Alpana Ghadge

Delayed versus Immediate Cord Clamping in Preterm Infants

Background The preferred timing of umbilical‐cord clamping in preterm infants is unclear. Methods We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late‐onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention‐to‐treat basis, accounting for multiple births. Results Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed‐clamping group and 9.0% in the immediate‐clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. Conclusions Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088.)

Clinicians in 25 countries prefer to use lower levels of oxygen to resuscitate preterm infants at birth

This study determined current international clinical practice and opinions regarding initial fractional inspired oxygen (FiO2) and pulse oximetry (SpO2) targets for delivery room resuscitation of preterm infants of less than 29 weeks of gestation.

Placental transfusion in preterm neonates of 30–33 weeks’ gestation: a randomized controlled trial

ObjectivesTo compare effect of placental transfusion by delayed cord clamping (DCC) or cord milking (CM) with early cord clamping (ECC) on a composite of mortality or abnormal neurological status at 40 weeks’ post-menstrual age (PMA) and 24–30 months’ chronological age in neonates of 30–33 weeks’ gestation.Study designRandomized, controlled trial.OutcomesA composite of mortality or abnormal neurological status at 40 weeks PMA and survival free of neurodevelopmental abnormalities at 24–30 months’ chronological age.ResultsA total of 461 neonates were randomized to placental transfusion (n = 233) or to ECC (n = 228). Among those assigned to placental transfusion group, 173 underwent DCC while in the remaining 60, CM was done. Incidence of mortality or abnormal neurological status at 40 weeks PMA (43 (18%) vs 35 (15%), RR (95% CI) 1.2 (0.8, 1.8), p = 0.4) and survival free of neurodevelopmental impairment at 24–30 months of chronological age (99 (47%) vs. 100 (50%); RR (95% CI): 0.9 (0.8, 1.2); P = 0.9) was similar between the study groups. The placental transfusion group showed a trend towards lower incidence of necrotizing enterocolitis.ConclusionIn 30–33 weeks’ gestation preterm neonates, placental transfusion as compared to early cord clamping resulted in similar mortality or abnormal neurological status at 40 weeks PMA and at 24–30 months of chronological age.

Protocol for the Lactoferrin Infant Feeding Trial (LIFT): a randomised trial of adding lactoferrin to the feeds of very-low birthweight babies prior to hospital discharge

Introduction Very-low birthweight (VLBW, <1500 g) infants comprise about 1%–1.4% of all births in high-income countries. Every year, about 3000 VLBW babies in Australia and New Zealand receive intensive care. Many die or else survive with severe brain injury, retinopathy, late-onset sepsis or necrotising enterocolitis (NEC), each of which carries substantial risk of disability. Methods and analysis This trial tests whether adding bovine lactoferrin (bLF) to feeds in VLBW infants improves (1) survival to hospital discharge free from brain injury, late-onset sepsis, NEC and treated retinopathy of prematurity (primary composite end point); (2) each component of the primary composite end point and (3) time to reach full enteral feeds, number of blood transfusions, chronic lung disease and length of hospital stay. It includes a cost-effectiveness analysis of bLF in improving survival free from major morbidity, and evaluates the effect of bLF on survival and developmental outcomes at 24 to 36 months corrected gestational age. This is a multicentre, two-arm, randomised trial comparing the treatment group receiving bLF added to breast milk or formula milk daily (up to 250 mg/kg/day bLF) versus the control group receiving no bLF supplementation. The intervention is administered until 34 completed weeks corrected gestation or for 2 weeks, whichever is longer, or until discharge home, if earlier. The target sample size of 1500 participants yields 85% power, at the two-sided 5% level significance, to detect a difference in proportions meeting the primary outcome assuming the true probability is 74% in controls and 80.5% in the bLF group. Ethics and dissemination This protocol was approved by Northern Sydney Local Human Research Ethics Committee in January 2017 (Version 2.0, Reference 1003-118M) and other relevant ethics committees. The findings of the trial will be disseminated through peer-reviewed journals and conference presentations. Trial registration number ACTRN12611000247976; Pre-results.

169 Hospital Mortality in 2,437 Infants in the Australian, New Zealand and UK Boost II Trials of Neonatal Oxygen Saturation Targeting

Background The optimal oxygen saturation (SpO2) for preterm infants is unknown. Three BOOST II trials in Australia, New Zealand and UK are comparing outcomes in infants < 28 weeks after randomisation to SpO2 targeting of 85–89% vs 91–95%, using masked oximeters.1 In interim analysis the high target increased 36 week survival in infants whose oximeter had been upgraded with new, more accurate software.2,3 Methods Pooled analysis of hospital mortality by target, overall and by old or new software. Results Abstract 169 Table 1 Hospital mortality of infants by SpO2 target overall SpO2 85–89% SpO2 91–95% Risk Ratio (95% CI) p value Hospital mortality 235/1220 (19.3%) 202/1217 (16.6%) 1.16 (0.98–1.38) 0.09 Abstract 169 Table 2 Hospital mortality of infants by SpO2 target, by old vs new software Old software New software SpO2 85–89% SpO2 91–95% Risk Ratio (95% CI) p value SpO2 85–89% SpO2 91–95% Risk Ratio (95% CI) p value Hospital mortality* 98/629 (15.6%) 109/630 (17.3%) 0.90 (0.70–1.16) 0.41 137/591 (23.2%) 93/587 (15.8%) 1.46 (1.15–1.85) 0.0015** There was no significant mortality difference between SpO2 targets overall. There was significant heterogeneity between old and new software on mortality (test for interaction p=0.006).* Using new software, targeting 91–95% increased hospital survival by 7.4% (from 76.8% to 84.2%) versus targeting 85–89% (p=0.0015).** Conclusions Pending the primary outcome of disability free survival at 2 years it appears wise not to target 85–89%. References Askie. BMC Pediatrics 2011; 11:6. Stenson. NEJM 2011; 364:1680–2. Johnston. Arch Dis Child Fetal Neonatal Ed. 2011; 96:429–33.