Glucose levels in first 3 days and neurodevelopmental outcome at 1 year in low birth weight infants: A cohort study

Background: Definition of neonatal hypoglycemia is still controversial. Objective: To find the effect of blood glucose (BG) levelsin the first 3 days of life, on developmental outcome at 1 year in low birth weight neonates <2000 g. Methods: A prospective cohortstudy was conducted in tertiary level neonatal intensive care unit and follow-up clinic in south India. Intramural neonates admittedfrom September 2009 to August 2010 were enrolled. Perinatal and neonatal variables were recorded. Respiratory support, fluids,and feeding management were based on the standard protocols. BG was measured within 2 h, then 6 hourly for 72 h by glucometerand BG <50 mg% was analyzed by hexokinase method. Infants were followed until 1 year corrected age and development age(DA) assessed by Developmental Assessment Scales for Indian Infants (DASII). Motor and mental DA at various BG levelswere compared. Composite outcome of motor or mental developmental delay; or cerebral palsy or hearing impairment or visualimpairment was analyzed, and logistic regression analysis was performed. Results: The mean birth weight and gestation of the studygroup (n=129) was 1493 g and 32.5 weeks. The 10th centile of BG in the first 72 h was 51 mg%. BG below 10th centile was seen in60 infants. The mean motor and mental DA of the infants by DASII assessment at 1 year was 11.3 and 11.5 months, respectively.The motor DA and mental DA were significantly higher until 50 mg% lowest BG level, and positive correlation was seen (r=0.26motor, 0.2 mental DA). Mean BG level, the presence of symptoms; number of episodes or small for gestation did not influence theDA. The adjusted odds for poor composite outcome when BG was below 51 mg% is 2.83 (0.65-12.3). Conclusion: Even thoughhigh-risk neonates with BG <51 mg% have a lower motor DA and mental DA at 1 year, than neonates with BG >50 mg%; othermorbidities do determine their composite outcome

The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial

Background The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants’ lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. Methods/design SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children’s Abilities-Revised (PARCA-R) at 2 years of corrected age. Discussion There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. Trial registration The protocol is registered at www.clinicaltrials.gov (NCT05907317; registered 18 June 2023)

Cerebral oximetry monitoring versus usual care for extremely preterm infants: a study protocol for the 2-year follow-up of the SafeBoosC-III randomised clinical trial

Background: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks' postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment. Methods: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks' postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children's Abilities-Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all. Discussion: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data-driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow-up study. As funding is limited, a pragmatic approach is necessary

Gastric residual volumes versus abdominal girth measurement in assessment of feed tolerance in preterm neonates : a randomized controlled trial

Background: Preterm neonates often have feed intolerance that needs to be differentiated from necrotizing enterocolitis. Gastric residual volumes (GRV) are used to assess feed tolerance but with little scientific basis. Purpose: To compare prefeed aspiration for GRV and prefeed measurement of abdominal girth (AG) in the time taken to reach full feeds in preterm infants. Methods: This was a randomized controlled trial. Infants with a gestational age of 27 to 37 weeks and birth weight of 750 to 2000 g, who required gavage feeds for at least 48 hours, were included. Infants were randomized into 2 groups: infants in the AG group had only prefeed AG measured. Those in the GRV group had prefeed gastric aspiration obtained for the assessment of GRV. The primary outcome was time to reach full enteral feeds at 150 mL/kg/d, tolerated for at least 24 hours. Secondary outcomes were duration of hospital stay, need for parenteral nutrition, episodes of feed intolerance, number of feeds withheld, and sepsis. Results: Infants in the AG group reached full feeds earlier than infants in the GRV group (6 vs 9.5 days; P = .04). No significant differences were found between the 2 groups with regard to secondary outcomes. Implications for Practice: Our research suggests that measurement of AG without assessment of GRV enables preterm neonates to reach full feeds faster than checking for GRV. Implications for Research: Abdominal girth measurement as a marker for feed tolerance needs to be studied in infants less than 750 g and less than 26 weeks of gestation

Efficacy of modified Tochen’s formula for optimum endotracheal tube placement in low birth weight neonates- an RCT

<div>Abstract:</div><div>Objective: To study the effectiveness of modified Tochen’s formula (hereafter known as the alternative formula) when compared to Tochen’s formula for optimal placement of endotracheal tubes in LBW neonates.</div><div>Study Design: A randomized controlled trial conducted in 70 neonates. Neonates requiring intubation for ventilation, with a confirmatory chest radiograph, were included in the study. They were intubated using Tochen’s formula (birth weight in kg + 6cm) or Alternative formula (birth weight in kg + 5cm). Tube tip placement was verified and modified, if necessary, after auscultation. The incidence of inadequate placement and optimum length of ET insertion were estimated from the chest radiographs. Incidence of adverse events in the two groups were noted.</div><div>Results: A total number of 92 babies were eligible for the study. One family refused consent and twenty-one families could not be approached and hence not included in study. A total of 70 neonates were randomized and included in the study; 34 in Tochen’s group and 33 in alternative formula group. Baseline characteristics between the two groups had no statistically significant differences (p->0.05).</div><div>Measurements in the alternative formula group were significantly (p - 0.006) closer to the optimal position (distance from optimum - 0.50 cm ± 0.41) when compared to Tochen’s group (distance from optimum - 0.86 cm ± 0.06) The adverse events were significantly (p- 0.005) greater in the group that was intubated using Tochen’s formula (16 of 34, 47.05%) when compared to the group where the alternative formula was applied (5 of 33, 15.15%). Though the percentage of optimum (8 of 33, 24.24%) and adequate placements (29 of 33, 87.87%) of the ET tube was higher in the group of the alternative formula when compared to the optimal (3 of 34, 8.82%) and adequate placement (24 of 34, 70.58%) of ET tube in the Tochen’s group, this was not statistically significant (p- >0.05). The depth of ET placement was found to be overestimated in the Tochen’s group as compared to the group of the alternative formula</div><div>Conclusion: The incidence of adequate and optimal placement of ET tube was higher in alternative formula group and the distance from optimal was significantly smaller when compared to the Tochen’s group. The adverse events were significantly fewer in the alternative formula group. Hence, the use of the alternative formula in low birth weight babies may enable the more accurate placement of ET tubes in low birth weight babies when compared to the Tochen’s formula.</div><div><br></div

Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial

Importance: Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population. Objective: To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates. Design, setting, and participants: This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin in extremely premature neonates conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 874 extremely premature neonates born at 24 to 27 weeks' gestation who were enrolled in the PENUT study. Secondary analysis was performed in November 2021. Exposures: Primary exposure was peak FB during the first 14 postnatal days. The FB was calculated as percent change in weight from birth weight (BW) as a surrogate for FB. Main outcomes and measures: The primary outcome was mechanical ventilation on postnatal day 14. The secondary outcome was a composite of severe bronchopulmonary dysplasia (BPD) or death. Results: A total of 874 neonates (449 [51.4%] male; mean [SD] BW, 801 [188] g; 187 [21.4%] Hispanic, 676 [77.3%] non-Hispanic, and 11 [1.3%] of unknown ethnicity; 226 [25.9%] Black, 569 [65.1%] White, 51 [5.8%] of other race, and 28 [3.2%] of unknown race) were included in this analysis. Of these 874 neonates, 458 (52.4%) received mechanical ventilation on postnatal day 14, and 291 (33.3%) had severe BPD or had died. Median peak positive FB was 11% (IQR, 4%-20%), occurring on postnatal day 13 (IQR, 9-14). A total of 93 (10.6%) never decreased below their BW. Neonates requiring mechanical ventilation at postnatal day 14 had a higher peak FB compared with those who did not require mechanical ventilation (15% above BW vs 8% above BW, P < .001). On postnatal day 3, neonates requiring mechanical ventilation were more likely to have a higher FB (5% below BW vs 8% below BW, P < .001). The median time to return to BW was shorter in neonates who received mechanical ventilation (7 vs 8 days, P < .001) and those with severe BPD (7 vs 8 days, P < .001). After adjusting for confounding variables, for every 10% increase in peak FB during the first 14 postnatal days, there was 103% increased odds of receiving mechanical ventilation at postnatal day 14 (adjusted odds ratio, 2.03; 95% CI, 1.64-2.51). Conclusions and relevance: In this secondary analysis of a randomized clinical trial, peak FB was associated with mechanical ventilation on postnatal day 14 and severe BPD or death. Fluid balance in the first 3 postnatal days and time to return to BW may be potential targets to help guide management and improve respiratory outcomes

Caffeine and kidney function at two years in former extremely low gestational age neonates

BackgroundExtremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months. MethodsSecondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates 30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used. Results598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m(2) (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25). ConclusionsLonger caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status. ImpactIn participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age.When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD.More work is necessary to understand the long-term impact of caffeine on the developing kidney

Additional file 1 of Cerebral oximetry monitoring versus usual care for extremely preterm infants: a study protocol for the 2-year follow-up of the SafeBoosC-III randomised clinical trial

Additional file 1

Cerebral Oximetry Monitoring in Extremely Preterm Infants

BACKGROUND The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.)