Jack E. James

Caffeine, a habit-forming substance of no nutritional value, is consumed daily by most pregnant women. This focused narrative review examines evidence of association between maternal caffeine consumption and negative pregnancy outcomes, and assesses whether current advice guidelines are consistent with the available evidence. The majority finding from original empirical studies, systematic reviews, and meta-analyses is that maternal consumption of caffeine is reliably associated with serious negative pregnancy outcomes and negative outcomes in offspring. Evidence of harm is strong for miscarriage, stillbirth, and low birth weight and/or small for gestational age, while being less strong for childhood acute leukemia, childhood overweight and obesity, and childhood behavioural and neurocognitive development. In contrast, preterm birth appears not to be at increased risk. Many studies report significant dose-response associations indicative of causation and the absence of a threshold of consumption below which associations are absent. In general, findings are robust to threats from potential confounding and misclassification. Notwithstanding compelling grounds to the contrary, national and international authorities continue to suggest that “moderate” caffeine consumption during pregnancy is safe. Rather, pregnant women and women contemplating pregnancy should be advised not to consume coffee, tea, sodas, or energy drinks that contain caffeine.

Background: Alcohol use impairs psychosocial and neurocognitive development and increases the vulnerability of youth to academic failure, substance use disorders, and other mental health problems. The early onset of alcohol use in adolescents is of particular concern, forecasting substance abuse in later adolescence and adulthood. To date, evidence suggests that youth in rural areas are especially vulnerable to contextual and community factors that contribute to the early onset of alcohol use. Objective: The objective of the Young Mountaineer Health Study is to investigate the influence of contextual and health behavior variables on the early onset of alcohol use among middle school–aged youth in resource-poor Appalachian rural communities. Methods: This is a program of prospective cohort studies of approximately 2200 middle school youth from a range of 20 rural, small town, and small city (population <30,000) public schools in West Virginia. Students are participating in 6 waves of data collection (2 per year) over the course of middle school (sixth to eighth grades; fall and spring) from 2020 to 2023. On the basis of an organizational arrangement, which includes a team of local data collection leaders, supervising contact agents in schools, and an honest broker system to deidentify data linked via school IDs, we are able to collect novel forms of data (self-reported data, teacher-reported data, census-linked area data, and archival school records) while ensuring high rates of participation by a large majority of youth in each participating school. Results: In the spring of 2021, 3 waves of student survey data, 2 waves of data from teachers, and a selection of archival school records were collected. Student survey wave 1 comprised 1349 (response rate 80.7%) participants, wave 2 comprised 1649 (response rate 87%) participants, and wave 3 comprised 1909 (response rate 83.1%) participants. The COVID-19 pandemic has had a negative impact on the sampling frame size, resulting in a reduced number of eligible students, particularly during the fall of 2020. Nevertheless, our team structure and incentive system have proven vitally important in mitigating the potentially far greater negative impact of the pandemic on our data collection processes. Conclusions: The Young Mountaineer Health Study will use a large data set to test pathways linking rural community disadvantage to alcohol misuse among early adolescents. Furthermore, the program will test hypotheses regarding contextual factors (eg, parenting practices and neighborhood collective efficacy) that protect youth from community disadvantage and explore alcohol antecedents in the onset of nicotine, marijuana, and other drug use. Data collection efforts have been successful despite interruptions caused by the COVID-19 pandemic in 2020 and 2021. International Registered Report Identifier (IRRID): DERR1-10.2196/40451

BACKGROUND Alcohol use impairs psychosocial and neurocognitive development and increases youth vulnerability to academic failure, substance use disorder and other mental health problems. Early adolescent alcohol use onset is of particular concern, forecasting substance abuse in later adolescence and adulthood. Evidence to date suggests that youth in rural areas are especially vulnerable to contextual and community factors that contribute to early onset of alcohol use. OBJECTIVE The objective of the Young Mountaineer Health Study (YMHS) is to investigate the influence of contextual and health behavior variables on early onset of alcohol use among middle school-aged youth in resource-poor Appalachian rural communities. METHODS This is a program of prospective cohort studies of ~2,200 middle school youth from a range of twenty rural, small town, and small city (< 30k) public schools in West Virginia. Students participate in 6 waves of data collection (2 per year), over the course of middle school (6th- 8th grades, fall and spring). Based on an organizational arrangement which includes a team of local data collection leaders, supervising contact agents in schools, and an “honest broker” system to de-identify data linked via school IDs, we have been able to collect novel forms of data (self-report, teacher-report, census linked area data, and archival school records) while ensuring high rates of participation by a large majority of youth in each participating school. RESULTS To date, three waves of student survey data, two waves of teacher data, and a selection of archival school records have been collected. Student survey Wave 1: N = 1,349 (response rate = 80.7%), Wave 2: N = 1,649 (response rate = 87.0%), and Wave 3: N = 1,909 (response rate = 83.1%). The COVID-19 pandemic had a negative impact on the sampling frame size, resulting in a reduced number of eligible students, particularly during the fall of 2020. Nevertheless, our team structure and incentive system has proven vitally important in mitigating a potentially far greater negative impact of the pandemic on our data collection processes. CONCLUSIONS The YMHS will employ a large dataset to test pathways linking rural community disadvantage to alcohol misuse among early adolescents. Further, the program will test hypotheses regarding contextual factors (e.g., parenting practices, neighborhood collective efficacy) that protect youth from community disadvantage, and explore alcohol antecedents in the onset of nicotine, marijuana, and other drug use. So far, data collection efforts have been successful despite interruptions caused by the COVID-19 pandemic. Data quality checking, preliminary analyses, and manuscript preparations are currently under way. CLINICALTRIAL N/A

Rationale: The majority of pregnant women regularly consume caffeine, a habit-forming substance of no nutritional value for mother or baby. Objectives: To examine evidence of association between maternal caffeine consumption and childhood behavioural and neurocognitive development, and to consider the soundness of current health guidance concerning the consumption of caffeine during pregnancy. Methods: Database searches identified a large pool of peer-reviewed articles, which when culled for relevance yielded a modest corpus of animal and human research for inclusion in this focussed narrative review of potential caffeine-related threats to childhood behavioural and neurocognitive development. Results: High biological plausibility of potential harm from maternal caffeine exposure indicated by early animal research is confirmed by more recent animal studies that sought to mimic human consumption patterns. Reported negative outcomes include increased neuronal network excitability and susceptibility to seizures in offspring, and disruptions to electrophysiological activity, learning, and memory. In contrast, human observational studies have yielded inconsistent findings. Some studies have reported evidence of negative behavioural and neurocognitive outcomes, including hyperkinetic disorder, attention deficit disorder, and intelligence level in preschool- and elementary-aged children. Other studies, however, reported no associations with maternal caffeine consumption for similar parameters. Conclusions: Current understanding of caffeine-related increased risk of harm for childhood development is limited due to inconsistent findings from human research. However, persistent reports of possible negative outcomes indicate high priority need for further research. In the meantime, the cumulative scientific evidence supports advice to pregnant women and women contemplating pregnancy to avoid caffeine.

Objectives Caffeine is a habit-forming substance consumed daily by the majority of pregnant women. Accordingly, it is important that women receive sound evidence-based advice about potential caffeine-related harm. This narrative review examines evidence of association between maternal caffeine consumption and negative pregnancy outcomes, and assesses whether current health advice concerning maternal caffeine consumption is soundly based. Methods Database searches using terms linking caffeine and caffeinated beverages to pregnancy outcomes identified 1261 English language peer-reviewed articles. Screening yielded a total of 48 original observational studies and meta-analyses of maternal caffeine consumption published in the past two decades. The articles reported results for one or more of six major categories of negative pregnancy outcomes: miscarriage, stillbirth, low birth weight and/or small for gestational age, preterm birth, childhood acute leukaemia, and childhood overweight and obesity. Results Of 42 separate sets of findings reported in 37 observational studies, 32 indicated significantly increased caffeine-related risk and 10 suggested no or inconclusive associations. Caffeine-related increased risk was reported with moderate to high levels of consistency for all pregnancy outcomes except preterm birth. Of 11 studies reporting 17 meta-analyses, there was unanimity among 14 analyses in finding maternal caffeine consumption to be associated with increased risk for the four outcome categories of miscarriage, stillbirth, low birth weight and/or small for gestational age, and childhood acute leukaemia. The three remaining meta-analyses were also unanimous in reporting absence of a reliable association between maternal caffeine consumption and preterm birth. No meta-analyses were identified for childhood overweight and obesity, although four of five original observational studies reported significant associations linking maternal caffeine consumption to that outcome category. Conclusions The substantial majority finding from observational studies and meta-analyses is that maternal caffeine consumption is reliably associated with major negative pregnancy outcomes. Reported findings were robust to threats from potential confounding and misclassification. Among both observational studies and meta-analyses, there were frequent reports of significant dose–response associations suggestive of causation, and frequent reports of no threshold of consumption below which associations were absent. Consequently, current evidence does not support health advice that assumes 'moderate' caffeine consumption during pregnancy is safe. On the contrary, the cumulative scientific evidence supports pregnant women and women contemplating pregnancy being advised to avoid caffeine.

Concerns have long been expressed about industry entanglement in healthcare. Early editorial commentary to raise awareness¹ was soon followed by editorial policy requiring authors to disclose financial ties to industry.³ Disclosure provisions later earned international imprimatur by being added to the World Medical Association’s Declaration of Helsinki . The aim of the present commentary is to examine the effectiveness of disclosure for mitigating bias and harm from industry entanglement in healthcare research, education, and practice.

Open access has long been an ideal of academic publishing. Yet, contrary to initial expectations, cost of access to published scientific knowledge increased following the advent of the Internet and electronic processing. An analysis of the ethicality of current arrangements in academic publishing shows that monetization and the sequestering of scientific knowledge behind paywalls breach the principle of fairness and damage public interest. Following decades of failed effort to redress the situation, there are ethical grounds for consumers of scientific knowledge to invoke the right of collective civil disobedience, including support for pirate open access. Could this be the best option available to consumers of scientific knowledge for removing paywalls to knowledge that rightly belongs in the public domain?

To the Editor Using UK Biobank data from more than 400 000 people, Loftfield and colleagues examined associations between coffee drinking and mortality. Uniquel

Public financing to incentivise private sector innovation in antimicrobial pharmaceuticals is believed by many to be necessary to defeat growing threats from antimicrobial resistance. Large cash incentives from the public sector are said to be essential to stimulate ‘normal’ market forces capable of unleashing much-needed innovation. However, there is little evidence to suggest that lack of innovation in drug development is peculiar to antimicrobials or that current deficits in the supply of antimicrobials is due to unique inefficiencies in the antimicrobial market. Neither the history of drug development in general nor of antimicrobial innovation in particular supports economic interventions intended to stimulate private sector supply of new antimicrobials. On the contrary, public underwriting of the private sector, which by definition is compelled to prioritise profit, risks dire consequences for future global health.