Outcome of Children with Marked Changes in Maternal Screening Tests and Normal Karyotype

Abstract

OBJECTIVES: First and second trimester screening for aneuploidies has been routinely used in prenatal care for 15 years in Estonia. Although the primary aim of the screening is to identify pregnancies at risk of aneuploidy, marked changes in screening markers may give insight into other adverse pregnancy outcomes. METHOD: Aim of our study was to investigate whether chromosomally normal foetuses with marked changes (<0.25 MoM or >3.0 MoM) in maternal serum screening markers (first or second trimester) and first trimester ultrasound marker (nuchal translucency, NT >3 mm) have increased risk of adverse perinatal outcome, congenital anomalies or delayed development at 2 years of age. RESULTS: The present study based on screening test evaluated during 12 months: 1517 first trimester serum screening (PAPP-A and free beta-HCG) tests, 4418 second trimester serum screening (AFP, HCG, uE3) tests, and 1589 NT measurements. Of all evaluated tests 148 (4.7%) had marked changes at least in one marker. Second trimester miscarriage was diagnosed in 30 of them, most often in cases of low uE3 and HCG and increased AFP values. Complication during pregnancy, preterm birth and/ or complication during labour was associated with all markers, most often with low free beta-HCG, in 9/13 cases. The postnatal study group included 35 chromosomally normal infants born from mother with marked changes in screening test and consulted by geneticist during pregnancy. There were 4 (11.4%) preterm birth and low birth weight was documented in 6 (17%) cases. Postnatal growth problems were documented in 4 (11.4%) cases, delayed milestones in 6 (17%) cases. We diagnosed congenital anomalies or genetic disease in 6 (17%) cases: heart anomaly (4 cases), Silver-Russell syndrome (1 case) and congenital adrenal hypoplasia (1 case). CONCLUSIONS: In conclusion, marked changes in maternal screening markers are associated with increased risk of pregnancy complications. Children with increased NT, normal karyotype and normal ultrasound findings during pregnancy had no increased risk for developmental delay at 2 years of age. Foetuses with marked changes in biochemical markers and normal karyotype had postnatal increased risk for congenital disease (17%), growth problems and developmental delay at the age of 2 years