|Year : 2020 | Volume
| Issue : 1 | Page : 62-66
Evaluate the correlations of maternal systemic ınflammatory markers such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio with gestation age
Elif Didem Ozdemir1, Halis Ozdemir2
1 Department of Gyn and Obs, Akropol Hospital, Ankara, Turkey
2 Department of Gyn and Obs, Faculty of Medicine, Gazi University, Ankara, Turkey
|Date of Submission||30-Apr-2019|
|Date of Decision||13-Dec-2019|
|Date of Acceptance||02-Apr-2020|
|Date of Web Publication||14-Aug-2020|
Dr. Elif Didem Ozdemir
Nasuh Akar Mahallesi, Ziyabey Cd. No: 18, 06520 Cankaya/Ankara
Source of Support: None, Conflict of Interest: None
Objective: In this study, we aim to study the correlation between the maternal systemic inflammatory markers such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) including complete blood count (CBC) variables with gestation age, at the labor of our patients.
Materials and Methods: This retrospective study was performed with 1127 patients and their infants. We used the maternal CBC variables analyzed within the last day before active labor. We analyzed the statistical differences between the NLR, PLR, and other CBC variables in terms of gestational age.
Results: There was no statistically significant difference between the gestational age with NLR and PLR values, (P = 0.414 and P = 0.341, respectively). When we compare the NLR and PLR values in normal spontaneous vaginal delivery (NSVD) group, no statistically significant difference was found (P = 0.250; P = 0.995, respectively). In correlation analyses, no statistically significant correlation was detected between NLR and PLR with a birth weight of the infant and gestational age (P = 0.132 and P = 0.344, respectively). A linear, negative, weak correlation, and statistically significant correlation was detected between white blood cell count (WBC) with the infant's birth weight and gestational week (P < 0.01 and P = 0.024, respectively).
Conclusions: Inflammation plays an important role especially at the beginning of the labor. In our study, we showed no correlation of the NLR and PLR with a gestational week or infant's birth weight at labor. Also, in our research, the NLR and PLR values did not differ statistically among the four groups in terms of the gestational age of delivery with the highest values in the preterm birth (<37 weeks) groups (P = 0.414, P = 0.341, retrospectively).
Keywords: Gestation week; inflammation; neutrophil to lymphocyte ratio; platelet to lymphocyte ratio.
|How to cite this article:|
Ozdemir ED, Ozdemir H. Evaluate the correlations of maternal systemic ınflammatory markers such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio with gestation age. Trop J Obstet Gynaecol 2020;37:62-6
|How to cite this URL:|
Ozdemir ED, Ozdemir H. Evaluate the correlations of maternal systemic ınflammatory markers such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio with gestation age. Trop J Obstet Gynaecol [serial online] 2020 [cited 2021 Jan 25];37:62-6. Available from: https://www.tjogonline.com/text.asp?2020/37/1/62/292002
| Introduction|| |
The signals and mechanisms that synchronize the timing of human parturition remain a mystery, and a better understanding of these processes is essential to avert adverse pregnancy outcomes. The length of human gestation is related to many signals and mechanisms, such as fetal organs and systems maturation, production of hormones, and other soluble mediators (including alarmins) that promote inflammation and immune cascades, which trigger the parturition. So, it is considered that inflammation also plays a role in the timing of human parturition.,,
It appears that the presence of activated platelets in circulation rapidly and transiently induces systemic leukocyte rolling, giving the animal a head start on inflammation. Platelets and leukocytes are the main cellular elements for inflammation pathophysiology. The total white blood cell count (WBC) is a composite variable and a relatively crude marker of inflammation. The ratio of subtypes of blood cells like neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), which can be easily measured, are suggested as strong predictors of inflammation.,
Inflammatory markers have been suggested previously to be potential predictors of birth weight and in another study predictors of preterm deliveries. Therefore, in this study, we aim to study the correlation between the maternal systemic inflammatory markers such as NLR, PLR, and complete blood count (CBC) variables with the gestational age at the labor of our patients.
| Materials and Methods|| |
It is a retrospective study that has been conducted with 1430 patients who delivered in a hospital, between August 2016 and December 2018. The Ethics Committee approved this study. The study included healthy mothers between ages 18 and 43 years bearing a single fetus, taking no medications except iron and multivitamin preparations, and without any systemic comorbidities. Patients smoking a cigarette, having a fever of unknown origin, or any signs and symptoms of active infection (urinary infection, chorioamnionitis) or severe anemia, were not included in the study. We also excluded twin pregnancies, hypertension, diabetes, hypothyroidism, hyperthyroidism, and patients with any chronic inflammatory diseases like ulcerative colitis, Crohn's disease, rheumatoid arthritis. Because of this exclusion criteria, in total, we excluded 303 patients, and the study continued with 1127 patients. The gestational week was determined based on the first day of the last menstrual period or the first-trimester ultrasonographic measurement of the crown-rump length. The clinical data including the age, gravida, parity, gestation week at delivery, the gender of the baby, type of delivery, and the laboratory data such as CBC were recorded for each participant. Keçirören Education and Research Hospital Ethics, Committee number: 2012-KAEK-15/1735, Approval date:12.09.2018.
The study group was further divided into four groups according to the gestational age. The first group was preterm delivery defined as birth between 20+0 and 37+0 weeks of gestation, the second group was the early term, which was defined as 37+0 and 38+6 weeks of gestation, the third group was the full term, which is defined as 39+0 to 40+6 weeks of gestation, and the fourth group was the late term, which was 41+0 to 41+6 weeks of gestation. Postterm was ≥42+0 weeks of gestation (≥294 days from the first day of the last menstrual period and ≥14 days from the estimated day of delivery).,, There was no patient at that interval. The clinical and laboratory data were compared between groups.
We used the maternal CBC variables analyzed within the last day before active labor. CBC variables including hemoglobin (HBG), white blood cell (WBC), lymphocyte, neutrophil, platelet (PLT), platelet distribution width (PDW), red cell distribution width (RDW), and mean platelet volume (MPV) were measured by an automatic hematology analyzer at the central laboratory of the hospital. The NLR and PLR calculated quickly from the CBC was an assessable index, which had already been used as a prognostic tool in several clinical conditions. NLR and PLR values were calculated by dividing the absolute neutrophil, and platelet counts, respectively, by the total lymphocyte counts.
Statistical analyses were conducted with Statistical Package for the Social Sciences (SPSS) Statistics (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0, IBM Corp., Armonk NY) and MS-Excel 2007 software. The variables such as age, parity, gestational week of delivery, type of delivery, the sex of the baby, and birth weight were expressed in number and percentage. Shapiro-Wilk test was used to analyze normally distributed data including values of each variable. Comprehensive data related to these variables were represented in the mean, standard deviation, and median. The one-way analysis of variance (ANOVA) was applied to determine the differences between the means of independent groups for homogeneous groups with the normal distribution. All non-normally distributed data were compared using the Kruskal–Wallis test. The Tukey honestly significant difference (HSD) test was used when homogeneous distribution and Tamhane's T2 test were used when non-homogeneous distribution at post-hoc analysis. The box-plot graphs were drawn for the NLR and PLR variables. Correlation analyses were made to determine the relationship between the gestational and the weight of the baby with the variables of the CBC. The Spearman rho coefficients were also calculated. A P value <0.05 was considered statistically significant.
| Results|| |
In this study, a total of 1127 mothers and their babies were enrolled. The patients were divided into four groups based on their gestational week at delivery. First group was preterm delivery (<37 weeks), second group was early term (37+0 to 38+6 weeks), third group was full term (39+0 to 40+6 weeks), and fourth group was late term (41 + 0 to 41 + 6 weeks), which were consisted of 3.72% (n = 42), 56.61% (n = 638), 38.33% (n = 432), and 1.33% (n = 15) patients, respectively. Of the study participants, 66.01% (n = 744) underwent cesarean section (CS), whereas 33.98% (n = 383) had normal spontaneous vaginal delivery (NSVD). In addition, the gender of the infants were 52.4% (n = 591) males and 47.6% (n = 536) females.
The mean age of the participants was 29 ± 4.34 years, whereas the mean weight of the infants was 3294 ± 428 g. The demographic data of the groups such as age, parity, and birth weight were comparable between groups in [Table 1]. Also, the results related to the comparisons of CBC variables between the groups were summarized in [Table 1]. As seen in the table, admission levels of HGB, WBC, PLT, lymphocyte, neutrophil, platelets distribution width (PDW), red blood cell distribution width (RDW), mean platelet volume (MPV), NLR, and PLR values were compared among the groups. In terms of WBC values, there was a significant difference between the preterm group, with the early term and term group, respectively (P = 0.015; P = 0.042), no difference was observed among the other groups.
Lymphocyte and neutrophil percentages values were statistically different between groups in the Kruskal–Wallis test, but in the posthoc analysis, between groups, there was no statistical significance in the binary comparison.
The mean values of the NLR in study groups were assessed as follows: 3.79 ± 2.24 in the group of preterm delivery, 3.09 ± 1.99 in the group of early term, 3.27 ± 1.94 in the group of term, 3.67 ± 1.49 in the group of late term [Table 1], [Figure 1]. Also, the mean values of the PLR in study groups were assessed as follows: 116 ± 44 in the group of preterm delivery, 113 ± 45 in the group of early term, 112 ± 56 in the group of term, 107 ± 30 in the group of late term [Table 2], [Figure 2]. Furthermore, there was no statistically significant difference between the birth of gestation week with NLR and PLR values, (P = 0.414 and P = 0.341, respectively).
|Table 2: Correlation analyses in CBC variables between the birth weight and the gestational age|
Click here to view
The mean maternal hemoglobin (HGB) values included in the early term and term pregnancy groups were found to be 11.8 ± 1.5 and 12.2 ± 1.5, respectively, showing a significant difference between the delivery groups in the posthoc analysis (p = 0.001), there was no statistically significant difference between the other groups. In PLT, PDW, and RDW values, there was no statistically significant difference between groups. Furthermore, there was no statistically significant difference in binary comparison between groups for MPV values. When we compared the NLR and PLR values in the NSVD group, no statistically significant difference was found (p: 0.250 and p: 0.995, respectively). Also in the NSVD group regarding the WBC, lymphocyte (%), neutrophil (%), HGB, RDW, MPV, and PLT values there was no significant difference. Only PDW values were significantly different between early term and term groups (p = 0.044).
In correlation analyses, no statistically significant correlation was detected between NLR and PLR with the birth weight of the infant and gestational week (P = 0.132 and P = 0.344, respectively). A linear, negative, weak correlation, and statistically significant correlation was detected between WBC with the infant's birth weight and gestational week (P < 0.01 and P = 0.024, respectively). A linear, negative, weak correlation, and statistically significant correlation was detected between PLT with the infant's birth weight and gestational week (P = 0.018 and P < 0.01, respectively). A linear, positive, weak correlation, and statistically significant correlation was detected between HGB with the gestational week (p = <0.01) [Table 2].
| Discussion|| |
In our study, the main finding is no correlation of the NLR and PLR with a gestational week or infant's birth weight at labor.
Several studies have shown that maternal and maternal-fetal inflammation may trigger premature labor., Inflammation plays an important role especially at the beginning of the labor. Because of this, many studies have been designed to establish which mechanisms initiate labor. In our study, the main hypothesis is also this idea.
In the literature, although Akgun et al., showed a negative correlation between the NLR and PLR with gestational week and the infant's birth weight, in our study we showed no association of the NLR and PLR with a gestational week or infant's birth weight at labor [Table 2]. Also, in our study the NLR and PLR values did not differ statistically among the four groups in terms of the gestational week of delivery with the highest values in the preterm birth (<37 weeks) groups (P = 0.414 and P = 0.341, retrospectively) [Table 1].
In the literature, anemia was associated with preterm delivery (Relative Risk [RR]:1.63, 95% CI: 1.33, 2.01). But this study did not confirm this condition. Probably this is because of the low number of patients in the preterm and late-term group. Also, it has been affected by the patients with high socio-economic levels which are followed up at a private hospital.
The RDW blood test measures the amount of red blood cell variation in volume and size. High RDW values may mean you have a nutrient deficiency, anemia or other underlying condition. RDW seems to be a predictor for a wide range of conditions due to systemic factors such as inflammation and oxidative stress that alter erythrocyte hemostasis. In RDW values there were no statistically significant differences between groups in this study. In the course of a healthy pregnancy, RDW values increase, as the gestational week progresses. This knowledge did not support our research (Spearman rho correlation 0.028, P = 0.352).
In the literature, PDW which is the measurement of platelet anisocytosis calculated from the distribution of individual platelet volumes and it is an assessment of circulating platelet mass, and it is defined as a marker of coagulation. In the PLT and PDW values, there were no statistically significant differences between groups. MPV is a measure of platelet size that shows platelet function and activation and can be measured by full blood count analyzers as part of a routine CBC test cycle, with no additional cost. Based on data showing that PDW and MPV values are associated with inflammation, we investigated if any alterations PDW and MPV, during the gestational age. We found no significant difference. Furthermore, there was no statistically significant difference in binary comparison between groups for MPV values.
The first major limitation of our study is, it is a retrospective design. Nonetheless, the second limitation of our study is the unequal distribution of the number of cases among the groups. Although the total number of cases was sufficient for analysis, it was challenging to reveal the statistical differences due to the unequal distribution among the groups. This is one private center study. Only low-risk patients with mid and high socioeconomic levels were involved in this study. We can say this homogenous distribution of the patients is the powerful side of our research.
In conclusion, this retrospective study is one of the few studies in the literature which investigates the correlation of NLR and PLR with the gestational week of labor. Also, to the best of our knowledge, this is the first study using term pregnancy classification.,, Our study suggested that the maternal NLR and PLR are not correlated with the gestation week of birth and weight of the infant.
The authors report no declarations of interest.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Menon R, Bonney EA, Condon J, Mesiano S, Taylor RN. Novel concepts on pregnancy clocks and alarms: Redundancy and synergy in human parturition. Hum Reprod Update 2016;22:535-60.
Kelly RW. Inflammatory mediators and parturition. Rev Reprod 1996;1:89-96.
Romero R, Miranda J, Chaiworapongsa T, Korzeniewski SJ, Chaemsaithong P, Gotsch F, et al
. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol 2014;72:458-74.
Wagner DD. New links between inflammation and thrombosis. Arterioscler Thromb Vasc Biol 2005;25:1321-4.
Gibson PH, Cuthbertson BH, Croal BL, Rae D, El-Shafei H, Gibson G, et al
. Usefulness of neutrophil/lymphocyte ratio as a predictor of new-onset atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 2010;105:186-91.
Li N. Platelet-lymphocyte cross-talk. J Leukoc Biol 2008;83:1069-78.
Akgun N, Kalem NM, Yuce E, Kalem Z, Aktaş H. Correlations of maternal neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with birth weight. J Matern Fetal Neonatal Med 2017;30:2086-91.
Daglar HK, Kirbas A, Kaya B, Kilincoglu F. The value of complete blood count parameters in predicting preterm delivery. Eur Rev Med Pharmacol Sci 2016;20:801-5.
ACOG Committee Opinion No 579: Definition of term pregnancy. Obstet Gynecol 2013;122:1139-40.
Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ. Births: Final data for 2015. Natl Vital Stat Rep 2017;66:1.
Pantzaris ND, Platanaki C, Pierrako C, Karamouzos V, Velissaris D. Neutrophil-to-lymphocyte ratio relation to sepsis severity scores and inflammatory biomarkers in patients with community-acquired pneumonia: A case series. J Transl Int Med 2018;6:43-6.
Oaks B, Stewart C, Laugero K, Adu-Afarwuah S, Lartey A, Baldiviez L, et al
., Associations of maternal cortisol, ınflammation, hemoglobin, ıron status, and BMI with birth outcomes in pregnant women in Ghana. FASEB J 2015;29 (1_supplement).
Stout MJ, Cao B, Landeau M, French J, Macones GA, Mysorekar IU. Increased human leukocyte antigen-G expression at the maternal–fetal interface is associated with preterm birth. J Matern Fetal Neonatal Med 2015;28:454-9.
Rahman MM, Abe SK, Rahman MS, Kanda M, Narita S, Bilano V, et al
. Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: Systematic review and meta-analysis. Am J Clin Nutr 2016;103:495-504.
Özer S, Yılmaz R, Sönmezgöz E, Karaaslan E, Taşkın S, Bütün İ, et al
. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever. Med Si Monit 2015;21:298-303.
Lurie S, Mamet Y. Red blood cell survival and kinetics during pregnancy. Eur J Obstet Gynecol Reprol Biol 2000;93:185-92.
Vagdatli E, Gounari E, Lazaridou E, Katsibourlia E, Tsikopoulou F, Labrianou I. Platelet distribution width: A simple, practical and specific marker of activation of coagulation. Hippokratia 2010;14:28-32.
Sandhaus LM, Meyer P. How useful are CBC and reticulocyte reports to clinicians? Am J Clin Pathol 2002;118:787-93.
[Figure 1], [Figure 2]
[Table 1], [Table 2]