The incidence of perineal Hypoxic-ischemic encephalopathy (HIE) in developing countries is several higher compared to other countries, ranging from 4.6 per 1000 full-term neonates with case fatality rates of more than 40% . HIE can induce permanent perineal morbidity, neurological handicap, and mortality. The early prediction of such disease is very important as the outcomes of HIE are permanent and devastating. In addition to its low therapeutic window and major side effects that can result from interventions of neuro protective equipment .
In this study, the median Apgar score at 5 min in the HIE group was 2.5 which was significantly lower compared to the control group which was 10; this finding was aligned with other studies that revealed low Apgar score associated with neonates born with perinatal asphyxia who later developed HIE [12, 13].
As regards NRBC, previous studies had issued NRBC as a hematopoietic marker in newborn babies with a strong relation to the intrauterine hypoxia, as the increase in NRBC count in infant’s blood circulation results from the boosting activity of erythropoietin. Moreover, it’s not only considered a biomarker for HIE but also predicts the risk of complications that occurred during HIE [14, 15]. In this study, we found the levels of NRBC/100 WBC in venous blood were higher in the HIE group than the control group achieving a mean of 6.60 in the HIE group and zero in the control group which was a huge difference compared to other studies who mentioned the NRBCs count level [11–18]. This difference between this study and other studies was because they measured NRBCs count in umbilical cord blood, but we measured this count in venous blood.
Also, the NRBC/100 WBC set to diagnose HIE achieved sensitivity of 100%, specificity 73.3%, NPV 88%, PPV 77%, accuracy 81% at best cutoff > 2.5. Moreover, the area under the curve of ROC was 0.917 with a p-value < 0.001. This comes in agreement with some studies, which stated that the levels of NRBC per 100 WBC were higher in HIE than in control one when they detect the variable in cord blood [13, 15]. Even though the exact mechanism is still unclear, it may be accompanied by the increase in erythropoietin level in blood which in turn induces the increase in NRBCs count over the increase in mitotic divisions of normoblasts [16, 17].
Regards serum lactate level, the mean serum lactate level in the HIE group was 71.03 mg/dl while it was 15.5 mg/dl in the control group revealing a highly significant difference between both groups as the p-value was < 0.001. But there was no association between grades of HIE and level of serum lactate level as moderate is the highest value of lactate level while mild is the lowest one . This comes in agreement with another study that showed that the serum lactate level was higher in HIE neonates than the control; however, it stated that the more severe form of neonatal hypoxia the more serum lactate . The association between the severity of HIE grades and neurological development issues in neonates was stated by some studies, hence early prediction of HIE signs with early proper treatment is a must [19, 20].
In this study, blood levels of lactate set to diagnose HIE were > 71.03 mg/dl that yielded a sensitivity of 100%, specificity 80%, NPV 100%, and PPV 83%. Also, the overall accuracy was good with 90% with area under ROC curve of 0.913, p < 0.001 with cutoff > 51.56. This comes in alignment with some studies that stated that the blood level of lactate with reasonable sensitivity and specificity scores could be used as a predictor of intrapartum hypoxia [18–21].
As regard serum vitamin D level, the HIE group mean was 7.11 pg/ml while it was 56.15 pg/ml in the control group with a highly significant lower score in the HIE group than the control group (p-value < 0.001). This finding was primarily because of maternal deficiency and poor supplements. Also, this comes in agreement with some studies which showed a strong association between HIE disease and vitamin D deficiency [20–22], and the serum level of vitamin D in neonates often continues to decline for about 72h . Although there is an association between HIE and Vit D deficiency, the exact interactions and mechanism still unclear.
All past studies [13–23] that illustrated the NRBCs count per 100 WBC, Vitamin D level, and serum lactate level were measuring these variables by umbilical cord blood; however we measured the same variables in venous blood levels and figured out matched results compared to umbilical cord blood results.
This study focused on venous blood as there are few studies that mentioned NRBC/100 WBC, serum lactate, and Vit D in venous blood, rather than many studies that focused on cord blood samples. The results of this study adds to knowledge of being a mid-high reliable source assessing these parameters in venous blood.
The first limitation of this study was the small sample size enrolled, as there were no chance to collect data from other hospital rather than the two hospitals included in this study; thus giving the results low impact in the medical knowledge. Besides, the study was a cross sectional case control which may maximize the standard error of the study, as well as the limitations shared of cross-sectional studies. We recommend further clinical trials with higher sample size to precise these results along with few limitations.