Long-Term Infectious Morbidity of Premature Infants: Is There a Critical Threshold?

Sharon Davidesko,Gali Pariente,Eyal Sheiner,Tamar Wainstock

doi:10.3390/jcm9093008

Sharon Davidesko, Gali Pariente + Show 2 more

Open Access

https://doi.org/10.3390/jcm9093008

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Abstract

In this study, we sought to ascertain a relationship between gestational age at birth and infectious morbidity of the offspring via population-based cohort analysis comparing the long-term incidence of infectious morbidity in infants born preterm and stratified by extremity of prematurity (extreme preterm birth: 24 + 0–27 + 6, very preterm birth: 28 + 0–31 + 6, moderate to late preterm birth: 32 + 0−36 + 6 weeks of gestation, and term deliveries). Infectious morbidity included hospitalizations involving a predefined set of International Classification of Diseases 9 (ICD9) codes, as recorded in hospital records. A Kaplan–Meier survival curve compared cumulative incidence of infectious-related morbidity. A Cox proportional hazards model controlled for confounders and time to event. The study included 220,594 patients: 125 (0.1%) extreme preterm births, 784 (0.4%) very preterm births, 13,323 (6.0%) moderate to late preterm births, and 206,362 term deliveries. Offspring born preterm had significantly more infection-related hospitalizations (18.4%, 19.8%, 14.9%, and 11.0% for the aforementioned stratification, respectively, p < 0.001). Multivariate analysis found being born very or late to moderate preterm was independently associated with long-term infectious morbidity (adjusted hazard ratio (aHR) 1.5, 95% confidence interval (CI) 1.27–1.77 and aHR 1.23, 95% CI 1.17–1.3, respectively, p < 0.001). A comparable risk of long-term infectious morbidity was found in the two groups of premature births prior to 32 weeks gestation. In our population, a cutoff from 32 weeks and below demarks a significant increase in the risk of long-term infectious morbidity of the offspring.

Highlights

Preterm birth refers to deliveries occurring prior to 37 completed weeks of gestation
Diabetes was more common in women delivered preterm, not for those who delivered extremely preterm, most likely due to these women delivering before the recommended gestational age for screening during pregnancy
We showed that infectious morbidity is increasingly common with decreasing gestational age at birth, as shown in both the Kaplan–Meier survival curve and the Cox regression analysis model

Summary

Introduction

Preterm birth refers to deliveries occurring prior to 37 completed weeks of gestation. Most preterm births are spontaneous, while up to 30% may be due to iatrogenic causes such as preeclampsia, fetal growth restriction, or multiple gestation [1]. The global incidence of preterm birth is reported to be between 5% and 18%, depending on location, with an average of 11% [2]. This translates to 15 million premature newborns, with this number increasing progressively [2]. Recognized risk factors for preterm birth include previous preterm delivery [3], infectious or inflammatory disease [4], smoking [5], and multiple gestation [6]. It is well recognized that infectious disease explains at least partially the pathophysiology of premature onset of labor in the majority of cases as demonstrated by pathological evidence of chorioamnionitis in up to 75% of submitted placentas and positive membrane cultures in up to 60% of patients who delivered prematurely [7]

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