Antenatal corticosteroid therapy has improved the prognosis of prematurity. The Liggins and Howie trial (betamethasone versus placebo), conducted from 1969 to 1974 in New Zealand, was the first to demonstrate a reduction in hyaline membrane disease after antenatal corticosteroid therapy (1,2). Further progress followed. Now, more than 90% of individuals born before 37 weeks gestation reach adulthood.
However, apart from the after-effects of neonatal complications, they suffer from more morbidities than people born at term. In particular, they would present an increased cardio-metabolic risk.
Looking back 50 years, Walters et al. were able to specify, thanks to a medical questionnaire and/or using data from medico-administrative databases, the state of health of 470 individuals born in the original trial of antenatal corticosteroid therapy, and who survived at least until ‘at the age of 1 year (3). Specifically, participants who died before follow-up were assessed using administrative data only. The primary endpoint was a composite endpoint combining: type 2 diabetes, prediabetes, treated hypertension, treated dyslipidemia or previous major cardiovascular event.
The cardio-metabolic risk of individuals born prematurely does not appear to be increased overall.
In the original trial, 1121 infants were born alive to 1025 women and 964 survived to one year of age. Of the 470 included participants, 424 were evaluated at a mean age of 49.3 years and 46 died after infancy. A total of 326 subjects were born prematurely, at a median gestational age of 34 weeks. Of these, 25 had died before the age of 50, and 301 were still alive at 50. Among the 144 participants ultimately born at full term after the threat of premature birth, 21 died before the age of 50.
Compared to full-term subjects, former premature infants have a higher rate of major events (≥1 hospitalization for myocardial infarction, coronary revascularization, stroke, peripheral vascular disease, heart failure; death from cardiovascular causes) and/or risk factors (diabetes/pre-diabetes, treated high blood pressure, treated dyslipidemia) slightly higher (34.5% versus 29.9%), but the adjusted relative risk (RRa) is not significantly increased (RRa: 1.14; [IC 95 % : 0,85-1,54] ; p >>0,05).
In detail, cardiovascular events are less frequent in former premature babies than in full-term individuals (2.8% vs 6.9%; RRa: 0.33, 95% CI: 0.14-0.79), while cardiovascular risk factors did not differ between the two groups. However, although they are not treated more often for high blood pressure, former premature babies report relatively more high blood pressure (34.7% vs. 19.8%; RRa: 1.74; [1,16-2,61]).
-Overweight and obesity, asthma and chronic obstructive pulmonary disease (COPD), chronic kidney failure have similar prevalences in former premature babies and individuals born at term. Mental disorders are rarer in former premature babies.
If, between the time of randomization to receive either betamethasone or placebo and the age of 50, mortality was twice as high in former premature babies as in individuals born at term (22.4% vs 9.9%), after the age of 1 year there was no longer a significant difference.
A healthy optimism
Thus, former premature babies aged 50 years have a cardio-metabolic risk generally similar to that of individuals born at term. In detail, their risk of major cardiovascular events is lower; on the other hand the risk of high blood pressure seems higher.
The optimistic view that this study gives of the health of premature infants reaching adulthood is at odds with the findings of large follow-up cohorts. It should nevertheless be noted that the population of this study is small, not very premature, and only includes 46% of the individuals from the original study presumed alive at the age of 50, due to loss to follow-up and refusals. of participation.
However, apart from its historical aspect, the study presents a double interest, as highlighted in the editorial which accompanies the article (4). It illustrates two of the difficulties of very long-term follow-up studies of premature babies: attrition of the original population and the effect of censoring mortality. It undermines the hypothesis that morbidity in adulthood is determined solely by gestational age and/or birth weight of premature infants in the absence of after-effects of neonatal complications.
