First trimester low maternal serum pregnancy associated plasma protein-A (PAPP-A) as a screening method for adverse pregnancy outcomes

Tiina Kantomaa; Marja Vääräsmäki; Mika Gissler; Mikko Sairanen; Jaana Nevalainen

doi:10.1515/jpm-2022-0241

Article

First trimester low maternal serum pregnancy associated plasma protein-A (PAPP-A) as a screening method for adverse pregnancy outcomes

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Published/Copyright: September 23, 2022

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From the journal Journal of Perinatal Medicine Volume 51 Issue 4

Abstract

Objectives

To evaluate different cut-off values of first trimester pregnancy associated plasma protein-A (PAPP-A) in screening for adverse pregnancy outcomes in a retrospective cohort study.

Methods

During the study period of 1.1.2014–31.12.2018, total of 23,482 women with singleton pregnancies participated in first trimester combined screening for chromosomal abnormalities. Maternal serum PAPP-A multiple of medians (MoM) levels were measured, and study population was divided into three study groups of PAPP-A ≤0.40 (n=1,030), ≤0.35 (n=630) and ≤0.30 (n=363) MoM.

Results

Small for gestational age (SGA), preterm birth (PTB) and composite outcome (SGA, hypertensive disorder of pregnancy (HDP) and/or PTB) were more frequent in all three PAPP-A MoM study groups and pre-eclampsia in ≤0.40 and ≤0.35 study groups than in their control groups (p < 0.05). The odds ratio (OR) for SGA varied from 3.7 to 5.4 and sensitivity and specificity from 6.9 to 13.8% and from 95.9 to 98.6%, between study groups. Using PAPP-A ≤0.30 MoM as a screening cut-off instead of PAPP-A ≤0.40 MoM, resulted in approximately 50% reduction in screening detection of SGA and PTB.

Conclusions

PAPP-A ≤0.40 MoM should be considered as a primary screening cut-off for adverse pregnancy outcomes as approximately 23% will develop either SGA, HDP or PTB. It seems to be the best cut-off to screen for SGA.

Keywords: first trimester screening; hypertensive disorders of pregnancy; pre-eclampsia; pregnancy associated plasma protein-A (PAPP-A); preterm birth; small for gestation age

Corresponding author: Jaana Nevalainen, PhD, MD, Associate Professor, Department of Obstetrics & Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, PL 24, 90100 OYS, Oulu, Finland, Phone: +358-405801857, E-mail: marttjaa@paju.oulu.fi

Funding source: Suomen Lääketieteen Säätiö

Award Identifier / Grant number: 4487

Research funding: This study received funding from the Finnish Medical Foundation (Suomen Lääketieteen Säätiö, no. 4487).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: TK none. JN none. MV none. MG none. MS is an employee at PerkinElmer which is the company that sells first trimester screening equipment for Finnish laboratories.
Informed consent: Not applicable.
Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the Institutional Ethics Committee of Northern Ostrobothnia Hospital District and the Finnish Institute for Health and Welfare (reference number 99/2018), no individual consent from the participants was needed.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2022-0241).

Received: 2022-05-16

Accepted: 2022-09-07

Published Online: 2022-09-23

Published in Print: 2023-05-25

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Keywords for this article

first trimester screening; hypertensive disorders of pregnancy; pre-eclampsia; pregnancy associated plasma protein-A (PAPP-A); preterm birth; small for gestation age