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Cho, Shin, Kim, Ji, Kwak, Cha, Choi, Oh, Lee, Roh, and Kim: SECOND TRIMESTER MATERNAL SERUM MARKER AND ADVERSE PREGNANCY OUTCOME
Original Article

Korean J Obstet Gynecol 2011;54(11):651-658.

Published online: 21 January 2011

DOI: https://doi.org/10.5468/KJOG.2011.54.11.651

SECOND TRIMESTER MATERNAL SERUM MARKER AND ADVERSE PREGNANCY OUTCOME

Se-Eun Cho, MD1, Yoo Jeong Shin, MD1, Hyo Jeong Kim, MD1, Hyun-Young Ji, MD1, Hye-Min Kwak, MD1, Hyun-Hwa Cha, MD1, Suk-Joo Choi, MD1, Soo-Young Oh, MD, PhD1, Soo-Youn Lee, MD, PhD2, Cheong-Rae Roh, MD, PhD1, Jong-Hwa Kim, MD, PhD1

1Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Corresponding author: Soo-Young Oh, MD, PhD Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea Tel: +82-2-3410-3517 Fax: +82-2-3410-0630 E-mail: ohsymd@skku.edu

Received 31 May 2011       Revised 16 August 2011       Accepted 15 September 2011

Copyright © 2011 Korean Society of Obstetrics and Gynecology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

The aim of this study is to assess the risk of adverse pregnancy outcome by maternal serum markers in Quad test and to compare the existing cutoff (2.0 MoM) with 95 percentile cutoff generated from our consecutive population in predicting adverse pregnancy outcome.

Methods

We generated 95 percentile cutoff as our own reference using 3,000 consecutive women who performed Quad test. Except for follow-up loss, fetal aneuploidy and anomaly, 2,598 women were analyzed for the assessment of adverse pregnancy outcome consisted of preeclampsia (PE), preterm birth (<32 weeks), low birth weight and fetal death in utero.

Results

We confirmed high levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and inhibin A are associated with development of PE, preterm birth, and low birth weight. In general, 95 percentile cutoff corresponded similarly with 2.0 MoM except AFP. Combination of serum markers increased the odds ratio for predicting adverse pregnancy outcome. The women with higher level of both AFP and inhibin A (2.0 ≥ MoM) had 9.8 times higher risk for PE, 24.8 times higher risk for preterm birth, and 5.6 times higher risk for low birth weight. The women with higher level of AFP, hCG, and inhibin A had 8.2 times higher risk for PE, 29.4 times higher risk for preterm birth. Notably, negative predictive value of serum markers for PE and preterm birth are over 98% either in alone and in combination.

Conclusion

Maternal serum makers either in alone and in combination offer valuable information on the risk assessment of adverse pregnancy outcome.

Keywords: Quad test, Adverse pregnancy outcome, Alpha-fetoprotein, Human chorionic gonadotropin, Inhibin A

REFERENCES

1. Dugoff L. Society for Maternal-Fetal Medicine. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes. Obstet Gynecol. 2010; 115:1052–61.
crossref
2. Krause TG, Christens P, Wohlfahrt J, Lei U, Westergaard T, N⊘rgaard-Pedersen B, et al. Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome (1). Obstet Gynecol. 2001; 97:277–82.
3. Yaron Y, Cherry M, Kramer RL, O'Brien JE, Hallak M, Johnson MP, et al. Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome. Am J Obstet Gynecol. 1999; 181:968–74.
4. Muttukrishna S. Role of inhibin in normal and high-risk pregnancy. Semin Reprod Med. 2004; 22:227–34.
crossref
5. Muttukrishna S, Knight PG, Groome NP, Redman CW, Ledger WL. Activin A and inhibin A as possible endocrine markers for pre-eclampsia. Lancet. 1997; 349:1285–8.
crossref
6. Dugoff L, Hobbins JC, Malone FD, Vidaver J, Sullivan L, Canick JA, et al. Quad screen as a predictor of adverse pregnancy outcome. Obstet Gynecol. 2005; 106:260–7.
crossref
7. Berkeley AS, Killackey MA, Cederqvist LL. Elevated maternal serum alpha-fetoprotein levels associated with breakdown in fetal-maternal-placental barrier. Am J Obstet Gynecol. 1983; 146:859–61.
8. Perkes EA, Baim RS, Goodman KJ, Macri JN. Second-trimester placental changes associated with elevated maternal serum alpha-fetoprotein. Am J Obstet Gynecol. 1982; 144:935–8.
9. Chandra S, Scott H, Dodds L, Watts C, Blight C, Van Den Hof M. Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes. Am J Obstet Gynecol. 2003; 189:775–81.
10. Spencer K. Second-trimester prenatal screening for Down syndrome and the relationship of maternal serum biochemical markers to pregnancy complications with adverse outcome. Prenat Diagn. 2000; 20:652–6.
crossref
11. Wald NJ, Cuckle HS, Densem JW, Nanchahal K, Canick JA, Haddow JE, et al. Maternal serum unconjugated oestriol as an antenatal screening test for Down's syndrome. Br J Obstet Gynaecol. 1988; 95:334–41.
crossref
12. Schoen E, Norem C, O'Keefe J, Krieger R, Walton D, To TT. Maternal serum unconjugated estriol as a predictor for Smith-Lemli-Opitz syndrome and other fetal conditions. Obstet Gynecol. 2003; 102:167–72.
crossref
13. Oh HM, Kim SY, Lee SP, Sohn YK, Lee GH, Kim JM. The association between adverse pregnancy outcomes and the serum inhibin A levels in mid-trimester of gestation. Korean J Obstet Gynecol. 2008; 51:1239–44.
14. Jelliffe-Pawlowski L, Baer R, Moon-Grady AJ, Currier RJ. Second trimester serum predictors of congenital heart defects in pregnancies without chromosomal or neural tube defects. Prenat Diagn. 2011; 31:466–72.
crossref
15. Zhong Y, Bradshaw R, Stanley AP, Odibo AO. The impact of assisted reproductive technology on the association between first-trimester pregnancy-associated plasma protein a and human chorionic gonadotropin and adverse pregnancy outcomes. Am J Perinatol. 2011; 28:347–54.
crossref
16. Health Insurance Review & Assessment Service [Internet]. Seoul (KR): Health Insurance Review & Assessment Service;c2010. [cited 2011 Oct 15]. Available from:. http://www.hira.or.kr/.
17. Aquilina J, Thompson O, Thilaganathan B, Harrington K. Improved early prediction of pre-eclampsia by combining second-trimester maternal serum inhibin-A and uterine artery Doppler. Ultrasound Obstet Gynecol. 2001; 17:477–84.
crossref
18. Aquilina J, Maplethorpe R, Ellis P, Harrington K. Correlation between second trimester maternal serum inhibin-A and human chorionic gonadotrophin for the prediction of preeclampsia. Placenta. 2000; 21:487–92.
crossref
19. Muller F, Savey L, Le Fiblec B, Bussières L, Ndayizamba G, Co-lau JC, et al. Maternal serum human chorionic gonadotropin level at fifteen weeks is a predictor for preeclampsia. Am J Obstet Gynecol. 1996; 175:37–40.
crossref

Fig. 1.
ROC curve comparing maternal serum marker for prediction of adverse pregnancy outcome. FDIU, fetal death in utero; ROC, receiver operator characteristic; AUROC, area under receiver operator characteristic; AFP, alpha-fetoprotein; uE3, unconjugated estriol; hCG, human chorionic gonadotropin.
kjog-54-651f1.tif
Table 1.
Distribution of abnormal serum marker combination (n=2,598)
Marker combination n (%) of cases
AFP ≥ 2.0 MoM only 45 (1.7)
uE3 ≤ 0.5 MoM only 25 (1.0)
hCG ≥ 2.0 MoM only 120 (4.6)
Inhibin A ≥ 2.0 MoM only 120 (4.6)
AFP ≥ 2.0 MoM and inhibin A ≥ 2.0 MoM only 14 (0.5)
hCG ≥ 2.0 MoM and inhibin A ≥ 2.0 MoM only 45 (1.7)
AFP ≥ 2.0 MoM and hCG ≥ 2.0 MoM and inhibin A ≥ 2.0 MoM only 8 (0.3)
AFP ≥ 95 percentile only 123 (4.7)
uE3 ≤ 5 percentile only 129 (5.0)
hCG ≥ 95 percentile only 129 (5.0)
Inhibin A ≥ 95 percentile only 126 (4.8)
AFP ≥ 95 percentile and inhibin A ≥ 95 percentile only 21 (0.8)
hCG ≥ 95 percentile and inhibin A ≥ 95 percentile only 49 (1.9)
AFP ≥ 95 percentile and hCG ≥ 95 percentile and inhibin A ≥ 95 percentile only 13 (0.5)

AFP, alpha‐fetoprotein; uE3, unconjugated estriol; hCG, human chorionic gonadotropin.

Table 2.
Correlation between all serum markers
Serum marker Coefficient of correlation (r) P‐value
AFP and uE3 0.137 <0.01
AFP and hCG 0.226 <0.01
AFP and inhibin A 0.233 <0.01
uE3 and hCG -0.43 0.03
uE3 and inhibin A -0.39 0.04
hCG and inhibin A 0.578 <0.01

AFP, alpha‐fetoprotein; uE3, unconjugated estriol; hCG, human chorionic gonadotropin.

Table 3.
Association between selected serum markers and adverse pregnancy outcomes
  Preeclampsia Preterm birth Low birth weight FDIU
<32 wk <10 percentile
AFP ≥ 2.0 MoM 4.270 (1.273–14.326) 9.127 (3.055–27.269) 3.093 (1.570–6.091) 14.483 (1.586–132.218)
AFP ≥ 95 P 3.175 (1.381–7.647) 4.981 (2.005–12.374) 2.165 (1.368–3.426) 13.503 (2.236–81.557)
uE3 ≤ 0.5 MOM 0.990 (0.986–0.994) 0.990 (0.986–0.994) 4.231 (1.778–10.068) 0.990 (0.987–0.994)
uE3 ≤ 5 P 0.990 (0.426–4.500) 0.635 (0.086–4.694) 2.030 (1.286–3.203) 4.814 (0.534–43.385)
hCG ≥ 2.0 MOM 3.978 (1.738–9.103) 4.100 (1.546–10.873) 2.071 (1.300–3.299) 5.197 (0.576–46.861)
hCG ≥ 95 P 3.905 (1.707–8.934) 4.027 (1.519–10.675) 1.913 (1.408–4.022) 5.107 (0.567–46.044)
Inhibin A ≥ 2.0 MoM 3.978 (1.738–9.103) 5.164 (2.078–12.837) 1.884 (1.165–3.048) 5.197 (0.576–46.861)
Inhibin A ≥ 95 P 3.768 (1.648–8.614) 4.894 (1.971–12.154) 2.379 (1.408–4.022) 4.936 (0.548–44.488)

Data was presented odds ratio and 95% confidence interval. AFP, alpha‐fetoprotein; uE3, unconjugated estriol; hCG, human chorionic gonadotropin; P, percentile; FDIU, fetal death in utero.

Table 4.
Diagnostic value of individual and combination of serum markers interpretation of adverse pregnancy outcomes
  Sensitivity Specificity PPV NPV OR (95% CI)
Preeclampsia
 AFP 6.7 98.4 6.7 98.4 4.270 (1.273–14.326)
 hCG 15.6 95.6 5.8 98.5 3.978 (1.738–9.103)
 Inh 15.6 95.6 5.8 98.5 3.978 (1.738–9.103)
 AFP + Inh 4.4 99.5 14.3 98.3 9.849 (2.139–45.347)
 hCG + Inh 6.7 98.4 6.7 98.4 4.270 (1.273–14.326)
 AFP + hCG + Inh 2.2 99.7 12.5 98.3 8.266 (0.996–68.618)
Preterm birth < 32 wk
 AFP 12.9 98.4 8.9 98.9 9.127 (3.055–27.269)
 hCG 16.1 95.5 4.2 99.0 4.100 (1.546–10.873)
 Inh 19.4 95.6 5.0 99.0 5.164 (2.078–12.837)
 AFP + Inh 9.7 99.6 21.4 98.9 24.896 (6.586–94.116)
 hCG + Inh 12.9 98.4 8.9 98.9 9.127 (3.055–27.269)
 AFP + hCG + Inh 6.5 99.8 25.0 98.9 29.437 (5.701–151.999)
Low birth weight < 10 percentile
 AFP 4.1 98.6 27.9 88.9 3.093 (1.570–6.091)
 hCG 8.1 95.9 20.3 89.0 2.071 (1.300–3.299)
 Inh 7.5 95.9 19.0 89.0 1.884 (1.165–3.048)
 AFP + Inh 1.7 99.7 41.7 88.7 5.628 (1.775–17.848)
 hCG + Inh 4.1 98.6 27.3 88.9 2.995 (1.525–5.881)
 AFP + hCG + Inh 0.7 99.8 28.6 88.6 3.122 (0.603–16.165)
Fetal death in utero
 AFP 20.0 98.3 2.2 99.8 14.483 (1.586–132.218)
 hCG 20.0 95.4 0.8 99.8 5.197 (0.576–46.861)
 Inh 20.0 95.4 0.8 99.8 5.197 (0.576–46.861)
 AFP + Inh 0 99.5 0 99.8 0.995 (0.992–0.997)
 hCG + Inh 20.0 98.5 2.2 99.8 14.483 (1.586–132.218)
 AFP + hCG + Inh 0 99.7 0 99.8 0.997 (0.995–0.999)

PPV, positive predictive value; NPV, negative predictive value; OR, odds ratio; CI, confidence interval; AFP, AFP ≥ 2.0 MoM; hCG, hCG ≥ 2.0 MoM; Inh, Inhibin A ≥ 2.0 MoM; AFP + Inh, AFP ≥ 2.0 MoM and Inhibin A ≥ 2.0 MoM; hCG + Inh, hCG ≥ 2.0 MoM and Inhibin A ≥ 2.0 MoM; AFP + hCG + Inh, AFP ≥ 2.0 MoM and hCG ≥ 2.0 MoM and Inhibin A ≥ 2.0 MoM.

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