Faster identification of infants at high risk of ROP by evaluating the effects of maternal and fetal vascular malperfusion

(Image Credit: AdobeStock/geargodz)

Investigators in The Netherlands may have found a faster way to identify infants who are at high risk of developing retinopathy of prematurity (ROP), namely, by assessing the effects of maternal and fetal vascular malperfusion,¹ according to lead author Salma El Emrani, BSc, from the Ophthalmology, Leiden University Medical Center, and Neonatology, Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, both in Leiden, The Netherlands.

ROP results from abnormal vessel development and can occur in from 10% to 25% of premature neonates born before 32 weeks’ gestation.² Currently, low gestational age at birth and low birthweight are the primary risk factors used to screen for ROP. Oxygen therapy, (cardio)respiratory support, and sepsis are included as risk factors in some countries,^3,4 according to El Emrani and colleagues.

They also pointed out their recent finding that placental inflammation is directly associated with ROP through acute histologic chorioamnionitis and funisitis.⁵ However, little is known about the association between uteroplacental malperfusion and ROP.

Uteroplacental malperfusion can be both maternal and fetal in nature. The former is an umbrella term for histologic changes in the maternal decidual vasculature or villous parenchyma, according to the authors, which can affect the maternal circulation to the fetus usually in the form of decreased uterine and intervillous blood flow.⁶ The fetal form is a collective term for pathological lesions mainly caused by umbilical cord obstruction resulting in absent/reduced perfusion of the villous parenchyma leading to fetal hypoxia.⁷

The study cohort and methods

The study included 591 neonates with a gestational age of 32 weeks or less or a birthweight of 1,500 grams or less. The patients’ clinical data were collected retrospectively and the placentas were examined prospectively to identify maternal vascular malperfusion, for example, abruption, infarct, distal villous hypoplasia, ischemia, and decidual necrosis, and fetal vascular malperfusion, for example, thrombosis, fetal hypoxia, and hydrops parenchyma.

The primary study outcome was ROP. Secondary outcomes were gestational age, birthweight, small for gestational age, mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis, El Emrani and colleagues recounted.

Analysis results

The analysis showed that maternal vascular malperfusion was associated with higher gestational age, lower birthweight, and increased small for gestational age rates, except for placental abruption, which was associated with lower small for gestational age rates. Fetal vascular malperfusion was associated with lower birthweight, increased small for gestational age rates and lower duration of mechanical ventilation, the authors reported.

An analysis of placentas without inflammation revealed increased rates of distal villous hypoplasia (44% vs. 31%) and hydrops parenchyma (7% vs. 0%) in neonates with ROP. Multivariate regression analyses identified 3 placenta factors that were independently associated with ROP: distal villous hypoplasia (odds ratio [OR] = 1.7; 95% confidence interval [CI], 1.0–3.0), severe acute histologic chorioamnionitis (OR = 2.1; 95% CI, 1.1–3.9), and funisitis (OR = 1.8; 95% CI, 1.0–3.1).

The investigators commented that the 3 newly identified risk factor for ROP are “novel and valuable addition to the ROP risk profile. Evaluation of these placental risk factors shortly after birth can aid in identifying high-risk infants in an earlier stage than currently possible,” they said.

In addition, the confirmation can then be used for personalized neonatal treatment to prevent ROP from developing. “In the future,” they stated, “these newly found placental risk factors may be used as placental therapy targets to prevent ROP in these vulnerable extremely premature neonates.”

References

1. El Emrani S, Jansen EJS, Goeman JJ, et al. Enhancing the retinopathy of prematurity risk profile through placental evaluation of maternal and fetal vascular malperfusion. Invest Ophthalmol Vis Sci. 2024;65:9; doi:10.1167/iovs.65.11.9

2. Owen LA, Morrison MA, Hoffman RO, Yoder BA, DeAngelis MM. Retinopathy of prematurity: a comprehensive risk analysis for prevention and prediction of disease. PLoS One. 2017;12:e0171467

3. Modrzejewska M, Bosy-Gąsior W. Most up-to-date analysis of epidemiological data on the screening guidelines and incidence of retinopathy of prematurity in Europe—a literature review. J Clin Med. 2023;12:3650.

4. Kościółek M, Kisielewska W, Ćwiklik-Wierzbowska M, Wierzbowski P, Gilbert C. Systematic review of the guidelines for retinopathy of prematurity. Eur J Ophthalmol. 2023; 33: 667–681.

5. El Emrani S, Smit-Jansen E, Goeman J, et al. Histological chorioamnionitis and funisitis as new risk factors for retinopathy of prematurity: a meta-analysis. Am J Perinatol. 2024; 41(S01): e3264–e3273.

6. Ernst LM. Maternal vascular malperfusion of the placental bed. APMIS. 2018;126:551–560.

7. Redline RW, Ravishankar S. Fetal vascular malperfusion, an update. APMIS. 2018;126: 561–569.