Determining resuscitation threshold for extremely preterm infants based on the survival rates without severe neurological injury

Abstract

Background: Published guidelines on decision-making and resuscitation of extremely preterm infants primarily focus on high-income countries. For rapidly industrializing ones like China, there is a lack of population-based data for informing prenatal management and practice guidelines.

Methods: The Sino-northern Neonatal Network conducted a prospective multi-centre cohort study between 1 January 2018 and 31 December 2021. Infants with a gestational age (GA) between 22 (postnatal age in days = 0) and 28 (postnatal age in days = 6) admitted to 40 tertiary NICUs in northern China were included and evaluated for death or severe neurological injury before discharge.

Results: For all extremely preterm infants (n = 5838), the proportion of admission to the neonatal was 4.1% at 22-24 weeks, 27.2% at 25-26 weeks, and 75.2% at 27 and 28 weeks. Among 2228 infants admitted to the NICU, 216 (11.1%) were still elected for withdrawal of care (WIC) due to non-medical factors. Survival rates without severe neurological injury were 6.7% for infants at 22-23 weeks, 28.0% at 24 weeks, 56.7% at 24 weeks, 61.7% at 25 weeks, 79.9% at 26 weeks, and 84.5% at 27 and 28 weeks. Compared with traditional criterion at 28 weeks, the relative risk for death or severe neurological injury were 1.53 (95% confidence interval (CI) = 1.26-1.86) at 27 weeks, 2.32 (95% CI = 1.73-3.11) at 26 weeks, 3.62 (95% CI = 2.43-5.40) at 25 weeks, and 8.91 (95% CI = 4.69-16.96) at 24 weeks. The NICUs with higher proportion of WIC also had a higher rate of death or severe neurological injury after maximal intensive care (MIC).

Conclusions: Compared to the traditional threshold of 28 weeks, more infants received MIC after 25 weeks, leading to significant increases in survival rates without severe neurological injury. Therefore, the resuscitation threshold should be gradually adjusted from 28 to 25 weeks based on reliable capacity.

Registration: China Clinical Trials Registry. ID: ChiCTR1900025234.

Figure 1

Internal comparison between NICUs in SNN. The grouping criteria were based on the quartiles of the proportion of MIC from highest to lowest into four groups. The incidence of mortality or SNI after MIC was calculated after standardization of potential confounders including male gender, antenatal corticosteroids, SNAPPE-II>20 and multiple births. The denominator for death or SNI was infants received MIC. SNI – severe neurological injury, WIC – withdrawal of care, MIC – maximal intensive care.

Figure 2

The restricted cubic spline curves based on multivariable adjusted hazard ratios for death or SNI according to GA. Solid red line shows the multivariable adjusted hazard ratios, with dashed black lines showing 95% CIs derived from restricted cubic spline regressions with three knots. The dark blue shows the survival rate without SNI according to GA. Purple curve shows the fraction of the population with different GA. We adjusted the analyses for male gender, antenatal corticosteroids, SNAPPE-II>20 and multiple births at baseline.