Impact of Th-17 Cytokines on the Regulation of Transporters in Human Placental Explants.

Activated T helper 17 (Th-17) cytokines play a role in the pathophysiology of autoimmune and infectious diseases. While these diseases affect many women of childbearing age, little is known about the effect of these cytokines on placental transporters. As several pro-inflammatory cytokines impact the expression of ABC and SLC placental transporters, we hypothesized that these transporters may be similarly altered by elevated levels of circulating Th-17 cytokines. Cultured term human villous explants were treated with IL-17A, IL-22, or IL-23, alone or in combination. Samples were analyzed using qRT-PCR and Western blotting. The mRNA expression of OATP2B1 was significantly downregulated in explants by all individual cytokines and combination treatments, while decreased protein expression was seen with IL-23 and combination (p < 0.01). Combination treatment decreased the mRNA expression of BCRP and OAT4 but increased that of OCT3 (p < 0.01). Decreased accumulation of the OATP substrate, cascade blue, was seen in IL-23-treated choriocarcinoma JAr cells (p < 0.01). Elevated Th-17 cytokines, which are seen in infectious and autoimmune diseases, affect the expression and activity of OATP2B1, as well as mRNA expression of placental BCRP, OAT4, and OCT3. This dysregulation could impact the fetal exposure to endogenous and exogenous substrates.

Meta-Analysis of Pregnancy Outcomes after Exposure to TNF-α Inhibitors During Pregnancy for the Treatment of Arthritic Diseases.

TITLE: Pregnancy Outcomes after Exposure to TNF-α Inhibitors During Pregnancy for the Treatment of Arthritic Diseases: A Meta-Analysis   Authors: Mirdamadi K, Salinas T, Vali R, Papadimitripulous M, Piquette-Miller M Background: Auto-immune arthritic diseases affect many women of child-bearing age. Tumor necrosis factor (TNF)-α inhibitors are currently used for the treatment of various immune-mediated diseases during pregnancy. However, there has been no evaluation of safety in the treatment of arthritic diseases during gestation.     Objective: To analyze the risk of adverse pregnancy and neonatal outcomes after treatment of arthritic diseases with TNF-α inhibitors.     Methods: Major databases including Ovid MEDLINE, Embase, and Web of Science, were searched inclusive to April 2016. Observational prospective cohort studies evaluating pregnancy outcomes after exposure to TNF-α inhibitors for the treatment of arthritic diseases during pregnancy were included. Data on pregnancy and neonatal outcomes was extracted from all included studies. A meta-analysis was performed using inverse-variance random effect with a 95% confidence interval (95%CI) and p<0.05.     Results: Eight prospective studies with comparison groups were included in the meta-analysis. TNF-α inhibitors were associated with significantly higher risks of low birth weight (odds ratio (OR), 1.43; 95%CI, 1.00-2.04) and significantly lower rates of live birth (OR, 0.61; 95%CI, 0.38-0.98). However, birth defects, therapeutic abortion, spontaneous abortion, and preterm birth were not significantly different between the two groups.     Conclusion: Treatment of arthritic diseases with TNF-α inhibitors during pregnancy increases the risk of lower birth weight and decreases the rate of live birth in this population. While duration of treatment and gestational age at exposure may play a role in these outcomes, evaluation of risk versus benefit is crucial in this patient population.   Key words: TNF-α inhibitors, pregnancy outcomes, arthritic disease, meta-analysis.

H1N1 and influenza viruses: why pregnant women might be hesitant to be vaccinated.

QUESTION: I have been encouraging pregnant women to receive both the H1N1 and influenza vaccines since I became aware of Health Canada's guidelines. However, some of the women in my practice have heard conflicting information, often from media sources, and they are hesitant to be vaccinated. What is the evidence behind these guidelines, and should I really be convincing these women to be vaccinated? ANSWER: Pregnant women and growing fetuses are considered a population vulnerable to H1N1 and influenza viruses. Health Canada published a report in late 2010 estimating that this population was at increased risk of hospitalization and severe outcomes of H1N1 infection. Recommendations included pregnant women as a priority group to receive the H1N1 vaccine as well as the influenza vaccine. This information should be explained unambiguously to pregnant women, and they should be made aware of the sensationalism of media reports, which are often based on opinion and not evidence.

Pregnant women's perception of risk with use of the H1N1 vaccine.

OBJECTIVE: During the H1N1 influenza pandemic in 2009, The Motherisk Program, a counselling service providing teratology information, received many calls from pregnant women inquiring about the safety of the H1N1 vaccine. We wished to explore pregnant women's perception of risk and the factors associated with deciding whether or not to receive the vaccine. METHODS: Pregnant women who called Motherisk between October 1 and November 30, 2009, requesting counselling regarding the safety of the H1N1 vaccine, and who had not yet received the vaccine, were contacted for follow-up using a structured questionnaire. RESULTS: One hundred thirty women completed the questionnaire; 104 (80%) had received the H1N1 vaccination following their call to Motherisk, and 26 (20%) had not. More than 70% of the women cited confusing and frightening information in the media as a trigger for their concern, prompting them to call Motherisk. Sixty percent stated that information from their primary health care providers or Motherisk contributed to their decision making. CONCLUSION: The H1N1 vaccination rate in pregnant women who contacted Motherisk was higher than the rate in the general population, as many followed Motherisk's recommendation to receive the vaccine. During this period, the media appeared to provide pregnant women with confusing information. In any future pandemic scare, accessibility to primary health care providers or specialized information services such as Motherisk will be key to providing guidance for pregnant women.