The Importance of Determining Human

JMB 2009; 28 (2) DOI: 10.2478/v10011-009-0003-1

UDK 577.1 : 61 ISSN 1452-8258

JMB 28: 97–100, 2009 Original paper Originalni nau~ni rad

THE IMPORTANCE OF DETERMINING HUMAN PLACENTAL LACTOGEN IN THE THIRD TRIMESTER OF PREGNANCY ZNA^AJ ODRE\IVANJA HUMANOG PLACENTALNOG LAKTOGENA U TRE]EM TRIMESTRU TRUDNO]E

Jasmina Durkovi}1, Bojana Mandi}2

1Department of Genetics , Town Hospital, Subotica, Serbia 2Mega Lab, Biochemical Laboratory, Subotica, Serbia

Summary: Human placental lactogen (HPL) is a hormone Kratak sadràj: Humani placentalni laktogen (HPL) jeste produced by the placenta with a role in the re gu lation of hormon koji izlu~uje placenta i regulator je fetoplacen- fetoplacental growth. In this paper, the results of HPL de- talnog rasta. U radu su prikazani rezultati odre|ivanja HPL- termination in the third trimester of pregnancy are pre- a u tre}em trimestru trudno}e, sa ciljem da se ispita senzi - sented with the aim of testing the sensitivity of this bio - tivnost tog biohemijskog markera za otkrivanje poreme}aja chemical marker for detecting placental dysfunction, fetal funkcije placente, vitaliteta fetusa i rizika za lo{ ishod. vitality and risk of bad outcome. The tests were performed Ispitivanje je obavljeno na uzorku od 370 rizi~nih trudno}a on 370 women with high-risk pregnancy, between the 20th izme|u 20 i 36 nedelje trudno}e. HPL je odre|en ELISA and 36th week of pregnancy. HPL was determined by an metodom, testovima »Bioserv Diagnostics«, a rezultati su ELISA method using Bioserv Diagnostics tests and the o~itani na rideru »STAT–FAX 303+«. Utvr|en je zna~ajno results were read by a STAT-FAX 303+ reader. When com - snièn nivo biomarkera HPL kod preeklampsije u pore- pared to normal pregnancy, a significant decrease in the |enju sa normalnom trudno}om (p<0,01), dok je kod level of HPL biomarker was identified in preeclampsia dijabetesa serumski nivo HPL zna~ajno vi{i od normalnog (p<0.01), whereas in diabetes the serum level of HPL was (p<0,01). Ustanovljena je zna~ajna pozitivna korelacija significantly higher (p<0.01). A significant positive correla - izme|u nivoa HPL u trudno}i i teìne novoro|en~eta, tion between the level of HPL during pregnancy and the obima glave i Apgar skora. Rezultati istraìvanja ukazuju na weight of a newborn child, its head circumference and to da je maternalna koncentracija biomarkera HPL direktno Apgar score was obtained. The results of the research povezana sa vitalitetom placentalnog tkiva, te se HPL u tre- indicate that the maternal concentration of the HPL bio- }em trimestru trudno}e moè koristiti kao pokazatelj pla- marker is directly connected to the vitality of placental tis- centalne insuficijencije i vitaliteta fetusa. sue, so that HPL in the third trimester of pregnancy can be used as an indicator of placental insufficiency and fetal Klju~ne re~i: humani placentalni laktogen, placentalna vitality. insuficijencija Keywords: human placental lactogen, placental insuf fi- ciency

Introduction centration of which is dependant on fetal and placental physiology (1). The first hormone test in the Biochemical antenatal tests present biomarker observation of fetal vitality was the determination of analyses in maternal serum and urine, the con - estriol in maternal serum and urine, and later Human Placental Lactogen (HPL), which proved more sensitive in the observation of fetoplacental unit Address for correspondence: function, was discovered (2, 3). Prim Dr sci. med. Jasmina Durkovi} Department of Genetics Human placental lactogen (HPL) is a hormone Town Hospital, Subotica, Serbia produced by the placenta and has a role in the Izvorska 3 regulation of fetoplacental growth, so it is also known Tel: 024 555 222 ext. 404, Fax: 024 555 267 Mobile phone: 063 224 324 as the human chorionic somatotropin hormone (4). e-mail: megalabªnadlanu.com HPL is coded by the genes HPL-3 and HPL-4 within 98 Durkovi}, Mandi}: Human placental lactogen in the third trimester of pregnancy the HGH-V gene locus (human growth hormone birth. Correlation between the level of HPL in the variant gene) and stipulates the expression of normal serum of a pregnant woman and the weight of a placental function (5). Thyroid hormone (T3) stimu - newborn child, its head size measurement and Apgar lates the synthesis and release of the HPL hormone, score was obtained. In the statistical calculation t – one of the most important secretion products in the ratio was used (7). syncytiotrophoblast cells. It is determined in the serum of a pregnant woman, most often in the third trimester of pregnancy, and is used to indicate pla- Results cental function (6). The HPL was determined in maternal serum Placental insufficiency leads to complications in three times in the third trimester of pregnancy, bet- pregnancy due to reduced nutritive placental function ween the 24th and 36th week, and included two and oxygenation of the fetus leading to dysfunction of groups of women with high-risk pregnancy, 37 with fetal growth and vitality. Certain conditions in a preg- to xe mia and 46 with diabetes. Fifty normal pregnant woman, such as hypertension, diabetes, kidney nancies represented the control group (Table I and II). insufficiency, can lead to placental dysfunction. Nor- mally, the concentration of the HPL hormone in ma - ternal serum increases as the pregnancy progresses, Discussion whereas in the case of placental insufficiency its level High-risk pregnancies are accompanied by two decreases. A significant decrease of HPL has been problems – the fetal weight, which is either small for identified in threatened abortions, bleeding, placental the gestation age or too high, and prematurity. Both calcification, intrauterine fetal growth halt, intra- problems lead to high perinatal morbidity and uterine fetal death and in pregnancies which re sulted mortality (8–9). A comparison of the HPL biomarker in children born with fetal distress and asphyxia. in high-risk pregnancy and normal pregnancy was In the states of preeclampsia associated with hy- made and it was noticed that the value of the pertension, and the possible risk of toxemia, the de- biomarker in maternal serum in each tested week of ter mination of HPL biomarker can help us monitor the third trimester of pregnancy was significantly placental function and fetal vitality after the 20th week lower in preeclampsia and significantly higher in of pregnancy. A significant increase in the secretion of HPL biomarker has been noticed in the states of hyperplasia of syncytiotrophoblast, diabetes, Rh Table I The values of HPL marker in the serum of a incompatibility, placental trophoblast tumor and pregnant woman with high risk pregnancy and normal molar pregnancy. The aim of the research has been pregnancy. directed towards the study of HPL biomarker in the serum of women with high risk pregnancy and its HPL (mg/L) Preeclampsia Normal Diabetes connection with the pregnancy outcome. average value pregnancy 24–26 weeks 2.07 ± 1.75 4.15 ± 2.55 6.22 ± 3.05 t = 5.714 t = 7.341 Methods 28–30 weeks 3.36 ± 1.74 5.6 ± 2.91 8.96 ± 4.46 The analysis of HPL biomarker was done in the t = 1.985 t = 8.094 Town Hospital in Subotica between 2002 and 2007. The tests were performed on 370 women with high 34–36 weeks 5.15 ± 1.47 8.35 ± 3.35 11.19 ± 4.02 risk pregnancy, between the 20th and 36th week of t = 9.620 t = 1.460 pregnancy. The indications for analyses were the sta tes associated with a risk of preeclampsia, hypertension, 24–26 weeks p<0.01 df = 85 normal pregnancy kidney insufficiency, proteinuria and edema, dia betes, – preeclampsia as well as ultrasonic detection of intrauterine fetal growth halt and a threatened abortion. p<0.01 df = 94 normal pregnancy – diabetes In high risk pregnancies, 46 with diabetes and 37 with preeclampsia, the HPL was checked three 28–30 weeks p=0.025 df = 85 normal pregnancy times in the third trimester of pregnancy. The HPL – preeclampsia marker level in 50 normal pregnancies represented a p<0.01 df = 94 normal pregnancy control group. – diabetes HPL was determined by an ELISA method using 34–36 weeks p<0.01 df = 85 normal pregnancy Bioserv Diagnostics tests and the results were read by – preeclampsia a STAT-FAX 303+ reader. The weight of a newborn child and the Apgar p=0.082 df = 94 normal pregnancy – diabetes score were monitored in the first minute after the JMB 2009; 28 (2) 99

Table II The parameters of a newborn child in high-risk in uteroplacental circulation reduces the oxygenation pregnancy and normal pregnancy. of the intervillous space (14). Parameters Preeclampsia Normal Diabetes In hypoxia the mitotic activity of cytotrophoblast (average value) pregnancy increases leading to its differentiation into syn cytio- trophoblast. The production of human placental Weight (g) 2895 3314 4190 lactogen is increased in proliferous syncytiotro - t = 13.492 t = 16.197 phoblast which has a diabetogenous effect, and thus explains the regular occurrence of gestational dia- Apgar/1 min 7.15 9.2 8.56 t = 15.348 t = 6.342 betes in high-risk pregnancies (15). In this paper, a significant correlation between Head size 32.9 33.5 34.7 the level of HPL biomarker in the serum of a pregnant measurement (cm) t = 3.385 t = 8.710 woman and the weight of a newborn child in normal pregnancies and pregnancies complicated by diabe - Weight p<0.01 df = 85 normal pregnancy tes and preeclampsia (p<0.01) has been established. – preeclampsia When HPL is low in the maternal serum of pregnant p<0.01 df = 94 normal pregnancy women suffering from preeclampsia, the weight at – diabetes birth is significantly lower, whereas when HPL is hig h- Apgar p<0.01 df = 85 normal pregnancy er in pregnant women suffering from diabetes, the – preeclampsia weight of a newborn child is significantly higher in p<0.01 df = 94 normal pregnancy – diabetes comparison to the weight of the babies born after normal pregnancies. This correlation between the Head size p<0.01 df = 85 normal pregnancy measurement – preeclampsia level of HPL biomarker and the weight of a newborn p<0.01 df = 94 normal pregnancy child can be explained by its somatotrophic activity on – diabetes a fetus. There is also a significant correlation between the level of HPL and the head size measurement of a newborn child in normal pregnancies and high-risk diabetes compared to normal pregnancy. There is a pregnancies affected by preeclampsia and diabetes 99% probability (p<0.01) between the 24th and 34th (p<0.01). There is a significant correlation between week of pregnancy, which is very relevant, whereas HPL and the Apgar score in the first minute after birth probability is over 91% between the 34th and 36th (p<0.01) indicating that the HPL biomarker can be week, meaning there is no significant loss of statistical used as an indicator of fetal vitality. quality. A high value of t–statistics indicates a The results of this study match with some other considerable difference in the level of the HPL bio- studies on the sensitivity of HPL biomarker published marker in high-risk pregnancy and normal pregnancy. elsewhere in the world (16, 17). The results of the Similar results have been published by some research have shown that HPL in the third trimester of other authors (10). pregnancy can be used as an indicator of placental insufficiency and disturbed fetal vitality. In high-risk Maternal concentration of the HPL biomarker is pregnancies accompanied by preeclampsia and directly connected to the vitality of placental tissue diabetes it should be controlled several times during (11). Decreased concentration of the HPL marker in pregnancy. Since placental dysfunction is related to the serum in preeclampsia is conditioned by placental disturbed oxygenation of the fetus, the determination dysfunction. of HPL biomarker in the third trimester of pregnancy The metabolism of carbohydrates and fat is also has predictive characteristics. High-risk pregnancies affected by human placental lactogen which can be must undergo regular clinical and laboratory control, responsible for diabetogenous status in high-risk glucose tolerance tests, ultrasonic control of fetal pregnancies. (12, 13). Adipose tissues are also direc - biometry and biophysical profile assessment, doppler tly influenced by the activity of HPL hormone. Inade - tests of uteroplacental and fetoplacental circulation quate perfusion of placenta due to a higher resistance and, if necessary, monitoring of the labour itself. 100 Durkovi}, Mandi}: Human placental lactogen in the third trimester of pregnancy

References 1. Aikin D, Duff G, Evans J. Antenatal biochemical screen - complications during pregnancy. Philadelphia: Saun- ing to predict low birth weight. Br J Obstet Gynecol ders Co, 1988: 95–116. 1983; 90: 129. 10. Kandil O, El-Sheikha Z, Ahmed AM, Soliman A, El- 2. Pearson JF. Monitoring high risk pregnancy. In: Bonnar J, Mekkawi T, Wahab M. Serum human placental lacto - editor. Recent Advances in Obstetrics Gynecology. Lon - gen in normal, toxaemic and diabetic pregnant women don: Churchill Livingstone, Edinburgh, 1982: 14–24. during pregnancy and its relation to outcome of pregnancy. J Egpt Soc Of Obstet Gynecol Vol 12, 1986. 3. Spellacy WN. The use of human placental lactogen in the antepartum monitoring of pregnancy. Clinical Obs 11. Klopper A, Jaundial V, Wilson G. Plasma steroid assay Gyn 1979; 6: 245. in the assessment of fetoplacental function. J Steroid Bioch 1975; 6: 651. 4. Freemark M. Human Placental Lactogen (Human Cho- rionic Somatomammotropin). In: Knobil E, Neill JD, 12. Simon JA, Buster JE. Placental endocrinology and dia g - editors. Encyclopedia of Reproduction. California, Aca- nosis of pregnancy. In: Gabbe SG, Niebyl JP, Simpson JL, demic Press, 1998: Vol 2, 694–700. editors. Obstetrics: normal and problem pregnan cies. London: Churchill Livingstone New York, 1986: 79–84. 5. Peters TJ, Chapman BM, Wolfe MW, Soares TJ. 13. Varmer MW, Hauser KS. Current status of placental Placental lactogen-I gene activation in differentiating lactogen. Semin-Perinatol 1981; 5: Suppl 2: 123. trophoblast cells: extrinsic and intrinsic regulation invol- ving mitogen-activated protein kinase signaling path- 14. Toshio F, Makio M. Syncytiotrophoblastic vesicles in pla- ways. J Endocrinol 2000; 165 (2): 443–56. cental intervillous space. Am J Obstet Gynecol 2006; 195 (1): 304–7. 6. Klopper A. Fetal monitoring: Biochemical Methods. In: Whitte MJ, editor. Clinical Obstetrics Gynecology. 15. Spellacy WN, Cohn JE. Human placental lactogen Baillier Tindal, London, Philadelphia, 1987: 13. levels and daily insulin requirements in patients with diabetes mellitus complicating pregnancy. Obstet 7. Aslan D, Sandberg S. Simple statistic in diagnostic tests. Gynecol 1973; 42: 230. Journal of Medical Biochemistry 2007, 26: 309–13. 16. Aikin D, Duff G, Evans J. Antenatal biochemical 8. Gabbe SG. Antepartum fetal evaluation. In: Gabbe SG, screening to predict low birth weight. Br J Obstet Nieby JP, Simpson JL, editors. Obstetrics: normal and Gynecol 1983; 90: 129. problem pregnancies. London: Churchill Livingstone, New York, Edinburgh, 1986: 269–79. 17. Handwerger S, Freemark M. The roles of placental growth hormone and placental lactogen in the regu - 9. Thomas CK, Robert R. Obstetric management of risk lation of human fetal growth and development. J Pe- patient. In: Gerard NB, Thomas F, editors. Medical diatr Endocrinol Metab 2000; 13 (4): 343–56.

Received: October 10, 2008 Accepted: December 13, 2008