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May ratio of neutrophil to lymphocyte be useful in predicting the risk of


developing preeclampsia? A pilot study

Article  in  The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies,
the International Society of Perinatal Obstetricians · March 2014
DOI: 10.3109/14767058.2014.905910 · Source: PubMed

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ISSN: 1476-7058 (print), 1476-4954 (electronic)

J Matern Fetal Neonatal Med, Early Online: 1–3


! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.905910

ORIGINAL ARTICLE

May ratio of neutrophil to lymphocyte be useful in predicting the risk of


developing preeclampsia? A pilot study
Emel Kurtoglu, Arif Kokcu, Handan Celik, Migraci Tosun, and Erdal Malatyalioglu

Department of Obstetrics and Gynecology, School of Medicine, University of Ondokuz Mayis, Samsun, Turkey
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 78.163.92.33 on 04/11/14

Abstract Keywords
Objective: The aim of the study was to evaluate the relationship between neutrophil to Lymphocyte, neutrophil, preeclampsia,
lymphocyte ratio (NLR) and preeclampsia. pregnancy
Methods: Demographic data and laboratory tests for NLR of 203 pregnant women (73 normo-
tensive pregnants, 23 pregnants with mild preeclampsia and 107 pregnants with severe History
preeclampsia) were retrospectively analyzed. Neutrophil to lymphocyte ratios were compared
between the study groups. Received 7 February 2014
Results: Preeclamptic pregnant women had smaller gestation weeks, lower hemoglobin Accepted 16 March 2014
level and fetal birth weight than that of normal pregnant women. NLR in preeclamptic group Published online 9 April 2014
was significantly higher than that of normal group (p ¼ 0.023) and area under ROC curve was
found statistically significant (p ¼ 0.023). However, there was no statistically significant
relationship between NLR and severity, proteinuria level, subjective symptoms and onset
For personal use only.

time of the disease.


Conclusion: The findings showed that the measurement of NLR periodically may be useful
to predict high-risk pregnancies in terms of preeclampsia, but further studies are needed to
determine its contribution.

Introduction Methods
Preeclampsia is a hypertensive and multisystem disorder that We retrospectively analyzed demographic data and laboratory
affects 4–6% of all pregnancies [1,2]. Although the etiology tests for NLR of 203 pregnant women who were admitted to
has not been clearly defined, studies have suggested several labor and delivery unit of Ondokuz Mayis University Hospital
factors including hyper-reactivation of inflammatory cells and between January 2012 and December 2014. The study group
immunologic responses in which neutrophils and lymphocytes was divided into three groups: group 1: the normotensive
take place by releasing inflammatory cytokins and auto- pregnant women (n ¼ 73), group 2: the pregnants with severe
antibodies, and leading to endothelial dysfunction [3–8]. preeclampsia (n ¼ 107) and group 3: the pregnants with mild
Apart from the probable effects of these two subsets of preeclampsia (n ¼ 23).
leukocytes in preeclampsia, recently, the ratio of neutrophil Preeclampsia with systolic blood pressure 140 mm Hg or
to lymphocyte (NLR) has been of much interest in terms of diastolic blood pressure 90 mm Hg on two occasions at least
their prognostic and predictive values in several different two hours apart after 20 weeks of gestation in a previously
topics such as cancers and cardiac diseases [9–12]. normotensive patient and proteinuria 0.3 g in a 24-h
Considering this information in the literature, we aimed specimen or protein dipstick + if a quantitative measurement
to evaluate the relationship between NLR and clinical features is unavailable was defined as mild preeclampsia. The cases
of preeclampsia. To the best of our knowledge, this is the with one or more of the following criteria were diagnosed
first study doing research on the relationship between NLR with severe preeclampsia: new onset of severe headache or
and preeclampsia. visual disturbance, severe epigastric pain, or serum trans-
aminase concentration  twice normal or both, systolic blood
pressure 160 mm Hg or diastolic  110 mmHg on two
occasions at least two hours apart while the patient is on
bed rest, thrombocytopenia (100.000 mic/L), serum creatin-
ine  1.1 mg/dL or pulmoner edema.
Address for correspondence: Arif Kokcu, Department of Obstetrics and
Patients were excluded from this study if any of the
Gynecology, School of Medicine, University of Ondokuz Mayis;
Kurupelit, 55139 Samsun, Turkey. Tel: (+90) 0362 3121919-2452. followings present: hypertension, diabetes mellitus, metabolic
Fax: (+90) 362-4576029. E-mail: arifkokcu@yahoo.com syndrome, nephropathy, renal or hepatic dysfunction, left
2 E. Kurtoglu et al. J Matern Fetal Neonatal Med, Early Online: 1–3

Table 1. Comparison of demographic features between normal and


preeclamptic pregnancies.

Control group Preeclamptic


Features (n ¼ 73) group (n ¼ 130) p Value
Age (year) 30.1 ± 4.9 29.2 ± 7.1 0.308
Gravida 2 (1–7) 2 (1–9) 0.545
Parity 1 (0–5) 0 (0–5) 0.943
Gestational age (week) 38 (25–41) 36 (25–41) 0.005*
Hb (g/dL) 11.9 ± 1.2 11.4 ± 1.9 0.019*
Fetal birth weight (g) 2726.3 ± 947.1 2335.6 ± 942.2 0.005*

*Statistically significant (p50.05)

ventricular dysfunction, valvular heart disease, known malig-


nancy, abnormal thyroid function tests, previous history of
local or systemic infection, any medication that related to
inflammatory condition of patient such as corticosteroids, Figure 1. Comparison of NLR levels between control and preeclamptic
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 78.163.92.33 on 04/11/14

ruptured membranes. Following admission of the pregnants groups. Horizontal lines in the middle of each box indicates the median
value.
to delivery unit, demographic features, complete blood
count with differentials including the NLR, blood pressures,
proteinuria, subjective findings, past medical history were Table 2. Distribution of NLRs according to the clinical features of
preeclamptic group.
recorded before delivery, and fetal birth weight, 1st and 5th
minute Apgar scores were recorded after delivery. Features NLR p Value
Data analysis was performed by using SPSS for Windows,
version 11.5 (SPSS Inc., Chicago, IL). Whether the distribu- Onset time
32 weeks (n ¼ 33) 4.8 (1.9–20.2) 0.934
tions of continuous and metric discrete variables were 432 weeks (n ¼ 97) 4.7 (1.1–39.6)
normally or not was determined by the Kolmogorov– Severity
For personal use only.

Smirnov test. The Levene test was used for the evaluation Mild (n ¼ 23) 4.5 (2.2–34.2) 0.355
Severe (n ¼ 107) 4.8 (1.1–39.6)
of homogeneity of variances. Data were shown as mean ± SD
Headache
or median (min–max), where applicable. Yok (n ¼ 94) 4.7 (1.1–39.6) 0.710
While the mean differences between groups were com- Var (n ¼ 36) 4.7 (2.2–35.3)
pared by Student’s t test, otherwise, Mann–Whitney U-test Epigastric pain
No (n ¼ 121) 4.7 (1.1–39.6) 0.170
was applied for comparisons of the median values. The Yes (n ¼ 9) 5.6 (3.1–35.3)
Kruskal–Wallis test was used for determining the differences Visual disturbance
in median values among more than two groups. Degrees No (n ¼ 124) 4.7 (1.1–39.6) 0.478
of association between continuous and metric discrete vari- Yes (n ¼ 6) 5.4 (3.1–13.9)
Proteinuria
ables were evaluated by Spearman’s rank correlation analyses. I (n ¼ 35) 4.4 (2.2–17.4) 0.257
Categorical data were analyzed by Pearson’s Chi-square or II (n ¼ 54) 5.0 (1.1–39.6)
Fisher’s exact test, where applicable. III (n ¼ 41) 4.7 (1.7–35.3)
The optimal cut-off points of NLR to discriminate case and
control groups each other was evaluated by ROC analysis
calculating area under the curve as giving the maximum group was significantly higher than that of normal group
sum of sensitivity and specificity for the significant test. (p ¼ 0.023) (Figure 1). In preeclamptic group, there was no
Sensitivity, specificity, positive and negative predictive values statistically significant relationship between NLR and sever-
were also calculated at the best cut-off point for NLR. p Value ity, proteinuria level, subjective symptoms and onset time of
less than 0.05 was considered statistically significant. the disease (p40.05) (Table 2). ROC analysis was performed
to discriminate the two study groups and area under ROC
curve was found statistically significant (p ¼ 0.023). The
Results
findings are shown in Table 3.
The study included 130 pregnant women diagnosed with
preeclampsia and 73 healthy pregnant women. The compari-
Discussion
son of demographic features between the groups is shown
in Table 1. There was no statistically significant difference NLR has become popular recently so that many studies have
between two groups in terms of median age, gravida and been done to find out the predictive value of NLR in many
parity. However, preeclamptic pregnants had smaller gestation different topics, particularly cancers. Pre-treatment NLR has
weeks, lower hemoglobin level and fetal birth weight than that been mentioned to be significantly elevated and useful as a
of normal pregnant women (p ¼ 0.005 and p ¼ 0.019, prognostic indicator by several researchers [10,12,13]. To
respectively). date, there have been several studies about predictive markers
Median NLR was 4.1 (1.5–21.6) in the control group, 4.7 and prognostic factors of preeclampsia, but, unfortunately
(1.1–39.6) in the preeclamptic group. NLR in preeclamptic only a few have been found to be significant [14–17].
DOI: 10.3109/14767058.2014.905910 Ratio of neutrophil to lymphocyte in preeclampsia 3
Table 3. The results of ROC analysis for NLR discrimination of preeclamptic and control groups.

Cut-off value of NLR Sensitivity Specificity PPV NPV AUC p Value Accuracy
4.48 75/130 (57.7%) 46/73 (63.0%) 75/102 (73.5%) 46/101 (45.5%) 0.596 0.023 121/203 (59.6%)

AUC: area under the curve; PPV: positive predictive value; NPV: negative predictive value.

Leukocytosis is one of the well-documented phenomenon 4. Laresgoiti-Servitje E, Gómez-López N, Olson DM. An immuno-
logical insight into the origins of pre-eclampsia. Hum Reprod
of pregnancy. The total blood leukocyte count may increase as Update 2010;16:510–24.
high as 16.000/mL [18]. In normal pregnancies, leukocytosis 5. Wallukat G, Homuth V, Fischer T, et al. Patients with preeclampsia
is also considered to be evidence of an increased inflamma- develop agonistic autoantibodies against the angiotensin AT1
tory response. Since preeclampsia is suggested to be an receptor. J Clin Invest 1999;103:945–52.
6. Benyo DF, Smarason A, Redman CW, et al. Expression of
inflammatory process, alteration in white blood cell count inflammatory cytokines in placentas from women with preeclamp-
has been investigated in order to find out the relationship sia. J Clin Endocrinol Metab 2001;86:2505–12.
between leukocytosis and preeclampsia. Studies found 7. Gu Y, Lewis DF, Deere K, et al. Elevated maternal IL-16 levels,
increased leukocyte counts in preeclamptic group and enhanced IL-16 expressions in endothelium and leukocytes, and
increased IL-16 production by placental trophoblasts in women
significantly elevated levels in severe cases, including
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 78.163.92.33 on 04/11/14

with preeclampsia. J Immunol 2008;181:4418–22.


HELLP syndrome [19–21]. However, in this study, we 8. Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia:
chose to research the relationship between preeclampsia and current concepts. Am J Obstet Gynecol 1998;179:1359–75.
NLR, considering the number of leukocytes can be affected 9. Cho H, Hur HW, Kim SW, et al. Pre-treatment neutrophil to
lymphocyte ratio is elevated in epithelial ovarian cancer and
by many factors. Also, the previous studies found increased, predicts survival after treatment. Cancer Immunol Immunother
particularly, neutrophil count, not other subsets, in pre- 2009;58:15–23.
eclamptic patients [1,19,20]. In this study, it was seen that 10. Thavaramara T, Phaloprakarn C, Tangjitgamol S, et al. Role of
NLR in preeclamptic pregnancies was significantly higher neutrophil to lymphocyte ratio as a prognostic indicator for
epithelial ovarian cancer. J Med Assoc Thai 2011;94:871–7.
than that in the normal group (Figure 1). However, there 11. Szkandera J, Stotz M, Eisner F, et al. External validation of the
was no significant relationship between NLR and the severity derived neutrophil to lymphocyte ratio as a prognostic marker on a
of preeclamsia (Table 2). large cohort of pancreatic cancer patients. PLoS One 2013;8:
For personal use only.

Since previous studies supporting increased leukocyte e78225.


12. Unal D, Eroglu C, Kurtul N, et al. Are neutrophil/lymphocyte and
count in preeclampsia also mentioned increased neutrophils platelet/lymphocyte rates in patients with non-small cell lung
rather than other subsets, elevation in NLR is not considered cancer associated with treatment response and prognosis? Asian
to be surprising [1,20]. Nevertheless, it may be questioned Pac J Cancer Prev 2013;14:5237–42.
that if there is a valuable cut-off point for NLR in 13. Kim JY, Park T, Jeong SH, et al. Prognostic importance of
baseline neutrophil to lymphocyte ratio in patients with advanced
preeclampsia, so we did ROC analysis and found area under papillary thyroid carcinomas. Endocrine 2013 Nov 23 [Epub ahead
curve statistically significant with a optimal cut-off point of print].
¼ 4.48. NLR was also evaluated according to this cut-off 14. Cheifetz S, Bellon T, Cales C, et al. Endoglin is a component of the
value and no significant difference was found in terms of transforming growth factor-beta receptor system in human endo-
thelial cells. J Biol Chem 1992;267:19027–30.
severity and onset time of the disease (Table 3). 15. Hromadnikova I, Vechetova L, Vesela K, et al. Non-invasive fetal
In conclusion, in antenatal follow-up, we think that the RHD exon 7 and exon 10 genotyping using real-time PCR testing
measurement of NLR periodically may be useful to predict of fetal DNA in maternal plasma. Fetal Diagn Ther 2005;20:
high-risk pregnancies in terms of preeclampsia. It should be 275–80.
16. Cho C, Turner L, Primakoff P, Myles DG. Genomic organization of
noted that this is a pilot study. In this regard, there is a need the mouse fertilin beta gene that encodes an ADAM family protein
for further prospective clinical studies. active in sperm-egg fusion. Dev Genet 1997;20:320–8.
17. Bohn H, Kraus W, Winckler W. Purification and characterization of
Declaration of interest two new soluble placental tissue proteins (PP13 and PP17).
Oncodev Biol Med 1983;4:343–50.
The authors report no declarations of interest. 18. Daniel AK, Brain JK. Maternal physiology during pregnancy.
In: Decherney AH, Nathan L, Goodwin TM, Laufer N, eds.
Current diagnosis and treatment obstetrics and gynecology. 10th ed.
References
New York (NY): McGraw Hill Company; 2007:156–71.
1. Canzoneri BJ, Lewis DF, Groome L, et al. Increased neutrophil 19. Piktin RM, Witte DL. Platelet and leukocyte counts in pregnancy.
numbers account for leukocytosis in women with preeclampsia. JAMA 1979;242:2696–8.
Am J Perinatol 2009;26:729–32. 20. Lurie S, Frenkel E, Tuvbin Y. Comparison of the differential
2. Chappell LC, Enye S, Seed P, et al. Adverse perinatal outcomes and distribution of leukocytes in preeclampsia versus uncomplicated
risk factors for preeclampsia in women with chronic hypertension: pregnancy. Gynecol Obstet Invest 1998;45:229–31.
a prospective study. Hypertension 2008;51:1002–9. 21. Terrone DA, Rinehart BK, May WL, et al. Leukocytosis
3. Ahmad S, Ahmed A. Elevated placental soluble vascular endothe- is proportional to HELLP syndrome severity: evidence for
lial growth factor receptor-1 inhibits angiogenesis in preeclampsia. an inflammatory form of preeclampsia. South Med J 2000;93:
Circ Res 2004;95:884–91. 768–71.

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