Influence of gravidity and foetal gender on the value of screening variables in the first trimester of pregnancy Tamara Illescas a, *, Cristina Ferna ´ ndez b , Dolores Ortega c , Miriam de la Puente a , Pluvio Coronado a , Joaquı ´n Montalvo a a Servicio de Ginecologı´a y Obstetricia, Hospital Clı´nico San Carlos, Madrid, Spain b Servicio de Medicina Preventiva, Hospital Clı´nico San Carlos, Madrid, Spain c Unidad de Ana ´lisis Clı´nicos, Hospital Clı´nico San Carlos, Madrid, Spain 1. Introduction Combined screening for chromosome abnormalities in the first trimester of pregnancy currently forms part of standard obstetric practice in Spain. Screening is based on maternal age, nuchal translucency (NT) and biochemical markers such as pregnancy- associated plasma protein (PAPP-A) and free beta human chorionic gonadotropin (free b-hCG). The widespread use of combined screening in the first trimester has enabled extensive databases to be generated, and this facilitates the study of the possible influence of materno-foetal characteristics on the value of these biochemical markers in screening. Apart from the poorly understood physiological factors, there are genetic factors and/or additional maternal factors that influence the levels of these serum markers. To improve reliability of screening methods it is essential that the variables are accurately measured and that adjustments for confounding factors, such as maternal and gestational characteristics, are introduced in the measurements of free b-hCG and PAPP-A. In the screening process in the first trimester, each measured value of PAPP-A and free b-hCG is converted to a multiple of the median (MoM) expected for a pregnancy of the same gestational age, maternal weight, ethnicity, form of conception, and smoking habit. It is assumed that the distributions of these biochemical parameters are Gaussian, not only in the euploid foetus but also European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2012) xxx–xxx A R T I C L E I N F O Article history: Received 24 November 2011 Received in revised form 22 September 2012 Accepted 23 October 2012 Keywords: Screening for chromosome abnormalities First trimester of pregnancy Foetal gender Gravidity A B S T R A C T Objectives: Combined screening for chromosome abnormalities in the first trimester of pregnancy is based on maternal age, nuchal translucency (NT) and biochemical markers (PAPP-A and free b-hCG). We sought to assess the value of the variables used in the combined screening strategy taking into account maternal gravidity and foetal gender. Study design: Between July 1999 and December 2009, a total of 21,193 singleton pregnancies were screened for aneuploidy in the first trimester, in the Hospital Clı ´nico San Carlos (Madrid, Spain). In the original database foetal gender data were available in 4370 euploid cases, and there were 2343 women with at least two consecutive pregnancies. We conducted a retrospective assessment of ultrasound and biochemical markers taking into account foetal gender and maternal gravidity, and evaluated the effect on the performance of screening, in terms of detection rates and false positive rates. Information on pregnancy outcome was obtained from the hospital’s intranet medical records or by contacting the patient by telephone postpartum. Karyotype was ascertained by amniocentesis or chorionic villus sampling, and euploid status was assumed in newborns with normal phenotype. Student’s t-tests (paired or unpaired as appropriate) were applied to the data, and the Bland–Altmann method was applied in evaluating individual differences in markers between successive gestations. Results: PAPP-A decreased significantly between the first and the second pregnancy (p < 0.01). PAPP-A and free b-hCG values were significantly higher (p = 0.04 and p < 0.01 respectively) and NT was lower (p = 0.02) in pregnancies with a female foetus. Conclusions: Correlations between the biochemical variables in relation to gravidity and foetal gender can introduce a bias in the calculated risk of chromosome abnormalities. Differences in NT measurements with respect to foetal gender do not seem to be of clinical importance. NT is independent of gravidity so routine use of NT compensates for the influence of these maternal–foetal variables on the values of biochemical parameters. Hence, the bias in overall combined screening is small. ß 2012 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Delta Ultrasound Diagnostic Center in Obs/Gyn, Calle Conde de Pen ˜ alver, 14, 18 izquierda, 28006 Madrid, Spain. Tel.: +34 659644955. E-mail address: tamaraillescas@hotmail.com (T. Illescas). G Model EURO-7886; No. of Pages 4 Please cite this article in press as: Illescas T, et al. Influence of gravidity and foetal gender on the value of screening variables in the first trimester of pregnancy. Eur J Obstet Gynecol (2012), http://dx.doi.org/10.1016/j.ejogrb.2012.10.023 Contents lists available at SciVerse ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology jou r nal h o mep ag e: w ww .elsevier .co m /loc ate/ejo g rb 0301-2115/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejogrb.2012.10.023