Strategies to improve neurodevelopmental outcomes in babies at risk of neonatal hypoglycaemia.
Ontology highlight
ABSTRACT:
SUBMITTER: Alsweiler JM
PROVIDER: S-EPMC8528170 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundNeonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk.Methods and findingsWe conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand. Babies at risk of hypoglycaemia (infant of a mother with diabetes, late preterm delivery, small or large birthweight, or other risk factors) but without indication for admission to a neonatal intensive care unit (NICU) were randomly allocated either to one of four treatment groups: 40% dextrose at one of two doses (0.5 ml/kg = 200 mg/kg, or 1 ml/kg = 400 mg/kg), either once at 1 h of age or followed by three additional doses of dextrose (0.5 ml/kg before feeds in the first 12 h); or to one of four corresponding placebo groups. Treatments were administered by massaging gel into the buccal mucosa. The primary outcome was hypoglycaemia (<2.6 mM) in the first 48 h. Secondary outcomes included admission to a NICU, admission for hypoglycaemia, and breastfeeding at discharge and at 6 wk. Prespecified potential dose limitations were tolerance of gel, time taken to administer, messiness, and acceptability to parents. From August 2013 to November 2014, 416 babies were randomised. Compared to babies randomised to placebo, the risk of hypoglycaemia was lowest in babies randomised to a single dose of 200 mg/kg dextrose gel (relative risk [RR] 0.68; 95% confidence interval [CI] 0.47-0.99, p = 0.04) but was not significantly different between dose groups (p = 0.21). Compared to multiple doses, single doses of gel were better tolerated, quicker to administer, and less messy, but these limitations were not different between dextrose and placebo gel groups. Babies who received any dose of dextrose gel were less likely to develop hypoglycaemia than those who received placebo (RR 0.79; 95% CI 0.64-0.98, p = 0.03; number needed to treat = 10, 95% CI 5-115). Rates of NICU admission were similar (RR 0.64; 95% CI 0.33-1.25, p = 0.19), but admission for hypoglycaemia was less common in babies randomised to dextrose gel (RR 0.46; 95% CI 0.21-1.01, p = 0.05). Rates of breastfeeding were similar in both groups. Adverse effects were uncommon and not different between groups. A limitation of this study was that most of the babies in the trial were infants of mothers with diabetes (73%), which may reduce the applicability of the results to babies from other risk groups.ConclusionsThe incidence of neonatal hypoglycaemia can be reduced with a single dose of buccal 40% dextrose gel 200 mg/kg. A large randomised trial (Hypoglycaemia Prevention with Oral Dextrose [hPOD]) is under way to determine the effects on NICU admission and later outcomes.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12613000322730.
| S-EPMC5079625 | biostudies-literature
Project description:Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes.Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors.The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken.After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26).Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.
| S-EPMC5517008 | biostudies-other
Project description:ObjectiveTo determine the effect of prophylactic dextrose gel for prevention of neonatal hypoglycaemia on neurodevelopment and executive function at 2 years' corrected age.DesignProspective follow-up of a randomised trial.SettingNew Zealand.PatientsParticipants from the pre-hypoglycaemia Prevention with Oral Dextrose (pre-hPOD) trial randomised to one of four dose regimes of buccal 40% dextrose gel or equivolume placebo.Main outcome measuresCoprimary outcomes were neurosensory impairment and executive function. Secondary outcomes were components of the primary outcomes, neurology, anthropometry and health measures.ResultsWe assessed 360 of 401 eligible children (90%) at 2 years' corrected age. There were no differences between dextrose gel dose groups, single or multiple dose groups, or any dextrose and any placebo groups in the risk of neurosensory impairment or low executive function (any dextrose vs any placebo neurosensory impairment: relative risk (RR) 0.77, 95% CI 0.50 to 1.19, p=0.23; low executive function: RR 0.50, 95% CI 0.24 to 1.06, p=0.07). There were also no differences between groups in any secondary outcomes. There was no difference between children who did or did not develop neonatal hypoglycaemia in the risk of neurosensory impairment (RR 1.05, 95% CI 0.68 to 1.64, p=0.81) or low executive function (RR 0.73, 95% CI 0.34 to 1.59, p=0.43).ConclusionProphylactic dextrose gel did not alter neurodevelopment or executive function and had no adverse effects to 2 years' corrected age, but this study was underpowered to detect potentially clinically important effects on neurosensory outcomes.
| S-EPMC8062278 | biostudies-literature
Project description:Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited.We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function.Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome.In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
| S-EPMC4646166 | biostudies-literature
Project description:Identifying patients at high risk of breast cancer recurrence has important implications not only for enabling the ability to provide accurate information to patients but also the potential to improve patient outcomes. Patients at high recurrence risk can be offered appropriate treatment to improve the overall survival. However, the major challenge is identifying patients with early-stage breast cancer at lower risk who may be spared potentially toxic therapy. The successful integration of molecular assays into clinical practice may address the problem of overtreatment and improve overall patient outcomes.
| S-EPMC4603628 | biostudies-other
Project description:ImportanceHypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown.ObjectiveTo test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia.Design, setting, and participantsThe Children With Hypoglycemia and Their Later Development (CHYLD) Study is a prospective cohort investigation of moderate to late preterm and term infants born at risk of hypoglycemia. Clinicians were masked to neonatal interstitial glucose concentrations; outcome assessors were masked to neonatal glycemic status. The setting was a regional perinatal center in Hamilton, New Zealand. The study was conducted from December 2006 to November 2010. The dates of the follow-up were September 2011 to June 2015. Participants were 614 neonates born from 32 weeks' gestation with at least 1 risk factor for hypoglycemia, including diabetic mother, preterm, small, large, or acute illness. Blood and masked interstitial glucose concentrations were measured for up to 7 days after birth. Infants with hypoglycemia (whole-blood glucose concentration <47 mg/dL) were treated to maintain blood glucose concentration of at least 47 mg/dL.ExposuresNeonatal hypoglycemic episode, defined as at least 1 consecutive blood glucose concentration less than 47 mg/dL, a severe episode (<36 mg/dL), or recurrent (?3 episodes). An interstitial episode was defined as an interstitial glucose concentration less than 47 mg/dL for at least 10 minutes.Main outcomes and measuresCognitive function, executive function, visual function, and motor function were assessed at 4.5 years. The primary outcome was neurosensory impairment, defined as poor performance in one or more domains.ResultsIn total, 477 of 604 eligible children (79.0%) were assessed. Their mean (SD) age at the time of assessment was 4.5 (0.1) years, and 228 (47.8%) were female. Those exposed to neonatal hypoglycemia (280 [58.7%]) did not have increased risk of neurosensory impairment (risk difference [RD], 0.01; 95% CI, -0.07 to 0.10 and risk ratio [RR], 0.96; 95% CI, 0.77 to 1.21). However, hypoglycemia was associated with increased risk of low executive function (RD, 0.05; 95% CI, 0.01 to 0.10 and RR, 2.32; 95% CI, 1.17 to 4.59) and visual motor function (RD, 0.03; 95% CI, 0.01 to 0.06 and RR, 3.67; 95% CI, 1.15 to 11.69), with highest risk in children exposed to severe, recurrent, or clinically undetected (interstitial episodes only) hypoglycemia.Conclusions and relevanceNeonatal hypoglycemia was not associated with increased risk of combined neurosensory impairment at 4.5 years but was associated with a dose-dependent increased risk of poor executive function and visual motor function, even if not detected clinically, and may thus influence later learning. Randomized trials are needed to determine optimal screening and intervention thresholds based on assessment of neurodevelopment at least to school age.
| S-EPMC5710616 | biostudies-literature
Project description:BACKGROUND:Neonatal interventions are largely focused on reduction of mortality and progression towards Millennium Development Goal 4 (child survival). However, little is known about the global burden of long-term consequences of intrauterine and neonatal insults. We did a systematic review to estimate risks of long-term neurocognitive and other sequelae after intrauterine and neonatal insults, especially in low-income and middle-income countries. METHODS:We searched Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Embase for studies published between Jan 1, 1966, and June 30, 2011, that reported neurodevelopmental sequelae after preterm or neonatal insult. For unpublished studies and grey literature, we searched Dissertation Abstracts International and the WHO library. We reviewed publications that had data for long-term outcome after defined neonatal insults. We summarised the results with medians and IQRs, and calculated the risk of at least one sequela after insult. FINDINGS:Of 28,212 studies identified by our search, 153 studies were suitable for inclusion, documenting 22,161 survivors of intrauterine or neonatal insults. The overall median risk of at least one sequela in any domain was 39·4% (IQR 20·0-54·8), with a risk of at least one severe impairment in any insult domain of 18·5% (7·7-33·3), of at least one moderate impairment of 5·0% (0·0-13·3%), and of at least one mild impairment of 10·0% (1·4-17·9%). The pooled risk estimate of at least one sequela (weighted mean) associated with one or more of the insults studied (excluding HIV) was 37·0% (95% CI 27·0-48·0%) and this risk was not significantly affected by region, duration of the follow-up, study design, or period of data collection. The most common sequelae were learning difficulties, cognition, or developmental delay (n=4032; 59%); cerebral palsy (n=1472; 21%); hearing impairment (n=1340; 20%); and visual impairment (n=1228; 18%). Only 40 (26%) studies included data for multidomain impairments. These studies included 2815 individuals, of whom 1048 (37%) had impairments, with 334 (32%) having multiple impairments. INTERPRETATION:Intrauterine and neonatal insults have a high risk of causing substantial long-term neurological morbidity. Comparable cohort studies in resource-poor regions should be done to properly assess the burden of these conditions, and long-term outcomes, such as chronic disease, and to inform policy and programme investments. FUNDING:The Bill & Melinda Gates Foundation, Saving Newborn Lives, and the Wellcome Trust.
| S-EPMC3273721 | biostudies-literature
Project description:Tracing the early paths leading to developmental disorders is critical for prevention. In previous work, we detected an interaction between genomic risk scores for schizophrenia (GRSs) and early-life complications (ELCs), so that the liability of the disorder explained by genomic risk was higher in the presence of a history of ELCs, compared with its absence. This interaction was specifically driven by loci harboring genes highly expressed in placentae from normal and complicated pregnancies [G. Ursini et al., Nat. Med. 24, 792-801 (2018)]. Here, we analyze whether fractionated genomic risk scores for schizophrenia and other developmental disorders and traits, based on placental gene-expression loci (PlacGRSs), are linked with early neurodevelopmental outcomes in individuals with a history of ELCs. We found that schizophrenia's PlacGRSs are negatively associated with neonatal brain volume in singletons and offspring of multiple pregnancies and, in singletons, with cognitive development at 1 y and, less strongly, at 2 y, when cognitive scores become more sensitive to other factors. These negative associations are stronger in males, found only with GRSs fractionated by placental gene expression, and not found in PlacGRSs for other developmental disorders and traits. The relationship of PlacGRSs with brain volume persists as an anlage of placenta biology in adults with schizophrenia, again selectively in males. Higher placental genomic risk for schizophrenia, in the presence of ELCs and particularly in males, alters early brain growth and function, defining a potentially reversible neurodevelopmental path of risk that may be unique to schizophrenia.
| S-EPMC7896349 | biostudies-literature
Project description:Both cardiovascular and reproductive complications may have origins in utero or in early life. Women in the Bogalusa Heart Study (n = 1401) had been linked to birth certificates for birthweight and gestational data, which were examined relative to childhood (ages 4-16) cardiometabolic indicators, indicated by mean levels overall and total risk factor burden as estimated by area under the curve (AUC) computed from longitudinal quadratic random-effects growth models. Women reported the birthweight and gestational age of each of their own pregnancies, and delivery medical records were linked to interview data where possible. Path analyses were conducted to examine the relationships among a woman's own birth outcomes, childhood and preconception adult cardiovascular health, and birth outcomes. Mean blood pressure (systolic blood pressure (SBP) adjusted relative risk (aRR) per 1-SD increase, 1.27, 95% CI 1.04-1.57) and low-density lipoprotein (aRR 1.21, 95% CI 1.02-1.44) in childhood predicted preterm birth (PTB), while mean SBP (aRR 1.33, 95% CI 1.02-1.74) predicted term low birthweight. The AUC data suggested an association between blood pressure and PTB (aRR for SBP top 10%, 1.86, 95% CI 1.08-3.21). Pre-pregnancy total cholesterol was negatively associated with gestational age. In path analyses, positive associations were found for each step between own birthweight, childhood BMI, pre-pregnancy BMI, and child's birthweight. Childhood levels of some, though not all, cardiovascular risk factors may predict adverse birth outcomes (preterm birth and reduced fetal growth).
| S-EPMC8791492 | biostudies-literature
Project description:Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit) sedation is common in the NICU (neonatal intensive care unit). A growing body of basic and animal evidence suggests potential long-term harm associated with neonatal opioid therapy. Morphine increases apoptosis in human microglial cells, and animal studies demonstrate long-term changes in behavior, brain function, and spatial recognition memory following morphine exposure. This comprehensive review examines existing preclinical and clinical evidence on the long-term impacts of neonatal pain and opioid therapy.
| S-EPMC4101480 | biostudies-other