Disease-severity in subsequent pregnancies with RhD immunization: a nationwide cohort

OBJECTIVE(S): to evaluate the severity of HDFN in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. DESIGN: prospective cohort. SETTING: the Netherlands. POPULATION: nationwide selection of all pregnant women with RhD antibodies. METHODS: women with two subsequent RhD immunized pregnancies with RhD-positive children after antibodies were detected were included. MAIN OUTCOME MEASURE: the severity of HDFN in the first and subsequent pregnancy at risk. RESULTS: 62 RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased significantly in the subsequent pregnancy (P<.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, severe HDFN in the next pregnancy was uncommon (22%), especially when no therapy or only non-intensive phototherapy was indicated during the first pregnancy (6%), or if the ADCC result remained <10%. Contrarily, women with antibodies detected during the first pregnancy of a RhD positive child (>= 27th week), most often before they had ever received RhIg prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION(S): RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of a RhD-positive child are at highest risk of severe disease in the next pregnancy.

SIGNIFICANCE OF LOW MATERNAL SERUM Β-HCG LEVELS IN THE ASSESSMENT OF THE RISK OF ATYPICAL CHROMOSOMAL ABNORMALITIES

Introduction: The introduction of prenatal cell-free DNA as a screening test has surpassed traditional combined first-trimester screening (cFTS) in the detection of common trisomies. However, its current limitation in detecting only common trisomies is affecting the diagnostic yield for other clinically significant chromosomal abnormalities. Methods: In efforts to optimize the detection of fetuses with genetic abnormalities, we have analyzed the relationship between the cFTS risk score and biomarkers with atypical chromosomal abnormalities. Furthermore, we have evaluated the impact of prenatal cell-free DNA screening on the detection of chromosomal abnormalities in our population. For these purposes, we performed a retrospective study of 877 singleton pregnancies who underwent chromosomal microarray analysis (CMA) between 2013 to 2020 and for whom first-trimester screening data were available. Results: The results demonstrated that low levels of free beta human chorionic gonadotropin (β-hCG) (≤ 0.37 MoM) and increased fetal nuchal translucency (NT) (≥ 3.5mm) were statistically associated with the presence of atypical chromosomal abnormalities. In fact, the risk of pathogenic CMA results increased from 6% to 10% when fetal NT was increased and from 6% to 20% when a low serum β-hCG level was detected in the high-risk cFTS group. Moreover, our results showed that altered serum levels of β-hCG can have a substantial impact on the early detection of clinically relevant copy number variants. Discussion/Conclusion: Traditional cFTS can potentially identify a substantial proportion of atypical chromosomal aberrations, and women with increased NT or low maternal serum β-hCG levels are at increased risk of having pathogenic CMA results. Our results may help clinicians and women decide whether invasive testing or prenatal cell-free DNA screening testing are more appropriate for each situation.

The relationship between first and second trimester biochemical parameters used to screen down syndrome and intrahepatic cholestasis of pregnancy

Objective: To assess the role of first and second-trimester screening biomarkers pregnancy-associated plasma protein-A(PAPP-A), free beta-human chorionic gonadotropin(free ß-hCG), estriol, alpha-fetoprotein and total β-hCG in the early diagnosis of intrahepatic cholestasis of pregnancy (ICP). Materials and Methods: Patients with ICP admitted to Mersin University Hospital for delivery between 2015 and 2019 and had first and second-trimester aneuploidy screening tests performed in the same facility were retrospectively assessed. Randomly 60 pregnant women without comorbid conditions during the same period were included as controls. Data regarding demographic characteristics, laboratory values including free ß-hCG and PAPP-A in first-trimester screening and total ß-hCG, estriol and alpha- fetoprotein in second-trimester screening were compared. Results: There were 46 eligible patients with ICP. In first trimester screening, it was found that PAPP-A MoM was significantly lower (0.89±0.55 vs. 1.94±0.73; p=0.035) while free ß-hCG MoM was significantly higher in ICP group when compared to controls (1.84±0.59 vs. 0.99±0.47; p=0.018). In second trimester screening, no significant difference was detected in aneuploidy markers between groups. For prediction of ICP development, first trimester free β-hCG >1.44 MoM was found to have a sensitivity of 50%, a specificity of 80% and positive and negative predictive values of 33% and 88.9% respectively. Similarly first trimester PAPP-A values <1.075 MoM was found to have 80% and 75% sensitivity and specificity with positive and negative predictive values of 75% and 44% respectively. Conclusion: Low PAPP-A MoM value and elevated free ß-hCG in first trimester seem to be associated with ICP development.