Estimate Risk Ratios Research Articles

The Association of Adverse Pregnancy Outcomes With Overactive Bladder Anticholinergics.

The pregnancy safety and teratogenicity of overactive bladder (OAB) anticholinergic medications in humans are unknown. The aim of this study was to determine if the use of OAB anticholinergics during pregnancy was associated with adverse pregnancy outcomes or congenital malformation. Using routinely collected health care data from Ontario, Canada, we conducted a retrospective cohort study and identified women aged 18-45 years who gave birth between 2004 and 2022 and were eligible for provincial drug benefits. We used gestational age and birth dates to approximate conception dates. The primary exposure was filling a prescription for an OAB anticholinergic during pregnancy (compared with nonusers). The coprimary outcomes were pregnancy complication (which included preterm birth or low birth weight) and congenital malformation. Poisson regression models with generalized estimating equations and inverse probability of treatment weighting were used to estimate risk ratios (RRs). We identified 138,271 births, of which 479 (0.3%) had exposure to an OAB anticholinergic, for a median of 60 (interquartile range, 30-120) days. The most common OAB anticholinergic was oxybutynin (84%). In the weighted cohort, the risk of a pregnancy complication was significantly elevated (RR, 1.65; 95% confidence interval [CI], 1.40-1.95; P < 0.01; absolute risk difference + 9.9% [95% CI, +5.9, +13.9]), with a dose-response relationship close to statistical significance (P = 0.07). The risk of congenital malformations with OAB anticholinergic use was not significant (RR, 1.24; 95% CI, 0.85-1.80; P = 0.26). Pregnant women who take OAB anticholinergic medications have a higher risk of pregnancy complications, but not congenital malformations, compared with non-OAB anticholinergic users. This information can be used when counseling women of child-bearing age about these medications.

Target trial emulation of preconception serum vitamin D status on fertility outcomes: a couples-based approach

To evaluate associations between preconception 25-hydroxyvitamin D (25(OH)D) levels and biomarkers in female and male partners on live birth (LB), pregnancy loss, and semen quality. Secondary analysis using the folic acid and zinc supplementation trial of couples seeking infertility treatment at four US centers (2013-2017). A target trial emulation framework was applied to estimate associations. Couples were observed for 9 months or through pregnancy. Clinics that provide reproductive endocrinology and infertility care in the US. Couples seeking infertility treatment. Preconception concentrations of 25(OH)D (primary) and associated biomarkers: vitamin D binding protein, calcium, free vitamin D, bioavailable vitamin D. Live birth and pregnancy loss were ascertained via self-report and medical records. Semen quality was ascertained 6 months after enrollment. Log-binomial regression estimated risk ratios and 95% confidence intervals (CIs). Individual and joint models and effect measure modification by preconception body mass index were considered. Among 2,370 couples, 19.5% of females and 29.9% of males were 25(OH)D deficient. Females with sufficient status had a 28%-higher likelihood of LB than deficient females (95% CI, 1.05-1.56). Female and male 25(OH)D status were associated with LB among those with normal body mass index (sufficient vs. deficient: female adjusted risk ratio [aRR], 1.39; 95% CI, 1.00-1.99; male aRR, 1.51; 95% CI, 1.01-2.25) and among obese female partners (sufficient vs. deficient: aRR, 1.33; 95% CI, 0.95-1.85). Couples whose both partners had higher 25(OH)D status had increased likelihood of LB (both not deficient vs. both deficient aRR, 1.26; 95% CI, 1.00-1.58). No associations were observed with pregnancy loss or semen quality. Similar results were found for all biomarkers except calcium. Preconception vitamin D status and bioavailability impact fertility among couples seeking infertility therapy, likely unrelated to semen quality. Body mass index stratified analyses demonstrated heterogeneous associations. NCT01857310.

Effect of the COVID-19 Lockdown on Mobile Payments for Maternal Health: Regression Discontinuity Analysis.

The COVID-19 pandemic resulted in the unprecedented popularity of digital financial services for contactless payments and government cash transfer programs to mitigate the economic effects of the pandemic. The effect of the pandemic on the use of digital financial services for health in low- and middle-income countries, however, is poorly understood. This study aimed to assess the effect of the first COVID-19 lockdown on the use of a mobile maternal health wallet, with a particular focus on delineating the age-dependent differential effects, and draw conclusions on the effect of lockdown measures on the use of digital health services. We analyzed 819,840 person-days of health wallet use data from 3416 women who used health care at 25 public sector primary care facilities and 4 hospitals in Antananarivo, Madagascar, between January 1 and August 27, 2020. We collected data on savings, payments, and voucher use at the point of care. To estimate the effects of the first COVID-19 lockdown in Madagascar, we used regression discontinuity analysis around the starting day of the first COVID-19 lockdown on March 23, 2020. We determined the bandwidth using a data-driven method for unbiased bandwidth selection and used modified Poisson regression for binary variables to estimate risk ratios as lockdown effect sizes. We recorded 3719 saving events, 1572 payment events, and 3144 use events of electronic vouchers. The first COVID-19 lockdown in Madagascar reduced mobile money savings by 58.5% (P<.001), payments by 45.8% (P<.001), and voucher use by 49.6% (P<.001). Voucher use recovered to the extrapolated prelockdown counterfactual after 214 days, while savings and payments did not cross the extrapolated prelockdown counterfactual. The recovery duration after the lockdown differed by age group. Women aged >30 years recovered substantially faster, returning to prelockdown rates after 34, 226, and 77 days for savings, payments, and voucher use, respectively. Younger women aged <25 years did not return to baseline values. The results remained robust in sensitivity analyses using ±20 days of the optimal bandwidth. The COVID-19 lockdown greatly reduced the use of mobile money in the health sector, affecting savings, payments, and voucher use. Savings were the most significantly reduced, implying that the lockdown affected women's expectations of future health care use. Declines in payments and voucher use indicated decreased actual health care use caused by the lockdown. These effects are crucial since many maternal and child health care services cannot be delayed, as the potential benefits will be lost or diminished. To mitigate the adverse impacts of lockdowns on maternal health service use, digital health services could be leveraged to provide access to telemedicine and enhance user communication with clear information on available health care access options and adherence to safety protocols.

Variations in the use of oxytocin for augmentation of labour in Sweden: a population-based cohort study

National Swedish data shows substantial variation in the use of oxytocin for augmentation of spontaneous labour between obstetric units. This study aimed to investigate if variations in the use of oxytocin augmentation are associated with maternal and infant characteristics or clinical factors. We used a cohort design including women allocated to Robson group 1 (nulliparous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation and spontaneous onset of labour) and 3 (parous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation, spontaneous onset of labour, and no previous caesarean birth). Crude and adjusted logistic regression models with marginal standardisation were used to estimate risk ratios (RR) and risk differences (RD) with 95% confidence intervals (CI) for oxytocin use by obstetric unit. An interaction analysis was performed to investigate the potential modifying effect of epidural. The use of oxytocin varied between 47 and 73% in Robson group 1, and 10% and 33% in Robson group 3. Compared to the remainder of Sweden, the risk of oxytocin augmentation ranged from 13% lower (RD − 13.0, 95% CI − 15.5 to − 10.6) to 14% higher (RD 14.0, 95% CI 12.3–15.8) in Robson group 1, and from 6% lower (RD − 5.6, 95% CI − 6.8 to − 4.5) to 18% higher (RD 17.9, 95% CI 16.5–19.4) in Robson group 3. The most notable differences in risk estimates were observed among women in Robson group 3 with epidural. In conclusion, variations in oxytocin use remained despite adjusting for risk factors. This indicates unjustified differences in use of oxytocin in clinical practice.

Physical activity initiated from midlife on risk of dementia and cognitive impairment: The Health and Retirement Study.

Physical activity is associated with lower risk of dementia and cognitive impairment, but existing randomized controlled trials have shown conflicting results. As cognitive decline occurs decades before the onset of dementia, physical activity interventions initiated in late life may have missed the potential window for prevention. An ideal trial of physical activity initiated from midlife and lasts till incident dementia and cognitive impairment in late life is not feasible. We aimed to estimate the effectiveness of a hypothetical physical activity intervention initiated from midlife on reducing dementia and cognitive impairment by emulating target trials using observational data. The Health and Retirement Study was used to emulate target trials among noninstitutionalized participants aged 45 to 65 years with normal cognition who were physically inactive in the previous 2 years. Cognitive status was determined based on Langa-Weir classification of cognitive function (including immediate and delayed word recall tests, serial sevens subtraction, counting backward). Individuals were categorized as initiating physical activity or not, based on the self-reported physical activity. Intention-to-treat and per-protocol analysis were conducted with pooled logistic regression models with inverse-probability of treatment and censoring weights to estimate risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated with 200 sets of bootstrapping. Among 1505 participants (average age 57.6 ± 4.8 years, 67% women, 76.5% White), 72 cases of dementia and 409 cases of cognitive impairment occurred. After 12 years of follow-up, physical activity reduced dementia (RR = 0.70, 95% CI: 0.43, 0.99) for intention-to-treat analysis, and reduced dementia (RR = 0.51, 95% CI: 0.19, 0.99) and cognitive impairment (RR = 0.77, 95% CI: 0.61, 0.92) for per-protocol analysis. No significant reduction was found among older adults. Physical activity initiated during midlife may reduce dementia and cognitive impairment in late life, which highlights the importance of preventing cognitive outcomes at an earlier stage of life.

ZIBGLMM: Zero-Inflated Bivariate Generalized Linear Mixed Model for Meta-Analysis with Double-Zero-Event Studies.

Double-zero-event studies (DZS) pose a challenge for accurately estimating the overall treatment effect in meta-analysis. Current approaches, such as continuity correction or omission of DZS, are commonly employed, yet these ad hoc methods can yield biased conclusions. Although the standard bivariate generalized linear mixed model can accommodate DZS, it fails to address the potential systemic differences between DZS and other studies. In this paper, we propose a zero-inflated bivariate generalized linear mixed model (ZIBGLMM) to tackle this issue. This two-component finite mixture model includes zero-inflation for a subpopulation with negligible or extremely low risk. We develop both frequentist and Bayesian versions of ZIBGLMM and examine its performance in estimating risk ratios (RRs) against the bivariate generalized linear mixed model and conventional two-stage meta-analysis that excludes DZS. Through extensive simulation studies and real-world meta-analysis case studies, we demonstrate that ZIBGLMM outperforms the bivariate generalized linear mixed model and conventional two-stage meta-analysis that excludes DZS in estimating the true effect size with substantially less bias and comparable coverage probability.

The Relationship between Immunogenicity and Reactogenicity of Seasonal Influenza Vaccine Using Different Delivery Methods.

Vaccine immunogenicity and reactogenicity depend on recipient and vaccine characteristics. We hypothesized that healthy adults reporting higher reactogenicity from seasonal inactivated influenza vaccine (IIV) developed higher antibody titers compared with those reporting lower reactogenicity. We performed a secondary analysis of a randomized phase 1 trial of a trivalent IIV delivered by microneedle patch (MNP) or intramuscular (IM) injection. We created composite reactogenicity scores as exposure variables and used hemagglutination inhibition (HAI) titers as outcome variables. We used mixed-model analysis of variance to estimate geometric mean titers (GMTs) and titer fold change and modified Poisson generalized estimating equations to estimate risk ratios of seroprotection and seroconversion. Estimates of H3N2 GMTs were associated with the Systemic and Local scores among the IM group. Within the IM group, those with high reaction scores had lower baseline H3N2 GMTs and twice the titer fold change by day 28. Those with high Local scores had a greater probability of seroconversion. These results suggest that heightened reactogenicity to IM IIV is related to low baseline humoral immunity to an included antigen. Participants with greater reactogenicity developed greater titer fold change after 4 weeks, although the response magnitude was similar or lower compared with low-reactogenicity participants.

Assisted Reproductive Technology During COVID-19: A Population-Based Study Of Pregnancy Outcomes.

We assessed the impact of the COVID-19 pandemic on the pregnancy outcomes of patients who used assisted reproductive technology. We conducted a population-based cohort study of 443,101 patients who conceived naturally or with assisted reproductive technology between December 2015 and July 2021 and had a delivery in hospitals of Quebec, Canada. The main exposure measure was use of assisted reproductive technology before or during the pandemic. Outcomes included preeclampsia, preterm birth, and other pregnancy complications. We used adjusted log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of assisted reproductive technology with adverse pregnancy outcomes compared with natural conception before vs. during the pandemic. In secondary analyses, we examined the association of COVID-19 infection with pregnancy outcomes among women who used assisted reproductive technology. Compared with natural conception, assisted reproductive technology was associated with an increased risk of preeclampsia (RR 1.43; 95% CI 1.21-1.68), preterm birth (RR 2.07; 95% CI 1.84-2.33), and low birth weight (RR 1.94; 95% CI 1.72-2.20) during the pandemic. However, the same risks were also present before the pandemic. Compared with no infection, COVID-19 infection was not associated with adverse outcomes among women who conceived with assisted reproductive technology. This study suggests that the COVID-19 pandemic did not significantly impact the pregnancy outcomes of women who underwent assisted reproductive procedures in Quebec. The findings are reassuring for patients concerned about the potential reproductive effects of the pandemic.

Sex differences in association of joint glycemic, blood pressure and lipid control and two-year risk of falls among older adults with diabetes

AimsTo characterize the risk of falls among males and females by joint glycemic, blood pressure (BP) and cholesterol control among older adults (≥65 years) with diagnosed diabetes in USA. MethodsUsing longitudinal data from the Health and Retirement Study (2006–2019), we studied the association of joint glycemic (HbA1c < 7.5 %), BP (systolic <140 and diastolic <90 mmHg) and cholesterol (total < 200 mg/dL) control with two-year risk of falls. We estimated risk ratios (RR) to describe the associations for joint ABC control and independent biomarker control by sex, using modified Poisson regressions after adjusting for known individual and household risk factors. ResultsThe analytic sample consisted of 4509 observations from 2829 older adults (54.7 % female) with a mean age of 72.2 (SD: 6.6) years and duration of diabetes of 9.9 years. Joint ABC control was not associated with risk of falls among females but was associated with lower risk among males (0.91 [95%CI: 0.81–1.02]). Furthermore, achievement of glycemic control (0.85 [95%CI: 0.73–0.98]) and BP control (0.89 [95%CI: 0.79–1.01]) were associated with lower risk but cholesterol control (1.15 [95%CI: 0.99, 1.34]) was associated with higher risk of falls among males. ConclusionsJoint achievement of glycemic, BP and cholesterol targets may prevent falls among older males. Future studies among people with diabetes should consider biomarker control as a preventive factor for falls.

Racial and ethnic differences in the risk of dementia diagnosis under hypothetical blood pressure-lowering interventions: The Multi-Ethnic Study of Atherosclerosis.

Substantial racial and ethnic disparities in hypertension and dementia exist in the United States. We evaluated the effect of maintaining systolic blood pressure (SBP) below clinical thresholds on dementia incidence. We included 6806 Multi-Ethnic Study of Atherosclerosis participants (44 to 84 years old). We implemented the parametric g-formula to simulate the hypothetical interventions to reduce SBP below 120 and 140mmHg over time, accounting for time-varying confounding. We estimated risk ratios (RRs) and risk differences for dementia incidence at 19 years. The RRs (95% confidence intervals [CIs]) comparing an intervention reducing SBP below 120mmHg to no intervention were 0.93 (0.87 to 0.99) for total sample, 0.95 (0.88 to 1.02) for White, 0.90 (0.79 to 1.02) for Black, 0.90 (0.78 to 1.05) for Latino, and 1.16 (0.83 to 1.55) for Chinese American participants. Results for lowering SBP below 140mmHg and with death as competing event were attenuated. The reduction of SBP below 120mmHg over time has modest effects on reducing dementia incidence. More work is needed to understand the heterogeneity across racial and ethnic groups. There is a potential beneficial effect in lowering SBP to reduce the risk of dementia, which may vary by race and ethnicity. The percentage of participants who would need intervention on blood pressure to meet clinical thresholds is greater for Black and Latino communities. Results are sensitive to the way that death is specified in the research question and analysis.

Increased Risk of Preterm Delivery Subtypes and Hypertensive Disorders of Pregnancy in First Deliveries of Patients With Systemic Vasculitis.

The goal of this study was to investigate the risk of preterm birth subtypes and hypertensive disorders of pregnancy in patients with systemic vasculitis using large, statewide databases. Births to nulliparous patients with prevalent systemic vasculitides (Takayasu arteritis [TAK], Behçet disease [BD], antineutrophil cytoplasmic antibody-associated vasculitis [AAV], and Kawasaki disease [KD]) were identified using International Classification of Diseases, Ninth Revision codes in linked administrative data and birth records from the California Department of Health Care Access and Information and California Vital Statistics from 1991 to 2012. Hypertensive disorders of pregnancy and preterm delivery (PTD) subtypes were identified. Multivariable-adjusted Poisson models estimated risk ratios (RRs) of these outcomes compared with the general birthing population without history of rheumatic disease. A total of 96 births to nulliparous patients with systemic vasculitis were identified (TAK, 14; AAV, 31; BD, 26; KD, 15) and compared with 4,191,900 births of the nulliparous general population. Adjusted RRs for all PTD types were elevated in patients with vasculitis (RR 3.21, 95% confidence interval [CI] 2.15-4.79), as were the RRs of all PTD subtypes including preterm premature rupture of membranes (RR 4.30, 95% CI 2.05-9.01) and spontaneous PTD (RR 4.99, 95% CI 3.01-8.28). Of the spontaneous PTDs among patients with vasculitis, 16.7% were early PTDs (20-31 weeks), with the remaining 83.3% occurring between 32 to 36 weeks. Patients with vasculitis also had an elevated risk of hypertensive disorders of pregnancy (RR 2.96, 95% CI 1.72-5.10). Among first-time births, we found that patients with systemic vasculitis have an elevated risk of PTD subtypes as well as hypertensive disorders of pregnancy.

A simple Cox approach to estimating risk ratios without sharing individual-level data in multi-site studies.

Epidemiologic studies frequently use risk ratios to quantify associations between exposures and binary outcomes. When the data are physically stored at multiple data partners, it can be challenging to perform individual-level analysis if data cannot be pooled centrally due to privacy constraints. Existing methods either require multiple file transfers between each data partner and an analysis center (e.g., distributed regression) or only provide approximate estimation of the risk ratio (e.g., meta-analysis). Here we develop a practical method that requires a single transfer of eight summary-level quantities from each data partner. Our approach leverages an existing risk-set method and software originally developed for Cox regression. Sharing only summary-level information, the proposed method provides risk ratio estimates and confidence intervals identical to those that would be provided - if individual-level data were pooled - by the modified Poisson regression. We justify the method theoretically, confirm its performance using simulated data, and implement it in a distributed analysis of COVID-19 data from the U.S. Food and Drug Administration's Sentinel System.

O-313 Increased risk of preterm deliveries in long term survivors of children, adolescent, and young adult exposure to chemotherapy or chemo-radiotherapy: a systematic review and meta-analysis

Abstract Study question What is the long-term impact on pregnancy outcomes of a childhood adolescent, and young adult (AYA) exposure to chemotherapy or chemo-radiotherapy? Summary answer Whereas preterm delivery and pregnancy loss were significantly increased in chemotherapy and chemo-radiotherapy groups compared to control group, live birth rate was not affected. What is known already The impact of radiotherapy on the uterus has been widely described. Lately, studies have underlined the potential negative effect of chemotherapy on the womb. Indeed, three recent publications have reported that adult females treated with hematopoietic stem cell transplantation (HSCT) in childhood had a reduced uterus volume, both after conditioning by total body irradiation (TBI) and after alkylating agents-based regimen. The pregnancy outcome will depend in part on the uterine volume and its vascularization. Therefore, a history of chemotherapy or chemo-radiotherapy may be associated to an increased risk of obstetrical complications. Study design, size, duration A systematic review and meta-analysis were performed on comparative studies. Searches were conducted on Medline, Embase and the Cochrane Library from 1990 to April 2023, using the main following search terms: cancer survivors, bone marrow transplantation, chemotherapy, radiotherapy, pregnancy outcome, pregnancy complications, preterm delivery, and pregnancy loss. All studies reporting live birth rate (LBR) in adult females who have received chemotherapy and/or chemo-radiotherapy during childhood and AYA &amp;lt; 25 years were included. Participants/materials, setting, methods Two independent reviewers carried out the study selection, the bias assessment using the ROBINS-I tool and data extraction. The primary outcome was the LBR. The main secondary outcomes were preterm delivery and pregnancy loss rates. For each outcome, a random-effect frequentist network meta-analysis (NMA) was carried out to estimate risk ratios with their 95% confidence intervals. Sensitivity analyses were conducted by excluding studies at high risk of bias and leave-one out method. Main results and the role of chance After reviewing 2,328 abstracts, 25 studies were retained for review. Eight studies were included in the meta-analysis on LBR: 3,997 females became pregnant leading to 2,878 live births. The NMA shows a moderate heterogeneity/inconsistency (τ²= 0.012, I²=58% [11%; 80%]) and did not show any significant impact of treatments on LBR. Sensitivity analyses lead to the same conclusions. Six studies reported a total of 125 preterm deliveries out of 1,976 started pregnancies and were included in the NMA (τ²= 0.07, I²=19% [0%; 62%]). Chemo-radiotherapy was significantly associated with higher risk of preterm delivery compared to the control group (3.44 [1.94; 6.09]) and chemotherapy group (1.93 [1.19; 3.15]). The chemotherapy group was associated with a statistically higher risk of preterm delivery than the control group (1.78 [1.01; 3.13]). Eight studies including 606 pregnancy loss out of 3,653 started pregnancies were entered in the NMA (τ²= 0, I²=0% [0%; 65%]). Chemo-radiotherapy was associated with significantly higher risk of pregnancy loss compared to the control group (1.80 [1.34; 2.43]) and chemotherapy group (1.68 [1.26; 2.25]). No statistical difference was shown in the risk of pregnancy loss between the chemotherapy and the control groups (1.07 [0.87; 1.32]). Limitations, reasons for caution Study selection was focused on live birth rate; therefore, the research was probably not exhaustive for the secondary outcomes. Adjustment on parity or history of hormonal replacement therapy (HRT) was not performed because of a lack of data. Subgroup analysis on the type of chemotherapy was not possible. Wider implications of the findings This meta-analysis reports a negative impact of chemotherapy or chemo-radiotherapy on obstetric outcomes. Further studies including clear information on parity and use of HRT are needed. Moreover, a description on the type of chemotherapy could help to refine these conclusions. Trial registration number Not applicable

Non-benzodiazepine Hypnotics and Police-Reported Motor Vehicle Crash Risk among Older Adults: A Sequential Target Trial Emulation.

Non-benzodiazepine hypnotics ( "Z-drugs") are prescribed for insomnia, but might increase risk of motor vehicle crash (MVC) among older adults through prolonged drowsiness and delayed reaction times. We estimated the effect of initiating Z-drug treatment on the 12-week risk of MVC in a sequential target trial emulation. After linking New Jersey driver licensing and police-reported MVC data to Medicare claims, we emulated a new target trial each week (July 1, 2007 - October 7, 2017) in which Medicare fee-for-service beneficiaries were classified as Z-drug-treated or untreated at baseline and followed for an MVC. We used inverse probability of treatment and censoring weighted pooled logistic regression models to estimate risk ratios (RR) and risk differences with 95% bootstrap confidence limits (CLs). There were 257,554 person-trials, of which 103,371 were Z-drug-treated and 154,183 untreated, giving rise to 976 and 1,249 MVCs, respectively. The intention-to-treat RR was 1.06 (95%CLs 0.95, 1.16). For the per-protocol estimand, there were 800 MVCs and 1,241 MVCs among treated and untreated person-trials, respectively, suggesting a reduced MVC risk (RR 0.83 [95%CLs 0.74, 0.92]) with sustained Z-drug treatment. Z-drugs should be prescribed to older patients judiciously but not withheld entirely over concerns about MVC risk.

Sexual orientation disparities in gestational diabetes and hypertensive disorders of pregnancy.

Sexual minority (SM) individuals (e.g., those with same-sex attractions/partners or who identify as lesbian/gay/bisexual) experience a host of physical and mental health disparities. However, little is known about sexual orientation-related disparities in gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP; gestational hypertension [gHTN] and preeclampsia). To estimate disparities in GDM, gHTN and preeclampsia by sexual orientation. We used data from the Nurses' Health Study II-a cohort of nurses across the US enrolled in 1989 at 25-42 years of age-restricted to those with pregnancies ≥20 weeks gestation and non-missing sexual orientation data (63,518 participants; 146,079 pregnancies). Our primary outcomes were GDM, gHTN and preeclampsia, which participants reported for each of their pregnancies. Participants also reported their sexual orientation identity and same-sex attractions/partners. We compared the risk of each outcome in pregnancies among heterosexual participants with no same-sex experience (reference) to those among SM participants overall and within subgroups: (1) heterosexual with same-sex experience, (2) mostly heterosexual, (3) bisexual and (4) lesbian/gay participants. We used modified Poisson models to estimate risk ratios (RR) and 95% confidence intervals (CI), fit via weighted generalised estimating equations, to account for multiple pregnancies per person over time and informative cluster sizes. The overall prevalence of each outcome was ≤5%. Mostly heterosexual participants had a 31% higher risk of gHTN (RR 1.31, 95% CI 1.03, 1.66), and heterosexual participants with same-sex experience had a 31% higher risk of GDM (RR 1.31, 95% CI 1.13, 1.50), compared to heterosexual participants with no same-sex experience. The magnitudes of the risk ratios were high among bisexual participants for gHTN and preeclampsia and among lesbian/gay participants for gHTN. Some SM groups may be disparately burdened by GDM and HDP. Elucidating modifiable mechanisms (e.g., structural barriers, discrimination) for reducing adverse pregnancy outcomes among SM populations is critical.

Slavery, Home Ownership, and Contemporary Perinatal Outcomes in the Southeast: A Test of Mediation and Moderation.

To estimate the effect of geographic variation in historic slavery on perinatal outcomes [chronic hypertension, hypertensive disorders of pregnancy (HDP), very preterm birth (VPTB), or very low birth weight birth (VLBW)] among Black people living in states where slavery was legal in 1860 and test mediation by Black homeownership. We linked data from the 1860 census (the proportion of enslaved residents) to natality data on outcomes (2013-2021) using resident county. The percent of Black residents in a county who owned their home was a potential mediator. We fit log binomial models to estimate risk ratios (RRs) representing total and controlled direct effects (accounting for Black homeownership) of proportion enslaved on outcomes, accounting for potential confounding using marginal structural models. Among 2,443,198 included births, 8.8% (213,829) experienced HDP, 4.1% (100,549) chronic hypertension, 3.3% (81,072) VPTB, and 2.6% (62,538) VLBW. There was an increase in chronic hypertension and VPTB risk, but not HDP or VLBW, in counties with a 10% greater proportion enslaved in 1860 [adjusted RR: 1.06, 95% CI: (1.02, 1.1); 1.02 (1.00, 1.05); 1.00 (0.98, 1.02); 1.01 (1.00, 1.03)]. There was not evidence of mediation by Black homeownership. Historic slavery remains relevant for perinatal health.

Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa

BackgroundHypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes.MethodsWe conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120–129 and dBP < 80), stage 1 hypertension (sBP 130–139 or dBP 80–89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group.ResultsFrom May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes.ConclusionThe ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.

Negative association of sea lice from fish farms on recreational fishing catches of Atlantic salmon

Abstract The question of whether and to what extent sea‐louse (Lepeophtheirus salmonis) infestations from salmon farms influence wild Atlantic salmon survival has been subject to sustained scientific debate and political controversy. Documenting population‐level effects of sea lice on wild salmon remains inherently challenging. We employ comprehensive sea‐lice data and recreational catch data from Norway to assess the impact of farm sea‐louse infestations on wild salmon catches in different production areas (PAs). Our analysis finds a significant correlation between declines in wild Atlantic salmon catches and increasing amounts of adult female sea lice per km2. The effect is most pronounced in PA 4 on the west coast of Norway, an area within the government's” traffic light” management system where out‐migrating salmon smolts are deemed to face high risk of louse‐induced mortality. Our model predicts below‐average catches when the total sea‐louse load exceeds the limit of 0.1 average adult female sea louse per farmed fish within some production areas. Furthermore, our results indicate that the risk of below‐average catches increases by approximately 47% when salmon farms exceed this limit (estimated risk ratio of 1.47, 95% CI [1.10, 1.96]). Synthesis and applications: Our study expands the existing body of evidence demonstrating a negative association between fish farming and the ecosystem services provided by wild salmon stocks. This has important implications for aquaculture management. First, it shows that farm sea lice directly affect peoples, rights holders and interest groups, such as landowners and anglers, who rely on viable populations of wild salmon. Second, it suggests that a &gt;0.1 sea lice limit may be insufficient to prevent subpar catches in some areas. Furthermore, in the context of allowing further growth in farmed salmon biomass, setting absolute sea‐louse limits for entire production areas may be a more effective regulatory instrument than setting average lice limits per farmed fish. Our findings contribute to advancing a scientific basis for setting appropriate louse limits on farm and area scales.

Does reversible postpartum contraception reduce the risk of pregnancy condition recurrence? A longitudinal claims-based study from Maine

PurposeTo estimate the effect of reversible postpartum contraception use on the risk of recurrent pregnancy condition in the subsequent pregnancy and if this effect was mediated through lengthening the interpregnancy interval (IPI). MethodsWe used data from the Maine Health Data Organization's Maine All Payer Claims dataset. Our study population was Maine women with a livebirth index pregnancy between 2007 and 2019 that was followed by a subsequent pregnancy starting within 60 months of index pregnancy delivery. We examined recurrence of three pregnancy conditions, separately, in groups that were not mutually exclusive: prenatal depression, hypertensive disorders of pregnancy (HDP), and gestational diabetes (GDM). Effective reversible postpartum contraception use was defined as any intrauterine device, implant, or moderately effective method (pills, patch, ring, injectable) initiated within 60 days of delivery. Short IPI was defined as ≤ 12 months. We used log-binomial regression models to estimate risk ratios and 95 % confidence intervals, adjusting for potential confounders. ResultsApproximately 41 % (11,448/28,056) of women initiated reversible contraception within 60 days of delivery, the prevalence of short IPI was 26 %, and the risk of pregnancy condition recurrence ranged from 38 % for HDP to 55 % for prenatal depression. Reversible contraception initiation within 60 days of delivery was not associated with recurrence of the pregnancy condition in the subsequent pregnancy (aRR ranged from 0.97 to 1.00); however, it was associated with lower risk of short IPI (aRR ranged from 0.67 to 0.74). Conclusion(s)Although initiation of postpartum reversible contraception within 60 days of delivery lengthens the IPI, our findings suggest that it does not reduce the risk of prenatal depression, HDP, or GDM recurrence. This indicates a missed opportunity for providing evidence-based healthcare and health interventions in the intrapartum period to reduce the risk of recurrence.

Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock

There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. To determine whether prolonged β-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of β-lactam antibiotics in critically ill adults with sepsis or septic shock. Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of β-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. PROSPERO Identifier: CRD42023399434.