During the study period 10,476 infants 401-1000g BW and ≥ 23 and ≤ 30 weeks estimated GA were managed at 19 participating academic centers. After excluding outborn infants (n=1209), those with major congenital anomalies (n=242), infants who were not candidates for CPR and mechanical ventilation (n=331), and those missing data related to chest compressions or medications in the delivery- room (n=9), 8685 infants comprised the study cohort (; available at www.jpeds.com
). Among these infants, 1333 (15%) received DR-CPR and 7352 (85%) did not. Demographic factors among infants who did and did not receive DR-CPR are compared in . No differences were found in proportions of multiple births between DR-CPR and No DR-CPR infants. Infants whose mothers had hypertension or had received antenatal steroids were less likely to receive DR-CPR. Antepartum hemorrhage, vaginal breech delivery, younger GA, lower BW, and male sex increased the likelihood of receiving DR-CPR. There were more black and fewer Hispanic infants in the DR-CPR group.
Flow diagram of patient selection
Demographic and maternal clinical characteristics of infants who received DR-CPR vs those with No DR-CPR
By bivariate analysis, DR-CPR infants experienced more death within 12 hours of birth, had more early onset sepsis, more pneumothorax, pulmonary hemorrhage, Grade 3 or 4 IVH, BPD and use of postnatal steroids than infants who did not receive DR-CPR (). No difference was found in proportions of infants with PDA, PVL, late-onset sepsis, or NEC. includes the adjusted OR and 95% CI for each short term outcome for all infants receiving DR-CPR. Results of adjusted analyses indicated similar associations as unadjusted analyses except pulmonary hemorrhage did not reach significance after logistic modeling. Among DR-CPR infants who died during the initial hospitalization before 120 days, 38% died within 12 hours, 44% by 24 hours, 61% by 72 hours, and 88% by day 28.
Short-Term and long-term outcomes of infants who received DR-CPR vs those with No DR-CPR
DR-CPR recipients had higher rates of death by 18-22 month follow-up, more NDI, and thus more composite NDI or death according to bivariate analysis (). The individual components of NDI such as MDI < 70, PDI < 70, moderate or severe cerebral palsy and hearing aid in both ears were higher in DR-CPR infants although there was no difference in blindness. DR-CPR infants also had lower mean ± sd MDI (76±18 (n=587) vs 80±18 (n=4420), p<0.0001) and PDI (80±20 (n=574) vs 84±18 (n=4375), p<0.0001) scores. Adjusted analyses for neurodevelopmental outcomes were similar to bivariate analyses () except for MDI < 70 which no longer reached significance. DR-CPR increased the risk of death by 18-22 months follow-up, NDI at 18-22 months, NDI or Death, PDI < 70, moderate or severe CP and need for hearing aid in both ears. There were too few cases of blindness in both eyes to perform logistic modeling for this variable.
Outcome data for death or NDI were available for 84% of study patients. Infants lost to follow-up were of higher GA (26.2±1.8 vs 26.0±1.7 wks, p=0.0003) and BW (797±138 vs 786±134 g, p=0.0091) compared with those who completed follow-up. Infants lost to follow-up had similar rates of DR-CPR compared with those who completed the follow-up visit (11% vs 12%, p=0.26). Those lost to follow-up had less PDA (39 vs 44%, p=0.0002) and IVH Grade 3 or 4 (8 vs 12%, p<0.0001) and were more likely to have been discharged prior to 120 days in the hospital (84 vs 82%, p=0.047) but had similar rates of pneumothorax, PVL, NEC, BPD and use of postnatal steroids.
Of the previously described 1333 DR-CPR infants, 9 were missing 5 minute Apgar score data. This left a cohort of 1324 DR-CPR infants for further analysis of associations between low 5 minute Apgar score and outcomes: 271 (20%) infants with 5 minute Apgar < 2 and 1053 (80%) with 5 minute Apgar ≥ 2. Perinatal and demographic factors for DR-CPR infants with 5 minute Apgar < 2 and 5 minute Apgar ≥ 2 infants are compared in . DR-CPR infants with 5 minute Apgar < 2 were less likely to be exposed to maternal hypertension and antenatal steroids than those with 5 minute Apgar ≥ 2, but more likely to be of younger GA, lower BW and male sex. Racial distribution between groups did not differ.
Demographic characteristics for all infants who received DR-CPR and had 5 minute Apgar < 2 versus ≥ 2
DR-CPR infants with 5 minute Apgar < 2 were more likely to die before 12 hours of life or by hospital day 120 in both unadjusted and adjusted analyses (). They were also more likely to suffer Grade 3 or 4 IVH and develop BPD compared with those with higher 5 minute Apgar scores. There were no significant differences in early-onset sepsis, pneumothorax, pulmonary hemorrhage, PDA, PVL, late-onset sepsis, NEC or use of postnatal steroids with either unadjusted or adjusted analyses.
Short-term and long-term outcomes for all infants who received DR-CPR and had 5 minute Apgar < 2 versus ≥ 2
Outcomes at 18-22 months for infants with 5 minute Apgar < 2 versus ≥ 2 are also shown in . Mortality was higher in DR-CPR infants with 5 minute Apgar < 2 by 18-22 month follow-up compared with those with 5 minute Apgar ≥ 2; however, there were no differences in NDI or the individual components of NDI. The combined NDI or death outcome was available for 87% of DR-CPR recipients and was greater in the low 5 minute Apgar group. DR-CPR infants lost to follow-up had similar proportions of 5 minute Apgar < 2 (13 versus 12%, p>0.99) compared with those who presented for follow-up. Odds ratios and 95% CI for long-term outcomes for DR-CPR infants with 5 minute Apgar < 2 following logistic regression are included in . Similar to the bivariate analysis, increased risk of death by time of follow-up and the combined NDI or death outcome remained significant and NDI, MDI < 70 and PDI < 70 did not.
Rates of DR-CPR differed among network centers and ranged from 7% to 28%; the percentage of infants receiving DR-CPR increased with decreasing GA (; available at www.jpeds.com
Proportion of ELBW infants receiving DR-CPR by A, center and B, gestational age. Note: There were center differences (p<0.0001) and gestational age differences (p<0.0001) in the proportion of infants who needed DR-CPR.