ROP is defined as a multifactorial disease, and its pathogenesis consists of two phases. In the first phase, retinal vascularization is inhibited due to postnatal hyperoxia. In the second phase, the retina becomes hypoxic due to a retinal vascularization disorder. Afterward, neovascularization begins as a result of increased levels of mediators such as VEGF, erythropoietin, and IGF-1 [15]. Studies also show that there is a “pre-phase” due to placental inflammation that develops in the mother during the intrauterine period [11]. Studies have shown that both neonatal and maternal systemic inflammatory responses are important in the etiology of ROP [2, 16].
So far, inflammatory markers from complete blood counts have been suggested as potential markers of inflammation in a variety of diseases, including bronchopulmonary dysplasia and kidney diseases [17, 18]. With the increasing importance of the role of inflammation in ROP, studies in this area have increased in recent years. However, in the early period of a newborn's life, many factors such as birth stress, early or late cord clamping, normoblasts, and antenatal steroid use may cause inconsistent results in the pediatric complete blood count [19, 20]. Prenatal maternal inflammation may also influence the pathogenesis of ROP. Therefore, in this study, we investigated whether maternal inflammatory markers could predict TR-ROP.
In the study of Celik et al. [10], the complete blood count parameters of preterm infants who received ROP treatment and those who did not develop ROP and their mothers (1 day before birth) were evaluated. While maternal WBC was found to be significantly higher in the TR-ROP group, maternal NLR, LMR, PLR, and PCI were not significantly different. (maternal WBC AUC = 0.69). In addition, infant WBC was found to be significantly lower in the TR-ROP group. Woo et al. [21] found clinical chorioamnionitis (excluding histological chorioamnionitis) and increased maternal WBC to be significant independent risk factors for the development of ROP at any stage. We found a significant reduction in maternal lymphocyte count in the TR-ROP. However, we think that GA may affect the results when interpreting neonatal CBC results. Previous studies have reported that neutrophil abnormalities and lymphocyte maturation are altered in GA [22, 23]. When the lymphocyte counts adjusted for GA were evaluated, there was no significant difference between the groups (p = 0.06).
Novel inflammatory prognostic markers generated from the peripheral blood of infant, including the NLR, PKI, LMR, and PLR, have been researched for their prognostic significance in the development of ROP [7, 8, 24]. The prognostic effects of PLR, NLR, and LMR on ROP were investigated, and only LMR showed a significant difference in multivariate analysis. Similar LMR results were obtained in the hemogram study of infants with ROP by Hu et al [7]. Therefore, it can be said that both maternal and infant LMR values are more significant than NLR and PLR in terms of diagnostic value in ROP. In contrast to the study by HU et al., all infants in our study had ROP. The significant difference in infants with TR-ROP shows that LMR is also an effective parameter in the prognosis of ROP.
The SII is a new immune marker [25]. The SII was calculated by the formula = neutrophil x platelet/lymphocyte. Akdogan et al. [8] reported the only study in the literature on the relationship between SII and ROP, and our study is the first on the relationship between maternal SII and ROP relationship. Akdogan et al. reported that infants with ROP had a higher SII value than infants without ROP in the 1-month period, and they stated that for ROP, SII could be an independent predictor for ROP. In our results, we did not find a significant difference in maternal SII between the groups. We concluded that maternal SII values are not of sufficiently important in predicting the diagnosis and prognosis of ROP.
In the study of Korkmaz et al. [9], they compared premature infants who received laser photocoagulation therapy and premature infants who did not receive treatment, and they found no difference in PMI values between the groups in the first phase of ROP, but they found a significant difference between the study groups in the second phase of ROP. Their result showed that PMI levels in the second phase of ROP may be important in the follow-up of ROP. They stated that PMI levels may also increase in parallel with the increase in VEGF in the second phase of ROP, as platelets play a role in the transport, storage, and release of VEGF. Our study is the first to show an association between maternal PMI and ROP. The fact that there was no difference in maternal PMI between the groups suggests that maternal PMI levels are not as significant as infant PMI levels in TR-ROP.
Mean platelet volume (MPV) is a parameter that indicates platelet activity, and MPV values have also been studied in the development of ROP. Ozkaya [26] reported that there was no difference between the groups in terms of other platelet parameters such as PMI, MPV, platelet count, and platelet distribution width (PDW). Similar results were obtained in our study, and there was no difference between the groups in maternal; MPV, platelet count, or PMI values.
This study showed that LMR values during the prenatal period can be a guide for the treatment of ROP development. Considering the significantly different results of LMR in infants with ROP in previous studies, our results support the importance of LMR in terms of the diagnosis and prognosis of ROP. The association of maternal SII, PMI, and MPV parameters with TR-ROP is also shown for the first time in this study.
This study has several limitations. The first limitation of this study is its retrospective nature. Second, the limited sample size in the study.