PRENATAL DIAGNOSIS Prenat Diagn 2007; 27: 303–311. Published online 31 January 2007 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/pd.1661 Maternal serum free-β -chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10–13 +6 weeks in relation to co-variables in pregnant Saudi women Mohammed-Salleh M. Ardawi 1,6 *, Hasan A. Nasrat 2 , Abdulrahim A. Rouzi 2 , Mohammed H. Qari 3 , Mohammed H. Al-Qahtani 4,6 and Adel M. Abuzenadah 5,6 1 Department of Clinical Biochemistry, Faculty of Medicine and King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia 2 Obstetrics & Gynecology, Faculty of Medicine and King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia 3 Haematology, Faculty of Medicine and King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia 4 Medical Biology, Faculty of Medicine and King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia 5 Department of Medical Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia 6 Genomic Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia Objective To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free β -human chorionic gonadotrophin (β -hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13 +6 weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. Methods A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free β -hCG and PAPP-A were determined at 10 to 13 +6 weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. Results All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free β -hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r =−0.296) or parity (r =−0.311), whereas both free β -hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free β -hCG in female fetuses. Smoking decreased MoM values of free β -hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free β -hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free β -hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). Conclusions The normative values and distribution parameters for fetal NT, maternal serum free β -hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined. Copyright  2007 John Wiley & Sons, Ltd. KEY WORDS: first trimester; fetal nuchal translucency; maternal serum screening; co-variables INTRODUCTION Recent studies have shown that screening for trisomy 21 using a combination of maternal serum biochemical *Correspondence to: Mohammed-Salleh M. Ardawi, Department of Clinical Biochemistry, Faculty of Medicine and King Abdulaziz University Hospital, King Abdulaziz University, PO Box 20724, Jeddah 21465, Saudi Arabia. E-mail: ardawims@yahoo.com markers, namely, free β -chorionic gonadotrophin (free β -hCG) and pregnancy associated plasma protein-A (PAPP-A) together with fetal nuchal translucency (NT) thickness, can achieve detection rates of about 77 to 90% in the first trimester of pregnancy with false- positive detection (FPD) rates ranging from 3.3 to 5.2% (Orlandi et al., 1997; De Biasio et al., 1999; Krantz et al., 2000; Niemimaa et al., 2001; Bindra et al., 2002; Crossley et al., 2002; Schuchter et al., 2002; Spencer Copyright  2007 John Wiley & Sons, Ltd. Received: 12 September 2006 Revised: 23 November 2006 Accepted: 28 November 2006 Published online: 31 January 2007