A randomized controlled trial of fluid supplementation in term neonates with severe hyperbilirubinemia

OBJECTIVE: To evaluate the effectiveness of fluid supplementation in decreasing the rate of exchange transfusion and the duration of phototherapy in term neonates with severe nonhemolytic hyperbilirubinemia. STUDY DESIGN: This was a randomized controlled trial conducted in a tertiary care referral unit in northern India. Seventy-four term neonates with severe nonhemolytic hyperbilirubinemia (total serum bilirubin > 18 mg/dL [308 micromol/L] to < 25 mg/dL [427 micromol/L]). The subjects were randomized to an "extra fluids" group (intravenous fluid supplementation for 8 hours and oral supplementation for the duration of phototherapy; n = 37) or a control group (n = 37). RESULTS: At inclusion, 54 infants (73%) had high serum osmolality, including 28 (75%) in the extra fluids group and 26 (70%) in the control group. The proportion of infants who underwent exchange transfusion was lower in the extra fluids group than in the control group: 6 (16%) versus 20 (54%)(P = .001; relative risk = 0.30; 95% confidence interval = 0.14 to 0.66). The duration of phototherapy was also shorter in the extra fluids group: 52 +/- 18 hours versus 73 +/- 31 hours (P = .004). CONCLUSION: Fluid supplementation in term neonates presenting with severe hyperbilirubinemia decreased the rate of exchange transfusion and duration of phototherapy.     

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial

Aim: To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). Methods: In this double‐blind, randomized, controlled trial, full ‐ term newborns (≥37 weeks), appropriate for gestational age, with severe non‐haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. Results: Forty‐two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. Conclusion: In full‐term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.     

Multicenter randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis

OBJECTIVE: To determine whether therapy with intravenous immunoglobulin G (IVIG) would decrease mortality in neonatal sepsis. SETTING: Three tertiary care neonatal intensive care units in the city of Bangalore. METHODS: All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled. Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded. The neonates were randomized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo. The rest of the treatment including antibiotics and supportive care was as per the treating physician's decision. The main outcome variable was survival. RESULTS: The trial was carried out over a period of 8 months and recruited 58 neonates. Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group, and one baby who received only one dose of IVIG was excluded from the analysis. Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm. The neonates in the therapy and placebo groups were comparable in terms of birth weight (2144+/-675 g vs. 2072+/-682 g), gestation (37.0+/-3.56 vs. 35.8+/-3.52 weeks), sex distribution, duration of stay, and number requiring ventilation. The placebo group had a significantly higher number of babies with positive blood culture. Seven babies in each group died (p>0.05). There was no significant benefit in using IVIG (OR 1.0; 95% CI 0.25-4.07) (p = 0.74). CONCLUSION: In the sample studied therapy with IVIG did not reduce mortality in neonatal sepsis     

Effect of multisensory stimulation on analgesia in term neonates: a randomized controlled trial

Many attempts have been made to obtain safe and effective analgesia in newborns. Oral glucose-water has been found to have analgesic properties in neonates. We investigated whether other sensory stimulation added to oral glucose provided more effective analgesia than oral glucose alone. In a randomized prospective double-blind trial, we studied 120 term newborns during heel prick. The babies were divided randomly into six groups of 20, and each group was treated with a different procedure during heel prick: A) control; B) 1 mL 33% oral glucose given 2 min before the heel prick; C) sucking; D) 1 mL 33% oral glucose plus sucking; E) multisensory stimulation including 1 mL 33% oral glucose (sensorial saturation); F) multisensory stimulation without oral glucose. Sensorial saturation consisted in massage, voice, eye contact, and perfume smelling during heel prick. Each heel prick was filmed and assigned a point score according to the Douleur Aigu? du Nouveau-né (DAN) neonatal acute pain scale. Camera recording began 30 s before the heel prick, so it was impossible for the scorers to distinguish procedure A (control) from B (glucose given 2 min before), C (sucking water) from D (sucking glucose), and E (multisensory stimulation and glucose) from F (multisensory stimulation and water) from the video. Procedure E (multisensory stimulation and glucose) was found to be the most effective procedure, and the analgesia was even more effective than that produced by procedure D (sucking glucose). We conclude that sensorial saturation is an effective analgesic technique that potentiates the analgesic effect of oral sugar. It can be used for minor painful procedures on newborns.     

布拉氏酵母菌联合光疗治疗新生儿高胆红素血症的疗效：前瞻性随机对照研究

目的 探讨布拉氏酵母菌联合光疗治疗新生儿高胆红素血症的疗效。方法 将2018年1~12月入院治疗的高胆红素血症新生儿随机分为观察组（n=61）和对照组（n=63）。观察组给予光疗+布拉氏酵母菌散,对照组给予光疗+安慰剂,比较两组的治疗效果。治疗72 h后收集患儿粪便样本,通过16s rRNA高通量测序方法分析比较两组新生儿肠道菌群特征。结果 观察组和对照组治疗前总胆红素水平差异无统计学意义（P > 0.05）。观察组治疗24、48、72 h后的总胆红素水平均显著低于对照组（P < 0.05）。观察组需要再次给予光疗的新生儿比例（12例,20%）显著低于对照组（47例,75%）（P < 0.05）。治疗72 h后观察组肠道内拟杆菌属丰度较对照组高（P < 0.05）,大肠埃希菌属和葡萄球菌属丰度较对照组低（P < 0.05）。结论 光疗联合布拉氏酵母菌治疗对于降低高胆红素血症新生儿胆红素水平及预防黄疸退而复现有较好的疗效。布拉氏酵母菌可能通过调节患儿肠道菌群改善治疗疗效。     

Orlistat treatment of unconjugated hyperbilirubinemia in Crigler-Najjar disease: a randomized controlled trial

Unconjugated hyperbilirubinemia in Crigler-Najjar (CN) disease is conventionally treated with phototherapy and phenobarbital. Orlistat treatment increases fecal fat excretion and decreases plasma unconjugated bilirubin (UCB) concentrations in Gunn rats, the animal model for CN disease. We determined in CN patients the effects of orlistat treatment on plasma UCB concentrations, and on fecal excretion of fat and UCB. A randomized, placebo-controlled, double-blind, cross-over trial was conducted in 16 patients, simultaneous with their regular treatment (phototherapy, n = 11, and/or phenobarbital, n = 6). Patients received orlistat or placebo, each for 4-6 wk. Compared with placebo, orlistat increased fecal fat excretion (+333%) and fecal UCB excretion (+43%). Orlistat treatment significantly decreased plasma UCB concentration (-9%). In 7 of 16 patients, the decrease in plasma UCB levels was clinically relevant (>10%, mean 21%). In patients with a clinically relevant response, plasma UCB concentrations during orlistat were strongly, negatively correlated with fecal fat excretion (r = -0.93). Clinically relevant response to orlistat treatment was not correlated with age, sex, CN type, BMI, or co-treatment with phototherapy or phenobarbital, but appeared correlated with a relatively lower dietary fat intake. In conclusion, orlistat treatment decreases plasma UCB concentrations, particularly in a subgroup of CN patients. Dietary fat intake may determine the responsiveness to orlistat treatment.     

Seeing through the blind! Ability of hospital staff to differentiate morphine from placebo, in neonates at a placebo controlled trial

AIM: To investigate whether professional training and/or clinical experience affect the ability of caregiver to assess clinical signs of pre-emptive morphine analgesia. METHODS: In the Neurological Outcomes & Pre-emptive Analgesia In Neonates trial preterm infants undergoing mechanical ventilation were randomized to receive continuous infusion, either of morphine or placebo blinded. Staff from centres in Sweden (Stockholm and Orebro) completed an assessment form. RESULTS: A total of 360 assessment forms were collected from 52 neonates. In 59% of the cases, caregivers correctly identified patients group. Comparable proportion of answers were correct between physicians, nurses and assistant nurses (63, 60 and 54%, respectively, p = 0.60). Staff with Neonatal intensive care unit experience <1 year identified 63%, as compared to 65% for working 1-5 year, and 55% that has been working >5 years (p = 0.28). Staff's ability to correctly identify group assignment was reduced by amount of additional morphine (p < 0.01) and severity of illness (p = 0.01). CONCLUSIONS: Clinical medical staffs, including neonatologists, have great difficulties in assessing the presence and severity of pain. Further studies should focus on the methods for assessment of prolonged pain in preterm neonates, define the effects of adequate analgesia, and investigate the clinical factors that may alter neonatal responses to acute and prolonged pain.     

Comparison of analgesic effect of direct breastfeeding, oral 25% dextrose solution and placebo during 1st DPT vaccination in healthy term infants: A randomized, placebo controlled trial

Objective

To compare analgesic effect of direct breast feeding, 25% dextrose solution and placebo as we give 1st intramuscular whole cell DPT injection to 6week — 3month old infants.

Design

Randomized, placebo controlled trial.

Setting

Immunization clinic of Department of Pediatrics, LLRM Medical College.

Participants

Infants coming for their 1st DPT vaccination were randomized in to three groups of 40 each.

Outcome measures

The primary outcome variable was the duration of cry after vaccination. Secondary outcome variables were Modified Facial Coding Score (MFCS) and latency of onset of cry.

Results

120 babies were equally enrolled in breast feed group, 25% dextrose fed group and distilled water fed group. Median (interquartile range) of duration of cry was significantly lower in breast fed (33.5 (17–54) seconds) and 25% dextrose fed babies (47.5 (31–67.5) seconds) as compared to babies given distilled water (80.5 (33.5–119.5) seconds) (P<0.001). MFCS at 1 min and 3 min was significantly lower in direct breast fed and dextrose fed babies.

Conclusions

Direct breastfeeding and 25% dextrose act as analgesic in young infants undergoing DPT vaccination in young infants less than 3 month of age.     

布拉氏酵母菌联合光疗治疗新生儿高胆红素血症的疗效：前瞻性随机对照研究

目的 探讨布拉氏酵母菌联合光疗治疗新生儿高胆红素血症的疗效。方法 将2018年1~12月入院治疗的高胆红素血症新生儿随机分为观察组（n=61）和对照组（n=63）。观察组给予光疗+布拉氏酵母菌散,对照组给予光疗+安慰剂,比较两组的治疗效果。治疗72 h后收集患儿粪便样本,通过16s rRNA高通量测序方法分析比较两组新生儿肠道菌群特征。结果 观察组和对照组治疗前总胆红素水平差异无统计学意义（P > 0.05）。观察组治疗24、48、72 h后的总胆红素水平均显著低于对照组（P < 0.05）。观察组需要再次给予光疗的新生儿比例（12例,20%）显著低于对照组（47例,75%）（P < 0.05）。治疗72 h后观察组肠道内拟杆菌属丰度较对照组高（P < 0.05）,大肠埃希菌属和葡萄球菌属丰度较对照组低（P < 0.05）。结论 光疗联合布拉氏酵母菌治疗对于降低高胆红素血症新生儿胆红素水平及预防黄疸退而复现有较好的疗效。布拉氏酵母菌可能通过调节患儿肠道菌群改善治疗疗效。     

Routine neonatal postextubation chest physiotherapy: a randomized controlled trial

OBJECTIVE: To test the effects of a neonatal postextubation programme on the incidence of postextubation collapse and adverse outcomes. METHODS: A randomized controlled trial was carried out at the Mater Mothers' Hospital, Brisbane. Mechanically ventilated infants were randomized into one of two groups, physiotherapy group--which involved a regimen of chest wall percussion and oropharyngeal suctioning and control group - which involved suctioning without the percussion unless indicated. Chest X-rays were taken at 6 h and at 24 h postextubation. The primary outcome measure was postextubation collapse as determined by a paediatric radiologist blinded to the group allocation. RESULTS: One hundred and seventy-seven neonates were enrolled in the trial between 1997 and 1999. After an interim analysis, the trial was stopped early. No statistically significant difference was shown in the rate of postextubation collapse (15 of 87 (17.2%) physiotherapy group and 17 of 86 (19.8%) control group (P = 0.85)). No differences were shown between the groups in the number of apnoeic or bradycardic events, duration of requirement for supplemental oxygen or the need for re-intubation within 24 h postextubation. CONCLUSION: The results of this trial suggest that a routine neonatal postextubation chest physiotherapy programme for all infants is not indicated. There was no evidence that chest physiotherapy is associated with any adverse outcomes.     

Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial

OBJECTIVE: To study whether prophylactic theophylline can reduce the incidence and/or severity of renal failure in term infants with perinatal asphyxia. STUDY DESIGN: Term neonates with severe perinatal asphyxia were randomized to receive a single dose of either theophylline (study group, n = 40) or placebo (control group, n = 30) during the first hour of life. Daily weight, output/input ratio, 24-hour fluid intake, and urine volumes were recorded during the first 5 days of life. Those infants with asphyxial renal failure were followed up for 1 year. RESULTS: The incidence of severe renal dysfunction was increased in the control group. Creatinine clearance was higher and excretion of beta 2 microglobulin (beta2M) was lower in the theophylline group. Conversely, the glomerular filtration rate was lower in the control group. In infants with renal failure, serum creatinine and creatinine clearance returned to normal in the neonatal period, and the increased beta2M excretion normalized by age 6 weeks. CONCLUSIONS: A single dose of theophylline within the first hour of birth in term neonates with perinatal asphyxia results in a significant decrease in serum creatinine level and urinary excretion of beta2M, along with an increase in creatinine clearance.