1T Maternal Fetal Screen 1TMFS

Result Interpretation    Risk Calculation: 
Each marker level is converted into a multiple of the GA specific median (MoM) and is then adjusted as applicable based on the patient's race, weight, diabetic status, multiple pregnancy status, egg donor status, and smoking status.  The likelihood ratio for each analyte is calculated as the ratio of the probability density function in affected pregnancies divided by the probability density function for unaffected pregnancies.  
Patient specific risks for Down syndrome and trisomy18/13 are calculated using Bayes’ rule. The prior risk, based on demographic factors, is multiplied by the likelihood ratios for each maker appropriate for the condition screened. 
Patient specific risks for pre-term preeclampsia are calculated following the competing risks approach developed by the Fetal Medicine Foundation (FMF) using Bayes theorem to combine the a priori risk from maternal characteristics and medical history with the results of the  biophysical and biochemical measurements.   This approach assumes that if the pregnancy was to continue indefinitely all women would eventually develop PE and whether they do so or not depends on competition between which comes first, delivery or the development of PE. This approach allows the estimation of the individual patient-specific risks of delivery with preeclampsia before 37 weeks gestational age. 

An interpretive risk report including the patient's marker levels, cut-off values and risks for trisomy 21, trisomies 18/13 and pre-term preeclampsia will be provided.

Down’s Syndrome (trisomy 21) Interpretation: 
The risk cut-off is set equal to the first-trimester risk of a 35 year old (1/250).  This test may detect 98% of cases with Down’s syndrome at an approximate 2% false positive rate. 

Edward Syndrome (trisomy 18)/Patau Syndrome (trisomy 13) Interpretation: 
The risk cut-off is set equal to 1/100. This cut-off is chosen to balance the detection and false positive rates.  This test may detect 95% of cases with T18/13 at an approximate 0.5% false positive rate.

Pre-Term Preeclampsia Interpretation:
The risk cut-off is set equal to 1/150.  This test may detect over 80% of cases destined to develop preeclampsia necessitating delivery prior to 37weeks gestational age including over 90% of cases <34 weeks at an approximate 15% false positive rate.

Since the prior risk of twins is high, most twins will screen positive. Comparison of the after screening risk to the before screening risk may be of assistance in evaluating the pregnancy.

Test Follow Up: 
If the patient's risk is less than the cut-off risk the test is considered "Within Normal Range" and no further action is required. If the patient’s risk is greater than or equal to the cut-off risk the test is considered "Increased Risk". 

Patients at increased risk of trisomy 21 or trisomies 18/13 are offered detailed ultrasound, NIPT and/or diagnostic amniocentesis.

Patients at increased risk for preterm preeclampsia may be offered: 
1.    Education regarding the signs and symptoms of preeclampsia
2.    Increased monitoring including the option of home blood pressure monitoring
3.    Prophylactic low-dose aspirin starting prior to 16 weeks to reduce the risk of preeclampsia, IUGR and Preterm Delivery.

Upon receiving screening results, all information used in the risk calculations should be reviewed for accuracy (i.e., weight, diabetic status, gestational dating). If any information is incorrect, the laboratory should be contacted for recalculation of the estimated risks. ‘Within Range’ risk results typically do not warrant further evaluation. The screen results are dependent on accurate demographic information.  Inaccurate information can lead to significant alterations in the estimated risk. In particular, erroneous assessment of gestational age can result in false-positive or false-negative screen results. 

Disclaimers
This is a screening test, not a diagnostic test. A ‘Within Range’ risk result indicates low risk for the conditions screened but does not guarantee the absence of those conditions or other abnormalities. An ‘Increased Risk’ result indicates an increased risk for the condition screened but does not infer a definitive diagnosis. 

Cautions
Valid measurements of maternal serum markers cannot be made after CVS or amniocentesis. Triplets and higher order multiple pregnancies cannot be interpreted. In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. Caution should be used in interpretation of results and the laboratory should be alerted if the result does not correlate with the clinical presentation.

Each center offering 1T  Maternal Fetal Screening to patients should establish a standard screening protocol, which provides pre- and post-screening education and appropriate follow-up for ‘Increased Risk’ results.

Clinical References 
1.    ACOG Practice Bulletin 226 - Screening for Fetal Chromosomal Abnormalities.  Obstet Gynecol VOL. 136, NO. 4, OCTOBER 2020. 
2.    NJ Wald, C Rodeck, AK Hackshaw, J Walters, L Chitty, AM Mackinson.  First and second trimester antenatal screening for Down’s syndrome:  the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). (2003) Health Technology Assessment Vol. 7: No. 11. 
3.    Fergal D. Malone, M.D., Jacob A. Canick, Ph.D., Robert H. Ball, M.D., David A. Nyberg, M.D., Christine H. Comstock, M.D., Radek Bukowski, M.D., Richard L. Berkowitz, M.D., Susan J. Gross, M.D., Lorraine Dugoff, M.D., Sabrina D. Craigo, M.D., Ilan E. Timor-Tritsch, M.D., Stephen R. Carr, M.D., Honor M. Wolfe, M.D., Kimberly Dukes, Ph.D., Diana W. Bianchi, M.D., Alicja R. Rudnicka, Ph.D., Allan K. Hackshaw, M.Sc., Geralyn Lambert-Messerlian, Ph.D., Nicholas J. Wald, F.R.C.P., and Mary E. D’Alton, M.D., for the First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium* (2005) First-Trimester or Second-Trimester Screening, or Both, for Down’s Syndrome.  N Engl J Med 353;19 2001-2011. 
4.    Carmichael JB, Liu HP, Janik D, Hallahan TW, Nicolaides KH and Krantz DA.  Expanded conventional first trimester screening.  Prenatal Diagnosis 2017, 37, 802–807. 
5.    Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017;377: 613–22.
6.    Akolekar R, Syngelaki A, Poon L, Wright D, Nicolaides KH. Competing risks model in early screening for preeclampsia by biophysical and biochemical markers. Fetal Diagn Ther 2013;33: 8–15.
7.    Rolnik DL, Wright D, Poon LCY, et al.  ASPRE trial: performance of screening for pre-term pre-eclampsia. Ultrasound Obstet Gynecol 2017;50:492–5.
8.     Chaemsaithong P, Sahota DS, Poon LC.  First trimester preeclampsia screening and prediction. Am J Obstet Gynecol. 2022 Feb;226(2S):S1071-S1097.e2.
9.    Foster AB, Park, F, Hyett J.  Do first‐trimester screening algorithms for preeclampsia aligned to use of preventative therapies reduce the prevalence of pre‐term preeclampsia: A systematic review and meta‐analysis.  Prenatal Diagnosis. 2023;43:950–958.