Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia.

OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

Comparison of Three Modalities of Feeding in Preterm Infants ≤32 Weeks and ≤1,250 G: A Randomized Controlled Trial.

OBJECTIVE: Early establishment of enteral feeds is desirable in very preterm infants, but it may be associated with feeding intolerance. Several feeding methods have been studied with no strong evidence to suggest the preferred feeding method to establish early full enteral feeds. We studied three modalities of feeding in preterm infants ≤32 weeks and ≤1,250 g: continuous infusion (CI), intermittent bolus by infusion (IBI), and intermittent bolus by gravity (IBG) for their effect on time to reach full enteral feeds of 180 mL/kg/d. STUDY DESIGN: We randomized 146 infants, 49 infants in each CI and IBI group and 48 infants in the IBG group. In the CI group, feeds were delivered by an infusion pump continuously over 24 hours. In the IBI group, feeds were given every 2 hours and infused over 15 minutes by an infusion pump. In the IBG group, feeds were delivered by gravity over 10 to 30 minutes. The intervention was continued till infants reached direct breast/cup feeds. RESULTS: The mean (standard deviation) gestation in CI, IBI, and IBG groups were 28.4 (2.2), 28.5(1.9), and 28.6 (1.8) weeks, respectively. The time to reach full feeds in CI, IBI, and IBG were not significantly different (median [interquartile range]: 13 [10-16], 11.5 [9-17], and 13 [9.5-14.2] d, respectively, p = 0.71). The proportions of infants who developed feeding intolerance in CI, IBI, and IBG were similar (n [%]: 21 [51.2%], 20 [52.6%], and 22 [64.7%], respectively, p = 0.45). There was no difference in necrotizing enterocolitis ≥2 (p = 0.80), bronchopulmonary dysplasia (p = 0.86), intraventricular hemorrhage ≥2 (p = 0.35), patent ductus arteriosus requiring treatment (p = 0.44), retinopathy of prematurity requiring treatment (p = 0.51), and growth parameters at discharge. CONCLUSION: In preterm infants, ≤32 weeks of gestation and birth weight ≤1,250 g, there was no difference in time to reach full enteral feeds in the three modalities of feeding. This study is registered with Clinical Trials Registry India (CTRI) and the registration number is CTRI/2017/06/008792. KEY POINTS: · Gavage feeding in preterm infants is either continuous or intermittent bolus feeding.. · Intermittent bolus feeding was evaluated in a controlled time by infusion over 15 minutes.. · The time to reach full feeds was comparable for all three methods..

Neonatologist-Performed Ultrasound-Guided Internal Jugular Vein Cannulation.

We retrieved data of ultrasound-guided neonatal internal jugular vein (IJV) cannulations done between November, 2020 and March, 2021. Of the 33 ultrasound-guided IJV cannulation in neonates, 32 were successful with overall success rate of 97%. Median (IQR) number of attempts per insertion was 2 (1,3.5). There were no major complications observed during the insertion of the catheter. In one instance, inadvertent carotid artery puncture was encountered, without significant bleeding.

Amplitude integrated EEG: how much it helps in prognostication in neonatal encephalopathy?

INTRODUCTION: Neonatal encephalopathy (NE) is associated with a high risk of adverse neurological outcomes. Several neurodiagnostic tests have been evaluated to predict the prognosis. Amplitude integrated Electroencephalogram (aEEG) is now being commonly used for bedside evaluation of cerebral function. There is limited data on the role of aEEG for prognostication in NE, from resource-limited settings. OBJECTIVE: To evaluate the predictive ability of aEEG for abnormal neurological outcomes in neonatal encephalopathy or neonates with encephalopathy. METHODS: Neonates above 35 weeks of gestation admitted to NICU in a tertiary care hospital with a diagnosis of encephalopathy were enrolled. Clinical characteristics severity of encephalopathy and seizures were recorded. Amplitude integrated recording was started at admission and continued till recovery of trace to normal or for 10 days. The primary outcome was death or abnormal neurological status at 3-6 months of age. The study was registered in the Clinical Trial Registry of India (CTRI/2013/05/003612). RESULTS: The incidence of NE was 6% of total admission. Moderate and severe encephalopathy occurred in 58 and 39% of babies respectively. Hypoxic-ischemic encephalopathy was the most common cause. Clinical seizures occurred in 91% of cases. An abnormal aEEG trace was observed in 51 (76.1%) infants with NE. For adverse neurological outcomes at an age average of 4.5 months of age, aEEG had a sensitivity, specificity, NPV, and PPV of 100, 54.2, 100, and 77.5, respectively. CONCLUSIONS: Clinical staging and aEEG has good predictive ability to detect an adverse neurological outcome. aEEG improves the ability to predict abnormal outcome in babies with moderate encephalopathy. Early recovery of aEEG abnormality correlates with better neurodevelopmental outcomes.KEY MESSAGESWhat's known: aEEG is a useful modality to assess neurodevelopmental outcomes however data from developing countries is lacking.What's new: aEEG monitoring in babies in neonatal encephalopathy may improve the prediction of abnormal neurological outcomes in babies with moderate encephalopathy.

Duration of Antibiotic Therapy in Neonatal Gram-negative Bacterial Sepsis-10 Days Versus 14 Days: A Randomized Controlled Trial.

BACKGROUND: Optimal duration of antibiotic therapy in Gram-negative bacterial (GNB) sepsis in non-VLBW infants has not been specifically evaluated in previous studies. METHODS: This was an open labeled noninferiority randomized controlled trial. Non-VLBW infants with GNB sepsis without meningitis whose blood culture were sterile after day 7 of treatment and who were in clinical remission on day 9 of appropriate antibiotic were randomized to short duration (SDR) group and long duration (LDR) group. Infants in SDR group and LDR group received antibiotic therapy for 10 days and 14 days respectively. Primary objective was to compare treatment failure. Secondary objectives were to compare duration of hospitalization, complications of intravenous (IV) therapy and its duration, episodes of new-onset sepsis and all-cause mortality. RESULTS: Of 222 infants with GNB sepsis, 58 eligible infants were randomized in each group and 113 of these were analyzed. There was no difference in proportion of infants with multidrug-resistant (MDR) organism in SDR versus LDR group [33(60%) versus 32(55.1%) (P = 0.84)]. There were no treatment failures in either group. Median (IQR) duration of hospital stay was higher in LDR group as compared with SDR group: 20(18, 23) versus 16(13, 20) days (P < 0.001). Infants in LDR group required IV therapy for a longer duration as compared with SDR group mean (SD): 15.2(1.2) versus 10.9(0.8) days (P < 0.001). Median (IQR) episodes of extravasation were higher in LDR group: 5(4.7) versus 3(2.3) (P < 0.001). There was no difference in episodes of phlebitis and hematoma. No infants had died on follow up. CONCLUSION: In suitably selected non-VLBW infants with Gram-negative sepsis, 10 days therapy is noninferior to 14 days therapy.

Macronutrient analysis of human milk and factors associated with its composition in mothers of preterm infants ≤ 32 weeks.

We conducted an exploratory longitudinal study to evaluate the macronutrient composition of human milk in mothers delivering very preterm infants ≤ 32 weeks over the first 4 weeks of lactation and the association of human milk composition with maternal and neonatal factors A total of 213 human milk samples collected in the morning between 8 am and 12 pm from 60 eligible mothers were analyzed on 7 (n = 60), 14 (n = 60), 21 (n = 52), and 28 (n = 41) days of lactation by infrared transmission spectroscopy. The true protein content decreased significantly over 4 weeks (mean difference (95% confidence interval)) (MD (95% CI)) week 1 and week 4 = 0.2 g (0.037 to 0.363, P = 0.009)). On the contrary, the mean fat and calorie content showed significant increase over time (MD (95% CI)) = - 1.03 g (- 1.719 to - 0.343, P = 0.001) and - 9.0 kcal/dl (- 15.170 to - 2.830, P = 0.001), respectively). There was no difference in the carbohydrate content of human milk over 4 weeks. Macronutrient composition was independent of maternal parity, mode of delivery, pre-pregnancy body mass index, umbilical artery Doppler flows, previous breast feeding experience, neonatal centile status, gestation, and infant's weight at birth. Multiple regression analysis of human milk composition with mother's dietary components showed no significant association. CONCLUSION : We conclude that in mothers who deliver very preterm infants ≤ 32 weeks, true protein content decreased, fat and calorie content increased, and carbohydrate content remained stable in human milk during first 4 weeks of lactation. Human milk macronutrient composition was independent of various maternal and neonatal factors including maternal body mass index and dietary intake. TRIAL REGISTRATION : CTRI/2017/02/007895 What is Known: • Preterm human milk has high temporal and inter-individual variation in the macronutrient composition. What is New: • In mothers who deliver very preterm infants < 32 weeks, true protein content decreases, fat and calorie content increases, and carbohydrate content remains stable in human milk during first 4 weeks of lactation. • Human milk macronutrient composition is independent of various maternal and neonatal factors including maternal body mass index and dietary intake.

Use of Point of Care Ultrasound for Confirming Central Line Tip Position in Neonates.

OBJECTIVE: To assess feasibility of ultrasound (USG) evaluation of tip position of central catheter in neonates and to determine agreement between radiograph and USG-based assessments. METHODS: This prospective observational study was conducted in a tertiary neonatal intensive care unit from April, 2019 to August, 2019. Point of care USG and radiograph were performed on infants who underwent central line placement. Agreement between the two was determined using Kappa statistics. RESULTS: Of the 141 central catheters insertions performed, USG was performed for 65 central catheters. On USG, catheter tip position could be assessed and defined in 62 (95%) of cases. Of these 62 central lines, 24 (38.7%) were defined as optimally placed on radiograph and 20 (32.2%) were defined as optimally placed on USG. There was excellent agreement between radiographic and USG assessment of catheter tip position [K (95% CI) = 0.86 (0.73-0.99), P <0.001]. All 38 lines found to be mal-positioned on radiograph were assessed as sub-optimal on USG as well. CONCLUSIONS: Point of care USG has excellent agreement with radiography for confirming central line tip position.

Correction to: Neonatal Sepsis: Mortality and Morbidity in Neonatal Sepsis due to Multidrug-Resistant (MDR) Organisms: Part 1.

The article Neonatal Sepsis: Mortality and Morbidity in Neonatal Sepsis due to Multidrug-Resistant (MDR) Organisms: Part 1, written by Chand Wattal, Neelam Kler, J. K. Oberoi, Anurag Fursule, Anup Kumar and Anup Thakur, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 11 December 2019 with open access.

Neonatal Sepsis: Mortality and Morbidity in Neonatal Sepsis due to Multidrug-Resistant (MDR) Organisms: Part 1.

The major causes of emergence of multidrug-resistant organisms (MDRO) in neonatal sepsis include empiric antibiotic prescriptions, unregulated use of over-the-counter drugs, high incidence of healthcare associated infections (HAI), lack of awareness about antibiotic stewardship program and under staffing of neonatal intensive care units. In general, mortality due to MDRO sepsis is significantly higher as compared to non MDRO sepsis. Reported morbidities include prolonged use of total parenteral nutrition, need for central venous catheter, invasive ventilation, increased duration of hospital stay and neurologic sequelae.

Normative Data of Optimally Placed Endotracheal Tube by Point-of-care Ultrasound in Neonates.

OBJECTIVE: To derive normative data of the distance between optimally placed endotracheal tube tip and arch of aorta by ultrasound in neonates across different weight and gestation. DESIGN: Cross-sectional study. SETTING: Tertiary care neonatal intensive care unit from April 2015 to May 2016. PARTICIPANTS: All neonates requiring endotracheal intubation were eligible for the study. METHODS: During intubation, insertional length was determined using weight-based formula. The distance between endotracheal tube tip and arch of aorta was measured by ultrasound. Endotracheal tube position was confirmed by chest radiograph. RESULTS: Out of 133 enrolled infants, 101 (75.9%) had optimally placed endotracheal tubes. The mean (SD) distance between endotracheal tube tip and arch of aorta by ultrasound was 0.78 (0.21) cm in infants <1500 g and 1.04 (0.32) cm in infants ≥1500 g. The regression equation to estimate insertional length from weight, crown heel length (CHL), occipito-frontal circumference (OFC), nasal tragus length (NTL) and sternal length (SL) were Wt(kg)+4.95, 0.15×CHL(cm)+0.57, 0.22×OFC(cm)+0.49, 0.82× NTL(cm)+1.24 and 0.75×SL(cm)+2.26, respectively. CONCLUSIONS: Our study reports normative data of the distance between optimally placed endotracheal tube tip and arch of aorta by ultrasound in neonates. The distance between endotracheal tube tip and arch of aorta increases with increase in weight and gestation. Insertional length correlates strongly with all the anthropometric parameters.

Impact of Quality Improvement Program on Expressed Breastmilk Usage in Very Low Birth Weight Infants.

OBJECTIVE: To improve the usage of expressed breast milk in very low birth weight infants admitted in the neonatal intensive care unit of a tertiary centre in India. METHODS: Between April 2015 and August 2016, various Plan-do-act-study cycles were conducted to test change ideas like antenatal counselling including help of brochure and video, post-natal telephonic reminders within 4-6 hours of birth, standardization of Kangaroo mother care, and non-nutritive sucking protocol. Data was analyzed using statistical process control charts. RESULTS: 156 very low birth weight infants were delivered during the study period, of which 31 were excluded due to various reasons. Within 6 months of implementation, the proportion of very low birth weight infants who received expressed breast milk within 48 hours improved to 100% from 38.7% and this was sustained at 100% for next 8 months. The mean time of availability and volume of expressed breast milk within 48 hours, improved gradually from 73.3 h to 20.9 h and 4.7 mL to 15.8 mL, respectively. The mean proportion of expressed breast milk once infant reached a feed volume of 100 mL/kg/day also improved from 61.3% to 82.3%. CONCLUSIONS: Quality improvement interventions showed promising results of increased expressed breast milk usage in very low birth weight infants.

Early versus delayed cord clamping in small for gestational age infants and iron stores at 3 months of age - a randomized controlled trial.

BACKGROUND: Delayed cord clamping is the standard of care in infants not requiring resuscitation; however effects of cord clamping strategies have not been evaluated systematically in small for gestational age (SGA) infants. The primary objective was to compare effects of delayed cord clamping (DCC) and early cord clamping (ECC) on serum ferritin at 3 months in SGA infants born at ≥35 weeks. The secondary objectives were to compare hematological parameters, clinical outcomes in neonatal period and growth at 3 months of age. METHODS: All eligible infants with fetal growth restriction were randomized to two groups, DCC at 60 s or ECC group in which the cord was clamped immediately after birth. RESULTS: Total of 142 infants underwent randomization and subsequently 113 infants underwent definite inclusion. At 3 months, the median (IQR) serum ferritin levels were higher in DCC group, compared to ECC; 86 ng/ml (43.35-134.75) vs 50.5 ng/ml (29.5-83.5), p = 0.01. Fewer infants had iron deficiency in DCC group compared to ECC group; 9 (23.6%) vs 21 (47.7%), p = 0.03 [NNT being 4; 95% CI (2-25)].The proportion of infants with polycythemia was significantly higher in DCC group; 23 (41.81) % vs 12 (20.6%), p = 0.01. There was no difference in proportion of infants with symptomatic polycythemia or those who underwent partial exchange transfusions. Clinical outcomes and mortality were similar. CONCLUSIONS: DCC improves iron stores in SGA infants ≥35 weeks at 3 months of age without increasing the risk of symptomatic polycythemia, need for partial exchange transfusions or morbidities associated with polycythemia. TRIAL REGISTRATION: Our trial was retrospectively registered on 29th May 2015 through Clinical trials registry India. Registration number: CTRI 2015/05/005828 .

Effect of Differential Enteral Protein on Growth and Neurodevelopment in Infants <1500 g: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to determine whether higher enteral protein intake leads to improved head growth at 40 weeks postmenstrual age (PMA) in preterm infants <32 weeks or 1500 g. METHODS: Randomized controlled trial in which 120 infants were assigned to either group A with higher enteral protein intake achieved by fortification with higher protein containing fortifier (1 g/100 mL expressed breast milk) or to group B with lower enteral protein intake where fortification was done with standard available protein fortifier (0.4 g /100 mL expressed breast milk). RESULTS: The mean (standard deviation) protein intake was higher in group A as compared to group B; 4.2 (0.47) compared with 3.6 (0.37) g ·â€Škg ·â€Šday, P < 0.001. At 40 weeks PMA, the mean (standard deviation) weekly occipitofrontal circumference gain was significantly higher in group A as compared to group B; 0.66 (0.16) compared with 0.60 (0.15) cm/week (mean difference 0.064, 95% confidence interval [0.004-0.123], [P = 0.04]). Weight growth velocity in group A was 11.95 (2.2) g ·â€Škg ·â€Šday as compared to 10.78 (2.6) g ·â€Škg ·â€Šday in group B (mean difference 1.10, 95% confidence interval [0.25-2.07], [P = 0.01]). No difference was observed in the length between the 2 groups. There was no difference in growth indices and neurodevelopmental outcomes at 12 to 18 months corrected age in the 2 groups. CONCLUSIONS: Fortification of expressed human milk with fortifier containing higher protein results in better head growth and weight gain at 40 weeks PMA in preterm infants <32 weeks or 1500 g without any benefits on long-term growth and neurodevelopment at 12 to 18 months corrected age (CTRI/2014/06/004661).