Biochemical markers in screening for preeclampsia and intrauterine growth restriction.

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(1)&. '. (. ). *. +. ,. -. +. ,. .. . . . . /. 0. 1. /. 1. . . 2. 1. . . . . . . . . DOI: 10.17772/gp/57863. !. ". #. $. . %. $. . poł oż ni c two. Biochemical markers in screening for preeclampsia and intrauterine growth restriction Markery biochemiczne w predykcji stanu przedrzucawkowego i zahamowania wewnątrzmacicznego wzrastania płodu (ZHOLQD/LWZLĔVND10DJGDOHQD/LWZLĔVND23U]HP\VáDZ2V]XNRZVNL1.U]\V]WRI6]DÀLN2, :DOGHPDU/LWZLĔVNL30DFLHM.RUF]3LRWU.DF]PDUHN 1 2 3 4. Perinatology and Gynecology Clinic, Polish Mother’s Memorial Hospital-Research Institute, Lodz, Poland Gynecology, Fertility and Fetal Therapy Clinic, Polish Mother’s Memorial Hospital-Research Institute, Lodz, Poland Gynecology and Obstetrics Outpatients’ Practice “Medyk”, Wloclawek, Poland Operative Gynecology and Oncological Gynecology Clinic, Polish Mother’s Memorial Hospital-Research Institute, Lodz, Poland. Abstract Objectives: The aim of the study was to evaluate the relationship between the concentrations of substances released by the placenta: placental growth factor (PlGF), pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (`-hCG) and the risk of early and late preeclampsia (PE) and intrauterine fetal growth restriction (IUGR). Material and methods: A total of 180 pregnant women between 11+0 and 13+6 weeks gestation were recruited for a case-control study. Twenty-two patients suffered from early PE, 29 patients from late PE. Data analyzed during the study included maternal history and concentrations of PAPP-A, PlGF, `-hCG. Results: The multiple of the median (MoM) value of the PAPP-A concentrations was 1.01 in the control group (interquartile range (IQR), 0.65-1.55), 0.67 (IQR, 0.382-0.82) in the group of patients with early preeclampsia and 0.74 (IQR, 0.33-1.09) in the group of patients suffering from late preeclampsia. MoM value of the PlGF concentrations was 1.21 in the control group (IQR, 0.93-1.57), 0.62 (IQR, 0.51-0.96) in the group of patients with early preeclampsia and 0.92 (IQR, 0.63-1.09) in the group of patients suffering from late preeclampsia. MoM value of `-hCG concentrations was 1.14 in the control group (IQR, 0.75-1.49), 1.08(IQR, 0.74-1.23) in the group of patients with early preeclampsia and 1,25(IQR, 1,05-1,49) in the group of patients suffering from late preeclampsia. The performance of screening was determined by the areas under the curve and detection rates, with a fixed falsepositive rate of 10%. Conclusions: Decreased levels of PAPP-A and PlGF are related to an increased risk of preeclampsia and its complications.. Key words: preeclampsia / PAPP-A / PlGF /. Correspondence address: Ewelina Litwińska Perinatology and Gynecology Clinic, Polish Mother’s Memorial Hospital-Research Institute, Lodz, Rzgowska 281/289 str., 93-338 Lodz, Poland e-mail: ewelina.litwinska@gmail.com. . . . . . . . . . . . . . . . .

(2). . . . . . . . . . Otrzymano: 18.12.2014 Zaakceptowano do druku: 26.02.2015. . . . . .

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(4) 3. 4. 5. 6. 7. 8. 4. 9. :. ;. <. 5. =. <. 7. &. '. (. ). *. +. ,. -. +. ,. .. . . . . /. 0. 1. /. 1. . . 2. 1. . . DOI: 10.17772/gp/57863. poł oż n i c two. Ewelina Litwińska et al. Biochemical markers in screening for preeclampsia and intrauterine growth restriction.. Streszczenie Cel pracy: Celem przedstawionego badania była ocena zależności między stężeniami uwalnianych przez łożysko substancji – łożyskowego czynnika wzrostu (PlGF), ciążowego białka A (PAPP-A) oraz podjednostki beta ludzkiej gonadotropiny kosmówkowej (`-hCG) a ryzykiem wystąpienia wczesnej i późnej postaci stanu przedrzucawkowego oraz zahamowania wewnątrzmacicznego wzrastania płodu. Materiał i metody: Badaniem kliniczno-kontrolnym objęto grupę 180 pacjentek ciężarnych w 11+0-13+6 tygodniu ciąży. U 22 pacjentek wystąpiła wczesna postać stanu przedrzucawkowego, u 29 pacjentek rozwinęła się późna postać preeklampsji. Dane analizowane w toku badania obejmowały wywiad ciężarnych oraz stężenia PAPP-A, PlGF, `-hCG. Wyniki: Wartość środkowa wielokrotności mediany stężenia PAPP-A wyniosła 1,01 (przedział międzykwartylowy (IQR), 0,65-1,55) w grupie kontrolnej, 0,67 (IQR, 0,382-0,82) w grupie pacjentek z ciążą powikłaną wczesną postacią preeklampsji i 0,74 (IQR, 0,33-1,09) w grupie pacjentek z ciążą powikłaną poźną postacią preeklampsji. Wartość środkowa wielokrotności mediany stężenia PlGF wyniosła 1,21 (IQR, 0,93-1,57) w grupie kontrolnej, 0,62 (IQR, 0,51-0,96) w grupie pacjentek z ciążą powikłaną wczesną postacią preeklampsji i 0,92 (IQR, 0,63-1,09) w grupie pacjentek z ciążą powikłaną poźną postacią preeklampsji. Wartość środkowa wielokrotności mediany stężenia `-hCG wyniosła 1,14 (IQR, 0,75-1,49) w grupie kontrolnej, 1,08 (IQR, 0,74-1,23) w grupie pacjentek z ciążą powikłaną wczesną postacią preeklampsji i 1,25( IQR, 1,05-1,49) w grupie pacjentek z ciążą powikłaną późną postacią preeklampsji. Wyniki dopasowania predykcji zastosowanych testów przedstawiono za pomocą pola pod wykresem (AUC) oraz współczynnika wykrywalności dla odsetka wyników fałszywie dodatnich (FPR) na poziomie 10%. Wnioski: Obniżone stężenia PAPP-A i PlGF są związane z podwyższonym ryzykiem rozwoju stanu przedrzucawkowego i jego powikłań.. Słowa kluczowe: VWDQSU]HGU]XFDZNRZ\/ PAPP-A / PlGF /. Introduction. Materials and methods. +\SHUWHQVLRQLQSUHJQDQF\UHPDLQVFRQVLVWHQWO\RQHRIWKH PDMRU SUREOHPV RI FRQWHPSRUDU\ REVWHWULFV$QQXDOO\ DSSUR[L PDWHO\PLOOLRQSUHJQDQWZRPHQZRUOGZLGHDUHGLDJQRVHGZLWK K\SHUWHQVLRQDQGDERXWWKRXVDQGSUHJQDQWZRPHQGLHIURP WKHGLVHDVHDQGLWVFRPSOLFDWLRQV>@ )URPWKHFOLQLFDOSRLQWRIYLHZWKHPRVWLPSRUWDQWIRUPRI K\SHUWHQVLRQLQSUHJQDQF\LVSUHHFODPSVLD7KHLQFLGHQFHRISUH HFODPSVLDLQSULPLSDUDVLVHVWLPDWHGDWDURXQGWR>@,WLV DV\VWHPLFGLVHDVHDVVRFLDWHGZLWKKLJKPDWHUQDOPRUWDOLW\

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Konflikt interesów: +_^Y\dc XSO dQ¨K]dKT UYX»SU^_ SX^O\O]éa Y\Kd XSO Y^\dcWKVS. żadnego wynagrodzenia związanego z powstawaniem pracy.. Re f er enc es 1. Roberts JM, Cooper DW. Pathogenesis and genetics of preeclampsia. Lancet. 2001, 357, 53–56. 2. Davison JM, Homuth V, Jeyabalan A, [et al.]. New aspects in the pathophysiology of preeclampsia. J Am Soc Nephrol. 2004, 15, 2440–2448. 3. ACOG practice bulletin: Hypertension in pregnancy. Establishing the diagnosis of preeclamsia and eclampsia. Obstet Gynecol. 2013, 17-20. 4. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005, 365, 785-799. 5. Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987-2004. Am J Hypertens. 2008, 21, 521-526. 6. CEMACH. Why mothers die 2000-2002. In: The sixth report of the confi dential enquiries into maternal deaths in the United Kingdom. Ed. Lewis G. London: RCOG Press. 2004, 340. 7. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009, 33, 130137. 8. Goldenberg RL, Culhane JF, Iams JD, [et al.]. Epidemiology and causes of preterm birth. Lancet. 2008, 371, 75-84. 9. Barton JR, Istwan NB, Rhea D, [et al.]. Costsavings analysis of an outpatient management program for women with pregnancy-related hypertensive conditions. Dis Manag. 200, 9, 236241. 10. Liu A, Wen SW, Bottomley J, [et al.]. Utilization of health care services of pregnant women complicated by preeclampsia in Ontario. Hypertens Pregnancy. 2009, 28, 76-84. 11. Maynard SE, Karumanchi SA. Angiogenic factors and preeclampsia. Semin Nephrol. 2011, 31, 33–46. 12. Ong CY, Liao AW, [et al.]. First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG. 2000, 107 (10), 1265-1270. 13. Smith GC, Stenhouse EJ, Crossley JA, [et al.]. Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab. 2002, 87 (4), 1762-1767. 14. Yaron Y, Heifetz S, Ochshorn Y, [et al.]. Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome. Prenat Diagn. 2002, 22 (9), 778-782. 15. Poon LC, Maiz N, Valencia C, [et al.]. First-trimester maternal serum pregnancy-associated plasma protein-A and pre-eclampsia. Ultrasound Obstet Gynecol. 2009, 33 (1), 23-33. 16. Spencer K, Cowans NJ, Chefetz I, [et al.]. First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol. 2007, 29 (2), 128-134. 17. Poon LC, Nicolaides KH. First-trimester maternal factors and biomarker screening for preeclampsia. Prenat Diagn. 2014, 25. 18. D’Anna R, Baviera G, Corrado F, [et al.]. Adiponectin and insulin resistance in early- and lateonset pre-eclampsia. BJOG. 2006, 113 (11), 1264-1269. 19. Spencer K, Yu CK, Cowans NJ, [et al.]. Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free beta-hCG and with second-trimester uterine artery Doppler. Prenat Diagn. 2005, 25 (10), 949-953. 20. Cowans NJ, Spencer K. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system. Prenat Diagn. 2007, 27 (3), 264-271. 21. Erez O, Romero R, Espinoza J, [et al.]. The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J Matern Fetal Neonatal Med. 2008, 21, 279–287. 22. Akolekar R, Zaragoza E, Poon LC, [et al.]. Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2008, 32 (6), 732-739. 23. Ong CY, Liao AW, Cacho AM, [et al.]. First-trimester maternal serum levels of placenta growth factor as predictor of preeclampsia and fetal growth restriction. Obstet Gynecol. 2001, 98 (4), 608-611. 24. Taylor RN, Grimwood J, Taylor RS, [et al.]. Longitudinal serum concentrations of placentalgrowth factor: evidence for abnormal placental angiogenesisin pathologic pregnancies. Am J Obstet Gynecol. 2003, 188, 177–182. 25. Crispi F, Dominguez C, Llurba E, [et al.]. Placental angiogenic growth factors and uterineartery Doppler findings for characterization of different subsets in preeclampsia and in isolated intrauterine growth restriction. Am J Obstet Gynecol. 2006, 195, 201–207. 26. Ohkuchi A, Hirashima C, Matsubara S, [et al.]. Alterationsin placental growth factor levels before and after the onset ofpreeclampsia are more pronounced in women with early onsetsevere preeclampsia. Hypertens Res. 2007, 30, 151–159. 27. Kosiński P, Samaha RB, Bomba-Opoń DA, [et al.]. Reference values for placental growth factor (PlGF) concentration and uterine artery doppler pulsatility index (PI) at 11-13(+6) weeks of gestation in the Polish population. Ginekol Pol. 2014, 85 (7), 488-493. 28. Cowans NJ, Stamatopoulou A, Matwejew E, [et al.]. First-trimester placental growth factor as a marker for hypertensive disorders and SGA. Prenat Diagn. 2010, 30 (6), 565-570. 29. Vandenberghe G, Mensink I, Twisk JW, [et al.]. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia. Prenat Diagn. 2011, 31 (10), 955-961. 30. Di Lorenzo G, Ceccarello M, Cecotti V, [et al.]. First trimester maternal serum PIGF, free -hCG, PAPP-A, PP-13, uterine artery Doppler and maternal history for the prediction of preeclampsia. Placenta. 2012, 33,495-501.. Conclusion 7KH ELRFKHPLFDO H[SRQHQW RI DEQRUPDO SODFHQWDWLRQ DQG FRQVHTXHQWO\ SODFHQWDO IXQFWLRQ LV D GHFUHDVHG VHFUHWLRQ RI VXEVWDQFHV RI SODFHQWDO RULJLQ 7KH UHYHDOV D VLJQL¿FDQW FRUUHODWLRQEHWZHHQUHGXFHGOHYHOVRISODFHQWDOJURZWKIDFWRUDQG SUHJQDQF\DVVRFLDWHGSODVPDSURWHLQ$LQWKHJURXSRISDWLHQWV ZLWKSUHHFODPSVLDFRPSDUHGWRWKHFRQWUROJURXS 7KHLGHQWL¿FDWLRQRIDJURXSRISDWLHQWVDWKLJKHUULVNGXULQJ URXWLQH¿UVWWULPHVWHUH[DPLQDWLRQGHVSLWHWKHODFNRIFRPPRQO\ UHFRJQL]HG SUHYHQWLYH PHWKRGV ZLOO DOORZ LQWHQVL¿HG REVWHWULF VXSHUYLVLRQDQGDGHTXDWHUHVSRQVHLQWKHFDVHRIFRPSOLFDWLRQV. Oświadczenie autorów 1. Ewelina Litwińska – autor koncepcji i założeń pracy, przygotowanie manuskryptu i piśmiennictwa – autor zgłaszający i odpowiedzialny za manuskrypt. 2. Magdalena Litwińska – zebranie materiału, analiza statystyczna wyników, współautor tekstu pracy. 3. Przemysław Oszukowski – korekta i akceptacja ostatecznego kształtu manuskryptu. 5\dc]d^YP =dK»SU q UY\OU^K Sw KUMOZ^KMTK Y]^K^OMdXOQY U]d^K¨^_. manuskryptu. 5. Waldemar Litwiński – zebranie materiału, korekta i aktualizacja literatury. 6. Maciej Korcz – zebranie materiału, korekta oraz aktualizacja piśmiennictwa. 7. Piotr Kaczmarek – ostateczna weryfikacja i akceptacja manuskryptu.. . . . . . . . . . . . . . . . .

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