Table 3. In-Hospital Treatments and Outcomes for Infants Surviving More Than 12 Hours After Birth.
| Variablesa | No./total (%), by gestational age in weeksb | Adjusted difference (95% CI)d | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 2013-2018 | 2008-2012c | |||||||||
| 22 (n = 159) | 23 (n = 856) | 24 (n = 1298) | 25 (n = 1546) | 26 (n = 1788) | 27 (n = 1943) | 28 (n = 2376) | 22-28 (n = 9966) | 22-28 (n = 8034) | ||
| Peridelivery interventions | ||||||||||
| Delivery room intubation | 153/159 (96.2) | 818/856 (95.6) | 1123/1298 (86.5) | 1215/1546 (78.6) | 1133/1787 (63.4) | 946/1943 (48.7) | 954/2374 (40.2) | 6342/9963 (63.7) | ||
| Delayed umbilical cord clamping or cord milkinge | 38/86 (44.2) | 146/450 (32.4) | 233/637 (36.6) | 296/756 (39.2) | 344/859 (40.0) | 402/930 (43.2) | 523/1163 (45.0) | 1982/4881 (40.6) | ||
| Interventions during hospitalization | ||||||||||
| Treatments withheld, limited, or withdrawn to limit caref | 57/159 (35.8) | 248/856 (29.0) | 226/1298 (17.4) | 190/1544 (12.3) | 121/1787 (6.8) | 97/1941 (5.0) | 66/2371 (2.8) | 1005/9956 (10.1) | ||
| Surfactant | 158/159 (99.4) | 849/856 (99.2) | 1241/1298 (95.6) | 1407/1546 (91.0) | 1480/1788 (82.8) | 1364/1943 (70.2) | 1458/2376 (61.4) | 7957/9966 (79.8) | ||
| Postnatal corticosteroid (systemic) | 50/154 (32.5) | 328/808 (40.6) | 443/1196 (37.0) | 379/1470 (25.8) | 284/1724 (16.5) | 197/1913 (10.3) | 110/2359 (4.7) | 1791/9624 (18.6) | 971/7936 (12.2) | 4.0 (3.1 to 4.9) |
| Inhaled nitric oxide | 55/159 (34.6) | 172/856 (20.1) | 230/1297 (17.7) | 171/1544 (11.1) | 147/1788 (8.2) | 126/1941 (6.5) | 108/2374 (4.5) | 1009/9959 (10.1) | ||
| Vitamin A | 70/159 (44.0) | 229/848 (27.0) | 309/1275 (24.2) | 340/1531 (22.2) | 370/1758 (21.0) | 279/1910 (14.6) | 202/2315 (8.7) | 1799/9796 (18.4) | ||
| Patent ductus arteriosus medicationg | 36/158 (22.8) | 278/855 (32.5) | 487/1296 (37.6) | 480/1544 (31.1) | 462/1786 (25.9) | 316/1941 (16.3) | 272/2374 (11.5) | 2331/9954 (23.4) | ||
| Patent ductus arteriosus surgery or cardiac catheterization for closure | 20/158 (12.7) | 121/855 (14.2) | 192/1295 (14.8) | 169/1543 (11.0) | 119/1787 (6.7) | 73/1941 (3.8) | 47/2374 (2.0) | 741/9953 (7.4) | ||
| Probioticse | 13/68 (19.1) | 31/391 (7.9) | 41/570 (7.2) | 53/715 (7.4) | 91/837 (10.9) | 89/908 (9.8) | 125/1141 (11.0) | 443/4630 (9.6) | ||
| Receipt of human milk in first 28 dh | 116/159 (73.0) | 711/848 (83.8) | 1140/1282 (88.9) | 1369/1514 (90.4) | 1661/1760 (94.4) | 1820/1928 (94.4) | 2202/2339 (94.1) | 9019/9830 (91.7) | ||
| Parenteral nutrition, median (IQR), d | 15 (7-38) [n = 158] | 25 (12-44) [n = 855] | 25 (14-40) [n = 1297] | 22 (14-35) [n = 1545] | 18 (13-30) [n = 1788] | 15 (11-24) [n = 1938] | 13 (10-20) [n = 2373] | 17 (11-30) [n = 9954] | ||
| Red blood cell transfusion | 156/159 (98.1) | 837/856 (97.8) | 1267/1298 (97.6) | 1471/1544 (95.3) | 1561/1788 (87.3) | 1345/1941 (69.3) | 1170/2374 (49.3) | 7807/9960 (78.4) | ||
| Mechanical ventilation | 159/159 (100.0) | 855/856 (99.9) | 1282/1298 (98.8) | 1476/1545 (95.5) | 1579/1786 (88.4) | 1466/1940 (75.6) | 1571/2367 (66.4) | 8388/9951 (84.3) | 6983/8030 (87.0) | −2.1 (−3.2 to −0.9) |
| Tracheostomy | 1/159 (0.6) | 5/856 (0.6) | 12/1298 (0.9) | 16/1545 (1.0) | 18/1788 (1.0) | 11/1941 (0.6) | 4/2374 (0.2) | 67/9961 (0.7) | ||
| Morbidities during hospitalization | ||||||||||
| NEC stage ≥IIAi | 19/159 (11.9) | 130/854 (15.2) | 150/1298 (11.6) | 178/1544 (11.5) | 144/1787 (8.1) | 140/1941 (7.2) | 129/2373 (5.4) | 890/9956 (8.9) | 825/8032 (10.3) | −1.6 (−2.5 to −0.8) |
| Surgery for NEC | 12/159 (7.5) | 78/854 (9.1) | 82/1298 (6.3) | 78/1544 (5.1) | 48/1787 (2.7) | 47/1941 (2.4) | 41/2373 (1.7) | 386/9956 (3.9) | ||
| Early-onset sepsis and/or meningitisj | 11/158 (7.0) | 38/856 (4.4) | 52/1298 (4.0) | 39/1545 (2.5) | 31/1787 (1.7) | 38/1941 (2.0) | 29/2372 (1.2) | 238/9957 (2.4) | 165/8032 (2.1) | 0.2 (−0.2 to 0.6) |
| Infants surviving >3 d | 133 | 779 | 1216 | 1481 | 1753 | 1913 | 2347 | 9622 | 7738 | |
| Late-onset sepsis and/or meningitisj | 61/132 (46.2) | 319/778 (41.0) | 407/1215 (33.5) | 379/1479 (25.6) | 322/1752 (18.4) | 242/1911 (12.7) | 181/2343 (7.7) | 1911/9610 (19.9) | 1890/7737 (24.4) | −4.9 (−6.0 to −3.7) |
| Cranial sonogram within 28 d | 136/159 (85.5) | 819/855 (95.8) | 1251/1298 (96.4) | 1501/1545 (97.2) | 1752/1788 (98.0) | 1905/1941 (98.1) | 2343/2375 (98.7) | 9707/9961 (97.5) | 7852/8034 (97.7) | −0.2 (−0.6 to 0.3) |
| Intracranial hemorrhage grade III or IVk | 52/136 (38.2) | 298/819 (36.4) | 308/1251 (24.6) | 260/1500 (17.3) | 202/1752 (11.5) | 143/1905 (7.5) | 123/2342 (5.3) | 1386/9705 (14.3) | 1149/7851 (14.6) | −1.0 (−1.9 to −0.1) |
| Shunt for posthemorrhagic hydrocephalus | 3/136 (2.2) | 21/819 (2.6) | 33/1251 (2.6) | 24/1501 (1.6) | 24/1752 (1.4) | 23/1905 (1.2) | 16/2342 (0.7) | 144/9706 (1.5) | ||
| Cranial imaging within 28 d or after 28 d and closest to 36 wk postmenstrual age | 136/159 (85.5) | 821/855 (96.0) | 1255/1298 (96.7) | 1507/1545 (97.5) | 1756/1788 (98.2) | 1913/1941 (98.6) | 2353/2375 (99.1) | 9741/9961 (97.8) | 7876/8034 (98.0) | −0.1 (−0.5 to 0.3) |
| Finding of cystic periventricular leukomalacia | 6/135 (4.4) | 64/820 (7.8) | 103/1254 (8.2) | 96/1505 (6.4) | 70/1755 (4.0) | 57/1911 (3.0) | 48/2351 (2.0) | 444/9731 (4.6) | 352/7872 (4.5) | −0.2 (−0.8 to 0.3) |
| Infants still hospitalized at 28 d | 77 | 609 | 1053 | 1352 | 1655 | 1813 | 2254 | 8813 | ||
| ROP examination | 70/77 (90.9) | 568/609 (93.3) | 1013/1053 (96.2) | 1307/1351 (96.7) | 1626/1655 (98.2) | 1786/1811 (98.6) | 2216/2253 (98.4) | 8586/8809 (97.5) | ||
| ROP | 65/70 (92.9) | 499/567 (88.0) | 871/1013 (86.0) | 922/1307 (70.5) | 944/1626 (58.1) | 752/1786 (42.1) | 660/2216 (29.8) | 4713/8585 (54.9) | 3821/6789 (56.3) | −2.1 (−3.5 to −0.7) |
| Severe ROP (stage ≥3) | 22/70 (31.4) | 216/567 (38.1) | 322/1013 (31.8) | 249/1307 (19.1) | 166/1626 (10.2) | 79/1786 (4.4) | 45/2216 (2.0) | 1099/8585 (12.8) | 839/6789 (12.4) | 0.5 (−0.1 to 1.2) |
| Intervention and/or treatment for ROPl | 19/69 (27.5) | 180/566 (31.8) | 242/1009 (24.0) | 164/1299 (12.6) | 96/1611 (6.0) | 40/1777 (2.3) | 20/2208 (0.9) | 761/8539 (8.9) | ||
| ROP status at discharge, transfer, death, or 120 d | ||||||||||
| Determined, favorable in both eyes | 6/70 (8.6) | 95/564 (16.8) | 255/1003 (25.4) | 403/1284 (31.4) | 589/1588 (37.1) | 685/1736 (39.5) | 859/2088 (41.1) | 2892/8333 (34.7) | ||
| Determined, severe ROP in 1 or both eyes | 13/70 (18.6) | 153/564 (27.1) | 197/1003 (19.6) | 132/1284 (10.3) | 85/1588 (5.4) | 32/1736 (1.8) | 21/2088 (1.0) | 633/8333 (7.6) | ||
| Undetermined in either eye (neither eye with severe ROP) | 51/70 (72.9) | 316/564 (56.0) | 551/1003 (54.9) | 749/1284 (58.3) | 914/1588 (57.6) | 1019/1736 (58.7) | 1208/2088 (57.9) | 4808/8333 (57.7) | ||
| Infants surviving to 36 wk postmenstrual agem | 64 | 559 | 1015 | 1302 | 1634 | 1823 | 2291 | 8688 | 6909 | |
| Evaluation for BPD | ||||||||||
| Oxygen use at 36 wkn | 50/64 (78.1) | 470/557 (84.4) | 769/1009 (76.2) | 837/1296 (64.6) | 822/1629 (50.5) | 722/1814 (39.8) | 637/2272 (28.0) | 4307/8641 (49.8) | 3064/6853 (44.7) | 4.3 (2.8 to 5.8) |
| Mode of support at 36 wko | ||||||||||
| No BPD | 6/64 (9.4) | 46/553 (8.3) | 145/984 (14.7) | 315/1266 (24.9) | 573/1554 (36.9) | 850/1725 (49.3) | 1325/2159 (61.4) | 3260/8305 (39.3) | ||
| Grade 1 | 9/64 (14.1) | 198/553 (35.8) | 358/984 (36.4) | 488/1266 (38.5) | 518/1554 (33.3) | 500/1725 (29.0) | 566/2159 (26.2) | 2637/8305 (31.8) | ||
| Grade 2 | 36/64 (56.3) | 209/553 (37.8) | 316/984 (32.1) | 340/1266 (26.9) | 347/1554 (22.3) | 278/1725 (16.1) | 216/2159 (10.0) | 1742/8305 (21.0) | ||
| Grade 3 | 13/64 (20.3) | 100/553 (18.1) | 165/984 (16.8) | 123/1266 (9.7) | 116/1554 (7.5) | 97/1725 (5.6) | 52/2159 (2.4) | 666/8305 (8.0) | ||
| Assisted ventilation by 36 wk postmenstrual age, median (IQR), dp | ||||||||||
| Total | 93 (81-95) [n = 63] | 81 (69-88) [n = 555] | 71 (57-81) [n = 996] | 57 (43-72) [n = 1291] | 44 (28-61) [n = 1617] | 29 (12-45) [n = 1810] | 17 (6-32) [n = 2268] | 41 (19-62) [n = 8600] | ||
| Invasive only | 65 (50-81) [n = 64] | 51 (36-70) [n = 557] | 37 (23-57) [n = 1003] | 23 (7-40) [n = 1295] | 8 (2-26) [n = 1627] | 2 (0-9) [n = 1812] | 1 (0-5) [n = 2276] | 7 (1-31) [n = 8634] | ||
| Length of hospitalization, median (IQR), d | ||||||||||
| All patients | 26 (7-142) [n = 159] | 121 (18-156) [n = 856] | 115 (82-148) [n = 1298] | 104 (83-129) [n = 1546] | 93 (75-116) [n = 1788] | 80 (65-98) [n = 1943] | 69 (56-85) [n = 2376] | 88 (63-117) [n = 9966] | ||
| Surviving infants only | 156 (135-217) [n = 60] | 143 (122-175) [n = 535] | 127 (108-156) [n = 972] | 110 (93-134) [n = 1266] | 96 (80-118) [n = 1608] | 82 (68-99) [n = 1787] | 70 (57-85) [n = 2267] | 93 (72-122) [n = 8495] | ||
Abbreviations: BPD, bronchopulmonary dysplasia; ROP, retinopathy of prematurity.
Distributions of the variables reported differed significantly across gestational age; adjusted P < .01 for all except adjusted P = .04 for tracheostomy, by Wald χ2, likelihood ratio χ2, or F test, adjusting for study center, small for gestational age, male sex, multiple gestation, and maternal race and ethnicity. Study center could not be included in models fit to vitamin A use and probiotic use because some centers reported no use.
Data are expressed as No./total (%) of infants unless otherwise indicated.
From Stoll et al.1 Infants included were restricted to those with birth weights of 401 g to 1500 g, consistent with Neonatal Research Network eligibility criteria during prior years. This criterion primarily restricted eligibility for infants born at 22 weeks’ gestational age. The current cohort includes infants born at 22-28 weeks’ gestational age with any birth weight, including 163 (1.5%) with birth weights less than 401 g and 79 (0.7%) with birth weights greater than 1500 g.
Where possible given data reported by Stoll et al, differences adjusted for gestational age are shown between the proportion reported for infants born at 22-28 weeks’ gestational age in the 2013-2018 cohort vs in 2008-2012 along with associated 95% confidence intervals for the difference. A positive difference indicates that the proportion increased in the 2013-2018 cohort compared with the 2008-2012 cohort; a negative difference indicates that the proportion decreased in the 2013-2018 cohort compared with the earlier cohort.
Collected beginning in 2016.
Treatments included intubation/ventilation, nutrition/hydration, and/or medication.
Patent ductus arteriosus medication included indomethacin, ibuprofen, and acetaminophen.
Human milk includes both maternal and donor milk.
Bell18 staging of necrotizing enterocolitis (NEC) as modified by Walsh and Kliegman19: stage IA, suspected NEC without gross hematochezia; stage IB, suspected NEC with gross hematochezia; stage IIA, definite NEC, mildly ill; stage IIB, definite NEC, moderately ill; stage IIIA, advanced NEC, severely ill, bowel intact; stage IIIB, advanced NEC, severely ill, bowel perforated.
Early-onset (≤72 hours) and late-onset (>72 hours) sepsis was defined by positive blood culture and appropriate therapy for 5 or more days or intent to treat if death occurred within 5 days. Early-onset and late-onset meningitis were defined by positive cerebrospinal fluid culture and appropriate therapy for 7 or more days or intent to treat if death occurred within 7 days. In 2008-2012, the reported proportions of early-onset and late-onset sepsis did not include meningitis. In the current cohort, 2 (0.8%) of 238 infants with early-onset sepsis and/or meningitis had meningitis alone. Of the 1911 infants with late-onset sepsis and/or meningitis, 24 (1.3%) had meningitis alone.
Intracranial hemorrhage was determined based on the cranial sonogram with the most severe findings performed within 28 days after birth and was classified by the criteria of Papile et al20: grade I, subependymal hemorrhage; grade II, intraventricular hemorrhage without ventricular dilatation; grade III, intraventricular hemorrhage with ventricular dilatation; grade IV, intraventricular hemorrhage with parenchymal hemorrhage.
Interventions and treatments for ROP included any of retinal ablation (laser and/or cryotherapy), scleral buckle, vitrectomy, and/or bevacizumab or other antivascular endothelial growth factor therapies.
Infants surviving to 36 weeks’ postmenstrual age include infants still in the hospital at 36 weeks (90%) or discharged home or transferred before 36 weeks.
For surviving infants who were discharged or transferred before 36 weeks’ postmenstrual age, BPD was defined as supplemental oxygen use at 36 weeks if known or use at discharge or transfer. Of the 8641 infants evaluated, 7782 (90%) were still in the hospital at 36 weeks’ postmenstrual age, 541 (6%) had been discharged home, and 318 (4%) had been transferred to another hospital after a median of 41 days in the birth hospital.
Based on the optimal definition (definition 15) from Jensen et al.21 This definition classifies BPD based on the mode of support received at 36 weeks’ postmenstrual age or at discharge home if earlier: no BPD, no support or breathing room air; grade 1, nasal cannula at a flow rate of 2 L/min or less; grade 2, nasal cannula at a flow rate of more than 2 L/min or noninvasive positive airway pressure; and grade 3, invasive mechanical ventilation. BPD was undefined for infants transferred prior to 36 weeks’ postmenstrual age unless status at 36 weeks was known. Of the 8305 infants evaluated, 7764 (93%) were still in the hospital at 36 weeks’ postmenstrual age, 538 (6%) had been discharged home, and 3 (<1%) had been transferred to another hospital.
Total includes high-frequency ventilation, conventional ventilation, nasal intermittent positive pressure ventilation, and/or continuous positive airway pressure. Invasive includes high-frequency and/or conventional ventilation.