Association between fetal growth-restriction and retinopathy of prematurity using a unique identical twin model

Research in singletons identified fetal growth restriction (FGR) as a risk factor for retinopathy of prematurity (ROP), but is generally subject to confounding by genetic, obstetric, and maternal factors. We investigated the effect of FGR on ROP in growth-discordant identical twins, thereby controlling for confounding factors.

All data of monochorionic (MC) twin pairs with a birth weight discordance ≥20% born in our center between 2010 and 2021 were retrospectively reviewed for the presence of ROP. Potential risk factors for ROP were analyzed. Outcomes were compared between the smaller and larger twin.

We included 88 MC twin pairs with growth discordance. In 34% (30/88), both neonates were at risk of ROP. Prevalence of ROP was higher among the smaller twin compared to the larger twin, 30% (9/30) versus 13% (4/30), respectively (OR 2.8, 95% CI: 1.2-6.6). The smaller twin had a longer duration of mechanical ventilation (8 (1-20) versus 2 (1-4) days) and received their first red blood cell transfusion at an earlier postmenstrual age (29.6 (28.1-31.6) versus 30.4 (29.7-32.6) weeks).

In this identical twin model, FGR is associated with almost tripled odds of ROP development, suggesting that both unfavorable antenatal growth conditions and adverse neonatal outcomes affect postnatal retinal vascular proliferation.

Fetal growth restriction in growth-discordant identical twins is associated with almost tripled odds of developing retinopathy of prematurity in the smaller twin. Since these twins do not only differ in birth weight but also duration of mechanical ventilation and timing of the first red blood cell transfusion, both unfavorable antenatal growth conditions and adverse neonatal outcomes can affect postnatal retinal vascular proliferation. More attention for preventing retinopathy of prematurity is needed in those with fetal growth restriction who received prolonged duration of mechanical ventilation, oxygen supplementation, or a first red blood cell transfusion <32 weeks postmenstrual age.