Early Breathing in Very Preterm Infants during Deferred Cord Clamping (DCC) Is Related to Gestational Age and Is Not Independently Associated with Important Neonatal Outcomes: A 5-Year Cohort Study.

Deferred cord clamping (DCC) has been associated with reduced mortality in preterm infants, and a period of at least 30 s has been recommended before clamping. However, preterm infants assessed as being in need of resuscitation have often had earlier cord clamping. In this study, we aimed to compare neonatal outcomes for preterm infants undergoing DCC who established early breathing movements compared to those who were not breathing. After a 5 yr recruitment period, we recently completed the ABC study, in which preterm infants <31 weeks undergoing 50 s of DCC who were not breathing by 15 s of age were randomised into two groups: one received intermittent positive pressure ventilation (IPPV) and the other was a standard group, which received no breathing support. The outcomes in the two groups were similar, and for the present analysis, the groups were combined. Infants in the ABC study were compared with the cohort excluded from the original ABC study because they were breathing by 15 s (called the Breathing Before Clamping or BBC group). There were significant differences in demographics between the ABC and BBC groups. Spontaneous preterm labour was more common in the BBC group, and these infants were more likely to be delivered vaginally. Gestational age and birth weight were significantly higher in the BBC group (p < 0.01). Soon after birth, Apgar scores were significantly higher in the BBC group, with a lower base deficit on first obtained blood gas, and a smaller proportion were intubated in the delivery room. Fewer BBC infants were hypothermic (<36.5 °C) on admission. Multivariate regression analysis indicated whether infants were breathing or not at 15 s of age was linked predominantly to gestation. Important neonatal outcomes and a composite of these outcomes (mortality, severe intraventricular haemorrhage, bronchopulmonary dysplasia) were not significantly different between the ABC and BBC groups (odds ratio for the composite outcome was 1.77 CI 0.84-3.76 corrected for gestation). For very preterm infants undergoing DCC, important neonatal outcomes were related to gestational age and not independently associated with early breathing. There was a small group (7% of total) who were deemed compromised at birth and did not undergo DCC. These infants had significantly worse neonatal outcomes.

Effect of Breathing Support in Very Preterm Infants Not Breathing During Deferred Cord Clamping: A Randomized Controlled Trial (The ABC Study).

OBJECTIVE: To determine if providing respiratory support to very preterm infants who fail to breathe regularly during deferred cord clamping (DCC) decreased red cell transfusion. STUDY DESIGN: Infants less than 31 weeks of gestation undergoing DCC who were apneic or not breathing regularly at 15 seconds underwent stratified randomization. Pale, limp, and nonresponsive infants were excluded. The standard group received gentle stimulation in a neutral position for 50 seconds; the intervention group received intermittent positive pressure ventilation via face mask and T piece from 20 to 50 seconds of age with a fractional inspired oxygen of 0.3. The primary outcome was the proportion transfused, with a secondary composite outcome of death, severe intraventricular hemorrhage, or chronic lung disease. RESULTS: Of 311 assessed infants, 113 met the inclusion criteria and were studied; 57 received the intervention and 56 standard treatment. Patient characteristics were similar. Overall, 105 infants (93%) received the intended 50 seconds DCC (54 in the intervention group and 51 in the standard group). Rates of transfusion were similar (28% vs 30% in the intervention vs control groups), as were rates of the composite outcome (46% vs 38% in the intervention vs the control arms; P = .45). CONCLUSIONS: Providing breathing support during 50 seconds of DCC in this single-center cohort seemed to be safe and feasible, but did not decrease the transfusion rates or improve outcomes. TRIAL REGISTRATION: http://www.anzctr.org.au/ACTRN12615001026516.aspx.

The Assisted Breathing before Cord Clamping (ABC) Study Protocol.

Major physiologic changes occur during the transition after birth. For preterm infants, current understanding favours allowing the initial changes to occur prior to cord clamping. Amongst other improved outcomes, systematic reviews have indicated a significant reduction in neonatal blood transfusions following delayed cord clamping. This may be due to a placental transfusion, facilitated by the onset of respiration. If breathing is compromised, placental transfusion may be reduced, resulting in a greater red cell transfusion rate. We designed a randomised trial to investigate whether assisting respiration in this high-risk group of babies would decrease blood transfusion and improve outcomes. The Assisted Breathing before Cord Clamping (ABC) study is a single-centre randomised controlled trial. Preterm infants < 31 weeks that have not established regular breathing before 15 s are randomised to a standard or intervention group. The intervention is intermittent positive pressure ventilation via T piece for 30 s, whilst standard management consists of 30 s of positioning and gentle stimulation. The cord is clamped at 50 s in both groups. The primary outcome is the proportion of infants in each group receiving blood transfusion during the neonatal admission. Secondary outcomes include requirement for resuscitation, the assessment of circulatory status and neonatal outcomes.

Provision of respiratory support compared to no respiratory support before cord clamping for preterm infants.

BACKGROUND: Placental transfusion (by means of delayed cord clamping (DCC), cord milking, or cord stripping) confers benefits for preterm infants. It is not known if providing respiratory support to preterm infants before cord clamping improves outcomes. OBJECTIVES: To assess the efficacy and safety of respiratory support provided during DCC compared with no respiratory support during placental transfusion (in the form of DCC, milking, or stripping) in preterm infants immediately after delivery. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 5), MEDLINE via PubMed (1966 to 19 June 2017), Embase (1980 to 19 June 2017), and CINAHL (1982 to 19 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA: Randomized, cluster randomized, or quasi-randomized controlled trials enrolling preterm infants undergoing DCC, where one of the groups received respiratory support before cord clamping and the control group received no respiratory support before cord clamping. DATA COLLECTION AND ANALYSIS: All review authors assisted with data collection, assessment, and extraction. Two review authors assessed the quality of evidence using the GRADE approach. We contacted study authors to request missing information. MAIN RESULTS: One study fulfilled the review criteria. In this study, 150 preterm infants of less than 32 weeks' gestation undergoing 60 second DCC were randomized to a group who received respiratory support in the form of continuous positive airway pressure (CPAP) or positive pressure ventilation during DCC and a group that did not receive respiratory support during the procedure. Mortality during hospital admission was not significantly different between groups with wide confidence intervals (CI) for magnitude of effect (risk ratio (RR) 1.67, 95% CI 0.41 to 6.73). The study did not report neurodevelopmental disability and death or disability at two to three years of age. There were no significant differences between groups in condition at birth (Apgar scores or intubation in the delivery room), use of inotropic agents (RR 1.25, CI 0.63 to 2.49), and receipt of blood transfusion (RR 1.03, 95% CI 0.70 to 1.54). In addition, there were no significant differences in the incidences of any intraventricular haemorrhage (RR 1.50, 95% CI 0.65 to 3.46) and severe intraventricular haemorrhage (RR 1.33, 95% CI 0.31 to 5.75). Several continuous variables were reported in subgroups depending on method of delivery. Unpublished data for each group as a whole was made available and showed peak haematocrit in the first 24 hours and duration of phototherapy did not differ significantly. Overall, the quality of evidence for several key neonatal outcomes (e.g. mortality and intraventricular haemorrhage) was low because of lack of precision with wide CIs. AUTHORS' CONCLUSIONS: The results from one study with wide CIs for magnitude of effect do not provide evidence either for or against the use of respiratory support before clamping the umbilical cord. A greater body of evidence is required as many of the outcomes of interest to the review occurred infrequently. Similarly, the one included study cannot answer the question of whether the intervention is or is not harmful.

Effect of delayed cord clamping (DCC) on breathing and transition at birth in very preterm infants.

BACKGROUND: The effects of delayed cord clamping (DCC) on transition in preterm infants are important as this procedure is becoming increasingly recommended. The aim of this study was to compare the effects of DCC with an historical cohort. METHOD: In this observational study, outcomes for infants ≤ 29 weeks were compared with a group born before the introduction of DCC. The intended intervention was DCC for 40s. Primary outcomes were the need for resuscitation and intubation in infants undergoing DCC, whilst taking note of their breathing during the procedure. Neonatal morbidities were analysed, including the association between breathing during DCC and outcome. RESULTS: There were 62 infants in the DCC group, and 62 who received immediate cord clamping (ICC). Maternal and infant characteristics including gestational age (p = 0.76) and birth weight (p = 0.74) between groups were not significantly different. 70% of the DCC group breathed regularly at birth. Comparing the DCC and ICC groups, there was no significant difference in 1 min and 5 min Apgar scores or in the number requiring intubation at birth (p = 0.88). Likewise, admission temperatures were similar (p = 0.57). There was a significant increase in the rate of chronic lung disease in the DCC group (p = 0.013). When comparing the infants who breathed during DCC with the non-breathers; the non-breathing group was more likely to be intubated (p = 0.01), have chronic lung disease (p = 0.02), and severe intraventricular haemorrhage (p = 0.02). CONCLUSION: DCC in these very preterm infants was well tolerated and the majority established spontaneous respiration whilst DCC was occurring. Infants who did not breathe during DCC had worse outcomes.