Treatment for gestational diabetes mellitus (GDM) aims to reduce maternal hyperglycaemia. The TARGET Trial assessed whether tighter compared with less tight glycaemic control reduced maternal and ...perinatal morbidity. In this stepped-wedge, cluster-randomised trial, identification number ACTRN12615000282583, 10 hospitals in New Zealand were randomised to 1 of 5 implementation dates. The trial was registered before the first participant was enrolled. All hospitals initially used less tight targets (fasting plasma glucose (FPG) <5.5 mmol/L (<99 mg/dL), 1-hour <8.0 mmol/L (<144 mg/dL), 2 hour postprandial <7.0 mmol/L (<126 mg/dL)) and every 4 months, 2 hospitals moved to use tighter targets (FPG less than or equal to5.0 mmol/L (less than or equal to90 mg/dL), 1-hour less than or equal to7.4 mmol/L (less than or equal to133 mg/dL), 2 hour postprandial less than or equal to6.7 mmol/L) (less than or equal to121 mg/dL). Women with GDM, blinded to the targets in use, were eligible. The primary outcome was large for gestational age. Secondary outcomes assessed maternal and infant health. Analyses were by intention to treat. Between May 2015 and November 2017, data were collected from 1,100 women with GDM (1,108 infants); 598 women (602 infants) used the tighter targets and 502 women (506 infants) used the less tight targets. The rate of large for gestational age was similar between the treatment target groups (88/599, 14.7% versus 76/502, 15.1%; adjusted relative risk adjRR 0.96, 95% confidence interval CI 0.66 to 1.40, P = 0.839). The composite serious health outcome for the infant of perinatal death, birth trauma, or shoulder dystocia was apparently reduced in the tighter group when adjusted for gestational age at diagnosis of GDM, BMI, ethnicity, and history of GDM compared with the less tight group (8/599, 1.3% versus 13/505, 2.6%, adjRR 0.23, 95% CI 0.06 to 0.88, P = 0.032). No differences were seen for the other infant secondary outcomes apart from a shorter stay in intensive care (P = 0.041). Secondary outcomes for the woman showed an apparent increase for the composite serious health outcome that included major haemorrhage, coagulopathy, embolism, and obstetric complications in the tighter group (35/595, 5.9% versus 15/501, 3.0%, adjRR 2.29, 95% CI 1.14 to 4.59, P = 0.020). There were no differences between the target groups in the risk for pre-eclampsia, induction of labour, or cesarean birth, but more women using tighter targets required pharmacological treatment (404/595, 67.9% versus 293/501, 58.5%, adjRR 1.20, 95% CI 1.00 to 1.44, P = 0.047). The main study limitation is that the treatment targets used may vary to those in use in some countries. Tighter glycaemic targets in women with GDM compared to less tight targets did not reduce the risk of a large for gestational age infant, but did reduce serious infant morbidity, although serious maternal morbidity was increased. These findings can be used to aid decisions on the glycaemic targets women with GDM should use.
The aim of this trial was to determine if midwives or doctor leaders are more effective at implementing a clinical practice guideline for oral dextrose gel to treat neonatal hypoglycaemia. This was a ...cluster-randomised, controlled, trial. New Zealand maternity hospitals were randomised to guideline implementation by a midwife or doctor implementation leader. The primary outcome was the change in the proportion of hypoglycaemic babies (blood glucose concentration <2.6 mmol/L in the first 48 hours after birth), treated with dextrose gel from before, to three months after, implementation. Twenty-one maternity hospitals that cared for babies at risk of hypoglycaemia consented to participate, of which 15 treated babies with hypoglycaemia at both time points (7 randomised to midwifery led, 8 randomised to doctor led implementation). The primary outcome included 463 hypoglycaemic babies (292 midwifery led, 171 doctor led implementation). There was no difference in the primary outcome between hospitals randomised to midwifery or doctor led implementation (proportion treated with gel, mean(SD); midwifery led: before 71 (38)%, 3 months after 87 (12)%; doctor led: before 63 (43)%, 3 months after 86 (16)%; adjusted mean change in proportion (95%CI); 19.3% (-4.5–43.1), p = 0.11). There was an increase in the proportion of eligible babies treated with oral dextrose gel from before to 3 months after implementation of the guideline (122/153 (80%) v 144/163 (88%), OR (95%CI); 3.42 (1.67–6.98), p<0.001). Implementation of a clinical practice guideline improved uptake of oral dextrose gel. There was no evidence of a difference between midwife and doctor implementation leaders for implementing this guideline for treatment of hypoglycaemic babies. The trial was prospectively registered on the ISRCTN registry on the 20/05/2015 (ISRCTN61154098).
Objective To determine neurodevelopmental outcome at 2 years' corrected age in children randomized to treatment with dextrose gel or placebo for hypoglycemia soon after birth (The Sugar Babies ...Study). Study design This was a follow-up study of 184 children with hypoglycemia (<2.6 mM 47 mg/dL) in the first 48 hours and randomized to either dextrose (90/118, 76%) or placebo gel (94/119, 79%). Assessments were performed at Kahikatea House, Hamilton, New Zealand, and included neurologic function and general health (pediatrician assessed), cognitive, language, behavior, and motor skills (Bayley Scales of Infant and Toddler Development, Third Edition), executive function (clinical assessment and Behaviour Rating Inventory of Executive Function-Preschool Edition), and vision (clinical examination and global motion perception). Coprimary outcomes were neurosensory impairment (cognitive, language or motor score below −1 SD or cerebral palsy or blind or deaf) and processing difficulty (executive function or global motion perception worse than 1.5 SD from the mean). Statistical tests were two sided with 5% significance level. Results Mean (±SD) birth weight was 3093 ± 803 g and mean gestation was 37.7 ± 1.6 weeks. Sixty-six children (36%) had neurosensory impairment (1 severe, 6 moderate, 59 mild) with similar rates in both groups (dextrose 38% vs placebo 34%, relative risk 1.11, 95% CI 0.75-1.63). Processing difficulty also was similar between groups (dextrose 10% vs placebo 18%, relative risk 0.52, 95% CI 0.23-1.15). Conclusions Dextrose gel is safe for the treatment of neonatal hypoglycemia, but neurosensory impairment is common among these children. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN 12608000623392.
Nutritional intake can promote early neonatal brain development in very preterm born neonates (< 32 weeks' gestation). In a group of 7-year-old very preterm born children followed since birth, we ...examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p < 0.001) but lower intakes of fat (β = - 0.06; 95% CI - 0.09, - 0.02, p = 0.001) and carbohydrates (β = - 0.03; 95% CI - 0.04, - 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children.
Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown.
To test the hypothesis that neurodevelopment at 4.5 ...years is related to the severity and frequency of neonatal hypoglycemia.
The 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.
Neonatal 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.
Cognitive 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.
In 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.
Neonatal 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.
Neonatal hypoglycemia is common, occurring in up to 50% of infants at risk for hypoglycemia (infant of diabetic mother IDM, small for gestational age SGA, large for gestational age LGA, and preterm) ...and is associated with long-term neurodevelopmental impairment. Guidelines recommend screening infants at risk of hypoglycemia. The proportion of infants who require screening for neonatal hypoglycemia is unknown.
To determine the proportion of infants eligible for neonatal hypoglycemia screening using criteria from the highest-scoring critically appraised clinical guideline.
This systematic review of the literature was conducted to identify clinical practice guidelines for neonatal hypoglycemia and took place at a tertiary maternity hospital in Auckland, New Zealand. Eligible guidelines were critically appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Using screening criteria extracted from the highest-scoring guideline, the proportion of infants eligible for neonatal hypoglycemia screening was determined in a retrospective observational cohort study of infants born January 1, 2004, to December 31, 2018. Data were analyzed by logistic regression. Infant participants were included if gestational age was 35 weeks or more, birth weight was 2000 g or more, and they were not admitted to a neonatal intensive care unit less than 1 hour after birth. The data were analyzed from November 2022 through February 2023. A total of 101 372 infants met the inclusion criteria.
Risk factors for neonatal hypoglycemia.
Proportion of infants eligible for neonatal hypoglycemia screening.
The study team screened 2366 abstracts and 18 guidelines met inclusion criteria for appraisal. There was variability in the assessed quality of guidelines and a lack of consensus between screening criteria. The highest-scoring guideline defined screening criteria as: IDM, preterm (less than 37 weeks' gestation), SGA (less than 10th percentile), birth weight of less than 2500 g or more than 4500 g, LGA (more than 90th percentile), or gestational age more than 42 weeks. A total of 101 372 infants met criteria for inclusion in the cohort study; median (IQR) gestational age was 39 (38-40) weeks and 51% were male. The overall proportion of infants eligible for screening was 26.3%. There was an increase in the proportion of eligible infants from 25.6% to 28.5% over 15 years, which was not statistically significant after adjustment for maternal age, body mass index, ethnicity, and multiple pregnancy (odds ratio, 0.99; 95% CI, 0.93-1.03; change in proportion per year).
A systematic review found that practice guidelines providing recommendations for clinical care of neonatal hypoglycemia were of variable quality with is a lack of consensus regarding definitions for infants at risk for hypoglycemia. In the cohort study, one-quarter of infants were eligible for hypoglycemia screening. Further research is required to identify which infants may benefit from neonatal hypoglycemia screening.
Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years McKinlay, Christopher J D; Alsweiler, Jane M; Ansell, Judith M ...
New England journal of medicine/The New England journal of medicine,
2015-Oct-15, Volume:
373, Issue:
16
Journal Article
Peer reviewed
Open access
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.).
Advances in nutrition of the newborn infant Harding, Jane E, Prof; Cormack, Barbara E, MHSc; Alexander, Tanith, MSc ...
The Lancet (British edition),
04/2017, Volume:
389, Issue:
10079
Journal Article
Peer reviewed
Summary Nutrition of newborn infants, particularly of those born preterm, has advanced substantially in recent years. Extremely preterm infants have high nutrient demands that are challenging to ...meet, such that growth faltering is common. Inadequate growth is associated with poor neurodevelopmental outcomes, and although improved early growth is associated with better cognitive outcomes, there might be a trade-off in terms of worse metabolic outcomes, although the contribution of early nutrition to these associations is not established. New developments include recommendations to increase protein supply, improve formulations of parenteral lipids, and provide mineral supplements while encouraging human milk feeding. However, high quality evidence of the risks and benefits of these developments is lacking. Clinical trials are also needed to assess the effect on preterm infants of experiencing the smell and taste of milk, to determine whether boys and girls should be fed differently, and to test effects of insulin and IGF-1 supplements on growth and developmental outcomes. Moderate-to-late preterm infants have neonatal nutritional challenges that are similar to those infants born at earlier gestations, but even less high quality evidence exists upon which to base clinical decisions. The focus of research in nutrition of infants born at term is largely directed at new formula products that will improve cognitive and metabolic outcomes. Providing the most effective nutrition to preterm infants should be prioritised as an important focus of neonatal care research to improve long-term metabolic and developmental outcomes.
To determine whether tight glycemic control of neonatal hyperglycemia changes neurodevelopment, growth, and metabolism at school age.
Children born very low birth weight and randomized as ...hyperglycemic neonates to a trial of tight vs standard glycemic control were assessed at 7 years corrected age, including Wechsler Intelligence Scale for Children Fourth Edition, Movement Assessment Battery for Children 2, visual and neurologic examinations, growth measures, dual X-ray absorptiometry, and frequently sampled intravenous glucose tolerance test. The primary outcome was survival without neurodevelopmental impairment at age 7 years. Outcomes were compared using linear regression, adjusted for sex, small for gestational age, birth plurality, and the clustering of twins. Data are reported as number (%) or mean (SD).
Of the 88 infants randomized, 11 (13%) had died and 57 (74% of eligible children) were assessed at corrected age 7 years. Survival without neurodevelopmental impairment occurred in 25 of 68 children (37%), with no significant difference between tight (14 of 35; 40%) and standard (11 of 33; 33%) glycemic control groups (P = .60). Children in the tight group were shorter than those in the standard group (121.3 6.3 cm vs 125.1 5.4 cm; P < .05), but had similar weight and head circumference. Children in the tight group had greater height-adjusted lean mass (18.7 0.3 vs 17.6 0.2 kg; P < .01) and lower fasting glucose concentrations (84.6 6.30 vs 90.0 5.6 mg⋅dL−1; P < .05), but no other differences in measures of body composition or insulin-glucose metabolism.
Tight glycemic control for neonatal hyperglycemia does not change survival without neurodevelopmental impairment, but reduces height, increases height-adjusted lean mass, and reduces fasting blood glucose concentrations at school age.
ACTRN: 12606000270516.
Most moderate-to-late-preterm infants need nutritional support until they are feeding exclusively on their mother's breast milk. Evidence to guide nutrition strategies for these infants is lacking.
...We conducted a multicenter, factorial, randomized trial involving infants born at 32 weeks 0 days' to 35 weeks 6 days' gestation who had intravenous access and whose mothers intended to breast-feed. Each infant was assigned to three interventions or their comparators: intravenous amino acid solution (parenteral nutrition) or dextrose solution until full feeding with milk was established; milk supplement given when maternal milk was insufficient or mother's breast milk exclusively with no supplementation; and taste and smell exposure before gastric-tube feeding or no taste and smell exposure. The primary outcome for the parenteral nutrition and the milk supplement interventions was the body-fat percentage at 4 months of corrected gestational age, and the primary outcome for the taste and smell intervention was the time to full enteral feeding (150 ml per kilogram of body weight per day or exclusive breast-feeding).
A total of 532 infants (291 boys 55%) were included in the trial. The mean (±SD) body-fat percentage at 4 months was similar among the infants who received parenteral nutrition and those who received dextrose solution (26.0±5.4% vs. 26.2±5.2%; adjusted mean difference, -0.20; 95% confidence interval CI, -1.32 to 0.92; P = 0.72) and among the infants who received milk supplement and those who received mother's breast milk exclusively (26.3±5.3% vs. 25.8±5.4%; adjusted mean difference, 0.65; 95% CI, -0.45 to 1.74; P = 0.25). The time to full enteral feeding was similar among the infants who were exposed to taste and smell and those who were not (5.8±1.5 vs. 5.7±1.9 days; P = 0.59). Secondary outcomes were similar across interventions. Serious adverse events occurred in one infant.
This trial of routine nutrition interventions to support moderate-to-late-preterm infants until full nutrition with mother's breast milk was possible did not show any effects on the time to full enteral feeding or on body composition at 4 months of corrected gestational age. (Funded by the Health Research Council of New Zealand and others; DIAMOND Australian New Zealand Clinical Trials Registry number, ACTRN12616001199404.).
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