The what, where and how of delay activity.

Working memory is characterized by neural activity that persists during the retention interval of delay tasks. Despite the ubiquity of this delay activity across tasks, species and experimental techniques, our understanding of this phenomenon remains incomplete. Although initially there was a narrow focus on sustained activation in a small number of brain regions, methodological and analytical advances have allowed researchers to uncover previously unobserved forms of delay activity various parts of the brain. In light of these new findings, this Review reconsiders what delay activity is, where in the brain it is found, what roles it serves and how it may be generated.

Impact of hypertensive disorders of pregnancy and gestational diabetes mellitus on offspring cardiovascular health in early adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain. OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSION: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Socioeconomic disadvantage in pregnancy and postpartum risk of cardiovascular disease.

BACKGROUND: Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. However, the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. OBJECTIVE: To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. STUDY DESIGN: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic cardiovascular disease (ASCVD, composite of fatal and nonfatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2 to 7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD ≥10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. RESULTS: Among 4309 nulliparous individuals at baseline, the median age was 27 years (interquartile range [IQR]: 23-31) and the median ADI was 43 (IQR: 22-74). At 2 to 7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk ≥10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adjusted ß: 0.41; 95% confidence interval [CI]: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top 2 ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (adjusted risk ratio [aRR]: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSION: Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Rural-urban disparities in pregestational and gestational diabetes in pregnancy: Serial, cross-sectional analysis of over 12 million pregnancies.

OBJECTIVE: To compare trends in pregestational (DM) and gestational diabetes (GDM) in pregnancy in rural and urban areas in the USA, because pregnant women living in rural areas face unique challenges that contribute to rural-urban disparities in adverse pregnancy outcomes. DESIGN: Serial, cross-sectional analysis. SETTING: US National Center for Health Statistics (NCHS) Natality Files from 2011 to 2019. POPULATION: A total of 12 401 888 singleton live births to nulliparous women aged 15-44 years. METHODS: We calculated the frequency (95% confidence interval [CI]) per 1000 live births, the mean annual percentage change (APC), and unadjusted and age-adjusted rate ratios (aRR) of DM and GDM in rural compared with urban maternal residence (reference) per the NCHS Urban-Rural Classification Scheme overall, and by delivery year, reported race and ethnicity, and US region (effect measure modification). MAIN OUTCOME MEASURES: The outcomes (modelled separately) were diagnoses of DM and GDM. RESULTS: From 2011 to 2019, there were increases in both the frequency (per 1000 live births; mean APC, 95% CI per year) of DM and GDM in rural areas (DM: 7.6 to 10.4 per 1000 live births; APC 2.8%, 95% CI 2.2%-3.4%; and GDM: 41.4 to 58.7 per 1000 live births; APC 3.1%, 95% CI 2.6%-3.6%) and urban areas (DM: 6.1 to 8.4 per 1000 live births; APC 3.3%, 95% CI 2.2%-4.4%; and GDM: 40.8 to 61.2 per 1000 live births; APC 3.9%, 95% CI 3.3%-4.6%). Individuals living in rural areas were at higher risk of DM (aRR 1.48, 95% CI 1.45%-1.51%) and GDM versus those in urban areas (aRR 1.17, 95% CI 1.16%-1.18%). The increased risk was similar each year for DM (interaction p = 0.8), but widened over time for GDM (interaction p < 0.01). The rural-urban disparity for DM was wider for individuals who identified as Hispanic race/ethnicity and in the South and West (interaction p < 0.01 for all); and for GDM the rural-urban disparity was generally wider for similar factors (i.e. Hispanic race/ethnicity, and in the South; interaction p < 0.05 for all). CONCLUSIONS: The frequency of DM and GDM increased in both rural and urban areas of the USA from 2011 to 2019 among nulliparous pregnant women. Significant rural-urban disparities existed for DM and GDM, and increased over time for GDM. These rural-urban disparities were generally worse among those of Hispanic race/ethnicity and in women who lived in the South. These findings have implications for delivering equitable diabetes care in pregnancy in rural US communities.

Common Neural Mechanisms Control Attention and Working Memory.

Although previous studies point to qualitative similarities between working memory (WM) and attention, the degree to which these two constructs rely on shared neural mechanisms remains unknown. Focusing on one such potentially shared mechanism, we tested the hypothesis that selecting an item within WM utilizes similar neural mechanisms as selecting a visible item via a shift of attention. We used fMRI and machine learning to decode both the selection among items visually available and the selection among items stored in WM in human subjects (both sexes). Patterns of activity in visual, parietal, and to a lesser extent frontal cortex predicted the locations of the selected items. Critically, these patterns were strikingly interchangeable; classifiers trained on data during attentional selection predicted selection from WM, and classifiers trained on data during selection from memory predicted attentional selection. Using models of voxel receptive fields, we visualized topographic population activity that revealed gain enhancements at the locations of the externally and internally selected items. Our results suggest that selecting among perceived items and selecting among items in WM share a common mechanism. This common mechanism, analogous to a shift of spatial attention, controls the relative gains of neural populations that encode behaviorally relevant information.SIGNIFICANCE STATEMENT How we allocate our attention to external stimuli that we see and to internal representations of stimuli stored in memory might rely on a common mechanism. Supporting this hypothesis, we demonstrated that not only could patterns of human brain activity predict which items were selected during perception and memory, but that these patterns were interchangeable during external and internal selection. Additionally, this generalized selection mechanism operates by changes in the gains of the neural populations both encoding attended sensory representations and storing relevant memory representations.

Association of Living in a Food Desert and Poor Periconceptional Diet Quality in a Cohort of Nulliparous Pregnant Individuals.

BACKGROUND: A poor diet can result from adverse social determinants of health and increases the risk of adverse pregnancy outcomes. OBJECTIVE: We aimed to assess, using data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be prospective cohort, whether nulliparous pregnant individuals who lived in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert. METHODS: The exposure was living in a food desert based on a spatial overview of food access indicators by income and supermarket access per the Food Access Research Atlas. The outcome was periconceptional diet quality per the Healthy Eating Index (HEI)-2010, analyzed by quartile (Q) from the highest or best (Q4, reference) to the lowest or worst dietary quality (Q1); and secondarily, nonadherence (yes or no) to 12 key aspects of dietary quality. RESULTS: Among 7,956 assessed individuals, 24.9% lived in a food desert. The mean HEI-2010 score was 61.1 of 100 (SD: 12.5). Poorer periconceptional dietary quality was more common among those who lived in a food desert compared with those who did not live in a food desert (Q4: 19.8%, Q3: 23.6%, Q2: 26.5%, and Q1: 30.0% vs. Q4: 26.8%, Q3: 25.8%, Q2: 24.5%, and Q1: 22.9%; overall P < 0.001). Individuals living in a food desert were more likely to report a diet in lower quartiles of the HEI-2010 (i.e., poorer dietary quality) (aOR: 1.34 per quartile; 95% CI: 1.21, 1.49). They were more likely to be nonadherent to recommended standards for 5 adequacy components of the HEI-2010, including fruit, total vegetables, greens and beans, seafood and plant proteins, and fatty acids, and less likely to report excess intake of empty calories. CONCLUSIONS: Nulliparous pregnant individuals living in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert.

Bedside tracking of functional autonomic age in preterm infants.

BACKGROUND: Preterm birth predisposes infants to adverse outcomes that, without early intervention, impacts their long-term health. To assist bedside monitoring, we developed a tool to track the autonomic maturation of the preterm by assessing heart rate variability (HRV) changes during intensive care. METHODS: Electrocardiogram (ECG) recordings were longitudinally recorded in 67 infants (26-38 weeks postmenstrual age (PMA)). Supervised machine learning was used to generate a functional autonomic age (FAA), by combining 50 computed HRV features from successive 5-minute ECG epochs (median of 23 epochs per infant). Performance of the FAA was assessed by correlation to PMA, clinical outcomes and the infant's functional brain age (FBA), an index of maturation derived from the electroencephalogram. RESULTS: The FAA was strongly correlated to PMA (r = 0.86, 95% CI: 0.83-0.93) with a mean absolute error (MAE) of 1.66 weeks and also accurately estimated FBA (MAE = 1.58 weeks, n = 54 infants). The relationship between PMA and FAA was not confounded by neurodevelopmental outcome (p = 0.18, n = 45), sex (p = 0.88, n = 56), patent ductus arteriosus (p = 0.08, n = 56), IVH (p = 0.63, n = 56) or body weight at birth (p = 0.95, n = 56). CONCLUSIONS: The FAA, an index derived from the ubiquitous ECG signal, offers direct avenues towards estimating autonomic maturation at the bedside during intensive care monitoring. IMPACT: The development of a tool to track functional autonomic age in preterm infants based on heart rate variability features in the electrocardiogram provides a rapid and specialized view of autonomic maturation at the bedside. Functional autonomic age is linked closely to postmenstrual age and central nervous system function response, as determined by its relationship to functional brain age from the electroencephalogram. Tracking functional autonomic age during neonatal intensive care unit monitoring offers a unique insight into cardiovascular health in infants born extremely preterm and their maturational trajectories to term age.

Association between Individual versus Community-level Social Vulnerability and Neonatal Opioid Withdrawal Syndrome among Pregnant Individuals Receiving Buprenorphine for Opioid Use Disorder.

OBJECTIVE: Individual patient-level measures of adverse social determinants of health are associated with neonatal opioid withdrawal syndrome (NOWS), but the relative impact of community-level adverse social determinants of health remains to be defined. We examined the association between community-level social vulnerability and NOWS among pregnant individuals receiving buprenorphine for opioid use disorder. STUDY DESIGN: We conducted a secondary analysis of an established cohort of pregnant individuals and their infants participating in a multidisciplinary prenatal/addiction care program from 2013 to 2021. Addresses were geocoded using ArcGIS and linked at the census tract to the Centers for Disease Control and Prevention 2018 Social Vulnerability Index (SVI), incorporating 15 census variables. The primary exposure was the SVI as a composite measure of community-level social vulnerability, and secondarily, individual scores for four thematic domains (socioeconomic status, household composition and disability, minority status and language, and housing type and transportation). The primary outcome was a clinical diagnosis of NOWS defined as withdrawal requiring pharmacological treatment following buprenorphine exposure. RESULTS: Among 703 pregnant individuals receiving buprenorphine, 39.8% (280/703) of infants were diagnosed with NOWS. Among our patinets, those who were nulliparous, had post-traumatic stress disorder, a term birth (≥ 37 weeks) and had a male infant were more likely to have an infant diagnosed with NOWS. Individuals with and without an infant diagnosed with NOWS had similarly high community-level social vulnerability per composite SVI scores (mean [standard deviation]: 0.6 [0.4-0.7] vs. 0.6 [0.4-0.7], p = 0.2]. In adjusted analyses, SVI, as a composite measure as well as the four domains, was not associated with NOWS diagnosis. CONCLUSION: Among pregnant persons receiving buprenorphine enrolled in a multidisciplinary prenatal and addition care program, while individual risk factors that measure adverse social determinants of health were associated with an NOWS diagnosis in the infant, community-level social vulnerability as measured by the SVI was not associated with the outcome. KEY POINTS: · Community-level SVI was not associated with neonatal opioid use disorder.. · Certain individual risk factors were identified as being associated with NOWS.. · Homogeneity of composite SVI scores may have led to lack of significant findings..

Hospital Admissions from the Emergency Department and Subsequent Critical Care Interventions for Influenza during Pregnancy.

OBJECTIVE: The objectives of this study were to determine (1) whether obstetrical patients were more likely to be admitted from the emergency department (ED) for influenza compared with nonpregnant women, and (2) require critical care interventions once admitted. STUDY DESIGN: Using data from the 2006 to 2011 Nationwide Emergency Department Sample, ED encounters for influenza for women aged 15 to 54 years without underlying chronic medical conditions were identified. Women were categorized as pregnant or nonpregnant using billing codes. Multivariable log linear models were fit to evaluate the relative risk of admission from the ED and the risk of intensive care unit (ICU)-level interventions including mechanical ventilation and central monitoring with pregnancy status as the exposure of interest. Measures of association were described with adjusted risk ratios (aRRs) with 95% confidence intervals (CIs). RESULTS: We identified 15.9 million ED encounters for influenza of which 4% occurred among pregnant women. Pregnant patients with influenza were nearly three times as likely to be admitted as nonpregnant patients (aRR = 2.99, 95% CI: 2.94, 3.05). Once admitted, obstetric patients were at 72% higher risk of ICU-level interventions (aRR = 1.72, 95% CI: 1.61, 1.84). Of pregnant women admitted from the ED, 9.3% required ICU-level interventions such as mechanical ventilation or central monitoring. Older patients and those with Medicare were also at high risk of admission and ICU-level interventions (p < 0.01). CONCLUSION: Pregnancy confers three times the risk of admission from the ED for influenza and pregnant women are significantly more likely to require ICU-level medical interventions compared with women of similar age. These findings confirm the significant disease burden from influenza in the obstetric population and the public health importance of reducing infection risk. KEY POINTS: · Pregnancy confers three times the risk of admission from the ED for influenza.. · Pregnant women admitted with influenza are significantly more likely to require ICU-level care.. · Influenza represents a significant disease burden in the obstetric population.

Association between Diabetes in Pregnancy and Shoulder Dystocia by Infant Birth Weight in an Era of Cesarean Delivery for Suspected Macrosomia.

OBJECTIVE: We estimated the association between diabetes and shoulder dystocia by infant birth weight subgroups (<4,000, 4,000-4,500, and >4,500 g) in an era of prophylactic cesarean delivery for suspected macrosomia. STUDY DESIGN: A secondary analysis from the National Institute of Child Health and Human Development U.S. Consortium for Safe Labor of deliveries at ≥24 weeks with a nonanomalous, singleton fetus with vertex presentation undergoing a trial of labor. The exposure was either pregestational or gestational diabetes compared with no diabetes. The primary outcome was shoulder dystocia and secondarily, birth trauma with a shoulder dystocia. We calculated adjusted risk ratios (aRRs) with modified Poison's regression between diabetes and shoulder dystocia and the number needed to treat (NNT) to prevent a shoulder dystocia with cesarean delivery. RESULTS: Among 167,589 assessed deliveries (6% with diabetes), pregnant individuals with diabetes had a higher risk of shoulder dystocia at birth weight <4,000 g (aRR: 1.95; 95% confidence interval [CI]: 1.66-2.31) and 4,000 to 4,500 g (aRR: 1.57; 95% CI: 1.24-1.99), albeit not significantly at birth weight >4,500 g (aRR: 1.26; 95% CI: 0.87-1.82) versus those without diabetes. The risk of birth trauma with shoulder dystocia was higher with diabetes (aRR: 2.29; 95% CI: 1.54-3.45). The NNT to prevent a shoulder dystocia with diabetes was 11 and 6 at ≥4,000 and >4,500 g, versus without diabetes, 17 and 8 at ≥4,000 and >4,500 g, respectively. CONCLUSION: Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered. Guidelines providing the option of cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights. KEY POINTS: · >Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered.. · Cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights.. · These findings can inform delivery planning for providers and pregnant individuals with diabetes..

Patient Priorities, Decisional Comfort, and Satisfaction with Metformin versus Insulin for the Treatment of Gestational Diabetes Mellitus.

OBJECTIVE: We compared patient priorities, decisional comfort, and satisfaction with treating gestational diabetes mellitus (GDM) with metformin versus insulin among pregnant individuals with GDM requiring pharmacotherapy. STUDY DESIGN: We conducted a cross-sectional study of patients' perspectives about GDM pharmacotherapy in an integrated prenatal and diabetes care program from October 19, 2022, to August 24, 2023. The exposure was metformin versus insulin as the initial medication decision. Outcomes included standardized measures of patient priorities, decisional comfort, and satisfaction about their medication decision. RESULTS: Among 144 assessed individuals, 60.4% were prescribed metformin and 39.6% were prescribed insulin. Minoritized individuals were more likely to receive metformin compared with non-Hispanic White individuals (34.9 vs. 17.5%; p = 0.03). Individuals who were willing to participate in a GDM pharmacotherapy clinical trial were more likely to receive insulin than those who were unwilling (30.4 vs. 19.5%; p = 0.02). Individuals receiving metformin were more likely to report prioritizing avoiding injections (62.4 vs. 19.3%; adjusted odds ratio [aOR]: 2.83; 95% confidence interval [CI]: 1.10-7.31), wanting to take a medication no more than twice daily (56.0 vs. 30.4%; aOR: 3.67; 95% CI: 1.56-8.67), and believing that both medications can equally prevent adverse pregnancy outcomes (70.9 vs. 52.6%; aOR: 2.67; 95% CI: 1.19-6.03). Conversely, they were less likely to report prioritizing a medication that crosses the placenta (39.1 vs. 82.5%; aOR: 0.09; 95% CI: 0.03-0.25) and needing supplemental insulin to achieve glycemic control (21.2 vs. 47.4%; aOR: 0.36; 95% CI: 0.15-0.90). Individuals reported similarly high (mean score > 80%) levels of decisional comfort, personal satisfaction with medication decision-making, and satisfaction about their conversation with their provider about their medication decision with metformin and insulin (p ≥ 0.05 for all). CONCLUSION: Individuals with GDM requiring pharmacotherapy reported high levels of decision comfort and satisfaction with both metformin and insulin, although they expressed different priorities in medication decision-making. These results can inform future patient-centered GDM treatment strategies. KEY POINTS: · Pregnant individuals with GDM requiring pharmacotherapy expressed a high level of decisional comfort and satisfaction with medication decision making.. · Individuals placed different priorities on deciding to take metformin versus insulin.. · These results can inform interventions aimed at delivering person-centered diabetes care in pregnancy that integrates patient autonomy and knowledge about treatment options..

Microbiota links to neural dynamics supporting threat processing.

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive-interoceptive appraisal of threat-related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high-level ecological indices with threat-related AIC-dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota-derived metabolites in the observed relationship with threat-related brain processes.

Associations between HIV, antiretroviral therapy and preterm birth in the US Women's Interagency HIV Study, 1995-2018: a prospective cohort.

OBJECTIVE: To evaluate the associations of HIV infection with preterm birth (PTB), and of HIV antiretroviral therapy (ART) with PTB. METHODS: We analysed singleton live-born pregnancies among women from 1995 to 2019 in the Women's Interagency HIV Study, a prospective cohort of US women with, or at risk for, HIV. The primary exposures were HIV status and ART use before delivery [none, monotherapy or dual therapy, or highly active antiretroviral therapy (HAART)]. The primary outcome was PTB < 34 weeks, and, secondarily, < 28 and < 37 weeks. We analysed self-reported birth data, and separately modelled the associations between HIV and PTB, and between ART and PTB, among women with HIV. We used modified Poisson regression, and adjusted for age, race, parity, tobacco use and delivery year, and, when modelling the impact of ART, duration from HIV diagnosis to delivery, nadir CD4 count, and pre-pregnancy viral load and CD4 count. RESULTS: We analysed 488 singleton deliveries (56% exposed to HIV) to 383 women. The risk of PTB < 34 weeks was similar among women with and without HIV, but the risk of PTB < 37 weeks was higher [32% vs. 23%; adjusted risk ratio (aRR) = 1.43; 95% confidence interval (CI): 1.07-1.91] among women with HIV. The risk of PTB < 34 weeks was lower among women with HIV receiving HAART than among those receiving no ART (7% vs. 26%; aRR:0.19; 95% CI: 0.08-0.44). The associations between HAART and PTB < 28 and < 37 weeks were similar. CONCLUSIONS: Antiretroviral therapy exposure was associated with a decreased risk of PTB among a US cohort of women with HIV. Given the growing concerns about ART and adverse pregnancy outcomes, this finding that ART may be protective for PTB is reassuring.

Association of change in haemoglobin A1c with adverse perinatal outcomes in women with pregestational diabetes.

AIMS: To determine whether a net decline in glycosylated haemoglobin (HbA1c ) from early to late pregnancy is associated with lower risk of adverse perinatal outcomes at delivery among women with pregestational diabetes. METHODS: A retrospective analysis from 2012 to 2016 at a tertiary care centre. The exposure was the net change in HbA1c from early (<20 weeks gestation) to late pregnancy (≥20 weeks gestation). Primary outcomes were large for gestational age (LGA) and neonatal hypoglycaemia. The association between outcomes per 6 mmol/mol (0.5%) absolute decrease in HbA1c was evaluated using modified Poisson regression, and adjusted for age, body mass index, White Class, early HbA1c and haemoglobin and gestational age at HbA1c measurement and delivery. RESULTS: Among 347 women with pregestational diabetes, HbA1c was assessed in early (9 weeks [IQR 7,13]) and late pregnancy (31 weeks [IQR 29,34]). Mean HbA1c decreased from early (59 mmol/mol [7.5%]) to late (47 mmol/mol [6.5%]) pregnancy. Each 6 mmol/mol (0.5%) absolute decrease in HbA1c was associated with a 12% reduced risk of LGA infant (30%, aRR:0.88; 95% CI:0.81,0.95), and a 7% reduced risk of neonatal hypoglycaemia (35%, aRR:0.93; 95% CI:0.87,0.99). Preterm birth (36%, aRR:0.93; 95% CI:0.89,0.98) and neonatal intensive care unit admission (55%, aRR:0.95; 95% CI:0.91,0.98) decreased with a net decline in HbA1c , but not caesarean delivery, pre-eclampsia, shoulder dystocia and respiratory distress syndrome. CONCLUSIONS: Women with pregestational diabetes with a reduction in HbA1c may have fewer infants born LGA or with neonatal hypoglycaemia. Repeated assessment of HbA1c may provide an additional measure of glycaemic control.

Characteristics and perceptions associated with COVID-19 vaccination hesitancy among pregnant and postpartum individuals: A cross-sectional study.

OBJECTIVE: To assess the frequency and associated characteristics of COVID-19 vaccine hesitancy among pregnant and postpartum individuals. DESIGN: Cross-sectional study. SETTING: Prenatal care at a single academic tertiary care centre. POPULATION: Pregnant and postpartum individuals enrolled in prenatal care at a single academic tertiary care centre from 22 March 2021 to 2 April 2021, concurrent with state guidelines recommending COVID-19 vaccination in pregnancy. METHODS: We used logistic regression to identify characteristics associated with COVID-19 vaccine hesitancy, and adjusted for: age, parity, race, trimester of pregnancy, and chronic comorbidities. MAIN OUTCOME MEASURES: COVID-19 vaccine hesitancy, defined as uncertainty or refusal of the vaccine, despite the availability of vaccine services, in accordance with the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on vaccine hesitancy. RESULTS: Of the 485 individuals screened and approached, 456 (94%) enrolled and completed the survey (435/456, 95% pregnant). The frequency of COVID-19 vaccine hesitancy was 46% (95% CI 41%-51%). Sociodemographic characteristics, including non-Hispanic Black race, younger age, lower education, public health insurance receipt, parity >1, and reported substance use, were associated with a higher odds of COVID-19 vaccine hesitancy, but not clinical risk conditions. Individuals who had a family or friend vaccinated for COVID-19, prior or planned vaccination for tetanus, diphtheria and acellular pertussis (Tdap) and/or influenza, and who perceived that vaccination benefited the baby were less likely to express COVID-19 vaccine hesitancy. CONCLUSIONS: COVID-19 vaccine hesitancy was frequent among pregnant and postpartum individuals. Those who may face barriers to accessing healthcare services were more likely to report vaccine hesitancy. These results can inform interventions to increase COVID-19 vaccine uptake in pregnancy. TWEETABLE ABSTRACT: COVID-19 vaccination hesitancy is frequent among pregnant and postpartum individuals, and those who face barriers to accessing healthcare services are more likely to report COVID-19 vaccine hesitancy.

Association of initial COVID-19 vaccine hesitancy with subsequent vaccination among pregnant and postpartum individuals.

OBJECTIVE: To examine the association between initial COVID-19 vaccine hesitancy and subsequent vaccination among pregnant and postpartum individuals. DESIGN: Prospective cohort. SETTING: A Midwestern tertiary-care academic medical center. Individuals completed a baseline vaccine hesitancy assessment from 22 March 2021 to 2 April 2021, with subsequent ascertainment of vaccination status at 3-6 months follow-up. METHODS: We used multivariable Poisson regression to estimate the relative risk of vaccination by baseline vaccine hesitancy status, and then characteristics associated with vaccination. MAIN OUTCOME MEASURES: Self-report of COVID-19 vaccination, and secondarily, consideration of COVID-19 vaccination among those not vaccinated. RESULTS: Of 456 individuals (93% pregnant, 7% postpartum) initially surveyed, 290 individuals (64%; 23% pregnant, 77% postpartum) provided subsequent vaccination status (median = 17 weeks). Of these 290 individuals, 40% (116/290) reported COVID-19 vaccine hesitancy upon enrolment, of whom 52% reported subsequent vaccination at follow-up. Few individuals transitioned during the study period from vaccine hesitant to vaccinated (10%); in comparison, 80% of those who were not vaccine hesitant were vaccinated at follow-up (aRR 0.19, 95% CI 0.11-0.33). Among those who remained unvaccinated at follow-up, 38% who were vaccine hesitant at baseline were considering vaccination, compared with 71% who were not vaccine hesitant (aRR 0.48, 95% CI 0.33-0.67). Individuals who were older, parous, employed and of higher educational attainment were more likely to be vaccinated, and those who identified as non-Hispanic black, were Medicaid beneficiaries, and were still pregnant at follow-up were less likely to be vaccinated. CONCLUSIONS: COVID-19 vaccine hesitancy persisted over time in the peripartum period, and few individuals who reported hesitancy at baseline were later vaccinated. Interventions that address vaccine hesitancy in pregnancy are needed.

Association between Prenatal Marijuana and Tobacco Smoke Exposures and Small for Gestational Age at Birth.

OBJECTIVE: The aim of this study was to determine the association of prenatal marijuana exposure with and without tobacco smoke exposure and small for gestational age (SGA) at birth. STUDY DESIGN: We conducted a secondary analysis of the prospective Lifestyle and Early Achievement in Families (LEAF) cohort enrolled from 2010 to 2015. We included singleton nonanomalous liveborn pregnancies. We assessed marijuana use inclusive of any pregnancy urine specimen with a Δ9-THC-COOH concentration of more than 15 ng/mL by mass spectrometry, self-report on questionnaire, and/or electronic health record; and self-reported maternal tobacco use. Because of the high co-frequency of marijuana with tobacco exposure in pregnancy and the known association between tobacco and fetal growth restriction, we modeled the exposure as: both marijuana and tobacco (hereafter "co-use"), only marijuana, only tobacco, and neither (reference). Incidence of SGA in each group was compared with the neither group. The primary outcome was SGA less than 10th percentile, and secondarily less than 5th percentile, using parity-specific definitions per 2017 US natality reference data. RESULTS: Among 325 assessed mothers, 46% had neither exposure, 11% had only prenatal marijuana exposure, 20% only tobacco exposure, and 23% co-use exposure. A third (33%) of infants were SGA less than 10th percentile and 20% SGA less than 5th percentile. Marijuana exposure only was associated with an increased risk of SGA less than 10th percentile (43 vs. 26%; adjusted relative risk [aRR]: 1.66; 95% confidence interval [CI]: 1.02-2.69), and SGA less than5th percentile (30 vs. 13%; aRR: 2.26; 95% CI: 1.15-4.47). Tobacco was not associated with SGA less than 10th percentile, but was with SGA less than 5th percentile (26 vs. 13%; aRR: 2.01; 95% CI: 1.13, 3.56). Co-use was not associated with increased SGA risk in multivariate analysis, but was in sensitivity analysis when tobacco use was defined using a cotinine assay rather than self-report (SGA <10th percentile, aRR: 1.97; 95% CI: 1.24-3.15) and (SGA <5th percentile, aRR: 2.03; 95% CI: 1.09-3.78). CONCLUSION: Prenatal marijuana exposure in addition to tobacco may increase the risk of SGA. Given the rising prevalence of marijuana use in pregnancy, further research is warranted to understand how in utero marijuana exposure may impact fetal growth and birth weight with and without tobacco exposure. KEY POINTS: · Marijuana and tobacco are commonly used together in pregnancy.. · Prenatal marijuana and tobacco exposure may increase the risk of a small for gestational age infant.. · Further research is warranted to understand how in utero marijuana exposure impacts fetal growth..

External Validation of Postpartum Hemorrhage Prediction Models Using Electronic Health Record Data.

OBJECTIVE: A recent study leveraging machine learning methods found that postpartum hemorrhage (PPH) can be predicted accurately at the time of labor admission in the U.S. Consortium for Safe Labor (CSL) dataset, with a C-statistic as high as 0.93. These CSL models were developed in older data (2002-2008) and used an estimated blood loss (EBL) of ≥1,000 mL to define PPH. We sought to externally validate these models using a more recent cohort of births where blood loss was measured using quantitative blood loss (QBL) methods. STUDY DESIGN: Using data from 5,261 deliveries between February 1, 2019 and May 11, 2020 at a single tertiary hospital, we mapped our electronic health record (EHR) data to the 55 predictors described in previously published CSL models. PPH was defined as QBL ≥1,000 mL within 24 hours after delivery. Model discrimination and calibration of the four CSL models were measured using our cohort. In a secondary analysis, we fit new models in our study cohort using the same predictors and algorithms as the original CSL models. RESULTS: The original study cohort had a substantially lower rate of PPH, 4.8% (7,279/228,438) versus 25% (1,321/5,261), possibly due to differences in measurement. The CSL models had lower discrimination in our study cohort, with a C-statistic as high as 0.57 (logistic regression). Models refit in our study cohort achieved better discrimination, with a C-statistic as high as 0.64 (random forest). Calibration improved in the refit models as compared with the original models. CONCLUSION: The CSL models' accuracy was lower in a contemporary EHR where PPH is assessed using QBL. As institutions continue to adopt QBL methods, further data are needed to understand the differences between EBL and QBL to enable accurate prediction of PPH. KEY POINTS: · Machine learning methods may help predict PPH.. · EBL models do not generalize when QBL is used.. · Blood loss estimation alters model accuracy..

Gestational Weight Gain and Adverse Maternal and Neonatal Outcomes for Pregnancies Complicated by Pregestational and Gestational Diabetes.

OBJECTIVE: This study aimed to investigate the association between excess and less than recommended gestational weight gain (GWG) and adverse maternal and neonatal outcomes in women with pregestational and gestational diabetes. STUDY DESIGN: We conducted a secondary analysis of the National Institute of Child Health and Human Development (NICHD) Consortium on Safe Labor (CSL) study. We included deliveries >23 weeks of nonanomalous singletons with either pregestational or gestational diabetes. The exposure was GWG greater than or less than compared with the U.S. Institute of Medicine recommendations for total pregnancy weight gain per prepregnancy body mass index. Consistent with the 2020 Delphi outcome for diabetes in pregnancy, maternal outcomes included cesarean delivery and preeclampsia and neonatal outcomes included small for gestational age (SGA), large for gestational age (LGA), macrosomia >4,000 g, preterm birth <37 weeks, stillbirth, and neonatal death. We modeled both absolute GWG and GWG z-scores, standardized for gestational duration. Multivariable logistic regression with generalized estimating equations was used, adjusting for age, race/ethnicity, parity, prior cesarean delivery, chronic hypertension, tobacco use, U.S. region, and delivery year. RESULTS: Of 8,322 deliveries (n = 8,087 women) complicated by pregestational or gestational diabetes, 47% were in excess, 27% were within, and 26% were less than GWG recommendations. Deliveries with excess absolute GWG were at higher adjusted odds of cesarean delivery, preeclampsia, LGA, and macrosomia, compared with those within recommendations. Similar results were observed when using standardized GWG z-scores, in addition to higher likelihood of preterm birth and neonatal death. Less than recommended GWG was associated with a lower likelihood of these adverse outcomes but higher SGA. Additionally, less GWG by z-score was associated with a lower likelihood of stillbirth. CONCLUSION: Excess GWG increases the risk of adverse maternal and neonatal outcomes for women with pregestational and gestational diabetes. Less GWG than recommended may decrease this risk. KEY POINTS: · Understanding the impact of GWG modeled using both absolute and standardized measures is needed.. · Among pregnant women with diabetes, excess GWG was common and increased the risk of adverse outcomes and less than recommended GWG may decrease the risk of adverse outcomes, including stillbirth.. · Current recommendations may require revision for women with diabetes in pregnancy..

Differences in Hemoglobin A1c during Pregnancy between Non-Hispanic Black versus White Women with Prepregnancy Diabetes.

OBJECTIVE: The objective of this was to determine whether the change in hemoglobin A1c (HbA1c) from early to late pregnancy differs between non-Hispanic Black and White women with prepregnancy diabetes. STUDY DESIGN: A retrospective analysis was performed from an integrated prenatal and diabetes care program from 2012 to 2016. We compared HbA1c as a continuous measure and secondarily, HbA1c <6.5%, cross-sectionally, and longitudinally in early (approximately 10 weeks) and late (approximately 31 weeks) pregnancies. Linear and logistic regression were used and adjusted for age, body mass index, White diabetes class, medication use, diabetes type, gestational age at baseline HbA1c measurement, and baseline hemoglobin. RESULTS: Among 296 non-Hispanic Black (35%) and White pregnant women (65%) with prepregnancy diabetes (39% type 1 and 61% type 2), Black women were more likely to experience increased community-level social determinants of health as measured by the Social Vulnerability Index (SVI) and were less likely to have type 1 diabetes and have more severe diabetes versus White women (p < 0.05). Black women had higher mean HbA1c (7.8 vs. 7.4%; beta: 0.75; 95% confidence interval [CI]: 0.30-1.19) and were less likely to have HbA1c < 6.5% at 10 weeks compared with White women (24 vs. 35%; adjusted odds ratio: 0.45; 95% CI: 0.24-0.81) but not after adjusting for SVI. At 31 weeks, both groups had similar mean HbA1c (both 6.5%) and were equally as likely to have HbA1c < 6.5% (57 vs. 54%). From early to late pregnancy, Black women had a higher percentage decrease in HbA1c (1.3 vs. 0.9%; beta = 0.63; 95% CI: 0.27-0.99) and were equally as likely to have an improvement or stable HbA1C < 6.5% from 10 to 31 weeks, with both groups having a similar mean HbA1c (6.5%) at 31 weeks. CONCLUSION: Despite experiencing greater community-level social determinants of health, Black women with pregestational diabetes had a larger reduction in HbA1c and were able to equally achieve the target of HbA1c < 6.5% by late pregnancy compared with White women as part of an integrated diabetes and prenatal care program. KEY POINTS: · An integrated diabetes and pregnancy care program may decrease racial and ethnic disparities in glycemic control.. · Black women had a larger reduction in HbA1c versus White women.. · Black women were able to equally achieve the target of HbA1c < 6.5% by late pregnancy versus White women..