Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial.

Recommendations for umbilical cord management in intrauterine growth-restricted (IUGR) neonates are lacking. The present randomized controlled trial compared hemodynamic effects of umbilical cord milking (UCM) with delayed cord clamping (DCC) in IUGR neonates > 28 weeks of gestation, not requiring resuscitation. One hundred seventy IUGR neonates were randomly allocated to intact UCM (4 times squeezing of 20 cm intact cord; n = 85) or DCC (cord clamping after 60 s; n = 85) immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24 ± 2 h. Secondary outcomes assessed were anterior cerebral artery (ACA) and superior mesenteric artery (SMA) blood flow indices, right ventricular output (RVO), regional cerebral oxygen saturation (CrSO2) and venous hematocrit at 24 ± 2 h, peak total serum bilirubin (TSB), incidences of in-hospital complications, need and duration of respiratory support, and hospital stay. SVC flow was significantly higher in UCM compared to DCC (111.95 ± 33.54 and 99.49 ± 31.96 mL/kg/min, in UCM and DCC groups, respectively; p < 0.05). RVO and ACA/SMA blood flow indices were comparable whereas CrSO2 was significantly higher in UCM group. Incidences of polycythemia and jaundice requiring phototherapy were similar despite significantly higher venous hematocrit and peak TSB in UCM group. The need for non-invasive respiratory support was significantly higher in UCM group though the need and duration of mechanical ventilation and other outcomes were comparable. CONCLUSIONS:  UCM significantly increases SVC flow, venous hematocrit, and CrSO2 compared to DCC in IUGR neonates without any difference in other hemodynamic parameters and incidences of polycythemia and jaundice requiring phototherapy; however, the need for non-invasive respiratory support was higher with UCM. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2021/03/031864). WHAT IS KNOWN: • Umbilical cord milking (UCM) increases superior vena cava blood flow (SVC flow) and hematocrit without increasing the risk of symptomatic polycythemia and jaundice requiring phototherapy in preterm neonates compared to delayed cord clamping (DCC). • An association between UCM and intraventricular hemorrhage in preterm neonates < 28 weeks of gestation is still being investigated. WHAT IS NEW: • Placental transfusion by UCM compared to DCC increases SVC flow, regional cerebral oxygenation, and hematocrit without increasing the incidence of symptomatic polycythemia and jaundice requiring phototherapy in intrauterine growth-restricted neonates. • UCM also increases the need for non-invasive respiratory support compared to DCC.

Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial.

Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate.   Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia.   Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.

Serum Calcium and Melatonin Levels in Neonates Undergoing Phototherapy.

Phototherapy-induced hypocalcemia has been postulated to result from a decline in serum melatonin levels. The present observational study evaluated the effects of phototherapy on serum calcium and melatonin levels, and assessed their correlation, if any. Eighty-nine neonates with a total serum bilirubin levels of 14.1 ± 2.8 mg/dL were recruited at the mean age of 51.9 ± 21.7 h. After a median interquartile range (IQR) duration of phototherapy for 24.0 (24-25.5) h, serum calcium levels decreased significantly, from 9.6 ± 0.8 to 9.4 ± 0.6 mg/dL; p = 0.02, leading to asymptomatic hypocalcemia in 2.2% of the neonates. Median (IQR) serum melatonin levels also decreased from 187.8 (133.5-227.6) to 176.3 (145.6-202.5) pg/mL after phototherapy, the difference being statistically insignificant. No significant correlation was documented between the duration of phototherapy with calcium and melatonin levels. The authors conclude that phototherapy resulted in a small but significant reduction of serum calcium levels without any significant correlation with serum melatonin.

Effects of delayed cord clamping in intrauterine growth-restricted neonates: a randomized controlled trial.

The time of cord clamping in intrauterine growth-restricted (IUGR) neonates remains an area of uncertainty. This assessor-blinded randomized controlled trial compared the effects of delayed cord clamping (DCC) with early cord clamping (ECC) on the systemic blood flow (SBF) and cerebral hemodynamics in IUGR neonates of gestational age ≥28 weeks, not requiring resuscitation. Eligible newborns were randomized to DCC (cord clamping after 60 s; n=55) or ECC (cord clamping within 30 s; n=55) group immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24±2 h. The secondary outcome variables were right ventricular output (RVO), anterior cerebral artery (ACA) blood flow velocity (BFV), superior mesenteric artery (SMA)-BFV and venous hematocrit at 24±2 h, peak total serum bilirubin (TSB), incidences of polycythemia, intraventricular hemorrhage, respiratory distress, feeding intolerance, and necrotizing enterocolitis, outcome, duration of hospital stay, screening audiometry, and serum ferritin levels at the postnatal age of 3 months. Compared to ECC, DCC was associated with significantly higher SVC flow (101.22±21.02 and 81.27±19.12 mL/kg/min, in DCC and ECC groups, respectively; p<0.0001), and significantly increased RVO, SMA-BFV, venous hematocrit, and serum ferritin levels. Though peak TSB was significantly higher with DCC, duration of phototherapy was comparable. ACA-BFV, incidence of polycythemia, and other outcomes were comparable between the groups.Conclusions: DCC was a safe and beneficial intervention in IUGR infants with an improved SBF and SMA-BFV and an increased hematocrit and serum ferritin levels without higher incidences of polycythemia and requirement of phototherapy for significant hyperbilirubinemia.Trial registration: Clinical Trials Registry of India (CTRI/2019/05/018904) What is Known: • Delayed cord clamping (DCC) increases superior vena cava (SVC) blood flow in preterm neonates. • DCC increases hematocrit and serum ferritin in intrauterine growth-restricted (IUGR) neonates, but there may be an associated risk of polycythemia and neonatal hyperbilirubinemia. What is New: • DCC increases SVC blood flow, right ventricular output, superior mesenteric artery blood flow velocity, venous hematocrit, and serum ferritin in IUGR neonates. • Incidences of polycythemia and duration of phototherapy for significant neonatal hyperbilirubinemia do not increase with DCC.

Early versus late fortification of breast milk in preterm infants: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the effects of early fortification (EF) versus late fortification (LF) of breast milk (BM) on growth of preterm infants. Randomized and quasi-randomized controlled trials (RCTs) dealing with the effects of EF versus LF on growth parameters, incidence of adverse events, and duration of hospital stay in preterm infants were included. Data were pooled using the RevMan 5.3 software. Quality of evidence for predefined outcomes was analyzed by GRADE. Available evidence (3 RCTs, 309 preterm infants) showed no statistically significant difference between EF and LF of BM for any of the growth parameters-weight (standardized mean difference (SMD) 0.13; 95% confidence interval (CI) - 0.09, 0.36); length (SMD 0.02; 95% CI - 0.20, 0.25); and head circumference (SMD - 0.10; 95% CI - 0.33, 0.12). Total parenteral nutrition days were similar. Duration of hospital stay was significantly higher with EF (MD 4.29; 95% CI 0.84, 7.75) with a trend of non-significant increase in feed intolerance and necrotizing enterocolitis (NEC).Conclusion: Very low quality evidence did not find any significant difference in growth parameters of preterm infants in association with EF or LF of BM. A significant increase in hospital stay and non-significant increase in feed intolerance and NEC were associated with EF.PROSPERO registration number: CRD42019139235What is Known:• Fortification of breast milk with essential macro- and micronutrients is necessary for optimization of nutrition in preterm infants.• There is no consensus regarding the breast milk feeding volume at which fortification should be initiated.What is New:• Very low quality evidence showed no significant difference between early and late fortification of breast milk on growth parameters of preterm infants.• Early fortification was associated with non-significant increase in feed intolerance and necrotizing enterocolitis and a significant increase in hospital stay.

Correction to: Oral vitamin A supplementation in very low birth weight neonates: a randomized controlled trial.

The authors regret that Ethical approval section was incorrect in the original publication; the authors have requested that this be noted.

Oral vitamin A supplementation in very low birth weight neonates: a randomized controlled trial.

This randomized double-blind placebo-controlled trial evaluated the effects of early postnatal oral vitamin A supplementation (VAS) in 196 inborn very-low birth weight (VLBW) infants requiring respiratory support at 24 h of age. Eligible infants were randomized to receive aqueous syrup of vitamin A (10,000 IU of retinol/dose; n = 98) or placebo (n = 98) on alternate days for 28 days. Primary outcome variable was composite incidence of all-cause mortality and/or oxygen requirement for 28 days. Secondary outcome variables were safety/tolerability of VAS, serum retinol concentration at recruitment and day 28, duration of oxygen requirement and respiratory support and incidences of complications. On intention-to-treat analysis, composite incidence of all-cause mortality and oxygen requirement for 28 days was significantly lower in vitamin A group (relative risk (95% confidence interval), 0.440 (0.229-0.844); p < 0.05, number needed to benefit, 7). Requirement and duration of oxygen supplementation and non-invasive respiratory support, incidences of late-onset sepsis, patent ductus arteriosus, and duration of hospital stay were also significantly lower in vitamin A group. Serum retinol concentration improved significantly after VAS. No major adverse effect was observed.Conclusions: Early postnatal oral VAS was associated with better composite outcome of all-cause mortality and oxygen requirement without any major adverse effects.Clinical Trial Registration: Clinical Trials Registry of India (CTRI/2017/03/008131). What is Known: • Postnatal intramuscular vitamin A supplementation improves the survival, respiratory outcome and other morbidities in very low birth weight neonates without major adverse effects. • Limited studies on oral vitamin A supplementation did not document substantial benefits. What is New: • Early postnatal alternate-day oral vitamin A supplementation at the dose of 10,000 IU/dose for 28 days improves the composite outcome of death and oxygen requirement in very low birth weight neonates with respiratory distress • No major adverse effects were documented.

Determinants of Capillary Refill Time in Healthy Neonates.

OBJECTIVES: Traditionally Capillary refilling time (CRT) has been used as a widely accepted method to assess cardiac output and peripheral circulation in neonates. There are only few studies describing normal values and the correct method of recording CRT. The value of CRT is affected by various factors like ambient or skin temperature, age, site of measurement, duration as well as amount of pressure and inter observer variation. However, none of these have been standardized. Hence, we conducted this study to establish the normal value and factors affecting Capillary Refilling Time (CRT) in healthy neonates in Varanasi. DESIGN: Prospective observational study done over a period of 2 years. SETTING: Maternity wards and Neonatal intensive care unit of Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. PARTICIPANTS: Healthy neonates between 35-42 weeks of gestation staying with their mothers and admitted in neonatal intensive care unit. MATERIALS AND METHODS: CRT was measured by standard technique four times during first week of life on day 1, 3, 5 and 7. STATISTICS ANALYSIS: Student t-test was used for analysis. A p-value less than 0.05 was taken as statistically significant. RESULTS: The mean capillary refilling time (CRT) was 2.23 ± 0.37 seconds in healthy neonates during first week of life. We studied each neonate four times in first week of life. Significantly lower values of CRT were noted in low birth weight babies throughout first week in healthy neonates. Babies under phototherapy and radiant warmer had also shorter CRT values. Values were not affected by age, sex and gestation. CONCLUSION: The normal value of capillary refilling time (CRT) in healthy neonate is less than three seconds. The major determinants of CRT in healthy neonate are birth weight, radiant warmer and phototherapy. CRT alone in neonatal age is less informative haemodynamic parameter; it should be evaluated along with either blood pressure or oxygen saturation with pulse oxymeter. Further studies are needed to assess the reliability and validity of CRT as a clinical tool to measure perfusion in neonates.

Zinc supplementation for neonatal hyperbilirubinemia: a randomized controlled trial.

OBJECTIVE: To determine the efficacy of oral zinc for treatment of idiopathic neonatal hyperbilirubinemia in near-term and term (35-41 weeks) neonates. DESIGN: Randomized placebo-controlled trial. SETTING: Tertiary-care teaching hospital. PARTICIPANTS: Eighty newborns with idiopathic neonatal hyperbilirubinemia. INTERVENTION: Neonates were randomized to receive either oral zinc sulfate (10 mg/d) or placebo for 7 days. MAIN OUTCOME MEASURES: Primary: total serum bilirubin levels at 48 (±12) h, 96 (±12) h and 144 (±12) h after intervention. Secondary: duration of phototherapy, and serum zinc and copper levels. RESULTS: Baseline mean (SD) total serum bilirubin levels were 14.8 (3.8) and 14.4 (3.5) mg/dL in zinc and placebo groups, respectively. No significant differences were observed in total bilirubin levels between the two groups after the intervention. Mean (SD) total serum bilirubin levels in zinc and placebo groups were 13.9 (2.5) vs. 13.4 (1.9) mg/dL (mean difference 0.566; 95% CI -0.535, 1.668, P=0.038) at 48 h, 13.1 (2.7) vs. 12.8 (2.3) mg/dL (mean difference 0.234; 95% CI -1.011, 1.479, P =0.708) at 96 h and 8.0 (2.0) vs. 8.6 (1.2) mg/dL (mean difference -0.569, 95% CI -1.382, 0.242, P=0.166) at 144 h. Although the mean duration of phototherapy in the zinc group was less by 21.3 h (95% CI 11.6, 30.9, P=0.052), the difference was not significant. Post-intervention, serum zinc levels were significantly higher in the zinc-supplemented group while serum copper levels were comparable between the two groups. CONCLUSIONS: Oral zinc sulfate, in a dose of 10 mg/day, is not effective in the management of idiopathic neonatal hyperbilirubinemia.

Difference in cerebral blood flow velocity in neonates with and without hyperbilirubinemia.

PURPOSE: To evaluate the difference in cerebral blood flow velocity (CBFV) in neonates with and without hyperbilirubinemia. METHODS: CBFV of 70 healthy late-preterm and term newborns with unconjugated hyperbilirubinemia (UCH) reaching the threshold of phototherapy requirement was compared with 70 gestational- and postnatal age-matched controls without hyperbilirubinemia. Resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV) and vascular diameter were measured in internal carotid, vertebral and middle cerebral arteries by transcranial color Doppler ultrasound at the beginning of phototherapy, after 48-72h of starting phototherapy and at 5-7days after its stoppage. In controls CBFV was assessed once at inclusion. RESULTS: Both the groups were comparable. An increase in CBFV (decreased RI and PI, increased PSV and vasodilation) was observed in the UCH group. A further increase in CBFV was noticed after 48h of phototherapy. After 5-7days of stoppage of phototherapy, though there was a significant reduction in CBFV in mild-to-moderate UCH (serum bilirubin ⩽25mg/dL), in severe UCH (serum bilirubin >25mg/dL), CBFV remained increased. Four neonates developed features of acute bilirubin encephalopathy and had significantly higher CBFV compared to those with normal outcome. CONCLUSIONS: An increase in CBFV was observed in neonates with UCH compared to those without hyperbilirubinemia.

Efficacy of high-dose Lactobacillus rhamnosus GG in controlling acute watery diarrhea in Indian children: a randomized controlled trial.

AIM: To evaluate the effective dose of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhea (AWD) in Indian children. SETTING: Hospital-based study. DESIGN: Randomized, controlled, blinded trial. METHODS: All patients of AWD admitted over 1 year were included in the study. They were randomized into 3 groups to receive either only oral rehydration solution (ORS) (group A/control), ORS+LGG powder containing 10(10) colony forming units (CFU) (group B), or ORS+LGG powder containing 10(12) CFU (group C) twice daily for a minimum period of 7 days or until diarrhea stopped along with correction of dehydration. None of them received any other drug such as antibiotic or antidiarrheal medication. The duration and frequency of diarrhea and vomiting were studied. Data were analyzed by SPSS-10 software. RESULTS: The study comprised of 559 patients, group A/controls (n=185), group B (n=188), and group C (n=186). All the groups were similar with respect to age, number of breastfed infants, presentation with dehydration, degree of protein energy malnutrition, and rotavirus infection. The frequency and duration of diarrhea, requirement for intravenous therapy, and hospital stay were significantly lower in both the intervention groups compared with the controls. There was no significant difference between the 2 intervention groups. No complication was observed from the doses of LGG used. CONCLUSIONS: Both the doses of LGG (10(10) and 10(12) CFU) were equally effective to decrease the frequency and duration of diarrhea and reduction in hospital stay in patients of AWD.

Lipid peroxidation and antioxidants in neonatal septicemia.

Free radicals have been implicated in the pathogenesis of neonatal septicemia. The present study was planned to estimate the lipid peroxidation and antioxidant status in neonatal septicemia. The study was done to evaluate the lipid peroxidation and antioxidant status, both enzymatic and non-enzymatic in neonates with septicemia. This prospective study included 44 septicemic babies as cases and a group of 84 matched healthy babies formed the control. Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione peroxidase (GTPx), Catalase, Uric acid (UA) and Albumin (Alb) were estimated in the serum and compared between the groups. The statistical analysis was done by using SPSS-10 software. Neonates with septicemia had significantly higher levels of MDA, SOD, GTPx, and Catalase, while the levels of UA and Alb were significantly lower as compared to controls (p<0.001). Significantly elevated levels of MDA (p<0.05) and depressed levels of UA (p<0.001) were found in babies with late onset sepsis. Neonates who ultimately succumbed had significantly elevated levels of MDA, SOD, GTPx and Catalase, whereas levels of UA and Alb were significantly depressed (p<0.001). Neonates with sepsis are handicapped in terms of their defense mechanism against free radicals. The utility of supplementation of antioxidant enzymes in neonates with septicemia needs further evaluation.