Residents' paper
First-trimester pregnancy-associated plasma protein A and subsequent abnormalities of fetal growth

Presented at the 28th Annual Meeting of the Society for Maternal-Fetal Medicine, Jan. 28-Feb. 2, 2008, Dallas, TX.
https://doi.org/10.1016/j.ajog.2007.12.026Get rights and content

Objective

The purpose of this study was to describe the relationship between first-trimester pregnancy-associated plasma protein A (PAPP-A) and birthweight along its continuum and at its extremes.

Study Design

This was a retrospective cohort of 1371 women who underwent first-trimester screening for fetal aneuploidy and who delivered at our hospital.

Results

First-trimester PAPP-A has a positive relationship with birthweight. As PAPP-A decreases, the risk of small-for-gestational-age (SGA) infants increases. PAPP-A of <10%, <5%, and <1% were associated with an increasing adjusted odds ratio for SGA infants (2.0 [95% CI, 1.2-3.5; P = .012]; 2.4 [95% CI, 1.2-4.7; P = .015]; 9.3 [95% CI, 3.4-25.5; P = .001], respectively). PAPP-A levels of >90% were associated with an adjusted odds ratio for birthweight of >4500 g of 2.9 (95% CI, 1.02-8.17; P = 0.046).

Conclusion

First-trimester PAPP-A is a marker of placental function that correlates with birthweight along its continuum and at its extremes. The strong association between low PAPP-A and SGA warrants further investigation of its usefulness as a screening tool.

Section snippets

Materials and Methods

Data from an obstetric and genetic database were merged to create the retrospective cohort that was used in this study. After approval by the University of Pittsburgh Institutional Review Board was obtained, all women who underwent first-trimester screening between January 2004 and April 2007 were identified (n = 3709 women). Women were screened between the gestational ages of 11 weeks 0 days and 13 weeks 6 days. PAPP-A concentration was determined by an enzyme-linked 2-site immunosorbent assay

Results

Demographics of the cohort are in Table 1. Seven percent of neonates (n = 93) were SGA, and 11% of neonates (n = 152) were LGA. Figure 1 is a scatter plot and linear regression of birthweight and PAPP-A. For every increase in PAPP-A MoM of 1.0, birthweight increases by 119 g.

Logistic regression modeling of PAPP-A MoM and the probability of SGA or LGA infants are depicted in FIGURE 2, FIGURE 3, respectively. As PAPP-A decreases, the probability of SGA infants increases. Conversely, as PAPP-A

Comment

We demonstrated that first-trimester PAPP-A is associated with birthweight. The strong association between low PAPP-A and SGA is of particular clinical significance.

Low birthweight for gestational age significantly increases perinatal morbidity and mortality rates and increases both intrapartum and neonatal complications.9 Our data support the role of PAPP-A as an indicator of placental function throughout pregnancy. Further investigation is needed to elucidate whether poor fetal growth is due

References (10)

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Cited by (40)

  • Does Low PAPP-A Predict Adverse Placenta-Mediated Outcomes in a Low-Risk Nulliparous Population? the Great Obstetrical Syndromes (GOS) Study

    2018, Journal of Obstetrics and Gynaecology Canada
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    First trimester concentration of pregnancy-associated plasma protein A is commonly used for the screening of fetal aneuploidy. Several authors observed that low PAPP-A, typically reported as below 0.3 or 0.4 multiples of median, is associated with an increased risk of placenta-mediated complications, including preeclampsia, SGA fetuses, and fetal death.1–13 Although the SOGC does not recommend a specific management protocol for women with low PAPP-A, low-dose aspirin may be considered, with evidence suggesting its benefits for the prevention of PE, SGA, and fetal death when the regimen is initiated before 16 weeks of gestation.14–18

  • Maternal Serum Analytes as Predictors of Fetal Growth Restriction with Different Degrees of Placental Vascular Dysfunction

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    The aforementioned study by Dugoff and colleagues27 found that levels of PAPP-A at or less than the 5th percentile had an increased risk of all of these complications. First-trimester PAPP-A correlates with birth weight, and consequently, low PAPP-A increases the likelihood of having an FGR fetus.31 A large study in the United Kingdom by Spencer and colleagues,32 which included more than 46,000 women, found that PAPP-A levels less than the 5th percentile in chromosomally normal pregnancies were associated with a more than 3-fold increased risk of FGR but an overall detection rate of only 14%.

  • First trimester pregnancy-associated plasma protein-A and birth weight

    2016, European Journal of Obstetrics and Gynecology and Reproductive Biology
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    Women with PAPP-A measurements <1st percentile were at 3.8 to 4.5-fold higher risk of an SGA infant among each gestational age group compared to women with PAPP-A measurement in the reference range. Like others [11], we found that as the PAPP-A measurement increased, the risk of an SGA infant decreased. In addition, women with low PAPP-A were only half as likely to have an LGA infant.

  • First trimester placental retinol-binding protein 4 (RBP4) and pregnancy-associated placental protein A (PAPP-A) in the prediction of early-onset severe pre-eclampsia

    2015, Metabolism: Clinical and Experimental
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    Low levels may indicate impaired fetal growth or a risk for adverse outcome. Growth factors in very early pregnancy have been shown to be associated with pregnancy loss, hypertension, PE, preterm delivery, fetal growth restriction (birth weight below 5th percentile) and fetal death [13,14]. The prediction of PE is currently based on evaluating the well-known risk factors for PE and the appearance of proteinuria and novel hypertension during pregnancy [3].

  • Predictive value of combined serum biomarkers for adverse pregnancy outcomes

    2014, European Journal of Obstetrics and Gynecology and Reproductive Biology
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