The association between obesity and hematologic inflammatory markers in the first trimester pregnancies

Objective

Obesity is the defined as the abnormal or excessive accumulation of the fat which is harmful for the health, and its prevalence has been increasing. Many studies have shown that obesity alone leads to inflammation and causes poor gestational outcomes. In our study, we aimed to investigate the association between basic hematologic markers and obesity in the first trimester pregnancies.

Methods

A total of 321 pregnant women who admitted to the clinic of gynecology and obstetrics in a tertiary state hospital were included in the study. The patients were separated into three groups, which were normal weight (BMI: 18–24.9 kg/m2), overweight (BMI: 25–29.9 kg/m2), and obese (BMI>30 kg/m2). Of the patients, the demographic data (age, gravida, and parity) and the parameters of hemoglobin, hematocrit, white blood cell, neutrophil, lymphocyte, platelet (PLT), eosinophil, basophil, mean platelet volume (MPV), platelet distribution width (PDW), neutrophil/lymphocyte ratio (NLR), red blood cell distribution width (RDW), plateletcrit (PCT) and platelet/lymphocyte ratio (PLR) measured in the complete blood count which was checked in the first trimester routinely during the pregnancy follow-up were analyzed. The three groups were compared in terms of inflammatory markers.

Results

The patients were evaluated in three groups: 108 patients with normal weight (Group 1), 109 overweight patients (Group 2) and 104 obese patients (Group 3). No significant difference was found in terms of age, parity and gravida when the demographic data were analyzed among the groups (p>0.05). When the groups were compared in terms of hematologic markers, similar values were found in the markers other than white blood cell, neutrophil, lymphocyte, PLT and PCT values. The difference among white blood cell, neutrophil, lymphocyte, PLT and PCT values were between the patients with normal weight and obese patients, and the values of these markers were found higher in overweight / normal weight patient groups than the normal group (p<0.05).

Conclusion

The values of white blood cell, neutrophil, lymphocyte, PLT and PCT which were shown to be associated with inflammation were higher in the obese patients.

Keywords

Obesity, platelet, inflammation, hemoglobin

Introduction

Obesity is the defined as the abnormal or excessive accumulation of the fat which is harmful for the health. Since 1975, its rate increased three times all over the world.[1] According to the data of the World Health Organization (WHO) in 2016, 40% of adult women and 39% of adult men are overweight while 15% of adult women and 11% of adult men are obese.[2] According to the data of Public Health Agency of Turkey in 2010, 20.5% of men, 41% of women and 30.3% of the society are obese.[3] Clinically most appropriate marker for the classification of obesity is body mass index (BMI). BMI is found by dividing weight in kilograms by height in meters squared (kg/m2). WHO classified obesity in 6 groups according to BMI values: Underweight BMI<18.5 kg/m2, normal weight BMI: 18–24.9 kg/m2, overweight BMI: 25–29.9 kg/m2, obese class 1 BMI: 30–34.9 kg/m2, obese class 2 BMI: 35–39.9 kg/m2, and obese class 3 BMI>40 kg/m2.[1] Obesity a significant public health problem with many potential risks in the long term; cardiovascular disease, diabetes, osteoarthritis and cancer (breast, endometrium, ovary, liver, colon, prostate etc.) are among these risks. Maternal obesity is important in terms of the complications before, during and after pregnancy. Subfertility during preconceptional period, spontaneous abortion, gestational hypertension, preeclampsia, gestational diabetes, surmaturity, macrosomia, dystocia and intrauterine death during antenatal period, and increased risks of hemorrhage, infection and thromboembolism during postnatal period are associated with maternal obesity.[4] It is known that fat tissue is associated with inflammation and infection.[5] It is considered that obesity leads to inflammation and therefore causes poor obstetric outcomes (preeclampsia, gestational diabetes) and neonatal complications.[6] It is known that fat tissues in non-pregnant obese women call macrophage and initiate inflammatory process, and that they secrete high levels of proinflammatory cytokines such as tumor necrosis factor (TNF-a), IL 6, monocyte chemoattractant protein 1 (MCP 1), and transforming growth factor b (TGF-b).[5] The levels of high sensitivity C-reactive protein (HsCRP), leptin and MCP-1 were correlated with the increase of BMI in obese pregnant women.[6]
Complete blood count is a cheap and simple laboratory examination used routinely in pregnancy. When hematologic parameters are evaluated, it is known that NLR (neutrophil/lymphocyte ratio), PLR (platelet/lymphocyte ratio), RDW (red blood cell distribution width) and PCT (plateletcrit) have prognostic and predictive features in various diseases such as coronary artery disease, autoimmune diseases, inflammatory diseases, and gynecological and gastrointestinal cancers.[7,8] It was found that the levels of these markers increased in the inflammatory processes of pregnancy such as gestational diabetes, acute appendicitis, preeclampsia, etc.[9–11] In this study, we aimed to investigate the change of inflammatory markers according to BMI values in the first trimester pregnancies.

Methods

A total of 321 pregnant women during first trimester who admitted to the Clinic of Gynecology and Obstetrics of a tertiary state hospital between January 2019 and June 2019 were included in the study. The approval of the local ethics committee was obtained for this study. The patient data were accessed retrospectively from the hospital records.
The patients were classified as normal weight (BMI: 18–24.9 kg/m2), overweight (BMI: 25–29.9 kg/m2) and obese (BMI>30 kg/m2). Of the patients, the demographic data such as age, gravida and parity, and the levels of hemoglobin, hematocrit, white blood cell, neutrophil, lymphocyte, platelet, eosinophil, basophil, MPV, platelet distribution width (PDW), NLR, RDW, PCT and PLR measured in the complete blood count which was checked in the routine pregnancy follow-up were analyzed.
The patients on medications for those except pregestational diabetes, folic acid and infection which may cause chronic and acute inflammation were excluded from the study.
Statistical analysis
The data were analyzed by using Statistical Package Social Sciences (SPSS), version 22.0 (SPSS Inc., Chicago, IL, USA). The descriptive statistics were presented as standard deviations and mean values for numerical variables. In order to determine the normal distribution of the variables, Histogram and Kolmogorov-Smirnov test were used. Where applicable, Mann-Whitney U test and Student’s t-test were used for the comparisons of two groups. For multiple group comparisons, one-way ANOVA and Kruskal-Wallis H test were used. In the values with significant multiple group results, Tukey test was used for those with homogeneous variance and Mann-Whitney U test when non-parametric test was used. The value of p<0.05 was considered statistically significant.

Results

The results of demographic and hematologic comparisons according to BMI values are summarized in Table 1. The patients were evaluated in three groups, which were normal weight with 108 patients (Group 1), overweight with 109 patients (Group 2) and obese with 104 patients (Group 3). When the demographic data were evaluated among the groups, no significant difference was observed in terms of age, parity and gravida (p>0.05). In terms of hematological markers, all markers except white blood cell, neutrophil, lymphocyte, PLT and PCT levels were similar among the groups. The difference among white blood cell, neutrophil, lymphocyte, PLT and PCT values were between the patients with normal weight and obese patients.
The patients were also compared by separating them into two groups as the patients with normal weight and overweight/obese patients. The results of this comparison are shown in Table 2. The demographic data were similar between two groups (p>0.05). For the hematological markers, all markers except white blood cell, neutrophil, lymphocyte, PLT and PCT levels were similar among the groups. White blood cell, neutrophil, lymphocyte, PLT and PCT levels were higher overweight/obese patient groups than the normal group (p<0.05).

Discussion

Due to the rapid increase of obesity rates in the world, WHO has considered obesity as one of the most serious global health problems of the 21st century. The obesity prevalence in pregnancy has been reported between 1.8% and 25.3%.[4,12] The Centers for Disease Control and Prevention (CDC) reported that the obesity prevalence among the pregnant women completely reflects the obesity among women in fertility ages, 25% of the women at fertility ages in the USA were overweight and 25% of them were obese, and that maternal obesity is a major risk factor for maternal and perinatal mortality.[13]
The obesity has many adverse impacts on pregnancy. In Lashen et al. showed in their study that spontaneous abortion risk increases 1.2 times and recurring abortion risk increases 3.5 times in the first trimester of the pregnant women whose BMI was over 30 kg/m2.[14] There are also studies reporting that the obesity increases the incidences of gestational diabetes, preeclampsia and macrosomia,[15,16] and that it increases the rates of shoulder dystocia during delivery and cesarean section.[17] Pregestational maternal obesity is accounted for the most common reason of unexplained intrauterine fetal deaths.[18]
Chronic inflammatory conditions such as obesity causes elevated white blood cell (WBC) levels by increasing granulocyte production. It is known that the impaired glucose metabolism of WBC is associated with insulin resistance and type 2 diabetes.[19] It was reported that elevated WBC caused gestational diabetes during early pregnancy.[20] In our study, we found that WBC, neutrophil and lymphocyte levels which are directly associated with inflammation were significantly high in the obese group. This supports our hypothesis.
There are evidences showing that platelets do not only play a role in the coagulation mechanisms in the body, but also are associated with the development of immune response, allergic reactions and inflammation.[21] While the number of platelets decreases in order to provide hemostasis in the gestational thrombocytopenia, its functions and predispositions to aggression increase.[22] However, there are controversial opinions in terms of PDW, PCT and MPV levels in the blood during pregnancy. While some studies claim that there are differences between the trimesters,[23,24] there are also studies asserting that there is no difference between pregestational and post-gestational periods.[25,26]
MPV indicates mean platelet volume, and it ranges between 7.4 and 10.4 fl.[10] Elevated MPV levels are correlated with the increased hemostasis and coagulation systems. This is explained with higher activity with the increase of platelet levels.[23,27] Elevated MPV levels are also associated with diabetes and its complications.[28] Bozkurt et al. reported elevated MPV levels in the pregnant women with gestational diabetes who are at the 3rd trimester.[29] In our study, we did not find any difference among the BMI groups in the first trimester in terms of MPV levels.
PCT shows the volume of platelets by percentage in the blood, and it is calculated with the formula PLT ¥ MPV / 10,000 and it is much more significant parameter than PLT and MPV.[30] Its normal level in the blood is 0.22–0.24%.[31] Many studies investigated PCT level for many diseases associated with pregnancy. For example, it was high in hyperemesis gravidarum,[32] low in preeclamptic patients,[33] and there was no difference in molar pregnancies.[34] In our study, we found that PCT level was significantly higher in obese group than the normal weight group and in the obese/underweight groups than normal weight group.
PDW is a marker indicating the variations in the platelet volume. Its level varies according to the size and activation of platelets. Its normal reference range in the blood is between 8.3% and 56.6%.[30] It is known that PDW decreases during pregnancy compared to the pregestational period. Some studies reported that it has a positive correlation with preeclampsia severity and ectopic pregnancy,[33,35] while there is a negative correlation with ablatio placentae.[22] In our study, we did not find any increase in PDW level by elevated BMI value.
NLR and PLR levels are the systemic inflammatory indices associated with platelet. There is a study showing that NLR is associated with metabolic syndrome.[36] It is known that high NLR and PLR are associated with gestational diabetes and preterm labor.[9,37] We did not find any difference between the groups in terms of NLR and PLR values in our study.
RDW shows the variation in the red blood cell volume called anisocytosis, and its reference value is 11.5–15.5%.[10] While it is considered that high RDW levels indicate inflammation and oxidative stress, the mechanism is still unclear.[38] There are studies asserting that it is associated with the impairment of iron metabolism and the suppression of erythropoietin.[39] Many studies in the literature investigated the association of RDW level with the diseases in pregnant women. While there is no association with hyperemesis,[40] its association with preeclampsia is controversial,[8,11] and it is not associated with gestational diabetes.[41] In our study, RDW level was similar among the groups.
The limitations of our study are being retrospective, single-centered, limited number of patients, and not checking other inflammatory markers except hematologic markers. In addition, we did not investigate gestational and neonatal outcomes of inflammatory markers. There are no studies in the literature investigating the association between obesity during pregnancy and inflammatory markers. Further clinical researches which are planned prospectively, randomized controlled and investigating the obstetric outcomes of maternal obesity and inflammation values are needed.

Conclusion

Hematologic inflammatory markers are simple and cheap markers which can be detected in the hemogram count easily. The association between inflammation and obesity during pregnancy has been proven, and it is considered that it is associated with the potential poor outcomes during pregnancy. We found that white blood cell, neutrophil, lymphocyte, platelet and PCT levels are associated with high BMI values during pregnancy. Further studies are needed to confirm the association between these markers and poor obstetric and neonatal outcomes.

References

1. Tjepkema M. Adult obesity in Canada: measured height and weight. Ottawa: Statistics Canada; 2005.


2. Nishtar S, Gluckman P, Armstrong T. Ending childhood obesity: a time for action. Lancet 2016;387(10021):825–7. [PubMed] [CrossRef] 


3. TBSA. “Türkiye Beslenme ve Sağlık Araştırması 2010: Beslenme Durumu ve Alışkanlıklarının Değerlendirilmesi Sonuç Raporu.” Sağlık Bakanlığı Sağlık Araştırmaları Genel Müdürlüğü, Hacettepe Üniversitesi Sağlık Bilimleri Fakültesi Beslenme ve Diyetetik Bölümü, Ankara Numune Eğitim ve Araştırma Hastanesi. Ankara: Sağlık Bakanlığı Yayın No: 931.2014.


4. Lee CY, Koren G. Maternal obesity: effects on pregnancy and the role of pre-conception counselling. J Obstet Gynaecol 2010;30:101–6. [PubMed] [CrossRef] 


5. Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83:S461–5. [PubMed] [CrossRef] 


6. Madan JC, Davis JM, Craig WY, Collins M, Allan W, Quinn R, et al. Maternal obesity and markers of inflammation in pregnancy. Cytokine 2009;47:61–4. [PubMed] [CrossRef] 


7. Vilchez G, Lagos M, Kumar K, Argoti P. Is mean platelet volume a better biomarker in pre-eclampsia? J Obstet Gynaecol Res 2017;43:982–90. [PubMed] [CrossRef] 


8. Yücel B, Ustun B. Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, mean platelet volume, red cell distribution width and plateletcrit in preeclampsia. Pregnancy Hypertens 2017;7:29–32. [PubMed] [CrossRef] 


9. Yilmaz H, Celik HT, Namuslu M, Inan O, Onaran Y, Karakurt F, et al. Benefits of the neutrophil-to-lymphocyte ratio for the prediction of gestational diabetes mellitus in pregnant women. Exp Clin Endocrinol Diabetes 2014;122:39–43. [PubMed] [CrossRef] 


10. Sahbaz A, Cicekler H, Aynioglu O, Isik H, Ozmen U. Comparison of the predictive value of plateletcrit with various other blood parameters in gestational diabetes development. J Obstet Gynaecol 2016;36:589–93. [PubMed] [CrossRef] 


11. Çintesun E, Çintesun FN, Ezveci H, Akyürek F, Çelik C. Systemic inflammatory response markers in preeclampsia. J Lab Physicians 2018;10:316–9. [PubMed] [CrossRef] 


12. Sirimi N, Goulis DG. Obesity in pregnancy. Hormones (Athens) 2010;9:299–306. [PubMed] [CrossRef] 


13. Shaikh H, Robinson S, Teoh TG. Management of maternal obesity prior to and during pregnancy. Semin Fetal Neonatal Med 2010;15:77–82. [PubMed] [CrossRef] 


14. Lashen H, Fear K, Sturdee DW. Obesity is associated with increased first trimester and recurrent miscarriage: matched case-control study. Hum Reprod 2004;19:1644–6. [PubMed] [CrossRef] 


15. Davies GA, Maxwell C, McLeod L, Gagnon R, Basso M, Bos H, et al.; Society of Obstetricians and Gynaecologists of Canada. SOGC clinical practice guidelines: obesity in pregnancy. No. 239, February 2010. Int J Gyneacol Obstet 2010;110:167–73. [PubMed] [CrossRef] 


16. Robinson HE, O'Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol 2005;106:1357–64. [PubMed] [CrossRef] 


17. Sheiner E, Levy A, Menes TS, Silverberg D, Katz M, Mazor M. Maternal obesity as an independent risk factor for caesarean delivery. Paediatr Perinat Epidemiol 2004;18:196–201. [PubMed] [CrossRef] 


18. Fretts RC. Etiology and prevention of stillbirth. Am J Obstet Gynecol 2005;193:1923–35. [PubMed] [CrossRef] 


19. Yılmaz ZV, Yılmaz E, İçer B, Küçüközkan T. Association of complete blood count parameters with gestational diabetes mellitus. Gynecology Obstetrics & Reproductive Medicine 2017;23:65–9. [CrossRef] 


20. Pattanathaiyanon P, Phaloprakarn C, Tangjitgamol S. Comparison of gestational diabetes mellitus rates in women with increased and normal white blood cell counts in early pregnancy. J Obstet Gynaecol Res 2014;40:976–82. [PubMed] [CrossRef] 


21. Kocabaş CN. Alerjik inflamasyonda yeni aktör trombositler. Türkiye Çocuk Hastalıkları Dergisi 2016;10(2):XI–XII.


22. Arlier S, Adiguzel C, Yilmaz ES, Seyfettinoglu S, Helvacioglu Ç, Ekin GU, et al. The role of mean platelet volume and platelet distribution width in the prediction of placental abruption. J Obstet Gynaecol 2016;36:950–3. [PubMed] [CrossRef] 


23. Dundar O, Yoruk P, Tutuncu L, Erikci AA, Muhcu M, Ergur AR, et al. Longitudinal study of platelet size changes in gestation and predictive power of elevated MPV in development of pre-eclampsia. Prenat Diagn 2008;28:1052–6. [PubMed] [CrossRef] 


24. James TR, Reid HL, Mullings MA. Are published standards for haematological indices in pregnancy applicable across populations: an evaluation in healthy pregnant Jamaican women. BMC Pregnancy Childbirth 2008;8:8. [PubMed] [CrossRef] 


25. Holthe MR, Staff AC, Berge LN, Lyberg T. Different levels of platelet activation in preeclamptic, normotensive pregnant, and nonpregnant women. Am J Obstet Gynecol 2004;190:1128–34. [PubMed] [CrossRef] 


26. Ahmed Y, van Iddekinge B, Paul C, Sullivan HF, Elder MG. Retrospective analyses of platelet numbers and volumes in normal pregnancy and in preeclampsia. Br J Obstet Gynaecol 1993;100:216–20. [PubMed] [CrossRef] 


27. Kamath S, Blann A, Lip G. Platelet activation: assessment and quantification. Eur Heart J 2001;22:1561–71. [PubMed] [CrossRef] 


28. Leader A, Pereg D, Lishner M. Are platelet volume indices of clinical use? A multidisciplinary review. Ann Med 2012;44:805–16. [PubMed] [CrossRef] 


29. Bozkurt N, Yilmaz E, Biri A, Taner Z, Himmetoglu O. The mean platelet volume in gestational diabetes. J Thromb Thrombolysis 2006;22:51–4. [PubMed] [CrossRef] 


30. Budak YU, Polat M, Huysal K. The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency non-traumatic abdominal surgery: a systematic review. Biochem Med (Zagreb) 2016;26:178–93. [PubMed] [CrossRef] 


31. Wiwanitkit V. Plateletcrit, mean platelet volume, platelet distribution width: its expected values and correlation with parallel red blood cell parameters. Clin Appl Thromb Hemost 2004;10:175–8. [PubMed] [CrossRef] 


32. Tayfur C, Burcu DC, Gulten O, Betul D, Tugberk G, Onur O, et al. Association between platelet to lymphocyte ratio, plateletcrit and the presence and severity of hyperemesis gravidarum. J Obstet Gynaecol Res 2017;43:498–504. [PubMed] [CrossRef] 


33. Karateke A, Kurt RK, Baloglu A. Relation of platelet distribution width (PDW) and platelet crit (PCT) to preeclampsia. Ginekol Pol 2015;86:372–5. [PubMed] [CrossRef] 


34. Soylu Karapınar O, Benk Şilfeler D, Dolapçıoğlu K, Kurt Keskin R, Beyazıt A. The effect of molar pregnancies on platelet parameters. J Obstet Gynaecol 2016;36:912–5. [PubMed] [CrossRef] 


35. Artunc Ulkumen B, Pala HG, Calik E, Oruc Koltan S. Can mean platelet volume and platelet distrubition width be possible markers for ectopic pregnancy and tubal rupture? (MPV and PDW in ectopic pregnancy). Pak J Med Sci 2014;30:352–5. [PubMed] [CrossRef] 


36. Buyukkaya E, Karakas MF, Karakas E, Akçay AB, Tanboga IH, Kurt M, et al. Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost 2014;20:159–63. [PubMed] [CrossRef] 


37. Tamer LH, Aykanat Y, Sağır FG, Olmuşçelik O, Özdemir S. Status of neutrophil-lymphocyte ratio and 25-hydroxyvitamin D in preeclampsia and preterm birth. Perinatal Journal 2017;25:91–6. [CrossRef] 


38. Wen Y. High red blood cell distribution width is closely associated with risk of carotid artery atherosclerosis in patients with hypertension. Exp Clin Cardiol 2010;15:37–40. [PubMed] 


39. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011–23. [PubMed] [CrossRef] 


40. Beyazit F, Öztürk FH, Pek E, Ünsal MA. Evaluation of the hematologic system as a marker of subclinical inflammation in hyperemesis gravidarum: a case control study. Ginekol Pol 2017;88:315–9. [PubMed] [CrossRef] 


41. Erdoğan S, Özdemir O, Doğan HO, Sezer S, Atalay CR, Yılmaz FM, et al. Liver enzymes, mean platelet volume, and red cell distribution width in gestational diabetes. Turk J Med Sci 2014;44:121–5. [PubMed] [CrossRef] 

	File/Dsecription
	Table 1. The comparison of demographic data and hematologic markers between the patients with normal weight, and overweight and obese patients.
	Table 2. The comparison of demographic data and hematologic markers between the patients with normal weight and overweight/obese patients.