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We retrospectively included women with abnormal FTS analytes and compared outcomes between those with elevated and normal UtA-PI. Out of 582 women with abnormal FTS analytes, 65 (11.2%) had elevated UtA-PI. Neonates of women in this group had higher rates of birth weight <3rd, 5th, and 10th percentile. The area under the ROC curve for predicting FGR <10th percentile by UtA-PI was 0.584, for FGR<5th percentile 0.593, and for FGR<3rd percentile 0.720. In women with abnormal FTS, elevated UtA-PI is associated with higher rates of FGR, but its predictability is moderate-to-poor. [ABSTRACT FROM AUTHOR]

• Serum markers for aneuploidy screening are influenced by maternal characteristics. • Adjustments are needed before marker measurements can be used for risk estimation. • Appropriate adjustments will improve the accuracy of multiple marker screening. • New adjustment factors were generated for race, smoking, and insulin-dependent diabetes. The concentrations of maternal serum markers for aneuploidy screening are influenced by maternal characteristics such as race, smoking, insulin dependent diabetes mellitus (IDDM), and in vitro fertilization (IVF). Accurate risk estimation requires adjustment of initial values for these characteristics. This study aims to update and validate adjustment factors for race, smoking, and IDDM. The study included singleton pregnancies that received multiple marker screening in Ontario, Canada between January 2012, and December 2018, and had their information collected in the Better Outcomes Registry & Network (BORN) Ontario. Serum markers assessed included first trimester pregnancy-associated plasma protein A (PAPP-A), free β and total human chorionic gonadotropin (hCG), placental growth factor (PlGF) and αlpha-fetoprotein (AFP); second trimester AFP, unconjugated estriol (uE3), total hCG and inhibin A. The Mann-Whitney U test was used to assess the differences in the median multiple of the median (MoM) of serum markers between study and reference groups. New adjustment factors were generated by dividing the median MoM of a particular race, individuals who smoke tobacco, or have IDDM by those of the reference groups. The study included 624,789 pregnancies. There were statistically significant differences in serum marker concentrations among pregnant individuals who were Black, Asian, or First Nations compared to a White group, those who smoked compared to Non-smoking individuals, and those with IDDM compared to Non-IDDM group. New adjustment factors for race, smoking, and IDDM were validated by comparing median MoM of serum markers corrected using the current adjustment factors and new adjustment factors generated in this study. The adjustment factors generated in this study can adjust the effects of race, smoking, and IDDM on serum markers more accurately. [ABSTRACT FROM AUTHOR]

Cell-free fetal DNA screening is routinely offered to pregnant individuals to screen for aneuploidies. Although cell-free DNA screening is consistently more accurate than multiple-marker screening, it sometimes fails to yield a result. These test failures and their clinical implications are poorly described in the literature. Some studies suggest that a failed cell-free DNA screening result is associated with increased likelihood of cytogenetic abnormalities. This study aimed to assess the association between a failed cell-free DNA test and common aneuploidies. The objectives were to determine: (1) the proportion of test failures on first and subsequent attempts, and (2) whether a failed cell-free DNA screen on first attempt is associated with increased likelihood of common aneuploidies (trisomies 21, 18, and 13, and sex chromosome aneuploidies). This was a population-based retrospective cohort study using data from Ontario's prescribed maternal and child registry, Better Outcomes Registry and Network Ontario. The study included all singleton pregnancies in Ontario with an estimated date of delivery from September 1, 2016 to March 31, 2019 that had a cell-free DNA screening record in the registry. Specific outcomes (trisomies 21, 18, and 13, and sex chromosome aneuploidies) of pregnancies with a failed cell-free DNA screen on first attempt were compared with those of pregnancies with low-risk cell-free DNA-screening results using modified Poisson regression adjusted for funding status (publicly funded vs self-paid), gestational age at screening, method of conception, and maternal age for autosomal aneuploidies. Our cohort included 35,146 pregnancies that had cell-free DNA screening during the study period. The overall cell-free DNA screening failure rate was 4.8% on first attempt and 2.2% after multiple attempts. An abnormal cytogenetic result for trisomies 21, 18, and 13, or sex chromosome aneuploidies was identified in 19.4% of pregnancies with a failed cell-free DNA screening for which cytogenetic testing was performed. Pregnancies with a failed cell-free DNA screen on first attempt had a relative risk of 130.3 (95% confidence interval, 64.7–262.6) for trisomy 21, trisomy 18, or trisomy 13, and a risk difference of 5.4% (95% confidence interval, 2.6–8.3), compared with pregnancies with a low-risk result. The risk of sex chromosome aneuploidies was not significantly greater in pregnancies with a failed result compared with pregnancies with a low-risk result (relative risk, 2.7; 95% confidence interval, 0.9–7.9; relative difference, 1.2%; 95% confidence interval, −0.9 to 3.2). Cell-free DNA screening test failures are relatively common. Although repeated testing improves the likelihood of an informative result, pregnancies with a failed cell-free DNA screen upon first attempt remain at increased risk for common autosomal aneuploidies, but not sex chromosome aneuploidies. [ABSTRACT FROM AUTHOR]

Objective: To study the current literature on the association between IVF treatment and maternal serum screening marker levels and nuchal translucency thickness.Design: Systematic review.Settings: Not applicable.Patient(s): Eligible studies included those with an exposed group of pregnant women that used IVF with or without intracytoplasmic sperm injection to conceive and a control group of pregnant women who conceived spontaneously.Intervention(s): IVF treatment to conceive.Main Outcome Measure(s): Outcomes evaluated included maternal serum screening markers (pregnancy-associated plasma protein A [PAPP-A], alpha-fetoprotein, hCG, unconjugated estriol, dimeric inhibin-A) and nuchal translucency thickness.Result(s): Database searches identified 4,118 titles and abstracts that were independently screened, which resulted in 76 articles that were assessed for eligibility. Additionally, one study was added for consideration based on expert knowledge. There were 29 cohort and 11 case-control studies in the descriptive review. The most commonly reported markers were PAPP-A and free β-hCG, which were reported in 28 and 26 studies, respectively. The studies that reported effect sizes for PAPP-A and free β-hCG were not statistically significant.Conclusion(s): A decrease in PAPP-A and an increase in total hCG was consistently reported among the included studies. However, owing to the variability in the levels of the other maternal serum screening markers reported and the inability to conduct a meta-analysis, we were unable to generalize about the differences between prenatal screening results in the IVF population. [ABSTRACT FROM AUTHOR]

There are differences in the distribution and length of HBV CpG islands and the viral mutations contribute greatly to the development of HBV-related diseases. However, little is known regarding the effects of such difference and mutations in HBV genotypes B and C sequences on the regulation of HBV gene expression and their clinical outcomes. To study the distribution, length and genetic trait of CpG islands in normal and mutant sequences of HBV genotypes B and C, 320 HBV isolates from Chinese patients were retrieved from GenBank. Programs CLUSTALX 1.83 and MethPrimer were employed to perform multiple sequence alignments and to predict CpG islands, respectively. 72.0% genotype B isolates contained three conventional CpG islands, and 76.1% genotype C only contained CpG islands II and III. 14.6% genotype B and 7.5% genotype C contained three novel CpG islands. In genotype B, lengths of conventional CpG islands between normal and mutant isolates exhibited substantial variations, but in genotype C, those were relatively stable. CpG island II could be “truncated” or “split”. “Truncated” region mutations were associated with structural and functional abnormalities of HBV genes. Rate of “split” CpG island II in genotype B was much higher than that in genotype C. In the majority of isolates from HCC and HBV–ACLF, genotype C lacked CpG island I and novel islands. Distribution, length and genetic trait of CpG islands in HBV genotypes B and C might affect their methylation status, and further affect regulation of HBV gene expression, leading to different clinical outcomes. [ABSTRACT FROM AUTHOR]

Highlights: [•] Early life stress induced depressive-like behavior in adolescent rats. [•] Early life stress increased corticosterone level in adolescent rats. [•] Early life stress reduced prefrontal glutamate, glutamine, and N-acetylaspartate. [•] The findings underscore the long-lasting and detrimental effects of childhood adversities. [ABSTRACT FROM AUTHOR]