Britta Panda

Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway

Problem  Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre‐eclampsia, and pre‐term labor. aPL target the placenta directly by binding to beta2‐glycoprotein I (β2GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved.

Influenza vaccination during pregnancy and factors for lacking compliance with current CDC guidelines.

Background. The Center for Disease Control and Prevention (CDC) and the American College of Obstetricians and Gynecologists (ACOG) recommend influenza vaccination for all pregnant women during the influenza season. However, the actual rate of vaccination is substantially below the target levels. Given the recent emergence of novel influenza strains, there is an important need to address knowledge gaps in women and their healthcare providers to improve vaccination coverage for pregnant women during inter-pandemic and pandemic periods. This study attempted to identify potentially remediable attitudinal factors among women and their physicians that may present barriers to influenza vaccination and then assess the impact of interventions to increase the influenza vaccination rate in pregnant women. Methods. This prospective study initially analyzed patient and physician knowledge regarding the influenza vaccine in pregnancy and then examined the impact of several interventions aimed to increase immunization rates implemented over the following year. Influenza vaccination rates were assessed before and after the interventions. Results. Five hundred twenty patients were enrolled in the study during the influenza season 2007/2008. Only 19% of those patients reported receiving the influenza vaccination and only 28% recalled that the vaccine was offered. Following this, in the summer and fall of 2008, we performed a physician education program and distributed posters advertising the influenza vaccine to all offices offering prenatal care in our area in order to increase patient awareness of the need for the vaccine. In the following influenza season, we again reassessed the vaccination rate and patients knowledge and awareness of the vaccine in 480 postpartum women. Influenza vaccination rates increased from 19% to 31%. After the intervention, 51% of patients recalled that the vaccine was offered to them during the pregnancy as opposed to only 28% the year prior. Conclusion. Understanding the specific barriers to vaccination that our population faced was helpful in designing the interventions to improve knowledge and acceptance of influenza vaccination in pregnancy, which led to an increased vaccination rates in women.

Uptake of influenza vaccine in pregnant women during the 2009 H1N1 influenza pandemic

The goals of this study were to define the uptake of H1N1 and seasonal influenza vaccination during pregnancy among women delivering during the 2009 H1N1 pandemic and explore barriers to vaccination. All postpartum women at the Massachusetts General Hospital from January 2010 through March 2010 were invited to complete an anonymous questionnaire about demographics, vaccination status, and attitudes about vaccination during pregnancy. Among 370 participants (53% response rate), 81% accepted both the H1N1 and seasonal influenza vaccines during pregnancy. Patients who declined one or both vaccines cited concerns over safety as a major deterrent. Of the 36% of participants who reported having flu-like symptoms during this pregnancy only 8.6% took oseltamivir. While a high vaccination rate was identified in this study, further education is needed to reassure patients regarding vaccine safety. Education for providers and patients emphasizing the benefits of early treatment of pregnant women with flu-like symptoms should be a priority.

First-Trimester Cystic Hygroma: Relationship of Nuchal Translucency Thickness and Outcomes

OBJECTIVE: To estimate the relationship between nuchal translucency thickness and abnormal karyotype, major congenital anomaly, perinatal loss, and composite abnormal outcome in fetuses with first-trimester nuchal cystic hygroma. METHODS: We performed a retrospective cohort study of first-trimester fetuses with ultrasound-diagnosed nuchal cystic hygroma collected over a 10-year period. RESULTS: There were 944 first-trimester fetuses with nuchal cystic hygroma. A karyotype abnormality occurred in 54.9% (400 of 729) of fetuses. A major congenital anomaly occurred in 28.8% (61 of 212) of fetuses with a normal karyotype. Perinatal loss occurred in 39% (115 of 295) of fetuses not electively terminated. Overall, an abnormal outcome occurred in 86.6% (543 of 627) of fetuses. After adjusting for potential confounders, every 1-mm increase in nuchal translucency thickness increased the odds of an abnormal karyotype by 44% (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.29–1.60, P<.001), the odds of major congenital anomaly by 26% (adjusted OR 1.26, 95% CI, 1.08–1.47, P=.003), the odds of perinatal loss by 47% (adjusted OR 1.47, 95% CI 1.07–2.02, P=.019), and the odds of a composite abnormal outcome by 77% (adjusted OR 1.77, 95% CI 1.15–2.74, P=.01). CONCLUSION: First-trimester nuchal cystic hygroma is associated with high rates of karyotype abnormality, major congenital anomaly, perinatal loss, and abnormal outcome. As the thickness of the nuchal translucency increases, the odds of abnormal karyotype, major congenital anomaly, perinatal loss, and abnormal outcome increase. LEVEL OF EVIDENCE: II

ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells

Problem:  The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast.

Regulation of Nod1 and Nod2 in first trimester trophoblast cells.

Problem:  The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast.

Dendritic cells in the circulation of women with preeclampsia demonstrate a pro-inflammatory bias secondary to dysregulation of TLR receptors

Toll-like receptors (TLRs) are central components of the innate immune system that recognize both microbial ligands and host products released during tissue damage. Data from epidemiologic studies and animal models suggest that inappropriate activation of the immune system plays a critical role in the development of preeclampsia. This study evaluates in a systematic fashion the expression and function of TLRs in the circulation of patients with preeclampsia compared to healthy pregnant controls. We evaluated TLR expression and function in primary dendritic cells (DCs) of 30 patients with preeclampsia and 30 gestational age-matched healthy pregnant controls. DCs were stimulated with the different TLR ligands engaging TLR1/2, TLR2/6, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9. The expression of TLR-induced production of TNF-α, IFN-α, IL-6, and IL-12 were measured by multicolor flow cytometry. Basal expression of TLR3, TLR4 and TLR9 was significantly increased in DCs isolated from women with preeclampsia. Preeclamptic DCs also expressed significantly higher basal levels of cytokines. In contrast, preeclamptic DCs demonstrated a less robust response to stimulation with various TLR ligands as compared with healthy pregnant controls. Under basal conditions, DCs from preeclamptic individuals express higher levels of select TLRs and produce more pro-inflammatory cytokines as compared with healthy controls. As such, the ability of these cells to mount an inflammatory reaction in response to a TLR ligand is limited. These data demonstrate a dysregulated pattern of TLR expression and cytokine production in DCs from PE patients that may limit further activation by TLR engagement.

Longitudinal expression of Toll-like receptors on dendritic cells in uncomplicated pregnancy and postpartum

OBJECTIVE Toll-like receptors (TLRs) are integral parts of the innate immune system and have been implicated in complications of pregnancy. The longitudinal expression of TLRs on dendritic cells in the maternal circulation during uncomplicated pregnancies is unknown. The objective of this study was to prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal circulation at defined intervals throughout pregnancy and postpartum. STUDY DESIGN This was a prospective cohort of 30 pregnant women with uncomplicated pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was measured in unstimulated dendritic cells at 4 defined intervals during pregnancy and postpartum. Basal expression of TLRs and cytokines was measured by multicolor flow cytometry. The percent-positive dendritic cells for each TLRs were compared with both nonpregnant and postpartum levels with multivariate linear regression. RESULTS TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis factor alpha increased during pregnancy and returned to levels similar to nonpregnant controls during the postpartum period. The elevated levels of TLR 1 and IL-12 were persistent postpartum, challenging notions that immunologic changes during pregnancy resolve after the prototypical postpartum period. CONCLUSION Normal pregnancy is associated with time-dependent changes in TLR expression compared with nonpregnant controls; these findings may help elucidate immunologic dysfunction in complicated pregnancies.

Selected Viral Infections in Pregnancy

This article reviews the impact of seasonal influenza on pregnancy with particular emphasis on the 2009 novel H1N1 pandemic. Antiviral therapy for influenza, as well as recommendations and safety data on vaccination are discussed. In addition, the impact of hepatitis A, B, and C in pregnancy is addressed with a focus on prevention and treatment strategies for hepatitis B and C.

ORIGINAL ARTICLE: Antiphospholipid Antibodies Induce a Pro-Inflammatory Response in First Trimester Trophoblast Via the TLR4/MyD88 Pathway: EFFECT OF ANTI-β2GPI ANTIBODIES ON THE TROPHOBLAST

Problem  Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre‐eclampsia, and pre‐term labor. aPL target the placenta directly by binding to beta2‐glycoprotein I (β2GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved.