Down’s Syndrome Screening in the First Trimester with Additional Serum Markers: Indian Parameters
To derive a risk calculation algorithm suitable for use in India when screening for Down’s syndrome using four first-trimester maternal serum markers either alone or with ultrasound nuchal translucency (NT).
Stored maternal serum samples (− 20 °C) from 411 singleton unaffected pregnancies were retrieved and measured for pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (hCG), placental growth factor and α-fetoprotein. Samples were taken at 10–13 weeks’ gestation. Equations were derived to express marker levels in multiples of the gestation-specific normal median, adjusted for maternal weight. Gaussian model parameters were derived and compared with six published non-Indian studies; NT parameters were derived from 27,647 women screened in India. On the basis of the maternal age distribution in 64,473 Indian women screened in 2016–2017, the model was used to predict test performance.
The model predicted a detection rate for a serum-only protocol of 80% for a 5% false-positive rate. Using a 1 in 250 at term Down’s syndrome risk cut-off, the predicted detection rate was 78% and the false-positive rate was 4.1%. When NT was also included, the rates were 95% for 5% and 90% for 1.4%, respectively.
First-trimester screening using four serum markers only can be carried out in India. Performance is expected to be similar to the second-trimester Quad test and will also facilitate early screening for preeclampsia and open spina bifida. A protocol of NT plus the four serum markers enhances the performance compared with NT, PAPP-A and free β-hCG.
KeywordsFirst trimester Screening Down’s syndrome Prenatal diagnosis PlGF AFP
We thank Deepika Sai Reddy and Lakshmi Kiran, Fetal Medicine Consultants at Rainbow Children Hospital & Birth Right by Rainbow, for providing samples and discussions on data; Ashok Khurana, at the Ultrasound Laboratory, New Delhi, for discussions on data; Soundarya Vazhuthanassery and Prabhu Selvaraj of Perkin Elmer Health Sciences, Chennai, for managing the project from planning to execution and data generation in the laboratory.
Compliance with Ethical Standards
Conflict of interest
Howard Cuckle is a paid consultant of PerkinElmer Inc. All other authors declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
Informed consent was obtained from all patients for being included in the study.
- 1.Cuckle HS, Pergament E, Benn P. Multianalyte maternal serum screening for chromosomal abnormalities and neural tube defects. In: Milunsky A, Milunsky JM, editors. Genetic disorders and the fetus: diagnosis, prevention and treatment. 7th ed. Hoboken: Wiley-Blackwell; 2015.Google Scholar
- 8.Palomaki GE, Eklund EE, Neveux LM, et al. Evaluating first trimester maternal serum screening combinations for Down syndrome suitable for use with reflexive secondary screening via sequencing of cell free DNA: high detection with low rates of invasive procedures. Prenat Diagn. 2015;35(8):789–96.CrossRefGoogle Scholar