Clinical Importance of Low Level of PAPP-A in First Trimester of Pregnancy - An Obstetrical Dilemma in Chromosomally Normal Fetus

Vesna Livrinova; Igor Petrov; Igor Samardziski; Viktorija Jovanovska; Aleksandra Atanasova Boshku; Irena Todorovska; Drage Dabeski; Ajla Shabani

doi:10.3889/oamjms.2019.348

Authors

Vesna Livrinova University Clinic for Obstetrics and Gynecology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
Igor Petrov Universtity Clinic for Neurology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
Igor Samardziski University Clinic for Obstetrics and Gynecology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
Viktorija Jovanovska University Clinic for Obstetrics and Gynecology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
Aleksandra Atanasova Boshku University Clinic for Obstetrics and Gynecology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
Irena Todorovska University Clinic for Obstetrics and Gynecology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
Drage Dabeski University Clinic for Obstetrics and Gynecology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
Ajla Shabani University Clinic for Obstetrics and Gynecology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia

DOI:

https://doi.org/10.3889/oamjms.2019.348

Keywords:

First trimester, Screening, Pregnancy-associated plasma protein A, Perinatal outcome, Clinical, Implication

Abstract

BACKGROUND: A variety of recent evidence exists about the clinical implication of low level of Pregnancy-associated plasma protein A (PAPP-A) in pregnancy. This glycoprotein is a protease, which releases the Insulin-like growth factor from IGFBP 4. Its role is a trophoblastic invasion of decidua, stimulation of cell mitosis and differentiation. It has an immunosuppressive effect in the placenta, inhibition of coagulation and complex role for integration of all these processes in the placenta. Level of PAPP-A (under 0.4 MoM-Multiple of Medians) in first-trimester screening in chromosomally and morphologically normal fetuses, could influence fetal weight, preeclampsia, premature birth and stillbirth. As a result of the complications mentioned above, there is implication on timing, mode of delivery and condition of the newborn.

AIM: The study aims to evaluate the influence of low PAPP-A, measured in the first trimester on the outcome of pregnancy, with accent disorders which are the result of placental insufficiency. Also, gestational week, mode of delivery and condition of newborn secondary underlying conditions will be evaluated.

MATERIAL AND METHODS: After given information and consultation about the expectation from the screening, pregnant women with a singleton pregnancy were tested for First Trimester Screening to estimate the risk for Trisomy 21, 13, 18- the most frequent chromosomopathies. After exclusion of chromosomopathies and congenital malformations, one hundred and fourteen patients enrolled in the study. The target group (n = 64) with PAPP-A below 0.4 MoM and control group (n = 50) with PAPP-A equal and above 0.4 MoM. An assessment of mode and time of delivery and presence of small for gestational age newborns, preeclampsia, premature birth and newborn condition at delivery was made.

RESULTS: The percentage of the patients delivered in term was similar between the target group (n = 64) and the control group (n = 50), 82.81% vs 82.0% respectively. The rate of cesarean section was 29.7 % in the target group vs 32% in the control group. A significant difference was found about elective vs urgent cesarean section in favour of the target group. The difference was present about the complication in pregnancy before delivery, 56% vs 22%, p = 0.023, which were the main indication for cesarean section. The difference in newborn outcome was not significant.

CONCLUSION: There is a difference in frequency of complications, in the cases with PAPP-A under 0.4 MoM, such as premature birth, preeclampsia compound with SGA fetuses versus the control group. The difference for SGA newborn and premature birth among the groups has statistical significance. The patients delivered with cesarean section were with the main indications SGA or elevated blood pressure, often occurred combined with prematurity. Apgar score and birth weight were similar in target and control group, but the newborns with a birth weight under 2500 g. were more frequent in the target group. Because these results did not show another significance among two groups, probably lower cut-off is needed, combining with another test (Doppler of uterine arteries in the first trimester, biochemical test). Presence of other diseases which could hurt placental function should be emphasised.

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References

Spencer Ðš, Spencer CE, Power M, Dowson C, Nikolaides KH. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in one stop clinic: A review of three years experience. BJOG. 2003b; 110:281-6. https://doi.org/10.1046/j.1471-0528.2003.02246.x

Nikolaides KH. Nuchal translucensy and other first trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol. 2004; 191(1):45-67. https://doi.org/10.1016/j.ajog.2004.03.090

Lin TM, Halbert SP, Spellacy WN. Measurment of Pregnancy Associated Plasma proteins during Human Gestation. J Clin Invest. 1974; 53(3):576-582. https://doi.org/10.1172/JCI107794 PMid:4853116 PMCid:PMC301590

Tornehave D, Chemnitz J, Teisner B, Folkersen J,Westergaard JG. Immunohistochemical demonstration of pregnancy associatedplasma protein-A (PAPP-A) in the syncytiotrophoblast of the normal placenta at different gestational ages. Placenta. 1984; 5:427-431. https://doi.org/10.1016/S0143-4004(84)80023-5

Conover CA, Bale LK, Overgaard MT, Johnstone EW, Laursen UH, Fuchtbauer EM, Oxvig C, van Deursen J. Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. Development. 2004; 131:1187-1194. https://doi.org/10.1242/dev.00997 PMid:14973274

Lawrence JB, Oxvig C, Overgaard MT, Sottrup JL, Gleich GJ, Hays LG, Yates JR, Conover CA. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci USA. 1999; 96:3149-3153. https://doi.org/10.1073/pnas.96.6.3149 PMid:10077652 PMCid:PMC15910

Huynh L, Kingdom J, Akhtar S. Low pregnancy-associated plasma protein A level in the first trimester. Can Fam Physician. 2014; 60(10):899-903.

Brambati B, Lanzani A, Tului L. Ultrasound and biochemical assessment of first trimester pregnancy. InThe embryo 1991 (pp. 181-194). Springer, London. https://doi.org/10.1007/978-1-4471-1802-2_12

Fialova L, Malbohan IM. Pregnancy-associated plasma proteinA (PaPP-A):theoretical and clincal aspects. Bratisl Lek Listy. 2002; 103(6):194-205.

Morssink LP, Kornman LH, Hallahan TW, Kloosterman MD, Beekhuis JR, de Wolf BTHM, Mantingh A. Maternal serum levels of free Î²-hCG and PAPP-A in the first trimester of pregnancy are not associated with subsequent fetal growth retardation or preterm delivery. Prenat Diagn. 1998; 18:147-152. https://doi.org/10.1002/(SICI)1097-0223(199802)18:2<147::AID-PD231>3.0.CO;2-W

Tul N, PuÅ¡enjak S, Osredkar J, Spencer K, Novakâ€AntoliÄ Å½. Predicting complications of pregnancy with firstâ€trimester maternal serum freeâ€Î²hCG, PAPPâ€A and inhibinâ€A. Prenatal Diagnosis: Published in Affiliation with the International Society for Prenatal Diagnosis. 2003; 23(12):990-6. https://doi.org/10.1002/pd.735 PMid:14663836

Krantz D, Goetzl L, Simpson JL, Thom E, Zachary J, Hallahan TW, Silver R, Pergament E, Platt LD, Filkins K, Johnson A, Mahoney M, Hogge WA, Wilson RD, Mohide P, Hershey D, Wapner R. Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes. Am J Obstet Gynecol. 2004; 191:1452-1458. https://doi.org/10.1016/j.ajog.2004.05.068 PMid:15507982

Van Ravenswaaij R, Tesselaarâ€Van der Goot M, de Wolf S, van Leeuwenâ€Spruijt M, Visser GH, Schielen PC. Firstâ€trimester serum PAPPâ€A and fÎ²â€hCG concentrations and other maternal characteristics to establish logistic regressionâ€based predictive rules for adverse pregnancy outcome. Prenatal diagnosis. 2011; 31(1):50-7. https://doi.org/10.1002/pd.2610 PMid:20827668

Saruhan Z, Ozakinci M, Simsek M, Mendilcioglu I. Association of first trimester low PAPP-A with adverse pregnancy outcomes. Clin Exp Obstet Gynecol. 2012; 39(2):225-8.

Goetzinger KR, Cahill AG, et al. Association of first -trimester low PAPP-A levels with preterm birth. Prenat. Diagn. 2010; 30(4):309-13. https://doi.org/10.1002/pd.2452 PMid:20087924

Marttala Ðˆ, Peuhkurinen Ð¡, Laitinen P, Gissler M, Nieminen P, Ryynanen M. Low maternal PAPP-A is associated with small-for gestational age newborns and stillbirths. Acta Obstet gynecol Scand. 2010; 89(9):1226-8. https://doi.org/10.3109/00016349.2010.493195 PMid:20590503

Poon LC, Maiz N, Valencia C, Plasencia W, Nicolaides KH. First-trimester maternal serum PAPP-A and preeclampsia. Ultrasound Obstet Gynecol. 2009; 33(1):23-33. https://doi.org/10.1002/uog.6280 PMid:19090499

Abdel Moety GA, Almohamady M, Sherif NA, Raslana AN, Mohamed TF, El Moneam HM, Mohy AM, Youssef MA. Could first-trimester assessment of placental functions predict preeclampsia and intrauterine growth restriction? A prospective cohort study. The Journal of Maternal-Fetal & Neonatal Medicine. 2016; 29(3):413-7. https://doi.org/10.3109/14767058.2014.1002763 PMid:25594239

Livrinova V, Petrov I, Samardziski I, Jovanovska V, Simeonova Krstevska S, Todorovska I, Atanasova-Boshku A, Gjorgjievska M. Obstetric Outcome in Pregnant Patients with Low Level of Pregnancy-Associated Plasma Protein A in First Trimester. Open Access Maced J Med Sci. 2018; 6(6):1028-31. https://doi.org/10.3889/oamjms.2018.238 PMid:29983796 PMCid:PMC6026403

Thompson M, Murray R, Madipola N, Power M, Otigbah C, Spencer K. An obstetric outcome audit of pregnancies complicated by low first-trimester maternal serum pregnancy-associated plasma protein A levels at Barking, Havering and redbridge university teaching hospitals NHS trust. BJOG:An Intern Journal of Obstet and Gyn. 2016; 122(10):1370-76. https://doi.org/10.1111/1471-0528.13298 PMid:25639820

Dugoff L, Hobbins JC, Malone FD, et al. 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(6):1446-51. https://doi.org/10.1016/j.ajog.2004.06.052 PMid:15507981

Ranganathan A. Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational Study. Obstet Gynecol Rep. 2017; 1(3):4-6. https://doi.org/10.15761/OGR.1000116

Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst. Rev. 2010; (1):CD 007529. https://doi.org/10.1002/14651858.CD007529.pub2

Cooper S, Johnson JA, et al. The predictive value of 18 and 22 week uterine artery Doppler in patients with low first-trimester maternal serum PAPP-A. Prenat Diagn. 2009; 29(3):248-52. https://doi.org/10.1002/pd.2175 PMid:19222047