Perinatal risk factors for mortality in very preterm infants-A nationwide, population-based discriminant analysis

Abstract

Aim: To assess the strength of associations between interrelated perinatal risk factors and mortality in very preterm infants.

Methods: Information on all live-born infants delivered in Sweden at 22-31 weeks of gestational age (GA) from 2011 to 2019 was gathered from the Swedish Neonatal Quality Register, excluding infants with major malformations or not resuscitated because of anticipated poor prognosis. Twenty-seven perinatal risk factors available at birth were exposures and in-hospital mortality outcome. Orthogonal partial least squares discriminant analysis was applied to assess proximity between individual risk factors and mortality, and receiver operating characteristic (ROC) curves were used to estimate discriminant ability.

Results: In total, 638 of 8,396 (7.6%) infants died. Thirteen risk factors discriminated reduced mortality; the most important were higher Apgar scores at 5 and 10 min, GA and birthweight. Restricting the analysis to preterm infants <28 weeks' GA (n = 2939, 16.9% mortality) added antenatal corticosteroid therapy as significantly associated with lower mortality. The area under the ROC curve (the C-statistic) using all risk factors was 0.86, as determined after both internal and external validation.

Conclusion: Apgar scores, gestational age and birthweight show stronger associations with mortality in very preterm infants than several other perinatal risk factors available at birth.

Keywords: infant mortality; orthogonal partial least squares discriminant analysis; preterm infant.

FIGURE 1

2D representation of risk factor distribution in live‐born very preterm infants (N = 8396) surviving (unfilled squares, no mortality) or dying in‐hospital (filled squares, yes for mortality). Cross‐validated score vectors (tcv) related to outcome are distributed along the x‐axis, and orthogonal vectors (tocv) unrelated to outcome are distributed along the y‐axis.

FIGURE 2

Bar chart depicting significant contributions (with 95% confidence intervals) of perinatal risk factors for survival (tcv significantly above 0) or death (tcv significantly below 0) in very preterm infants <32 weeks of GA (N = 8396). Infold: truncated bar chart excluding risk factors without any statistically significant contribution to outcome. BE, base excess; min, minutes; IUGR, intrauterine growth retardation; OPLS‐DA, orthogonal partial least squares discriminant analysis; PPROM, preterm, prelabour rupture of membranes; ROM, rupture of membranes; Umb, umbilical

FIGURE 3

To the left (A): receiver operating characteristic (ROC) curve based on cross‐validated score values from orthogonal partial least squares discriminant analysis (OPLS‐DA) modelling of perinatal risk factors and mortality for very preterm infants. ROC area under the curve (AUC) is 0.86. To the right (B) mortality score (0 – 100) and the associated mortality for very preterm infants as given by OPLS‐DA cross‐validation

FIGURE 4

Truncated bar chart depicting significant contributions (with 95% confidence intervals) of perinatal risk factors for survival (tcv significantly above 0) or death (tcv significantly below 0) in extremely preterm infants <28 weeks of GA (n = 2939). Risk factors without any statistically significant contribution to outcome not shown (n = 17). BE, base excess; OPLS‐DA, orthogonal partial least squares discriminant analysis