First trimester maternal serum placental protein 13 levels in singleton vs. twin pregnancies with and without severe pre-eclampsia
Abstract
Aims: To determine first trimester maternal serum placental protein 13 (PP13) in singletons vs. twins with and without severe preeclampsia (PE).
Methods: Serum samples were prospectively collected at 8–14 weeks of gestation. PP13 was determined by solid-phase immunoassay. Patients were recruited in community clinics throughout the country, and from the twin antenatal assessment clinic in Assaf Harofeh Medical Center, Zerifin, Israel. Demographics, medical, and pregnancy history were obtained at enrollment. Pregnancy outcome was collected after delivery. PP13 was compared by the Wilcoxon rank sum test.
Results: In singletons, PP13 declined with maternal weight and was lower in in vitro fertilization. Levels were converted into multiples of the median (MoMs) accordingly. In twins, the median was 1.74 MoM (n=76) vs. 1.00 in singletons (n=676, P<0.0001). Among twins with severe PE (n=10), the median was 1.53 MoM vs. 1.74 in unaffected twins (P=0.10), and 2.26 (n=6) for mild PE (P=0.30). Among singletons with severe PE, the median was 0.44 MoM (n=26, P<0.0001), and for mild PE 0.62 (n=17, P<0.001).
Conclusion: PP13 is higher in twins than singletons, corresponding to the larger placental mass. Among singletons with severe PE, levels were significantly reduced, however, among twins, only a non-significant tendency for a reduction was recorded, and warrants further investigation in a larger series.
The authors thank Mrs. Esther Klug, RN CNM MPH, for the dedicated and professional assistance in recruiting the patients at Assaf Harofeh Medical Center, for sample collection, and for handling and collecting of the pregnancy outcomes. We also thank Ruti Cohen, PhD, Hy-Laboratories for assisting in collecting pregnancy outcomes of the community clinics, for meeting the requirements of the Israel Ministry of Health, and for support and advice throughout the preparation of this manuscript. The study was supported in part by the EU 6th R&D framework project Pregenesys (#037244).
References
[1] ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002;77:67–75.10.1016/S0029-7844(01)01747-1Suche in Google Scholar
[2] Akolekar R, Syngelaki A, Beta J, Kocylowski R, Nicolaides KH. Maternal serum placental protein 13 at 11–13 weeks of gestation in preeclampsia. Prenat Diagn. 2009;29:1103–8.10.1002/pd.2375Suche in Google Scholar PubMed
[3] Balogh A, Pozsgay J, Matkó J, Dong Z, Kim CJ, Várkonyi T, et al. Placental protein 13 (PP13/Galectin-13) undergoes lipid raft-associated subcellular redistribution in the syncytiotrophoblast in preterm preeclampsia and HELLP syndrome. Am J Obstet Gynecol. 2011;205:e1–14.10.1016/j.ajog.2011.03.023Suche in Google Scholar PubMed PubMed Central
[4] Bdolah Y, Lam C, Rajakumar A, Shivalingappa V, Mutter W, Sachs BP, et al. Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia? Am J Obstet Gynecol. 2008;198:428.e1–6.10.1016/j.ajog.2007.10.783Suche in Google Scholar PubMed
[5] Bujold E, Roberge S, Lacass Y, Bureau M, Audibert F, Marcoux S, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010;116:402–14.10.1097/AOG.0b013e3181e9322aSuche in Google Scholar PubMed
[6] Calhoun KC, Barnhart KT, Elovitz MA, Srinivas SK. Evaluating the association between assisted conception and the severity of preeclampsia. ISRN Obstet Gynecol. 2011;2011:928592.10.5402/2011/928592Suche in Google Scholar PubMed PubMed Central
[7] Caspi E, Raziel A, Sherman D, Arieli S, Bukovski I, Weinraub Z. Prevention of pregnancy-induced hypertension in twins by early administration of low-dose aspirin: a preliminary report. Am J Reprod Immunol. 1994;31:19–24.10.1111/j.1600-0897.1994.tb00842.xSuche in Google Scholar PubMed
[8] Cetin I, Huppertz B, Burton G, Cuckle H, Gonen R, Lapaire O, et al. Pregenesys pre-eclampsia markers consensus meeting: What do we require from markers, risk assessment and model systems to tailor preventive strategies? Placenta. 2011;32(Suppl 1):S4–16.10.1016/j.placenta.2010.11.022Suche in Google Scholar PubMed
[9] Chafetz I, Kuhnreich I, Sammar M, Tal Y, Gibor Y, Meiri H, et al. First-trimester placental protein 13 screening for pre-eclampsia and intrauterine growth restriction. Am J Obstet Gynecol. 2007;197:35.e1–7.10.1016/j.ajog.2007.02.025Suche in Google Scholar PubMed
[10] Cuckle H. Screening for preeclampsia–lessons from aneuploidy screening. Placenta. 2011;32(Suppl 1):S42–8.10.1016/j.placenta.2010.07.015Suche in Google Scholar PubMed
[11] Dumoulin JC, Land JA, Van Montfoort AP, Nelissen EC, Coonen E, Derhaag JG, et al. Effect of in vitro culture of human embryos on birthweight of newborns. Hum Reprod. 2010; 25:605–12.10.1093/humrep/dep456Suche in Google Scholar PubMed
[12] Gielen M, Lindsey PJ, Derom C, Loos RJ, Derom R, Nijhuis JG, et al. Curves of placental weights of live- born twins. Twin Res Hum Genet. 2006;9:664–72.10.1375/twin.9.5.664Suche in Google Scholar
[13] Giguère Y, Charland M, Bujold E, Bernard N, Grenier S, Rousseau F, et al. Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. Clin Chem. 2010;56:361–5.10.1373/clinchem.2009.134080Suche in Google Scholar PubMed
[14] Gonen R, Shahar R, Grimpel YI, Chefetz I, Sammar M, Meiri H, et al. Placental protein 13 as an early marker for preeclampsia: a prospective longitudinal study. Br J Obstet Gynaecol. 2008:115;1465–72.10.1111/j.1471-0528.2008.01902.xSuche in Google Scholar PubMed
[15] Grimpel YI, Kivity V, Cohen A, Meiri H, Sammar M, Gonen R, et al. Effects of calcium, magnesium, low-dose aspirin and low-molecular-weight heparin on the release of PP13 from placental explants. Placenta. 2011;32(Suppl 1):S55–64.10.1016/j.placenta.2010.11.019Suche in Google Scholar PubMed
[16] Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-rump length: reevaluation of relation to menstrual age (5–18 weeks) with high-resolution real-time US. Radiology. 1992;182:501–5.10.1148/radiology.182.2.1732970Suche in Google Scholar PubMed
[17] Huppertz B, Sammar M, Chefetz I, Neumaier-Wagner P, Bartz C, Meiri H. Longitudinal determination of serum placental protein 13 during development of pre-eclampsia. Fetal Diagn Ther. 2008;24:230–6.10.1159/000151344Suche in Google Scholar PubMed
[18] Khalil A, Cowans NJ, Spencer K, Goichman S, Meiri H, Harrington K. First-trimester markers for the prediction of preeclampsia in women with a-priori high risk. Ultrasound Obstet Gynecol. 2010;35:671–9.Suche in Google Scholar
[19] Klein K, Mailath-Pokorny M, Elhenicky M, Schmid M, Zeisler H, Worda C. Mean, lowest, and highest pulsatility index of the uterine artery and adverse pregnancy outcome in twin pregnancies. Am J Obstet Gynecol. 2011;205:549.e1–7.10.1016/j.ajog.2011.06.103Suche in Google Scholar PubMed
[20] Koster MP, Wortelboer EJ, Stoutenbeek P, Visser GH, Schielen PC. Distributions of current and new first-trimester Down syndrome screening markers in twin pregnancies. Prenat Diagn. 2010;30:413–7.10.1002/pd.2483Suche in Google Scholar PubMed
[21] Lindheimer MD, Taler SJ, Cunningham FG, American Society of Hypertension. ASH position paper: hypertension in pregnancy. J Clin Hypertens (Greenwich). 2009;11:214–25.10.1111/j.1751-7176.2009.00085.xSuche in Google Scholar PubMed PubMed Central
[22] Muller F, Dreux S, Dupoizat H, Uzan S, Dubin MF, Oury JF, et al. Second-trimester Down syndrome maternal serum screening in twin pregnancies: impact of chorionicity. Prenat Diagn. 2003;23:331–5.10.1002/pd.594Suche in Google Scholar
[23] Noble PL, Snijders RJ, Abraha HD, Sherwood RA, Nicolaides KH. Maternal serum free beta-hCG at 10 to 14 weeks of gestation in trisomic twin pregnancies. Br J Obstet Gynaecol. 1997;104:741–3.10.1111/j.1471-0528.1997.tb11989.xSuche in Google Scholar
[24] Orendi K, Gauster M, Moser G, Meiri H, Huppertz B. Effects of vitamins C and E, acetylsalicylic acid and heparin on fusion, beta-hCG and PP13 expression in BeWo cells. Placenta. 2010;31:431–8.10.1016/j.placenta.2010.02.017Suche in Google Scholar
[25] Publications Committee, Society for Maternal-Fetal Medicine, Sibai BM. Evaluation and management of severe preeclampsia before 34 weeks’ gestation. Am J Obstet Gynecol. 2011;205:191–8.10.1016/j.ajog.2011.07.017Suche in Google Scholar
[26] Romero R, Kusanovic JP, Than NG, Erez O, Gotsch F, Espinoza J, et al. First-trimester maternal serum PP13 in the risk assessment for preeclampsia. Am J Obstet Gynecol. 2008;199:122:e1–11.10.1016/j.ajog.2008.01.013Suche in Google Scholar
[27] Santolaya-Forgas J, De Leon JA, Cullen Hopkins R, Castracane VD, Kauffman RP, Sifuentes GA. Low pregnancy-associated plasma protein-a at 10(+1) to 14(+6) weeks of gestation and a possible mechanism leading to miscarriage. Fetal Diagn Ther. 2004;19:456–61.10.1159/000079000Suche in Google Scholar
[28] Sibai BM, Caritis SN, Thom E, Klebanoff M, McNellis D, Rocco L, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. New Engl J Med. 1993;329:1213–8.10.1056/NEJM199310213291701Suche in Google Scholar
[29] Sibai BM, Hauth J, Caritis S, Lindheimer MD, MacPherson C, Klebanoff M, et al. Hypertensive disorders in twin versus singleton gestations. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol. 2000;182:938–42.10.1016/S0002-9378(00)70350-4Suche in Google Scholar
[30] Spencer K. Screening for trisomy 21 in twin pregnancies in the first trimester using free beta-hCG and PAPP-A, combined with fetal nuchal translucency thickness. Prenat Diagn. 2000;20:91–5.10.1002/(SICI)1097-0223(200002)20:2<91::AID-PD759>3.0.CO;2-XSuche in Google Scholar
[31] Than NG, Romero R, Goodman M, Weckle A, Xing J, Dong Z, et al. A primate subfamily of galectins expressed at the maternal-fetal interface that promote immune cell death. Proc Natl Acad Sci USA. 2009;106:9731–6.10.1073/pnas.0903568106Suche in Google Scholar
[32] World Health Organization. Make every mother and child count. World Health Report, 2005. Geneva: World Health Organization; 2005.Suche in Google Scholar
The authors stated that there are no conflicts of interest regarding the publication of this article.
©2013 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Review Article
- Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?
- Original Articles – Obstetrics
- Differences and similarities in the transcriptional profile of peripheral whole blood in early and late-onset preeclampsia: insights into the molecular basis of the phenotype of preeclampsiaa
- The correlation of ultrasonographic placental architecture with placental histology in the low-risk primigravid population
- The course of angiogenic factors in early- vs. late-onset preeclampsia and HELLP syndrome
- Effect of maternal body mass index on oxytocin treatment for arrest of dilatation1)
- Maternal weight gain in women with gestational diabetes mellitus
- Clinical risk factors for complete and partial placental retention – a case-control study
- Diagnostic problems in case of twin pregnancies: US vs. MRI study
- Subsequent pregnancy after stillbirth: obstetrical and medical risks
- MTHFR C677T polymorphism, folate, vitamin B12 and homocysteine in recurrent pregnancy losses: a case control study among north Indian women
- Acupuncture and/or sweeping of the fetal membranes before induction of labor: a prospective, randomized, controlled trial
- First trimester maternal serum placental protein 13 levels in singleton vs. twin pregnancies with and without severe pre-eclampsia
- Relaparotomies after cesarean sections: risk factors, indications, and management
- The impact of route of anesthesia on maternal and fetal ischemia modified albumin levels at cesarean section: a prospective randomized study
- Infection and smoking are associated with decreased plasma concentration of the anti-aging protein, α-klothoa
- Effect of oxygen tension on bacteria-stimulated cytokine production by fetal membranes
- Original Articles – Fetus
- Is there a relationship between fetal brain function and the fetal behavioral state? A fetal MEG-study
- Original Articles – Newborn
- Infrared thermography for detailed registration of thermoregulation in premature infants
- Short Communication
- Are there gender related differences in neonatal abstinence syndrome following exposure to buprenorphine during pregnancy?
- Congress Calendar
- Congress Calendar
Artikel in diesem Heft
- Masthead
- Masthead
- Review Article
- Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?
- Original Articles – Obstetrics
- Differences and similarities in the transcriptional profile of peripheral whole blood in early and late-onset preeclampsia: insights into the molecular basis of the phenotype of preeclampsiaa
- The correlation of ultrasonographic placental architecture with placental histology in the low-risk primigravid population
- The course of angiogenic factors in early- vs. late-onset preeclampsia and HELLP syndrome
- Effect of maternal body mass index on oxytocin treatment for arrest of dilatation1)
- Maternal weight gain in women with gestational diabetes mellitus
- Clinical risk factors for complete and partial placental retention – a case-control study
- Diagnostic problems in case of twin pregnancies: US vs. MRI study
- Subsequent pregnancy after stillbirth: obstetrical and medical risks
- MTHFR C677T polymorphism, folate, vitamin B12 and homocysteine in recurrent pregnancy losses: a case control study among north Indian women
- Acupuncture and/or sweeping of the fetal membranes before induction of labor: a prospective, randomized, controlled trial
- First trimester maternal serum placental protein 13 levels in singleton vs. twin pregnancies with and without severe pre-eclampsia
- Relaparotomies after cesarean sections: risk factors, indications, and management
- The impact of route of anesthesia on maternal and fetal ischemia modified albumin levels at cesarean section: a prospective randomized study
- Infection and smoking are associated with decreased plasma concentration of the anti-aging protein, α-klothoa
- Effect of oxygen tension on bacteria-stimulated cytokine production by fetal membranes
- Original Articles – Fetus
- Is there a relationship between fetal brain function and the fetal behavioral state? A fetal MEG-study
- Original Articles – Newborn
- Infrared thermography for detailed registration of thermoregulation in premature infants
- Short Communication
- Are there gender related differences in neonatal abstinence syndrome following exposure to buprenorphine during pregnancy?
- Congress Calendar
- Congress Calendar