Technical Summary of Work:
Chromosomal abnormalities are a leading cause of developmental delay in children. Trisomies 21, 18 and 13 and sex chromosome aberrations are the most frequently occurring chromosomal abnormalities. Definitive prenatal diagnosis currently requires invasive sampling followed by chromosome analysis. However, invasive tests are costly and pose an inherent risk of procedure-related complications including miscarriage. Therefore, following appropriate screening, invasive tests should be performed only in high-risk pregnancies.
Screening based on maternal age in combination with second-trimester serum analyses has been established with detection rates of 60–84% for a false-positive rate of 5%. However, late diagnosis of chromosomal abnormalities and pregnancy termination at an advanced gestational age could incur unnecessary anxiety for families. In addition, women prefer to undergo first-trimester screening if the choice is available3.
First-trimester risk assessment of common chromosomal aneuploidies is based on a combination of maternal age, maternal serum-free β-human chorionic gonadotropin (fβ-hCG), pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness (NT) at 11 to 13 + 6 weeks. In various prospective studies the detection rate ranges from 74% to 93% for a fixed false-positive rate of 5%. Additional first-trimester ultrasound markers, namely absent nasal bone (NB), reversed ductus venosus (DV) flow and tricuspid regurgitation (TR), have separately been found to increase the effectiveness of trisomy 21 screening.
The first activity of “Hope Generation Foundation” was to develop and optimize prenatal screening of chromosomal abnormalities for the first time in Iran (supervised and audited by “Fetal Medicine Foundation” in London, UK). Following up the outcome of pregnancies in screened women was necessary to evaluate the screening performance indicators including detection rate and false positive rate.
Because of the need for follow up and systematic data mining, we defined the above project to design and organize a “Follow-up Department” after opening and start of “Hope Generation Foundation” (a medical center for control of birth defects and developmental delay). I, as an associate principal investigator in the above subprojects, designed the different parts of the department and trained different groups of personnel based on the status of the pregnancies they were supposed to follow up:
• I trained genetic counselors, who were general practitioners, for history taking from women with screen positive pregnancies (if they have carried out invasive tests, the results of karyotyping, pregnancy outcome and etc.)
• I trained genetic counselors, who were general practitioners, for history taking from women whose fetuses were affected with structural abnormalities (abnormal ultrasound findings) to know the clinical significance of the detected abnormality and pregnancy outcome (if they have terminated the pregnancy, any prenatal or perinatal treatment, if the abnormal finding had been resolved and etc.)
• I trained genetic counselors (who were general practitioners) for active follow up of pregnancies with fetuses, affected with multiple congenital anomalies in short intervals to know the pregnancy outcome (family decision, postnatal status of the affected newborn, if autopsy and genetic investigation had been carried out on terminated pregnancies and etc.)
• I trained expert personnel for history taking from the remaining women with low risk pregnancies (any pregnancy complication, anthropometric data of the newborn, delivery method, any birth defect or genetic disorder and etc.)
I could manage to follow up the outcome of pregnancies in >22000 screened women (high risk and low risk), as well as investigation of the clinical significance of prenatally detected ultrasound abnormalities by active follow up of the pregnancies with affected fetuses. My work also led to construction of a huge database including detailed prenatal, perinatal and postnatal data of 101000 pregnant women referred for first/second trimester screening and/or ultrasound study.
Moreover, we obtained useful practical data regarding the clinical significance of prenatal ultrasound findings which are mainly helpful for clinical decision making or intervention.
Furthermore, my works led to a collaborative project with Ministry of Health and Medical Education entitled: “National Program on Evaluation of Commercial Risk Assessment Software used in Prenatal Screening of Chromosomal Abnormalities”. I managed this project as part of a national project for standardization of screening programs. I have evaluated most of the commercial risk assessment software present in Iran. Ministry of Health and Medical Education issues the license of the companies based on my report on quality of risk assessment.