Respiratory distress syndrome and bronchopulmonary dysplasia after fetal growth restriction: Lessons from a natural experiment in identical twins | February 2021 | E Clinical Medicine

Sophie G.Groene, Jip A.Spekman, Arjan B.te Pas, Bastiaan T.Heijmans, Monique C.Haak, Jeanine M.M.van Klink, Arno A.W.Roest, Enrico Lopriore



Fetal growth restriction (FGR) is thought to negatively affect lung development resulting in increased respiratory morbidity. However, research performed in singletons is often limited by a certain level of bias caused by individual differences in genetic constitution, obstetrical and maternal factors.


Respiratory morbidity was compared between the smaller and the larger twin in monochorionic twins with selective fetal growth restriction (sFGR), defined as a birth weight discordance ≥ 20%, born in our center between 2010 and 2019 in this retrospective study. Respiratory distress syndrome (RDS) was diagnosed based on the clinical picture of a neonate with respiratory failure requiring mechanical ventilation and/or surfactant, confirmed by a chest X-ray. Bronchopulmonary dysplasia (BPD) was diagnosed when the neonate required treatment with >21% oxygen for at least 28 days.


Median gestational age at birth for the 94 included pregnancies was 32.4 (IQR 30.4–34.3) weeks. Within-pair analyses showed that the prevalence of RDS was lower in the smaller twin compared to the larger twin, 19.1% (18/94) vs 34.0% (32/94), respectively (p = 0.004). The odds of RDS for the larger twin was doubled (OR 2.1 (CI95% 1.3–3.5). In contrast, the rate of BPD in the smaller twin was higher as opposed to the larger twin, 16.7% (15/90) vs 6.7% (6/89), respectively (p = 0.008), with a more than doubled odds (OR 2.5 (CI95% 1.3–4.9)).


Despite being genetically identical, sFGR twins have different respiratory outcomes. Adverse growth condition in utero in the smaller twin is associated with a reduced odds of RDS at birth but a more than doubled odds of BPD, reflecting the pathophysiologic adverse effect of growth restriction on lung development.


The Dutch Heart Foundation (2017T075).

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