A Scoping Review of Guidelines and Quality Measures to Screen for Social and Caregiver Support and Cognitive Impairment in Primary Care.

High-risk patients-those patients with complex health care needs who are most likely to face hospitalization or death in the following two years-are most often initially seen in the primary care setting. This small group of patients uses a disproportionate amount of care resources. Contributing to the challenges of care planning for this population is that individuals are highly heterogeneous; no two patients present the same set of symptoms, diagnoses, and challenges related to social determinants of health (SDOH). Methods for early identification of these high-risk patients-and their care needs-have raised the possibility of timely enhanced care. In this study, the authors conduct a scoping review to identify existing measures of care quality; assessment and screening guidelines; and tools that (1) assess social support, the need for caregiver support, and the need for referral to social services and (2) screen for cognitive impairment (CI). Evidence-based screening guidelines define who and what should be assessed-and how often-to enhance care quality and improve health outcomes, whereas measures permit ascertainment that this assessment is occurring. Evidence-based guidelines and measures-those that are found to lead to better health care outcomes-would be candidates for inclusion in a measure dashboard for high-risk patients in primary care settings.

Managing Urinary Incontinence for Women in Primary Care: Environmental Scan (Base Year).

Urinary incontinence (UI) is a highly prevalent condition among women worldwide. Although effective nonsurgical treatments exist, including pharmacological, behavioral, and physical therapies, many women with the condition are never diagnosed because of a lack of information, stigma, and the absence of regular screening in primary care, and those who are diagnosed might not receive or adhere to treatment. In this study, the authors present an environmental scan of studies published from 2012 through 2022 that assess the dissemination and implementation of nonsurgical UI treatment-including screening, management, and referral strategies-for women in primary care. The scan was conducted as part of the RAND's support and evaluation contract for the Agency for Healthcare Research and Quality's Managing Urinary Incontinence initiative. The initiative, which builds on the agency's EvidenceNOW model, funds five grant projects to disseminate and implement improved nonsurgical treatment of UI for women within primary care practices in separate regions of the United States.

The Impact of Mindfulness Meditation Programs on Performance-Related Outcomes: Implications for the U.S. Army.

Although studies have suggested that mindfulness-based interventions might be effective in enhancing military readiness and resilience, this has not been rigorously evaluated. This study presents results from a systematic review and meta-analyses of research examining how mindfulness meditation affects 13 performance-related outcomes of interest to the U.S. Army and broader military. The authors supplemented the systematic review by examining how mindfulness meditation could support stress management and exploring characteristics of selected mindfulness programs. The goal was to develop recommendations for mindfulness meditation programs for soldiers, should the Army choose to implement such programs in the future. Findings suggest that mindfulness may improve some aspects of attention and emotion regulation, impulsivity, and work-related morale and social support. The available evidence does not suggest that mindfulness improves other outcomes of interest to the Army. Notably, mindfulness meditation programs reduce stress and may reduce parental stress, which could benefit Army families. Yet more research is needed to identify best practices for implementing mindfulness programs in the military. The authors recommend conducting high-quality evaluations of mindfulness meditation with soldiers and assessing the effect of mindfulness meditation on military families.

Quality Measures for Patients at Risk of Adverse Outcomes in the Veterans Health Administration: Expert Panel Recommendations.

Importance: Despite longstanding efforts to improve health care quality for patients with complex needs who are at highest risk for hospitalization or death, to our knowledge, no guidance exists on what constitutes measurable high-quality care for this heterogeneous population. Identifying quality measures that are cross-cutting (ie, relevant to multiple chronic conditions and disease states) may enable health care professionals and health care systems to better design and report on quality improvement efforts for this patient population. Objective: To identify quality measures of care and prioritize quality-of-care concepts in the ambulatory primary care setting for patients in the Veterans Health Administration (VHA) who have complex care needs and are at high risk for adverse outcomes, such as hospitalization or death. Evidence Review: In this expert panel assessment and prioritization, relevant measure concepts for future quality measure development in 3 care categories (assessment, management, and other features of health care) were extracted from a systematic review, conducted from June 2020 to June 2021, of published studies that suggested, evaluated, or used indicators of quality care for patients at high risk of adverse outcomes. Measure concepts associated with single conditions, surgical or other specialty care settings, and inpatient care were excluded. A panel of 14 experts (10 VHA leaders and staff, 2 non-VHA physician investigators, and 2 veterans) discussed and rated the importance of the remaining set of potentially relevant measure concepts using a modified RAND/UCLA Appropriateness Method on January 15, 2021. Measure concepts were rated on a scale of 1 to 9, with 9 being the highest priority. A median rating of 7.5 or greater was used as the cutoff to identify the highest-priority items. Findings: The systematic review identified 519 measure concepts, from which 15 domains and 49 measure concepts were proposed for expert panel consideration. After panel discussions and changes to measure concepts, the expert panel rated 63 measure concepts in 13 domains. The measure concepts with the highest median ratings focused on caregiver availability and support, COVID-19 vaccination, and pneumonia vaccination (all rated 9.0); housing instability (rated 8.5); and physical function, depression symptoms, cognitive impairment, prescription regimen, primary care follow-up after an emergency department visit or hospitalization, and timely transmission of discharge information to primary care (all rated 8.0). Recommendations to improve care included timely assessment of housing instability, caregiver support, physical function, depression symptoms, and cognitive impairment; annual prescription regimen review; coordinated transitions in care; and preventive care including vaccinations. Conclusions and Relevance: The expert panelists identified a parsimonious set of high-priority, evidence-based, cross-cutting quality measure concepts for improving care of patients at high risk for adverse health outcomes in the VHA. These quality measures may inform both future research for patients at high risk and health care system quality improvement.

Safety of vaccines used for routine immunization in the United States: An updated systematic review and meta-analysis.

BACKGROUND: Understanding the safety of vaccines is critical to inform decisions about vaccination. Our objective was to conduct a systematic review of the safety of vaccines recommended for children, adults, and pregnant women in the United States. METHODS: We searched the literature in November 2020 to update a 2014 Agency for Healthcare Research and Quality review by integrating newly available data. Studies of vaccines that used a comparator and reported the presence or absence of key adverse events were eligible. Adhering to Evidence-based Practice Center methodology, we assessed the strength of evidence (SoE) for all evidence statements. The systematic review is registered in PROSPERO (CRD42020180089). RESULTS: Of 56,603 reviewed citations, 338 studies reported in 518 publications met inclusion criteria. For children, SoE was high for no increased risk of autism following measles, mumps, and rubella (MMR) vaccine. SoE was high for increased risk of febrile seizures with MMR. There was no evidence of increased risk of  intussusception with rotavirus vaccine at the latest follow-up (moderate SoE), nor of diabetes (high SoE). There was no evidence of increased risk or insufficient evidence for key adverse events for newer vaccines such as 9-valent human papillomavirus and meningococcal B vaccines. For adults, there was no evidence of increased risk (varied SoE) or insufficient evidence for key adverse events for the new adjuvanted inactivated influenza vaccine and recombinant adjuvanted zoster vaccine. We found no evidence of increased risk (varied SoE) for key adverse events among pregnant women following tetanus, diphtheria, and acellular pertussis vaccine, including stillbirth (moderate SoE). CONCLUSIONS: Across a large body of research we found few associations of vaccines and serious key adverse events; however, rare events are challenging to study. Any adverse events should be weighed against the protective benefits that vaccines provide.

Taking Care of Yourself and Your Risk for Breast Cancer (CUIDARSE): A Randomized Controlled Trial of a Health Communication Intervention for Latinas.

Latinas in the United States are more likely to be diagnosed with late-stage breast cancer (BC) compared to non-Latinas. Literacy-appropriate and culturally sensitive cancer communication interventions can help address existing racial/ethnic BC disparities. We formatively developed a new BC prevention brochure for Spanish-speaking Latinas (≥35 years). Eligible women (n = 240) from a large public hospital in California were randomly assigned to one of three study arms: Group 1 received the new brochure, Group 2 included a community health worker (CHW) who delivered the new brochure's content, and a control group received a standard educational brochure. Participants completed three surveys (baseline, postintervention, 3-month follow-up) with a 100% completion rate for the first two surveys and 80.4% completion after 3 months. We assessed the difference in outcomes for BC risk knowledge, perceived BC susceptibility, and BC information self-efficacy between groups. Participant mean age was 52.3 years, and 82.1% reported low English proficiency. Mean knowledge scores increased and perceived BC susceptibility improved for all groups (p ≤ .05), yet treatment effects were not significant between groups for these outcomes. BC information self-efficacy also increased from baseline to postintervention for all groups to >80%. After 3 months, only Group 2 and the control group retained their increases and treatment effects were significant only for Group 2 compared to other groups in unadjusted and adjusted models. A CHW-delivered intervention may be more effective in improving BC information self-efficacy among Latinas compared to print material alone. More research is needed to examine the efficacy of CHW-delivered interventions.

Effects of medication assisted treatment (MAT) for opioid use disorder on functional outcomes: A systematic review.

This systematic review synthesizes evidence on the effects of Medication-Assisted Treatment (MAT) for opioid use disorder (OUD) on functional outcomes, including cognitive (e.g., memory), physical (e.g., fatigue), occupational (e.g., return to work), social/behavioral (e.g., criminal activity), and neurological (e.g., balance) function. Five databases were searched from inception to July 2017 to identify English-language controlled trials, case control studies, and cohort comparisons of one or more groups; cross-sectional studies were excluded. Two independent reviewers screened identified literature, abstracted study-level information, and assessed the quality of included studies. Meta-analyses used the Hartung-Knapp method for random-effects models. The quality of evidence was assessed using the GRADE approach. A comprehensive search followed by 1411 full text publication screenings yielded 30 randomized controlled trials (RCTs) and 10 observational studies meeting inclusion criteria. The studies reported highly diverse functional outcome measures. Only one RCT was rated as high quality, but several methodologically sound observational studies were identified. The statistical power to detect differences in functional outcomes was unclear in most studies. When compared with matched "healthy" controls with no history of substance use disorder (SUD), in two studies MAT patients had significantly poorer working memory and cognitive speed. One study found MAT patients scored worse in aggressive responding than did "healthy" controls. A large observational study found that MAT users had twice the odds of involvement in an injurious traffic accident as non-users. When compared with persons with OUD not on MAT, one cohort study found lower fatigue rates among buprenorphine-treated OUD patients. No differences were reported for occupational outcomes and results for criminal activity and other social/behavioral areas were mixed. There were few differences among MAT drug types. A pooled analysis of three RCTs found a significantly lower prevalence of fatigue with buprenorphine compared to methadone, while a meta-analysis of the same RCTs found no statistical difference in insomnia prevalence. Three RCTs that focused on cognitive function compared the effects of buprenorphine to methadone; no statistically significant differences in memory, cognitive speed and flexibility, attention, or vision were reported. The quality of evidence for most functional outcomes was rated low or very low. In sum, weaknesses in the body of evidence prevent strong conclusions about the effects of MAT for opioid use disorder on functional outcomes. Rigorous studies of functional effects would strengthen the body of literature.

Agency for Healthcare Research and Quality Evidence-based Practice Center methods provide guidance on prioritization and selection of harms in systematic reviews.

OBJECTIVES: Systematic reviews should provide balanced assessments of benefits and harms, while focusing on the most important outcomes. Selection of harms to be reviewed can be a challenge due to the potential for large numbers of diverse harms. STUDY DESIGN AND SETTING: A workgroup of methodologists from Evidence-based Practice Centers (EPCs) developed consensus-based guidance on selection and prioritization of harms in systematic reviews. Recommendations were informed by a literature scan, review of Evidence-based Practice Center reports, and interviews with experts in conducting reviews or assessing harms and persons representing organizations that commission or use systematic reviews. RESULTS: Ten recommendations were developed on selection and prioritization of harms, including routinely focusing on serious as well as less serious but frequent or bothersome harms; routinely engaging stakeholders and using literature searches and other data sources to identify important harms; using a prioritization process (formal or less formal) to inform selection decisions; and describing the methods used to select and prioritize harms. CONCLUSION: We provide preliminary guidance for a more structured approach to selection and prioritization of harms in systematic reviews.

Efficacy of mindfulness meditation for smoking cessation: A systematic review and meta-analysis.

BACKGROUND: Smokers increasingly seek alternative interventions to assist in cessation or reduction efforts. Mindfulness meditation, which facilitates detached observation and paying attention to the present moment with openness, curiosity, and acceptance, has recently been studied as a smoking cessation intervention. AIMS: This review synthesizes randomized controlled trials (RCTs) of mindfulness meditation (MM) interventions for smoking cessation. METHODS: Five electronic databases were searched from inception to October 2016 to identify English-language RCTs evaluating the efficacy and safety of MM interventions for smoking cessation, reduction, or a decrease in nicotine cravings. Two independent reviewers screened literature using predetermined eligibility criteria, abstracted study-level information, and assessed the quality of included studies. Meta-analyses used the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The quality of evidence was assessed using the GRADE approach. FINDINGS: Ten RCTs of MM interventions for tobacco use met inclusion criteria. Intervention duration, intensity, and comparison conditions varied considerably. Studies used diverse comparators such as the American Lung Association's Freedom from Smoking (FFS) program, quitline counseling, interactive learning, or treatment as usual (TAU). Only one RCT was rated as good quality and reported power calculations indicating sufficient statistical power. Publication bias was detected. Overall, mindfulness meditation did not have significant effects on abstinence or cigarettes per day, relative to comparator groups. The small number of studies and heterogeneity in interventions, comparators, and outcomes precluded detecting systematic differences between adjunctive and monotherapy interventions. No serious adverse events were reported. CONCLUSIONS: MM did not differ significantly from comparator interventions in their effects on tobacco use. Low-quality evidence, variability in study design among the small number of existing studies, and publication bias suggest that additional, high-quality adequately powered RCTs should be conducted.

Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis.

BACKGROUND: Chronic pain patients increasingly seek treatment through mindfulness meditation. PURPOSE: This study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults. METHOD: We conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use. RESULTS: Thirty-eight RCTs met inclusion criteria; seven reported on safety. We found low-quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life. CONCLUSIONS: While mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain.

Management of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline.

BACKGROUND: Gout is a common type of inflammatory arthritis in patients seen by primary care physicians. PURPOSE: To review evidence about treatment of acute gout attacks, management of hyperuricemia to prevent attacks, and discontinuation of medications for chronic gout in adults. DATA SOURCES: Multiple electronic databases from January 2010 to March 2016, reference mining, and pharmaceutical manufacturers. STUDY SELECTION: Studies of drugs approved by the U.S. Food and Drug Administration and commonly prescribed by primary care physicians, randomized trials for effectiveness, and trials and observational studies for adverse events. DATA EXTRACTION: Data extraction was performed by one reviewer and checked by a second reviewer. Study quality was assessed by 2 independent reviewers. Strength-of-evidence assessment was done by group discussion. DATA SYNTHESIS: High-strength evidence from 28 trials (only 3 of which were placebo-controlled) shows that colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids reduce pain in patients with acute gout. Moderate-strength evidence suggests that low-dose colchicine is as effective as high-dose colchicine and causes fewer gastrointestinal adverse events. Moderate-strength evidence suggests that urate-lowering therapy (allopurinol or febuxostat) reduces long-term risk for acute gout attacks after 1 year or more. High-strength evidence shows that prophylaxis with daily colchicine or NSAIDs reduces the risk for acute gout attacks by at least half in patients starting urate-lowering therapy, and moderate-strength evidence indicates that duration of prophylaxis should be longer than 8 weeks. Although lower urate levels reduce risk for recurrent acute attacks, treatment to a specific target level has not been tested. LIMITATION: Few studies of acute gout treatments, no placebo-controlled trials of management of hyperuricemia lasting longer than 6 months, and few studies in primary care populations. CONCLUSION: Colchicine, NSAIDs, and corticosteroids relieve pain in adults with acute gout. Urate-lowering therapy decreases serum urate levels and reduces risk for acute gout attacks. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol registration: http://effectivehealth-care.ahrq.gov/ehc/products/564/1992/Gout-managment-protocol-141103.pdf).

Diagnosis of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline.

BACKGROUND: Alternative strategies exist for diagnosing gout that do not rely solely on the documentation of monosodium urate (MSU) crystals. PURPOSE: To summarize evidence regarding the accuracy of clinical tests and classification algorithms compared with that of a reference standard of MSU crystals in joint aspirate for diagnosing gout. DATA SOURCES: Several electronic databases from inception to 29 February 2016. STUDY SELECTION: 21 prospective cohort, cross-sectional, and case-control studies including participants with joint inflammation and no previous definitive gout diagnosis who had MSU analysis of joint aspirate. DATA EXTRACTION: Data extraction and risk-of-bias assessment by 2 reviewers independently; overall strength of evidence (SOE) judgment by group. DATA SYNTHESIS: Recently developed algorithms including clinical, laboratory, and imaging criteria demonstrated good sensitivity (up to 88%) and fair to good specificity (up to 96%) for diagnosing gout (moderate SOE). Three studies of dual-energy computed tomography (DECT) showed sensitivities of 85% to 100% and specificities of 83% to 92% for diagnosing gout (low SOE). Six studies of ultrasonography showed sensitivities of 37% to 100% and specificities of 68% to 97%, depending on the ultrasonography signs assessed (pooled sensitivity and specificity for the double contour sign: 74% [95% CI, 52% to 88%] and 88% [CI, 68% to 96%], respectively [low SOE]). LIMITATION: Important study heterogeneity and selection bias; scant evidence in primary and urgent care settings and in patients with conditions that may be confused with or occur with gout. CONCLUSION: Multidimensional algorithms, which must be validated in primary and urgent care settings, may help clinicians make a provisional diagnosis of gout. Although DECT and ultrasonography also show promise for gout diagnosis, accessibility to these methods may be limited. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol registration: https://effectivehealthcare.ahrq.gov/ehc/products/564/1937/gout-protocol-140716.pdf).

Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews.

BACKGROUND: The prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. Systematic reviews of treatment efficacy and adverse events (AEs) of hyaluronic acid (HA) injections report conflicting evidence about the balance of benefits and harms. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review. METHODS: We searched PubMed and eight other databases and gray literature sources from 1990 to December 12, 2014. Double-blind placebo-controlled randomized controlled trials (RCTs) reporting functional outcomes or quality-of-life; RCTs and observational studies on delay/avoidance of arthroplasty; RCTs, case reports, and large cohort studies and case series assessing safety; and systematic reviews reporting on knee pain were considered for inclusion. A standardized, pre-defined protocol was applied by two independent reviewers to screen titles and abstracts, review full text, and extract details on study design, interventions, outcomes, and quality. We compared our results with those of a prior systematic review and found them to be discrepant; our analysis of why this discrepancy occurred is the focus of this manuscript. RESULTS: Eighteen RCTs reported functional outcomes: pooled analysis of ten placebo-controlled, blinded trials showed a standardized mean difference of -0.23 (95 % confidence interval (CI) -0.45 to -0.01) favoring HA at 6 months. Studies reported few serious adverse events (SAEs) and no significant differences in non-serious adverse events (NSAEs) (relative risk (RR) [95 % CI] 1.03 [0.93-1.15] or SAEs (RR [95 % CI] 1.39 [0.78-2.47]). A recent prior systematic review reported similar functional outcomes, but significant SAE risk. Differences in SAE inclusion and synthesis accounted for the disparate conclusions. CONCLUSIONS: Trials show a small but significant effect of HA on function on which recent systematic reviews agree, but lack of AE synthesis standardization leads to opposite conclusions about the balance of benefits and harms. A limitation of the re-analysis of the prior systematic review is that it required imputation of missing data.

Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Conflicting evidence exists regarding potential cardiovascular risks associated with high levels of calcium intake. PURPOSE: To update and reanalyze 2 systematic reviews to examine the effects of calcium intake on cardiovascular disease (CVD) among generally healthy adults. DATA SOURCES: MEDLINE; Cochrane Central Register of Controlled Trials; Scopus, including EMBASE; and previous evidence reports from English-language publications from 1966 to July 2016. STUDY SELECTION: Randomized trials and prospective cohort and nested case-control studies with data on dietary or supplemental intake of calcium, with or without vitamin D, and cardiovascular outcomes. DATA EXTRACTION: Study characteristics and results extracted by 1 reviewer were confirmed by a second reviewer. Two raters independently assessed risk of bias. DATA SYNTHESIS: Overall risk of bias was low for the 4 randomized trials (in 10 publications) and moderate for the 27 observational studies included. The trials did not find statistically significant differences in risk for CVD events or mortality between groups receiving supplements of calcium or calcium plus vitamin D and those receiving placebo. Cohort studies showed no consistent dose-response relationships between total, dietary, or supplemental calcium intake levels and cardiovascular mortality and highly inconsistent dose-response relationships between calcium intake and risks for total stroke or stroke mortality. LIMITATIONS: CVD disease outcomes were secondary end points in all trials. Dose-response metaregression analysis of cohort studies was limited by potential confounding, ecological bias, and imprecise measures of calcium exposures. Data were scarce regarding very high calcium intake-that is, beyond recommended tolerable upper intake levels. CONCLUSION: Calcium intake within tolerable upper intake levels (2000 to 2500 mg/d) is not associated with CVD risk in generally healthy adults. PRIMARY FUNDING SOURCE: National Osteoporosis Foundation.

Twelve recommendations for integrating existing systematic reviews into new reviews: EPC guidance.

OBJECTIVES: As time and cost constraints in the conduct of systematic reviews increase, the need to consider the use of existing systematic reviews also increases. We developed guidance on the integration of systematic reviews into new reviews. METHODS: A workgroup of methodologists from Evidence-based Practice Centers developed consensus-based recommendations. Discussions were informed by a literature scan and by interviews with organizations that conduct systematic reviews. RESULTS: Twelve recommendations were developed addressing selecting reviews, assessing risk of bias, qualitative and quantitative synthesis, and summarizing and assessing body of evidence. CONCLUSIONS: We provide preliminary guidance for an efficient and unbiased approach to integrating existing systematic reviews with primary studies in a new review.

Omega-3 Fatty Acids and Maternal and Child Health: An Updated Systematic Review.

OBJECTIVES: To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes. DATA SOURCES: MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews. REVIEW METHODS: We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide. RESULTS: We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.).Maternal Exposures and Outcomes: Gestational length and risk for preterm birth: Prenatal algal docosahexaenoic acid (DHA) or DHA-enriched fish oil supplementation had a small positive effect on length of gestation (moderate SoE), but no effect on risk for preterm birth (low SoE). Prenatal EPA (eicosapentaenoic acid) plus DHA-containing fish oil supplementation has no effect on length of gestation (low SoE). Supplementation with DHA, or EPA plus DHA-, or DHA-enriched fish oil does not decreaserisk for preterm birth (low SoE).Birth weight and risk for low birth weight: Changes in maternal n-3 FA biomarkers were significantly associated with birth weight. Prenatal algal DHA or DHA-enriched fish oil supplementation had a positive effect on birth weight among healthy term infants (moderate SoE), but prenatal DHA supplementation had no effect on risk for low birth weight (low SoE). Prenatal EPA plus DHA or alpha-linolenic acid (ALA) supplementation had no effect on birth weight (low SoE).Risk for peripartum depression: Maternal n-3 FA biomarkers had no association with risk for peripartum depression. Maternal DHA, EPA, or DHA-enriched fish oil supplementation had no effect on risk for peripartum depression (low SoE).Risk for gestational hypertension/preeclampsia: Prenatal DHA supplementation among high-risk pregnant women had no effect on the risk for gestational hypertension or preeclampsia (moderate SoE). Prenatal supplementation of any n-3 FA in normal-risk women also had no significant effect on risk for gestational hypertension or preeclampsia (low SoE).Fetal, Infant, and Child Exposures and Outcomes: Postnatal growth patterns: Maternal fish oil or DHA plus EPA supplementation had no effect on postnatal growth patterns (attainment of weight, length, and head circumference) when administered prenatally (moderate SoE) or both pre- and postnatally (low SoE). Fortification of infant formulas with DHA plus arachidonic acid (AA, an n-6 FA) had no effect on growth patterns of preterm or term infants (low SoE).Visual acuity: Prenatal supplementation with DHA had no effect on development of visual acuity (low SoE). Supplementing or fortifying preterm infant formula with any n-3 FA had no significant effect on visual acuity assessed by visual evoked potentials (VEP) at 4 or 6 months corrected age (low SoE). Data conflicted on the effectiveness of supplementing infant formula for term infants with n-3 FA depending on when and how visual acuity was assessed (i.e. by VEP or by behavioral methods) and the type of essential FA provided (low SoE).Neurological development: Prenatal or postnatal n-3 FA supplementation had no consistent effect on neurological development (low SoE).Cognitive development: Prenatal DHA supplementation with AA or EPA had no effect on cognitive development (moderate SoE). Supplementing breastfeeding women with DHA plus EPA also had no effect on cognitive development in infants and children (low SoE). Supplementing or fortifying preterm infants' formula with DHA plus AA had a positive effect on infant cognition at some short-term followup times (moderate SoE). Supplementing or fortifying infant formula for term infants with any n-3 FA had no effect on cognitive development (low SoE). Evidence is insufficient to support any effect of n-3 FA infant supplementation on long-term cognitive outcomes.Autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and learning disorders: Maternal or infant n-3 FA supplementation had no effect on risk for autism spectrum disorders or ADHD (low SoE). No studies on other learning disorders were identified.Atopic dermatitis (AD), allergies, and respiratory disorders: Pre- and postnatal (maternal and infant) n-3 FA supplementation had no consistent effect on the risk for AD/eczema, allergies, asthma, and other respiratory illnesses (moderate SoE). Biomarkers and intakes had no consistent association with the risk for AD, allergies, and respiratory disorders (low SoE).Adverse events: Prenatal and infant supplementation with n-3 FA or fortification of foods with n-3 FA did not result in any serious or nonserious adverse events (moderate SoE); with the exception of an increased risk for mild gastrointestinal symptoms. CONCLUSIONS: Most studies in this report examined the effects of fish oil (or other combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant formula fortified with DHA plus AA. As with the original report, with the exception of small increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and followup times for outcomes related to infant visual acuity, cognitive development and prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on populations with baseline n-3 FA intakes typical of those of most western populations.