Effect of prophylactic dextrose gel on the neonatal gut microbiome

ObjectiveTo determine the effect of prophylactic dextrose gel on the infant gut microbiome.DesignObservational cohort study nested in a randomised trial.SettingThree maternity hospitals in New Zealand.PatientsInfants at risk of neonatal hypoglycaemia whose parents consented to participation in the hypoglycaemia Prevention in newborns with Oral Dextrose trial (hPOD). Infants were randomised to receive prophylactic dextrose gel or placebo gel, or were not randomised and received no gel (controls). Stool samples were collected on days 1, 7 and 28.Main outcome measuresThe primary outcome was microbiome beta-diversity at 4 weeks. Secondary outcomes were beta-diversity, alpha-diversity, bacterial DNA concentration, microbial community stability and relative abundance of individual bacterial taxa at each time point.ResultsWe analysed 434 stool samples from 165 infants using 16S rRNA gene amplicon sequencing. There were no differences between groups in beta-diversity at 4 weeks (p=0.49). There were also no differences between groups in any other microbiome measures including beta-diversity (p=0.53 at day 7), alpha-diversity (p=0.46 for day 7 and week 4), bacterial DNA concentration (p=0.91), microbial community stability (p=0.52) and microbial relative abundance at genus level. There was no evidence that exposure to any dextrose gel (prophylaxis or treatment) had any effect on the microbiome. Mode of birth, type of milk fed, hospital of birth and ethnicity were all associated with differences in the neonatal microbiome.ConclusionsClinicians and consumers can be reassured that dextrose gel used for prophylaxis or treatment of neonatal hypoglycaemia does not alter the neonatal gut microbiome.Trial registration number12614001263684.

Clinical Profile of Neonatal Hypoglycaemia in a Tertiary Care Centre in Mahabubnagar, Telangana

BACKGROUND Hypoglycaemia is one of the most common metabolic problems seen in neonatal intensive care units (NICU). Most cases of neonatal hypoglycaemia are transient and respond readily to treatment and are associated with excellent prognosis. Development of clinical signs and symptoms may be a late sign of hypoglycaemia. Persistent hypoglycaemia may result in possible neurologic sequelae. The purpose of this study was to assess the clinical pattern of hypoglycaemia in neonates admitted in special newborn care unit in Government General hospital, Mahabubnagar, Telangana and to also assess the influence of gestational age, birth weight, various comorbid conditions on blood glucose levels. METHODS This is an observational hospital-based study done in Government General Hospital, Mahabubnagar from June 2020 to May 2021. Neonates with hypoglycaemia (blood glucose < 45 mg/dl) at the time of admission are included in our study. Blood glucose values were monitored 2nd hourly on 1st day and 6th hourly thereafter. Following the detection of hypoglycaemia, the neonates were treated as per institutional protocol. Clinical features, laboratory parameters are studied and analysed. RESULTS Among the 99 neonates studied, 68 (68.7 %) were males and 31 (31.3 %) females; Term babies were 75 (75.7 %) and pre term babies were 24 (24.2 %). Low birth weight newborns (51.5 %) were more affected with hypoglycaemia compared to normal weight newborns (38.4 %). Among the 99 neonates studied, 96.9 % were treated and discharged. Average duration of stay was around 05 to 07 days. CONCLUSIONS Hypoglycaemia is most common condition in neonates. Routine screening should be done to all newborns at the time of admission. Timely intervention reduces long term neurological sequelae. Neonates presenting with dull activity, refusal to feed, vomiting, jitteriness, seizures must routinely undergo regular glucose monitoring. As the study shows, most hypoglycaemic neonates presented with those symptoms. Among the various comorbidities, hypoglycaemia occurred more in birth asphyxia and respiratory distress syndrome. So, it should be made mandatory to do glucose monitoring in these cases. Glucose monitoring should be made as a common screening method to prevent morbidity and mortality in neonatal intensive care units. KEYWORDS Hypoglycaemia, Pre-Term, Term, Low Birth Weight, Special New Born Care Unit, Small for Gestational Age, Large for Gestational Age

Ramadan and gestational diabetes: maternal and neonatal outcomes

Aims The impact of Ramadan exposure to Gestational Diabetes Mellitus (GDM) pregnancies is not known. We therefore aimed to assess the association of Ramadan with maternal and neonatal outcomes among pregnant women with GDM. Methods Retrospective cohort study of 345 Muslim women with singleton pregnancies who attended a major Sydney teaching hospital during the period 1989–2010, was undertaken. Exposure to Ramadan was stratified by the: (1) total pregnancy days exposed to Ramadan, (2) duration (hours) of daily fasting and (3) trimester of exposure. Maternal and neonatal outcomes were examined by exposure status, and never exposed pregnancies were comparator in all three analyses. Fasting status was not recorded. Results We found no significant effect of Ramadan exposure on mean birthweight, macrosomia and maternal outcomes. However, we found a significant trend for increased neonatal hyperbilirubinemia with increasing Ramadan days exposure and later trimester exposure (ptrend ≤ 0.02 for both), with adjusted OR 3.9 (p=0.03) for those with ≥ 21 days exposure to Ramadan and adjusted OR 4.3 (p=0.04) for third trimester exposure. Conversely longer Ramadan exposure and late trimester exposure were independently associated with a lower prevalence of neonatal hypoglycaemia (adjusted OR 0.4 and 0.3 for ≥ 21 days and third trimester exposure, respectively). Furthermore, neonatal hypoglycaemia decreased for the fasting period of > 15 h group (adjusted OR 0.2, p = 0.01). Conclusions Ramadan exposure is associated with reduced neonatal hypoglycaemia, with no effect on birthweight, implying more favourable glycaemic control. However, the fourfold excess of neonatal hyperbilirubinemia indicates a need for further study of Ramadan and GDM.

Safe threshold of capillary blood glucose for predicting early future neonatal hypoglycaemia in babies born to mothers with gestational diabetes mellitus, an observational, retrospective cohort study

Background There is increasing pressure to get women and babies home rapidly after birth. Babies born to mothers with gestational diabetes mellitus (GDM) currently get 24-h inpatient monitoring. We investigated whether a low-risk group of babies born to mothers with GDM could be defined for shorter inpatient hypoglycaemia monitoring. Methods Observational, retrospective cohort study conducted in a tertiary maternity hospital in 2018. Singleton, term babies born to women with GDM and no other risk factors for hypoglycaemia, were included. Capillary blood glucose (BG) testing and clinical observations for signs of hypoglycaemia during the first 24-h after birth. BG was checked in all babies before the second feed. Subsequent testing occurred if the first result was < 2.0 mmol/L, or clinical suspicion developed for hypoglycaemia. Neonatal hypoglycaemia, defined as either capillary or venous glucose ≤ 2.0 mmol/L and/or clinical signs of neonatal hypoglycaemia requiring oral or intravenous dextrose (lethargy, abnormal feeding behaviour or seizures). Results Fifteen of 106 babies developed hypoglycaemia within the first 24-h. Maternal and neonatal characteristics were not predictive. All babies with hypoglycaemia had an initial capillary BG ≤ 2.6 mmol/L (Area under the ROC curve (AUC) 0.96, 95% Confidence Interval (CI) 0.91–1.0). This result was validated on a further 65 babies, of whom 10 developed hypoglycaemia, in the first 24-h of life. Conclusion Using the 2.6 mmol/L threshold, extended monitoring as an inpatient could have been avoided for 60% of babies in this study. Whilst prospective validation is needed, this approach could help tailor postnatal care plans for babies born to mothers with GDM.

Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P &lt; 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

Neonatal Hypoglycaemia: A Never-Ending Story?

Neonatal hypoglycaemia is a common metabolic disorder presenting in the first days of life and one potentially preventable cause of brain injury. However, a universal approach to diagnosis and management is still lacking. The rapid decrease in blood glucose (BG) after birth triggers homeostatic mechanisms. Most episodes of hypoglycaemia are asymptomatic, and symptoms, when they occur, are nonspecific. Therefore, neonatologists are presented with the challenge of identifying infants at risk who might benefit from a rapid and effective therapy while sparing others unnecessary sampling and overtreatment. There is much controversy regarding the definition of hypoglycaemia, and one level does not fit all infants since postnatal age and clinical situations trigger different accepted thresholds for therapy. The concentration and duration of BG which cause neurological damage are unclear. Recognizing which newborn infants are at risk of hypoglycaemia and establishing protocols for treatment are essential to avoid possible deleterious effects on neurodevelopment. Early breastfeeding may reduce the risk of hypoglycaemia, but in some cases, the amount of breast milk available immediately after birth is insufficient or non-existent. In these situations, other therapeutic alternatives such as oral dextrose gel may lower the risk for NICU admissions. Current guidelines continue to be based on expert opinion and weak evidence. However, malpractice litigation related to neurodevelopmental disorders is frequent in children who suffered hypoglycaemia in the neonatal period even if they had other important factors contributing to the poor outcome. This review is aimed to help the practicing paediatricians and neonatologists to comprehend neonatal hypoglycaemia from physiology to therapy, hoping it will result in a rational decision-making process in an area not sufficiently supported by evidence.