Of the 244 neonates included, 89 (36%) were born at 22 weeks, and 155 (64%) were born at 23 weeks (Fig. 1).
Fig. 1Distribution of patients according to gestational age at birth and study Epoch.
Compared to the 2015–2017 epoch, the subsequent epochs had fewer multiple gestations, less chorioamnionitis, more hypertension, and more antenatal steroid use. The neonates did not differ between epochs regarding birth weight, race, sex, and mode of delivery (Table 1).
Table 1 Neonates’ and pregnant individuals’ baseline characteristics according to Epoch.Amongst all live births, the odds ratio of receiving antenatal steroids was 3.8 (95% CI 1.8–7.8), p = 0.0004 in the 2018–2019 epoch and 2.7 (95% CI 1.3–5.5), p = 0.007 in the 2020–2023 epoch, compared to the 2015–2017 epoch.
Provision of intensive careAmongst neonates born at 22–23 weeks, 39 (61%), 80 (84%), and 76 (89%) received intensive care in the 2015–2017, 2018–2020, and 2021–2023 epochs, respectively. The odds ratio of receiving intensive care was 3.4 (95% CI 1.6–7.1), p = 0.0009, in the 2018–2020 epoch and 5.4 (95% CI 2.3–12.6), p < 0.0001, in the 2021–2023 epoch, as compared to the 2015–2017 epoch. This increased odds ratio of providing intensive care is driven by neonates born at 22 weeks gestation (Table 2); 0/19 (0%), 26/36 (72%), and 28/34 (82%) received intensive care in the 2015–2017, 2018–2020, and 2021–2023 epochs, respectively.
Table 2 Odds ratio of provision of intensive care according to gestational age and Epoch.SurvivalNext, we assessed the impact of our standardization on survival by gestational age, the primary outcome. We included only neonates who received intensive care (n = 195). During the entire study period, 83 (43%) neonates survived (Table 3).
Table 3 Characteristics according to the primary outcome, survival.Given that no neonate born at 22 weeks gestation received intensive care in the 2015–2017 epoch, none survived. However, five (19%) neonates survived during the 2018–2020 epoch, and seven (25%) neonates survived in the 2021–2023 epoch. For neonates born at 23 weeks gestation, survival remained stable across the study epochs: 19 (49%), 28 (52%), and 24 (50%) survived in the 2015–2017, 2018–2020, and 2021–2023 epochs, respectively, p = 0.95.
More neonates born at 22 weeks receiving intensive care did not negatively impact the overall survival of those who are born at 22–23 weeks gestation. In a logistic regressions model that included gestational age at birth, birthweight, sex, receipt of antenatal steroids, twin gestation, and chorioamnionitis, the adjusted odds ratio for survival was 1.0 (95% CI 0.40–2.51), p = 0.99 and 0.93 (95% CI 0.32–2.7), p = 0.89 in the 2018–2020 and 2021–2023 epochs, respectively.
MorbidityWe investigated whether the increase in resuscitation and intensive care provided to neonates born at 22 weeks gestation increased the overall morbidity of neonates born at 22–23 weeks gestation. We assessed morbidity in neonates who did not die within the first 12 h of life (n = 170). Over the study period, the rate of NEC decreased from 8/33 (24%) in the first epoch to 5/66 (8%) in the last epoch, p = 0.025. Intraventricular hemorrhage and patent ductus arteriosus rates trended downward but did not reach statistical significance (Table 4).
Table 4 Morbidities & resource utilization across the study period.Among survivors (n = 80), fewer neonates experienced NEC in the last epoch compared to the first epoch, 2/30 (7%) vs. 6/19 (32%), p = 0.021. There were also fewer neonates diagnosed with PDA in the last epoch compared to the first, 19/30 (63%) vs. 17/19 (89%), p = 0.026. Grade III BPD and severe IVH rates were down-trending but did not reach statistical significance (Table 4).
Resource utilizationIn terms of resource utilization, the median length of stay amongst those who did not experience early death was 109 [IQR 8–230] days in the 2015–2017 epoch and 45 [IQR 9–141] days in the 2021–2023 epoch (Fig. 2a), and the rate of abdominal surgery was stable at 6% (2/33) and 8% (5/66) in the 2015–2017 and 2021–2023 epochs, respectively (Table 4).
Fig. 2: Length of stay for neonates who received intensive care.a The median length of stay of neonates who did not experience early death was 109 [IQR 8–230], 53 [IQR 6–146], and 45 [IQR 9–141] days in 2015–2017, 2018–2020, and 2021–2023 epochs, respectively. b The median length of stay of neonates who survived was 208 [IQR 122–272], 149 [IQR 131–215], and 143 [IQR 118–223] days in 2015–2017, 2018–2020, and 2021–2023 epochs, respectively. ns: not significant by the Kruskal-Wallis test.
Amongst survivors, the median length of stay in the 2021–2023 epoch decreased by 65 days from 2015–2017 (208 vs. 143 days), but that was not statistically significant (Fig. 2b). The rate of neonates discharged on home oxygen also decreased from 42% (8/19) in the 2015–2017 epoch to 27% (8/30) in the 2021–2023 epoch (Table 4).
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