Although the role of inflammation in the pathophysiology of HEG is not clear, subclinical inflammation associated with oxidative stress might play an important role [8, 9]. Maternal inflammation causes an increase in cytokine and chemokine levels in the fetal/placental compartments. Uncontrolled inflammation may cause ischemia and destruction in the growing fetal tissues and adverse perinatal outcomes. Many studies on inflammation markers in HEG patients proposed strong associations between HEG development and inflammation. The increase in some cytokines and mediators such as TNF-alpha, IL-6, CRP, vaspin in HEG patients has indicated the inflammation in HEG[11, 12]. Also, increased Sirtuin-1 and CRP levels in the HEG patients supported this inflammatory response. Therefore, it is important to assess the degree of maternal inflammation to predict perinatal outcomes.
Complete blood count parameters have been investigated in many studies to predict adverse pregnancy outcomes such as preeclampsia, preterm birth, placental invasion anomalies, and preterm premature rupture of membranes (PPROM)[14–16], but there are not enough studies in which SII is used in obstetrics. However, Tanacan et al. showed that SII and platelet counts may be useful in the prediction of adverse outcomes in pregnancies complicated by PPROM. This study emphasized that the inflammation in PPROM and thus higher value of SII could be used as an additional parameter to predict adverse outcomes in these patients . In our study, we suggested that SII might be useful in demonstrating inflammation-related outcomes in HEG patients.
In recent studies, hematological parameters such as NLR, PLR, RDW, MPV, and PCT obtained from peripheral blood complete blood count have been shown to have prognostic and predictive value in various diseases such as inflammatory, autoimmune diseases, gynecological or gastrointestinal malignancies[18, 19]. In a study in which hematological parameters were evaluated as a marker of subclinical inflammation in HEG, NLR and PLR were found significantly higher in HEG patients than control groups. Also, in the same study, PDW and MPV, which are also used for platelet activation and diagnosis of many inflammatory diseases, did not differ significantly between HEG patients and the controls. However, Tayfur et al. showed the PCT value to be significantly higher in HEG patients . Studies on the relationship with systemic inflammatory markers obtained from complete blood count and ketonuria showed that these markers can be used in clinical practice. Our study found that NLR, PLR, PCT, and PDW increased as the degree of ketonuria increased. We also showed that SII significantly increased with the advancing degree of ketonuria, but lymphocytes, eosinophils, and LMR decreased. Increased levels of these parameters might be the consequences of an altered immune response of blood cells to physical stress in HEG.
Dehydration caused by vomiting can cause increased hemoconcentration, so hematocrit levels may raise in pregnant women with HEG. However, a previous study showed no significant changes in Hb and Hct values in patients with HEG(7). Although it was not statistically significant, our study found Hb and Hct values higher in patients with +3 and +4 ketonuria compared to those with +1 and +2 ketonuria. Hemoconcentration caused by dehydration can trigger systemic consequences such as oxidative stress and inflammation.
The relationship between the severity of disease and the degree of ketonuria is uncertain. Severe nausea and vomiting lead to ketonuria, which plays an important role in hospitalization. Some studies investigate whether HEG severity is associated with length of hospitalization, readmission, metabolic, biochemical, hematological, and clinical parameters, and inflammatory markers[22, 23]. The relationship between the degree of ketonuria and length of hospitalization was evaluated, and they found that ketonuria was not associated with the prolonged hospital stay. However, a previous study showed that women with a higher degree of ketonuria at hospital admission had a longer hospital stay. In our study, we examined the relationship between ketonuria and length of stay and we found a positive correlation between increased ketonuria and length of hospitalization.
Lymphocytes, neutrophils, and platelets, which are components of the SII formula, play a role in inflammation. Neutrophils are one of the major effectors of acute inflammation. They also contribute to chronic inflammatory circumstances and adaptive immune responses. While neutrophils have a destructive effect on the immune system, lymphocyte count decreases due to increased apoptosis in chronic inflammatory processes. Platelets enable to initiate and modulate immune functions by expressing several pro- and anti-inflammatory molecules. Considering the role of these blood cells in inflammation separately, we thought that their inclusion as a formula might be a better indicator of inflammation, so we evaluated SII as a study parameter.
As well as the role of NLR and PLR was described in HEG patients, there is not enough data on the use of SII in obstetrics in the literature. This is the first study in which SII has been used to predict the severity of HEG to date. Considering the positive relationship between ketonuria and length of hospitalization, the evaluation of SII in pregnant women with HEG may facilitate the clinical management of these patients. So it may differentiate the patients who need longer hospitalization, especially in this pandemic period. The fact that this parameter is cost-effective, practical, and noninvasive may expand its use in obstetrics.
The strength of the study was a large number of patients and study parameters. The limitations of this study were that it did not include long-term pregnancy outcomes.