Please wait a minute...
Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (4): 519-523    DOI: 10.31083/j.ceog.2020.04.5359
Original Research Previous articles | Next articles
Neutrophil gelatinase associated lipocalin-2 (Ngal) levels in preeclampsia
H. Yolli1, M.E. Demir2, *(), R. Yildizhan3
1Private Levent Hospital, Department of Obstetric and Gynecology, Istanbul, Turkey
2Yeni Yuzyil University Faculty of Medicine, Department of Nephrology, Istanbul, Turkey
3Florence Nightingale Hospital, Department of Obstetric and Gynecology, Istanbul, Turkey
Download:  PDF(172KB)  ( 185 ) Full text   ( 9 )
Export:  BibTeX | EndNote (RIS)      
Abstract  

Objectives: Lipocalin-2 (LCN-2) is an immune modulator. It is highly associated with inflammation, ischemia, neoplastic invasion, and transformation. Preeclampsia (PE) is a pregnancy-related disease resulting from the incomplete invasion of trophoblasts. Endothelial cytokines and inflammation have crucial roles in the pathogenesis of PE. We aimed to investigate serum LCN-2 levels in pregnant women with either no PE, mild PE or severe PE. Furthermore, we determined how LCN-2 levels relate to findings of Doppler ultrasound of the arteries in these patients. Material and Methods: Pregnant women with severe PE (n = 51), mild PE (n = 27), or no PE (n = 42) were involved in the study. Serum LCN-2 levels and Doppler ultrasonography (USG) evaluation were performed at the time of diagnosis of PE or in the cases of uncomplicated pregnancy, just prior to delivery. Women with non-complicated pregnancies were followed up for an additional 8 weeks after delivery. Intrauterine growth restriction (IUGR) was evaluated according to Alexander curve references. Results: Serum LCN-2 levels were significantly higher in pregnant women with PE. Higher LCN-2 levels were found in association with abnormal uterine blood flow and IUGR. Mean gestational age was lower in preeclamptic pregnancies and associated with high serum levels of LCN-2. Conclusion: PE is one of the most prevalent causes of pregnancy-associated complications. Early diagnosis and management of the disease are crucial. The level of serum LCN-2 may provide additional prognostic value along with other clinical and laboratory features of the disease.

Key words:  Lipocalin-2      Preeclampsia      Pregnancy     
Submitted:  28 August 2019      Accepted:  04 November 2019      Published:  15 August 2020     
*Corresponding Author(s):  M.E. Demir     E-mail:  demirmehmetemin@hotmail.com

Cite this article: 

H. Yolli, M.E. Demir, R. Yildizhan. Neutrophil gelatinase associated lipocalin-2 (Ngal) levels in preeclampsia. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 519-523.

URL: 

https://ceog.imrpress.com/EN/10.31083/j.ceog.2020.04.5359     OR     https://ceog.imrpress.com/EN/Y2020/V47/I4/519

Table 1  — Criteria for the diagnosis and classification of preeclampsia.
Definition of Preeclampsia;
Systolic blood pressure >140 mmHg and/or diastolic blood pressure; 90 mmHg
*two occasions at least 4 hours apart after 20 weeks in previously non-hypertensive patients
** and one or more of following;
·$\quad$ Proteinuria: ≥ 0.3 g/day in a 24h urine collection or the equivalent
·$\quad$ Low level of platelets: < 100,000 /microL
·$\quad$ High serum creatinine: > 1.1 mg/dL or doubling of creatinine in the absence of any other causes of renal disease
·$\quad$ Elevated serum transaminases: at least two-fold rise
·$\quad$ Pulmonary edema
·$\quad$ Cerebral or visual symptoms
Severe Preeclampsia;
Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 110 mmHg and proteinuria (with or without signs and symptoms of significant end-organ dysfunction).
or
Systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg (with or without proteinuria) and one or more of the mentioned signs and symptoms of significant end-organ dysfunction.
Table 2  — Demographic and labarotory findings of each group.
Normal Pregnancya
N = 42
Mild Preeclampsiab
N = 21
Severe Preeclampsiac
N = 57
p value
Age (years) 25.9 ± 6.7 26.2 ± 5.5 26.7 ± 5.2 a vs b; p > 0.05
b vs c; p > 0.05
a vs c; p > 0.05
BMI (kg/m2) 26.8 ± 3.5 28.1 ± 3.6 28.4 ± 3.8 a vs b; p > 0.05
b vs c; p > 0.05
a vs c; p > 0.05
Gestational age at the sampling time ( week) 33.9 ± 1.6 34.5 ± 1.2 34.1 ± 2.1 a vs b; p > 0.05
b vs c; p > 0.05
a vs c; p > 0.05
Gestational age during the delivery (week) 39.1 ± 1.2 38.8 ± 1.4 35 ± 2.1 a vs b; p < 0.05
b vs c; p < 0.001
a vs c; p < 0.001
Birth Weight (g) 3315 ± 412 2410 ± 298 2190 ± 298 a vs b; p < 0.001
b vs c; p < 0.05
a vs c; p < 0.001
Sistolyic blood pressure (mmHg) 126.2 ± 15.9 152.5 ± 7.1 165.9 ± 9.5 a vs b; p < 0.001
b vs c; p < 0.05
a vs c; p < 0.001
Diastolyic blood pressure (mmHg) 61.6 ± 9.3 90.3 ± 5.5 101.6 ± 7.4 a vs b; p < 0.001
b vs c; p < 0.001
a vs c; p < 0.001
Table 3  — High levels of LCN-2 are associated with Doppler Blood flow abnormality, the presence of HELLP syndrome and IUGR.
Normal Pregnancya
N = 42
Mild Preeclampsiab
N = 21
Severe Preeclampsiac
N = 57
p value
LCN-2 (ng/μL) 129.3 ± 74.8 172.6 ± 82.8 197.9 ± 80 a vs b; p < 0.001
b vs c; p < 0.001
a vs c; p < 0.001
Blood flow anbormality in Doppler (yes/no), n 1 (%14.1) 4 (%14.8) 12 (%23.5) a vs b; p < 0.001
b vs c; p < 0.001
a vs c; p < 0.001
HELLP (yes/no), n 1 (%2.4) 3 (%11.1) 20 (%39.2) a vs b; p < 0.001
b vs c; p < 0.001
a vs c; p < 0.001
IUGR (yes/no), n 4 (%9.5) 7 (%25.9) 13 (%25.5) a vs b; p < 0.001
b vs c; p > 0.05
a vs c; p < 0.001
[1] Gathiram P., Moodley J.: “Pre-eclampsia: its pathogenesis and pathophysiology”. Cardiovasc J Afr, 2016, 27(2), 71-78.
doi: 10.5830/CVJA-2016-009 pmid: 27213853
[2] Duckitt K., Harrington D.: “Risk factors for pre-eclampsia at antenatal booking, systemic review of controlled studies”. BMJ, 2005, 330(7491), 565.
doi: 10.1136/bmj.38380.674340.E0 pmid: 15743856
[3] Bartsch E., Medcalf K.E., Park A.L., Ray J.G.: “Clinical risk factors for pre-eclampsia determined in early pregnancy, systemic review and meta-analysis of large cohort studies”. BMJ, 2016, 353, i1753.
doi: 10.1136/bmj.i1753 pmid: 27094586
[4] Wu P., Haththotuwa R., Kwok C.S., Babu A., Kotronias R.A., Rushton C., et al.: “Preeclampsia and Future Cardiovascular Health, A Systematic Review and Meta-Analysis”. Circ Cardiovasc Qual Outcomes, 2017, 10(2), e003497.
doi: 10.1161/CIRCOUTCOMES.116.003497 pmid: 28228456
[5] Flo T.H., Smith K.D., Sato S., Rodriguez D.J., Holmes M.A., Strong R.K., Akira S., Aderem A.: “Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron”. Nature, 2004, 16,432(7019), 917-21.
[6] Devireddy L.R., Hart D.O., Goetz D.H., Green M.R.: “A mammalian siderophore synthesized by an enzyme with a bacterial homolog involved in nterobactin production”. Cell, 2010, 6, 1006-17.
[7] Mori K., Lee H.T., Rapaport D.: “Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury”. J Clin Invest, 2005, 115(3), 610-21.
doi: 10.1172/JCI23056 pmid: 15711640
[8] Chakraborty S., Kaur S., Guha S., Batra S.K.: “The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer”. Biochim Biophys Acta, 2012, 1826(1), 129-69.
doi: 10.1016/j.bbcan.2012.03.008 pmid: 22513004
[9] Cemgil Arikan D., Ozkaya M., Adali E.: “Plasma lipocalin-2 levels in pregnant women with pre-eclampsia, and their relation with severity of disease”. J Matern Fetal Neonatal Med, 2011, 24(2), 291-6.
doi: 10.3109/14767058.2010.487138 pmid: 20504246
[10] Boeldt D.S., Bird I.M.: “Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia”. J Endocrinol, 2017, 232(1), R27-R44.
doi: 10.1530/JOE-16-0340 pmid: 27729465
[11] Cnossen J.S., Morris R.K.: “Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction, a systematic review and bivariable meta-analysis”. CMAJ, 2008, 178(6), 701-11.
doi: 10.1503/cmaj.070430 pmid: 18332385
[12] Llurba E., Carreras E., Gratacós E., Juan M., Astor J., Vives A., Hermosilla E., Calero I., Millán P., García-Valdecasas B., Cabero L.: “Maternal history and uterine artery Doppler in the assessment of risk for development of early- and late-onset preeclampsia and intrauterine growth restriction”. Obstet Gynecol Int, 2009, 2009, 275613.
doi: 10.1155/2009/275613 pmid: 19936122
[13] Espinoza J., Kusanovic J.P., Bahado-Singh R., Gervasi M.T., Romero R., Lee W., et al.: “Should bilateral uterine artery notching be used in the risk assessment for preeclampsia., small-for-gestational-age., and gestational hypertension?”. J Ultrasound Med, 2010, 29(7), 1103-15.
doi: 10.7863/jum.2010.29.7.1103 pmid: 20587434
[14] American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy.: “Hypertension in pregnancy”. Report of the American College of Obstetricians and Gynecologists’. Obstet Gynecol, 2013, 122(5), 1122.
doi: 10.1097/01.AOG.0000437382.03963.88 pmid: 24150027
[15] Alexander G.R., Himes J.H., Kaufman R.B.: “A United States national reference for fetal growth”. Obstet Gynecol, 1996, 87(2), 163-8.
doi: 10.1016/0029-7844(95)00386-X pmid: 8559516
[16] Vyakaranam S., Bhongir A.V., Patlolla D., Chintapally R.: “Study of serum uric acid and creatinine in hypertensive disorders of pregnancy”. Int J Med Sci Public Health, 2015, 4(10), 1424-1428.
doi: 10.5455/ijmsph.2015.15042015294 pmid: 27175365
[17] Fisher S.J.: “Why is placentation abnormal in preeclampsia”. Am J Gynecol, 2015, 213(4 Suppl), S115-22.
doi: 10.1016/j.ajog.2015.08.042
[18] Brosens I., Pijnenborg R., Vercruysse L., Romero R.: “The “ Great Obstetrical Syndromes” are associated with disorders of deep placentation”. Am J Obstet Gynecol, 2011, 204(3), 193.
doi: 10.1016/j.ajog.2010.08.009
[19] Parry S., McElrath T.F., Pucci D.: “Clinical risk factors for preeclampsia in the 21st century”. Obstet Gynecol, 2014, 124(4), 763-70.
doi: 10.1097/AOG.0000000000000451
[20] Skjaervan R., Vatten L.J., Wilcox A.J.: “Recurrence of pre-eclampsia across generations, exploring fetal and maternal genetic components in a population based cohort”. BMJ, 2005, 331(7521), 877.
doi: 10.1136/bmj.38555.462685.8F pmid: 16169871
[21] Roberts J.M., Edep M.E., Goldfien A.: “Sera from preeclamptic women specifically activate human umblical vein endothelial cells in vitro, morphological and biochemical evidence”. Am J Reprod Immunol, 1992, 27(3-4), 101.
doi: 10.1111/j.1600-0897.1992.tb00735.x pmid: 1418401
[22] Maynnard S.E., Min J.Y., Merchan J.: “Excess placental soluble fms-like thyrosine kinase 1 (sFlt-1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia”. J Clin Invest, 2003, 111(5), 649.
doi: 10.1172/JCI17189 pmid: 12618519
[23] Cowland J.B., Borregaard N.: “Molecular characteriztion and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans”. Genomics, 1997, 45(1), 17-23.
doi: 10.1006/geno.1997.4896 pmid: 9339356
[24] Harmon A.C., Cornelius D.C., Amaral L.M.: “The role of inflammation in the pathology of preeclampsia”. Clin Sci (Lond), 2016, 130(6), 409-19.
doi: 10.1042/CS20150702
[25] Karampas G., Eleftheriades M., Panoulis K.: “Maternal serum levels of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and theircomplex MMP-9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate, a longitudinal study”. Prenat Diagn, 2014, 34(8), 726-33.
doi: 10.1002/pd.4337 pmid: 24550181
[26] D'Anna R., Baviera G., Giordano D., Todarello G., Corrado F., Buemi M.: “Second trimester neutrophil gelatinase-associated lipocalin as a potential prediagnostic marker of preeclampsia”. Acta Obstet Gynecol Scand, 2008, 87(12), 1370-1373.
doi: 10.1080/00016340802464463 pmid: 18951213
[27] Cesur S., Yucel A., Noyan V.: “Plasma lipocalin-2 levels in pregnancy”. Acta Obstet Gnecol Scand, 2012, 91(1), 112-6.
[28] Martin A.M., Bindra R., Curcio P.: “Screenining for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11-14 weeks of gestation”. Ultrasound Obstet Gynecol, 2001, 18, 583-6.
doi: 10.1046/j.0960-7692.2001.00594.x pmid: 11844193
[29] Youssef A., Righetti F., Morano D.: “Uterine artery Doppler and biochemical markers (PAPP-A., PIGF., sFlt-1., P-selectin., NGAL) at 11+0 to 13+6 weeks in the prediction of late (>34 weeks) pre-eclampsia”. Prenat Diagn, 2011, 31(12), 1141-6.
doi: 10.1002/pd.2848 pmid: 22034048
[1] Ali S. Alqahtani. Seroprevalence of Dengue virus among pregnant mothers and their-newborn infants in the southwest of Saudi Arabia[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 741-743.
[2] M. Elmahdy, I. Elfourtia, H. Maghraby. Office hysteroscopy in cases of recurrent implantation failure; Do or not to do[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 723-728.
[3] L.L. Xu, J.Q. Li, Y.Q. Pu, C. Zhou, S.W. Feng, Q. Luo. Effect of prenatal depression during late pregnancy on maternal and neonatal outcomes[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 681-686.
[4] Y.X. Wang, M. Zhong, H. Yi, H.F. He. Detection of group B streptococcus colonization in cervical and lower vaginal secretions of pregnant women[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 669-674.
[5] I.F. Urunsak, U.K. Gulec, E. Eser, M. Sucu, C. Akcabay, S. Buyukkurt. The role of dinoprostone for labor induction in postterm and high-risk term pregnancies[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 664-668.
[6] S. Han, S. Choi, S. Nah, Y.H. Lee. Preterm labor in mild carbon monoxide poisoning: a case report[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 805-806.
[7] H.S.O. Abduljabbar, H. Abduljabar. A systematic review and meta-analysis of the reported symptoms of Covid 19 in pregnancy[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 632-637.
[8] M. Varras, C. Loukas, N. Nikiteas, V.K. Varra, F.N. Varra, E. Georgiou. Comparison of laparoscopic surgical skills acquired on a virtual reality simulator and a box trainer: an analysis for obstetrics-gynecology residents[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 755-763.
[9] H.M. Kim, Y.S. Choo, W.J. Seong. Serum NT-proBNP levels as a marker for cardiopulmonary function in preeclampsia[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 511-515.
[10] K. Chikazawa, K. Imai, T. Kuwata, K. Takagi. Prophylactic laparoscopic adnexal surgery with low-pressure CO2 insufflation for ovarian cysts during the late first trimester or second trimester of pregnancy[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 537-540.
[11] J. A. Villarreal-Rodriguez, L. G. Mancillas Adame, J. Maldonado-Sanchez, A. Guzmán-López, O. R. Treviño-Montemayor, J. G. Gonzalez-Gonzalez, D. Saldívar-Rodríguez. A randomized controlled trial comparing acarbose vs. insulin therapy for gestational diabetes in individuals with inadequate glycemic control by diet alone[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 552-555.
[12] J. Ogawa, S. Suzuki. Risk factors of self-interruption of medications for mental disorders in pregnancy[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 576-578.
[13] A. Daniilidis, G. Dryllis, G. Chorozoglou, M. Politou, R. Dampali, K. Dinas. Substitution of hemoglobin levels in pregnant women with iron supplement: A prospective randomized clinical study[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 579-583.
[14] Z.Y. Chang, R. Cao, R.C. Xu, Y. Cheng, Q.J. Wan. Pregnancy in a peritoneal dialysis patient undergoing intermittent peritoneal dialysis during the third trimester of pregnancy: a case report and literature review[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 596-599.
[15] C.Y. Huang, T.C. Chao, H.C. Chien, Y.L. Liu. Outcome of shared decision-making in a patient with primary herpes gingivostomatitis during pregnancy: a case report[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 604-606.
No Suggested Reading articles found!