Custodes Futurifor the advancement of humanity

Factor 01 of 9

Biological factors

Barriers rooted in the body and brain, from chronic stress and early-life adversity to illness and substance use.

Barriers within this factor

Each barrier has its own page with the evidence and sources behind it.

  1. 1Chronic and toxic stress

    Prolonged activation of the stress response damages health and impairs learning, memory, and self-regulation. Shonkoff and Garner (2012) describe how repeated childhood adversity alters development in brain regions tied to planning and emotional control.

    Evidence and sources (2 evidence points, 6 actions, 4 experimental methods)

  2. 2Early-life adversity

    Adverse childhood experiences, meaning abuse, neglect, and household dysfunction, are associated with worse health and outcomes decades later.

    Evidence and sources (3 evidence points, 10 actions, 4 experimental methods)

  3. 3Birth weight and prenatal health

    Low birth weight raises the risk of infant death and disability, removing potential future contributors before any ability can develop. Whether it also lowers adult IQ and earnings is disputed.

    Evidence and sources (3 evidence points, 10 actions, 5 experimental methods)

  4. 4Genetic disorders

    Inherited disorders such as sickle cell disease cause many child deaths and learning difficulties, but much of the harm depends on whether screening and treatment are available. Newborn screening and early treatment for phenylketonuria show the barrier can be removed (U.S. Preventive Services Task Force, 2008).

    Evidence and sources (4 evidence points, 7 actions, 5 experimental methods)

  5. 5Health, nutrition, and sleep

    Early malnutrition, including iodine and iron deficiency, is linked to lasting cognitive effects. Chronic illness, pain, and sleep deprivation reduce the energy and attention available for growth.

    Evidence and sources (4 evidence points, 19 actions, 14 experimental methods)

  6. 6Substance use

    Addictive substances act on reward and decision-making circuits and can shift behavior toward short-term relief.

    Evidence and sources (3 evidence points, 9 actions, 8 experimental methods)

Evidence strength

Main findings behind this page, grouped by the strength ratings, from strongest to weakest. Each tier lists the findings that received that rating.

StrengthFindings
StrongNewborn screening and treatment for phenylketonuria. The concentration of later costs among children with persistent conduct problems.
ModerateChildhood adversity and adult outcomes (retrospective self-reports). Low birth weight and infant health. The burden of sickle cell disease. Undernutrition and later outcomes. Sleep restriction and cognition. Adolescent cannabis use as an association.
LimitedWHO's estimate of child deaths linked to undernutrition. Cannabis use as a cause of lower schooling. Cognition in sickle cell disease.
Contested or debatedBirth weight effects on adult IQ and earnings.

Actions that can reduce these barriers

This section identifies changes that governments, health systems, organizations, schools, employers, and families can make to reduce these barriers. Each action carries an evidence rating on the scale used in the strength ratings (A strong and replicated, B solid but limited, C weak or debated, D contested or failed), applied to the specific claim made. All sources were checked against their abstracts or full texts.

Each barrier page lists the actions that apply to it, with ratings and sources.

Who can act

ActorHighest-value biological actions
GovernmentsTobacco and alcohol taxes, minimum unit pricing, folic acid fortification, universal salt iodization, income support for families with young children, secondary school start times of 8:30 a.m. or later, national sickle cell screening linked to care
Health systemsMultiple micronutrient tablets and malaria prevention in pregnancy, enough antenatal visits, antenatal corticosteroids where newborn care exists, immediate kangaroo mother care, hydroxyurea and penicillin for sickle cell disease, trauma-focused therapy, blood pressure programs, opioid agonist treatment, brief alcohol advice, CBT for insomnia
Nonprofits and organizationsSupply chains for micronutrient tablets, nutrient supplements, and hydroxyurea, point-of-care sickle cell testing, free parenting programs, school violence prevention, independent evaluation of every program
Schools and employersSocial-emotional learning, school violence prevention, later start times, limits on extended overnight shifts (weak evidence)
Families and individualsAttending antenatal care, taking folic acid before conception, skin-to-skin care for small babies, newborn screening, responsive play, non-violent discipline, using iodized salt, seeking CBT for insomnia, delaying adolescent alcohol and cannabis use

Lessons across the actions

  1. Many of the strongest actions are cheap and already proven at national scale, so coverage is the main gap rather than knowledge.
  2. Several popular programs did not hold up when tested again at scale, including Nurse-Family Partnership, Triple P, DARE, and deworming for growth and cognition. Independent evaluation should be built into any program from the start.
  3. How and where an action is delivered matters as much as what it is. Corticosteroids helped in hospitals with newborn care but not when promoted where gestational age could not be assessed, and home visiting worked better with trained, supervised staff.

Limits: Much of the evidence on stress and adversity comes from the United States, and much of the evidence on birth outcomes and nutrition comes from low- and middle-income countries, so results may not transfer between settings. Costs per child for nutrient supplements and salt iodization, and the per-case cost of trauma-focused therapy, could not be confirmed.

Proposed and experimental methods

Each barrier also has a list of proposed and experimental methods. It covers methods that are proposed, under trial, approved in some places but not widely used, or tried and then failed or reversed, so readers can see what is being tested. Each method has a stage label and an evidence rating in parentheses. The stage labels are Theoretical (proposed but not yet tested as an intervention), Early trial (small or first studies), Large trial (large randomized or field trials), Approved but not scaled (legally approved or running in some places but not widely adopted), In wide use (widely adopted but newly tested or questioned), Sold commercially without trials (used for polygenic embryo screening), and Failed or reversed (tested and shown not to work, or adopted and then withdrawn). The word contested is added where the evidence is disputed. Failed, reversed, and unhelpful methods are listed last and begin with "Failed," "Reversed," or "Not shown to help." A stage label shows how far a method has progressed, not whether it works, and the rating shows the strength of the evidence.

Ideal conditions that counter this factor

Biological and health conditions

What the evidence shows

Early health sets limits that later opportunity cannot always fix. Raising blood lead from 2.4 to 30 µg/dL was linked to a loss of 6.9 IQ points (Lanphear et al., 2005), and low birth weight raises the risk of infant death (Maruyama and Heinesen, 2020). Wollstonecraft died of the childbed fever that Semmelweis showed was preventable, and children who die young are lost before any ability can develop.

Ideal:

  • Prenatal care and safe childbirth with infection control
  • Early nutrition
  • Newborn screening and treatment for genetic disorders
  • No lead or neurotoxins, and clean air and water
  • Control of malaria and other infectious diseases
  • Lifelong healthcare
  • Safety in research with new hazards

Evidence strength: Strong for most components, though some are weaker (see the strength ratings). Contested for birth weight effects on IQ and earnings.

All ten conditions

In the pioneer cases

Statements from the pioneer records that this site classifies under the biological factor. The classification is this site's.

PioneerEffectStatement
Albert EinsteinBarrier absentHealth and nutrition. A middle-class upbringing in Germany meant no malnutrition, parasites, or serious childhood disease.
Albert EinsteinNoteHis brain. Witelson, Kigar, and Harvey (1999) reported unusual parietal lobe features. Falk, Lepore, and Noe (2013) described an unusual prefrontal cortex and parietal lobes, calling their interpretations tentative. Hines (2014) concluded these studies do not show his brain structure explains his abilities. One brain and small comparison groups cannot establish cause.
Marie CurieNot overcomeShe died at 66 from aplastic anemia, most likely caused by radiation exposure, whose dangers were recognized only gradually. Curie urged lead screens and blood tests for radium workers in about 1925, and U.S. radiological societies formed a protection committee in 1929.
Srinivasa RamanujanNot overcomeIllness forced his return to India, and he died at 32.
Katalin KarikóBarrierIn 1995 Penn gave her a choice between abandoning her research and accepting a demotion with a pay cut, as she was diagnosed with cancer and her husband was stuck in Hungary. She described being demoted four times.
Tu YouyouBarrierTuberculosis at age 16 interrupted her schooling for two years.
Tu YouyouBarrierHer project began in 1969, during the Cultural Revolution, when most research had stalled and many experienced experts had been sidelined. With pharmaceutical workshops shut, her team extracted herbs in household vats, and several members, including Tu, developed health problems from solvent exposure.
Ignaz SemmelweisNoteThe evidence. In 1846, the clinic staffed by doctors and medical students lost 459 of 4,010 mothers (11.4%), while the clinic staffed by midwives lost 105 of 3,754 (2.8%). In 1848, after handwashing was fully in place, mortality in the doctors' clinic fell to 1.27%, slightly below the midwives' 1.33%.
Mary WollstonecraftNot overcomeShe died on 10 September 1797, eleven days after giving birth, of septicemia or puerperal fever. This is the disease that Semmelweis showed, fifty years later, was spread on unwashed hands. Her husband's candid memoir (1798) then damaged her reputation for most of the next century.
Baruch SpinozaNot overcomeThe only work he published under his own name in his lifetime was an exposition of Descartes. He died in 1677 at 44 of a lung illness, reported as tuberculosis. Inhaling glass dust from lens grinding has been suggested as a cause but is unproven.
Ludwig van BeethovenBarrierHis hearing began to fail in his mid to late twenties. He first described the problem in a letter of June 1801, at age 30, and was fully deaf by his mid forties.
Ludwig van BeethovenBarrierLead exposure. A 2024 letter in Clinical Chemistry tested two authenticated locks of his hair and estimated his blood lead at 69 to 71 µg/dL. Such levels are commonly associated with stomach and kidney problems and decreased hearing.
Ludwig van BeethovenNoteThe locks date from about 1820 to 1827, so they cannot show whether lead exposure preceded his hearing loss. The authors do not think lead alone caused his deafness or death. Lead exposure is well supported. Lead as the cause of his deafness is rated C.
Ludwig van BeethovenNot overcomeHis deafness, whose cause remains unknown.
Yuan LongpingBarrierHe witnessed mass starvation in rural Hunan during the famine that followed the Great Leap Forward.
Nikolai VavilovBarrierDeath in prison. He was sentenced to death. The sentence was commuted to 20 years in prison, and he died of starvation in Saratov prison on 26 January 1943.

Key figures

MeasureValueSource
Deaths from noncommunicable diseases, 2021At least 43 million, 75% of non-pandemic deathsWHO fact sheet on noncommunicable diseases
Noncommunicable disease deaths before age 7018 million, 82% of them in low- and middle-income countriesWHO fact sheet on noncommunicable diseases
People living with obesity, 20221 in 8 worldwide, including 890 million adultsWHO obesity and overweight fact sheet
Adults who were overweight, 20222.5 billion (43%)WHO obesity and overweight fact sheet
Growth in obesity since 1990Adult obesity more than doubled, adolescent obesity quadrupledWHO obesity and overweight fact sheet
Adults not meeting recommended activity levels, 202231%, about 1.8 billion people, up about 5 percentage points since 2010WHO (2024)
Physical inactivity by sex, 202234% of women, 29% of menWHO (2024)
Original ACE study9,508 adults, more than half reported at least one adverse childhood experience. Four or more categories carried 4 to 12 times the risk of alcoholism, drug abuse, depression, and suicide attemptFelitti et al. (1998)
ACE meta-analysis37 studies, 253,719 participants. Four or more ACEs raised risk for all 23 outcomes. Odds ratios were under 2 for inactivity, obesity, and diabetes and over 7 for problematic drug use and violenceHughes et al. (2017)
Children under 5 stunted, 2024150.2 million (23.2%), down from 40% in 1990WHO, UNICEF, and World Bank Joint Child Malnutrition Estimates, 2025 edition
Progress toward the 2030 stunting targetAt current progress the target will be missed by 46 million childrenWHO, UNICEF, and World Bank Joint Child Malnutrition Estimates, 2025 edition
Children under 5 wasted, 202442.8 millionWHO, UNICEF, and World Bank Joint Child Malnutrition Estimates, 2025 edition
Long-term effects of childhood undernutritionShorter adult height, less schooling, and reduced economic productivity. Height-for-age at 2 years was the best predictor of human capitalVictora et al. (2008), cohorts from five countries
Child deaths linked to undernutritionAround 45% of deaths among children under 5, and wasted children face a higher risk of death if not treated. The estimate comes from a 2013 Lancet analysis (Black et al., 2013) and is still cited by WHO. These deaths remove potential future contributors, including possible pioneers, before any ability can developWHO malnutrition page
Low birth weight, 202019.8 million newborns, 14.7% of all live births (under 2,500 grams), down from 16.6% in 2000. South Asia accounted for 44%. Birth weight data were unavailable for 28.7% of newborns, so the global figure is partly modeledUNICEF and WHO (Okwaraji et al., 2024)
Norwegian twin study of birth weightThe effects of birth weight on long-run outcomes such as height, IQ, earnings, and education were significant and similar in size to simple comparisons across all children, even though short-run effects within twin pairs were much smallerBlack, Devereux, and Salvanes (2007)
Newborn deaths from preterm or small-for-gestational-age births, 202055.3% of 2.4 million newborn deaths worldwide. About three quarters of these were preterm. The estimate covers these two groups, which overlap heavily with low birth weight but are not identical to itLawn et al. (2023)
First-year mortality in Danish children born 1981 to 19950.6% overall and 6.6% among babies under 2,500 gramsMaruyama and Heinesen (2020)
Twin studies of birth weight, United States and SwedenFound similar effects on education and income, though the U.S. effects were generally small. The Swedish study also linked lower birth weight to higher adult mortalityRoyer (2009), Bharadwaj et al. (2018)
Danish study of birth weightAbout two million births from 1981 to 2013, using a pregnancy complication that causes early birth, confirmed causal effects on infant death, health, and disability but found no strong evidence for effects on test scores, income, or IQ. The effect on infant deaths has weakened as newborn care has improvedMaruyama and Heinesen (2020)
Sickle cell disease worldwide, 2021An estimated 7.74 million people were living with it and 515,000 babies were born with it, mostly in the Caribbean and western and central sub-Saharan Africa. Deaths recorded as caused by it numbered 34,400, but deaths it contributed to totaled about 376,000, including 81,100 children under 5GBD 2021 Sickle Cell Disease Collaborators (2023)
Sickle cell disease and child mortality in AfricaAvailable data are consistent with 50% to 90% of children with the most common form dying in early childhood. The reviewers state that the data are inadequate for definitive statementsGrosse et al. (2011)
School performance with sickle cell disease, United StatesStudents scored 0.70, 0.87, and 0.80 standard deviations below norms in reading, math, and spelling, and repeated a grade about 10 times as often as Black students nationally. Students who had a stroke or silent stroke scored lower. Environmental factors such as socioeconomic status are also associated with cognitive outcomes in this groupHeitzer et al. (2021), Prussien et al. (2020)
Newborn deaths and child deaths from congenital disordersAn estimated 240,000 newborns in their first 28 days each year and 170,000 more children aged 1 month to 5 years. Nine of ten children born with a serious congenital disorder live in low- and middle-income countries. Congenital disorders have genetic and non-genetic causesWHO (2023)
Phenylketonuria screening and treatmentNewborn screening and early dietary treatment substantially improve brain development and prevent the severe intellectual disability the disorder otherwise causes. Even with early treatment, children often score below the IQ predicted from their parents and siblingsU.S. Preventive Services Task Force (2008), NICHD
Origin of the sickle cell gene in tropical regionsThe gene became common because carriers, who have one copy, are more likely to survive malaria. This links the barrier to the malaria barrierUyoga et al. (2019)
Sleep restriction experiment48 adults randomized to 4, 6, or 8 hours in bed for 14 days. 6 hours or less produced cognitive deficits equal to up to 2 nights of total sleep deprivation, and participants were largely unaware of their declineVan Dongen et al. (2003)
Deaths caused by alcohol and psychoactive drugs, 20192.6 million from alcohol (4.7% of all deaths) and 0.6 million from drugs. Men accounted for 2 million alcohol deaths and 0.4 million drug deathsWHO (2024)
People with alcohol use disorders, 2019An estimated 400 million, including 209 million with alcohol dependenceWHO (2024)
Adolescent cannabis use and schoolingCombining three Australian and New Zealand cohorts (3,765 people), those who used cannabis daily before age 17 had about 63% lower odds of finishing high school and 62% lower odds of earning a degree than those who never used it, after adjusting for many background factors. Whether cannabis causes this or marks earlier disadvantage is debated, and a published letter noted daily users did no worse than weekly users on schoolingSilins et al. (2014)

References cited on this page

  1. Silins, E., Horwood, L. J., Patton, G. C., et al. (2014). Young adult sequelae of adolescent cannabis use: an integrative analysis. Lancet Psychiatry, 1(4), 286-293. DOI
  2. Shonkoff, J. P., & Garner, A. S. (2012). The lifelong effects of early childhood adversity and toxic stress. Pediatrics, 129(1), e232-e246. DOI
  3. Felitti, V. J., et al. (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. American Journal of Preventive Medicine, 14(4), 245-258. DOI00017-8)
  4. Hughes, K., Bellis, M. A., Hardcastle, K. A., et al. (2017). The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health, 2(8), e356-e366. DOI30118-4)
  5. Black, S. E., Devereux, P. J., & Salvanes, K. G. (2007). From the cradle to the labor market? The effect of birth weight on adult outcomes. Quarterly Journal of Economics, 122(1), 409-439. DOI
  6. Royer, H. (2009). Separated at girth: US twin estimates of the effects of birth weight. American Economic Journal: Applied Economics, 1(1), 49-85. AEA
  7. Bharadwaj, P., Lundborg, P., & Rooth, D.-O. (2018). Birth weight in the long run. Journal of Human Resources, 53(1), 189-231. JHR
  8. GBD 2021 Sickle Cell Disease Collaborators (2023). Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021. Lancet Haematology, 10(8), e585-e599. DOI00118-7)
  9. Uyoga, S., Macharia, A. W., Mochamah, G., et al. (2019). The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study. Lancet Global Health, 7(10), e1458-e1466. DOI30328-6)
  10. Grosse, S. D., Odame, I., Atrash, H. K., Amendah, D. D., Piel, F. B., & Williams, T. N. (2011). Sickle cell disease in Africa: a neglected cause of early childhood mortality. American Journal of Preventive Medicine, 41(6 Suppl 4), S398-S405. DOI
  11. Heitzer, A. M., Hamilton, L., Stafford, C., Gossett, J., Ouellette, L., Trpchevska, A., King, A. A., Kang, G., & Hankins, J. S. (2021). Academic performance of children with sickle cell disease in the United States: a meta-analysis. Frontiers in Neurology, 12, 786065. DOI
  12. Prussien, K. V., et al. (2020). Correlates of cognitive function in sickle cell disease: a meta-analysis. Journal of Pediatric Psychology, 45(2), 145-155. DOI
  13. WHO: Congenital disorders fact sheet (2023)
  14. U.S. Preventive Services Task Force (2008). Screening for phenylketonuria: reaffirmation recommendation statement (American Family Physician)
  15. NICHD: Treatment regimens and their effectiveness, a meta-analytic review of the PKU literature (historical publication)
  16. Maruyama, S., & Heinesen, E. (2020). Another look at returns to birthweight. Journal of Health Economics, 70, 102269. DOI
  17. Lawn, J. E., Ohuma, E. O., Bradley, E., et al. (2023). Small babies, big risks: global estimates of prevalence and mortality for vulnerable newborns to accelerate change and improve counting. Lancet, 401(10389), 1707-1719. DOI00522-6)
  18. Okwaraji, Y. B., Krasevec, J., Bradley, E., et al. (2024). National, regional, and global estimates of low birthweight in 2020, with trends from 2000: a systematic analysis. Lancet, 403(10431), 1071-1080. Lancet01198-4/fulltext)
  19. UNICEF: Low birthweight data
  20. WHO: Malnutrition
  21. Victora, C. G., Adair, L., Fall, C., et al. (2008). Maternal and child undernutrition: consequences for adult health and human capital. Lancet, 371(9609), 340-357. DOI61692-4)
  22. Van Dongen, H. P. A., Maislin, G., Mullington, J. M., & Dinges, D. F. (2003). The cumulative cost of additional wakefulness. Sleep, 26(2), 117-126. DOI
  23. WHO: Noncommunicable diseases fact sheet
  24. WHO: Obesity and overweight fact sheet
  25. WHO: Nearly 1.8 billion adults not doing enough physical activity (2024)
  26. WHO, UNICEF, World Bank: Joint Child Malnutrition Estimates, 2025 edition
  27. WHO: Over 3 million annual deaths due to alcohol and drug use (2024)

Sources for the actions

  1. Abdullahi, S. U., Jibir, B. W., Bello-Manga, H., Gambo, S., Inuwa, H., Tijjani, A. G., et al. (2022). Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): A double-blind, multicentre, randomised, phase 3 trial. The Lancet Haematology, 9(1), e26-e37. link B Moderate
  2. Adams, R. J., McKie, V. C., Hsu, L., Files, B., Vichinsky, E., Pegelow, C., et al. (1998). Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. New England Journal of Medicine, 339(1), 5-11. link B Moderate
  3. Adolescent Sleep Working Group, Committee on Adolescence, & Council on School Health. (2014). School start times for adolescents. Pediatrics, 134(3), 642-649. link B Moderate
  4. Althabe, F., Belizán, J. M., McClure, E. M., Hemingway-Foday, J., Berrueta, M., Mazzoni, A., et al. (2015). A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial. The Lancet, 385(9968), 629-639. link (online October 2014) B Moderate
  5. Anda, R. F., Porter, L. E., & Brown, D. W. (2020). Inside the adverse childhood experience score: Strengths, limitations, and misapplications. American Journal of Preventive Medicine, 59(2), 293-295. link B Moderate
  6. Andrew, A., Attanasio, O., Fitzsimons, E., Grantham-McGregor, S., Meghir, C., & Rubio-Codina, M. (2018). Impacts 2 years after a scalable early childhood development intervention to increase psychosocial stimulation in the home: A follow-up of a cluster randomised controlled trial in Colombia. PLOS Medicine, 15(4), e1002556. link B Moderate
  7. Andreyeva, T., Marple, K., Marinello, S., Moore, T. E., & Powell, L. M. (2022). Outcomes following taxation of sugar-sweetened beverages: A systematic review and meta-analysis. JAMA Network Open, 5(6), e2215276. link B Moderate
  8. Arrigoni, M., Zwaveling-Soonawala, N., LaFranchi, S. H., van Trotsenburg, A. S. P., & Mooij, C. F. (2025). Newborn screening for congenital hypothyroidism: Worldwide coverage 50 years after its start. European Thyroid Journal, 14(1), e240327. link B Moderate
  9. Attanasio, O. P., Fernández, C., Fitzsimons, E. O. A., Grantham-McGregor, S. M., Meghir, C., & Rubio-Codina, M. (2014). Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: Cluster randomized controlled trial. BMJ, 349, g5785. link C Limited: for lasting benefit, B for the end-of-program effect
  10. Awasthi, S., Peto, R., Read, S., Clark, S., Pande, V., Bundy, D., & the DEVTA Team. (2013). Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial. The Lancet, 381(9876), 1469-1477. link B Moderate
  11. Bachmann, M. O. (2009). Cost effectiveness of community-based therapeutic care for children with severe acute malnutrition in Zambia: Decision tree model. Cost Effectiveness and Resource Allocation, 7, Article 2. link C Limited
  12. Baldwin, J. R., Caspi, A., Meehan, A. J., Ambler, A., Arseneault, L., Fisher, H. L., et al. (2021). Population vs individual prediction of poor health from results of adverse childhood experiences screening. JAMA Pediatrics, 175(4), 385-393. link A Strong
  13. Bernard, K., Dozier, M., Bick, J., & Gordon, M. K. (2015). Intervening to enhance cortisol regulation among children at risk for neglect: Results of a randomized clinical trial. Development and Psychopathology, 27(3), 829-841. link B Moderate
  14. Bhatt, S. (2026, April 9, updated April 13). One goal, 50 brands: Inside the scramble for India's post-patent semaglutide market. Outlook Business. link C Limited
  15. Bilimoria, K. Y., Chung, J. W., Hedges, L. V., et al. (2016). National cluster-randomized trial of duty-hour flexibility in surgical training. New England Journal of Medicine, 374(8), 713-727. link B Moderate
  16. Bougma, K., Aboud, F. E., Harding, K. B., & Marquis, G. S. (2013). Iodine and mental development of children 5 years old and under: A systematic review and meta-analysis. Nutrients, 5(4), 1384-1416. link C Limited
  17. Bullinger, L. R., Packham, A., & Raissian, K. M. (2023). Effects of universal and unconditional cash transfers on child abuse and neglect (NBER Working Paper No. 31733). National Bureau of Economic Research. link B Moderate
  18. Christopher, H., Josephat, E., Kaywanga, F., Saul, S., Mshana, I., Kunambi, P., et al. (2022). Potential of point of care tests for newborn screening for sickle cell disease: Evaluation of HemotypeSC™ and sickle SCAN® in Tanzania. International Journal of Laboratory Hematology, 44(5), 959-965. link B Moderate
  19. Cipriano, C., Strambler, M. J., Naples, L. H., Ha, C., Kirk, M., Wood, M., Sehgal, K., Zieher, A. K., Eveleigh, A., McCarthy, M., Funaro, M., Ponnock, A., Chow, J. C., & Durlak, J. (2023). The state of evidence for social and emotional learning: A contemporary meta-analysis of universal school-based SEL interventions. Child Development, 94(5), 1181-1204. link B Moderate
  20. Cluver, L. D., Meinck, F., Steinert, J. I., Shenderovich, Y., Doubt, J., Herrero Romero, R., et al. (2018). Parenting for Lifelong Health: A pragmatic cluster randomised controlled trial of a non-commercialised parenting programme for adolescents and their families in South Africa. BMJ Global Health, 3(1), e000539. link B Moderate
  21. Colchero, M. A., Popkin, B. M., Rivera, J. A., & Ng, S. W. (2016). Beverage purchases from stores in Mexico under the excise tax on sugar sweetened beverages: Observational study. BMJ, 352, h6704. link B Moderate
  22. Community Preventive Services Task Force. (2009). Alcohol: Excessive consumption: Maintaining limits on hours of sale. The Community Guide. link B Moderate
  23. Conde-Agudelo, A., & Díaz-Rossello, J. L. (2016). Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database of Systematic Reviews, 2016(8), CD002771. link A Strong
  24. Devries, K. M., Knight, L., Child, J. C., Mirembe, A., Nakuti, J., Jones, R., et al. (2015). The Good School Toolkit for reducing physical violence from school staff to primary school students: A cluster-randomised controlled trial in Uganda. The Lancet Global Health, 3(7), e378-e386. link B Moderate
  25. Dewey, K. G., Stewart, C. P., Wessells, K. R., Prado, E. L., & Arnold, C. D. (2021). Small-quantity lipid-based nutrient supplements for the prevention of child malnutrition and promotion of healthy development: Overview of individual participant data meta-analysis and programmatic implications. American Journal of Clinical Nutrition, 114(Suppl. 1), 3S-14S. link A Strong
  26. Dou, J., Gihleb, R., Giuntella, O., & Lonsky, J. (2026). Breaking the early bell: Lessons from the first statewide mandate on school start times (NBER Working Paper No. 35184). National Bureau of Economic Research. link B Moderate
  27. Dowswell, T., Carroli, G., Duley, L., Gates, S., Gülmezoglu, A. M., Khan-Neelofur, D., & Piaggio, G. (2015). Alternative versus standard packages of antenatal care for low-risk pregnancy. Cochrane Database of Systematic Reviews, 2015(7), CD000934. link B Moderate
  28. Dunster, G. P., de la Iglesia, L., Ben-Hamo, M., Nave, C., Fleischer, J. G., Panda, S., & de la Iglesia, H. O. (2018). Sleepmore in Seattle: Later school start times are associated with more sleep and better performance in high school students. Science Advances, 4(12), eaau6200. link C Limited
  29. Durlak, J. A., Weissberg, R. P., Dymnicki, A. B., Taylor, R. D., & Schellinger, K. B. (2011). The impact of enhancing students' social and emotional learning: A meta-analysis of school-based universal interventions. Child Development, 82(1), 405-432. link B Moderate
  30. European Union Drugs Agency. (n.d.). Planet Youth: Icelandic model [Xchange prevention registry entry]. link C Limited
  31. Faggiano, F., Minozzi, S., Versino, E., & Buscemi, D. (2014). Universal school-based prevention for illicit drug use. Cochrane Database of Systematic Reviews, 2014(12), CD003020. link B Moderate
  32. Feng, J., Huang, W. Y., Zheng, C., Jiao, J., Khan, A., Nisar, M., & Wong, S. H.-S. (2024). The overflow effects of movement behaviour change interventions for children and adolescents: A systematic review and meta-analysis of randomised controlled trials. Sports Medicine, 54(12), 3151-3167. link C Limited
  33. Field, M. S., Mithra, P., & Peña-Rosas, J. P. (2021). Wheat flour fortification with iron and other micronutrients for reducing anaemia and improving iron status in populations. Cochrane Database of Systematic Reviews, 2021(1), CD011302. link B Moderate
  34. Ford, G., & LaFranchi, S. H. (2014). Screening for congenital hypothyroidism: A worldwide view of strategies. Best Practice & Research Clinical Endocrinology & Metabolism, 28(2), 175-187. link B Moderate: (raised from C on October 7, 2026, because the 2025 update confirms the estimate)
  35. Freeman, D., Sheaves, B., Goodwin, G. M., Yu, L.-M., Nickless, A., Harrison, P. J., et al. (2017). The effects of improving sleep on mental health (OASIS): A randomised controlled trial with mediation analysis. The Lancet Psychiatry, 4(10), 749-758. link B Moderate
  36. Freijah, I., Jones, K. A., Coleman, T., Perlen, S. M., Kennedy, M., Passey, M. E., et al. (2026). Psychosocial interventions for supporting women to stop smoking in pregnancy. Cochrane Database of Systematic Reviews, 2026(4), CD001055. link A Strong: for abstinence, B for low birth weight
  37. Gamble, C., Ekwaru, J. P., & ter Kuile, F. O. (2006). Insecticide-treated nets for preventing malaria in pregnancy. Cochrane Database of Systematic Reviews, 2006(2), CD003755. link B Moderate
  38. Gaston, M. H., Verter, J. I., Woods, G., Pegelow, C., Kelleher, J., Presbury, G., et al. (1986). Prophylaxis with oral penicillin in children with sickle cell anemia: A randomized trial. New England Journal of Medicine, 314(25), 1593-1599. link B Moderate
  39. Gertler, P., Heckman, J., Pinto, R., Zanolini, A., Vermeersch, C., Walker, S., Chang, S. M., & Grantham-McGregor, S. (2014). Labor market returns to an early childhood stimulation intervention in Jamaica. Science, 344(6187), 998-1001. link B Moderate
  40. Goodman, W. B., Dodge, K. A., Bai, Y., Murphy, R. A., & O'Donnell, K. (2021). Effect of a universal postpartum nurse home visiting program on child maltreatment and emergency medical care at 5 years of age: A randomized clinical trial. JAMA Network Open, 4(7), e2116024. link C Limited
  41. Gubbels, J., van der Put, C. E., Stams, G. J. J. M., Prinzie, P. J., & Assink, M. (2021). Components associated with the effect of home visiting programs on child maltreatment: A meta-analytic review. Child Abuse & Neglect, 114, 104981. link A Strong
  42. Hadipour Dehshal, M., Tabrizi Namini, M., Ahmadvand, A., Manshadi, M., Sadeghian Varnosfaderani, F., & Abolghasemi, H. (2014). Evaluation of the national prevention program in Iran, 2007-2009: The accomplishments and challenges with reflections on the path ahead. Hemoglobin, 38(3), 179-187. link B Moderate
  43. Hamory, J., Miguel, E., Walker, M., Kremer, M., & Baird, S. (2021). Twenty-year economic impacts of deworming. Proceedings of the National Academy of Sciences, 118(14), e2023185118. link B Moderate
  44. Hawkins, J. D., Oesterle, S., Brown, E. C., Abbott, R. D., & Catalano, R. F. (2014). Youth problem behaviors 8 years after implementing the Communities That Care prevention system: A community-randomized trial. JAMA Pediatrics, 168(2), 122-129. link B Moderate
  45. Heller, S. B., Shah, A. K., Guryan, J., Ludwig, J., Mullainathan, S., & Pollack, H. A. (2017). Thinking, fast and slow? Some field experiments to reduce crime and dropout in Chicago. The Quarterly Journal of Economics, 132(1), 1-54. link B Moderate
  46. Hofmeyr, G. J., Black, R. E., Rogozińska, E., Heuer, A., Walker, N., Ashorn, P., et al. (2023). Evidence-based antenatal interventions to reduce the incidence of small vulnerable newborns and their associated poor outcomes. The Lancet, 401(10389), 1733-1744. link B Moderate
  47. Hoppen, T. H., Wessarges, L., Jehn, M., Mutz, J., Kip, A., Schlechter, P., Meiser-Stedman, R., & Morina, N. (2025). Psychological interventions for pediatric posttraumatic stress disorder: A systematic review and network meta-analysis. JAMA Psychiatry, 82(2), 130-141. link A Strong
  48. Humphrey, J. H., Mbuya, M. N. N., Ntozini, R., Moulton, L. H., Stoltzfus, R. J., Tavengwa, N. V., et al. (SHINE Trial Team). (2019). Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: A cluster-randomised trial. The Lancet Global Health, 7(1), e132-e147. link A Strong
  49. Imdad, A., Mayo-Wilson, E., Haykal, M. R., Regan, A., Sidhu, J., Smith, A., & Bhutta, Z. A. (2022). Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database of Systematic Reviews, 2022(3), CD008524. link A Strong
  50. International Agency for Research on Cancer. (2011). Effectiveness of tax and price policies for tobacco control (IARC Handbooks of Cancer Prevention, Vol. 14). IARC. link A Strong
  51. Jaffe, M. G., Lee, G. A., Young, J. D., Sidney, S., & Go, A. S. (2013). Improved blood pressure control associated with a large-scale hypertension program. JAMA, 310(7), 699-705. link C Limited
  52. John, C. C., Opoka, R. O., Latham, T. S., Hume, H. A., Nabaggala, C., Kasirye, P., et al. (2020). Hydroxyurea dose escalation for sickle cell anemia in sub-Saharan Africa. New England Journal of Medicine, 382(26), 2524-2533. link B Moderate
  53. Jonani, B., Nakawuka, B., Ssebunya, E., Kwizera, R., Bongomin, F., & Mboowa, G. (2026). Uganda's mandatory newborn sickle cell disease screening programme: Translating a decade of evidence into differentiated implementation. Pediatric Health, Medicine and Therapeutics, 17, 621156. link (article number as listed in PubMed, unconfirmed against publisher) B Moderate: for the launch fact, C for the cost figure
  54. J-PAL: Teaching at the Right Level B Moderate: conflict-of-interest rule applies, but the trials are randomized
  55. Kancherla, V., Wagh, K., & Pachón, H. (2026). A global update on the status of prevention of folic acid-preventable spina bifida and anencephaly in year 2024. Birth Defects Research, 118(5), e70065. link B Moderate
  56. Kaner, E. F. S., Beyer, F. R., Muirhead, C., Campbell, F., Pienaar, E. D., Bertholet, N., et al. (2018). Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database of Systematic Reviews, 2018(2), CD004148. link A Strong
  57. Kashi, B., Godin, C. M., Kurzawa, Z. A., Verney, A. M. J., Busch-Hallen, J. F., & De-Regil, L. M. (2019). Multiple micronutrient supplements are more cost-effective than iron and folic acid: Modeling results from 3 high-burden Asian countries. The Journal of Nutrition, 149(7), 1222-1229. link B Moderate
  58. Kayentao, K., Garner, P., van Eijk, A. M., Naidoo, I., Roper, C., Mulokozi, A., et al. (2013). Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: Systematic review and meta-analysis. JAMA, 309(6), 594-604. link A Strong
  59. Keats, E. C., Haider, B. A., Tam, E., & Bhutta, Z. A. (2019). Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database of Systematic Reviews, 2019(3), CD004905. link A Strong
  60. Kellam, S. G., Brown, C. H., Poduska, J. M., Ialongo, N. S., Wang, W., Toyinbo, P., et al. (2008). Effects of a universal classroom behavior management program in first and second grades on young adult behavioral, psychiatric, and social outcomes. Drug and Alcohol Dependence, 95(Suppl. 1), S5-S28. link B Moderate
  61. Keza, G. K., Diallo, D. A., Diagne, I., de Montalembert, M., Corbasson, A., Bernaudin, F., et al. (2023). Availability and cost of basic drugs for sickle cell disease in 13 African countries [Conference abstract]. Blood, 142(Suppl. 1). American Society of Hematology 65th Annual Meeting. link C Limited
  62. Kovski, N. L., Hill, H. D., Mooney, S. J., Rivara, F. P., & Rowhani-Rahbar, A. (2022). Short-term effects of tax credits on rates of child maltreatment reports in the United States. Pediatrics, 150(1), e2021054939. link B Moderate
  63. Kramer, M. S., Aboud, F., Mironova, E., Vanilovich, I., Platt, R. W., Matush, L., Igumnov, S., Fombonne, E., Bogdanovich, N., Ducruet, T., Collet, J.-P., Chalmers, B., Hodnett, E., Davidovsky, S., Skugarevsky, O., Trofimovich, O., Kozlova, L., Shapiro, S., & PROBIT Study Group. (2008). Breastfeeding and child cognitive development: New evidence from a large randomized trial. Archives of General Psychiatry, 65(5), 578-584. link B Moderate
  64. Kuznik, A., Habib, A. G., Munube, D., & Lamorde, M. (2016). Newborn screening and prophylactic interventions for sickle cell disease in 47 countries in sub-Saharan Africa: A cost-effectiveness analysis. BMC Health Services Research, 16, 304. link B Moderate
  65. Landrigan, C. P., Rothschild, J. M., Cronin, J. W., Kaushal, R., Burdick, E., Katz, J. T., et al. (2004). Effect of reducing interns' work hours on serious medical errors in intensive care units. New England Journal of Medicine, 351(18), 1838-1848. link C Limited: (lowered from B on October 7, 2026, because a later multicentre trial did not replicate it)
  66. Landrigan, C. P., Rahman, S. A., Sullivan, J. P., Vittinghoff, E., Barger, L. K., Sanderson, A. L., et al. (2020). Effect on patient safety of a resident physician schedule without 24-hour shifts. New England Journal of Medicine, 382(26), 2514-2523. link B Moderate
  67. Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., et al. (SELECT Trial Investigators). (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes. New England Journal of Medicine, 389(24), 2221-2232. link B Moderate
  68. Luby, S. P., Rahman, M., Arnold, B. F., Unicomb, L., Ashraf, S., Winch, P. J., et al. (2018). Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Bangladesh: A cluster randomised controlled trial. The Lancet Global Health, 6(3), e302-e315. link A Strong
  69. Madanitsa, M., Barsosio, H. C., Minja, D. T. R., Mtove, G., Kavishe, R. A., Dodd, J., et al. (2023). Effect of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine with and without azithromycin versus monthly sulfadoxine-pyrimethamine on adverse pregnancy outcomes in Africa: A double-blind randomised, partly placebo-controlled trial. The Lancet, 401(10381), 1020-1036. link B Moderate
  70. Manley, J., Alderman, H., & Gentilini, U. (2022). More evidence on cash transfers and child nutritional outcomes: A systematic review and meta-analysis. BMJ Global Health, 7(4), e008233. link B Moderate
  71. Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), CD002209. link A Strong: for retention and heroin use
  72. McConnell, M. A., Rokicki, S., Ayers, S., Allouch, F., Perreault, N., Gourevitch, R. A., et al. (2022). Effect of an intensive nurse home visiting program on adverse birth outcomes in a Medicaid-eligible population: A randomized clinical trial. JAMA, 328(1), 27-37. link B Moderate
  73. McGoldrick, E., Stewart, F., Parker, R., & Dalziel, S. R. (2020). Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews, 2020(12), CD004454. link A Strong
  74. Menting, A. T. A., Orobio de Castro, B., & Matthys, W. (2013). Effectiveness of the Incredible Years parent training to modify disruptive and prosocial child behavior: A meta-analytic review. Clinical Psychology Review, 33(8), 901-913. link B Moderate
  75. Minges, K. E., & Redeker, N. S. (2016). Delayed school start times and adolescent sleep: A systematic review of the experimental evidence. Sleep Medicine Reviews, 28, 86-95. link C Limited
  76. Moges, S., Kotiso, K. S., & Jaldo, M. M. (2026). The effectiveness of mandatory folic acid fortification compared with pre-fortification periods on reducing neural tube defects (NTDs): A systematic review and meta-analysis. BMC Nutrition, 12(1), 31. link (published 13 January 2026, PMID 41526993) B Moderate
  77. Neal, B., Wu, Y., Feng, X., Zhang, R., Zhang, Y., Shi, J., et al. (2021). Effect of salt substitution on cardiovascular events and death. New England Journal of Medicine, 385(12), 1067-1077. link B Moderate
  78. Neil-Sztramko, S. E., Caldwell, H., & Dobbins, M. (2021). School-based physical activity programs for promoting physical activity and fitness in children and adolescents aged 6 to 18. Cochrane Database of Systematic Reviews, 2021(9), CD007651. link A Strong
  79. Nnodu, O., Isa, H., Nwegbu, M., Ohiaeri, C., Adegoke, S., Chianumba, R., et al. (2019). HemoTypeSC, a low-cost point-of-care testing device for sickle cell disease: Promises and challenges. Blood Cells, Molecules, and Diseases, 78, 22-28. link B Moderate
  80. Noble, K., Magnuson, K., Duncan, G., Gennetian, L. A., Yoshikawa, H., Fox, N. A., et al. (2025). The effect of a monthly unconditional cash transfer on children's development at four years of age: A randomized controlled trial in the U.S. (NBER Working Paper No. 33844). National Bureau of Economic Research. link B Moderate
  81. Olaniyan, H. S., Briscoe, C., Muhongo, M., Pascoal, R., Armando, A., Santos, B., & McGann, P. T. (2023). Early diagnosis of sickle cell disease at birth hospitals and vaccination centers in Angola using point-of-care tests. Blood Advances, 7(19), 5860-5867. link B Moderate
  82. Olds, D. L., Eckenrode, J., Henderson, C. R., Jr., Kitzman, H., Powers, J., Cole, R., Sidora, K., Morris, P., Pettitt, L. M., & Luckey, D. (1997). Long-term effects of home visitation on maternal life course and child abuse and neglect: Fifteen-year follow-up of a randomized trial. JAMA, 278(8), 637-643. link B Moderate
  83. Opoka, R. O., Ndugwa, C. M., Latham, T. S., Lane, A., Hume, H. A., Kasirye, P., et al. (2017). Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): A trial for children with sickle cell anemia. Blood, 130(24), 2585-2593. link B Moderate
  84. Ota, E., Hori, H., Mori, R., Tobe-Gai, R., & Farrar, D. (2015). Antenatal dietary education and supplementation to increase energy and protein intake. Cochrane Database of Systematic Reviews, 2015(6), CD000032. link B Moderate
  85. Pagliarulo, N. (2023, December 8). Pricey new gene therapies for sickle cell pose access test. BioPharma Dive. link B Moderate
  86. Pasricha, S.-R., Mwangi, M. N., Moya, E., Ataide, R., Mzembe, G., Harding, R., et al. (2023). Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: A randomised controlled trial. The Lancet, 401(10388), 1595-1609. link B Moderate
  87. Pawar, A. K. S., Firmin, E. S., Wilens, T. E., & Hammond, C. J. (2024). Systematic review and meta-analysis: Medical and recreational cannabis legalization and cannabis use among youth in the United States. Journal of the American Academy of Child and Adolescent Psychiatry, 63(11), 1084-1113. link C Limited
  88. Qian, M., Wang, D., Watkins, W. E., Gebski, V., Yan, Y. Q., Li, M., & Chen, Z. P. (2005). The effects of iodine on intelligence in children: A meta-analysis of studies conducted in China. Asia Pacific Journal of Clinical Nutrition, 14(1), 32-42. link C Limited
  89. Raissian, K. M., & Bullinger, L. R. (2017). Money matters: Does the minimum wage affect child maltreatment rates? Children and Youth Services Review, 72, 60-70. link B Moderate
  90. Rankine-Mullings, A. E., & Owusu-Ofori, S. (2021). Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease. Cochrane Database of Systematic Reviews, 2021(3), CD003427. link B Moderate
  91. Robling, M., Bekkers, M.-J., Bell, K., Butler, C. C., Cannings-John, R., Channon, S., et al. (2016). Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): A pragmatic randomised controlled trial. The Lancet, 387(10014), 146-155. link B Moderate
  92. Rogers, N. T., Cummins, S., Forde, H., Jones, C. P., Mytton, O., Rutter, H., et al. (2023). Associations between trajectories of obesity prevalence in English primary school children and the UK soft drinks industry levy: An interrupted time series analysis of surveillance data. PLOS Medicine, 20(1), e1004160. link C Limited
  93. Sazawal, S., et al. (2016). Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: A community-based randomised controlled trial. Lancet Global Health, 4(11), e837-e844. link B Moderate
  94. Schwalm, J.-D., McCready, T., Lopez-Jaramillo, P., Yusoff, K., Attaran, A., Lamelas, P., et al. (2019). A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): A cluster-randomised controlled trial. The Lancet, 394(10205), 1231-1242. link B Moderate
  95. Semrau, K. E. A., et al. (2016). Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): A cluster-randomised controlled trial. Lancet Global Health, 4(11), e827-e836. link B Moderate
  96. Siegfried, N., Pienaar, D. C., Ataguba, J. E., Volmink, J., Kredo, T., Jere, M., & Parry, C. D. H. (2014). Restricting or banning alcohol advertising to reduce alcohol consumption in adults and adolescents. Cochrane Database of Systematic Reviews, 2014(11), CD010704. link C Limited
  97. Sinha, A., Sazawal, S., Pradhan, A., Ramji, S., & Opiyo, N. (2015). Chlorhexidine skin or cord care for prevention of mortality and infections in neonates. Cochrane Database of Systematic Reviews, 2015(3), CD007835. link B Moderate: for South Asia, D if applied to sub-Saharan Africa
  98. Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R. (2017). Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. BMJ, 357, j1550. link C Limited
  99. Stewart, C. P., Wessells, K. R., Arnold, C. D., Huybregts, L., Ashorn, P., Becquey, E., Humphrey, J. H., & Dewey, K. G. (2020). Lipid-based nutrient supplements and all-cause mortality in children 6-24 months of age: A meta-analysis of randomized controlled trials. American Journal of Clinical Nutrition, 111(1), 207-218. link B Moderate
  100. Swanson, K., Ayers, S., Oviedo, D., Zhou, R. A., Bates, M. A., Baicker, K., Chien, A. T., & McConnell, M. (2025). Intensive nurse home visiting and early childhood outcomes: A randomized clinical trial. JAMA Pediatrics, 179(8), 857-866. link B Moderate
  101. Taylor-Robinson, D. C., Maayan, N., Donegan, S., Chaplin, M., & Garner, P. (2019). Public health deworming programmes for soil-transmitted helminths in children living in endemic areas. Cochrane Database of Systematic Reviews, 2019(9), CD000371. link B Moderate
  102. Trauer, J. M., Qian, M. Y., Doyle, J. S., Rajaratnam, S. M. W., & Cunnington, D. (2015). Cognitive behavioral therapy for chronic insomnia: A systematic review and meta-analysis. Annals of Internal Medicine, 163(3), 191-204. link A Strong
  103. Troller-Renfree, S. V., Costanzo, M. A., Duncan, G. J., Magnuson, K., Gennetian, L. A., Yoshikawa, H., Halpern-Meekin, S., Fox, N. A., & Noble, K. G. (2022). The impact of a poverty reduction intervention on infant brain activity. Proceedings of the National Academy of Sciences, 119(5), e2115649119. link D Contested: (contested)
  104. Troncoso, P., & Humphrey, N. (2021). Playing the long game: A multivariate multilevel non-linear growth curve model of long-term effects in a randomized trial of the Good Behavior Game. Journal of School Psychology, 88, 68-84. link B Moderate
  105. Tshilolo, L., Tomlinson, G., Williams, T. N., Santos, B., Olupot-Olupot, P., Lane, A., et al. (2019). Hydroxyurea for children with sickle cell anemia in sub-Saharan Africa. New England Journal of Medicine, 380(2), 121-131. link C Limited: for mortality, B for feasibility and safety
  106. Tumukunde, V., Medvedev, M. M., Tann, C. J., et al. (2024). Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): A parallel-group, individually randomised controlled trial and economic evaluation. The Lancet, 403(10443), 2520-2532. link B Moderate
  107. UNICEF. (n.d.). Iodine [Data topic page]. UNICEF Data. link B Moderate
  108. U.S. Food and Drug Administration. (2023, December 8). FDA approves first gene therapies to treat patients with sickle cell disease [Press release]. link B Moderate
  109. van IJzendoorn, M. H., Schuengel, C., Wang, Q., & Bakermans-Kranenburg, M. J. (2023). Improving parenting, child attachment, and externalizing behaviors: Meta-analysis of the first 25 randomized controlled trials on the effects of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline. Development and Psychopathology, 35(1), 241-256. link B Moderate
  110. Velasco, I., Rueda-Etxebarria, M., Trak-Fellermeier, M. A., Taylor, P., Rabassa Bonet, M., Chi, Y., Janka, H., & Rueda, J. R. (2026). Iodine supplementation for preventing iodine deficiency disorders in children and adolescents. Cochrane Database of Systematic Reviews, 2026(9), CD014475. link B Moderate
  111. Wagenaar, A. C., Salois, M. J., & Komro, K. A. (2009). Effects of beverage alcohol price and tax levels on drinking: A meta-analysis of 1003 estimates from 112 studies. Addiction, 104(2), 179-190. link A Strong
  112. Walley, A. Y., Xuan, Z., Hackman, H. H., Quinn, E., Doe-Simkins, M., Sorensen-Alawad, A., Ruiz, S., & Ozonoff, A. (2013). Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: Interrupted time series analysis. BMJ, 346, f174. link C Limited
  113. West, S. L., & O'Neal, K. K. (2004). Project D.A.R.E. outcome effectiveness revisited. American Journal of Public Health, 94(6), 1027-1029. link A Strong
  114. WHO ACTION Trials Collaborators (Oladapo, O. T., Vogel, J. P., Piaggio, G., Nguyen, M. H., Althabe, F., Gülmezoglu, A. M., et al.). (2020). Antenatal dexamethasone for early preterm birth in low-resource countries. New England Journal of Medicine, 383(26), 2514-2525. link B Moderate
  115. WHO Immediate KMC Study Group (Arya, S., Naburi, H., Kawaza, K., Newton, S., Anyabolu, C. H., Bergman, N., et al.). (2021). Immediate "kangaroo mother care" and survival of infants with low birth weight. New England Journal of Medicine, 384(21), 2028-2038. link B Moderate
  116. Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., et al. (STEP 1 Study Group). (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989-1002. link B Moderate: (lowered from A on October 7, 2026, because the trial is manufacturer sponsored)
  117. Wilding, J. P. H., Batterham, R. L., Davies, M., Van Gaal, L. F., Kandler, K., Konakli, K., et al. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism, 24(8), 1553-1564. link B Moderate
  118. Wilson, P., Rush, R., Hussey, S., Puckering, C., Sim, F., Allely, C. S., Doku, P., McConnachie, A., & Gillberg, C. (2012). How evidence-based is an "evidence-based parenting program"? A PRISMA systematic review and meta-analysis of Triple P. BMC Medicine, 10, 130. link B Moderate
  119. World Health Organization. (2016). INSPIRE: Seven strategies for ending violence against children. World Health Organization. ISBN 978-92-4-156535-6. link B Moderate
  120. World Health Organization. (2021, December 13). Investing 1 dollar per person per year could save 7 million lives in low- and lower-middle-income countries [News release]. link B Moderate
  121. World Health Organization. (2025, December 1). WHO issues global guideline on the use of GLP-1 medicines in treating obesity [News release]. link B Moderate
  122. Wyper, G. M. A., Mackay, D. F., Fraser, C., Lewsey, J., Robinson, M., Beeston, C., & Giles, L. (2023). Evaluating the impact of alcohol minimum unit pricing on deaths and hospitalisations in Scotland: A controlled interrupted time series study. The Lancet, 401(10385), 1361-1370. link B Moderate
  123. Yang, S., Martin, R. M., Oken, E., et al. (2018). Breastfeeding during infancy and neurocognitive function in adolescence: 16-year follow-up of the PROBIT cluster-randomized trial. PLOS Medicine, 15(4), e1002554. link B Moderate
  124. ACEs Aware. (2026). ACEs Aware screening, training, and certification progress: July 2026 update. California Department of Health Care Services and Office of the California Surgeon General. link B Moderate
  125. Khoury, J. E., Bosquet Enlow, M., Plamondon, A., & Lyons-Ruth, K. (2019). The association between adversity and hair cortisol levels in humans: A meta-analysis. Psychoneuroendocrinology, 103, 104-117. link C Limited
  126. Miller, S., Rhodes, E., Bartik, A. W., Broockman, D. E., Krause, P. K., & Vivalt, E. (2024, revised 2026). Does income affect health? Evidence from a randomized controlled trial of a guaranteed income (NBER Working Paper No. 32711). National Bureau of Economic Research. link B Moderate
  127. RAND Corporation. (2025). California's ACEs Aware initiative has made substantial early progress, but sustained investment is needed (Research Brief RB-A2152-2). link B Moderate
  128. Sarafoglou, K., Kim, M. S., Lodish, M., Felner, E. I., Martinerie, L., Nokoff, N. J., et al. (2024). Phase 3 trial of crinecerfont in pediatric congenital adrenal hyperplasia. New England Journal of Medicine, 391(6), 493-503. link B Moderate
  129. Spierling, S. R., & Zorrilla, E. P. (2017). Don't stress about CRF: Assessing the translational failures of CRF1 antagonists. Psychopharmacology, 234(9-10), 1467-1481. link B Moderate
  130. Stalder, T., Steudte-Schmiedgen, S., Alexander, N., Klucken, T., Vater, A., Wichmann, S., et al. (2017). Stress-related and basic determinants of hair cortisol in humans: A meta-analysis. Psychoneuroendocrinology, 77, 261-274. link C Limited
  131. U.S. Food and Drug Administration. (2024). Novel drug approvals for 2024. link B Moderate
  132. Allegheny County Department of Human Services. (2023). Impact evaluation of the Allegheny Family Screening Tool (Phase 2) [Summary of an evaluation by J. Goldhaber-Fiebert and L. Prince, Stanford University]. link C Limited
  133. Bovell-Ammon, A., McCann, N. C., Mulugeta, M., Ettinger de Cuba, S., Raifman, J., & Shafer, P. (2022). Association of the expiration of child tax credit advance payments with food insufficiency in US households. JAMA Network Open, 5(10), e2234438. link B Moderate
  134. Chouldechova, A., Benavides-Prado, D., Fialko, O., & Vaithianathan, R. (2018). A case study of algorithm-assisted decision making in child maltreatment hotline screening decisions. Proceedings of Machine Learning Research, 81, 134-148. link B Moderate
  135. Duncan, G. J., Magnuson, K., Kunin-Batson, A. S., Yoshikawa, H., Fox, N. A., Halpern-Meekin, S., et al. (2025). Cash transfers and their effect on maternal and young children's health: A randomized clinical trial. JAMA Pediatrics, 179(8), 867-875. link B Moderate
  136. Gerchick, M., Jegede, T., Shah, T., Gutierrez, A., Beiers, S., Shemtov, N., et al. (2023). The devil is in the details: Interrogating values embedded in the Allegheny Family Screening Tool. In Proceedings of the 2023 ACM Conference on Fairness, Accountability, and Transparency (pp. 1292-1310). Association for Computing Machinery. link B Moderate
  137. Office of Governor Ned Lamont. (2024, January 17). Governor Lamont and Treasurer Russell announce 7,810 babies have been born eligible for Connecticut Baby Bonds [Press release]. link B Moderate
  138. Raffington, L., Willems, Y. E., Sperber, J. F., Zarandooz, S., Costanzo, M. A., Notterman, D. A., et al. (2026). Effects of a randomized controlled trial of unconditional cash transfers on epigenetic measures of ageing and cognition in children and mothers. Nature Human Behaviour. Advance online publication. link C Limited
  139. Shafer, P. R., Gutiérrez, K. M., Ettinger de Cuba, S., Bovell-Ammon, A., & Raifman, J. (2022). Association of the implementation of child tax credit advance payments with food insufficiency in US households. JAMA Network Open, 5(1), e2143296. link B Moderate
  140. Troller-Renfree, S. V., Costanzo, M. A., Duncan, G. J., Magnuson, K., Gennetian, L. A., Yoshikawa, H., et al. (2026). The impact of a monthly unconditional cash transfer on child brain activity: A 4-year follow-up. Developmental Cognitive Neuroscience, 78, 101673. link B Moderate
  141. Dieussaert, I., Hyung Kim, J., Luik, S., Seidl, C., Pu, W., Stegmann, J.-U., et al. (2024). RSV prefusion F protein-based maternal vaccine: Preterm birth and other outcomes. New England Journal of Medicine, 390(11), 1009-1021. link B Moderate
  142. Hoffman, M. K., Goudar, S. S., Kodkany, B. S., Metgud, M., Somannavar, M., Okitawutshu, J., et al. (2020). Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): A randomised, double-blind, placebo-controlled trial. The Lancet, 395(10220), 285-293. link B Moderate
  143. Kampmann, B., Madhi, S. A., Munjal, I., Simões, E. A. F., Pahud, B. A., Llapur, C., et al. (2023). Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. New England Journal of Medicine, 388(16), 1451-1464. link B Moderate
  144. McCook, A. (2024, December 4). An artificial womb for preemies? Philly company gets $50 million to pursue. The Philadelphia Inquirer. link B Moderate
  145. Partridge, E. A., Davey, M. G., Hornick, M. A., McGovern, P. E., Mejaddam, A. Y., Vrecenak, J. D., et al. (2017). An extra-uterine system to physiologically support the extreme premature lamb. Nature Communications, 8, 15112. link C Limited: B for lambs
  146. Pokaprakarn, T., Prieto, J. C., Price, J. T., Kasaro, M. P., Sindano, N., Shah, H. R., et al. (2022). AI estimation of gestational age from blind ultrasound sweeps in low-resource settings. NEJM Evidence, 1(5), EVIDoa2100058. link B Moderate
  147. Stringer, J. S. A., Pokaprakarn, T., Prieto, J. C., Vwalika, B., Chari, S. V., Sindano, N., et al. (2024). Diagnostic accuracy of an integrated AI tool to estimate gestational age from blind ultrasound sweeps. JAMA, 332(8), 649-657. link B Moderate
  148. Suzuki, D., Yamaji, N., Nishimura, E., Suzuki, H., Ishikawa, K., Rahman, M. O., et al. (2025). Effects of antibiotic prophylaxis during labour on maternal and neonatal outcomes in women planning vaginal birth. Cochrane Database of Systematic Reviews, 2025(8), CD016211. link A Strong
  149. Tita, A. T. N., Carlo, W. A., McClure, E. M., Mwenechanya, M., Chomba, E., Hemingway-Foday, J. J., et al. (2023). Azithromycin to prevent sepsis or death in women planning a vaginal birth. New England Journal of Medicine, 388(13), 1161-1170. link B Moderate
  150. U.S. Food and Drug Administration. (2023a, August 21). FDA approves first vaccine for pregnant individuals to prevent RSV in infants [Press release]. link B Moderate
  151. U.S. Food and Drug Administration. (2023b). Pediatric Advisory Committee meeting announcement, September 19-20, 2023. link B Moderate
  152. Willis, A., Lee, C., Krogue, J., Wickramanayake, A., Young-Lin, N., Caron, S., et al. (2026). Generalization of AI-based gestational age assessment using blind sweep ultrasonography. JAMA Network Open, 9(7), e2622484. link B Moderate
  153. World Health Organization. (2025, May 30). WHO outlines recommendations to protect infants against RSV [News release]. link B Moderate
  154. Yan, X., Zheng, W., Wang, J., Yuan, X., & Li, G. (2024). Low-dose aspirin for the prevention of preterm birth in nulliparous women: Systematic review and meta-analysis. BMC Pregnancy and Childbirth, 24(1), 260. link B Moderate
  155. Centers for Medicare & Medicaid Services. (2025, July 15). Innovation insight: CMS model delivers access to sickle cell gene therapy with expansive list of state participants. link B Moderate
  156. Centers for Medicare & Medicaid Services. (2026). Cell and Gene Therapy (CGT) Access Model [Model page, last modified September 30, 2026]. link B Moderate
  157. Ceyhan-Birsoy, O., Murry, J. B., Machini, K., Lebo, M. S., Yu, T. W., Fayer, S., et al. (2019). Interpretation of genomic sequencing results in healthy and ill newborns: Results from the BabySeq Project. American Journal of Human Genetics, 104(1), 76-93. link B Moderate
  158. Cohen, J. L., Chakraborty, P., Fung-Kee-Fung, K., Schwab, M. E., Bali, D., Young, S. P., et al. (2022). In utero enzyme-replacement therapy for infantile-onset Pompe's disease. New England Journal of Medicine, 387(23), 2150-2158. link C Limited
  159. Frangoul, H., Locatelli, F., Sharma, A., Bhatia, M., Mapara, M., Molinari, L., et al. (2024). Exagamglogene autotemcel for severe sickle cell disease. New England Journal of Medicine, 390(18), 1649-1662. link B Moderate
  160. Genomics England. (2024, October 3). First newborn babies tested for over 200 genetic conditions as world-leading study begins in NHS hospitals. link B Moderate
  161. Karavani, E., Zuk, O., Zeevi, D., Barzilai, N., Stefanis, N. C., Hatzimanolis, A., et al. (2019). Screening human embryos for polygenic traits has limited utility. Cell, 179(6), 1424-1435.e8. link B Moderate
  162. Musunuru, K., Grandinette, S. A., Wang, X., Hudson, T. R., Briseno, K., Berry, A. M., et al. (2025). Patient-specific in vivo gene editing to treat a rare genetic disease. New England Journal of Medicine, 392(22), 2235-2243. link C Limited
  163. Prasad, V., & Makary, M. A. (2025). FDA's new plausible mechanism pathway. New England Journal of Medicine, 393(23), 2365-2367. link B Moderate
  164. Turley, P., Meyer, M. N., Wang, N., Cesarini, D., Hammonds, E., Martin, A. R., et al. (2021). Problems with using polygenic scores to select embryos. New England Journal of Medicine, 385(1), 78-86. link B Moderate
  165. Ziegler, A., Koval-Burt, C., Kay, D. M., Suchy, S. F., Begtrup, A., Langley, K. G., et al. (2025). Expanded newborn screening using genome sequencing for early actionable conditions. JAMA, 333(3), 232-240. link B Moderate
  166. Andrée, B. P. J., Chamorro, A., Kraay, A., Spencer, P., & Wang, D. (2020). Predicting food crises (Policy Research Working Paper No. 9412). World Bank. link C Limited
  167. Bouscaren, D. (2026, August 31). Whatever happened to the U.S. famine alert system that Trump shut down, then reopened. NPR, via KPBS. link B Moderate
  168. Chen, R. Y., Mostafa, I., Hibberd, M. C., Das, S., Mahfuz, M., Naila, N. N., et al. (2021). A microbiota-directed food intervention for undernourished children. New England Journal of Medicine, 384(16), 1517-1528. link B Moderate
  169. Hartman, S. J., Hibberd, M. C., Mostafa, I., Nahar, N. N., Islam, M. M., Uz Zaman, M., et al. (2024). A microbiome-directed therapeutic food for children recovering from severe acute malnutrition [Preprint]. medRxiv. link B Moderate
  170. Mostafa, I., Hibberd, M. C., Hartman, S. J., Hafizur Rahman, M. H., Mahfuz, M., Hasan, S. M. T., et al. (2024). A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth. eBioMedicine, 104, 105166. link B Moderate
  171. Philippine Rice Research Institute. (2024, November 5). PhilRice seeks reconsideration of CA ruling on Malusog Rice. link B Moderate
  172. Popp, C. J., Hu, L., Kharmats, A. Y., Curran, M., Berube, L., Wang, C., et al. (2022). Effect of a personalized diet to reduce postprandial glycemic response vs a low-fat diet on weight loss in adults with abnormal glucose metabolism and obesity: A randomized clinical trial. JAMA Network Open, 5(9), e2233760. link B Moderate
  173. Pulta, B. (2024, April 23). CA issues Writ of Kalikasan vs. Golden Rice, Bt Eggplant. Philippine News Agency. link B Moderate
  174. Rohrer, G. (2026, March 24). Appeals court upholds Florida's ban on lab-grown meat. News Service of Florida, via WLRN. link B Moderate
  175. Sachs, A. J., & Johnson, E. A. (2024, May 7). Florida bans "cultivated" meat: First in a potential series of similar bans. Beveridge & Diamond. link B Moderate
  176. Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., et al. (2015). Personalized nutrition by prediction of glycemic responses. Cell, 163(5), 1079-1094. link B Moderate
  177. Castellano, J. M., Pocock, S. J., Bhatt, D. L., Quesada, A. J., Owen, R., Fernandez-Ortiz, A., et al. (2022). Polypill strategy in secondary cardiovascular prevention. New England Journal of Medicine, 387(11), 967-977. link B Moderate
  178. Comeras-Chueca, C., Marin-Puyalto, J., Matute-Llorente, A., Vicente-Rodriguez, G., Casajus, J. A., & Gonzalez-Aguero, A. (2021). Effects of active video games on health-related physical fitness and motor competence in children and adolescents with overweight or obesity: Systematic review and meta-analysis. JMIR Serious Games, 9(4), e29981. link C Limited
  179. Eli Lilly and Company. (2026, April 1). FDA approves Lilly's Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions [Press release]. link B Moderate
  180. Jastreboff, A. M., Kaplan, L. M., Davies, M. J., Wilding, J. P. H., Ahmad, N. N., Murray, M., et al. (2026). Retatrutide, a triple hormone receptor agonist, for treatment of obesity. New England Journal of Medicine. Advance online publication. link B Moderate
  181. Jastreboff, A. M., Kaplan, L. M., Frías, J. P., Wu, Q., Du, Y., Gurbuz, S., et al. (2023). Triple-hormone-receptor agonist retatrutide for obesity: A phase 2 trial. New England Journal of Medicine, 389(6), 514-526. link B Moderate
  182. Joseph, P., Roshandel, G., Gao, P., Pais, P., Lonn, E., Xavier, D., et al. (2021). Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: An individual participant data meta-analysis. The Lancet, 398(10306), 1133-1146. link A Strong
  183. Mueller, N., Rojas-Rueda, D., Khreis, H., Cirach, M., Andrés, D., Ballester, J., et al. (2020). Changing the urban design of cities for health: The superblock model. Environment International, 134, 105132. link C Limited
  184. Paraje, G., Valdés, N., Macaya, A. V., Corvalán, C., & Popkin, B. (2026). The impact of Chile's multipronged food labelling and advertising law on early childhood excess weight: A cohort difference-in-differences study. The Lancet, 407(10548), 2630-2640. link B Moderate
  185. Pérez, K., Palència, L., López, M. J., León-Gómez, B. B., Puig-Ribera, A., Gómez-Gutiérrez, A., et al. (2025). Environmental and health effects of the Barcelona superblocks. BMC Public Health, 25(1), 634. link C Limited
  186. Roshandel, G., Khoshnia, M., Poustchi, H., Hemming, K., Kamangar, F., Gharavi, A., et al. (2019). Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): A pragmatic, cluster-randomised trial. The Lancet, 394(10199), 672-683. link B Moderate
  187. Singh, B., Bennett, H., Miatke, A., Dumuid, D., Curtis, R., Ferguson, T., et al. (2025). Effectiveness of exercise for improving cognition, memory and executive function: A systematic umbrella review and meta-meta-analysis. British Journal of Sports Medicine, 59(12), 866-876. link B Moderate: A for exercise in general
  188. Taillie, L. S., Reyes, M., Colchero, M. A., Popkin, B., & Corvalán, C. (2020). An evaluation of Chile's Law of Food Labeling and Advertising on sugar-sweetened beverage purchases from 2015 to 2017: A before-and-after study. PLoS Medicine, 17(2), e1003015. link B Moderate
  189. Wharton, S., Aronne, L. J., Stefanski, A., Alfaris, N. F., Ciudin, A., Yokote, K., et al. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. New England Journal of Medicine, 393(18), 1796-1806. link B Moderate
  190. Israel, W., Mulitauopele, C., Ma, M., Levinson, A. H., Cikara, L., & Brooks-Russell, A. (2020). Adolescent health behaviors in schools with 4- versus 5-day school weeks. Journal of School Health, 90(10), 794-801. link C Limited
  191. Mignot, E., Mayleben, D., Fietze, I., Leger, D., Zammit, G., Bassetti, C. L. A., et al. (2022). Safety and efficacy of daridorexant in patients with insomnia disorder: Results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. The Lancet Neurology, 21(2), 125-139. link B Moderate
  192. National Institute for Health and Care Excellence. (2022, updated 2025). Sleepio to treat insomnia and insomnia symptoms (HealthTech guidance HTG624, formerly Medical technologies guidance MTG70). link B Moderate
  193. Pear Therapeutics. (2020, March 26). Pear Therapeutics obtains FDA authorization for SOMRYST, a prescription digital therapeutic for the treatment of adults with chronic insomnia [Press release]. Business Wire. link B Moderate
  194. Pear Therapeutics. (2023, April 7). Pear Therapeutics files for chapter 11 and will seek to sell assets through sales process (Form 8-K exhibit). US Securities and Exchange Commission. link B Moderate
  195. Rishi, M. A., Ahmed, O., Barrantes Perez, J. H., Berneking, M., Dombrowsky, J., Flynn-Evans, E. E., et al. (2020). Daylight saving time: An American Academy of Sleep Medicine position statement. Journal of Clinical Sleep Medicine, 16(10), 1781-1784. link C Limited: B for the transition harms
  196. Tomayko, E. J., Thompson, P. N., Smith, M. C., Gunter, K. B., & Schuna, J. M. (2021). Impact of reduced school exposure on adolescent health behaviors and food security: Evidence from 4-day school weeks. Journal of School Health, 91(12), 1055-1063. link C Limited
  197. 1News Reporters. (2024, February 27). Smokefree laws: Govt to repeal legislation under urgency. 1News. link B Moderate
  198. 22nd Century Group. (2026, September 24). 22nd Century Group urges policymakers and FDA to enact and implement the reduced nicotine content standard, citing years without a final rule [Press release]. Finviz. link B Moderate
  199. Action on Smoking and Health. (2026, April 29). APPG on Smoking and Health welcomes historic generational smoking ban becoming law [Press release]. link B Moderate
  200. Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., et al. (2022). Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 79(10), 953-962. link B Moderate
  201. Chalfin, A., del Pozo, B., & Mitre-Becerril, D. (2023). Overdose prevention centers, crime, and disorder in New York City. JAMA Network Open, 6(11), e2342228. link B Moderate
  202. Donny, E. C., Denlinger, R. L., Tidey, J. W., Koopmeiners, J. S., Benowitz, N. L., Vandrey, R. G., et al. (2015). Randomized trial of reduced-nicotine standards for cigarettes. New England Journal of Medicine, 373(14), 1340-1349. link B Moderate
  203. Food and Drug Administration. (2025, January 16). Tobacco product standard for nicotine yield of cigarettes and certain other combusted tobacco products (Proposed rule, Docket No. FDA-2024-N-5471). Federal Register, 90(10), 5032-5144. link B Moderate
  204. Hart, H., & Caddy, P. (2026, May 7). Tobacco and Vapes Act 2026 becomes law. Lewis Silkin. link B Moderate
  205. Hartmann-Boyce, J., Cahill, K., Hatsukami, D., & Cornuz, J. (2012). Nicotine vaccines for smoking cessation. Cochrane Database of Systematic Reviews, 2012(8), CD007072. link A Strong
  206. Hendershot, C. S., Bremmer, M. P., Paladino, M. B., Kostantinis, G., Gilmore, T. A., Sullivan, N. R., et al. (2025). Once-weekly semaglutide in adults with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 82(4), 395-405. link B Moderate
  207. Joshi, S., Rivera, B. D., Cerdá, M., Guy, G. P., Strahan, A., Wheelock, H., & Davis, C. S. (2023). One-year association of drug possession law change with fatal drug overdose in Oregon and Washington. JAMA Psychiatry, 80(12), 1277-1283. link B Moderate
  208. Judd, A. (2025, February 19). B.C. overhauls safe supply program, moving to witnessed model. Global News. link B Moderate
  209. Klausen, M. K., Justesen, S. K., Pedersen, J. N., Rasmussen, L., Jensen, A., Jensen, M. E., et al. (2026). Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: A randomised, double-blind, placebo-controlled trial. The Lancet, 407(10540), 1687-1698. link B Moderate
  210. Kosten, T. R., Domingo, C. B., Shorter, D., Orson, F., Green, C., Somoza, E., et al. (2014). Vaccine for cocaine dependence: A randomized double-blind placebo-controlled efficacy trial. Drug and Alcohol Dependence, 140, 42-47. link B Moderate
  211. New Zealand Parliament. (2024). Smokefree Environments and Regulated Products Amendment Act 2024 (2024 No 6). New Zealand Legislation. link B Moderate
  212. Nguyen, H. V., Mital, S., Bugden, S., & McGinty, E. E. (2024). British Columbia's Safer Opioid Supply policy and opioid outcomes. JAMA Internal Medicine, 184(3), 256-264. link C Limited
  213. Qeadan, F., McCunn, A., & Tingey, B. (2025). The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. Addiction, 120(2), 236-250. link C Limited
  214. Slaunwhite, A., Min, J. E., Palis, H., Urbanoski, K., Pauly, B., Barker, B., et al. (2024). Effect of Risk Mitigation Guidance opioid and stimulant dispensations on mortality and acute care visits during dual public health emergencies: Retrospective cohort study. BMJ, 384, e076336. link C Limited
  215. Spencer, N. (2023). Does drug decriminalization increase unintentional drug overdose deaths? Early evidence from Oregon Measure 110. Journal of Health Economics, 91, 102798. link D Contested
  216. Wilson, C. (2024, April 1). Oregon governor signs bill criminalizing drug possession. Oregon Public Broadcasting. link B Moderate
  217. Zoorob, M. J., Park, J. N., Kral, A. H., Lambdin, B. H., & del Pozo, B. (2024). Drug decriminalization, fentanyl, and fatal overdoses in Oregon. JAMA Network Open, 7(9), e2431612. link B Moderate

All references