The Impact of Vitamin D and Acute Phase Proteins in the Diagnosis of Hyperemesis Gravidarum

Dilay Karademir; Nazan Yurtçu

doi:10.7197/cmj.1347700

Research Article

The Impact of Vitamin D and Acute Phase Proteins in the Diagnosis of Hyperemesis Gravidarum

Year 2023, , 79 - 84, 30.09.2023

Dilay Karademir , Nazan Yurtçu

https://doi.org/10.7197/cmj.1347700

Abstract

Objective: Hyperemesis gravidarum (HG) has severe and dramatic consequences, and the cause of this severe disease has not yet been determined clearly. It is known that hormonal, metabolic, immunological, and inflammatory agents may be effective in their etiology. Our study aimed to investigate the possible role of vitamin D, Lactate Dehydrogenase (LDH), Procalcitonin (PCT), and C- reactive Protein (CRP) in the etiology of HG.

Method: In this retrospective study, between June 1, 2021, and January 1, 2022, 110 pregnant women between the ages of 18 and 35 were admitted to the Obstetrics and Gynecology Polyclinic of the Sivas Cumhuriyet University Faculty of Medicine. Fifty-five patients diagnosed with HG were taken as a study group, and fifty-five healthy pregnant women not diagnosed with HG were taken as a control group. Obstetric data and serum vitamin D, LDH, PCT, and CRP values of pregnant women were detected retrospectively.

Results: When the groups with and without HG were compared, although the CRP and LDH levels were high in the HG group, they were not statistically significant (p = 0.084, p = 0.546). Vitamin D and PCT were significantly higher in the HG group than in the control group (p = 0.001, p = 0.047).

Conclusion: Our study found that vitamin D and PCT levels were high in pregnant women with HG. Further studies with more participants are needed before these inflammatory markers can be used to diagnose HG.

Keywords

Hyperemesis gravidarum, CRP, vitamin D, inflammation, procalcitonin

References

1. Nawaz M; Rishma; Afridi SG, Khan A, Shams S. Frequency of Hyperemesis Gravidarum and associated risk factors among pregnant women. J Pak Med Assoc. 2020 Apr;70(4):613-617.
2. Onder AB, Guven S, Demir S, Mentese A, Guvendag Guven ES. Biotin deficiency in hyperemesis gravidarum. J Obstet Gynaecol. 2019 Nov;39(8):1160-1163.
3. Koot MH, Grooten IJ, Post JAM Van Der, Bais JMJ, Ris-stalpers C, Lee MMG, et al. European Journal of Obstetrics & Gynecology and Reproductive Biology Determinants of disease course and severity in hyperemesis gravidarum. 2020;245:162–7.
4. Ioannidou P, Papanikolaou D, Mikos T, Mastorakos G, Goulis DG. European Journal of Obstetrics & Gynecology and Reproductive Biology Predictive factors of Hyperemesis Gravidarum : A systematic review. Eur J Obstet Gynecol. 2019; 238:178–87.
5. Yoneyama Y, Suzuki S, Sawa R, Araki T. Plasma adenosine concentrations increase in women with hyperemesis gravidarum. Clin Chim Acta. 2004;342(1–2):99–103.
6. Zhang Y, Cantor RM, MacGibbon K, Romero R, Goodwin TM, Mullin PM, et al. Familial aggregation of hyperemesis gravidarum. Am J Obstet Gynecol. 2011;204(3):230.e1-230.e7.
7. Fell DB, Dodds L, Joseph KS, Allen VM, Butler B. Risk factors for hyperemesis gravidarum requiring hospital admission during pregnancy. Obstet Gynecol. 2006;107(2):277–84.
8. Roseboom TJ, Ravelli ACJ, Van Der Post JA, Painter RC. Maternal characteristics largely explain poor pregnancy outcomes after hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 2011;156(1):56–9.
9. Fiaschi L, Nelson-Piercy C, Tata LJ. Hospital admission for hyperemesis gravidarum: A nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies. Hum Reprod. 2016;31(8):1675–84.
10. Jenabi E, Fereidooni B. The association between maternal smoking and hyperemesis gravidarum: a meta-analysis. J Matern Neonatal Med. 2017;30(6):693–7.
11. Bolin M, Åkerud H, Cnattingius S, Stephansson O, Wikström AK. Hyperemesis gravidarum and risks of placental dysfunction disorders: A population-based cohort study. BJOG An Int J Obstet Gynaecol. 2013;120(5):541–7.
12. Coetzee RL, Cormack B, Sadler L, Bloomfield FH. Pregnancy and neonatal outcomes following hyperemesis gravidarum. J Dev Orig Health Dis. 2011;2(2):81–8.
13. Agmon N, Sade S, Pariente G, Rotem R, Weintraub AY. Hyperemesis gravidarum and adverse pregnancy outcomes. Arch Gynecol Obstet. 2019;300(2):347–53.
14. Oğlak SC, Aydin MF. Are neutrophil to lymphocyte ratio and platelet to lymphocyte ratio clinically useful for the prediction of early pregnancy loss? Ginekol Pol. 2020;91(9):524–7.
15. Yılmaz S, Cırık DA, 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. Turkish J Obstet Gynecol. 2016;13(3):123–6.
16. Christiansen OB, Nielsen HS, Kolte AM. Inflammation and miscarriage. Semin Fetal Neonatal Med. 2006;11(5):302–8.
17. Oğlak SC, Obut M. The Role of Systemic Inflammatory Markers in the Diagnosis of Hyperemesis Gravidarum. Muğla Sıtkı Koçman Üniversitesi Tıp Derg. 2020 Dec 29;7(3):124–7.
18. Kim HY, Cho GJ, Kim SY, Lee KM, Ahn KH, Han SW, Hong SC, Ryu HM, Oh MJ, Kim HJ, Kim SC. Pre-Pregnancy Risk Factors for Severe Hyperemesis Gravidarum: Korean Population Based Cohort Study. Life (Basel). 2020 Dec 26;11(1):12.
19. Aksoy H, Aksoy AN, Ozkan A, Polat H. Serum lipid profile, oxidative status, and paraoxonase 1 activity in hyperemesis gravidarum. J Clin Lab Anal. 2009;23(2):105–9.
20. Leylek OA, Toyaksi M, Erselcan T, Dokmetas S. Immunologic and biochemical factors in hyperemesis gravidarum with or without hyperthyroxinemia. Gynecol Obstet Invest. 1999;47(4):229–34.
21. Engin-Ustun Y, Tonguç E, Var T, Deveer R, Yilmaz N, Danisman N, et al. Vaspin and C-reactive protein levels in hyperemesis gravidarum. Eur Rev Med Pharmacol Sci. 2013;17(1):138–40.
22. Tunc SY, Agacayak E, Budak S, Tunc N, Icen MS, Findik FM, et al. Serum levels of neopterin , inflammatory markers and oxidative stress indicators in hyperemesis gravidarum. 2016;42(6):618–24.
23. Dockree S, Brook J, James T, Shine B, Vatish M. A pregnancy-specific reference interval for procalcitonin. Clin Chim Acta. 2021;513(October 2020):13–6.
24. Jekarl DW, Lee SY, Lee J, Park YJ, Kim Y, Park JH, et al. Procalcitonin as a diagnostic marker, and IL-6 as a prognostic marker for sepsis. Diagn Microbiol Infect Dis. 2013;75(4):342–7.
25. Hu Y, Yang M, Zhou Y, Ding Y, Xiang Z, Yu L. Establishment of reference intervals for procalcitonin in healthy pregnant women of the Chinese population. Clin Biochem. 2017;50(3):150–4.
26. Ma Y, Ye W, Tang Y. Gestational diabetes mellitus increases the baseline level of procalcitonin in maternal blood but not in umbilical cord blood in late pregnancy. A retrospective case-controlled study. Med (United States). 2019;98(11):1–5.
27. Karlı P, Özdemir AZ, Ayan D. Maternal serum and fetal cord blood C-reactive protein levels but not procalcitonin levels are increased in idiopathic intrauterine growth restriction. Med Sci Monit. 2019;25:6512–7.
28. Mangogna A, Agostinis C, Ricci G, Romano F, Bulla R. Overview of procalcitonin in pregnancy and pre-eclampsia. Clin Exp Immunol. 2019;198(1):37–46.
29. Lumbreras-Marquez MI, Lumbreras-Marquez J, Barraza-Salas M, Castillo-Reyther RA, De la Maza-Labastida S, Hernandez-Rayon YI, et al. Maternal and umbilical cord procalcitonin, high-sensitivity C-reactive protein, and interleukin-6 levels in preeclamptic and normotensive patients: A cross-sectional study. Pregnancy Hypertens. 2020;21(January):218–23.
30. Verberg MF, Gillott DJ, Al-Fardan N, Grudzinskas JG. Hyperemesis gravidarum, a literature review. Hum Reprod Update. 2005 Sep-Oct;11(5):527-39.
31. Minagawa M, Narita J, Tada T, Maruyama S, Shimizu T, Bannai M, et al. Mechanisms underlying immunologic states during pregnancy: Possible association of the sympathetic nervous system. Cell Immunol. 1999;196(1):1–13.
32. Kaplan PB, Gücer F, Sayin NC, Yüksel M, Yüce MA, Yardim T. Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy. Fertil Steril. 2003;79(3):498–502.
33. Kuscu NK, Yildirim Y, Koyuncu F, Var A, Uyanik BS. Interleukin-6 levels in hyperemesis gravidarum. Arch Gynecol Obstet. 2003;269(1):13–5.
34. Yavuz D, Mete T, Yavuz R, Altunoğlu A. D Vitamini, Kalsiyum & Mineral Metabolizması, D Vitaminin İskelet Dışı Etkileri ve Kronik Böbrek Yetmezliğinde Nütrisyonel D Vitamini Kullanımı. Ankara Med J. 2014;14(4):162–71.
35. Zehnder D, Evans KN, Kilby MD, Bulmer JN, Innes BA, Stewart PM, et al. The ontogeny of 25-hydroxyvitamin D3 1α-hydroxylase expression in human placenta and decidua. Am J Pathol. 2002;161(1):105–14.
36. Sekizawa A, Sugito Y, Iwasaki M, Watanabe A, Jimbo M, Hoshi S, et al. Cell-free fetal DNA is increased in plasma of women with hyperemesis gravidarum. Clin Chem. 2001;47(12):2164–5.
37. Çelik S, Soyer C, Güvey H, Yaşar B, Yazıcıoğlu B, Türe E, et al. Hiperemezis gravidarumda önemli bir nokta: d vitamini ve tiroid fonksiyonları. Jinekoloji-Obstetrik ve Neonatoloji Tıp Derg. 2020 Jun 25;17(2):331–4.
38. Gürbüz T, Dokuzeylük Güngör N. Hiperemezis gravidarum etiyopatogenezinde vitamin D eksikliğinin rolü var mı ? Adıyaman Üniversitesi Sağlık Bilim Derg. 2018;4(2):761–71.
39. Calleja-Agius J, Jauniaux E, Pizzey AR, Muttukrishna S. Investigation of systemic inflammatory response in first-trimester pregnancy failure. Hum Reprod. 2012;27(2):349–57.
40. Kalagiri RR, Carder T, Choudhury S, Vora N, Ballard AR, Govande V, et al. Inflammation in Complicated Pregnancy and Its Outcome. Am J Perinatol. 2016;33(14):1337–56.

Year 2023, , 79 - 84, 30.09.2023

Dilay Karademir , Nazan Yurtçu

https://doi.org/10.7197/cmj.1347700

Abstract

References

1. Nawaz M; Rishma; Afridi SG, Khan A, Shams S. Frequency of Hyperemesis Gravidarum and associated risk factors among pregnant women. J Pak Med Assoc. 2020 Apr;70(4):613-617.
2. Onder AB, Guven S, Demir S, Mentese A, Guvendag Guven ES. Biotin deficiency in hyperemesis gravidarum. J Obstet Gynaecol. 2019 Nov;39(8):1160-1163.
3. Koot MH, Grooten IJ, Post JAM Van Der, Bais JMJ, Ris-stalpers C, Lee MMG, et al. European Journal of Obstetrics & Gynecology and Reproductive Biology Determinants of disease course and severity in hyperemesis gravidarum. 2020;245:162–7.
4. Ioannidou P, Papanikolaou D, Mikos T, Mastorakos G, Goulis DG. European Journal of Obstetrics & Gynecology and Reproductive Biology Predictive factors of Hyperemesis Gravidarum : A systematic review. Eur J Obstet Gynecol. 2019; 238:178–87.
5. Yoneyama Y, Suzuki S, Sawa R, Araki T. Plasma adenosine concentrations increase in women with hyperemesis gravidarum. Clin Chim Acta. 2004;342(1–2):99–103.
6. Zhang Y, Cantor RM, MacGibbon K, Romero R, Goodwin TM, Mullin PM, et al. Familial aggregation of hyperemesis gravidarum. Am J Obstet Gynecol. 2011;204(3):230.e1-230.e7.
7. Fell DB, Dodds L, Joseph KS, Allen VM, Butler B. Risk factors for hyperemesis gravidarum requiring hospital admission during pregnancy. Obstet Gynecol. 2006;107(2):277–84.
8. Roseboom TJ, Ravelli ACJ, Van Der Post JA, Painter RC. Maternal characteristics largely explain poor pregnancy outcomes after hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 2011;156(1):56–9.
9. Fiaschi L, Nelson-Piercy C, Tata LJ. Hospital admission for hyperemesis gravidarum: A nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies. Hum Reprod. 2016;31(8):1675–84.
10. Jenabi E, Fereidooni B. The association between maternal smoking and hyperemesis gravidarum: a meta-analysis. J Matern Neonatal Med. 2017;30(6):693–7.
11. Bolin M, Åkerud H, Cnattingius S, Stephansson O, Wikström AK. Hyperemesis gravidarum and risks of placental dysfunction disorders: A population-based cohort study. BJOG An Int J Obstet Gynaecol. 2013;120(5):541–7.
12. Coetzee RL, Cormack B, Sadler L, Bloomfield FH. Pregnancy and neonatal outcomes following hyperemesis gravidarum. J Dev Orig Health Dis. 2011;2(2):81–8.
13. Agmon N, Sade S, Pariente G, Rotem R, Weintraub AY. Hyperemesis gravidarum and adverse pregnancy outcomes. Arch Gynecol Obstet. 2019;300(2):347–53.
14. Oğlak SC, Aydin MF. Are neutrophil to lymphocyte ratio and platelet to lymphocyte ratio clinically useful for the prediction of early pregnancy loss? Ginekol Pol. 2020;91(9):524–7.
15. Yılmaz S, Cırık DA, 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. Turkish J Obstet Gynecol. 2016;13(3):123–6.
16. Christiansen OB, Nielsen HS, Kolte AM. Inflammation and miscarriage. Semin Fetal Neonatal Med. 2006;11(5):302–8.
17. Oğlak SC, Obut M. The Role of Systemic Inflammatory Markers in the Diagnosis of Hyperemesis Gravidarum. Muğla Sıtkı Koçman Üniversitesi Tıp Derg. 2020 Dec 29;7(3):124–7.
18. Kim HY, Cho GJ, Kim SY, Lee KM, Ahn KH, Han SW, Hong SC, Ryu HM, Oh MJ, Kim HJ, Kim SC. Pre-Pregnancy Risk Factors for Severe Hyperemesis Gravidarum: Korean Population Based Cohort Study. Life (Basel). 2020 Dec 26;11(1):12.
19. Aksoy H, Aksoy AN, Ozkan A, Polat H. Serum lipid profile, oxidative status, and paraoxonase 1 activity in hyperemesis gravidarum. J Clin Lab Anal. 2009;23(2):105–9.
20. Leylek OA, Toyaksi M, Erselcan T, Dokmetas S. Immunologic and biochemical factors in hyperemesis gravidarum with or without hyperthyroxinemia. Gynecol Obstet Invest. 1999;47(4):229–34.
21. Engin-Ustun Y, Tonguç E, Var T, Deveer R, Yilmaz N, Danisman N, et al. Vaspin and C-reactive protein levels in hyperemesis gravidarum. Eur Rev Med Pharmacol Sci. 2013;17(1):138–40.
22. Tunc SY, Agacayak E, Budak S, Tunc N, Icen MS, Findik FM, et al. Serum levels of neopterin , inflammatory markers and oxidative stress indicators in hyperemesis gravidarum. 2016;42(6):618–24.
23. Dockree S, Brook J, James T, Shine B, Vatish M. A pregnancy-specific reference interval for procalcitonin. Clin Chim Acta. 2021;513(October 2020):13–6.
24. Jekarl DW, Lee SY, Lee J, Park YJ, Kim Y, Park JH, et al. Procalcitonin as a diagnostic marker, and IL-6 as a prognostic marker for sepsis. Diagn Microbiol Infect Dis. 2013;75(4):342–7.
25. Hu Y, Yang M, Zhou Y, Ding Y, Xiang Z, Yu L. Establishment of reference intervals for procalcitonin in healthy pregnant women of the Chinese population. Clin Biochem. 2017;50(3):150–4.
26. Ma Y, Ye W, Tang Y. Gestational diabetes mellitus increases the baseline level of procalcitonin in maternal blood but not in umbilical cord blood in late pregnancy. A retrospective case-controlled study. Med (United States). 2019;98(11):1–5.
27. Karlı P, Özdemir AZ, Ayan D. Maternal serum and fetal cord blood C-reactive protein levels but not procalcitonin levels are increased in idiopathic intrauterine growth restriction. Med Sci Monit. 2019;25:6512–7.
28. Mangogna A, Agostinis C, Ricci G, Romano F, Bulla R. Overview of procalcitonin in pregnancy and pre-eclampsia. Clin Exp Immunol. 2019;198(1):37–46.
29. Lumbreras-Marquez MI, Lumbreras-Marquez J, Barraza-Salas M, Castillo-Reyther RA, De la Maza-Labastida S, Hernandez-Rayon YI, et al. Maternal and umbilical cord procalcitonin, high-sensitivity C-reactive protein, and interleukin-6 levels in preeclamptic and normotensive patients: A cross-sectional study. Pregnancy Hypertens. 2020;21(January):218–23.
30. Verberg MF, Gillott DJ, Al-Fardan N, Grudzinskas JG. Hyperemesis gravidarum, a literature review. Hum Reprod Update. 2005 Sep-Oct;11(5):527-39.
31. Minagawa M, Narita J, Tada T, Maruyama S, Shimizu T, Bannai M, et al. Mechanisms underlying immunologic states during pregnancy: Possible association of the sympathetic nervous system. Cell Immunol. 1999;196(1):1–13.
32. Kaplan PB, Gücer F, Sayin NC, Yüksel M, Yüce MA, Yardim T. Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy. Fertil Steril. 2003;79(3):498–502.
33. Kuscu NK, Yildirim Y, Koyuncu F, Var A, Uyanik BS. Interleukin-6 levels in hyperemesis gravidarum. Arch Gynecol Obstet. 2003;269(1):13–5.
34. Yavuz D, Mete T, Yavuz R, Altunoğlu A. D Vitamini, Kalsiyum & Mineral Metabolizması, D Vitaminin İskelet Dışı Etkileri ve Kronik Böbrek Yetmezliğinde Nütrisyonel D Vitamini Kullanımı. Ankara Med J. 2014;14(4):162–71.
35. Zehnder D, Evans KN, Kilby MD, Bulmer JN, Innes BA, Stewart PM, et al. The ontogeny of 25-hydroxyvitamin D3 1α-hydroxylase expression in human placenta and decidua. Am J Pathol. 2002;161(1):105–14.
36. Sekizawa A, Sugito Y, Iwasaki M, Watanabe A, Jimbo M, Hoshi S, et al. Cell-free fetal DNA is increased in plasma of women with hyperemesis gravidarum. Clin Chem. 2001;47(12):2164–5.
37. Çelik S, Soyer C, Güvey H, Yaşar B, Yazıcıoğlu B, Türe E, et al. Hiperemezis gravidarumda önemli bir nokta: d vitamini ve tiroid fonksiyonları. Jinekoloji-Obstetrik ve Neonatoloji Tıp Derg. 2020 Jun 25;17(2):331–4.
38. Gürbüz T, Dokuzeylük Güngör N. Hiperemezis gravidarum etiyopatogenezinde vitamin D eksikliğinin rolü var mı ? Adıyaman Üniversitesi Sağlık Bilim Derg. 2018;4(2):761–71.
39. Calleja-Agius J, Jauniaux E, Pizzey AR, Muttukrishna S. Investigation of systemic inflammatory response in first-trimester pregnancy failure. Hum Reprod. 2012;27(2):349–57.
40. Kalagiri RR, Carder T, Choudhury S, Vora N, Ballard AR, Govande V, et al. Inflammation in Complicated Pregnancy and Its Outcome. Am J Perinatol. 2016;33(14):1337–56.

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Details

Primary Language	English
Subjects	Health Systems
Journal Section	Surgical Science Research Articles
Authors	Dilay Karademir 0000-0002-9813-4255 Nazan Yurtçu 0000-0003-4725-043X
Publication Date	September 30, 2023
Acceptance Date	September 11, 2023
Published in Issue	Year 2023

Cite

AMA	Karademir D, Yurtçu N. The Impact of Vitamin D and Acute Phase Proteins in the Diagnosis of Hyperemesis Gravidarum. CMJ. September 2023;45(3):79-84. doi:10.7197/cmj.1347700

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