the General Movements method. DISCUSSION: Early screening for CP is increasingly possible and an interim diagnosis of "high risk of CP" is recommended but not currently used in clinical care in Denmark. Additionally, there is a need to accelerate identification in mild or ambiguous cases to facilitate appropriate therapy early. Most studies on early diagnosis focus on identifying CP in infants below five months corrected age. Little is known about early diagnosis in the 50% of all CP cases that are discernible later in infancy. The current study aims at improving care of patients with CP even before they have an established diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov ID 22013292 (reg. date 31/MAR/2023) for the CP-EDIT cohort and ID 22041835 (reg. date 31/MAR/2023) for the GO-PLAY trial.

Efecto neuroprotector del sulfato de magnesio en prematuros. Análisis tras instaurar su protocolo de administración antenatal en un hospital terciario / Neuroprotective effect of magnesium sulfate in premature infants: Analysis after establishing an antenatal administration protocol in a tertiary care hospital

Introducción: En 2016 se desarrolló en nuestro centro un protocolo de administración antenatal de sulfato de magnesio en gestantes con riesgo de parto pretérmino inminente como método para disminuir el riesgo de parálisis cerebral (PC). Material y métodos: Se realizó un estudio observacional y retrospectivo en un hospital de nivel IIIC con objetivo principal de comparar la incidencia de PC previa y posteriormente a la puesta en marcha de este protocolo. Con respecto a los objetivos secundarios, a destacar la incidencia de déficit cognitivo, enterocolitis necrosante y mortalidad en ambos grupos. Los pacientes incluidos fueron recién nacidos prematuros por debajo de 32 semanas de edad gestacional nacidos en los años 2011-2012 (previo a la instauración del protocolo) y 2016-2018 (posteriormente a la instauración del protocolo, cuyas madres habían recibido sulfato de magnesio como neuroprotector). Las características clínicas y epidemiológicas de ambos grupos fueron comparables entre sí. Resultados: Se recogieron datos de un total de 523 pacientes, 263 y 260 de cada grupo. Con respecto al objetivo principal, no se encontraron diferencias estadísticamente significativas. Se objetivó, en el grupo de pacientes nacidos entre 2016-2018 y con edad gestacional entre 26+0 y 27+6 semanas, cuyas madres recibieron sulfato de magnesio, una reducción estadísticamente significativa de la mortalidad y del riesgo de enterocolitis necrosante grave. Conclusiones: En nuestro trabajo, el sulfato de magnesio administrado a madres en riesgo de parto prematuro, no disminuyó el riesgo de desarrollar PC. (AU)

Introduction: In 2016, a protocol was developed in our hospital for the antenatal administration of magnesium sulfate in pregnant women at risk of imminent preterm birth as a method to reduce the risk of cerebral palsy (CP). Material and methods: We conducted a retrospective observational study in a level IIIC hospital with the primary objective of comparing the incidence of CP before and after the implementation of this protocol. Among the secondary outcomes, we ought to highlight the incidence of cognitive deficits and necrotizing enterocolitis and the mortality in both groups. The sample consisted of preterm newborns delivered before 32 weeks of gestation in 2011-2012 (prior to the implementation of the protocol) and in 2016-2018 (after the implementation of the protocol, whose mothers had received magnesium sulfate for neuroprotection). The clinical and epidemiological characteristics of both groups were comparable. Results: We collected data for a total of 523 patients, 263 and 260 in each group. As regards the primary outcome, we did not find statistically significant differences between groups. We observed a statistically significant reduction in mortality and the risk of severe necrotizing enterocolitis in the group of patients born in the 2016-2018 period and between 26+0 and 27+6 weeks of gestation, whose mothers had received magnesium sulfate. Conclusions: In our study, the administration of magnesium sulfate to mothers at risk of preterm birth did not decrease the risk of developing CP. (AU)

Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas / A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae

Introduction. Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. Aim. The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. Patients and methods. We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. Results. Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. Conclusions. If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible. (AU)

Introducción: El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes.ObjetivoDescribir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas.Pacientes y métodosEstudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital.ResultadosSe incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio.ConclusionesAnte un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible. (AU)

A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.

INTRODUCTION: The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6 g MgSO4 1-24 h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation. MATERIAL AND METHODS: Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded. RESULTS: A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3 months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7 h, median 3.4 h). CONCLUSIONS: There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.

Neuroprotective effect of magnesium sulfate in premature infants. Analysis after establishing an antenatal administration protocol in a tertiary care hospital.

INTRODUCTION: In 2016, a protocol was developed in our hospital for the antenatal administration of magnesium sulfate in pregnant women at risk of imminent preterm birth as a method to reduce the risk of cerebral palsy (CP). MATERIAL AND METHODS: We conducted a retrospective observational study in a level IIIC hospital with the primary objective of comparing the incidence of CP before and after the implementation of this protocol. Among the secondary outcomes, we ought to highlight the incidence of cognitive deficits and necrotizing enterocolitis and the mortality in both groups. The sample consisted of preterm newborns delivered before 32 weeks of gestation in 2011-2012 (prior to the implementation of the protocol) and in 2016-2018 (after the implementation of the protocol, whose mothers had received magnesium sulfate for neuroprotection). The clinical and epidemiological characteristics of both groups were comparable. RESULTS: We collected data for a total of 523 patients, 263 and 260 in each group. As regards the primary outcome, we did not find statistically significant differences between groups. We observed a statistically significant reduction in mortality and the risk of severe necrotizing enterocolitis in the group of patients born in the 2016-2018 period and between 26+0 and 27+6 weeks of gestation, whose mothers had received magnesium sulfate. CONCLUSIONS: In our study, the administration of magnesium sulfate to mothers at risk of preterm birth did not decrease the risk of developing CP.

Prenatal Intravenous Magnesium at 30-34 Weeks' Gestation and Neurodevelopmental Outcomes in Offspring: The MAGENTA Randomized Clinical Trial.

Importance: Intravenous magnesium sulfate administered to pregnant individuals before birth at less than 30 weeks' gestation reduces the risk of death and cerebral palsy in their children. The effects at later gestational ages are unclear. Objective: To determine whether administration of magnesium sulfate at 30 to 34 weeks' gestation reduces death or cerebral palsy at 2 years. Design, Setting, and Participants: This randomized clinical trial enrolled pregnant individuals expected to deliver at 30 to 34 weeks' gestation and was conducted at 24 Australian and New Zealand hospitals between January 2012 and April 2018. Intervention: Intravenous magnesium sulfate (4 g) was compared with placebo. Main Outcomes and Measures: The primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge before 2 years' corrected age) or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years' corrected age. There were 36 secondary outcomes that assessed the health of the pregnant individual, infant, and child. Results: Of the 1433 pregnant individuals enrolled (mean age, 30.6 [SD, 6.6] years; 46 [3.2%] self-identified as Aboriginal or Torres Strait Islander, 237 [16.5%] as Asian, 82 [5.7%] as Maori, 61 [4.3%] as Pacific, and 966 [67.4%] as White) and their 1679 infants, 1365 (81%) offspring (691 in the magnesium group and 674 in the placebo group) were included in the primary outcome analysis. Death or cerebral palsy at 2 years' corrected age was not significantly different between the magnesium and placebo groups (3.3% [23 of 691 children] vs 2.7% [18 of 674 children], respectively; risk difference, 0.61% [95% CI, -1.27% to 2.50%]; adjusted relative risk [RR], 1.19 [95% CI, 0.65 to 2.18]). Components of the primary outcome did not differ between groups. Neonates in the magnesium group were less likely to have respiratory distress syndrome vs the placebo group (34% [294 of 858] vs 41% [334 of 821], respectively; adjusted RR, 0.85 [95% CI, 0.76 to 0.95]) and chronic lung disease (5.6% [48 of 858] vs 8.2% [67 of 821]; adjusted RR, 0.69 [95% CI, 0.48 to 0.99]) during the birth hospitalization. No serious adverse events occurred; however, adverse events were more likely in pregnant individuals who received magnesium vs placebo (77% [531 of 690] vs 20% [136 of 667], respectively; adjusted RR, 3.76 [95% CI, 3.22 to 4.39]). Fewer pregnant individuals in the magnesium group had a cesarean delivery vs the placebo group (56% [406 of 729] vs 61% [427 of 704], respectively; adjusted RR, 0.91 [95% CI, 0.84 to 0.99]), although more in the magnesium group had a major postpartum hemorrhage (3.4% [25 of 729] vs 1.7% [12 of 704] in the placebo group; adjusted RR, 1.98 [95% CI, 1.01 to 3.91]). Conclusions and Relevance: Administration of intravenous magnesium sulfate prior to preterm birth at 30 to 34 weeks' gestation did not improve child survival free of cerebral palsy at 2 years, although the study had limited power to detect small between-group differences. Trial Registration: anzctr.org.au Identifier: ACTRN12611000491965.

SuPreme Study: a protocol to study the neuroprotective potential of sulfate among very/extremely preterm infants.

INTRODUCTION: Antenatal maternal magnesium sulfate (MgSO4) administration is a proven efficacious neuroprotective treatment reducing the risk of cerebral palsy (CP) among infants born preterm. Identification of the neuroprotective component with target plasma concentrations could lead to neonatal treatment with greater efficacy and accessibility. METHODS AND ANALYSIS: This is a prospective observational cohort study, in three tertiary Australian centres. Participants are preterm infants, irrespective of antenatal MgSO4 exposure, born in 2013-2020 at 24+0 to 31+6 weeks gestation, and followed up to 2 years corrected age (CA) (to September 2023). 1595 participants are required (allowing for 17% deaths/loss to follow-up) to detect a clinically significant reduction (30% relative risk reduction) in CP when sulfate concentration at 7 days of age is 1 SD above the mean.A blood sample is collected on day 7 of age for plasma sulfate and magnesium measurement. In a subset of participants multiple blood and urine samples are collected for pharmacokinetic studies, between days 1-28, and in a further subset mother/infant blood is screened for genetic variants of sulfate transporter genes.The primary outcome is CP. Surviving infants are assessed for high risk of CP at 12-14 weeks CA according to Prechtl's Method to assess General Movements. Follow-up at 2 years CA includes assessments for CP, cognitive, language and motor development, and social/behavioural difficulties.Multivariate analyses will examine the association between day 7 plasma sulfate/magnesium concentrations with adverse neurodevelopmental outcomes. A population pharmacokinetic model for sulfate in the preterm infant will be created using non-linear mixed-effects modelling. ETHICS AND DISSEMINATION: The study has been approved by Mater Misericordiae Ltd Human Research Ethics Committee (HREC/14/MHS/188). Results will be disseminated in peer-reviewed journal publications, and provided to the funding bodies. Using consumer input, a summary will be prepared for participants and consumer groups.

Caffeine and cerebral palsy: A systematic review of randomized controlled trials and cohort studies.

OBJECTIVE: To systematically review the effects of caffeine on the development of cerebral palsy (CP). DESIGN: Systematic review. SETTING: A search of five databases was performed to identify randomized controlled trials (RCT) or cohort studies published through May 2022. Studies conducted on newborns at risk of developing CP upon receiving caffeine in the first days of life were included as well. Two independent researchers assessed the screening, data extraction, and methodological quality assessment. MAIN OUTCOME MEASURES: Percentage of children with CP. RESULTS: Four studies met our inclusion criteria. The only RCT found a decreased risk (approximately 40 %) of developing CP with 20 mg/kg caffeine citrate (OR 0.59, 95 % CI 0.39, 0.89). In addition, when comparing the period over which caffeine citrate was administered, one retrospective cohort study reported that infants who received caffeine up to the second day of life were also less likely to develop CP. Some methodological issues should be highlighted: in the RCT, the differences between the groups with respect to loss to follow-up were not explored. Similarly, intention-to-treat analyses were not performed. Most cohort studies have not adequately identified the primary confounding factors. CONCLUSIONS: Caffeine could be an important intervention in preventing CP. However, few studies have assessed the effects of caffeine on the risk of CP development. Due to methodological differences, no recommendation regarding its use can be safely made. The findings suggest a positive effect of caffeine citrate in the early stages of life with approximately 20 mg/kg of weight; however, well-designed RCTs with adequate sample size and power, randomization process, outcome measurement, and data analysis are still required.

Protecting the brain of the micropreemie.

Advances in perinatal care have seen substantial improvements in survival without disability for extremely preterm infants. Protecting the developing brain and reducing neurodevelopmental sequelae of extremely preterm birth are strategic priorities for both research and clinical care. A number of evidence-based interventions exist for neuroprotection in micropreemies, inclusive of prevention of preterm birth and multiple births with implantation of only one embryo during in vitro fertilisation, as well as antenatal care to optimize fetal wellbeing, strategies for supporting neonatal transition, and neuroprotective developmental care. Avoidance of complications that trigger ischemia and inflammation is vital for minimizing brain dysmaturation and injury, particularly of the white matter. Neurodevelopmental surveillance, early diagnosis of cerebral palsy and early intervention are essential for optimizing long-term outcomes and quality of life. Research priorities include further evaluation of putative neuroprotective agents, and investigation of common neonatal interventions in trials adequately powered to assess neurodevelopmental outcome.

Effectiveness of nutritional interventions to prevent nonprogressive congenital and perinatal brain injuries: a systematic review and meta-analysis of randomized trials.

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.

Prevention of perinatal depression with counseling in adolescents: a cost-effectiveness analysis.

OBJECTIVE: The US Preventive Services Task Force recently recommended that clinicians refer all pregnant and postpartum individuals at increased risk of perinatal depression to a counseling intervention. Adolescents are considered a high-risk group for perinatal depression. Therefore, we examined whether it is cost effective for all pregnant adolescents to be referred for preventive counseling. STUDY DESIGN: We developed a decision-analytic model using TreeAge Pro software to compare outcomes in pregnant adolescents who received versus did not receive counseling interventions. We used a theoretical cohort of 180,000 individuals, which is the estimated annual number of births to persons ≤ 19 years in the US. Outcomes included perinatal depression, chronic depression, maternal suicide attributed to depression, preterm delivery, neonatal death, cerebral palsy, and sudden infant death syndrome (SIDS), in addition to cost and quality-adjusted life years (QALYs). The willingness-to-pay (WTP) threshold was set to $100,000/QALY. We derived model inputs from the literature, and sensitivity analyses were used to assess robustness of the model. RESULTS: A strategy of referral to counseling interventions was cost effective in our theoretical cohort, with 8935 fewer cases of perinatal depression, 1606 fewer cases of chronic depression, 166 fewer preterm deliveries, 4 fewer neonatal deaths, 1 fewer case of cerebral palsy, 20 fewer cases of SIDS. In total, there were 21,976 additional QALYs and cost savings of $223,549,872, making it the dominant strategy (better outcomes with lower costs). We found that counseling interventions remained cost saving until the annual direct and indirect cost of chronic, severe depression was set below $30,000, at which point it became cost effective (baseline input: $182,309). CONCLUSION: We found it was cost effective to refer all pregnant adolescents for preventive counseling interventions. Clinicians should develop approaches to identify and refer pregnant adolescents for behavioral counseling to prevent perinatal depression.

Antenatal magnesium sulphate for preventing cerebral palsy: An economic evaluation of the impact of a quality improvement program.

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.

Maternal intake of folate during pregnancy and risk of cerebral palsy in the MOBAND-CP cohort.

BACKGROUND: Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders. OBJECTIVES: We investigated whether higher intakes of periconceptional or midpregnancy folate, as recommended, were associated with a reduced risk of offspring cerebral palsy (CP). METHODS: We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father, and Child Cohort Study [combined as MOthers and BAbies in Norway and Denmark (MOBAND-CP)]. A total of 190,989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22-25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairments, were our outcomes of interest. RESULTS: Periconceptional folic acid supplementation was not associated with CP [adjusted odds ratio (aOR), 1.02; 95% CI: 0.82-1.28]. However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR, 0.74; 95% CI: 0.57-0.96), and inverse associations were indicated for both the unilateral (aOR, 0.68; 95% CI: 0.46-1.02) and bilateral (aOR, 0.70; 95% CI: 0.49-1.02) spastic subtypes, although the associations were not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR, 0.49; 95% CI: 0.29-0.83), while for unilateral CP the aOR was 0.63 (95% CI: 0.34-1.22) for intakes of ≥500 compared to ≤199 dietary folate equivalents/day during midpregnancy. CONCLUSIONS: Our findings suggest that folate intakes in GWs 9 to 12 and midpregnancy were associated with lower risks of CP, while no association was observed for periconceptional supplementation.

Is Late Prevention of Cerebral Palsy in Extremely Preterm Infants Plausible?

Preterm birth continues to be associated with neurodevelopmental problems including cerebral palsy. Cystic white matter injury (WMI) is still the major neuropathology underlying cerebral palsy, affecting 1-3% of preterm infants. Although rates have gradually fallen over time, the pathogenesis and evolution of cystic WMI are still poorly understood. Hypoxia-ischemia (HI) remains an important contributor, yet there is no established treatment to prevent injury. Clinically, serial ultrasound and magnetic resonance imaging studies typically show delayed development of cystic lesions 2-4 weeks after birth. This raises the important and unresolved question as to whether this represents slow evolution of injury occurring around the time of birth or repeated injury over many weeks after birth. There is increasing evidence that tertiary injury after HI can contribute to impairment of white and grey matter maturation. In the present review, we discuss preclinical evidence that severe, cystic WMI can evolve for many weeks after acute HI and is associated with microglia activity. This suggests the intriguing hypothesis that the tertiary phase of injury is not as subtle as often thought and that there may be a window of therapeutic opportunity for 1 to 2 weeks after hypoxic-ischemic injury to prevent delayed cystic lesions, and so, further reduce the risk of cerebral palsy after preterm birth.

Antenatal magnesium sulfate to prevent cerebral palsy.

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.

37 segundos (2019). La asfixia neonatal, el minuto de oro en la reanimación y la hipotermia terapéutica desde el prisma del cine / 37 seconds (2019). perinatal asphyxia, the golden minute of birth and neonatal therapeutic hypothermia from a movie perspective

El artículo utiliza la película 37 segundos para llamar la atención en relación a un grave problema social que es la asfixia perinatal. Se aborda su prevención durante el acompañamiento prenatal, la importancia del minuto de oro en reanimación neonatal, la hipotermia como forma de prevención de secuela neurológica y el monitoreo con electroencefalograma para el diagnóstico de convulsiones. (AU)

The article uses the film 37 seconds to draw attention to a serious social problem that is perinatal asphyxia. They talk about prevention during antenatal care, the importance of the golden minute in neonatal resuscitation, hypothermia as a form of prevention of neurological sequelae, and monitoring with an electroencephalogram for the diagnosis of seizures. (AU)

Smoflipid Is Better Than Lipofundin for Long-Term Neurodevelopmental Outcomes in Preterm Infants.

Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospital with corresponding individual medical records up to July 2020 were analyzed. Long-term neurodevelopmental outcomes were defined by the international classification of disease codes -9 or -10. The prevalence of diseases was compared between LIPO and SMOF groups at five and five years old and further analyzed by stratification of 1500 g birth weight. The LIPO and SMOF groups each included 1120 neonates. Epilepsy, cerebral palsy, developmental disorder and attention-deficit hyperactivity disorder (ADHD) were significantly decreased at age two years in the SMOF group, and epilepsy, language delay (LD), ADHD and autism spectrum disorder (ASD) were significantly decreased in the SMOF group at age five years. In children with birth weight < 1500 g, ADHD was decreased in the SMOF group at ages two and five years, and ASD was decreased in the SMOF group at age five years. In children with birth weight ≥ 1500 g, epilepsy, LD and ADHD were decreased in the SMOF group at age two years. LD was decreased in the SMOF group at age five years. We conclude that lipid emulsions with fish oil improve the neurodevelopmental outcomes of children born prematurely.