Birinci Trimester Gebelikle İlişkili Plasma Protein-A Düzeyinin, İkinci Trimester Uterin Arter Doppler, Plasental Boyut ve Kötü Obstetrik Sonuçlarla İlişkisi

Öz

Amaç: Birinci trimester Down Sendromu taramasında 3. persentilin altında ( ≤0.30 Multiples of Median (MoM)) olan pregnancy associated plasma protein-A (PAPP-A)
düzeyinin, ikinci trimester ortalama uterin arter (UtA) pulsatilite indeksi (PI) ile plasental boyut ölçümü ve kötü obstetrik sonuçlarla ilişkisini araştırmayı amaçladık.
Gereç ve Yöntemler: Eylül 2010 ile Ocak 2011 tarihleri arasında Dr. Lütfi Kırdar Kartal Eğitim ve Araraştırma Hastanesi Perinatoloji polikliniğine başvuran birinci trimester tarama testinde PAPP-A düzeyi ≤ 0.30 düzeltilmiş MoM saptanan 32 (Grup 1), PAPP-A düzeyi >0.30 düzeltilmiş MoM saptanan 50 kadın (grup 2) çalışmaya dahil edildi. Gebeler 18-24 haftalarda plasenta boyut ölçümü ve UtA doppleri ile yeniden değerlendirildi. Artmış UtA direnç indeksi olarak ortalama UtA PI ≥1.45 anormal
kabul edildi. Gebeler düşük PAPP-A ve artmış UtA PI (Grup 1:n=7) ve normal PAPP-A ve normal UtA PI (Grup 2:n=75) olarak tekrar gruplandı ve doğum sonrası
preeklampsi, intrauterin gelişme geriliği (IUGG), oligohidramnios, erken doğum gibi gebelik komplikasyonları açısından sorgulandı.
Bulgular: PAPP-A düzeyine göre gruplar karşılaştırıldığında kötü obsterik sonuçlar düşük PAPP-A grubunda fazla iken istatiksel olarak anlamlı fark yalnızca preeklampside izlendi (p=0.02). İkinci trimester plasenta boyutu ve UtA PI değerlerinde gruplar arasında anlamlı fark saptanmadı. Gebeler PAPP-A ve UtA PI değerine
göre gruplandığında düşük PAPP-A ve yüksek UtA PI grubunda IUGG (p=0.03), oligohidramnios (p=0.04) daha fazla, doğum kilosu daha düşüktü p=(0.02) ve fark
istatistiksel olarak anlamlıydı, preeklampsi açısından anlamlı fark saptanmadı (p=0.23).
Sonuç: Sonuçları iştir ki, plasental yetmezliğin anne ve fetus üzerindeki olumsuz etkilerini tahmin etmek mümkündür, ancak tek başına kullanılabilecek bir tarama
metodu yoktur. Kötü obstetrik sonuçları tarama amaçlı, biyokimyasal ve ultrasonografik parametreleri bir arada kullanan daha geniş randomize klinik çalışmalara
ihtiyaç vardır.  

Anahtar Kelimeler

• Pregnancy associated plasma protein-A
• uterin arter doppler
• preeklampsi
• intrauterin gelişme geriliği

Relationship Between First Trimester Low Pregnancy Associated Plasma Protein A Levels With Second Trimester Uterine Artery Doppler, Placental Size and Adverse Obstetric Outcomes

Öz

Aim: We aimed to demonstrate the relationship between pregnancy associated plasma protein-A PAPP-A levels below 3th percentile ≤0.30 Multiples of Median MoM with second trimester placental size, mean Uterine Artery UtA doppler Pulsatility Index PI and adverse obstetric outcomes.Material and Methods: We recruited 32 women with PAPP-A levels ≤ 0.30 corrected MoM Group 1 , and 50 women with PAPP-A levels > 0.30 corrected MoM Group 2 , attended to Dr. Lütfi Kırdar Kartal Education and Research Hospital perinatology outpatient clinic, between September 2010 and January 2011. Pregnant women were reevaluated at 18-24 weeks with placental size measurement and mean UtA doppler indices. Mean UtA doppler PI ≥1.45 considered to be abnormal as increased UtA resistance. We also grouped women as low PAPP-A and increased mean UtA PI Group 1: n =7 and normal PAPP-A and normal mean UtA PI Group 2: n = 75 . All women are asked in postnatal period for pregnancy complications like preeclampsia PE , intrauterine growth retardation IUGR , preterm delivery, oligohydramniosis and stillbirth.Results: When women were grouped according to the PAPP-A level adverse pregnancy outcomes were more prevalent in low PAPP-A group but statistically significant difference was seen only in preeclampsia p=0.02 . Second trimester placental size and UtA PI levels were not significantly different between groups. When grouped according to the PAPP-A and UtA PI levels, IUGR and oligohydramniosis was significantly higher p= 0.03 and p=0.04 respectively and birth weight was significantly lower p=0.02 in low PAPP-A and high UtA PI group. There was no satistically significant difference in PE among groups p=0.23 .Conclusion: Our results have shown that it is possible to predict unfavorable effects of placental insufficiency on mother and fetus, but it is obvious that there is no single screening method. Randomised clinical trials with larger sample sizes using combination of biochemical and ultrasonographic parameters is necessary for prediction of adverse pregnancy outcomes.

Anahtar Kelimeler

• Pregnancy associated plasma protein-A
• uterine artery doppler
• preeclampsia
• intrauterine growth retardation

Kaynakça

1. Nayak NR,Giudice LC. Comparative biology of the IGF system in endometrium, decidua, and placenta, and clinical implications for foetal growth and implantation disorders. Placenta 2003; 24:281–296.
2. Kagan KO, Wright D, Baker A, Sahota D, NicolaidesKH. Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta-human chorionic gon- adotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 2008;31:618–624.
3. Handschuh K, Guibourdenche J, Guesnon M, Laurendeau I, Evain-Brion D, Fournier T. Modulation of PAPP-A expression by PPAR gamma in human first trimester trophoblast. Placenta 2006;27: S127–S134.
4. Giudice LC, Conover CA, Bale L,et al. 2002. Identification and regulation of the IGFBP-4 protease and its physiological inhibition in human trophoblasts and endometrial stroma: Evidence for paracrine regulation of IGF-II bioavailability in the placental bed during hu- man implantation. J Clin Endocrinol Metab 87:2359–2366.
5. Sun IYC, Overgaard MT, Oxvig C, Giudice LC. Pregnancy associated plasma protein a proteolytic activity is associated with the human placental trophoblast cell membrane. J Clin Endocrinol Metabol 2002; 87:5235–5240.
6. Spencer K, Cowans NJ, Avgidou K, Molina F, Nicolaides KH. First-trimester biochemical markers of aneuploidy and the prediction of small-for-gestational age fetuses. Ultra- sound Obstet Gynecol 2008; 31: 15–19.
7. Barrett SL, Bower C, Hadlow N. Use of the combined first-trimester screen result and low PAPP-A to predict risk of adverse fetal outcomes. Prenat Diagn 2008; 28: 28–35.
8. Yaron Y, Heifetz S, Ochshorn Y, Lehavi O, Orr-Urtreger A. Decreased first trimester PAPP- A is a predictor of adverse pregnancy outcome. Prenat Diagn 2002; 22: 778–782.

9. Smith GCS, Stenhouse EJ, Crossley J etal. Early pregnancy levels of pregnancy-asso- ciated plasma protein A and the risk of intrauterine growth restriction, premature birth, preeclampsia and stillbirth. J Clin Endocrin Metab 2002; 87: 1762–1767
10. Toal M, Keating S, Machin G, Dodd J, Adamson SL, Windrim RC, Kingdom JC. Deter- minants of adverse perinatal outcome in high-risk women with abnormal uterine artery Doppler images. Am J Obstet Gynecol 2008; 198: 330.
11. Albaiges G, Missfelder-Lobos H, Lees C, Parra M, Nicolaides KH. One-stage screening for pregnancy complications by color Doppler assessment of the uterine arteries at 23’ weeks gestation. Obstet Gynecol 2000: 96: 559–564.
12. Dugoff L, Hobbins JC, Malone FD, Porter TF, Luthy D, Comstock CH, Hankins G, Berkow- itz RL, Merkatz I, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Vidaver J, D’ Alton ME. First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial). Am J Obstet Gynecol 2004;191:1446–1451.
13. Smith GC, Shah I, Crossley JA, Aitken DA, Pell JP, Nelson SM, Cameron AD, Connor MJ, Dobbie R. Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome. Obstet Gynecol 2006;107: 161–166.
14. Spencer K, Yu CK, Cowans NJ, Otigbah C, Nicolaides KH. Prediction of pregnancy com- plications by first-trimester maternal serum PAPP-A and free β-hCG and with second- trimester uterine artery Doppler. Prenat Diagn 2005a. 25: 949–953.
15. Pihl K, Larsen T, Krebs L, Christiansen M. First trimester maternal serum PAPP-A, β-hCG and ADAM12 in prediction of small-for-gestational-age fetuses. Prenat Diagn 2008; 28: 1131–1135.
16. Florio K, Haratz N, Salafia C, VanHorn S, Pruthi K, and Smith A. Low PAPP-A levels and placental pathology: is there an association with adverse pregnancy outcome? Ameri- can Journal of Obstetrics and Gynecology, 2012; 206: 310.
17. Saruhan Z, Özekinci M, Mendilcioğlu I. Association of first trimester low PAPP-A levels with adverse pregnancy outcomes. Clin Exp Obstet Gynecol -2012;39;225-8.
18. Spencer K, Cowans NJ, Nicolaides KH. Low levels of maternal serum PAPP-A in the first trimester and the risk of preeclampsia. Prenat Diagn 2008; 28: 7–10.
19. Ajayi GO, Awoleke JO, Adegbola OI, Balogun O. Seroprevalence of Chlamdophila pneumoniae antibodies and pre-eclampsia: is there any link. Geburtshilfe Und Frauen- heilkunde 2008; 68: S153–S153.
20. Spencer K, Cowans NJ, Nicolaides KH. Maternal serum inhibin-A and activin-A levels in the first trimester of pregnancies developing pre-eclampsia. Ultrasound Obstet Gynecol. 2008; 32:622–626.
21. Zhong Y, Tuuli M, Odibo AO. First-trimester assessment of placenta function and the prediction of preeclampsia and intrauterine growth restriction. Prenat Diagn 2010;30:293–308.
22. Pilalis A, Souka AP, Antsaklis P, Daskalakis G, Papantoniou N, Mesogitis S, Antsaklis A. Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler and PAPP-A at 11–14 weeks’ gestation. Ultrasound Obstet Gynecol 2007; 29: 135–140.
23. Hafner E, Metzenbauer M, Hofinger D, et al. Placental growth from the first to the second trimester of pregnancy in SGA-foetuses and pre-eclamptic pregnancies compared to normal foetuses. Placenta. 2003; 24:336–342.
24. Proctor LK, Toal M, Keating S, Chitayat D, Okun N, Windrim RC, Smith GCS and King- dom LCP. Placental size in prediction of IUGR in women with low PAPP-A. Ultrasound Obstet Gynecol 2009; 34: 274–282.