Noncandidal vaginitis: a comprehensive approach to diagnosis and management.

Vaginitis is one of the most common causes of patient visits to gynecologists, primary care providers, and urgent care centers. However, many women leave without a clear diagnosis or experience recurrent symptoms despite treatment. The 3 most common etiologies of vaginitis are trichomonas, bacterial vaginosis, and vulvovaginal candidiasis, which account for an estimated 70% of cases. The remaining 30% may be related to other causes of vaginitis, including atrophic vaginitis, desquamative inflammatory vaginitis, and vaginal erosive disease. The purpose of this review is to describe the noncandidal causes of acute and recurrent vaginitis, with the goal of improving the likelihood of accurate diagnosis as well as efficient and effective therapy. We excluded candidal vaginitis from our review because there was a recently published review on this topic in the Journal. The clinical presentation and evaluation of patients with symptoms of vaginitis can be triaged into 1 of 2 diagnostic pathways: noninflammatory and inflammatory vaginitis. The most common noninflammatory cause is bacterial vaginosis. Features such as irritation, purulent discharge, and the presence of polymorphonuclear neutrophils are more suggestive of an inflammatory process. Trichomoniasis is the most common cause of inflammatory vaginitis. Other well-described forms of inflammatory vaginitis include atrophic vaginitis, desquamative inflammatory vaginitis, and erosive disease. We present a review of the pathogenesis, symptoms, examination findings, diagnostic testing, and treatment for each of these causes of noncandidal vaginitis.

Influence of Sexually Transmitted Infections in Pregnant Adolescents on Preterm Birth and Chorioamnionitis.

Background: Adolescents have an increased risk of preterm birth (PTB) and sexually transmitted infections (STIs). We examined the prevalence and impact of STIs (gonorrhea, chlamydia, and trichomonas) on PTB and chorioamnionitis in pregnant adolescents. Methods: This retrospective cohort study utilized the first pregnancy delivered at an urban hospital among patients ≤ 19 years old over a 5-year period. Poisson regression with robust standard errors was used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) of the association between STIs and PTB (<37 weeks) and chorioamnionitis identified by clinical or placental pathology criteria. Results: 739 deliveries were included. 18.8% (n = 139) of births were preterm. The overall prevalence of STIs during pregnancy was 16.5% (Chlamydia trachomatis: 13.1%, n = 97; Trichomonas vaginalis: 3.7%, n = 27; and Neisseria gonorrheae: 3.1%, n = 23). Detection of C. trachomatis, T. vaginalis, or N. gonorrheae was not associated with increased PTB. While infection with N. gonorrheae and C. trachomatis did not increase the likelihood of any chorioamnionitis, infection with T. vaginalis significantly increased the likelihood of any chorioamnionitis diagnosis (aPR 2.19, 95% CI 1.26-3.83). Conclusion: In this adolescent population with a high rate of PTB, in whom most received appropriate STI treatment, we did not find an association between STI during pregnancy and an increased rate of PTB. However, an infection with T. vaginalis was associated with an increased likelihood of chorioamnionitis. Early detection of STIs may prevent adverse pregnancy outcomes. Continued vigilance in STI screening during pregnancy, including consideration of universal Trichomonas vaginalis screening, is merited in this high-risk population.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination.

OBJECTIVE: The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. METHODS: We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. RESULTS: 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. CONCLUSION: OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed.

Timing of Maternal COVID-19 Vaccine and Antibody Concentrations in Infants Born Preterm.

Importance: COVID-19 vaccine-derived antibodies in pregnant people may protect infants from severe infection in the first 6 months of life via transplacental antibody transfer. Few data exist on maternally derived SARS-CoV-2 antibodies in preterm compared with full-term infants in association with vaccination timing. Objective: To compare SARS-CoV-2 anti-Spike (anti-S) antibody levels in preterm and full-term infants in the context of vaccine dose timing before delivery. Design, Setting, and Participants: This prospective cohort study enrolled pregnant individuals and collected paired maternal and cord blood samples at delivery at the University of Washington between February 1, 2021, and January 31, 2023. Participants who had received at least 2 doses of a messenger RNA COVID-19 vaccine before delivery and did not have a history of prior COVID-19 infection or detectable anti-SARS-CoV-2 nucleocapsid antibodies were included. Exposures: Timing of the last vaccine dose and preterm or full-term gestational age at delivery. Main Outcomes and Measures: Paired maternal and cord samples were tested for anti-S antibody, and linear regression was used to evaluate associations between preterm delivery and anti-S antibody levels. Covariates included timing of last dose, number of doses, insurance status, and immunosuppressing medications. Results: A total of 220 participants (median [IQR] age, 34 [32-37] years; 212 [96.4%] female) with 36 preterm and 184 full-term deliveries were studied. Before delivery, 121 persons received 2 vaccine doses and 99 persons received 3 or more vaccine doses. The geometric mean concentration of maternal anti-S antibodies was 674 (95% CI, 577-787) after 2 doses and 8159 (95% CI, 6636-10 032) after 3 or more doses (P < .001). The cord anti-S antibody geometric mean concentration was 1000 (95% CI, 874-1144) after 2 doses and 9992 (95% CI, 8381-11 914) after 3 or more doses (P < .001). After adjustment for vaccine timing and number of doses before delivery, no association was found between preterm delivery and cord anti-S antibody levels (ß = 0.44; 95% CI, -0.06 to 0.94). Conclusions and Relevance: In this prospective cohort study of pregnant individuals with preterm and full-term deliveries, receipt of 3 or more compared with 2 doses of COVID-19 vaccine before delivery resulted in 10-fold higher cord anti-S antibody levels. Maternal antibody concentration appeared more important than delivery gestational age in determining cord anti-S antibody levels. The number of doses and timing considerations for COVID-19 vaccine in pregnancy should include individuals at risk for preterm delivery.

Transfer of Respiratory Syncytial Virus Prefusion F Protein Antibody in Low Birthweight Infants.

Background: Respiratory syncytial virus (RSV)-associated lower respiratory tract infection contributes significantly to morbidity/mortality worldwide in low birthweight (LBW) infants (<2500 g). Studies have demonstrated decreased maternal immunoglobulin G (IgG) transfer of various antibodies to LBW infants. We aimed to evaluate naturally acquired RSV anti-prefusion F protein (anti-preF) antibody transfer in pregnancies with LBW versus normal birthweight (NBW) infants. Methods: In this cohort study conducted among pregnant individuals and their infants, we tested paired maternal and singleton infant cord samples for RSV anti-preF IgG via an electrochemiluminescence immunoassay, using linear regression to evaluate associations between LBW and anti-preF IgG. Covariates included seasonality, insurance, small-for-gestational-age birthweight, and gestational age at delivery. Results: We tested maternal/cord RSV anti-preF IgG from 54 and 110 pregnancies with LBW and NBW infants, respectively. Of LBW infants, 22 (40.7%) were born both preterm and with small-for-gestational-age birthweight. The median (interquartile range) gestational age at delivery and birthweight were 34.0 (31.7-37.1) weeks and 1902 (1393-2276) g for LBW infants versus 39.1 (38.3-39.9) weeks and 3323 (3109-3565) g for NBW infants (both P < .001). In unadjusted comparisons, preterm infants had significantly lower cord anti-preF IgG levels and cord-maternal IgG ratios compared with full-term infants, while LBW infants had significantly lower cord-maternal IgG ratios than NBW infants (all P < .01). After adjustment for covariates, there was no difference in cord-maternal IgG ratios (ß =-0.29 [95% confidence interval, -.63 to .05]) between LBW and NBW infants. Conclusions: We documented robust transfer of maternal RSV anti-preF IgG in pregnancies with both LBW and NBW infants. Further studies are needed to assess immune protection in at-risk infants.

Evaluation of transplacental maternal SARS-CoV-2 antibody transfer in small for gestational age infants.

Little is known about the potential benefits of maternal immunization in the setting of high-risk pregnancies resulting in small-for-gestational-age (SGA) infants. This study compares transplacental transfer of maternal SARS-CoV-2 anti-Spike antibody in pregnancies with SGA compared to appropriate-for-gestational-age infants.

Human Papillomavirus Vaccine: The Cancer Prevention Moonshot.

Cervical cancer is the fourth most common cancer in women worldwide with immense associated morbidity and mortality. Although most of the cervical cancer cases are caused by the human papillomavirus (HPV) and can effectively be prevented by HPV vaccination, vaccination unfortunately remains underused on a global scale with vast inequities in distribution. A vaccine as a tool to prevent cancer, cervical and others, is largely unprecedented. Then why do HPV vaccination rates globally remain so low? This article explores the burden of disease, development of the vaccine and its subsequent uptake, cost-effectiveness, and associated equity issues.

Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV.

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform ('Policy1-Cervix-HIV') to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7-33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3-5 years.

Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population.

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix, to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63-67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO's updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.

Analysis of Vaccine Reactions After COVID-19 Vaccine Booster Doses Among Pregnant and Lactating Individuals.

Importance: COVID-19 vaccine boosters or third doses are recommended for adolescents and adults who completed their initial COVID-19 vaccine course more than 5 months prior. Minimal data are available on COVID-19 vaccine booster or third dose reactogenicity among pregnant and lactating individuals. Objective: To describe the reactions to the booster or third dose of the COVID-19 vaccine and vaccine experiences among pregnant and lactating individuals. Design, Setting, and Participants: Beginning in October 2021, a follow-up Research Electronic Data Capture (REDCap) survey regarding a COVID-19 vaccine booster or third dose was sent to 17 504 participants in an ongoing online prospective cohort study on COVID-19 vaccines among pregnant and lactating individuals. A convenience sample of adults enrolled in the online prospective study who were pregnant, lactating, or neither pregnant nor lactating at the time of their booster or third dose was eligible for this follow-up survey; 17 014 (97.2%) completed the follow-up survey. Exposure: Receipt of a booster or third dose of the COVID-19 vaccine. Main Outcomes and Measures: Self-reported vaccine reactions less than 24 hours after the dose. Results: As of April 4, 2022, 17 014 eligible participants (mean [SD] age, 33.3 [3.5] years) responded to the booster or third dose survey; of these, 2009 (11.8%) were pregnant at the time of their booster or third dose, 10 279 (60.4%) were lactating, and 4726 (27.8%) were neither pregnant nor lactating. After a COVID-19 booster or third dose, most individuals (14 074 of 17 005 [82.8%]) reported a local reaction, and 11 542 of 17 005 (67.9%) reported at least 1 systemic symptom. Compared with individuals who were neither pregnant nor lactating, pregnant participants were more likely to report any local reaction to a COVID-19 booster or third dose (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.4; P = .01) but less likely to report any systemic reaction (aOR, 0.7; 95% CI, 0.6-0.8; P < .001). Most pregnant (1961 of 2009 [97.6%]) and lactating (9866 of 10 277 [96.0%]) individuals reported no obstetric or lactation concerns after vaccination. Conclusions and Relevance: This study suggests that COVID-19 vaccine boosters or third doses were well tolerated among pregnant and lactating individuals. Data to evaluate tolerability of boosters or additional doses among pregnant and lactating individuals will be important as they are considered for these populations.

Correlates of cervical cancer screening among women living with HIV in Kenya: A cross-sectional study.

OBJECTIVE: Cervical cancer is the leading cause of cancer-related death among Kenyan women. It is important to identify how demographics and knowledge of cervical cancer are associated with screening to determine best practices for targeted screening efforts. METHODS: We conducted a sub-analysis of women who were asked about cervical cancer from a cross-sectional study of women attending large HIV care and treatment programs across Kenya between June and September 2016. RESULTS: 1671 of 3007 (56%) women reported ever being screened, 804 (48%) of whom were screened within the last 12 months. Prevalence of screening was highest among women who were older (adjusted prevalence ratio [APR] age 35-49 vs. 18-24: 2.26, 95% CI: 1.68-3.05, P < 0.001), employed (APR: 1.55, 95% CI: 1.24-1.93, P < 0.001), married (APR: 1.27, 95% CI: 1.01-1.59, P = 0.047), had at least secondary education (APR: 1.45, 95% CI: 1.19-1.77, P < 0.001), with longer time since HIV diagnosis (APR: 1.09/year average increase, 95% CI: 1.04-1.13, P < 0.001). 36% knew cervical cancer is treatable. CONCLUSION: Characteristics linked to social or economic capital are correlated with cervical cancer screening. Integrating cervical cancer screening into HIV care and educating patients on the need for annual screening and potential treatment are important strategies for increasing screening uptake.

Cervical cancer screening and treatment, HIV infection, and age: Program implementation in seven regions of Namibia.

The aim of this study was to assess differences in cervical cancer screening and treatment outcomes by HIV status in a routine programmatic setting with a high generalized HIV prevalence. Women living with HIV (WLHIV) are at heightened risk of developing cervical cancer and the World Health Organization recommends all WLHIV who are sexually active be screened, regardless of age. In 2018, Namibia's Ministry of Health and Social Services introduced a screen-and-treat approach using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy or thermocoagulation with a focus on screening HIV-positive women due to Namibia's 11.5% prevalence of HIV in women aged 15-49. Using program data from October 2018 to March 2020 from seven of the country's 14 regions, we calculated descriptive statistics and chi-square tests to test the statistical significance of differences in VIA-positivity, ineligibility for ablative treatment, treatment completion, and same day treatment completion by HIV status. Between October 2018 and March 2020, the program conducted 14,786 cervical cancer screenings. Among 8,150 women who received their first VIA screening, more WLHIV screened VIA-positive (17%) than HIV-negative women (15%). This difference was statistically significant (p = 0.02). Among 2,272 women who screened VIA-positive at any screening, 1,159 (82%) completed ablative treatment. This suggests ablative treatment is feasible and acceptable in resource-limited settings. WLHIV were also more likely to complete treatment than HIV-negative women (p<0.01). Differences in health seeking behavior of sub-populations as well as resource availability between service delivery points should be considered for further investigation. Going forward in order to strengthen program implementation and expand screening access and uptake further investigation is needed to determine cancer incidence by HIV status, age, and time since last screening to assess cases that are averted as well as potential rates of overtreatment.

Achieving high coverage of H1N1 influenza vaccine in an ethnically diverse obstetric population: success of a multifaceted approach.

OBJECTIVE: To report on a multifaceted approach to increase uptake of the H1N1 vaccine in our ethnically diverse obstetrical population. METHODS: A review of our obstetric clinic vaccine registry and the approaches used to increase vaccine uptake. We created a real-time vaccine registry, educated patients in their own language via educational videos and use of cultural case workers, facilitated patient appointments and transportation, educated staff, and used other interventions to enhance immunization uptake. RESULTS: Within the first month of H1N1 availability, we vaccinated 120 of our total 157 obstetrics patients. Our overall coverage rate was 76% (number vaccinated/total number eligible.) Of the enrolled patients, the vaccine acceptance rates were similar in our English (59 (78%) of 76) versus non-English (59 (75%) of 79) speaking patients. CONCLUSIONS: High vaccine coverage is possible in an ethnically diverse, highly immigrant obstetrics population.

Antibody responses to prophylactic quadrivalent human papillomavirus vaccine at 48 months among HIV-infected girls and boys ages 9-14 in Kenya, Africa.

OBJECTIVES: HIV infected children remain at increased risk of HPV associated malignancies as they initiate sexual activity. Though they mount a vigorous immune response to the quadrivalent human papillomavirus (QHPV-6, -11,-16, and -18; Gardasil®) vaccine, durability of the immune response is uncertain. We assessed antibody responses to HPV 6, -11, -16 and -18 for up to 48 months following administration of quadrivalent human papillomavirus vaccine in HIV-infected girls and boys ages 9-14 years in Kenya. DESIGN: Of 178 girls and boys who had previously received three doses of the quadrivalent HPV vaccine, 176 enrolled into extended follow up for 4 years. HPV antibodies to -6, -11, -16 and -18 were measured at 24, 36 and 48 months after the first vaccine dose using the total immunoglobulin G immunoassay (IgG LIA). We evaluated the magnitude and trend in HPV vaccine response and the effect of plasma HIV-1 RNA on HPV vaccine response from month 24 to month 48 of follow up. RESULTS: At re-enrollment, 24 months after initial vaccination, median age of participants was 14 years (range 11-17); 167 (95%) were receiving antiretroviral therapy and 110 (66%) had plasma HIV RNA < 40 copies/mL. The rate of HPV seropositivity at 48 months was 83% for HPV-6; 80% for HPV-11; 90% for HPV-16; and 77% for HPV-18. There was a plateau in mean log10 HPV-specific antibody titer between month 24 and 48. The mean log10 HPV-type specific antibody titer for children with undetectable HIV viral load (<40) at the time of vaccination consistently remained higher for the 48 months of follow up compared to children with detectable viral load. CONCLUSION: Children with HIV infection may retain long term antibody response following HPV immunization. Further work to define whether HIV-infected children are protected from HPV acquisition with low levels of HPV antibodies is needed.

A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities.

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.

Validating Claims-Based Algorithms Determining Pregnancy Outcomes and Gestational Age Using a Linked Claims-Electronic Medical Record Database.

INTRODUCTION: Pregnancy outcome identification and precise estimates of gestational age (GA) are critical in drug safety studies of pregnant women. Validated pregnancy outcome algorithms based on the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) have not previously been published. METHODS: We developed algorithms to classify pregnancy outcomes and estimate GA using ICD-10-CM/PCS and service codes on claims in the 2016-2018 IBM® MarketScan® Explorys® Claims-EMR Data Set and compared the results with ob-gyn adjudication of electronic medical records (EMRs). Obstetric services were grouped into episodes using hierarchical and spacing requirements. GA was based on evidence with the highest clinical accuracy. Among pregnancies with obstetric EMRs, 100 full-term live births (FTBs), 100 preterm live births (PTBs), 100 spontaneous abortions (SAs), and 24 stillbirths were selected for review. Physicians adjudicated cases using Global Alignment of Immunization safety Assessment in pregnancy (GAIA) definitions applied to structured EMRs. RESULTS: The claims-based algorithms identified 34,204 pregnancies, of which 9.9% had obstetric EMRs. Of sampled pregnancies, 92 FTBs, 93 PTBs, 75 SAs, and 24 stillbirths were adjudicated. Among these pregnancies, the percent agreement was 97.8%, 62.4%, 100.0%, and 70.8% for FTBs, PTBs, SAs, and stillbirths, respectively. The percent agreement on GA within 7 and 28 days, respectively, was 85.9% and 100.0% for FTBs, 81.7% and 98.9% for PTBs, 61.3% and 94.7% for SAs, and 66.7% and 79.2% for stillbirths. CONCLUSIONS: The pregnancy outcome algorithms had high agreement with physician adjudication of EMRs and may inform post-market maternal safety surveillance.

Applicability of the GAIA Maternal and Neonatal Outcome Case Definitions for the Evaluation of Adverse Events Following Vaccination in Pregnancy in High-income Countries.

BACKGROUND: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. METHODS: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. RESULTS: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. CONCLUSIONS: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.

Obstetrics risk Assessment: Evaluation of selection criteria for vaccine research studies in pregnant women.

Vaccines designed for use in pregnancy and vaccine trials specifically involving pregnant women are rapidly expanding. One of the key challenges in designing maternal immunization trials is that developing exclusion criteria requires understanding and quantifying the background risk for adverse pregnancy outcomes in the pregnancy being studied, which can occur independent of any intervention and be unrelated to vaccine administration. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project has developed and published case definitions and guidelines for data collection, analysis, and evaluation of maternal immunization safety in trials involving pregnant women. Complementing this work, we sought to understand how to best assess obstetric risk of adverse outcomes and differentiate it from the assessment of vaccine safety. Quantification of obstetric risk is based on prior and current obstetric, and maternal medical history. We developed a step-wise approach to evaluate and quantify obstetric and maternal risk factors in pregnancy based on review of published literature and guidelines, and critically assessed these factors in the context of designing inclusion and exclusion criteria for maternal vaccine studies. We anticipate this risk assessment evaluation may assist clinical trialists with study design decisions, including selection of exclusion criteria for vaccine trials involving pregnant women, consideration of sub-group classification, such as high or low risk subjects, or schedule considerations, such as preferred trimester of gestation for an intervention during pregnancy. Additionally, this tool may be utilized in data stratification at time of study analyses.