Early-childhood linear growth faltering in low- and middle-income countries.

Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards)1,2. Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering-a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries (n = 32 cohorts, 52,640 children, ages 0-24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children's linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age.

Association between Transport Risk Index of Physiologic Stability in Extremely Premature Infants and Mortality or Neurodevelopmental Impairment at 18 to 24 Months.

OBJECTIVES: To examine the association between mortality or neurodevelopmental impairment at 18-24 months of corrected age and the Transport Risk Index of Physiologic Stability (TRIPS) score on admission to the neonatal intensive care unit (NICU) in extremely premature infants. STUDY DESIGN: Retrospective cohort study of extremely premature infants (inborn and outborn) born at 22-28 weeks of gestational age and admitted to NICUs in the Canadian Neonatal Network between April 2009 and September 2011. TRIPS scores and clinical data were collected from the Canadian Neonatal Network database. Follow-up data at 18-24 months of corrected age were retrieved from the Canadian Neonatal Follow-Up Network database. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, Edition III. The primary outcome was death or significant neurodevelopmental impairment at 18-24 months of corrected age. The secondary outcomes were individual components of the Bayley Scales of Infant and Toddler Development, Edition III assessment. RESULTS: A total of 1686 eligible infants were included. A TRIPS score of ≥20 on admission to the NICU was significantly associated with mortality (aOR 2.71 [95% CI, 2.02-3.62]) and mortality or significant neurodevelopmental impairment (aOR 1.91 [95% CI, 1.52-2.41]) at 18-24 months of corrected age across all gestational age groups of extremely premature infants. CONCLUSION: The TRIPS score on admission to the NICU can be used as an adjunctive, objective tool for counselling the parents of extremely premature infants early after their admission to the NICU.

A novel ITPA variant causes epileptic encephalopathy with multiple-organ dysfunction.

Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices (MIM:616647). ITPase plays an important role in purine metabolism. In this study, we identified two novel homozygous ITPA variants, c.264-1 G > A and c.489-1 G > A, in two unrelated consanguineous families. The probands had epilepsy, microcephaly with characteristic magnetic resonance imaging findings (T2 hyperintensity signals in the pyramidal tracts of the internal capsule, delayed myelination, and thin corpus callosum), hypotonia, and developmental delay; both died in early infancy. Our report expands the knowledge of clinical consequences of biallelic ITPA variants.

Sudden death in epilepsy and ectopic neurohypophysis in Joubert syndrome 23 diagnosed using SNVs/indels and structural variants pipelines on WGS data: a case report.

BACKGROUND: Joubert syndrome (JBTS) is a genetically heterogeneous group of neurodevelopmental syndromes caused by primary cilia dysfunction. Usually the neurological presentation starts with abnormal neonatal breathing followed by muscular hypotonia, psychomotor delay, and cerebellar ataxia. Cerebral MRI shows mid- and hindbrain anomalies including the molar tooth sign. We report a male patient with atypical presentation of Joubert syndrome type 23, thus expanding the phenotype. CASE PRESENTATION: Clinical features were consistent with JBTS already from infancy, yet the syndrome was not suspected before cerebral MRI later in childhood showed the characteristic molar tooth sign and ectopic neurohypophysis. From age 11 years seizures developed and after few years became increasingly difficult to treat, also related to inadequate compliance to therapy. He died at 23 years of sudden unexpected death in epilepsy (SUDEP). The genetic diagnosis remained elusive for many years, despite extensive genetic testing. We reached the genetic diagnosis by performing whole genome sequencing of the family trio and analyzing the data with the combination of one analysis pipeline for single nucleotide variants (SNVs)/indels and one for structural variants (SVs). This lead to the identification of the most common variant detected in patients with JBTS23 (OMIM# 616490), rs534542684, in compound heterozygosity with a 8.3 kb deletion in KIAA0586, not previously reported. CONCLUSIONS: We describe for the first time ectopic neurohypophysis and SUDEP in JBTS23, expanding the phenotype of this condition and raising the attention on the possible severity of the epilepsy in this disease. We also highlight the diagnostic power of WGS, which efficiently detects SNVs/indels and in addition allows the identification of SVs.

Neonatal seizures in preterm infants: A systematic review of mortality risk and neurological outcomes from studies in the 2000's.

INTRODUCTION: Neonatal seizures (NS) are associated with increased mortality and risk of cerebral palsy, epilepsy and intellectual disability. We performed a systematic review with the primary objective to delineate the rate of these outcomes following NS in preterm infants from studies published in the 2000's and the secondary objective to identify risk factors. METHODS: Inclusion criteria: original articles published between 1/1/2000 and 12/31/2018, written in English, evaluating newborns ≤37 weeks of gestational age and suffering from NS, in which at least one of these was evaluated: epilepsy, cerebral palsy, intellectual disability/developmental delay, normal outcome, death. RESULTS: Twenty-two papers were selected and all were observational, with a retrospective design in 15. Three were population-based and twenty-one have a comparison. It has been found a 22-80 % of mortality, 11.3-38.9 % of epilepsy, 12-84.6 % of cerebral palsy, and 20-42.7 % of intellectual disability/developmental delay rate. An increased risk for all outcomes considered was reported. Risk factors for specific outcomes were provided by a minority of studies. However, inclusion criteria, definition of NS and measured outcomes, follow-up lengths differed considerably between studies. DISCUSSION: Results of the selected studies are only partially comparable or generalizable because of differences in study design. They have a risk for potential biases, although they provide (if analyzed) readily available prognostic factors, easy to apply in clinical practice. Prospective, population-based studies with EEG-defined NS are warranted in order to produce evidence-based guidance for management of preterm newborns with seizures.

Very Preterm Infants with Technological Dependence at Home: Impact on Resource Use and Family.

OBJECTIVE: To examine the impact of medical complexity among very preterm infants on health care resource use, family, and neurodevelopmental outcomes at 18 months' corrected age. METHODS: This observational cohort study of Canadian infants born < 29 weeks' gestational age in 2009-2011 compared infants with and those without medical complexity defined as discharged home with assistive medical technology. Health care resource use and family outcomes were collected. Children were assessed for cerebral palsy, deafness, blindness, and developmental delay at 18 months. Logistic regression analysis was performed for group comparisons. RESULTS: Overall, 466/2,337 infants (20%) needed assistive medical technology at home including oxygen (79%), gavage feeding (21%), gastrostomy or ileostomy (20%), CPAP (5%), and tracheostomy (3%). Children with medical complexity were more likely to be re-hospitalized (OR 3.6, 95% CI 3.0-4.5) and to require ≥2 outpatient services (OR 4.4, 95% CI 3.5-5.6). Employment of both parents at 18 months was also less frequent in those with medical complexity compared to those without medical complexity (52 vs. 60%, p < 0.01). Thirty percent of children with medical complexity had significant neurodevelopmental impairment compared to 13% of those without medical complexity (p < 0.01). Lower gestational age, lower birth weight, bronchopulmonary dysplasia, sepsis, and surgical necrotizing enterocolitis were associated with a risk of medical complexity. CONCLUSION: Medical complexity is common following very preterm birth and has a significant impact on health care use as well as family employment and is more often associated with neurodevelopmental disabilities. Efforts should be deployed to facilitate care coordination upon hospital discharge and to support families of preterm children with medical complexity.

Obscuring effect of coding developmental disability as the underlying cause of death on mortality trends for adults with developmental disability: a cross-sectional study using US Mortality Data from 2012 to 2016.

OBJECTIVE: To determine whether coding a developmental disability as the underlying cause of death obscures mortality trends of adults with developmental disability. DESIGN: National Vital Statistics System 2012-2016 US Multiple Cause-of-Death Mortality files. SETTING: USA. PARTICIPANTS: Adults with a developmental disability indicated on their death certificate aged 18 through 103 at the time of death. The study population included 33 154 adults who died between 1 January 2012 and 31 December 2016. PRIMARY OUTCOME AND MEASURES: Decedents with a developmental disability coded as the underlying cause of death on the death certificate were identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code for intellectual disability, cerebral palsy, Down syndrome or other developmental disability. Death certificates that coded a developmental disability as the underlying cause of death were revised using a sequential underlying cause of death revision process. RESULTS: There were 33 154 decedents with developmental disability: 7901 with intellectual disability, 11 895 with cerebral palsy, 9114 with Down syndrome, 2479 with other developmental disabilities and 1765 with multiple developmental disabilities. Among all decedents, 48.5% had a developmental disability coded as the underlying cause of death, obscuring higher rates of choking deaths among all decedents and dementia and Alzheimer's disease among decedents with Down syndrome. CONCLUSION: Death certificates that recorded the developmental disability in Part I of the death certificate were more likely to code disability as the underlying cause of death. While revising these death certificates provides a short-term corrective to mortality trends for this population, the severity and extent of this problem warrants a long-term change involving more precise instructions to record developmental disabilities only in Part II of the death certificate.

Patterns of mortality among adults with intellectual and developmental disabilities in Ontario.

OBJECTIVES: To determine recent mortality rates among Ontarian adults with intellectual and developmental disabilities (IDDs) and investigate changes over time in contrast to the general population. To determine the most commonly reported underlying causes of death and explore related coding practices. METHODS: Using linked health administrative data, four cohorts of adults with IDD aged 25-99 living in Ontario were followed for 1 year (one cohort for each year between 2011 and 2014). Deaths (2011 to 2014) and causes of death (2011 to 2013) were identified, and age-standardized mortality rates were calculated annually. For 2013, overall and sex-specific standardized mortality ratios (SMRs) were calculated. Mortality ratios were also examined across 5-year age groups. Commonly reported causes of death were tabulated by ICD-10 chapter, differences by sex examined, and cause-specific SMRs calculated. All deaths with IDD diagnostic codes reported as underlying cause of death were identified. RESULTS: Mortality rates among individuals with IDD have been decreasing over time; in 2014, the mortality rate was 22.6 deaths per 1000 person-years. Disparities in mortality rates relative to the general population decreased with increasing age. Men with IDD had higher mortality rates than women with IDD. The most common causes of death among individuals with IDD were cardiovascular disease, neoplasms, and diseases of the respiratory system. An IDD diagnostic code was reported as cause of death in 3.8% of cases. CONCLUSIONS: The ongoing excess mortality among Ontarians with IDD should be closely monitored by policy makers and service providers. Attention to cause of death reporting should be considered so that cause of death can be thoroughly examined.

Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study.

BACKGROUND: Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy. METHODS: For this prospective cohort study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy at 20 centres in nine countries. Patients were followed up for 10 years. We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinically meaningful mobility and upper limb milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to stand from supine of 5 s or longer and 10 s or longer, and loss of stand from supine, four-stair climb, ambulation, full overhead reach, hand-to-mouth function, and hand function. Risk of death was also assessed. This study is registered with ClinicalTrials.gov, number NCT00468832. FINDINGS: 440 patients were enrolled during two recruitment periods (2006-09 and 2012-16). Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated (log-rank p<0·0001). Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1-4·4 years and upper limb milestones by 2·8-8·0 years compared with treatment for less than 1 month. Deflazacort was associated with increased median age at loss of three milestones by 2·1-2·7 years in comparison with prednisone or prednisolone (log-rank p<0·012). 45 patients died during the 10-year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related causes in patients with known duration of glucocorticoids usage. 28 (9%) deaths occurred in 311 patients treated with glucocorticoids for 1 year or longer compared with 11 (19%) deaths in 58 patients with no history of glucocorticoid use (odds ratio 0·47, 95% CI 0·22-1·00; p=0·0501). INTERPRETATION: In patients with Duchenne muscular dystrophy, glucocorticoid treatment is associated with reduced risk of losing clinically meaningful mobility and upper limb disease progression milestones across the lifespan as well as reduced risk of death. FUNDING: US Department of Education/National Institute on Disability and Rehabilitation Research; US Department of Defense; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases; and Parent Project Muscular Dystrophy.

Gender Affects Long-Term Neurological Outcome of Neonates.

OBJECTIVE: We evaluated the possible association between fetal gender and long-term pediatric neurological morbidity. METHODS: We performed a population-based retrospective cohort analysis comparing the risk of long-term neurological morbidity (up to age 18 years) of children born during the years 1991 to 2013 according to their gender. Neurological morbidity evaluated included hospitalizations in childhood involving pervasive developmental disorder, obstructive sleep apnea, cerebral palsy, epilepsy, and infantile spasms and disorders of eating as recorded in the hospital files. Multiple pregnancies and fetal congenital malformations were excluded. Kaplan-Meier survival curves were constructed to compare the cumulative neurological morbidity over the study period. A Cox proportional hazards model was used to control for obstetrical confounders, including gestational age at birth, birth weight, and maternal factors. RESULTS: During the study period, 240,953 newborns were included in the long-term analysis: 51.0% (n = 122,840) males and 49.0% (n = 118,113) females. Hospitalizations for neurological problems (up to age 18 years) were significantly more common in males compared with females (1.1% vs 0.8%, respectively, odds ratio 1.31, 95% confidence interval 1.2 to 1.4, P < 0.001). Specifically, pervasive developmental disorder and obstructive sleep apnea were found to be significantly more common in males, and cerebral palsy reached borderline significance (0.1% vs 0.04%, odds ratio 1.39, 95% confidence interval 0.9 to 1.9, P = 0.06). The Kaplan-Meier survival curves demonstrated males to have a significantly higher cumulative incidence of total neurological morbidity as well as of pervasive developmental disorder and obstructive sleep apnea (all log-rank test P values <0.001). In the Cox regression model, male gender exhibited an independent association with long-term neurological morbidity, while adjusting for birth weight, gestational age, and other confounding variables (adjusted hazard ratio 1.29, 95% confidence interval 1.2 to 1.4, P < 0.001). CONCLUSION: Males are at an increased risk for pediatric neurological morbidity independent of gestational age at birth and birth weight.

Neonatal critical illness and development: white matter and hippocampus alterations in school-age neonatal extracorporeal membrane oxygenation survivors.

AIM: To examine the neurobiology of long-term neuropsychological deficits after neonatal extracorporeal membrane oxygenation (ECMO). METHOD: This cross-sectional study assessed white matter integrity and hippocampal volume of ECMO survivors (8-15y) and healthy children (8-17y) using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI) respectively. Neuropsychological outcome was evaluated in ECMO survivors. Included clinical predictors of white matter integrity: age start ECMO, ECMO duration, highest oxygenation index before ECMO, highest mean airway pressure, and mechanical ventilation duration. RESULTS: ECMO survivors (n=23) had lower global fractional anisotropy than healthy children (n=54) (patients=0.368; comparison group=0.381; p=0.018), but similar global mean diffusivity (p=0.410). ECMO survivors had lower fractional anisotropy in the left cingulum bundle (ECMO survivors=0.345; comparison group=0.399; p<0.001) and higher mean diffusivity in a region of the left parahippocampal cingulum (patients=0.916; comparison group=0.871; p<0.001). Higher global mean diffusivity predicted worse verbal memory in ECMO survivors (n=17) (ß=-0.74, p=0.008). ECMO survivors (n=23) had smaller bilateral hippocampal volume than healthy children (n=43) (left, p<0.001; right, p<0.001) and this was related to worse verbal memory (left, ß=0.65, p=0.018; right, ß=0.71, p=0.006). INTERPRETATION: Neonatal ECMO survivors are at risk for long-term brain alterations, which may partly explain long-term neuropsychological impairments. Neuroimaging may contribute to better risk stratification of long-term impairments.

Survival and Neurodevelopmental Outcomes of Very Low Birth Weight Infants in a Regional Core Hospital in Kochi, Japan.

We sought to clarify the survival and neurodevelopmental outcomes of very low birth weight infants (VLBWIs) and to identify risk factors for death or neurodevelopmental impairment (NDI) in VLBWIs at our hospital. The total study population was 217 infants born in 2005-2012 weighing 1,500 g. We compared their outcomes with those from previous reports analyzed the causes of death. Risk factors for death after discharge or NDI were evaluated by a multivariate logistic regression analysis. The incidences of death or NDI reported revealed in this study and the database of Neonatal Research Network of Japan were 25.3% and 19.6% (p＝0.039), respectively. The main causes of death before discharge were intraventricular hemorrhage, sepsis, and persistent pulmonary hypertension of the newborn. The significant risk factors for death after discharge or NDI were early gestational age (weeks) and periventricular leukomalacia (adjusted odds ratio [95% confidence interval, p-value], 0.72 [0.54-0.94, 0.017] and 6.90 [1.35-38.25, 0.021], respectively). These factors must be addressed in order to improve treatment strategies for VLBWIs.

Hypothermia for neonatal hypoxic-ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field.

In this article, we summarize the NICHD Neonatal Research Network (NRN) trial of whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy in relation to other randomized controlled trials (RCTs) of hypothermia neuroprotection. We describe the NRN secondary studies that have been published in the past 10 years evaluating clinical, genetic, biochemical, and imaging biomarkers of outcome.

Perioperative risk factors for impaired neurodevelopment after cardiac surgery in early infancy.

OBJECTIVE: Historical cohort studies have reported adverse neurodevelopment following cardiac surgery during early infancy. Advances in surgical techniques and perioperative care have coincided with updating of neurodevelopmental assessment tools. We aimed to determine perioperative risk factors for impaired neurodevelopment at 2 years following surgery for congenital heart disease (CHD) in early infancy. DESIGN AND PATIENTS: We undertook a prospective longitudinal study of 153 full-term infants undergoing surgery for CHD before 2 months of age. Infants were excluded if they had a genetic syndrome associated with neurodevelopmental impairment. OUTCOME MEASURES: Predefined perioperative parameters were recorded and infants were classified according to cardiac anatomy. At 2 years, survivors were assessed using the Bayley Scales of Infant Development-III. RESULTS: At 2 years, 130 children (98% of survivors) were assessed. Mean cognitive, language and motor scores were 93.4±13.6, 93.6±16.1 and 96.8±12.5 respectively (100±15 norm). Twenty (13%) died and 12 (9%) survivors had severe impairment (score <70), mostly language (8%). The lowest scores were in infants born with single ventricle physiology with obstruction to the pulmonary circulation who required a neonatal systemic-to-pulmonary artery shunt. Additional risk factors for impairment included reduced gestational age, postoperative elevation of lactate or S100B and repeat cardiac surgery. CONCLUSIONS: In the modern era of infant cardiac surgery and perioperative care, children continue to demonstrate neurodevelopmental delays. The use of updated assessment tools has revealed early language dysfunction and relative sparing of motor function. Ongoing follow-up is critical in this high-risk population.

From Nonissue to Healthcare Crisis: A Historical Review of Aging and Dying With an Intellectual and Developmental Disability.

Individuals with intellectual and developmental disabilities are living unprecedentedly longer lives primarily due to the long-term benefits of the deinstitutionalization movement and widespread improvements in health outcomes. However, the consequences of this protracted aging process are significant, complex, and often poor not only for the individuals and their caregivers but for the mainstream healthcare community. This article will explore, utilizing a constructionist perspective, how these challenges evolved from a nonissue to an impending crisis in less than 25 years. Additionally, present-day efforts by researchers, policymakers, and practitioners to address these challenges will be explored and recommendations will be made for future directions.

Understanding Information About Mortality Among People with Intellectual and Developmental Disabilities in Canada.

BACKGROUND: This paper reviews what is currently known about mortality among Canadians with intellectual and developmental disabilities and describes opportunities for ongoing monitoring. METHODS: In-hospital mortality among adults with intellectual and developmental disabilities in Ontario was examined using hospital data. Mortality was compared between age-, sex- and residence area-matched groups of Manitobans with and without intellectual and developmental disabilities using linked administrative data. A retrospective cohort study of mortality among individuals with intellectual and developmental disabilities in a region of Ontario focused on measuring excess mortality and risk factors. FINDINGS: There is evidence of excess mortality in persons with intellectual and developmental disabilities in Canada. Some of the excess is attributable to comorbidities that are more common in this population. Women may have a greater risk of death than men. Excess mortality occurs at all ages but is more pronounced in early life. DISCUSSION: High-quality ongoing monitoring of mortality among individuals with intellectual and developmental disabilities is possible in Canada. Examination of sex differences should be a priority.

Mortality of People with Intellectual and Developmental Disabilities from Select US State Disability Service Systems and Medical Claims Data.

BACKGROUND: Monitoring population trends including mortality within subgroups such as people with intellectual and developmental disabilities and between countries provides crucial information about the population's health and insights into underlying health concerns and the need for and effectiveness of public health efforts. METHODS: Data from both US state intellectual and developmental disabilities service system administrative data sets and de-identified state Medicaid claims were used to calculate average age at death and crude mortality rates. RESULTS: Average age at death for people in state intellectual and developmental disabilities systems was 50.4-58.7 years and 61.2-63.0 years in Medicaid data, with a crude adult mortality rate of 15.2 per thousand. CONCLUSIONS: Age at death remains lower and mortality rates higher for people with intellectual and developmental disabilities. Improved case finding (e.g. medical claims) could provide more complete mortality patterns for the population with intellectual and developmental disabilities to inform the range of access and receipt of supportive and health-related interventions and preventive care.

No relationship between mode of delivery and neonatal mortality and neurodevelopment in very low birth weight infants aged two years.

BACKGROUND: To compare neonatal mortality and neurodevelopmental outcomes at two years of age in very low birth weight infants (≤1500 g) born by cesarean with those by vaginal delivery. METHODS: In this retrospective, case-control study, we evaluated neonatal mortality, medical conditions and neurodevelopmental outcomes at two years of corrected age in 710 very low birth weight (VLBW) infants born between January 2005 and December 2010. Of the 710 infants, 351 were born by the cesarean and 359/710 by vaginal route. RESULTS: There were no significant differences in neonatal mortality between the cesarean delivery group and vaginal delivery group [56/351 (15.9%) vs. 71/359 (19.8%), P=0.20]. VLBW infants delivered by the cesarean procedure had a higher incidence of respiratory distress syndrome than those born by the vaginal route [221/351 (63.0%) vs. 178/359 (49.6%), P<0.001]. There were no differences in other neonatal morbidities, including intraventricular hemorrhage [126/351 (35.9%) vs. 134/359 (37.3%), P=0.69], bronchopulmonary dysplasia [39/351 (11%) vs. 31/359 (8.6%), P=0.38] and necrotising enterocolitis [40/351 (11.4%) vs. 32/359 (8.9%), P=0.32] between the two groups. The incidence of poor neurodevelopment after cesarean delivery was similar to that after vaginal delivery [105/351 (29.9) vs. 104/359 (29.0%), P=0.78]. CONCLUSIONS: In neither neurodevelopment nor neonatal mortality did cesarean birth offered significant advantages to VLBW infants. Moreover, the operation might be associated with an increased risk of respiratory distress syndrome for VLBW infants. The mode of delivery of VLBW infants should be largely based on obstetric indications and maternal considerations rather than perceived better outcomes for the neonate.