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Translational Pediatrics Feb 2020Cerebral palsy (CP) is a disorder characterized by abnormal tone, posture and movement and clinically classified based on the predominant motor syndrome-spastic... (Review)
Review
Cerebral palsy (CP) is a disorder characterized by abnormal tone, posture and movement and clinically classified based on the predominant motor syndrome-spastic hemiplegia, spastic diplegia, spastic quadriplegia, and extrapyramidal or dyskinetic. The incidence of CP is 2-3 per 1,000 live births. Prematurity and low birthweight are important risk factors for CP; however, multiple other factors have been associated with an increased risk for CP, including maternal infections, and multiple gestation. In most cases of CP the initial injury to the brain occurs during early fetal brain development; intracerebral hemorrhage and periventricular leukomalacia are the main pathologic findings found in preterm infants who develop CP. The diagnosis of CP is primarily based on clinical findings. Early diagnosis is possible based on a combination of clinical history, use of standardized neuromotor assessment and findings on magnetic resonance imaging (MRI); however, in most clinical settings CP is more reliably recognized by 2 years of age. MRI scan is indicated to delineate the extent of brain lesions and to identify congenital brain malformations. Genetic tests and tests for inborn errors of metabolism are indicated based on clinical findings to identify specific disorders. Because CP is associated with multiple associated and secondary medical conditions, its management requires a multidisciplinary team approach. Most children with CP grow up to be productive adults.
PubMed: 32206590
DOI: 10.21037/tp.2020.01.01 -
Journal of Pediatric Neurosciences 2017Neonatal hypoxic-ischemic encephalopathy (HIE) is a devastating condition that may result in death or severe neurologic deficits in children. Neuroimaging with cranial... (Review)
Review
Neonatal hypoxic-ischemic encephalopathy (HIE) is a devastating condition that may result in death or severe neurologic deficits in children. Neuroimaging with cranial ultrasound (US), computed tomography and magnetic resonance imaging are valuable tools in the workup of patients with HIE. The pattern of brain injury depends on the severity and duration of hypoxia and degree of brain maturation. Mild to moderate HI injury results in periventricular leukomalacia and germinal matrix bleed in preterm neonates, and parasagittal watershed infarcts in full-term neonates. Severe HI injury involves deep gray matter in both term and preterm infants. Treatment of HIE is largely supportive. The current article reviews the etiopathophysiology and clinical manifestations of HIE, role of imaging in the evaluation of the condition, patterns of brain injury in term and preterm neonates, the treatment and the prognosis.
PubMed: 28553370
DOI: 10.4103/1817-1745.205646 -
Canadian Respiratory Journal 2018Invasive ventilation is often necessary for the treatment of newborn infants with respiratory insufficiency. The neonatal patient has unique physiological... (Review)
Review
Invasive ventilation is often necessary for the treatment of newborn infants with respiratory insufficiency. The neonatal patient has unique physiological characteristics such as small airway caliber, few collateral airways, compliant chest wall, poor airway stability, and low functional residual capacity. Pathologies affecting the newborn's lung are also different from many others observed later in life. Several different ventilation modes and strategies are available to optimize mechanical ventilation and to prevent ventilator-induced lung injury. Important aspects to be considered in ventilating neonates include the use of correct sized endotracheal tube to minimize airway resistance and work of breathing, positioning of the patient, the nursing care, respiratory kinesiotherapy, sedation and analgesia, and infection prevention, namely, the ventilator-associated pneumonia and nosocomial infection, as well as prevention and treatment of complications such as air leaks and pulmonary hemorrhage. Aspects of ventilation in patients under ECMO (extracorporeal membrane oxygenation) and in palliative care are of increasing interest nowadays. Online pulmonary mechanics and function testing as well as capnography are becoming more commonly used. Echocardiography is now a routine in most neonatal units. Near infrared spectroscopy (NIRS) is an attractive tool potentially helping in preventing intraventricular hemorrhage and periventricular leukomalacia. Lung ultrasound is an emerging tool of diagnosis and can be of added value in helping monitoring the ventilated neonate. The aim of this scientific literature review is to address relevant aspects concerning the respiratory care and monitoring of the invasively ventilated newborn in order to help physicians to optimize the efficacy of care.
Topics: Analgesia; Capnography; Cross Infection; Echocardiography; Extracorporeal Membrane Oxygenation; Humans; Infant, Newborn; Intubation, Intratracheal; Lung; Palliative Care; Patient Positioning; Pneumonia, Ventilator-Associated; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Respiratory Function Tests; Respiratory Insufficiency; Respiratory Mechanics; Tracheostomy; Ultrasonography; Ventilator-Induced Lung Injury
PubMed: 30186538
DOI: 10.1155/2018/7472964 -
Pediatric Research Mar 2020White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential... (Review)
Review
White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies.
Topics: Brain; Brain Injuries; Echoencephalography; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Neonatology; Predictive Value of Tests; White Matter
PubMed: 32218534
DOI: 10.1038/s41390-020-0781-1 -
Pediatrics Jul 2021The National Institute of Child Health and Human Development Neonatal Research Network recently proposed new, severity-based diagnostic criteria for bronchopulmonary...
BACKGROUND AND OBJECTIVES
The National Institute of Child Health and Human Development Neonatal Research Network recently proposed new, severity-based diagnostic criteria for bronchopulmonary dysplasia (BPD). This study provides the first benchmark epidemiological data applying this definition.
METHODS
Retrospective cohort study of infants born from 22 to 29 weeks' gestation in 2018 at 715 US hospitals in the Vermont Oxford Network. Rates of BPD, major neonatal morbidities, and common respiratory therapies, stratified by BPD severity, were determined.
RESULTS
Among 24 896 infants, 2574 (10.3%) died before 36 weeks' postmenstrual age (PMA), 12 198 (49.0%) did not develop BPD, 9192 (36.9%) developed grade 1 or 2 BPD, and 932 (3.7%) developed grade 3 BPD. Rates of mortality before 36 weeks' PMA and grade 3 BPD decreased from 52.7% and 9.9%, respectively, among infants born at 22 weeks' gestation to 17.3% and 0.8% among infants born at 29 weeks' gestation. Grade 1 or 2 BPD peaked in incidence (51.8%) among infants born at 25 weeks' gestation. The frequency of severe intraventricular hemorrhage or cystic periventricular leukomalacia increased from 4.8% among survivors without BPD to 23.4% among survivors with grade 3 BPD. Similar ranges were observed for late onset sepsis (4.8%-31.4%), surgically treated necrotizing enterocolitis (1.4%-17.1%), severe retinopathy of prematurity (1.2%-23.0%), and home oxygen therapy (2.0%-67.5%).
CONCLUSIONS
More than one-half of very preterm infants born in the United States died before 36 weeks' PMA or developed BPD. Greater BPD severity was associated with more frequent development of major neonatal morbidities, in-hospital mortality, and use of supplemental respiratory support at discharge.
Topics: Bronchopulmonary Dysplasia; Cerebral Intraventricular Hemorrhage; Gestational Age; Humans; Incidence; Infant; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Retrospective Studies; Severity of Illness Index; Vermont
PubMed: 34078747
DOI: 10.1542/peds.2020-030007 -
Acta Neuropathologica Sep 2017The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in... (Review)
Review
The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Diffuse WMI involves maturation-dependent vulnerability of the oligodendrocyte (OL) lineage with selective degeneration of late oligodendrocyte progenitors (preOLs) triggered by oxidative stress and other insults. The magnitude and distribution of diffuse WMI are related to both the timing of appearance and regional distribution of susceptible preOLs. Diffuse WMI disrupts the normal progression of OL lineage maturation and myelination through aberrant mechanisms of regeneration and repair. PreOL degeneration is accompanied by early robust proliferation of OL progenitors that regenerate and augment the preOL pool available to generate myelinating OLs. However, newly generated preOLs fail to differentiate and initiate myelination along their normal developmental trajectory despite the presence of numerous intact-appearing axons. Disrupted preOL maturation is accompanied by diffuse gliosis and disturbances in the composition of the extracellular matrix and is mediated in part by inhibitory factors derived from reactive astrocytes. Signaling pathways implicated in disrupted myelination include those mediated by Notch, WNT-beta catenin, and hyaluronan. Hence, there exists a potentially broad but still poorly defined developmental window for interventions to promote white matter repair and myelination and potentially reverses the widespread disturbances in cerebral gray matter growth that accompanies WMI.
Topics: Brain; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Nerve Fibers, Myelinated; Neuroglia; White Matter
PubMed: 28534077
DOI: 10.1007/s00401-017-1718-6 -
JAMA Sep 2015Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality.
IMPORTANCE
Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality.
OBJECTIVE
To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers.
DESIGN, SETTING, PARTICIPANTS
Prospective registry of 34,636 infants, 22 to 28 weeks' gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012.
EXPOSURES
Extremely preterm birth.
MAIN OUTCOMES AND MEASURES
Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex.
RESULTS
Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants]; P < .001), as did cesarean delivery (44% [625 of 1431 births] to 64% [1227 of 1921]; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks [37% {109 of 296} to 27% {85 of 320}]; adjusted relative risk [RR], 0.93 [95% CI, 0.92-0.94]). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks' gestation (26 weeks, 50% [130 of 258] to 55% [164 of 297]; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks' gestation (27% [41 of 152] to 33% [50 of 150]; adjusted RR, 1.09 [95% CI, 1.05-1.14]) and 24 weeks (63% [156 of 248] to 65% [174 of 269]; adjusted RR, 1.05 [95% CI, 1.03-1.07]), with smaller relative increases for infants at 25 and 27 weeks' gestation, and no change for infants at 22, 26, and 28 weeks' gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks' gestation, with no change for infants at 22 to 24 weeks' gestation.
CONCLUSIONS AND RELEVANCE
Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks' gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00063063.
Topics: Adrenal Cortex Hormones; Adult; Bronchopulmonary Dysplasia; Cesarean Section; Continuous Positive Airway Pressure; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Intensive Care, Neonatal; Intracranial Hemorrhages; Leukomalacia, Periventricular; Male; Pregnancy; Retinopathy of Prematurity; Survival Analysis; United States
PubMed: 26348753
DOI: 10.1001/jama.2015.10244 -
Biomedicines Dec 2022We asked whether hyperoxia might induce hypomyelination of the corpus callosum, clinically described as periventricular leukomalacia (PVL) of the severely preterm...
We asked whether hyperoxia might induce hypomyelination of the corpus callosum, clinically described as periventricular leukomalacia (PVL) of the severely preterm infant. Mouse pups and their nursing dams were placed in 80% oxygen from P4-P8, then removed to room air until P11. Corpus callosal sections were probed myelin immunofluorescence, tested for myelin basic protein concentration by Western blot, and both glial fibrillary acidic protein levels and apoptosis quantified. Density of corpus callosal capillaries were measured after lectin staining and hypoxia measured by Hypoxyprobe. Numbers of oligodendrocytes were quantified by immunohistochemistry. We next used hypoxiamimesis as a surrogate to hypoxia by comparing cerebral hypoxia inducible factor (HIF) stabilization to hepatic HIF stabilization. Hyperoxia induced hypomyelination and a reduction of corpus callosal capillaries. Hyperoxia decreased numbers of oligodendrocytes with an increase in corpus callosal fibrosis and apoptosis. Cerebral hypoxiamimesis induced hypomyelination whereas hepatic hypoxiamimesis alone increased myelination, oligodendrocyte numbers, and corpus callosal capillary density. Hepatic HIF-1 dependence on myelination was confirmed using the cre/lox hepatic HIF-1 knockout. These findings suggest that hyperoxia can induce hypomyelination through vasoobliteration and subsequent ischemia, adding a potential oxygen induced mechanism to the diverse causes of periventricular leukomalacia of the severely preterm infant. Targeting hepatic HIF-1 alone led to increased myelination.
PubMed: 36672545
DOI: 10.3390/biomedicines11010037 -
JAMA Network Open Aug 2021The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary...
IMPORTANCE
The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary neonatal intensive care units (NICUs) throughout China. National-level data on outcomes and care practices of very preterm infants (VPIs) in China are lacking.
OBJECTIVE
To assess the care practices in NICUs and outcomes among VPIs in China.
DESIGN, SETTING, AND PARTICIPANTS
A cohort study was conducted comprising 57 tertiary hospitals from 25 provinces throughout China. All infants with gestational age (GA) less than 32 weeks who were admitted to the 57 NICUs between January 1 and December 31, 2019, were included.
MAIN OUTCOMES AND MEASURES
Care practices, morbidities, and survival were the primary outcomes of the study. Major morbidities included bronchopulmonary dysplasia, severe intraventricular hemorrhage (grade ≥3) and/or periventricular leukomalacia, necrotizing enterocolitis (stage ≥2), sepsis, and severe retinopathy of prematurity (stage ≥3).
RESULTS
A total of 9552 VPIs were included, with mean (SD) GA of 29.5 (1.7) weeks and mean (SD) birth weight of 1321 (321) g; 5404 infants (56.6%) were male. Antenatal corticosteroids were used in 75.6% (6505 of 8601) of VPIs, and 54.8% (5211 of 9503)were born through cesarean delivery. In the delivery room, 12.1% of VPIs received continuous positive airway pressure and 26.7% (2378 or 8923) were intubated. Surfactant was prescribed for 52.7% of the infants, and postnatal dexamethasone was prescribed to 9.5% (636 of 6675) of the infants. A total of 85.5% (8171) of the infants received complete care, and 14.5% (1381) were discharged against medical advice. The incidences of the major morbidities were bronchopulmonary dysplasia, 29.2% (2379 of 8148); severe intraventricular hemorrhage and/or periventricular leukomalacia, 10.4% (745 of 7189); necrotizing enterocolitis, 4.9% (403 of 8171 ); sepsis, 9.4% (764 of 8171); and severe retinopathy of prematurity, 4.3% (296 of 6851) among infants who received complete care. Among VPIs with complete care, 95.4% (7792 of 8171) survived: 65.6% (155 of 236) at 25 weeks' or less GA, 89.0% (880 of 988) at 26 to 27 weeks' GA, 94.9% (2635 of 2755)at 28 to 29 weeks' GA, and 98.3% (4122 of 4192) at 30 to 31 weeks' GA. Only 57.2% (4677 of 8171) of infants survived without major morbidity: 10.5% (25 of 236) at 25 weeks' or less GA, 26.8% (48 of 179) at 26 to 27 weeks' GA, 51.1% (1409 of 2755) at 28 to 29 weeks' GA, and 69.3% (2904 of 4192) at 30 to 31 weeks' GA. Among all infants admitted, the survival rate was 87.6% (8370 of 9552)and survival without major morbidities was 51.8% (4947 of 9552).
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that survival and survival without major morbidity of VPIs in Chinese NICUs have improved but remain lower than in high-income countries. Comprehensive and targeted quality improvement efforts are needed to provide complete care for all VPIs, optimize obstetrical and neonatal care practices, and improve outcomes.
Topics: Adult; Birth Weight; China; Critical Care Outcomes; Delivery, Obstetric; Female; Gestational Age; Hospitalization; Humans; Infant; Infant Mortality; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Male; Morbidity; Pregnancy; Survival Rate
PubMed: 34338792
DOI: 10.1001/jamanetworkopen.2021.18904 -
The Cochrane Database of Systematic... Nov 2015Infants born preterm are at increased risk of developing cognitive and motor impairment compared with infants born at term. Early developmental interventions have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infants born preterm are at increased risk of developing cognitive and motor impairment compared with infants born at term. Early developmental interventions have been provided in the clinical setting with the aim of improving overall functional outcomes for these infants. Long-term benefits of these programmes remain unclear.
OBJECTIVES
Primary objective To compare the effectiveness of early developmental intervention programmes provided post hospital discharge to prevent motor or cognitive impairment in preterm (< 37 weeks) infants versus standard medical follow-up of preterm infants at infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Secondary objectives To perform subgroup analyses to determine the following.• Effects of gestational age, birth weight and brain injury (periventricular leukomalacia (PVL)/intraventricular haemorrhage (IVH)) on cognitive and motor outcomes when early intervention is compared with standard follow-up. ∘ Gestational age: < 28 weeks, 28 to < 32 weeks, 32 to < 37 weeks. ∘ Birth weight: < 1000 grams, 1000 to < 1500 grams, 1500 to < 2500 grams. ∘ Brain injury: absence or presence of grade III or grade IV IVH or cystic PVL (or both) or an abnormal ultrasound/magnetic resonance image (MRI) before initiation of the intervention.• Effects of interventions started during inpatient stay with a post-discharge component versus standard follow-up care.• Effects of interventions focused on the parent-infant relationship, infant development or both compared with standard follow-up care.To perform sensitivity analysis to identify the following.• Effects on motor and cognitive impairment when early developmental interventions are provided within high-quality randomised trials with low risk of bias for sequence generation, allocation concealment, blinding of outcome measures and selective reporting bias.
SEARCH METHODS
The search strategy of the Cochrane Neonatal Review Group was used to identify randomised and quasi-randomised controlled trials of early developmental interventions provided post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Advanced, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE (1966 to August 2015).
SELECTION CRITERIA
Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age. Interventions could commence on an inpatient basis but had to include a post-discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. Rates of cerebral palsy were documented.
DATA COLLECTION AND ANALYSIS
Two independent review authors extracted and entered data. Cognitive and motor outcomes were pooled by four age groups: infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Meta-analysis using RevMan 5.1 was carried out to determine the effects of early developmental interventions at each age range. Subgroup analyses focused on gestational age, birth weight, brain injury, commencement of the intervention, focus of the intervention and study quality.
MAIN RESULTS
Twenty-five studies met the inclusion criteria (3615 randomly assigned participants). Only 12 of these studies were randomised controlled trials with appropriate allocation concealment. Variability was evident with regard to focus and intensity of the intervention, participant characteristics and length of follow-up. Meta-analysis led to the conclusion that intervention improved cognitive outcomes at infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.32 standard deviations (SDs), 95% confidence interval (CI) 0.16 to 0.47; P value < 0.001; 16 studies; 2372 participants) and at preschool age (intelligence quotient (IQ); SMD 0.43 SDs, 95% CI 0.32 to 0.54; P value < 0.001; eight studies; 1436 participants). However, this effect was not sustained at school age (IQ: SMD 0.18 SDs, 95% CI -0.08 to 0.43; P value = 0.17; five studies; 1372 participants). Heterogeneity between studies for cognitive outcomes at infancy and at school age was significant. With regards to motor outcomes, meta-analysis of 12 studies showed a significant effect in favour of early developmental interventions at infancy only; however, this effect was small (motor scale DQ: SMD 0.10 SDs, 95% CI 0.01 to 0.19; P value = 0.03; 12 studies; 1895 participants). No effect was noted on the rate of cerebral palsy among survivors (risk ratio (RR) 0.82, 95% CI 0.52 to 1.27; seven studies; 985 participants). Little evidence showed a positive effect on motor outcomes in the long term, but only five included studies reported outcomes at preschool age (n = 3) or at school age (n = 2).
AUTHORS' CONCLUSIONS
Early intervention programmes for preterm infants have a positive influence on cognitive and motor outcomes during infancy, with cognitive benefits persisting into preschool age. A great deal of heterogeneity between studies was due to the variety of early developmental intervention programmes tested and to gestational ages of included preterm infants; thus, comparisons of intervention programmes were limited. Further research is needed to determine which early developmental interventions are most effective in improving cognitive and motor outcomes, and to discern the longer-term effects of these programmes.
Topics: Birth Weight; Cerebral Palsy; Cognition Disorders; Early Intervention, Educational; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Motor Skills Disorders; Movement Disorders; Patient Discharge; Psychomotor Disorders; Randomized Controlled Trials as Topic
PubMed: 26597166
DOI: 10.1002/14651858.CD005495.pub4