Cover Image

Maternal serum alpha-fetoprotein and free beta-human chorionic gonadotropin in the second trimester: implication for high risk of down’s syndrome in the ghanaian population

Debrah O., Srofenyo E., N. A. Aryee*, I. K. Quaye


Maternal serum screening during pregnancy for adverse changes in levels of alpha-fetoprotein (AFP) and free beta- Human Chorionic Gonadotropin (free β-HCG) in the second trimester to assess risk of Down’s syndrome (DS) is a rare obstetric practice in Ghana.  The aim of this study was to determine changes in the levels of these markers, and assess for risk of DS and adverse pregnancy outcomes in the Ghanaian population.  Levels of AFP and free β-HCG were determined in maternal serum samples from eighty one women with singleton pregnancy collected at recruitment (12-13 gestational weeks), and in the second trimester (16 gestational weeks).  AFP and free β-HCG markers were expressed in multiples of the normal median (MoM) for gestation.  Delivery outcomes and features of the new born at delivery were also noted.   The mean age of subjects at recruitment was 33.9±3.2 years.  AFP levels at recruitment and in the second trimester were 18.8 ± 7.5 ng/ml (mean ± SD) and 30.9 ± 9.8 ng/ml (mean ± SD) respectively.  Similarly, free β-HCG at recruitment and in the second trimester were 47.2 ± 12.2 ng/ml (mean ± SD) and 29.8 ± 11.3 ng/ml (mean ± SD) respectively.  The differences in the serum levels of AFP and free β-HCG between the first and second trimesters were significant (p<0.0001: 95% CI -14.9-(-9.3) and p<0.0001: 95% CI 13.6-21.2).  Whilst the AFP level did not correlate with weight, free β-HCG weakly correlated with maternal weight (p=0.29 and r2=0.017; p=0.08 and r2=0.055 respectively), but not age in the second trimester. There were no cases of DS observed in the study population.   The mean concentrations of free β-HCG in adverse pregnancies were higher than in normal pregnancies (38.4 ± 6.6; 29.3 ± 10.6) but not for AFP (p=0.059, and p=0.477 respectively). Although no DS was seen for comparison, free b-HCG appears to be a useful marker for risk assessments of poor pregnancy outcomes in the population.


Alpha-fetoprotein; free beta-Human Chorionic Gonadotropin; Down’s syndrome; prenatal screening; adverse pregnancies; Ghanaian population.

Full Text:



Adeyokunnu AA, The incidence of Down’s syndrome in Nigeria, J Med Genet, 1982, 19, 277-79.

Epstein CJ, Down’s syndrome (Trisomy 21), Ed. Scriver CR, Beaudet al., Sly WS, Valle D, The metabolic and molecular bases of inherited disease, McGraw-Hill, New York 1995, 749-94.

Cooley WC, Down syndrome, Ed. Osborn LM, Pediatrics, Elsevier Health Science Mosby Inc, USA, 2005, 1060-65.

Lewis R, Human genetics, Concepts and applications, 6th Ed, McGraw-Hill, New-York, 2005, 252-253.

Hook EB, Mutton DE, Ide R, Alberman E, Bobrow M, The natural history of Down syndrome conspectuses diagnosed prenatally that are not electively terminated, The Amer J Human Genet, 1995, 57, 875-81.

Morris JK, Wald NJ, Watt HC, Fetal loss in Down syndrome pregnancies. Prenatal Diagnosis, 1999, 19, 142-5.

Hook EB, Down syndrome: Frequency in human populations and factors pertinent to variation in rates, Ed. Dela Crul, FF, Gerald PS, Trisomy 21 (Down syndrome) Research perspectives, University Park Press, Baltimore, 1981, 3-67.

Wiseman FK, Alford KA, Tybulewicz VLJ, Fisher EMC, Down syndrome- recent progress and future prospects, Human Mol Genet 2009, 18(1), 75-83.

Newberger DS, Down syndrome: Prenatal risk assessment and diagnosis, Amer Family Phys 2000, 62, 825-32.

Cuckle HS, Wald NJ, Thompson SG, Estimating a woman’s risk of having a pregnancy associated with Down’s syndrome using her age and serum alpha-fetoprotein level. Brit J Obst Gynaecol, 1987, 94, 387-402.

Cuckle HS, Primary prevention of Down’s syndrome: Review. Int J Med Sci, 2005, 2(3), 93-99.

Morris JK, Cnossen JS, Langejans M, Robson SC, Kleijnen J, Riet G, Mol BW, Van der Post JAA, Khan KS, Serum screening with Down’s syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis, BMC Pregnancy and Childhood, 2008, 8, 33.

Hulter MA, Patel S, Jonasson J, Iwarsson E, On the origin of the maternal age effect in trisomy 21 down syndrome: The oocyte mosaicism selection model, Reproduction, 2010, 139, 1-9.

Dutta S, Nandagopal K, Gangopadhyay PK, Mukhopadhyay K, Molecular aspects of Down syndrome, Indian Pediatrics, 2005, 42(4), 339-44.

Khalil A, Pandya P, Screening for Down syndrome, J Obster Gynecol India, 2006, 56(3), 205-211.

Tapon D, Prenatal testing for Down syndrome: Comparison of screening practices in the UK and USA, J Genet Counselling, 2010, 19, 112-130.

Berry E, Aitken DA, Crossley JA, Macri JN, Connor JM, Screening for Down’s syndrome: Changes in marker levels and detection rates between first and second trimester, Brit J Obster Gynaecol, 1997, 104, 811-8.

Hsu JJ, Hsieh TT, Soong YK, Spencer K, Comparison of Down’s syndrome screening strategies in Asians combining serum free beta-hCG and alpha-fetoprotein with maternal age, Prenatal Diagnosis, 1997, 17(8), 707-716.

Ramy A, Screening for Down syndrome, ASJOG, 2005, 2, 327-331.

Baluja-Conde IB, Rodriguez-Lopez MR, Zulueta-Rodriguez O, Ruiz-Escandon B, Bermudez-Velasquez S, Biochemical serum markers for Down syndrome screening, Rev Biomed 2005, 16, 259-271.

Christianson AL, Down syndrome in sub-Saharan Africa, J Med Genet, 1996, 33, 89-92.

Christianson AL, Down syndrome in black South African infants and children, Clinical features and delayed diagnosis, South Africa Med J, 1997, 87, 992-995.

Crane E, Morris J, Changes in maternal age in England and Wales: Implications for Down syndrome, Down Syndrome Res Pract, 2006, 10(1), 41-43.

Zheng MM, Hu YL, Zhang CY, Ru T, Liu QL, Xu BY, Chen QG, et al., Comparison of second- trimester maternal serum free-β-human chorionic gonadotropin and α-fetoprotein between normal singleton and twin pregnancies: A population–based study, Chinese Med J 2010, 123(5), 555-58.

Kim CK, Yang YH, Alpha-fetoprotein values in maternal serum and amniotic fluid for prenatal screening of genetic disorders, Yonsei Med J, 1987, 28(3), 218-227.

Tang YP, Wu YS, Yin AH, Xu WW, Yuan PH, Li M, Determination of median levels of the free β subunit of human chorionic gonadotropin in women from mainland China using a new time-resolved fluoroimmunoassay, Clin Chem Lab Med, 2010, 48, 109-14.

Benn PA, Clive JM, Collins R, Medians for second-trimester maternal serum α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol: Differences between races or ethnic groups, Clin Chem, 1997, 43(2), 333-337.

Welch KK, Malone FD, Advances in prenatal screening: maternal serum screening for Down syndrome, New Reviews 2002, 3, 209.

Zournatzi V, Daniilidis A, Kalidas C, Tantanasis T, Loufopoulos A, Tzafettas J, et al., A prospective two years study of first trimester screening for Down's syndrome. Hippokratia 2008, 12(1), 28-32.

Reis FM, D’Antona D, Petraglia F, Predictive value of hormone measurements in maternal and fetal complications of pregnancy, Endocrine Reviews 2002, 23(2), 230-257.

Anfuso S, Soncini E, Bonelli P, Piantelli G, Gramellini D, Second-trimester maternal serum alpha-fetoprotein elevation and its association with adverse maternal/ fetal outcomes: Ten years’ experience, Acta Biomed, 2007, 78, 214-219.

Krause TG, Christens P, Wohlfahrt J, Lei U, Westergaard T, Norgaard-Pedersen B, Melbye M, Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome, Obstetr Gynecol, 2001, 97, 277-282.

Mizejewski GJ, Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome. Mini-review, Experimental Biol Med, 2007, 232, 993-1004.

Hsieh TT, Hsu JJ, Cheng PJ, Lee CN, Jou HJ, Chen CP, Total hCG versus free beta-hCG combined with alpha-fetoprotein for Down syndrome screening in Taiwan, Taiwanese J Obstetr Gynecol, 2007, 46(3), 230-235.

Wildschut HIJ, Peters TJ, Weiner CP, Screening in women’s health, with emphasis on fetal Down’s syndrome, breast cancer and osteoporosis, Hum Reprod Updates, 2006, 12(5), 499-512.



  • There are currently no refbacks.

Copyright (c) 2014 International Journal of Bioassays

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

International Journal of Bioassays is a member of the Publishers International Linking Association, Inc. (PILA), CROSSREF and CROSSMARK (USA). Digital Object Identifier (DOI) will be assigned to all its published content.