A latent class analysis of factors influencing preferences for infant respiratory syncytial virus (RSV) preventives among pregnant people in the United States.

A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups of pregnant people with different preferences for RSV preventives and respondent characteristics associated with subgroup membership. An online survey, including a discrete choice experiment (DCE), was conducted among US pregnant people. RSV preventive attributes included effectiveness, duration of protection during RSV season, injection recipient/timing, preventive type (vaccine or mAb), and type of visit required to receive injection. In DCE choice tasks, pregnant people selected between two hypothetical preventive profiles with varying attribute-levels and a no-preventive option. Logistic regression, including latent class analysis (LCA), was used to analyze the data. Of 992 pregnant people (mean age: 30.0 years), 60.3% were expecting their second/later birth. LCA identified three preference subgroups: 'Effectiveness' (preventive choice mostly driven by increases in effectiveness; 51.4% class membership probability), 'Season' (preventive choice mostly driven by improvement in duration of protection during the RSV season; 39.2% class membership probability), and 'No Preventive' (frequently chose no-preventive option; 9.4% class membership probability). 'Effectiveness' and 'Season' preferred maternal vaccine over mAb; mAb was preferred by 'No Preventive.' Perceiving RSV as serious for infants, higher health literacy, and lower household income were associated with 'Effectiveness.' Perceiving RSV as serious for pregnant people was associated with 'Season.' Perceiving RSV to not be serious for pregnant people and not being employed were associated with 'No Preventive.' Subgroups of pregnant people vary in preferences for RSV preventives. Most pregnant people preferred a maternal vaccine, although some may be more willing to accept alternative preventive options.

Pathogenic variant detection rate varies considerably in male breast cancer families and sporadic cases: minimal additional contribution beyond BRCA2, BRCA1 and CHEK2.

BACKGROUND: Male breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying component of high and moderate risk gene pathogenic variants (PVs) than female breast cancer, particularly in BRCA2. However, most studies only report overall detection rates without assessing detailed family history. METHODS: We reviewed germline testing in 204 families including at least one MBC for BRCA1, BRCA2, CHEK2 c.1100DelC and an extended panel in 93 of these families. Individuals had MBC (n=118), female breast cancer (FBC)(n=80), ovarian cancer (n=3) or prostate cancer-(n=3). Prior probability of having a BRCA1/2 PV was assessed using the Manchester Scoring System (MSS). RESULTS: In the 204 families, BRCA2 was the major contributor, with 51 (25%) having PVs, followed by BRCA1 and CHEK2, with five each (2.45%) but no additional PVs identified, including in families with high genetic likelihood on MSS. Detection rates were 85.7% (12/14) in MSS ≥40 and 65.5% with MSS 30-39 but only 12.8% (6/47) for sporadic breast cancer. PV rates were low and divided equally between BRCA1/2 and CHEK2. CONCLUSION: As expected, BRCA2 PVs predominate in MBC families with rates 10-fold those in CHEK2 and BRCA1. The MSS is an effective tool in assessing the likelihood of BRCA1/2 PVs.

Germline testing of BRCA1, BRCA2, PALB2 and CHEK2 c.1100delC in 1514 triple negative familial and isolated breast cancers from a single centre, with extended testing of ATM, RAD51C and RAD51D in over 400.

BACKGROUND: The identification of germline pathogenic gene variants (PGVs) in triple negative breast cancer (TNBC) is important to inform further primary cancer risk reduction and TNBC treatment strategies. We therefore investigated the contribution of breast cancer associated PGVs to familial and isolated invasive TNBC. METHODS: Outcomes of germline BRCA1, BRCA2 and CHEK2_c.1100delC testing were recorded in 1514 women (743-isolated, 771-familial), and for PALB2 in 846 women (541-isolated, 305-familial), with TNBC and smaller numbers for additional genes. Breast cancer free controls were identified from Predicting Risk Of Cancer At Screening and BRIDGES (Breast cancer RIsk after Diagnostic GEne Sequencing) studies. RESULTS: BRCA1_PGVs were detected in 52 isolated (7.0%) and 195 (25.3%) familial cases (isolated-OR=58.9, 95% CI: 16.6 to 247.0), BRCA2_PGVs in 21 (2.8%) isolated and 67 (8.7%) familial cases (isolated-OR=5.0, 95% CI: 2.3 to 11.2), PALB2_PGVs in 9 (1.7%) isolated and 12 (3.9%) familial cases (isolated-OR=8.8, 95% CI: 2.5 to 30.4) and CHEK2_c.1100delC in 0 isolated and 3 (0.45%) familial cases (isolated-OR=0.0, 95% CI: 0.00 to 2.11). BRCA1_PGV detection rate was >10% for all familial TNBC age groups and significantly higher for younger diagnoses (familial: <50 years, n=165/538 (30.7%); ≥50 years, n=30/233 (12.9%); p<0.0001). Women with a G3_TNBC were more likely to have a BRCA1_PGV as compared with a BRCA2 or PALB2_PGV (p<0.0001). 0/743 isolated TNBC had the CHEK2_c.1100delC PGV and 0/305 any ATM_PGV, but 2/240 (0.83%) had a RAD51D_PGV. CONCLUSION: PGVs in BRCA1 are associated with G3_TNBCs. Familial TNBCs and isolated TNBCs <30 years have a >10% likelihood of a PGV in BRCA1. BRCA1_PGVs are associated with younger age of familial TNBC. There was no evidence for any increased risk of TNBC with CHEK2 or ATM PGVs.

Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Positive Childhood Experiences and Chronic Pain Among Children and Adolescents in the United States.

Positive childhood experiences (PCEs) are associated with better mental and physical health outcomes and moderate the negative effects of adverse childhood experiences (ACEs). However, knowledge of the associations between PCEs and childhood chronic pain is limited. We conducted a cross-sectional analysis of 2019 to 2020 National Survey of Children's Health (NSCH) to evaluate associations between PCEs and childhood chronic pain. Parents of 47,514 children ages 6 to 17 years old reported on their child's exposure to 7 PCEs and 9 ACEs. Associations between PCEs and chronic pain were evaluated using weighted, multivariate logistic regression analyses adjusted for sociodemographic factors. We found that PCEs had dose-dependent associations with pediatric chronic pain; children exposed to higher numbers of PCEs (5-7 PCEs) had the lowest reported rate of chronic pain (7.1%), while children exposed to 2 or fewer PCEs had the highest rate of chronic pain (14.7%). The adjusted analysis confirmed that children experiencing 5 to 7 PCEs had significantly lower odds of chronic pain relative to children experiencing 0 to 2 PCEs (adjusted odds ratio (aOR): .47, 95% confidence interval (CI): .39-.61, P < .0001). PCEs moderated associations between ACEs and chronic pain: among children reporting 2 or more ACEs, those reporting 5 to 7 PCEs were significantly less likely to report chronic pain as compared to children only reporting 0 to 2 PCEs (aOR: .64, 95%CI: .45-.89, P = .009). In conclusion, children with greater PCEs exposure had lower prevalence rates of chronic pain. Furthermore, PCEs was associated with reduced prevalence of chronic pain among children exposed to ACEs. PERSPECTIVE: This article estimates associations between survey-measured PCEs and pediatric chronic pain among children in the United States. Promoting PCEs could improve pediatric pain outcomes.

Combination of Fundal Height and Ultrasound to Predict Small for Gestational Age at Birth.

OBJECTIVE: The objective of the study was to determine whether adding longitudinal measures of fundal height (FH) to the standard cross-sectional FH to trigger third trimester ultrasound estimated fetal weight (EFW) would improve small for gestational age (SGA) prediction. STUDY DESIGN: We developed a longitudinal FH calculator in a secondary analysis of a prospective cohort study of 1,939 nonobese pregnant women who underwent serial FH evaluations at 12 U.S. clinical sites. We evaluated cross-sectional FH measurement ≤ -3 cm at visit 3 (mean: 32.0 ± 1.6 weeks) versus the addition of longitudinal FH up to and including visit 3 to trigger an ultrasound to diagnose SGA defined as birth weight <10th percentile. If the FH cut points were not met, the SGA screen was classified as negative. If FH cut points were met and EFW was <10th percentile, the SGA screen was considered positive. If EFW was ≥10th percentile, the SGA screen was also considered negative. Sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were computed. RESULTS: In a comparison of methods, 5.8% of women were classified as at risk of SGA by both cross-sectional and longitudinal classification methods; cross-sectional FH identified an additional 4.0%, and longitudinal fundal height identified a separate, additional 4.5%.Using cross-sectional FH as an ultrasound trigger, EFW had a PPV and NPV for SGA of 69 and 92%, respectively. After adding longitudinal FH, PPV increased to 74%, whereas NPV of 92% remained unchanged; however, the number of women who underwent triggered EFW decreased from 9.7 to 5.7%. CONCLUSION: An innovative approach for calculating longitudinal FH to the standard cross-sectional FH improved identification of SGA birth weight, while simultaneously reducing the number of triggered ultrasounds. As an essentially free-of-charge screening test, our novel method has potential to decrease costs as well as perinatal morbidity and mortality (through better prediction of SGA). KEY POINTS: · We have developed an innovative calculator for fundal height trajectory.. · Longitudinal fundal height improves detection of SGA.. · As a low cost screening test, the fundal height calculator may decrease costs and morbidity through better prediction of SGA..

Healthcare claims-based Lyme disease case-finding algorithms in the United States: A systematic literature review.

BACKGROUND AND OBJECTIVE: Lyme disease (LD) is the fifth most commonly reported notifiable infectious disease in the United States (US) with approximately 35,000 cases reported in 2019 via public health surveillance. However, healthcare claims-based studies estimate that the number of LD cases is >10 times larger than reported through surveillance. To assess the burden of LD using healthcare claims data and the effectiveness of interventions for LD prevention and treatment, it is important to use validated well-performing LD case-finding algorithms ("LD algorithms"). We conducted a systematic literature review to identify LD algorithms used with US healthcare claims data and their validation status. METHODS: We searched PubMed and Embase for articles published in English since January 1, 2000 (search date: February 20, 2021), using the following search terms: (1) "Lyme disease"; and (2) "claim*" or "administrative* data"; and (3) "United States" or "the US*". We then reviewed the titles, abstracts, full texts, and bibliographies of the articles to select eligible articles, i.e., those describing LD algorithms used with US healthcare claims data. RESULTS: We identified 15 eligible articles. Of these, seven studies used LD algorithms with LD diagnosis codes only, four studies used LD diagnosis codes and antibiotic dispensing records, and the remaining four studies used serologic test order codes in combination with LD diagnosis codes and antibiotics records. Only one of the studies that provided data on algorithm performance: sensitivity 50% and positive predictive value 5%, and this was based on Lyme disease diagnosis code only. CONCLUSIONS: US claims-based LD case-finding algorithms have used diverse strategies. Only one algorithm was validated, and its performance was poor. Further studies are warranted to assess performance for different algorithm designs and inform efforts to better assess the true burden of LD.

Travelers' preferences for tick-borne encephalitis vaccination.

BACKGROUND: This study aimed to quantify preferences and risk tolerance for a tick-borne encephalitis (TBE) vaccination. RESEARCH DESIGN AND METHODS: A stated-preference survey instrument was administered to international travelers living in the United States to elicit preferences for a no-cost TBE vaccine when planning an international trip, conditional upon four different qualitative levels of endemic TBE risk. RESULTS: The likelihood of choosing the vaccine increased with a destination's level of endemic risk. Most respondents (94%) would choose to receive the vaccine at the highest risk level presented in the survey (i.e. when multiple TBE cases among humans are reported year after year); 6% of the sample would choose not to receive the vaccine at any risk level. Respondents who engage in outdoor activities were twice as likely as the average respondent to choose vaccination rather than opting out of vaccination, and were one-third more likely than the average respondent to choose to receive the vaccine at the lowest risk level. CONCLUSIONS: Respondents were highly interested in a TBE vaccine, assuming no cost, and most were willing to be vaccinated at all qualitative TBE risk levels. Respondents who participated in outdoor activities were more likely than the average respondent to choose the vaccine.

Cost-utility and cost-benefit analysis of pediatric PCV programs in Egypt.

New vaccine introductions (NVIs) raise issues of value for money (VfM) for self-financing middle-income countries like Egypt. We evaluate a pediatric pneumococcal conjugate vaccine (PCV) NVI in Egypt from health payer and societal perspectives, using cost-utility and cost-benefit analysis (CUA, CBA). We evaluate vaccinating 100 successive birth cohorts with the 13-valent PCV ("PCV13") and the 10-valent PCV ("PCV10") relative to no vaccination and each other. We quantify health effects with a disease incidence projection model and a multiple-cohort static disease model. Our CBA uses a health-augmented lifecycle model to generate willingness-to-pay for health gains from which we calculate rates of return (RoR). We obtain parameters from the published literature. We perform deterministic and probabilistic sensitivity analysis. Our base-case CUA finds incremental cost-effectiveness ratios (ICERs) for PCV13 and PCV10 relative to no program of $926 (95% confidence interval $512-$1,735) and $1,984 ($1,186-$3,805) per quality-adjusted life year (QALY), respectively; and for PCV13 relative to PCV10 of $174 ($88-$331) per QALY. Our base-case CBA finds RoRs to PCV13 and PCV10 relative to no program of 488% (188-993%) and 164% (33-336%), respectively, and to PCV13 relative to PCV10 of 3109% (1410-6602%). Both CUA and CBA find PCV13 to be good VfM relative to PCV10.

County-level vaccination coverage and rates of COVID-19 cases and deaths in the United States: An ecological analysis.

BACKGROUND: On Dec 14, 2020, the United States initiated a nationwide COVID-19 vaccination campaign. Demonstrating clear population-level impact following vaccine introduction helps to further elucidate and quantify the public-health benefits of vaccination. METHODS: Using a negative binomial regression model we evaluated the ecological association between county-level COVID-19 vaccine uptake and rates of COVID-19 cases and deaths in the United States from April 1, 2021 through October 31, 2021 controlling for a broad set of county-level environmental, sociodemographic, economic, and health-status-related characteristics. County-level data were obtained from several publicly available databases that were merged for analysis. FINDINGS: After adjustment for county-level characteristics, US counties with ≥ 80% of their residents ≥ 12 years of age fully vaccinated against COVID-19 had 30% (95% CI: 25-35; P < .001) and 46% (38-52; P < .001) lower rates of COVID-19 cases and deaths, respectively, versus those with <50% coverage (reference group). A dose response was observed: counties with 70-79% uptake had 20% (95% CI: 16-24; P < .001) and 35% (29-40; P < .001) lower rates of cases and deaths, respectively; counties with 60-69% uptake had 8% (5-11; P < .001) and 20% (15-24; P < .001) lower rates; and counties with 50-59% uptake had 2% (0-4; P =.09) and 8% (4-12; P < .001) lower rates. Restricting the analysis to the period when the Delta variant was predominant (June 1, 2021 ‒ October 31, 2021) showed similar findings. INTERPRETATION: Our results showed that US counties with higher proportions of persons ≥ 12 years of age fully vaccinated against COVID-19 had substantially lower rates of COVID-19 cases and deaths-a finding that showed dose response and persisted even in the period when Delta was predominant. FUNDING: Pfizer.

County-level Predictors of Coronavirus Disease 2019 (COVID-19) Cases and Deaths in the United States: What Happened, and Where Do We Go from Here?

BACKGROUND: The United States has been heavily impacted by the coronavirus disease 2019 (COVID-19) pandemic. Understanding microlevel patterns in US rates of COVID-19 can inform specific prevention strategies. METHODS: Using a negative binomial mixed-effects regression model, we evaluated the associations between a broad set of US county-level sociodemographic, economic, and health status-related characteristics and cumulative rates of laboratory-confirmed COVID-19 cases and deaths between 22 January 2020 and 31 August 2020. RESULTS: Rates of COVID-19 cases and deaths were higher in US counties that were more urban or densely populated or that had more crowded housing, air pollution, women, persons aged 20-49 years, racial/ethnic minorities, residential housing segregation, income inequality, uninsured persons, diabetics, or mobility outside the home during the pandemic. CONCLUSIONS: To our knowledge, this study provides results from the most comprehensive multivariable analysis of county-level predictors of rates of COVID-19 cases and deaths conducted to date. Our findings make clear that ensuring that COVID-19 preventive measures, including vaccines when available, reach vulnerable and minority communities and are distributed in a manner that meaningfully disrupts transmission (in addition to protecting those at highest risk of severe disease) will likely be critical to stem the pandemic.

Maternal Socioeconomic Factors and Racial/Ethnic Differences in Neonatal Anthropometry.

Disparities in birthweight by maternal race/ethnicity are commonly observed. It is unclear to what extent these disparities are correlates of individual socioeconomic factors. In a prospective cohort of 1645 low-risk singleton pregnancies included in the NICHD Fetal Growth Study (2009-2013), neonatal anthropometry was measured by trained personnel using a standard protocol. Socioeconomic characteristics included employment status, marital status, health insurance, annual income, and education. Separate adjusted generalized linear models were fit to both test the effect of race/ethnicity and the interaction of race/ethnicity and socioeconomic characteristics on neonatal anthropometry. Mean infant birthweight, length, head circumference, and abdominal circumference all differed by race/ethnicity (p < 0.001). We observed no statistically significant interactions between race/ethnicity and full-time employment/student status, marital status, insurance, or education in association with birthweight, neonatal exam weight, length, or head or abdominal circumference at examination. The interaction between income and race/ethnicity was significant only for abdominal circumference (p = 0.027), with no other significant interactions for other growth parameters, suggesting that racial/ethnic differences in neonatal anthropometry did not vary by individual socioeconomic factors in low-risk women. Our results do not preclude structural factors, such as lifetime exposure to poverty, as an explanation for racial/ethnic disparities.

Estimating the Impact of Switching from a Lower to Higher Valent Pneumococcal Conjugate Vaccine in Colombia, Finland, and The Netherlands: A Cost-Effectiveness Analysis.

INTRODUCTION: Widespread use of ten-valent (Synflorix™, GSK) or 13-valent (Prevenar 13™; Pfizer) conjugate vaccination programs has effectively reduced invasive pneumococcal disease (IPD) globally. However, IPD caused by serotypes not contained within the respective vaccines continues to increase, notably serotypes 3, 6A, and 19A in countries using lower-valent vaccines. Our objective was to estimate the clinical and economic benefit of replacing PCV10 with PCV13 in Colombia, Finland, and The Netherlands. METHODS: Country-specific databases, supplemented with published and unpublished data, informed the historical incidence of pneumococcal disease as well as direct and indirect medical costs. A decision-analytic forecasting model was applied, and both costs and outcomes were discounted. The observed invasive pneumococcal disease (IPD) trends from each country were used to forecast the future number of IPD cases given a PCV13 or PCV10 program. RESULTS: Over a 5-year time horizon, a switch to a PCV13 program was estimated to reduce overall IPD among 0-2 year olds by an incremental - 37.6% in Colombia, - 32.9% in Finland, and - 26% in The Netherlands, respectively, over PCV10. Adults > 65 years experienced a comparable incremental decrease in overall IPD in Colombia (- 32.2%), Finland (- 15%), and The Netherlands (- 3.7%). Serotypes 3, 6A, and 19A drove the incremental decrease in disease for PCV13 over PCV10 in both age groups. A PCV13 program was dominant in Colombia and Finland and cost-effective in The Netherlands at 1 × GDP per capita (€34,054/QALY). CONCLUSION: In Colombia, Finland, and The Netherlands, countries with diverse epidemiologic and population distributions, switching from a PCV10 to PCV13 program would significantly reduce the burden of IPD in all three countries in as few as 5 years.

Estimating the population health and economic impacts of introducing a pneumococcal conjugate vaccine in Malaysia- an economic evaluation.

Pneumococcal disease is a potentially fatal bacterial infection that is vaccine-preventable. Malaysia has yet to adopt a pneumococcal conjugate vaccine (PCV) into its national immunization program (NIP). In 2016, pneumonia was the 3rd leading cause of death in children under five in Malaysia, accounting for 3.8% of under-five deaths. Introducing a pneumococcal conjugate vaccine (PCV) is an effective strategy to reduce the disease burden. This study used a decision-analytic model to assess the potential impacts of introducing the available PCVs (13-valent and 10-valent) in Malaysia. Epidemiological and costs inputs were sourced from published literature. For each vaccination program, health outcomes and associated healthcare costs were estimated. The scenarios of initiating PCV13 vs. PCV10 and the status quo (no pneumococcal vaccine) were compared. Serotype trends of Finland and the U.K. were used to model the clinical impacts of PCV10 and PCV13 respectively. The base-case analysis used a societal perspective over a 5-year time horizon. Compared with PCV10, PCV13 was projected to avert an additional 190,628 cases of pneumococcal disease and 1126 cases of death. The acquisition of PCV13 was estimated to cost an incremental US$89,904,777, offset by a cost reduction of -US$250,219,914 on pneumococcal disease-related medical care and lost productivity. PCV13 demonstrated a higher cost-saving potential over PCV10. Compared with no vaccination, PCV13 was estimated as cost-saving. Results were robust across a series of sensitivity analyses. The introduction of PCV13 in a NIP was estimated to reduce a significant burden of disease and to be a cost-saving for the Malaysian health system.

Estimating the Clinical and Economic Impact of Switching from the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) to the 10-Valent Pneumococcal Conjugate Vaccine (PCV10) in Italy.

Background: Invasive and non-invasive pneumococcal diseases are significant health and economic burdens, especially in children and the elderly. Italy included the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the National Immunization Program in 2007 and 2010, respectively, allowing a dramatic reduction in the burden of pneumococcal disease. In the era of budget constraints, decision-makers may consider switching from the higher-valent, more costly PCV13, to the lower-cost PCV10. This study estimated the potential public health and economic impact of changing vaccine programs from PCV13 to PCV10 in Italy. Methods: A decision-analytic forecasting model estimated the impact of PCV programs. Real-world surveillance data were used to forecast serotype distribution and disease incidence among children and the elderly over a specified 5-year time horizon. Costs and outcomes included estimates of cases and deaths avoided, quality-adjusted life years (QALYs) gained, and total costs from a payer perspective, discounted at an assumed rate of 3.0%, and robustness validated through several scenarios and sensitivity analyses. Results: A switch from PCV13 to PCV10 would increase invasive pneumococcal disease (IPD) cases by 59.3% (4317 cases) over a 5-year horizon, primarily due to serotypes 3 and 19A. Pneumonia increased by 8.3% and acute otitis media (AOM) by 96.1%. Maintaining a PCV13 program would prevent a total incremental 531,435 disease cases (1.02M over a 10-year time horizon) and 641 deaths due to invasive pneumococcal disease (IPD), with €23,642 per QALY gained over 5 years versus PCV10. One-way and probabilistic sensitivity analyses showed that a PCV13-based program remained cost-effective in 99.7% of the simulations in Italy as parameters varied within their plausible range; percent vaccinated had the most impact. Conclusions: Maintaining the PCV13 strategy would provide substantial public health and economic benefits in Italy and is cost-effective. Switching from PCV13 to PCV10 would increase the incidence of pneumococcal disease primarily linked to re-emergence of serotypes 3 and 19A.

Maternal Serum Lipid Trajectories and Association with Pregnancy Loss and Length of Gestation.

OBJECTIVE: We characterized lipid trajectories and investigated lipids and rate of pregnancy lipid change with the risk of pregnancy loss or preterm delivery <37 weeks. STUDY DESIGN: In a secondary analysis of 337 women with one to two prior losses assigned to placebo in a randomized controlled trial at four centers (2007-2012), cholesterol, low- and high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured up to 6 months prepregnancy (time 0) and pregnancy up to 7 visits. Trajectories were created using linear mixed models. Multivariable logistic regression with adjustment for maternal characteristics and cholesterol was performed. RESULTS: Lipids decreased from prepregnancy to 4 to 5 weeks, followed by an increase, and were biphasic or triphasic depending on the lipid component. Between 4 and 8 weeks, for every 1-unit increase in HDL-C, there was a 22% decreased odds of loss <14 weeks (odds ratio: 0.78; 95% confidence interval: 0.60, 0.99) and 24% decreased odds of loss or preterm delivery 14 to <37 weeks (odds ratio: 0.76; 95% confidence interval: 0.60, 0.96). CONCLUSION: There were no associations with other lipid components or other time points. An impaired rise of HDL-C early in pregnancy may signal maladaptation to pregnancy that is associated with pregnancy loss or preterm delivery.

Commentary: Why Has Uptake of Pneumococcal Vaccines for Children Been So Slow? The Perils of Undervaluation.

Pediatric pneumococcal disease exacts a substantial burden on global health, much of which is vaccine-preventable. Despite this considerable burden and the demonstrably high efficacy of pneumococcal conjugate vaccines (PCVs), the overall level of PCV uptake remains concerningly low, especially compared with that of other childhood-recommended vaccines, such as tuberculosis and polio. A broad set of plausible explanations exists for this low uptake, including logistical challenges, psychosocial factors and affordability. One additional and systematic cause of low uptake, which is the focus of our discussion, is economists' and policymakers' tendency to undervalue vaccination in general by adopting a narrow health sector perspective when performing economic evaluations of vaccines. We present an alternative, societal framework for economic evaluations that encompasses a broader set of socioeconomic benefits in addition to health benefits. Quantifying a more comprehensive taxonomy of PCV's benefits will help to address potential undervaluation and may be sufficient not only to justify recommendation and reimbursement but also to stimulate efforts and investment toward closing coverage gaps.

Fetal growth patterns in pregnancy-associated hypertensive disorders: NICHD Fetal Growth Studies.

BACKGROUND: Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking. OBJECTIVE: The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders. STUDY DESIGN: This is a study based on data from a prospective longitudinal cohort study of fetal growth performed at 12 US sites (2009-2013). Project gestational age was confirmed by ultrasound between 8 weeks 0 days and 13 weels 6 days, and up to 6 ultrasounds were performed across gestation. Hypertensive disorders were diagnosed based on 2002 American College of Obstetricians and Gynecologists guidelines and grouped hierarchically as severe preeclampsia (including eclampsia or HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome), mild preeclampsia, severe gestational hypertension, mild gestational hypertension, or unspecified hypertension. Women without any hypertensive disorder constituted the normotensive group. Growth curves for estimated fetal weight and individual biometric parameters including biparietal diameter, head circumference, abdominal circumference, and femur and humerus length were calculated for each group using linear mixed models with cubic splines. Global and weekly pairwise comparisons were performed between women with a hypertensive disorder compared with normotensive women to analyze differences while adjusting for confounding variables. Delivery gestational age and birthweights were compared among groups. RESULTS: Of 2462 women analyzed, 2296 (93.3%) were normotensive, 63 (2.6%) had mild gestational hypertension, 54 (2.2%) mild preeclampsia, 32 (1.3%) severe preeclampsia, and 17 (0.7%) unspecified hypertension. Compared with normotensive women, those with severe preeclampsia had estimated fetal weights that were reduced between 22 and 38 weeks (all weekly pairwise values of P < .008). Women with severe preeclampsia compared with those without hypertension also had significantly smaller fetal abdominal circumference between 23-31 and 33-37 weeks' gestation (weekly pairwise values of P < .04). Scattered weekly growth differences were noted on other biometric parameters between these 2 groups. The consistent differences in estimated fetal weight and abdominal circumference were not observed between women with other hypertensive disorders and those who were normotensive. Women with severe preeclampsia delivered significantly earlier (mean gestational age 35.9 ± 3.2 weeks) than the other groups (global P < .0001). Birthweights in the severe preeclampsia group were also significantly lower (mean -949.5 g [95% confidence interval, -1117.7 to -781.2 g]; P < .0001) than in the normotensive group. CONCLUSION: Among women with pregnancy-associated hypertensive disorders, only those destined to develop severe preeclampsia demonstrated a significant and consistent difference in fetal growth (ie, smaller estimated fetal weight and abdominal circumference) when compared with normotensive women.