Preterm birth and the risk of chronic disease multimorbidity in adolescence and early adulthood: A population-based cohort study

Background People who were born prematurely have high risks of many individual diseases and conditions in the early part of the life course. However, our knowledge of the burden of multiple diseases (multimorbidity) among prematurely born individuals is limited. We aimed to investigate the risk and patterns of chronic disease multimorbidity in adolescence and early adulthood among individuals born across the spectrum of gestational ages, comparing preterm and full-term born individuals. Methods and findings We used individual-level data from linked nationwide registers to examine the associations of gestational age at birth with specialised healthcare records of ≥2 chronic diseases (multimorbidity) in adolescence (age 10–17 years) and early adulthood (age 18–30 years). Our study population comprised 951,116 individuals (50.2% females) born alive in Finland between 1st January 1987 and 31st December 2006, inclusive. All individuals were followed from age 10 years to the onset of multimorbidity, emigration, death, or 31 December 2016 (up to age 30 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for multimorbidity using flexible parametric survival models. During 6,417,903 person-years at risk (median follow-up: 7.9 years), 11,919 individuals (1.3%) had multimorbidity in adolescence (18.6 per 10,000 person-years). During 3,967,419 person-years at risk (median follow-up: 6.2 years), 15,664 individuals (1.7%) had multimorbidity in early adulthood (39.5 per 10,000 person-years). Adjusted HRs for adolescent multimorbidity, comparing preterm to full-term born individuals, were 1.29 (95% CI: 1.22 to 1.36) and 1.26 (95% CI: 1.18 to 1.35) in females and males, respectively. The associations of preterm birth with early adult multimorbidity were less marked, with the adjusted HRs indicating 1.18-fold risk in females (95% CI: 1.12 to 1.24) and 1.10-fold risk in males (95% CI: 1.04 to 1.17). We observed a consistent dose-response relationship between earlier gestational age at birth and increasing risks of both multimorbidity outcomes. Compared to full-term born males, those born at 37–38 weeks (early term) had a 1.06-fold risk of multimorbidity in adolescence (95% CI: 0.98 to 1.14) and this risk increased in a graded manner up to 6.85-fold (95% CI: 5.39 to 8.71) in those born at 23–27 weeks (extremely premature), independently of covariates. Among females, the same risks ranged from 1.16-fold (95% CI: 1.09 to 1.23) among those born at 37–38 weeks to 5.65-fold (95% CI: 4.45 to 7.18) among those born at 23–27 weeks. The corresponding risks of early adult multimorbidity were similar in direction but less marked in magnitude, with little difference in risks between males and females born at 36–37 weeks but up to 3-fold risks observed among those born at 23–27 weeks. Conclusions Our findings indicate that an earlier gestational age at birth is associated with increased risks of chronic disease multimorbidity in the early part of the life course. There are currently no clinical guidelines for follow-up of prematurely born individuals beyond childhood, but these observations suggest that information on gestational age would be a useful characteristic to include in a medical history when assessing the risk of multiple chronic diseases in adolescent and young adult patients.

Age at Surgical Ligation of Patent Ductus Arteriosus Affects Prognosis in Extremely Premature Infants

Background: This study aimed to evaluate outcomes, prognosis, and safety associated with the timing of surgical ligation for patent ductus arteriosus (PDA) in extremely premature infants (EPI). Methods: We reviewed the clinical data of 44 EPI (gestational age at birth 26.8 ± 0.67 weeks; birth weight 997 ± 152 g) who received surgical ligation for hemodynamically significant PDA (hsPDA) in the Neonatal Intensive Care Unit (NICU) of Bayi Children’s Hospital in China between January 2021 and December 2014. We compared the general characteristics, underlying diseases, postoperative surgical complications, and prognoses in two groups of patients who received early ligation (≤ 14 days after birth) and late ligation (> 14 days after birth). Results: The gender, gestational age at birth, birth weight, Apgar score, postoperative surgical complications, rates of bronchopulmonary dysplasia (BPD), retinopathy of prematurity, necrotic enterocolitis, periventricular leukomalacia, total hospitalization, and medical costs of both groups were compared. According to the results, the late ligation group had a higher rate of severe BPD (66.3% cf. 35%) and required significantly longer time to reach total enteral feeding and weaning of respiratory support compared with the early ligation group. Conclusions: In EPI with hsPDA, for whom medical treatment failed or is contraindicated, early surgical closure of the ductus arteriosus can promote earlier total enteral feeding, shorten the duration of mechanical ventilation, and reduce the rates of severe BPD.

Spatially and Temporally Resolved Ambient PM2.5 in Relation to Preterm Birth

Growing evidence suggests that maternal exposure to ambient fine particulate matter (PM2.5) during pregnancy is associated with preterm birth; however, few studies have examined critical windows of exposure, which can help elucidate underlying biologic mechanisms and inform public health messaging for limiting exposure. Participants included 891 mother–newborn pairs enrolled in a U.S.-based pregnancy cohort study. Daily residential PM2.5 concentrations at a 1 × 1 km2 resolution were estimated using a satellite-based hybrid model. Gestational age at birth was abstracted from electronic medical records and preterm birth (PTB) was defined as <37 completed weeks of gestation. We used Critical Window Variable Selection to examine weekly PM2.5 exposure in relation to the odds of PTB and examined sex-specific associations using stratified models. The mean ± standard deviation PM2.5 level averaged across pregnancy was 8.13 ± 1.10 µg/m3. PM2.5 exposure was not associated with an increased odds of PTB during any gestational week. In sex-stratified models, we observed a marginal increase in the odds of PTB with exposure occurring during gestational week 16 among female infants only. This study does not provide strong evidence supporting an association between weekly exposure to PM2.5 and preterm birth.

Course of Stress during the Neonatal Intensive Care Unit Stay in Preterm Infants

<b><i>Introduction:</i></b> Understanding the course of stress during the neonatal intensive care unit stay may provide targets for interventions. Our aim was to describe the course of stress in preterm infants during the first 28 days of life, the influence of gestational age, and associations with clinical characteristics. <b><i>Methods:</i></b> In a single centre prospective cohort study, we included infants with a gestational age &#x3c;30 weeks and/or birth weight &#x3c;1,000 g. We measured stress over the first 28 days using the Neonatal Infant Stressor Scale (NISS). We plotted daily NISS total and subcategory scores by gestational age. The subcategories were (1) nursing, (2) skin-breaking, (3) monitoring and imaging, and (4) medical morbidity-related scores. We assessed associations of cumulative NISS scores over the first 7, 14, and 28 days with clinical characteristics using regression analyses. <b><i>Results:</i></b> We included 45 infants, with a median gestational age of 27 weeks. The mean daily NISS score was 66.5 (SD 8.7), with highest scores in the first 7 days of life. Scores decreased the slowest for the lowest gestational ages, in particular for nursing scores, rather than skin-breaking, monitoring and imaging, and medical morbidity-related scores. Adjusted for gestational age, infants with lower Apgar scores, sepsis, intraventricular haemorrhages, and on mechanical ventilation had significantly higher cumulative NISS scores at 7, 14, and 28 days. <b><i>Conclusion:</i></b> NISS scores varied greatly within infants and over time, with the highest mean scores in the first week after birth. The course of declining NISS scores in the first 28 days depended on gestational age at birth.