Ilona Goldfarb

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.

Use of the combined tetanus-diphtheria and pertussis vaccine during pregnancy.

OBJECTIVE A recent increase in pertussis cases prompted the Advisory Committee on Immunization Practices to recommend administering the perinatal tetanus, diphtheria, and pertussis (Tdap) vaccine during each pregnancy. We sought to describe uptake of Tdap and identify predictors of vaccination in pregnancy. STUDY DESIGN We conducted a retrospective study of all women delivering at a university hospital between February and June 2013. Demographic, pregnancy, and vaccination data were abstracted from the medical record. The relationship between maternal age, parity, gestational age, race/ethnicity, marital status, prenatal provider/site, insurance, influenza vaccination status, and Tdap vaccine was described by univariate analysis. Independent predictors were identified by multivariable logistic regression. RESULTS In our cohort of 1467 women, 1194 (81.6%) received a Tdap vaccine. After adjusting for potential confounders, 3 factors were found to be independent predictors of receiving the vaccine. Patients were more likely to receive Tdap if they had been vaccinated against influenza during this pregnancy (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.4-2.3). Black women were less likely to receive Tdap when compared with other women (aOR, 0.42; 95% CI, 0.27-0.67). Also, women who delivered preterm were less likely to receive the Tdap vaccine (aOR, 0.33; 95% CI, 0.22-0.48). CONCLUSION A high overall Tdap vaccination rate was observed following implementation of the Advisory Committee on Immunization Practices guidelines. Black women, however, had significantly lower vaccine uptake than other women. Further research is needed to understand and minimize this disparity. Women who delivered prematurely also had a decreased rate of Tdap vaccination; vaccinating earlier should be considered to better capture this population.

Wireless Fetal Heart Rate Monitoring in Inpatient Full-Term Pregnant Women: Testing Functionality and Acceptability

We tested functionality and acceptability of a wireless fetal monitoring prototype technology in pregnant women in an inpatient labor unit in the United States. Women with full-term singleton pregnancies and no evidence of active labor were asked to wear the prototype technology for 30 minutes. We assessed functionality by evaluating the ability to successfully monitor the fetal heartbeat for 30 minutes, transmit this data to Cloud storage and view the data on a web portal. Three obstetricians also rated fetal cardiotocographs on ease of readability. We assessed acceptability by administering closed and open-ended questions on perceived utility and likeability to pregnant women and clinicians interacting with the prototype technology. Thirty-two women were enrolled, 28 of whom (87.5%) successfully completed 30 minutes of fetal monitoring including transmission of cardiotocographs to the web portal. Four sessions though completed, were not successfully uploaded to the Cloud storage. Six non-study clinicians interacted with the prototype technology. The primary technical problem observed was a delay in data transmission between the prototype and the web portal, which ranged from 2 to 209 minutes. Delays were ascribed to Wi-Fi connectivity problems. Recorded cardiotocographs received a mean score of 4.2/5 (± 1.0) on ease of readability with an interclass correlation of 0.81(95%CI 0.45, 0.96). Both pregnant women and clinicians found the prototype technology likable (81.3% and 66.7% respectively), useful (96.9% and 66.7% respectively), and would either use it again or recommend its use to another pregnant woman (77.4% and 66.7% respectively). In this pilot study we found that this wireless fetal monitoring prototype technology has potential for use in a United States inpatient setting but would benefit from some technology changes. We found it to be acceptable to both pregnant women and clinicians. Further research is needed to assess feasibility of using this technology in busy inpatient settings.

Chromosomal microarray use among women undergoing invasive prenatal diagnosis

To study the offer and uptake of chromosomal microarray analysis (CMA) among women undergoing invasive prenatal testing.

Fetal and Placental DNA Stimulation of TLR9: A Mechanism Possibly Contributing to the Pro-inflammatory Events During Parturition

Introduction: While there is evidence for a relationship between cell-free fetal DNA (cffDNA) and parturition, questions remain regarding whether cffDNA could trigger a pro-inflammatory response on the pathway to parturition. We hypothesized that placental and/or fetal DNA stimulates toll-like receptor 9 (TLR9) leading to secretion of pro-inflammatory cytokines by macrophage cells. Methods: Four in vitro DNA stimulation studies were performed using RAW 264.7 mouse peritoneal macrophage cells incubated in media containing the following DNA particles: an oligodeoxynucleotide (ODN2395), intact genomic DNA (from mouse placentas, fetuses and adult liver), mouse DNA complexed with DOTAP (a cationic liposome forming compound), and telomere-depleted mouse DNA. Interleukin 6 (IL6) secretion was measured in the media by enzyme-linked immunosorbent assay; and the cell pellet was homogenized for protein content (picograms IL6/mg protein). Results: Robust IL6 secretion was observed in response to ODN2395 (a CpG-rich TLR9 agonist), mouse DNA-DOTAP complexes, and telomere-depleted mouse DNA in concentrations of 5 to 15 μg/mL. In contrast, ODN A151 (containing telomere sequence motifs), intact genomic mouse DNA, and restriction enzyme-digested DNA had no effect on IL6 secretion. The IL6 response was significantly inhibited by chloroquine (10 μg/mL), thereby confirming the important role for TLR9 in the response by macrophage cells. Conclusions: DNA derived from mouse placentas and fetuses, and depleted of telomeric sequences, stimulates a robust pro-inflammatory response by macrophage cells, thereby supporting the hypothesis that cffDNA is able to stimulate an innate immune response that could trigger the onset of parturition. These findings are of clinical importance, as we search for effective treatment/prevention of preterm parturition.

Association Between a Positive Screen on the STOP-BANG Obstructive Sleep Apnea Tool and Preeclampsia

INTRODUCTION: Obstructive sleep apnea (OSA) as diagnosed by polysomnography has been associated with preeclampsia and intrauterine growth restriction (IUGR). The use of validated screening tools in pregnancy is unknown. We sought to examine the association between a positive screen on one validated OSA tool, the STOP-BANG Questionnaire, and preeclampsia or IUGR. METHODS: We performed a cross sectional study of pregnant women admitted to the antepartum unit. Demographic and pregnancy data were obtained from the medical record. Obstructive sleep apnea screening was performed using the STOP-BANG Questionnaire. The relationship between OSA screen positive status and the preeclampsia or IUGR was analyzed using a &khgr;2 test for proportions and a multivariable logistic regression to control for potential confounders. RESULTS: One hundred three pregnant women participated in the study; 19 (18.3%) screened positive on the STOP-BANG Questionnaire. Forty-two percent of women who screened positive had pregnancies complicated by preeclampsia compared with 13% who screened negative (P=.003). This association was maintained after adjusting for potential confounders (adjusted odds ratio 6.1, 95% confidence interval 1.7–22.1). There was no association between screen positive status and IUGR. Fifty-three percent of participants stated they would accept a formal sleep study during pregnancy if recommended by their health care provider. There was no difference in acceptance rate between screen negative and positive patients (50% compared with 68% P=.146). CONCLUSION: In pregnancy, a positive screen on the STOP-BANG Questionnaire was associated with preeclampsia. Future studies are needed to validate the performance of this tool against polysomnography during pregnancy, which most participants stated they would be willing to complete.

Responsible Care in the Face of Shifting Recommendations and Imperfect Diagnostics for Zika Virus

The US Centers for Disease Control and Prevention (CDC) recently released updated interim guidance for when pregnant women should receive serologic testing for the Zika virus.1 The circumstances within which these recommendations emerge are complex: the public concern about the Zika virus is declining, the severity of epidemics around the globe is abating, and as a critical consideration in the development of recommendations, the rate of false-positive Zika virus test results (and the consequential unnecessary anxiety) is high. After more than 12 months of recommending serologic testing for all Zika-exposed pregnant women regardless of the nature, timing, and duration of exposure or symptoms, the CDC now recommends testing only for pregnant women who present with symptoms consistent with Zika infection or those with ongoing Zika exposure throughout pregnancy. The reasons cited by the CDC for these changes are sound from a public health standpoint and may help mitigate the risks associated with inflated rates of false-positive diagnoses. However, the new recommendations create challenges and complexities for the context of clinical care, as nuanced decisions about (and responsibilities for) testing of

Pregnant women’s attitudes toward Zika virus vaccine trial participation

INTRODUCTION As Zika virus infection during pregnancy can cause a range of congenital anomalies, pregnant women may be a target population for vaccination in future outbreaks. Their inclusion in vaccine trials is critical to ensure safe and effective vaccines in pregnancy. Though many vaccine candidates are in development, pregnant womens willingness to participate in Zika virus vaccine research is unknown. This study aims to describe pregnant womens attitudes toward Zika virus vaccine research participation, as well as perceived barriers to and facilitators of enrollment. METHODS Pregnant and recently postpartum women (n = 128) attending prenatal care at Massachusetts General Hospital completed surveys querying their willingness to participate in four hypothetical Zika virus vaccine trials and their motivations for participation. Demographics, information on prior Zika virus exposure, and vaccine acceptance were collected. RESULTS Most women (77%) accepted participation in at least one hypothetical Zika virus vaccine trial, and women were significantly more likely to accept prospective enrollment in an inactivated vaccine trial compared to a live-attenuated vaccine trial (p-value <0.0001) or a nucleic acid-based vaccine trial (p-value <0.0444). Important motivators for participation included evidence from research with pregnant and non-pregnant people, a desire to protect the baby from Zika, perceptions of vaccine safety, and provider recommendation. CONCLUSIONS A majority of women in this cohort were willing to participate in a Zika virus vaccine trial while pregnant, however, differences in acceptance exist between vaccine platforms. The high value placed on evidence by participants highlights the importance of gathering and communicating pregnancy-specific data to potential research participants and their providers. Womens motivations for accepting research participation during pregnancy are important to inform the Zika virus vaccine research agenda, candidate prioritization, and trial design.

The histologic evolution of revealed, acute abruptions☆☆☆★

There is considerable interest in using pathology to confirm acute abruptions. It has been suggested that pathologic findings can help to determine the timing of abruptions. Because of the dearth of evidence in the literature supporting this claim and its medicolegal implications, we undertook this study to explore further the possibility of timing abruptions by histopathology. We sought to correlate bleeding interval (duration from maternal presentation with vaginal bleeding [revealed abruption] to placental delivery) with placental histopathologic findings. We performed a retrospective review of clinical data and placental pathology from all cases of clinically diagnosed, acute, revealed abruptions at a single, large institution in New England between 2000 and 2015. Cases were identified based on clinical diagnoses, bleeding intervals were calculated from clinical notes, and histologic evaluations were performed by 2 pathologists blinded to the bleeding intervals. A total of 177 cases were analyzed. Of these, 103 (58%) had histologic findings corroborating the clinical diagnosis of abruption. The most frequent finding was maternal surface indentation (51 cases) followed by intravillous hemorrhage (50 cases). The former was also the earliest finding, with a minimum bleeding interval of 4 minutes. In multivariate modeling, plasma cell deciduitis was significantly associated with a longer bleeding interval (median 63 hours). If there were 2 pathologic findings, there was a trend toward a longer bleeding interval. There was modest sensitivity for the pathologic diagnosis of acute revealed abruption. Although there was not a clear, stepwise progression of histologic lesions; the presence of 2 or more findings tended to be seen with longer bleeding intervals. Our results suggest that histologic findings cannot be used to time acute revealed abruptions reliably, and any interpretation of such should be made with caution.