Role of first-trimester free beta subunit of human chorionic gonadotropin (β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) as markers for intrauterine fetal growth restriction

OBJECTIVES: This study aimed to investigate the association between first-trimester screening maternal serum markers (free human chorionic gonadotropin-beta (β-hCG), pregnancy-associated plasma protein-A, and adverse pregnancy outcomes (gestational hypertension, preeclampsia, preterm delivery, intrauterine growth restriction, oligohydramnios, intrauterine ex-fetus, abruptio placentae, and gestational diabetes mellitus). STUDY DESIGN: This was a retrospective cohort study including 1516 women who delivered a singleton pregnancy at GATA Haydarpasa Education Hospital from 2006 to 2009. Patients with multiple pregnancies, chromosome aberrations, or fetal anomalies were excluded. Extreme values of corrected- pregnancy-associated plasma protein-A and free β-hCG, and their association with adverse pregnancy outcomes were analyzed. RESULTS: Adverse pregnancy outcomes at the cutoff level of ≤0.25 c-pregnancy-associated plasma protein-A MOM values positive likelihood ratio (+LR) was 7.5 (95%CI 2.426-19.836) and had a significant correlation (r=0.108, p<0.01). It was also a significant correlation with adverse pregnancy outcomes (r=0.189, p<0.01) at the cut-off level of ≤0.50 corrected-pregnancy-associated plasma protein-A MOM values and the +LR was 2.388 (95%CI 1.889-2.991). Association between low corrected-pregnancy-associated plasma protein-A MOM values and adverse pregnancy outcomes were statistically significant and had a poor association (AUC, 0.630 95%CI 0.596-0.663, p<0.01). Preeclampsia was statistically significant, however had a fair association (AUC, 0.74 95% CI 0.690-0.802, p<0.01). Preterm birth was statistically significant but had a poor association (AUC, 0.568 95% CI 0.512-0.624, p<0.05). CONCLUSION: First-trimester maternal serum low pregnancy-associated plasma protein-A values are significantly associated with adverse pregnancy outcomes. It may be a useful tool to predictive not only chromosome anomalies but also adverse pregnancy outcomes.

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Four Years' Experience With an Interlaboratory Comparison Program Involving First-Trimester Markers of Down Syndrome

Archives of Pathology & Laboratory Medicine ◽

10.5858/2009-0670-oar.1 ◽

2010 ◽

Vol 134 (11) ◽

pp. 1685-1691

Author(s):

Glenn E. Palomaki ◽

George J. Knight ◽

Geralyn Lambert-Messerlian ◽

Jacob A. Canick ◽

James E. Haddow

Keyword(s):

Down Syndrome ◽

Chorionic Gonadotropin ◽

Plasma Protein ◽

Human Chorionic Gonadotropin ◽

Interlaboratory Comparison ◽

Protein A ◽

First Trimester ◽

Nuchal Translucency ◽

Second Trimester ◽

Coefficients Of Variation

Abstract Context.—We initiated a voluntary, self-funded interlaboratory comparison program in the fall of 2005 because no proficiency testing program was available to laboratories in North America offering first-trimester, combined serum and ultrasound, Down syndrome screening. Objectives.—To evaluate the first 4 years of the interlaboratory comparison program against stated goals, to identify areas of concern, and to create new initiatives as indicated. Design.—Five serum samples are distributed 3 times a year to be tested for pregnancy-associated plasma protein A, human chorionic gonadotropin or its β subunit, and dimeric inhibin-A; participants convert these results into multiples of the median. Patient histories include nuchal translucency information that enables the calculation of the risk of Down syndrome. Also included are educational components linked to interlaboratory comparison program results. Assessment of integrated (first- and second-trimester markers) risks is accomplished by having participants combine interlaboratory comparison program results with their results from a second-trimester proficiency testing program administered by the College of American Pathologists. Results.—The precision profile for pregnancy-associated plasma protein A shows decreasing coefficients of variation with increasing pregnancy-associated plasma protein A concentrations and multiples of the median (25% to 11% and 30% to 15%, respectively). In contrast, coefficients of variation are a relatively constant 12% throughout the entire range of human chorionic gonadotropin results. On a logarithmic scale, the median coefficient of variation of the risk of Down syndrome is 9%. Conclusions.—Participants in the interlaboratory comparison program reliably measure analytes, compute multiples of the median, and calculate consistent Down syndrome risks. Assays for the measurement of pregnancy-associated plasma protein A are not standardized and are less precise than those for human chorionic gonadotropin. Participants calculate reliable median equations given sonographer-specific sets of paired crown-rump length and nuchal translucency measurements.

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Beta Subunit of Human Chorionic Gonadotropin (β-hCG)

Encyclopedia of Cancer ◽

10.1007/978-3-540-47648-1_590 ◽

2008 ◽

pp. 332-333

Keyword(s):

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Beta Subunit ◽

Β Hcg

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Evaluation of a Dried Blood Spot Assay to Measure Prenatal Screening Markers Pregnancy-Associated Plasma Protein A and Free β-Subunit of Human Chorionic Gonadotropin

Clinical Chemistry ◽

10.1373/clinchem.2012.194894 ◽

2013 ◽

Vol 59 (6) ◽

pp. 968-975 ◽

Cited By ~ 9

Author(s):

Nicholas J Cowans ◽

Mikko Suonpaa ◽

Heikki Kouru ◽

David Wright ◽

Kevin Spencer

Keyword(s):

Relative Humidity ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Prenatal Screening ◽

Protein A ◽

First Trimester ◽

Β Subunit ◽

Drying Process ◽

Serum Assay ◽

Blood Spot

BACKGROUND First-trimester prenatal screening for aneuploidy by use of dried blood spots (DBSs) may offer practical benefits in settings where the instability of intact human chorionic gonadotropin (hCG) is problematic. We evaluated a DBS pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of hCG (free hCGβ) dual assay and compared it to serum screening. METHODS Hematocrit-corrected DBS PAPP-A and free-hCGβ concentrations were measured and compared with serum concentrations in 252 first-trimester samples. Serum intact hCG was also measured and, with serum free hCGβ, was used to fit a model to predict serum-equivalent DBS free-hCGβ concentrations. In a separate experiment, we investigated the effects of temperature and relative humidity during the blood spot drying process. RESULTS The DBS assay for PAPP-A performed similarly to the serum assay, whereas free-hCGβ DBS measurements were consistently higher than in serum. Purifying blood spots of intact hCG suggested that the free-hCGβ DBS assay is measuring a composite of free hCGβ and additional β-subunits from intact hCG. The drying experiment showed that increased temperature and relative humidity during the drying process resulted in increased free hCGβ and reduced PAPP-A. CONCLUSIONS Despite measuring additional free hCGβ compared to the serum assay, DBS analysis has a role in first-trimester combined screening for trisomy 21.

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