Association between fetal fraction of cell-free DNA and adverse pregnancy outcomes.

PURPOSE: To determine the association between fetal fraction (FF) levels in cell-free fetal DNA (cffDNA) testing and adverse pregnancy outcomes. METHODS: This retrospective cohort study, conducted at a single center, involved 2063 pregnant women with normal 1st and 2nd trimester non-invasive prenatal test (NIPT) results between 2016 and 2021. Pregnancy outcomes were examined by determining the < 4% and < 5th percentile (3.6%) cut-off values for low fetal fraction (LFF). Pregnancy outcomes were also examined by dividing the FF into population-based quartiles. Adverse pregnancy outcomes were pregnancy-induced hypertensive diseases (PIHD), gestational diabetes mellitus (GDM), spontaneous preterm birth (PTB), intrahepatic cholestasis of pregnancy (ICP), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, and 1st and 5th minutes low APGAR scores (< 7). RESULTS: PIHD was significantly higher in LFF (< 4% and < 5th percentile) cases (p = 0.015 and p < 0.001, respectively). However, in population-based quartiles of FF, PIHD did not differ significantly between groups. Composite adverse maternal outcomes were significantly higher in the FF < 4% group (p = 0.042). When analyzes were adjusted for maternal age, BMI, and gestational age at NIPT, significance was maintained at < 4%, < 5th percentile LFF for PIHD, and < 4% LFF for composite adverse maternal outcomes. However, there was no significant relationship between LFF with GDM, ICP and PTB. Additionally, there was no significant association between low APGAR scores, SGA, LGA, LBW, macrosomia, and LFF concerning neonatal outcomes. CONCLUSION: Our study showed that LFF in pregnant women with normal NIPT results may be a predictor of subsequent PIHD.

Experiences in the molecular genetic and histopathological evaluation of calpainopathies.

Calpainopathy is mainly characterized by symmetric and progressive weakness of proximal muscles. Several reports showed that the most common LGMD subtype is LGMDR1 or calpainopathy, which had previously been defined as LGMD2A. Until now, more than 500 likely pathogenic/pathogenic variants in the CAPN3 gene have been reported. However, a clear genotype-phenotype association had not yet been established and this causes major difficulties in predicting the prognosis in asymptomatic patients and in providing genetic counseling for prenatal diagnosis. In this report, we aimed to add new data to the literature by evaluating 37 patients with likely pathogenic/pathogenic variants for the detected variants' nature, patients' phenotypes, and histopathological features. As a result, the general clinical presentation of the 23 different variants was presented, the high frequency of NM_000070.3:c.550delA mutation in Exon 4 was discussed, and some novel genotype-phenotype associations were suggested. We have underlined that calpainopathy can be misdiagnosed with inflammatory myopathies histopathologically. We have also emphasized that, in young or adult patients with mild to moderate proximal muscle weakness and elevated CK levels, calpainopathy should be the first suspected diagnosis.