IS HYPEREMESIS GRAVIDARUM AN INFLAMMATORY PROCESS?

Abstract

Objective: Hyperemesis gravidarum (HG) is a condition that associated with intractable nausea and vomiting, causing maternal morbidity and mortality and its etiology remains unclear. It is considred that inflammatory processes take place in the etiology of the disease. In our study, we aimed to evaluate white blood cell count (WBC), monocyte to lymphocyte ratio (MLR), C-reactive protein (CRP), and ferritin levels in pregnants that has HG compared with healthy controls.
Methods: We included to our study 99 pregnants that has HG and 101 healty pregnants that has similar characteristics with study group who applied to Samsun Obstetrics and Gynecology Hospital and Health Sciences University Samsun Educational and Research Hospital Obstetrics and Gynecology Department between January 2017 and July 2018. WBC, MLR, CRP and ferritin levels of these pregnants were evaluated retrospectively.
Results: According to our findings pregnants who had HG had higher vomiting count and weight loss than healthy controls (p<0.001; p<0.01). Also gravida (p=0.03), parity (p=0.02), living child (p=0.02) and abort (p=0.01) counts of hyperemesis patients were higher than healty controls. 31.3% (n=31) of HG cases had (+) keton, 26.2% (n=26) had (++) keton and 42.4% (n=42) had (+++) keton in urine. While WBC (p=0.03) and MLR (p=0.001) levels of HG patients were found significantly higher (p<0.05), there was no significant difference between ferritin (p=0.14) and CRP (p=0.34) levels of the groups. Also ferritin (p=0.01) and CRP (p=0.01) levels of keton (+++) cases were found higher than keton (++) cases respectively (p<0.05).
Conclusion: The WBC and MLR levels were detected higher in HG group in our study which supports the idea that HG has inflammatory background, but we consider that studies which are prospective and have larger sampling would contribute to the literature about the issue.

Keywords

• Hyperemesis garvidarum,inflammation,white blood cell count,monocyte to lymhocyte ratio,C-reactive protein

HİPEREMEZİS GRAVİDARUM İNFLAMATUAR BİR SÜREÇ Mİ?

Öz

Amaç: Hiperemezis gravidarum (HG), inatçı bulantı kusmayla seyreden, maternal morbidite ve mortaliteye neden olabilen etiyolojisi tam olarak ortaya konulamamış bir durumdur. Hastalığın etiyolojisinde enflamatuar süreçlerin yer aldığı düşünülmektedir. Biz de çalışmamızda HG tanısı alan ve sağlıklı gebelerde enflamatuar belirteçler olan beyaz küre sayısı (BK), monosit/lenfosit oranı (MLR), C-reaktif protein (CRP) ve ferritin düzeylerini değerlendirmeyi amaçladık.
Yöntem: Çalışmamıza 2017 Ocak -2018 Temmuz tarihleri arasında Samsun Kadın Hastalıkları ve Doğum Hastanesi ve Sağlık Bilimleri Üniversitesi Samsun Eğitim ve Araştırma Hastanesi Kadın Hastalıkları ve Doğum Bölümü’ne başvuran HG olan 99 gebe ve vaka grubuyla benzer özelliklere sahip sağlıklı 101 gebe dahil edildi. Bu gebelerin BK, MLR, CRP ve ferritin düzeyleri retrospektif olarak değerlendirildi.
Bulgular: Bulgularımıza göre HG görülen gebelerin kusma sayıları, kilo kaybı miktarı daha yüksektir (p<0,001; p<0,01). Ayrıca gravida (p=0,03), parite (p=0,02), yaşayan çocuk (p=0,02) ve abort (p=0,01) sayıları da HG grubunda daha yüksek saptanmıştır (p<0,05). HG olgularının %31,3’ünde (n=31) keton (+) iken, %26,2’sinde (n=31) keton (++), %42,4’sinde (n=42) keton (+++) olarak saptanmıştır. HG olan gebelerde BK (p=0,03) ve MLR (p=0,001) seviyeleri anlamlı olarak daha yüksek saptanırken (p<0,05), ferritin (p=0,14) ve CRP (p=0,34) seviyeleri arasında anlamlı bir fark saptanmadı. Ayrıca keton +++ olan hastalarda ++ olanlara göre ferritin (p=0,01) ve CRP (p=0,01) seviyeleri anlamlı olarak yüksek saptanmıştır (p<0,05).
Sonuç: Çalışmamızda BK ve MLR düzeyleri HG olan hastalarda yüksek saptanmış olup HG’nin enflamatuar bir zemini olduğunu desteklemektedir ancak prospektif daha büyük örneklemle yapılacak çalışmaların konuyla ilgili katkıda bulunacağını düşünmekteyiz.

Anahtar Kelimeler

• Hiperemezis gravidarum,enflamasyon,beyaz küre,monosit/lenfosit oranı,C-reaktif protein

References

1. American College of Obstetricians & Gynecologists. Nausea and vomiting of pregnancy. Practice Bulletin No. 153. Obstet Gynecol. 2015;126(3):e12-24. doi:10.1097 /AOG.0000000000001048
2. London V, Grube S, Sherer DM, Abulafia O. Hyperemesis gravidarum: A review of recent literature. Pharmacology. 2017;100(3-4):161-171. doi:10.1159/000477853
3. Ioannidou P, Papanikolaou D, Mikos T, Mastorakos G, Goulis DG. Predictive factors of Hyperemesis Gravidarum: A systematic review. Eur J Obstet Gynecol Reprod Biol. 2019. doi:10.1016/j.ejogrb.2019.04.043
4. Engin-Ustun Y, Tonguç E, Var T, et al. Vaspin and C-reactive protein levels in hyperemesis gravidarum. Eur Rev Med Pharmacol Sci. 2013;17(1):138-140.
5. Kurt R, Güler A, Silfeler D, Özçil M, Karateke A, Hakverdi A. Relation of inflammatory markers with both presence and severity of hyperemesis gravidarum. Polish Gynaecol. 2015;85(8):589-593. doi:10.17772/gp/1776
6. Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014;6(4):748-773. doi:10.1039/c3mt00347g
7. Austin K, Wilson K, Saha S. Hyperemesis Gravidarum. Nutr Clin Pract. 2019;34(2):226-241. doi:10.1002/ncp.10205
8. Minagawa M, Narita J, Tada T, et al. Mechanisms underlying immunologic states during pregnancy: Possible association of the sympathetic nervous system. Cell Immunol. 1999;196(1):1-13. doi:10.1006/cimm.1999.1541

9. Verberg MFG, Gillott DJ, Al-Fardan N, Grudzinskas JG. Hyperemesis gravidarum, a literature review. Hum Reprod Update. 2005;11(5):527-539. doi:10.1093/humupd/dmi0 21
10. Sekizawa A, Sugito Y, Iwasaki M, et al. Cell-free fetal DNA is increased in plasma of women with hyperemesis gravidarum. Clin Chem. 2001;47(12):2164-2165.
11. Kuscu NK, Yildirim Y, Koyuncu F, Var A, Uyanik BS. Interleukin-6 levels in hyperemesis gravidarum. Arch Gynecol Obstet. 2003;269(1):13-15. doi:10.1007/s00404-002-0412-6
12. Tayfur C, Burcu DC, Gulten O, et al. Association between platelet to lymphocyte ratio, plateletcrit and the presence and severity of hyperemesis gravidarum. J Obstet Gynaecol Res. 2017;43(3):498-504. doi:10.1111/jog.13228
13. 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(6):315-319. doi:10.5603/GP.a 2017.0059
14. Yildirim M, Demir Cendek B, Desdicioglu R, Yavuz Avsar AF. The Existence of Continuous Systemic Inflammation in Pregnant Women with Hyperemesis Gravidarum. Cyprus J Med Sci. 2017;1(3):46-50. doi:10.5152/cjms.2016.167
15. Çintesun E, Akar S, Gul A, Nur F, Çintesun I, Sahin G. Subclinical inflammation markers in hyperemesis gravidarum and ketonuria : A case – control study. J Lab Physicians. 2019;11(2):149-153. doi:10.4103/JLP.JLP
16. Garshasbi A, Ghazanfari T, Zayeri F, Kamali M. Maternal serum levels of interleukin-6 and β-hCG in women with hyperemesis gravidarum in the first trimester of pregnancy. J Basic Clin Pathophysiol. 2017;5(1):13-18. doi:10.22070/ jbcp.2017.1953.1069
17. Tunc SY, Agacayak E, Budak S, et al. Serum levels of neopterin, inflammatory markers and oxidative stress indicators in hyperemesis gravidarum. J Obstet Gynaecol Res. 2016;42(6):618-624. doi:10.1111/jog.12949
18. Yılmaz S, Akdağ Cırık D, Demirtaş C, Timur H, Şahin A, Danışman N, et al. Do vitamin D and high- sensitivity-C reactive protein levels differ in patients with hyperemesis gravidarum? A preliminary study. J Turkish Soc Obstet Gynecol. 2016;13(3):123–126.
19. Ryan Wessells K, Peerson JM, Brown KH. Within-individual differences in plasma ferritin, retinol-binding protein, and zinc concentrations in relation to inflammation observed during a short-term longitudinal study are similar to between-individual differences observed cross-sectionally. Am J Clin Nutr. 2019;109(5):1484-1492. doi:10.1093/ajcn /nqz014
20. Namaste SM, Aaron GJ, Varadhan R, Peerson JM, Suchdev PS. Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106:333S-347S. doi:10.3945/ajcn.116.142273
21. Panagiotakos DB, Pitsavos C. Socio-economic status in relation to risk factors associated with cardiocascular disease, in healthy individuals from the ATTICA study. Eur J Cardiovasc Prev Rehabil. 2005;12(1):68-74.
22. Naess A, Nilssen SS, Mo R, Eide GE, Sjursen H. Role of neutrophil to lymphocyte and monocyte to lymphocyte ratios in the diagnosis of bacterial infection in patients with fever. Infection. 2017;45(3):299-307. doi:10.1007/s15 010-016-0972-1
23. Conrad K, Wu P, Sieper J, Syrbe U. In vivo pre-activation of monocytes in patients with axial spondyloarthritis. Arthritis Res Ther. 2015;17(1):1-12. doi:10.1186/s13075-015-0694-2
24. Xiang J, Zhou L, Li X, et al. Preoperative monocyte-to-lymphocyte ratio in peripheral blood predicts stages, metastasis, and histological grades in patients with ovarian cancer. Transl Oncol. 2017;10(1):33-39. doi:10.1016/ j.tranon.2016.10.006
25. Wang W, Wang LF, Liu YY, Yang F, Zhu L, Zhang XH. Value of the ratio of monocytes to lymphocytes for monitoring tuberculosis therapy. Can J Infect Dis Med Microbiol. 2019;2019:1-5. doi:10.1155/2019/3270393
26. Gao K, Zhu W, Liu W, et al. Diagnostic value of the blood monocyte–lymphocyte ratio in knee osteoarthritis. J Int Med Res. 2019;47(9):4413-4421. doi:10.1177/0300060519 860686
27. Chen H, Li M, Liu L, Dang X, Zhu D, Tian G. Monocyte/lymphocyte ratio is related to the severity of coronary artery disease and clinical outcome in patients with non-ST-elevation myocardial infarction. Medicine (Baltimore). 2019;98(26):e16267. doi:10.1097/MD.000 0000000016267
28. Ismail SK, Kenny L. Review on hyperemesis gravidarum. Best ŞPractice Res. 2007;21(5):755-769. doi:10.1016/j.bpg .2007.05.008
29. Michael O, Stephanie O. Hyperemesis gravidarum – a serious issue during pregnancy : in-depth clinical review and treatment modalities. MOJ Womens Helath. 2015;1(2):38-47. doi:10.15406/mojwh.2015.01.00010
30. Buyukkayaci N, Oguzhan D. Hyperemesis gravidarum affects maternal sanity , thyroid hormones and fetal health : a prospective case control study. Matern Med. 2015;292(2):307-312. doi:10.1007/s00404-015-3632-2
31. Agmon N, Sade S, Pariente G, Rotem R, Weintraub AY. Hyperemesis gravidarum and adverse pregnancy outcomes. Arch Gynecol Obstet. 2019;300(2):347-353. doi:10.1007/s00404-019-05192-y