Analysing the risk factors and clinical features of intraventricular haemorrhage-periventricular leukomalacia in premature infants and association with a new marker: Neutrophil-to-lymphocyte ratio

Analysing the Risk Factors and Clinical Features of Intraventricular Haemorrhage -Periventricular Leukomalacia in Premature Infants and Association with A New Marker: Neutrophil-to-Lymphocyte Ratio Germinal matrix haemorrhage and intraventricular haemorrhage (GMH-IVH) remain common and clinically substantial challenges amongst premature infants, especially in extremely premature infants. Periventricular leukomalacia (PVL), a significant cause of neurological morbidity among premature infants, arise from ischemic loss of white matter. Neutrophil-to-lymphocyte ratio (NLR) is a marker that newly came into use which might be an indicator of systemic inflammation and has been linked with prognosis of many diseases. In this study we aim to identify GMH-IVH, severe GMH-IVH and PVL with their associated risk factors and short-term complications in addition to investigate the correlation between GMH-IVH and PVL with a new marker neutrophil-to-lymphocyte ratio, CBC and coagulation parameters. In our study we evaluated prenatal, natal, postnatal factors and lab results of premature infants diagnosed with GMH-IVH and/or PVL in 5 years period from 2016 to 2020. In our study the data of 132 premature infants, 106 with GMH-IVH and 61 with PVL, were reviewed. GMH-IVH frequency was %9.69 and there were no statistically significant relation with GMH-IVH and prenatal, natal or postnatal factors except with the intubation in the delivery room. However, when associated factors of severe GMH-IVH reviewed, grade 3-4 GMH-IVH ratio was significantly less in those who received full dose of antenatal steroid, whose 1-minute Apgar and 5-minute Apgar scores were between 7-10, and whose blood sodium levels were in the normal range. Statistically significant effects on developing GMH-IVH of antenatal steroid administration, 1-minute Apgar and 5-minute Apgar scores, delivery room intubation and blood sodium levels were seen in the regression analysis. Statistically significant relations were found between grade 3-4 GMH-IVH and delivery room intubation or CPR, invasive mechanical ventilator use, GIS perforations, hypotension, acidosis, caffeine, and transfusions of following: ES, thrombocyte, TDP and cryoprecipitate. In the regression analysis, statistically significant effects of hypotension, hypotension developing after the 7th day, blood and blood component transfusions on the development of grade 3-4 GMH-IVH were observed. Grade 3-4 GMH-IVH was found significantly associated with hydrocephaly, shunt insertion, and exitus. PVL frequency observed as %5.58. High statistical significances found between the development of PVL and hypercarbia, hypocarbia, repetitive transfusions of ES, abnormal EEG results, seizures and seizures seen in the first 24 hours. In the regression analysis, statistically significant effects of seizure presence on the development of PVL were observed. Surgical interventions were found statistically significant with development of PVL, and mortality ratio was %11.48. Our study revealed that the following parameters of premature babies with GMH-IVH and PVL had sublimit values of their age groups at the time of first diagnosis; Hb(g/dL), HCT(%), MCV(fL), Macro-R(%). These parameters observed significantly decreased over the time after the 14th day except for the Macro-R(%) which showed significant increases after the 14th day. In both cases new CBC parameters and detection of microcytic erythrocytes will contribute to the early diagnosis and treatment of iron deficiency anaemia. Furthermore, LYMPH(10^3/uL), LYMPH(%), HFLC(10^3/uL), PDW(fL), MPV(fL), PCT(%) levels were on the rise while NEUT(%) levels were descending in the premature infants with GMH-IVH and PVL. Contrary to infants with PVL, we observed significant decrease on NLR among infants with GMH-IVH. The increase in PLT(10^3/uL), PDW(fL), MPV(fL), PCT(%) values of both the GMH-IVH and PVL groups over time and the low platelet counts measured at the time of initial diagnosis in both groups might have contributed to the bleeding and/or hypoxia. Lastly, prolonged PTT(sn) levels before the diagnosis observed as shortened after the diagnosis in GMH-IVH group while APTT levels observed as decreased after the diagnosis in the PVL group. In the GMH-IVH group day 0 and day 14 NLR values found higher in exitus cases comparing the non-exitus cases. Seizures, hydrocephaly and shunt insertion found irrelevant with the NLR values in GMH-IVH group. In the GMH-IVH group day 0 NLR values predicted exitus cases with 90% sensitivity and 74.19% specificity for cut-off >2.41 while day 14 NLR values predicted exitus cases with 100% sensitivity and 69.35% specificity for cut-off >1 in the same group. In the PVL group day 14 NLR values were higher in exitus cases comparing to non-exitus cases. In this group day 14 NLR values predicted exitus cases with 100% sensitivity and 95.45% specificity for cut-off >2.49. In PVL group there were no significant relevance between seizures and NLR values. In conclusion, assessment of GMH-IVH, severe GMH-IVH and PVL associated risk factors may provide important information for preventive approaches especially towards severe GMH-IVH and PVL. Enhanced use of antenatal steroids with proper indications, reducing the need of mechanical ventilation, preventing hypotension, acidosis, and fluctuations in blood serum sodium, avoiding unnecessary transfusions of blood and blood components will lower the chances of developing GMH-IVH, especially grade 3-4. Frequency of PVL will decrease with preventing the PaCO2 irregularities in blood gas, avoiding repetitive transfusions of ES, preserving premature infants from occasions such as seizure and surgical interventions which might contribute developing PVL. New CBC parameters and coagulation parameters might be beneficial for early diagnosis, treatment and determine the mortality. NLR might be used as a prognostic marker for GMH-IVH and as a parameter to predict mortality in GMH-IVH and PVL groups. This ratio will contribute specially to reduce the mortality and morbidity of GMH-IVH and PVL likewise it will help to recognize the risk factors associated with GMH-IVH, severe GMH-IVH and PVL. Keywords: Premature, Germinal Matrix Haemorrhage and Intraventricular Haemorrhages, Periventricular Leukomalacia, New Complete Blood Count and Coagulation Parameters, Neutrophil-To-Lymphocyte Ratio