The Association between Low Fetal Fraction of Non-Invasive Prenatal Testing and Adverse Pregnancy Outcomes for Placental Compromise.

(1) Background: Non-invasive prenatal testing (NIPT) is a screening test for fetal aneuploidy using cell-free fetal DNA. The fetal fragments (FF) of cell-free DNA (cfDNA) are derived from apoptotic trophoblast of the placenta. The level of fetal cfDNA is known to be influenced by gestational age, multiple pregnancies, maternal weight, and height. (2) Methods: This study is a single-center retrospective observational study which examines the relationship between the fetal fraction (FF) of cell-free DNA in non-invasive prenatal testing (NIPT) and adverse pregnancy outcomes in singleton pregnancies. A total of 1393 samples were collected between 10 weeks and 6 days, and 25 weeks and 3 days of gestation. (3) Results: Hypertensive disease of pregnancy (HDP) occurred more frequently in the low FF group than the normal FF group (5.17% vs. 1.91%, p = 0.001). Although the rates of small for gestational age (SGA) and placental abruption did not significantly differ between groups, the composite outcome was significantly higher in the low FF group (7.76% vs. 3.64%, p = 0.002). Furthermore, women who later experienced complications such as HDP or gestational diabetes mellitus (GDM) had significantly lower plasma FF levels compared to those without complications (p < 0.001). After adjustments, the low FF group exhibited a significantly higher likelihood of placental compromise (adjusted odds ratio: 1.946). (4) Conclusions: Low FF in NIPT during the first and early second trimesters is associated with adverse pregnancy outcomes, particularly HDP, suggesting its potential as a predictive marker for such outcomes.

Evaluation of fetal and neonatal outcomes after ingestion of Cnidium root (Cnidium officinale Makino) during pregnancy.

Cnidium officinale Makino is a perennial plant, a member of the Umbelliferae family. Cnidium root has traditionally been used as a medicinal herb. It has analgesic, antiinflammatory, antipyretic, antibacterial, antispasmodic, vasodilatory, hypertensive, and sedative effects. However, there are no studies of reproductive toxicity in humans. Therefore, this study aimed to prospectively evaluate the fetal and neonatal outcomes in the children of women who inadvertently used Cnidium root during pregnancy. In a prospective cohort study design, 111 singleton pregnant women taking Cnidium root for various reasons, and 219 age-matched singleton pregnant women unexposed to any herbal agent (unexposed group), were followed up until delivery. In the exposed group, Cnidium root was indicated as controlling cough and cold in 54.1% of patients, at the maximal dose of 12,000 mg/day between 1 day to 12.4 weeks of gestation. Fetal outcomes, including birth weight and 1- and 5-min Apgar score, were similar for the two groups. There were four babies born with major malformations in the exposed group vs. 14 in the unexposed group (OR = 0.5; 95% CI 0.2-1.6; p = 0.190). The gestational age, length, and head circumference were relatively shorter among babies born in the exposed group. Even after adjusting for gender, there was a tenfold increase in the frequency of shorter newborns (<2SD) in the exposed group (OR = 10.1; 95% CI 1.2-87.6; p = 0.019). Our study suggests that Cnidium root is not a major human teratogen. Whether lesser gestational ages at birth and shorter birth lengths are clinically relevant after exposure to Cnidium remains to be elucidated in further studies.

Functional analysis of cell-free RNA using mid-trimester amniotic fluid supernatant in pregnancy with the fetal growth restriction.

The prediction and monitoring of fetal growth restriction (FGR) fetuses has become with the use of ultrasound. However, these tools lack the fundamental evidence for the growth of fetus with FGR excluding pathogenic factors.Amniotic fluid samples were obtained from pregnant women for fetal karyotyping and genetic diagnosis at 16 to 19 weeks of gestation. For this study, 15 FGR and 9 control samples were selected, and cell-free fetal RNA was isolated from each supernatant of the amniotic fluid for microarray analysis.In this study, 411 genes were differentially expressed between the FGR and control group. Of these genes, 316 genes were up-regulated, while 95 genes were down-regulated. In terms of gene ontology, the up-regulated genes were highly related to metabolic process as well as protein synthesis, while the down-regulated genes were related to receptor activity and biological adhesion. In terms of tissue-specific expression, the up-regulated genes were involved in various organs while down-regulated genes were involved only in the brain. In terms of organ-specific expression, many genes were enriched for B-cell lymphoma, pancreas, eye, placenta, epithelium, skin, and muscle. In the functional significance of gene, low-density lipoprotein receptor-related protein 10 (LRP10) was significantly increased (6-fold) and insulin-like growth factor (IGF-2) was dramatically increased (17-fold) in the FGR cases.The results show that the important brain-related genes are predominantly down-regulated in the intrauterine growth restriction fetuses during the second trimester of pregnancy. This study also suggested possible genes related to fetal development such as B-cell lymphoma, LRP10, and IGF-2. To monitor the fetal development, further study may be needed to elucidate the role of the genes identified.