Search

Background: International professional organizations recommend aspirin prophylaxis to women screened high risk for preterm preeclampsia (PE) in the first trimester. The UK Fetal Medicine Foundation (FMF) screening test for preterm PE using mean arterial pressure (MAP), uterine artery pulsatility index (UTPI) and placental growth factor (PlGF) was demonstrated to have lower detection rate (DR) in Asian population studies. Additional biomarkers are therefore needed in Asian women to improve screening DRs as a significant proportion of women with preterm and term PE are currently not identified., Objectives: To evaluate maternal serum inhibin-A at 11-13 weeks as an alternative to PlGF or as an additional biomarker within the FMF screening test for preterm PE., Study Design: This is a nested case-control study using pregnancies initially screened at 11-13 weeks for preterm PE using the FMF triple test in a non-intervention study conducted between December 2016 and June 2018. Inhibin-A levels were retrospectively measured in 1,792 singleton pregnancies, 112 (1.7%) with PE matched for time of initial screening with 1,680 unaffected pregnancies. Inhibin-A levels were transformed to multiple of the expected median (MoM). The distribution of log10 inhibin-A MoM in PE and unaffected pregnancies and the association between log10 inhibin-A MoM and gestational age (GA) at delivery in PE were assessed. The screening performance determined by area under receiver operating characteristic curves (AUC) and detection rates (DRs) at a 10% fixed false positive rate (FPR), for preterm and term PE was determined. All risks for preterm and term PE were based on the FMF competing risk model and Bayes theorem. Differences in AUC (ΔAUC) between different biomarker combinations were compared using the Delong test. McNemar's test was used to assess the off-diagonal change in screening performance at a fixed 10% FPR after adding inhibin-A or replacing PlGF in the preterm PE adjusted risk estimation model., Results: Inhibin-A levels in unaffected pregnancies were significantly dependent on GA, maternal age and weight and were lower in parous women with no previous history of PE. Mean log10 inhibin-A MoM in any-onset PE (p<0.001), preterm (p<0.001) and term PE (p = 0.015) pregnancies were all significantly higher than that of unaffected pregnancies. Log10 inhibin-A MoM was inversely but not significantly correlated (p = 0.165) with GA at delivery in PE pregnancies. Replacing PlGF with inhibin-A in the FMF triple test reduced AUC and DR from 0.859 and 64.86% to 0.837 and 54.05%, the ΔAUC was not statistically significant. AUC and DR when adding inhibin-A to the FMF triple test were 0.814, 54.05% and the -0.045 reduction in AUC was statistically significant (p = 0.001). At a fixed 10% FPR, replacing PlGF with inhibin-A identified 1 (2.7%) additional pregnancy but missed 5 (13.5%) pregnancies which subsequently developed preterm PE identified by the FMF triple test. Adding inhibin-A missed 4 (10.8%) pregnancies and did not identify any additional pregnancies with preterm PE., Conclusion: Replacing PlGF by inhibin-A or adding inhibin-A as an additional biomarker in and to the FMF triple screening test for preterm PE does not improve screening performance and will fail to identify pregnancies that are currently identified by the FMF triple test., Competing Interests: LCP has received speaker fees and consultancy payments from Roche Diagnostics and Ferring Pharmaceuticals. LCP and DS have received in‐kind contributions from Roche Diagnostics, PerkinElmer, Thermo Fisher Scientific, and GE Healthcare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other co-authors report no conflicts of interest., (Copyright: © 2023 Moungmaithong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Zika virus (ZKV) infection in a pregnant woman, especially during the first trimester, often results in congenital anomalies. However, the pathogenic mechanism is unknown and one-third of ZKV infected pregnancies are asymptomatic. Neutralizing antibodies against ZKV has been reported in 70% of Thai adults, but the prevalence among pregnant women is unknown. Currently, vaccines and specific treatments for ZKV are under development. A better understanding of the immune status of pregnant women will increase the success of effective prevention guidelines. The prevalence of ZKV infection in pregnant women in antenatal care clinics was investigated during the rainy season from May to October 2019 at Siriraj Hospital, Bangkok, Thailand. We recruited 650 pregnant women (39.42% first, 52.26% second and 7.36% third trimester) and found that 30.77% had ZKV-specific IgG, and 39.81% had neutralizing antibodies (nAb) against ZKV (titer ≥10). Specific and neutralizing antibody levels varied by maternal age, trimester, and month. We further characterized the cross-reaction between ZKV and the four Dengue virus (DENV) serotypes by focused reduction neutralization test (FRNT) and found that cross-reactions were common. In conclusion, about 60% of pregnant women who living in central Thailand may be at risk of ZKV infection due to the absence of neutralizing antibodies against ZKV. The functions of cross-reactive antibodies between related viral genotypes require further study. These findings have implications for health care monitoring in pregnant women including determining the risk of ZKV infection, assisting the development of a flavivirus vaccine, and informing the development of preventative health policies., Competing Interests: The authors have declared that no competing interests exist.

Backgrounds & Aims: We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection., Methods: This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment. RASs in NS5A and NS3 were determined by population sequencing., Results: The frequency of signature RASs at position D168 of NS3 was 68%, and at positions L31 and Y93 of NS5A was 79 and 76%, respectively. The frequency of dual signature RASs in NS5A (L31-RAS and Y93-RAS) was 63%. RASs at L28, R30, P32, Q54, P58, and A92 in addition to dual signature RAS were detected in 5, 5, 1, 22, 2, and 0 patients, respectively. In total, triple, quadruple, and quintuple RASs in combination with dual signature RAS were detected in 35, 10, and 1.5% patients, respectively. These RASs were detected in patients without baseline RASs or who prematurely discontinued therapy. Co-existence of D168 RAS in NS3 and L31 and/or Y93 RAS in NS5A was observed in 62% of patients., Conclusion: Treatment-emergent RASs after failure with DCV/ASV combination therapy are highly complex in more than 50% of the patients. The identification of complex RAS patterns, which may indicate high levels of resistance to NS5A inhibitors, highlights the need for RAS sequencing when considering re-treatment with regimens including NS5A inhibitors., Competing Interests: The authors have declared that no competing interests exist.