Dr Jessica Teoh1, Ms Elizabeth Austin1, Dr Jose Garcia Flores1, Dr Ritu Mogra1, Dr Rajit Narayan1
1Royal Prince Alfred Hospital, Camperdown, Australia
Biography:
Jessica is an early career clinician-researcher and an O&G unaccredited registrar at Royal Prince Alfred Hospital. She is a Clinical Associate Lecturer at USYD and a published author in peer-reviewed journals. She was recipient of grants including the Churchill Fellowship, Avant Early Career Research and Nemettallah Kamle Habib Family Scholarship.
Abstract:
Cell-free fetal DNA testing is a non-invasive prenatal test (NIPT) widely accepted as the most accurate screening technique for detecting fetal aneuploidy, yet approximately 4% of tests yield an indeterminant result. One significant reason is a low fetal fraction of DNA in samples. Placental trophoblastic tissue is postulated to be the main contributor to cell-free “Fetal” DNA (cffDNA), with apoptosis the likely mechanism for release into the maternal circulation. This might explain why women with autoimmune disease and consequent disruption of immune mechanics leading to altered apoptosis, are more likely to have lower fetal fractions. Furthermore, it is postulated that variance in the apoptotic mechanism at the placental level could contribute to altered cffDNA levels in complications including intrauterine growth restriction (IUGR), pre-eclampsia, or preterm birth.
The study aimed to compare cffDNA fraction and rate of indeterminant NIPT results in women with autoimmune disease, to women without. Secondly, to compare rates of adverse outcomes (IUGR, pre-eclampsia, preterm birth) in pregnancies with underlying autoimmune disease based on cffDNA fraction. Finally, evaluate the value of incorporation of NIPT to improve existing first-trimester predictive modeling for adverse pregnancy outcomes.
This is a retrospective cohort study conducted at a tertiary medical obstetric clinic. Autoimmune conditions included are listed by the National Institute of Allergy and Infectious Diseases. Outcomes include incidence and demographics of women with autoimmune disease, severity, control with anticoagulants or immunomodulators, rate of indeterminant results and low cffDNA, fetal sex, gestation, and incidence of IUGR, pre-eclampsia, preterm birth, and gestational diabetes.
We are not aware of existing studies that have explored obstetric outcomes of women with autoimmune disease stratified by cffDNA levels and NIPT performance in the first trimester. If an association is found, it would open the enticing prospect of incorporating NIPT into existing screening algorithms for the great obstetric syndromes.
Keywords
Autoimmune disease, NIPT, cell free fetal DNA fraction, indeterminant result, predictive modelling, adverse outcomes, IUGR, pre-eclampsia, preterm birth, gestational diabetes
References
1. Revello R, Sarno L, Ispas A, Akolekar R, Nicolaides KH. Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2016;47(6):698–704.
2. Tjoa, M. L., T. Cindrova-Davies, O. Spasic-Boskovic. Trophoblastic oxidative stress and the release of cell-free fetoplacental DNA. Am. J. Pathol. 2006; 169: 400–404.
3. Hui CYY, Tan WC, Tan EL, Tan LK. Repeated failed non-invasive prenatal testing in a woman with immune thrombocytopenia and antiphospholipid syndrome: lessons learnt. BMJ Case Rep 2016;2016:bcr2016216593.