Salma El Emrani

Existing prediction models for retinopathy of prematurity (ROP) primarily focus on screening reduction which occur 5 to 7 weeks after birth. We hypothesized that high-risk neonates could be identified much earlier if placental and early postnatal risk factors are incorporated, so that this high risk can be considered during neonatal treatment well before ROP screening begins. We included 591 neonates born ≤32 weeks of gestational age (GA) and/or birthweight (BW) ≤1500 grams. Data were retrospectively collected, and placentas were examined for histological abnormalities. The "Placenta as an Additional Predictor for ROP" (PAPROP) model included: GA, BW, mechanical ventilation, postnatal corticosteroids, severe histological chorioamnionitis, and distal villous hypoplasia. This model was internally validated with five-fold cross-validation and compared to a reference model using only GA and BW. The PAPROP model had a discriminatory ability between ROP presence and absence of 0.81 (95% confidence interval [CI] = 0.76-0.86) compared to 0.78 in the reference GA&BW model. This model had a sensitivity of 0.97 and specificity of 0.44 in the test set (threshold 10%). Using clinically relevant thresholds of 10% to 15%, implementing this model in the second postnatal week could lead to a 25% reduction in ROP screenings without missing stage 2 and severe ROP. The PAPROP model has a high ability to predict ROP development at the end of the second postnatal week, has a potential high clinical utility, and is likely cost-effective. After further external validation, it may aid in creating a personalized neonatal treatment approach for ROP prevention in high-risk neonates.

Purpose: Red blood cell (RBC) transfusions are believed to be associated with retinopathy of prematurity (ROP), but the underlying mechanism is not fully understood, partly due to the lack of information on RBC transfusion timing. The aim was to determine the association between the timing and amount of RBC transfusions and the development and severity of ROP.Methods: This retrospective dual‐center cohort study included 1177 neonates born in 2004–2022 with a gestational age at birth ≤28 weeks. Primary outcomes were any stage ROP and severe ROP based on maximum staging. Phase I of ROP was defined as ≤32.0 weeks postmenstrual age and phase II as >32.0 weeks postmenstrual age. Logistic regression analyses were adjusted for gestational age at birth, small for gestational age, mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis.Results: Multivariate analysis showed independent associations with severe ROP for RBC transfusion (OR 5.1; 95% CI 1.8–14.3), number of RBC transfusions (OR 1.2; 95% CI 1.1–1.3), RBC transfusion in phase I (OR 2.5; 95% CI 1.2–5.3), number of RBC transfusions in phase I (OR 1.2; 95% CI 1.0–1.3), RBC transfusion in phase II (OR 4.1; 95% CI 2.7–6.3) and number of RBC transfusions in phase II (OR 1.9; 95% CI 1.5–2.4).Conclusion: Based on maximum ROP staging, RBC transfusions in phases I and II are both associated with a high risk of severe ROP. A randomized controlled trial is urgently needed to determine the potential effect of RBC transfusions in phase II on ROP progression.

Objective Fetomaternal transfusion (FMT) is associated with increased perinatal mortality and morbidity, but data on postnatal outcomes are scarce. Our aim was to determine the incidence of adverse short-term and long-term sequelae of severe FMT. Design Retrospective cohort study. Setting Dutch tertiary neonatal intensive care unit. Patients Liveborn neonates with FMT admitted in 2017–2022. Main outcome measures Severe FMT was defined as ≥30 mL of fetal red blood cells in the maternal circulation diagnosed with positive Kleihauer-Betke/flow cytometry test. Adverse outcomes were compared between severe and mild FMT (10–30 mL blood loss) to highlight the impact of FMT severity. Primary outcome was an adverse composite outcome consisting of neonatal mortality or severe neurological morbidity (ie, severe cerebral injury and/or neurodevelopmental impairment (NDI) at 2 years). Secondary outcome was perinatal asphyxia. Results 109 neonates with FMT were included, 16 with severe FMT and 93 with mild FMT. Neonatal mortality occurred in 19% (3/16) of neonates with severe FMT and in 4% (4/93) with mild FMT (p=0.063). Perinatal asphyxia was diagnosed in 25% (4/16) of neonates with severe FMT compared with 6% (6/93) with mild FMT (p=0.038). Long-term outcome was assessed in 60 neonates. NDI occurred in 22% (2/9) of children with severe FMT compared with 16% (8/51) with mild FMT (p=0.637). Adverse outcome occurred in 43% (95% CI 38 to 50%) of neonates with severe FMT compared with 18% (95% CI 17% to 24%) with mild FMT (p=0.074). Conclusion Neonatal mortality or long-term neurological morbidity occurred in 38%–50% of children with fetal blood loss and anaemia due to severe FMT.

Purpose: To determine the independent effect of uteroplacental malperfusion on the development of retinopathy of prematurity (ROP). Methods: This cohort study included 591 neonates with a gestational age (GA) ≤ 32 weeks or birthweight (BW) ≤ 1500 g. Clinical data was retrospectively collected and placentas were prospectively examined for maternal vascular malperfusion (e.g., abruption, infarct, distal villous hypoplasia, ischemia, and decidual necrosis) and fetal vascular malperfusion (e.g., thrombosis, fetal hypoxia, and hydrops parenchyma). The primary outcome was ROP. Secondary outcomes were GA, BW, small for gestational age (SGA), mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis. Results: Maternal vascular malperfusion was associated with higher GA, lower BW, and increased SGA rates, except placental abruption, which was associated with lower SGA rates. Fetal vascular malperfusion was associated with lower BW, increased SGA rates and lower duration of mechanical ventilation. Subgroup analysis of placentas without inflammation showed increased rates of distal villous hypoplasia (44% vs. 31%) and hydrops parenchyma (7% vs. 0%) in neonates with ROP. Multivariate regression analyses revealed three placenta factors to be independently associated with ROP: distal villous hypoplasia (OR = 1.7; 95% CI, 1.0–3.0), severe acute histological chorioamnionitis (OR = 2.1; 95% CI, 1.1–3.9) and funisitis (OR = 1.8; 95% CI, 1.0–3.1). Conclusions: Placental evaluation of distal villous hypoplasia, severe acute chorioamnionitis and funisitis is a 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.

Objective Neonatal sepsis has been established as a risk factor for retinopathy of prematurity (ROP) but previous meta-analyses have predominately focused on late-onset sepsis (LOS). This meta-analysis aims to explore the association between early-onset sepsis (EOS) and the risk of ROP. Study Design Observational studies reporting (unadjusted) data on proven EOS in neonates with ROP were included. PubMed, Embase, and Cochrane Library were searched. Proven EOS was defined as a positive blood or cerebrospinal fluid culture. Effect sizes were calculated by using logistic random-effects models and meta-regression analyses. Primary outcomes were any stage ROP and severe ROP (≥stage 3, type I, aggressive [posterior] ROP, plus disease or requiring treatment). Potential confounders explored were gestational age at birth, birth weight, small for gestational age, maternal steroid use, necrotizing enterocolitis, LOS, and mechanical ventilation duration. Results Seventeen studies reporting the incidence of proven EOS in neonates with ROP were included. Proven EOS showed no significant association with any stage ROP (odds ratio [OR] = 1.90; 95% confidence interval [CI]: 0.96–3.79, p = 0.067) but heterogeneity between studies was significantly high. Neonates with proven EOS had an increased risk for severe ROP (OR = 2.21; 95% CI: 1.68–2.90), and no significant confounders influencing this effect size were found in the meta-regression analysis. Conclusion Neonates with proven EOS are at increased risk of severe ROP. Neonatologists need to be aware that EOS is an early predictor of ROP and should adapt their policy and treatment decisions where possible to reduce ROP. Key Points

A 43-year-old female presented with blood loss and persistent abdominal pain at 14 weeks of gestation. Ultrasound examination and subsequent magnetic resonance imaging (MRI) revealed bilateral multicystic uterine adnexa. Exploratory laparotomy was performed at 17 weeks of gestation and bilateral serous ovarian adenocarcinoma FIGO stage IIIC was diagnosed. Complete cytoreductive surgery (CRS) was not feasible at that moment. Nine days after the exploratory laparotomy, immature rupture of membranes and contractions occurred and she delivered a premature boy after 19 weeks of gestation. Pathological examination of the placenta revealed that her ovarian cancer metastasized to the membranes. We describe the first case of ovarian cancer metastasized to the decidua of the placental membranes with histological, immunohistochemical, and molecular confirmation. This case highlights the importance of conscientious evaluation of placenta and membranes in pregnant women with ovarian cancer.

Objective The role of placental inflammation in neonatal morbidities is underestimated due to lack of placental examination. This meta-analysis aims to assess the association between histological chorioamnionitis (HCA) with and without funisitis (FUN) and risk of retinopathy of prematurity (ROP). Study Design Forty-five studies reporting (unadjusted) data on HCA without FUN and HCA with FUN in neonates with ROP were included. Primary outcomes were any stage ROP and severe ROP. Potential confounders explored were gestational age (GA) at birth, birthweight, maternal steroid use, necrotizing enterocolitis, sepsis (suspected/proven) and mechanical ventilation duration. Results Neonates with HCA had increased risk for any stage ROP (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3–2.4) and severe ROP (OR 1.5; 95% CI 1.2–1.8) compared with neonates without HCA. The rates of any stage ROP (OR 1.8; 95% CI 1.4–2.2) and severe ROP (OR 1.4; 95% CI 1.1–1.6) were higher in neonates with FUN compared with neonates without FUN. Multivariate meta-regression analysis suggests that lower GA increases the effect size between FUN and severe ROP. Conclusion This meta-analysis confirms that presence of HCA and FUN are risk factors for any stage ROP and severe ROP. Structured histological placental examination of HCA and FUN may be a tool to further refine the ROP risk profile. Key Points