COVID-19 in Pregnancy: An Update for Clinicians.

In this review, we will discuss the risks of COVID-19 on maternal, obstetric, and neonatal outcomes. We will also review the safety of COVID-19 vaccination in pregnancy, as well as review the management of COVID-19 in pregnancy.

Optimal timing of delivery for growth restricted fetuses with gastroschisis: A decision analysis.

OBJECTIVE: Our objective was to determine the optimal timing of delivery of growth restricted fetuses with gastroschisis in the setting of normal umbilical artery (UA) Dopplers. METHODS: We designed a decision analytic model using TreeAge software for a hypothetical cohort of 2000 fetuses with isolated gastroschisis, fetal growth restriction (FGR), and normal UA Dopplers across 34-39 weeks of gestation. This model accounted for costs and quality adjusted life years (QALYs) for the pregnant individual and the neonate. Model outcomes included stillbirth, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), short gut syndrome (SGS), neonatal sepsis, neonatal death, and neurodevelopmental disability (NDD). RESULTS: We found 38 weeks to be the optimal timing of delivery for minimizing overall perinatal mortality and leading to the highest total QALYs. Compared to 37 weeks, delivery at 38 weeks resulted in 367.98 more QALYs, 2.22 more cases of stillbirth, 2.41 fewer cases of RDS, 0.02 fewer cases of NEC, 1.65 fewer cases of IVH, 0.5 fewer cases of SGS, 2.04 fewer cases of sepsis, 11.8 fewer neonatal deaths and 3.37 fewer cases of NDD. However, 39 weeks were the most cost-effective strategy with a savings of $1,053,471 compared to 38 weeks. Monte Carlo analysis demonstrated that 38 weeks was the optimal gestational age for delivery 51.70% of the time, 39 weeks were optimal 47.40% of the time, and 37 weeks was optimal 0.90% of the time. CONCLUSION: Taking into consideration a range of adverse perinatal outcomes and cost effectiveness, 38-39 weeks gestation is ideal for the delivery of fetuses with gastroschisis, FGR, and normal UA Dopplers. However, there are unique details to consider for each case, and the timing of delivery should be individualized using shared multidisciplinary decision making.

Adverse Perinatal and Neonatal Outcomes among Adolescent Pregnancies in the United States.

OBJECTIVE: Despite a downward trend in recent years, adolescent pregnancies in the United States remain higher than any other western country. Adolescent pregnancies have been inconsistently associated with adverse perinatal outcomes. The objective of this study is to investigate the association between adolescent pregnancies and adverse perinatal and neonatal outcomes in the United States. STUDY DESIGN: This is a retrospective cohort study of singleton births in the United States from 2014 to 2020 using national vital statistics data. Perinatal outcomes included gestational diabetes, gestational hypertension, preterm delivery <37 weeks (preterm birth [PTB]), cesarean delivery (CD), chorioamnionitis, small for gestational age (SGA), large for gestational age (LGA), and neonatal composite outcome. Chi-square tests were used to compare outcomes among adolescent (13-19 years) versus adult (20-29 years) pregnancies. Multivariable logistic regression models were used to examine association of adolescent pregnancies with perinatal outcomes. For each outcome, we utilized three models: unadjusted logistic regression, adjusted for demographics, and adjusted for demographics and medical comorbidities. Similar analyses were used to compare younger (13-17 years) and older (18-19 years) adolescent pregnancies to adults. RESULTS: In a cohort of 14,014,078 pregnancies, we found that adolescents were at an increased risk of PTB (adjusted odds ratio [aOR]: 1.12, 99% confidence interval (CI): 1.12-1.13) and SGA (aOR: 1.02, 99% CI: 1.01-1.03) compared with adult pregnancies. We also found that multiparous adolescents with a prior history of CD were at an increased risk of CD, compared with adults. For all other outcomes, adult pregnancies were at higher risk for adverse outcomes in the adjusted models. When comparing birth outcomes among adolescents, we found that older adolescents are at an increased risk of PTB, whereas younger adolescents are at an increased risk of both PTB and SGA. CONCLUSION: After adjusting for confounders, our study demonstrates adolescents have an increased risk of PTB and SGA, compared with adults. KEY POINTS: · Adolescents as a whole subgroup have an increased risk of PTB and SGA compared with adults.. · Younger adolescents have a risk of PTB and SGA, whereas older adolescents have a risk of PTB only.. · Adverse birth outcomes in adults are gestational diabetes, chorioamnionitis, LGA, and worse neonatal composite score..

Association Between Rates of Down Syndrome Diagnosis in States With vs Without 20-Week Abortion Bans From 2011 to 2018.

Importance: Many states enacted 20-week abortion bans from 2011 to 2018. Such bans affect individuals who receive diagnoses of fetal anomalies and aneuploidy in the second trimester, preventing pregnant individuals from having the choice of whether or not to continue the pregnancy. Objectives: To examine the trends of neonatal Down syndrome rates and assess the association between enactment of 20-week abortion bans and rates of Down syndrome diagnosis. Design, Setting, and Participants: This population-based, historical cohort study used National Vital Statistics System data on 31 157 506 births in the US from 2011 to 2018. Statistical analysis was performed from May 2021 to February 2023. Exposure: States were categorized as those with or without a 20-week abortion ban enacted during the study period. Main Outcomes and Measures: Demographic characteristics between the ban and no-ban states were compared using χ2 tests and 2-sample t tests. Multivariable logistic regression evaluated the adjusted odds of Down syndrome among births in states that enacted 20-week abortion bans after the abortion ban enactment, adjusting for state, year of birth, maternal race and ethnicity, age, educational level, insurance, and number of prenatal visits. Results: The cohort consisted of 31 157 506 births (mean [SD] maternal age, 28.4 [5.9] years) in the United States, of whom 15 951 neonates (0.05%) received a diagnosis of Down syndrome at birth. A total of 17 states enacted 20-week abortion bans during the study period, and 33 states did not enact bans. In both states with and states without bans, the birth prevalence of neonatal Down syndrome increased over time; in states with bans, rates increased from 48.0 to 58.4 per 100 000 births; in states without bans, rates increased from 47.4 to 53.3 per 100 000 births. In multivariable logistic regression assessing the interaction of time and presence of a 20-week abortion ban, the odds of Down syndrome were higher in states that enacted 20-week abortion bans after enactment of the law compared with the years prior to enactment of the ban (adjusted odds ratio, 1.22; 95% CI, 1.11-1.35). Conclusions and Relevance: In the US from 2011 to 2018, neonatal Down syndrome diagnoses increased more in states that enacted 20-week abortion bans compared with states that did not enact bans. Because these abortion bans were enacted throughout the study period and are known to inhibit choice in patient decision-making, it is possible that the difference in the rates of diagnosis is associated with these policies.

Universal Tetanus-Diphtheria-Pertussis Vaccination During Pregnancy: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the cost effectiveness of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination in pregnant patients in the United States. METHODS: A decision-analytic model in TreeAge was developed to compare universal Tdap vaccination in pregnancy with no Tdap vaccination in pregnancy using a theoretical cohort of 3.66 million pregnant individuals, the approximate number of deliveries per year in the United States. Outcomes included infant pertussis infections, infant hospitalizations, infant encephalopathy cases, infant deaths, and maternal pertussis infections. All probabilities and costs were derived from the literature. Utilities were applied to discounted life expectancies at a rate of 3% to generate quality-adjusted life-years (QALYs). A strategy was considered cost effective if it had an incremental cost-effectiveness ratio of less than $100,000 per QALY. Univariable and multivariable sensitivity analyses were performed to assess the robustness of the model to changes in the baseline assumptions. RESULTS: With a baseline assumption of vaccine cost at $47.75, Tdap vaccination was cost effective at $7,601 per QALY. The vaccination strategy was associated with a decrease of 22 infant deaths, 11 infant encephalopathy cases, 2,018 infant hospitalizations, 6,164 infant pertussis infections, and 8,585 maternal pertussis infections, with an increase of 19,489 QALYs. In sensitivity analyses, the strategy was cost effective until the incidence of maternal pertussis became lower than 1.6 cases per 10,000 individuals, the cost of the Tdap vaccine was greater than $540, or previous pertussis immunity was present in more than 92.1% of pregnant individuals. CONCLUSION: In a theoretical U.S. cohort of 3.66 million pregnant individuals, Tdap vaccination during pregnancy is cost effective and reduces infant morbidity and mortality compared with no vaccination during pregnancy. These findings are especially relevant given that approximately half of individuals are not vaccinated during pregnancy and recent data have shown that postpartum maternal vaccination and cocooning strategies are ineffective. Public health strategies to encourage greater uptake of Tdap vaccination should be used to reduce the morbidity and mortality of pertussis infection.

Outcomes among Nulliparous Women Undergoing Nonmedically Indicated Induction of Labor at 39 Weeks Compared with Expectant Management Differ by Maternal Age.

OBJECTIVE: Prior studies have demonstrated the potential benefit of nonmedically indicated induction of labor for nulliparous women at 39 weeks of gestation, yet few have studied the impact of this management strategy in different maternal age groups on obstetric outcomes. We sought to assess whether obstetric outcomes among women undergoing nonmedically indicated induction of labor at 39 weeks of gestation as compared with expectant management vary based on maternal age. STUDY DESIGN: This was a retrospective cohort study of singleton, nonanomalous, deliveries between 2007 and 2012 in California. We defined nonmedically indicated induction of labor as induction of labor without a specific medical indication, and women with planned cesarean sections were excluded. We compared induction of labor with expectant management beyond the gestational age of induction and examined this comparison in different maternal age groups. Numerous maternal and neonatal outcomes were examined. Chi-squared and multivariable logistic regression analyses were used for statistical comparisons and a p-value of less than 0.05 was used to indicate statistical significance. RESULTS: A total of 630,485 women-infant dyads met our inclusion criteria and were included in this study. At 39 weeks' gestation, 6% of women underwent nonmedically indicated induction of labor and 94% underwent expectant management. Women 20 to 34 and ≥35 years old had lower odds of cesarean delivery if they underwent induction of labor. Women of all ages undergoing nonmedically indicated induction of labor had higher odds of operative vaginal delivery. Neonatal outcomes were better with nonmedically indicated induction of labor, including lower odds of neonatal intensive care unit admission and neonatal respiratory distress. CONCLUSION: Our study demonstrated that obstetric outcomes vary among women undergoing nonmedically indicated induction of labor compared with expectant management when stratified by maternal age. These findings illustrate the importance of understanding age-related differences in outcomes associated with nonmedically indicated induction of labor. KEY POINTS: · Outcomes are different by age with nonmedically indicated induction of labor (IOL).. · The odds of cesarean delivery with IOL decreases with increasing maternal age compared with expectant management.. · Neonatal outcomes were improved with IOL compared with expectant management..

Association of interpregnancy interval and gestational diabetes mellitus.

OBJECTIVE: To evaluate the association between interpregnancy interval (IPI) and risk for gestational diabetes mellitus (GDM). METHODS: We conducted a retrospective cohort study among singleton, non-anomalous, live birth pregnancies of 5,705,812 pregnant individuals in the United States from 2016 to 2018. We examined IPI of 4-<6 months, 6-11 months, 12-17 months, 24-35 months, 36-47 months, 48-59 months, 60-71 months, and ≥72 months in comparison to the reference interval of 18-23 months in relation to risk for GDM. We used logistic regression to evaluate the association between IPI and risk for GDM. RESULTS: There is a significantly increased risk for GDM associated with IPIs of 6-11 months and 12-17 months compared to the reference of 18-23 months (adjusted Odds Ratio [aOR] 1.05, 95% CI: 1.03-1.07; aOR 1.02, 95% CI: 1.01-1.03). The risk for GDM is greater for longer IPIs (36-47 months aOR 1.10, 95% CI: 1.05-1.08; 48-59 months aOR 1.11, 95% CI: 1.09-1.13; 60-71 months aOR 1.14, 95% CI: 1.12-1.16; ≥72 months aOR 1.31, 95% CI: 1.30-1.33). CONCLUSION: Our findings support the growing evidence that shorter and longer IPI increase the risk of GDM in pregnant individuals. Screening guidelines for detection of GDM may need to be re-evaluated and updated to include longer IPIs (≥36 months) as a risk factor for earlier screening prior to current recommendation of 24 weeks gestational age.

Universal Hepatitis B Antibody Screening and Vaccination in Pregnancy: A Cost-Effectiveness Analysis.

OBJECTIVE: To evaluate the cost effectiveness of universal screening for hepatitis B immunity and vaccination among pregnant women in the United States. METHODS: We designed a decision-analytic model to evaluate the outcomes, costs, and cost effectiveness associated with universal hepatitis B virus (HBV) immunity screening in pregnancy with vaccination of susceptible individuals compared with no screening. A theoretical cohort of 3.6 million women, the approximate number of annual live births in the United States, was used. Outcomes included cases of HBV, hepatocellular carcinoma, decompensated cirrhosis, liver transplant and death, in addition to cost and quality-adjusted life-years (QALYs). Model inputs were derived from the literature, and the willingness-to-pay threshold was $50,000 per QALY. Univariate sensitivity analyses and Monte Carlo simulation models were performed to evaluate the robustness of the results. RESULTS: In a theoretical cohort of 3.6 million women, universal HBV immunity screening and vaccination resulted in 1,702 fewer cases of HBV, seven fewer cases of decompensated cirrhosis, four fewer liver transplants, and 11 fewer deaths over the life expectancy of a woman after pregnancy. Universal screening and vaccination were found to be cost effective, with an incremental cost-effectiveness ratio of $1,890 per QALY. Sensitivity analyses demonstrated the model was robust even when the prevalence of HBV immunity was high and the annual risk of HBV acquisition low. CONCLUSION: Among pregnant women in the United States, universal HBV immunity screening and vaccination of susceptible persons is cost effective compared with not routinely screening and vaccinating.

Therapeutic hypothermia in severe hypoxic-ischemic encephalopathy: a cost-effectiveness analysis.

BACKGROUND: The incidence of hypoxic-ischemic encephalopathy (HIE) is 0.5 per 1,000 live births. Current standard treatment is therapeutic hypothermia (cooling) begun within 6 hours of life. In infants with severe HIE, this results in fewer deaths; however, more infants survive with major neurodevelopmental disability. OBJECTIVE: We sought to determine whether cooling is cost-effective compared to no cooling in cases of severe HIE, and to compare it to the cost-effectiveness of cooling in cases of moderate HIE. STUDY DESIGN: A decision analytic model using TreeAge Pro (2020) software was designed comparing cooling to no cooling in a cohort of 5,800 term neonates with HIE. Model inputs were derived from the literature. Utilities were applied to life expectancy to generate quality-adjusted life years (QALYs). All costs and QALYs were discounted at an annual rate of 3%. The strategy was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were conducted to assess the robustness of the results. RESULTS: Cooling for the management of severe HIE resulted in increased costs and increased QALYs, with an ICER of 6,864. In our theoretical cohort, cooling resulted in 835 fewer neonatal deaths, but 52 additional cases of severe neurological disability with cooling due to increased survival. When varying the probability of a healthy child with cooling in univariate sensitivity analysis, cooling was found to be the cost-effective strategy across all ranges and the dominant (lower costs, higher QALYs) strategy above 68% (baseline estimate: 63%). Multivariate sensitivity analysis found cooling was the cost-effective strategy 99.7% of the time. CONCLUSION: Cooling is the cost-effective intervention with improved outcomes for neonates with severe perinatal hypoxic-ischemic encephalopathy over a wide range of assumptions. Despite the increased cost, more neonates survive morbidity free when compared with no cooling.

Antenatal corticosteroids for pregnant women with COVID-19 infection and preterm prelabor rupture of membranes: a decision analysis.

BACKGROUND: While antenatal corticosteroids are routinely used to decrease adverse neonatal outcomes following preterm delivery, corticosteroids are also associated with worse outcomes in patients with viral respiratory infections. Currently in the setting of the COVID-19 pandemic, it is unclear whether antenatal corticosteroids for infant benefit outweigh the potential harm to a pregnant woman with a COVID-19 infection. OBJECTIVE: To determine at which gestational ages administering antenatal corticosteroids is the optimal management strategy for hospitalized women with preterm prelabor rupture of membranes (PPROM) who have a COVID-19 infection. METHODS: We designed a decision-analytic model to assess the maternal and infant outcomes associated with antenatal corticosteroid administration for risk of preterm delivery following rupture of membranes in the setting of a COVID-19 infection. We used a theoretical cohort of 10,000 women at each gestational age between 24 and 32 weeks who were hospitalized with PPROM and found to be COVID-19 positive. Maternal outcomes included intensive care unit admission and death related to COVID-19 infection. The infant outcomes of interest included respiratory distress syndrome, intraventricular hemorrhage, neurodevelopmental delay, and death, and were assessed along with maternal and infant quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were used to evaluate model assumptions. RESULTS: In our theoretical cohort of 10,000 women with COVID-19 infection and preterm prelabor rupture of membrane between 24 and 32 weeks, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths at each gestational age. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths at each gestational age. Antenatal corticosteroid administration also resulted in fewer cases of respiratory distress syndrome, intraventricular hemorrhage, and infant death. Overall, we found that between 24 and 30 weeks of gestation, administering antenatal corticosteroids was the optimal management strategy as it resulted in higher combined QALYs than no corticosteroid use. For 31 and 32 weeks of gestation, antenatal corticosteroid administration resulted in lower combined QALYs. On sensitivity analyses, we found that with increasing gestational age, the probability which antenatal corticosteroids was the optimal management strategy decreased. CONCLUSION: Administration of antenatal corticosteroids was an effective management strategy compared to no corticosteroid administration at gestational ages less than 31 weeks. These results provide data for clinicians to utilize when counseling pregnant patients hospitalized with PPROM and have a COVID-19 infection.

Cesarean delivery rates by hospital type among nulliparous and multiparous patients.

BACKGROUND: Cesarean delivery rates continue to remain high despite recent attempts to decrease these rates. Prior data suggest that there is great variation in cesarean rates by hospital. OBJECTIVE: The intent of this study is to examine the association of several hospital characteristics and cesarean delivery rates in California. METHODS: We performed a retrospective study of singleton, non-anomalous, term (37-42 week) deliveries in California. We excluded hospitals with <50 deliveries per year and missing hospital information. We separated hospitals by volume based on previously published categories: low-volume (<1200 deliveries/year), medium-volume (1200-2399 deliveries/year), and medium-high-volume (2400-3599 deliveries/year, and high-volume (3600 deliveries/year). We also evaluated rural versus urban and non-teaching versus teaching hospitals. We examined overall cesarean rates as well as stratified by parity and with and without prior cesarean. We analyzed data with chi-square tests and multivariable logistic regression models. RESULTS: In a total of 2,545,464 pregnancies, 772,539 (30.35%) resulted in cesarean deliveries. After controlling for race/ethnicity, age, body mass index, education, and insurance, rates of cesarean delivery were higher in low-volume hospitals (aOR: 1.07; 95% CI: 1.0-1.08) and lower in medium-high-volume hospitals (aOR: 0.97; 95% CI: 0.96-0.98) as compared to high-volume hospitals. Rural hospitals had higher rates of cesarean delivery (aOR: 1.08; 95% CI: 1.06-1.10) as compared to urban hospitals while non-teaching hospitals had higher odds of cesarean deliveries (aOR: 1.27; 95% CI: 1.25-1.28) as compared with teaching hospitals. Among nulliparous patients, medium- and medium-high-volume hospitals had lower rates of cesarean deliveries (aOR: 0.95; 95% CI: 0.93-0.96; aOR: 0.93; 95% CI: 0.91-0.94) as compared to high-volume hospitals, while non-teaching hospitals had higher rates of cesarean deliveries than teaching hospitals (aOR: 1.11; 95% CI: 1.10-1.13). Multiparous patients without prior cesarean had higher rates of cesarean delivery at low-volume hospitals and lower rates of cesarean delivery at medium-high-volumes (aOR: 1.07; 95% CI: 1.05-1.10; aOR: 0.96; 95% CI: 0.94-0.098) as compared to high-volume hospitals. Additionally, multiparous patients without prior cesarean had higher rates of cesarean delivery at non-teaching hospitals than teaching hospitals (aOR: 1.16; 95% CI: 1.13-1.19). Multiparous patients with prior cesarean had high rates of cesarean delivery at all volume hospitals with the highest odds at low-volume hospitals (aOR: 1.81; 95% CI: 1.74, 1.89) as well as at rural and non-teaching hospitals. CONCLUSION: Cesarean delivery rates were higher at low and high-volume hospitals for nulliparous and multiparous patients without prior cesarean, but increased with decreasing hospital volume for multiparous patients with prior cesarean. Additionally, cesarean delivery was more likely at rural and non-teaching hospitals. Our results suggest that further investigation is necessary to determine the structural and mechanistic causes of the differences in practice by hospital type in order to identify targets for approaches in reducing cesarean deliveries.

Fetoscopic compared with open repair of myelomeningocele: a 2-delivery cost-effectiveness analysis.

BACKGROUND: Recent studies have compared maternal and neonatal outcomes associated with fetoscopic surgical approach for repair of myelomeningocele compared with an open approach. OBJECTIVE: In this study, we compared the cost-effectiveness of these techniques in the setting of a woman seeking future pregnancies. STUDY DESIGN: A decision-analytical model using TreeAge software was designed to compare the costs and outcomes of fetoscopic vs open repair in patients with prenatally diagnosed myelomeningocele. We assumed a theoretical cohort of 500 women with a pregnancy affected by myelomeningocele planning to have a future pregnancy. Our model accounted for costs and quality-adjusted life years of the woman, the neonate with myelomeningocele, and the neonate in a subsequent pregnancy. Neonatal outcomes from the incident pregnancy included motor function >2 levels better than the anatomic level, motor function <2 levels better than the anatomic level, and same motor function as the anatomic level, preterm birth in the index pregnancy, neonatal death in the index pregnancy, and major neurodevelopmental disability as a result of preterm birth in the index pregnancy. Neonatal outcomes in the subsequent pregnancy included stillbirth, preterm birth, and neonatal and major neurodevelopmental disability as a result of preterm birth. Probabilities were derived from the literature, and we used a willingness-to-pay threshold of $100,000 per quality-adjusted life year. RESULTS: In the index pregnancy, fetoscopic surgical technique resulted in 140 fewer cases of preterm birth and fewer cases of neurodevelopmental disability and neonatal death. Fetoscopic technique resulted in 130 more cases of functional level >2 levels better than the anatomic level, 35 fewer cases of functional level >2 levels worse than the anatomic level, and 107 fewer cases of function same as the anatomic level. In the subsequent pregnancy, fetoscopic surgery led to 22 fewer cases of delivery complications (uterine dehiscence, uterine rupture, and excessive bleeding), 24 fewer cases of stillbirth, and 22 fewer cases of preterm birth. Although the fetoscopic approach was more costly, it was cost-effective with an incremental cost-effectiveness ratio of $1029 per quality-adjusted life year in our theoretical cohort of 500 patients. Monte Carlo probabilistic sensitivity analysis showed that fetoscopic technique is cost-effective 100% of the time. CONCLUSION: In our theoretical cohort, the fetoscopic approach was more costly, but resulted in improved outcomes when a subsequent pregnancy was considered.

Increased rates of adverse perinatal outcomes in women with gestational diabetes and depression.

OBJECTIVE: We sought to examine the impact of depression on adverse perinatal outcomes in women with Gestational Diabetes Mellitus (GDM). METHODS: We performed a retrospective cohort study comparing the rates of perinatal complications among singleton, nonanomalous births to women with GDM and the diagnosis of depression compared to GDM women without depression between 2007 and 2011 in California. Perinatal outcomes were analyzed using chi-square and multivariable logistic regression to compare frequencies of characteristics and outcomes and to determine the strength of association of depression and adverse perinatal outcomes among women with GDM. Statistical comparisons with a p-value of less than .05 and 95% CI that did not cross the null were considered statistically significant. RESULTS: Among the cohort of 170,572 women with GDM, 2090 (1.22%) were diagnosed with antenatal depression. Women with GDM and depression had significantly higher rates of preeclampsia (adjusted Odds Ratio [aOR] 1.28, 95% CI 1.11-1.49) and gestational hypertension (aOR 1.23, 95% CI 1.05-1.44). Women with GDM and depression also had higher rates of preterm delivery at <37, and <34 weeks gestational age (aOR 1.33, 95% CI 1.18-1.50 and 1.36, 95% CI 1.15-1.61, respectively). CONCLUSION: Women with GDM and a diagnosis of depression have higher rates of adverse perinatal outcomes than women with GDM alone. Identifying and managing depression among women with GDM has the potential to improve the care and health of this high-risk population.

Antenatal Corticosteroids for Pregnant Women at High Risk of Preterm Delivery with COVID-19 Infection: A Decision Analysis.

OBJECTIVE: Antenatal corticosteroids given prior to preterm deliveries reduce the risk of adverse neonatal outcomes. However, steroid administration in the setting of a viral respiratory infection can worsen maternal outcomes. Therefore, the decision to administer corticosteroids must balance the neonatal benefits with the potential harm to the mother if she is infected with the novel coronavirus disease 2019 (COVID-19). This study aimed to determine the gestational ages for which administering antenatal corticosteroids to women at high risk of preterm labor with concurrent COVID-19 infection results in improved combined maternal and infant outcomes. STUDY DESIGN: A decision-analytic model using TreeAge (2020) software was constructed for a theoretical cohort of hospitalized women with COVID-19 in the United States. All model inputs were derived from the literature. Outcomes included maternal intensive care unit (ICU) admission and death, along with infant outcomes of death, respiratory distress syndrome, intraventricular hemorrhage, and neurodevelopmental delay. Quality-adjusted life years (QALYs) were assessed from the maternal and infant perspectives. Sensitivity analyses were performed to determine if the results were robust over a range of assumptions. RESULTS: In our theoretical cohort of 10,000 women delivering between 24 and 33 weeks of gestation with COVID-19, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths. Overall, we found that corticosteroid administration resulted in higher combined QALYs up to 31 weeks of gestation in all hospitalized patients, and up to 29 weeks of gestation in ICU patients. CONCLUSION: Administration of antenatal corticosteroids at less than 32 weeks of gestation for hospitalized patients and less than 30 weeks of gestation for patients admitted to the ICU resulted in higher combined maternal and infant outcomes compared with expectant management for women at high risk of preterm birth with COVID-19 infection. These results can guide clinicians in their counseling and management of these pregnant women. KEY POINTS: · Antenatal steroids reduce adverse neonatal outcomes.. · Steroids worsen maternal outcomes in COVID-19.. · Steroids given < 32 weeks result in improved outcomes..

Past speculations of future health technologies: a description of technologies predicted in 15 forecasting studies published between 1986 and 2010.

OBJECTIVE: To describe and classify health technologies predicted in forecasting studies. DESIGN AND METHODS: A portrait describing health technologies predicted in 15 forecasting studies published between 1986 and 2010 that were identified in a previous systematic review. Health technologies are classified according to their type, purpose and clinical use; relating these to the original purpose and timing of the forecasting studies. DATA SOURCES: All health-related technologies predicted in 15 forecasting studies identified in a previously published systematic review. MAIN OUTCOME MEASURE: Outcomes related to (1) each forecasting study including country, year, intention and forecasting methods used and (2) the predicted technologies including technology type, purpose, targeted clinical area and forecast timeframe. RESULTS: Of the 896 identified health-related technologies, 685 (76.5%) were health technologies with an explicit or implied health application and included in our study. Of these, 19.1% were diagnostic or imaging tests, 14.3% devices or biomaterials, 12.6% information technology systems, eHealth or mHealth and 12% drugs. The majority of the technologies were intended to treat or manage disease (38.1%) or diagnose or monitor disease (26.1%). The most frequent targeted clinical areas were infectious diseases followed by cancer, circulatory and nervous system disorders. The most frequent technology types were for: infectious diseases-prophylactic vaccines (45.8%), cancer-drugs (40%), circulatory disease-devices and biomaterials (26.3%), and diseases of the nervous system-equally devices and biomaterials (25%) and regenerative medicine (25%). The mean timeframe for forecasting was 11.6 years (range 0-33 years, median=10, SD=6.6). The forecasting timeframe significantly differed by technology type (p=0.002), the intent of the forecasting group (p<0.001) and the methods used (p<001). CONCLUSION: While description and classification of predicted health-related technologies is crucial in preparing healthcare systems for adopting new innovations, further work is needed to test the accuracy of predictions made.

Accuracy of pharmaceutical company licensing predictions: projected versus actual licensing dates.

OBJECTIVES: To determine the accuracy of pharmaceutical companies' predictions of drug licensing timeframes for their products in late stage clinical development. METHODS: We compared predicted licensing dates provided to the National Institute for Health Research Horizon Scanning Research and Intelligence Centre by pharmaceutical companies against actual marketing authorisation application (MAA) and marketing authorisation (MA) dates published by the European Medicines Agency for drugs granted authorisation between 2009 and 2013. KEY FINDINGS: One hundred and twenty-three drugs met our inclusion criteria. About 78% were new drugs and 16% had orphan designation. Less than half (44%) and less than a quarter (24%) of MAA and MA predictions respectively were considered accurate (same month or 1 month either side of the actual date). Pharmaceutical companies were significantly more accurate in predicting MAA dates than MA dates (P < 0.001). For accurate predictions, the mean duration between the prediction being made and the actual MAA and MA dates were 17.5 and 18.7 months respectively. Out of the total 108 MA predictions, almost two-thirds (65.4%, 16/26) of short-term predictions (made in the 2 years prior to the actual MA) were accurate. For predicted dates that were earlier than the actual MA date, there was a positive relationship between accuracy and the time between the prediction and authorisation. CONCLUSIONS: Even in predicting near events from well-informed sources, accuracy is imperfect. There appears to be an optimum time for the provision of accurate information on predicted MAA and MA dates for drugs. This information is crucial for effective early awareness and alert activities.

Past speculations of the future: a review of the methods used for forecasting emerging health technologies.

OBJECTIVES: Forecasting can support rational decision-making around the introduction and use of emerging health technologies and prevent investment in technologies that have limited long-term potential. However, forecasting methods need to be credible. We performed a systematic search to identify the methods used in forecasting studies to predict future health technologies within a 3-20-year timeframe. Identification and retrospective assessment of such methods potentially offer a route to more reliable prediction. DESIGN: Systematic search of the literature to identify studies reported on methods of forecasting in healthcare. PARTICIPANTS: People are not needed in this study. DATA SOURCES: The authors searched MEDLINE, EMBASE, PsychINFO and grey literature sources, and included articles published in English that reported their methods and a list of identified technologies. MAIN OUTCOME MEASURE: Studies reporting methods used to predict future health technologies within a 3-20-year timeframe with an identified list of individual healthcare technologies. Commercially sponsored reviews, long-term futurology studies (with over 20-year timeframes) and speculative editorials were excluded. RESULTS: 15 studies met our inclusion criteria. Our results showed that the majority of studies (13/15) consulted experts either alone or in combination with other methods such as literature searching. Only 2 studies used more complex forecasting tools such as scenario building. CONCLUSIONS: The methodological fundamentals of formal 3-20-year prediction are consistent but vary in details. Further research needs to be conducted to ascertain if the predictions made were accurate and whether accuracy varies by the methods used or by the types of technologies identified.

Bringing regenerative medicines to the clinic: the future for regulation and reimbursement.

Significant investments in regenerative medicine necessitate discussion to align evidentiary requirements and decision-making considerations from regulatory, health system payer and developer perspectives. Only with coordinated efforts will the potential of regenerative medicine be realized. We report on discussions from two workshops sponsored by NICE, University of Alberta, Cell Therapy Catapult and Centre for Commercialization of Regenerative Medicine. We discuss methods to support the assessment of value for regenerative medicine products and services and the synergies that exist between market authorization and reimbursement regulations and practices. We discuss the convergence in novel adaptive licensing practices that may promote the development and adoption of novel therapeutics that meet the needs of healthcare payers.

EUROSCAN INTERNATIONAL NETWORK MEMBER AGENCIES: THEIR STRUCTURE, PROCESSES, AND OUTPUTS.

OBJECTIVES: The EuroScan International Network is a global network of publicly funded early awareness and alert (EAA) systems for health technologies. We describe the EuroScan member agency systems and methods, and highlight the potential for increased collaboration. METHODS: EuroScan members completed postal questionnaires supplemented with telephone interviews in 2012 to elicit additional information and check equivalence of responses. Information was updated between March and May 2013. RESULTS: Fifteen of the seventeen member agencies responded. The principal purpose of agencies is to inform decisions on coverage or reimbursement of health services and decisions on undertaking secondary research. The main users of information are national governments; health professionals; health services purchasers, commissioners, and decision makers; and healthcare providers. Most EuroScan agencies are small with almost half having fewer than two whole time equivalent staff. Ten agencies use both active and passive identification approaches, four use only active approaches. Most start identification in the experimental or investigational stages of the technology life cycle. All agencies assessed technologies when they are between the investigational and established, but under diffusion stages. Barriers to collaboration revolve around different system aims, purposes, and requirements; a lack of staff, finance, or opportunity; language differences; and restrictions on dissemination. CONCLUSIONS: Although many barriers to collaboration were identified, the majority of agencies were supportive of increased collaboration either involving the whole EuroScan Network or between individual agencies. Despite differences in the detailed identification processes, members thought that this was the most feasible phase to develop additional collaboration.

Diagnosing Alzheimer's disease: are we any nearer to useful biomarker-based, non-invasive tests?

BACKGROUND: Alzheimer's disease (AD) accounts for 60-80% of cases of dementia and causes significant morbidity in patients and carers, and expense for health and social services. There is a need for a validated, non-invasive and cheap test to diagnose early AD, as diagnosis may enable prompt treatment and service planning. AIM: To identify emerging biomarker-based tests for the early diagnosis of AD which could be available for use in primary or generalist care in the near future. DESIGN: Horizon scanning review. METHODS: We searched online sources to identify emerging non-invasive, biomarker-based tests. Tests were included if they used blood, saliva or urine; and there was evidence of use in trials in patients with AD. For tests licensed for use in clinical or research settings we requested information from the developer on the intended place of use and plans for availability in Europe. RESULTS: We identified 6 biomarker-based tests of which 5 are available for research or clinical use. The closest to market were AclarusDX™ (ExonHit Therapeutics) a gene signature test, and INNO-BIA plasma Aß forms assay (Innogenetics N.V.) which may be CE marked for clinical use in 2015. We found no evidence of clinical utility or cost. CONCLUSION: Although biomarker-based tests are nearing clinical availability and may have a future role to help target AD-specific treatment and guide prognosis, they are not yet ready for trials of clinical utility in primary care.