Authored by Shereen B Elbohoty*
Abstract
Aim: To evaluate neutrophil lymphocytic ratio (N/L) and platelet lymphocytic (P/L) ratio in detection of subclinical Chorioamnoitis in pregnant females suffering from premature rupture of membranes and to compare them with CRP and TLC.
Design: Clinical randomized controlled study.
Methods: 100 pregnant patients were selected suffering from PROM , and prepared for termination of pregnancy either normal or cesarean , all had no clinical signs of chorioamnoitis , blood markers ( CRP, TL, N/L ratio and P/L ratio) were taken before termination , the results statistically analyzed according to the result of pathological examination of amniotic membrane for detection of early inflammatory signs for chorioamnoitis.
Results: There was significant relationship for the P/L ratio and the finding of early chorioamnoitis by pathological examination with P value 0.0004 , however other markers failed to show any significant relationship with early chorioamnoitis , But CRP was found to have a significant relationship with the presence of postpartum complications with P value 0.0003 and other markers had insignificant relationship, There was insignificant relationship with all the four markers with the method of delivery , CRP and TLC had lower specificity in detection of subclinical chorioamnoitis as compared by N/L ratio and P/L ratio , also P/L ratio had the higher sensitivity 85.71% , so by comparing the four markers P/L ratio is the most accurate 90% and N/L ratio had accuracy more than TLC and CRP ( 80%).
Conclusion: P/L ratio and N/L ratio are available cheap markers for detection of subclinical chorioamnoitis, and they show more specificity and accuracy than CRP and TLC in detection of subclinical chorioamnoitis, also P/L ration had higher sensitivity.
Keywords: Subclinical chorioamnoitis, PROM , N/L ratio , P/L ratio , CRP , TLC
Introduction
Amniotic membrane, which is considered as a closed envelope around the fetus, is the most important barrier for protecting fetus from exterior , and the contained amniotic fluid gives the fetus the space to move and a media for excretion and also nutrion [1], Amniotic sac should remain intact till near the end of second stage of labour , Any break in the sac before that should be considered as a premature rupture of membrane (PROM), if it occurred before 36 weeks gestation it will be considered as preterm premature rupture of membranes [2].
The second most common cause of preterm labour is preterm PROM , as rupture of membranes will lead to local release of inflammatory mediators which in turn lead to premature uterine contractions that may end to preterm labour with its all hazards to the fetus [3]. But the most dangerous and most important concern about preterm PROM is the occurrence of chorioamnoitis [4]. Chorioamnoitis is inflammation of fetal membranes and may proceed to underlying decidua, it may lead to maternal toxemia and even septic shock, with very bad fetal outcome [5].
Occurrence of chorioamnoitis should be excluded in every case suffering from PROM , as it has dangerous consequences , and also may affect the course of labour when decision of labour is taken, as the uterus may not respond efficiently to uterotonic drugs in case of vaginal delivery that lead to increase rate of cesarean section , which also may complicated with surgical infection with all its hazards , with increase susceptibility to atonic postpartum hemorrhage [6].
Diagnosis of subclinical infection in case of PROM is a medical challenge. The most important and widely used markers are CRP and TLC , both had accepted specificity but low sensitivity making its use alone had many disadvantages and many misdiagnosed cases [7].
Neutrophil lymphocytic ratio (N/L) and platelet lymphocytic ratio (P/L) had been suggested to be used as alternative markers [8].
Methods
Study design: Prospective cohort study
Setting: Tanta University Hospital
Number of cases: 100 patients.
Timing of the study: from jun. 1, 2018 to august,31, 2019.
Cases selection: The cases were selected from the pregnant females whom attending Tanta University Hospital,
They were selected according to the following criteria:
1. Pregnant females with gestational age above 20 weeks gestation
2. Suffering from premature rupture of membranes
3. All the patients selected at time of termination of pregnancy whatever indication is except for acute chorioamnoitis ( like lung maturity , preterm labor pain , PROM before 24 weeks gestation)
And they were excluded if:
1. Presence of any clinical sign of chorioamnoitis ( fever , offensive vaginal discharge , tender uterus and non-reassuring non stress test)
2. If vaginal termination of pregnancy took more than 24 hours.
3. Patient with multiple gestations
4. Any systemic disease may affect N/L ratio or P/L ratio like Hematological disorders ,Malignancy, Hepatic diseases, autoimmune disease and Chronic renal diseases
5. Gestational D.M and pre-eclampsia.
6. Acute or chronic infectious or inflammatory diseases.
7. Cigarette smoker
Sample size calculation: The sample size was calculated using Epi-Info 7 specific program.
Methods:
• Written consent was taken from all patients submitted to the study with clarification of the methods, value and hazards of the study.
• Detailed history taking from all patients
• All patients before pregnancy termination were evaluated for absence of signs of acute chorioamnoitis
• Then blood sample was taken from the patient at time of termination of pregnancy if termination was normal , and before induction of anesthesia if termination was cesarean section , the blood sample used for :
1. C-reactive protein done by latex agglutination test. We took 2 mg/dl as a cut off value
2. Another 2ml of venous blood was collected into an EDTA contained bottle for .CBC measuring using an automated blood counter(ERMA PCE-210N) to measure the following :
A. Total leucocytic count ( normal 4000-11000/ul)
B. Platelet count (PCT), lymphocyte count and neutrophilic count were recorded so P/L ratio will be calculated; we took 125 as a cut off value.
C. Neutrophil –lymphocyte ratio(NLR) was calculated as absolute neutrophil count is divided by absolute lymphocyte count. We took 2.5 as a cut off value.
• Then after successful delivery of the baby, multiple samples from amniotic membrane were taken and sent for pathological examination for confirmation or exclusion of presence of inflammatory reaction so diagnosis of subclinical chorioamnoitis may or may not excluded.
• Correlation of the blood test with the pathological findings of absence or prescience of subclinical chorioamnoitis was evaluated using suitable statistical methods.
• Also, evaluation of the uterus and female postpartum was assessed for any complication.
Outcome:
A. Primary:
• Value of N/L ration and P/L ratio for diagnosis of subclinical chorioamnoitis and compared with CRP and TLC
B. Secondary:
• Relation of N/L ration and P/L ratio with timing of termination of pregnancy and compared with CRP and TLC
• Relation of N/L ration and P/L ratio with method of termination of pregnancy and compared with CRP and TLC
• Relation of N/L ration and P/L ratio with postpartum condition of mother and the uterus and compared with CRP and TLC
Ethical approval: This study was approved by local ethical committee of Tanta University before the start of this study.
Results
100 patients were selected in the course of study, all were suffering from PROM , and prepared for termination of pregnancy either normal or cesarean , all had no clinical signs of chorioamnoitis , blood markers were taken before termination , and the results statistically analyzed according to the result of pathological examination of amniotic membrane for detection of early inflammatory signs for chorioamnoitis.
Studying of patients’ data were demonstrated in Table 1, the gestational age at which termination of pregnancy was decided in the cases recruited for the study were range from 22-39 weeks gestation with mean 33.8 weeks, and the period of rupture of membranes range from 1-14 days with mean 5.05 days, of course in some cases the period of rupture of membranes was less than 1 day, those patient the duration of rupture of membrane was approximated to be 1 day.
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