ABSTRACT Introduction Recent respiratory illness, especially influenza, may trigger acute cardiac events via elevated inflammatory mediators. During the 2018 influenza season in Bangladesh, this study examined whether recent acute clinical respiratory illness (CRI) or laboratory-confirmed influenza was associated with elevated hs-CRP and IL-6, linked to acute cardiac events. Methods A total of 139 participants aged ≥40 were recruited from a Dhaka cardiac hospital: 70 with acute myocardial infarction (AMI), 30 with other acute cardiac events, and 39 healthy individuals. CRI was defined as fever with cough and/or respiratory symptoms within seven days. Respiratory swabs were tested for influenza, and blood was analyzed for hs-CRP and IL-6. Results Median hs-CRP and IL-6 were higher in participants with CRI or influenza but not significantly. Cardiac patients had elevated hs-CRP (9.98 mg/L in other cardiac; 4.86 mg/L in AMI vs. 1.73 mg/L in healthy) and IL-6 (0.1 pg/mL in other cardiac; 0.145 pg/mL in AMI vs. 0.08 pg/mL in healthy) (p<0.001). CRI was not significantly associated with elevated hs-CRP or IL-6, though influenza in healthy participants was linked to higher IL-6. Cardiac patients had a higher risk of hs-CRP ≥3 mg/L and elevated IL-6. Conclusion Cardiac patients showed significantly increased inflammatory markers, but CRI was not clearly linked to inflammation. Further research should assess biomarker utility for early cardiac risk. Highlights The study explores inflammatory biomarkers linking recent respiratory illness and acute cardiac events. Cardiac patients showed elevated hs-CRP and IL-6, confirming inflammation–cardiac risk association. Association between prior influenza infection and high IL-6 was significant among healthy individuals as opposed to the cardiac group, suggesting effect modification. hs-CRP and IL-6 may indicate underlying cardiac pathology and potential early cardiac risk markers.

Supplementary data from Cutaneous β HPVs, Sun Exposure, and Risk of Squamous and Basal Cell Skin Cancers in Australia

Introduction: Patients with sedative overdose may have residual cognitive impairment at the time they are deemed medically cleared for discharge. Impairment could affect the performance of high-risk activities, including driving. The Trail Making Test is an alpha-numeric assessment that can be performed at the bedside to assess cognitive function. We examined whether there were differences in cognitive function when medically cleared between patients that overdosed on sedative and non-sedative drugs. Methods: A prospective, observational study assessed cognitive function using the Trail Making Test between 2018 and 2021. Patients (16 years and greater) completed testing upon medical clearance if they spoke English and had no previous neurological injury. Continuous covariates were compared using t-tests or Mann-Whitney U tests and multiple linear regression; binary variables were modelled using logistic regression. Results: Of 171 patients enrolled, 111 (65 per cent) had sedative overdose; they were older (median 32.1 versus 22.2 years) and more likely to be male (58.6 per cent versus 36.7 per cent). Benzodiazepines and paracetamol were the commonest drug overdoses. Patients with sedative overdose performed worse on Trail Making Test part A (37.0 versus 33.1 seconds, P = 0.017) and Trail Making Test part B (112.4 versus 81.5 seconds, P = 0.004). Multiple linear regression analysis indicated that patient age (P < 0.001, 1.7 seconds slower per year, 95 per cent confidence interval: 0.9-2.6 seconds) and perception of recovery (P = 0.006, 36.4 seconds slower if perceived not recovered, 95 per cent confidence interval: 10.8-62.0 seconds) were also associated with Trail Making Test part B times. Patients with sedative overdose were more likely to be admitted to the intensive care unit (Odds Ratio: 4.9, 95 percent confidence interval: 1.1-22.0; P = 0.04). DiscussionOur results are broadly in keeping with previously published work, but include a wider range of drug overdose scenarios (polypharmacy and recreational drugs). While patients demonstrated some perception of their cognitive impairment, our model could not reliably be used to provide individual discharge advice. The study design did not allow us to prove causation of cognitive impairment, or to make comparison between the strength of an overdose to the trail making test time. Conclusions: Trail Making Test results suggested that patients who had sedative drug overdoses may have significant cognitive deficits even when medically cleared. Risk of harm may be minimised with advice to avoid high-risk activities such as driving. More profound impacts seen on the Trail Making Test part B than A may mean higher-order thinking is more affected than simple cognitive function.

Background and AimsSeveral studies imply that influenza and other respiratory illnesses could lead to acute myocardial infarction (AMI), but data from low-income countries are scarce. We investigated the prevalence of recent respiratory illnesses and confirmed influenza in AMI patients, while also exploring their relationship with infarction severity as defined by ST-elevation MI (STEMI) or high troponin levels.MethodsThis cross-sectional study, held at a Dhaka tertiary hospital from May 2017 to October 2018, involved AMI inpatients. The study examined self-reported clinical respiratory illnesses (CRI) in the week before AMI onset and confirmed influenza using baseline real-time reverse transcription polymerase chain reaction (qRT-PCR).ResultsOf 744 patients, 11.3% reported a recent CRI, most prominently during the 2017 influenza season (35.7%). qRT-PCR testing found evidence of influenza in 1.5% of 546 patients, with all positives among STEMI cases. Frequencies of CRI were higher in patients with STEMI and in those with high troponin levels, although these relationships were not statistically significant after adjusting for other variables. The risk of STEMI was significantly greater during influenza seasons in the unadjusted analysis (relative risk: 1.09, 95% confidence interval [CI]: 1.02-1.18), however, this relationship was not significant in the adjusted analysis (adjusted relative risk: 1.03, 95% CI: 0.91-1.16).ConclusionIn Bangladesh, many AMI patients had a recent respiratory illness history, with some showing evidence of influenza. However, these illnesses showed no significant relationship to AMI severity. Further research is needed to understand these relationships better and to investigate the potential benefits of infection control measures and influenza vaccinations in reducing AMI incidence.

Objectives:To assess the effectiveness of oral Gastrografin treatment and outcomes in adult patients with complete distal intestinal obstruction syndrome (cDIOS). Background:DIOS is an important gastrointestinal complication of cystic fibrosis (CF). Conservative treatment options for cDIOS are largely empirical, and the optimal management remains unclear. Surgery should be reserved for patients who have failed nonoperative treatment or have immediate indications for surgery. Methods:A retrospective single-institution cohort study was undertaken of adults with CF who had undergone lung transplantation and were admitted with an episode of cDIOS between 2004 and 2020. The outcomes of treatment in a high-volume CF transplant center with routine oral Gastrografin-based therapy were assessed. Results:Forty-seven episodes of cDIOS were recorded in 29 (23.3%) of 124 patients who had undergone lung transplantation for CF, and mean age at cDIOS was 30.3 years (SD ±11.2). Mean follow-up post cDIOS was 75.6 months (SD ±45.5). Twelve patients had >1 cDIOS episode. One episode occurred during recovery after transplantation, and 5 patients were readmitted within 30 days posttransplant with cDIOS. A history of previous abdominal surgery was associated with the development of cDIOS (P < 0.001). Oral Gastrografin therapy was used in 95.7% of the episodes, at varying doses. Three patients (7.0%) were resistant to oral Gastrografin treatment, requiring laparotomy. There were no deaths due to DIOS. Conclusions:Oral Gastrografin is effective and safe for the treatment of cDIOS, with low treatment failure rates. It should be considered as a first-line treatment option for patients with CF presenting with complete distal intestinal obstruction.

Current evidence suggests that recent acute respiratory infections and seasonal influenza may precipitate acute myocardial infarction (AMI). This study examined the potential link between recent clinical respiratory illness (CRI) and influenza, and AMI in Bangladesh. Conducted during the 2018 influenza season at a Dhaka tertiary-level cardiovascular (CV) hospital, it included 150 AMI cases and two control groups: 44 hospitalized cardiac patients without AMI and 90 healthy individuals. Participants were matched by gender and age groups. The study focused on self-reported CRI and laboratory-confirmed influenza ascertained via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) within the preceding week, analyzed using multivariable logistic regression. Results showed that cases reported CRI, significantly more frequently than healthy controls (27.3% vs. 13.3%, adjusted odds ratio (aOR): 2.21; 95% confidence interval (CI): 1.05-4.06), although this was not significantly different from all controls (27.3% vs. 22.4%; aOR: 1.19; 95% CI: 0.65-2.18). Influenza rates were insignificantly higher among cases than controls. The study suggests that recent respiratory illnesses may precede AMI onset among Bangladeshi patients. Infection prevention and control practices, as well as the uptake of the influenza vaccine, may be advocated for patients at high risk of acute CV events.

BACKGROUND:The aim of this study was to investigate whether there is a delay in treatment for patients having pre-operative CT imaging with both intravenous and oral contrast (CTIVO) compared to intravenous contrast alone (CTIV).METHODS:A retrospective review of patients who underwent emergency appendicectomy at a single hospital during a two-year period (1/1/2019-31/12/2020) was performed. Demographic details, imaging timing/modality; biochemical markers; American Society of Anaesthesiologists (ASA) physical status classification, anaesthetic induction time; operative report findings; histopathology, peri-operative complications, admission/discharge times were recorded. The Sunshine Appendicitis Grading System (SAGS) score was used for severity of appendicitis.RESULTS:Pre-operative CT was performed in 294 patients; CTIVO: 159 (54%), CTIV: 135 (46%). Both groups were comparable for age, sex, ASA status and inflammatory markers. The median time from CT request to scanning was longer with CTIVO (CTIVO: 170 min, CTIV: 65 min, P < 0.0001). The median time from CT request to induction of anaesthesia was also longer with CTIVO (CTIVO: 780 minutes, CTIV: 406 min, P < 0.0001). A delay to theatre was not significantly associated with severity of appendicitis (SAGS score). The diagnostic accuracy was not reduced in the CTIV group compared to the CTIVO group.CONCLUSION:CTIVO scans significantly delay CT diagnosis and surgical treatment of appendicitis compared to CTIV. Omitting oral contrast does not result in a reduction in diagnostic accuracy for appendicitis.

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality in aged-care facilities worldwide. The attention of infection control in aged care needs to shift towards the built environment, especially in relation to using the existing space to allow social distancing and isolation. Physical infrastructure of aged care facilities has been shown to present challenges to the implementation of isolation procedures. To explore the relationship of the physical layout of aged care facilities with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack rates among residents, a meta-analysis was conducted. Methods Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P), studies were identified from 5 databases using a registered search strategy with PROSPERO. Meta-analysis for pooled attack rates of SARS-CoV-2 in residents and staff was conducted, with subgroup analysis for physical layout variables such as total number of beds, single rooms, number of floors, number of buildings in the facility, and staff per 100 beds. Results We included 41 articles across 11 countries, reporting on 90 657 residents and 6521 staff in 757 facilities. The overall pooled attack rate was 42.0% among residents (95% CI, 38.0%-47.0%) and 21.7% in staff (95% CI, 15.0%-28.4%). Attack rates in residents were significantly higher in single-site facilities with standalone buildings than facilities with smaller, detached buildings. Staff-to-bed ratio significantly explains some of the heterogeneity of the attack rate between studies. Conclusions The design of aged care facilities should be smaller in size, with adequate space for social distancing.

Background:Vaccine derived poliovirus (VDPV) remains a major barrier to polio eradication, and recent growing emergences are concerning. This paper presents the global epidemiology of circulating VDPV (cVDPV) by exploring associations between demographic and socioeconomic factors with its recent rise. Methods:Data on reported cVDPV cases and isolates between January 1 2016 and June 30 2021 were compiled from EPIWATCH, an open-source observatory for outbreak scanning and analysis, the World Health Organisation (WHO) and ProMed, and analysed descriptively. Reports containing cVDPV case information were included while duplicates and defective links were excluded. Data collection occurred from April 5 2021 to July 16 2021. To identify factors associated with cVDPV, a retrospective case-control study comparing socioeconomic profiles of countries which reported cVDPV with those that did not was undertaken with weighted logistic regression analysis. Findings:cVDPV caused by serotype 2 poliovirus was the predominant strain (95%) of 1818 total human cVDPV cases reported. Of 40 countries reporting cVDPV cases or isolates, 22 (55%) had polio vaccination coverages below 80%. Low vaccination coverage (Adjusted OR = 83·41, 95% CI: [5·01, 1387·71], p = 0·0020) was found to be associated with increased odds of reporting cVDPV after adjusting for confounding effects of GDP per capita, female adult literacy rates, maternal mortality rate, and Global Peace Index. Interpretation:Our findings reinforce the importance of maintaining high levels of vaccination, as risk of re-emergence rises when immunity wanes. Interventions to increase vaccination and standards of living in developing countries, coupled with robust surveillance are required if humanity hopes to eradicate polio in the near future. Funding:This research was supported by the MRFF 2021 Frontier Health and Medical Research Grant (ID RFRHPI000280), Department of Health, the Australian Government.

BACKGROUND:With a stretched healthcare system and elective surgery backlog, measures to improve efficiency and decrease costs associated with surgical procedures need to be prioritized. This study compares the benefits of multi-disciplinary involvement in an enhanced recovery after surgery (ERAS) protocol-led overnight model following total hip replacement (THR) and total knee replacement (TKR).METHODS:Patients in each of two private hospitals undergoing THR or TKR were prospectively enrolled. One hospital (Overnight) was fully committed to the ERAS protocol implementation on all levels and formed the treatment group while in the other hospital (control), patients only had the anaesthetic and operative procedure as part of the ERAS protocol but did not follow the perioperative measures of the protocol. Outcomes on hospital length of stay (LOS), inpatient rehabilitation, functional outcomes, satisfaction, adverse events and readmission rates were investigated.RESULTS:Median LOS in the Overnight group was significantly smaller than in the control group (1 vs. 3 days, P < 0.0001). The Overnight group had lower rates of inpatient rehabilitation utilization (4% vs. 41.2%, P < 0.0001), similar improvements in functional hip and knee scores and no increased rate of adverse events or readmission. All patients in both groups were satisfied with their treatment.CONCLUSION:Overnight THR and TKR can safely be performed in the majority of patients, with a multi-disciplinary approach protocol and involvement of all perioperative stakeholders.

AbstractBackground:Sun exposure causes cutaneous squamous (SCC) and basal cell (BCC) carcinomas. Human papillomavirus (HPV) infection might cause SCC.Methods:We examined associations of β and γ HPV infection in skin-swab DNA and serum antibodies with skin cancer risk, and modification of the carcinogenic effects of sun exposure by them, in case–control studies of 385 SCC cases, 832 BCC cases, and 1,100 controls nested in an Australian prospective cohort study (enrolled 2006–2009).Results:Presence of β-1 and β-3 HPV DNA appeared to increase risks for SCC and BCC by 30% to 40% (P adjusted <0.01). BCC was also associated with genus β DNA, OR = 1.48; 95% confidence interval (CI), 1.10 to 2.00 (P adjusted <0.01). Associations were strengthened with each additional positive β HPV DNA type: SCC (OR = 1.07; 95% CI, 1.02–1.12) and BCC (OR = 1.06; 95% CI, 1.03–1.10), Ptrend<0.01. Positivity to genus β or γ in serology, and genus γ in DNA, was not associated with either cancer. There was little evidence that any β HPV type was more strongly associated than others with either cancer. A weaker association of sun exposure with SCC and BCC in the presence of β-3 HPVs than in their absence suggests that β-3 HPVs modify sun exposure's effect.Conclusions:Our substantive findings are at the level of genus β HPV. Like SCC, BCC risk may increase with increasing numbers of β HPV types on skin.Impact:The consistency in our findings that HPV infection may moderate the effects of sun exposure, the main environmental cause of SCC and BCC, merits further investigation.

Introduction In a majority of low- and middle-income countries (LMICs), levels of child growth failure (CGF) have steadily declined since 2000. However, some countries show a different trend. Despite continued investment from the government of Ethiopia as well as donors, CGF levels are still high in Ethiopia. This study aimed to assess trends in CGF and associated sociodemographic, economic and water, sanitation, and hygiene (WASH) factors from 2000 to 2016 in Ethiopia. Methods Data were taken from four rounds of the Ethiopia Demographic and Health Survey (EDHS). Children aged between 0 to 59 months were included. CGF indicators were categorised based on height-for-age z-score (HAZ) < -2 Standard deviation (SD), weight-for-age z-score (WAZ) < -2 SD and weight-for-height z-score (WHZ) < -2 SD. CGF trends were estimated for predicted probabilities and odds ratios (ORs) between 2000 and 2016. Results A total sample size of 31978 for HAZ, 32045 for WAZ and 32246 for WHZ were included in the current study. Stunting decreased from an adjusted odds ratio (AOR) = 0.77 (95% CI: 0.67 to 0.88) in 2005 to an AOR = 0.45 (95% CI: 0.39 to 0.53) in 2016 compared with the year 2000. Compared with data in 2000, underweight decreased from an AOR of 0.70 (95% CI: 0.61 to 0.80) in 2005 to an AOR of 0.43 (95% CI: 0.36 to 0.50) in 2016. Wasting declined from an AOR of 0.91 (95% CI: 0.75 to 1.10) in 2005 to an AOR of 0.76 (95% CI: 0.61 to 0.94) in 2016, compared with data in 2000. Conclusions Between 2000 to 2016, there was a decline in CGF levels albeit the levels are still relatively high compared with the World Health Organization (WHO) cut-off levels for public health concern. Observed rates of change varied across sociodemographic, economic and WASH factors which suggest that interventions tailored towards addressing the imbalances across those factors are required.

In any wastewater recycling scheme, the protection of public health is of primary importance. In Australia, the public health requirements applying to the treatment of recycled water are stringent. They use the Disability-Adjusted Life Year (DALY) metric to set a level of negligible public health risk. The target maximum risk of 10–6 DALY per person per year has been adopted in Australian water recycling guidelines since 2006. A key benefit of the DALY approach is its ability to standardise the understanding of risk across disparate areas of public health. To address the key challenge of translating the results of monitoring of microorganisms in the recycled water into this quantitative public health metric, we have developed a novel method. This paper summarises an approach where microbial surrogate organisms indigenous to wastewater are used to measure the efficiency of water recycling treatment processes and estimate public health risk. An example of recent implementation in the Greater Sydney region of Australia is provided.

BACKGROUND:Some studies have shown that statins reduce the efficacy of influenza vaccine. The aim was to examine the impact of statins on influenza and influenza vaccine effectiveness (VE). METHODS:This study was a post-hoc analysis of subjects in a prospective case-control study of influenza and acute myocardial infarction, where data on influenza infection, vaccination and statin use was collected. Study participants, aged ≥40 years were recruited from tertiary hospitals in Sydney from 2008 to 2010. Univariate and logistic regression analysis was performed. RESULTS:Of total 559 participants, 276 (49.4%) had been vaccinated and 196 (35.1%) were taking statins. The rate of laboratory confirmed influenza was significantly higher in unvaccinated statin users (adjusted odds ratio (AOR), 2.44; 95% CI: 1.06-5.62) compared to unvaccinated non-users. The VE was 98% overall, and not significantly different between statin users (92.4%) and non-statin users (100%). In adjusted analysis of all subjects, vaccination was significantly protective (AOR, 0.02; 95% CI: 0.01-0.15), and statins remained significantly associated with influenza risk (AOR, 2.47; 95% CI: 1.08-5.64). CONCLUSION:There was no significant difference in influenza VE by statin use, and vaccine was highly effective in both statin users and non-users. There was a significantly higher risk of influenza among statin users, independent of vaccination. Statins may increase the risk of influenza through immunomodulatory mechanisms, or this may be confounded by other risk factors for influenza. It is important that people on statins should be vaccinated against influenza.

Background Globally, radon is the leading risk factor for lung cancer in never-smokers (LCINS). In this study, we systematically reviewed and meta-analysed the evidence of the risk of LCINS associated with residential radon exposure. Methods Medline and Embase databases were searched using predefined inclusion and exclusion criteria to identify relevant studies published from 1 January 1990 to 5 March 2020 focused on never-smokers. We identified four pooled collaborative studies (incorporating data from 24 case–control studies), one case–control study and one cohort study for systematic review. Meta-analysis was performed on the results of the four pooled studies due to different measures of effect and outcome reported in the cohort study and insufficient information reported for the case–control study. In a post hoc analysis, the corresponding risk for ever-smokers was also examined. Results Risk estimates of lung cancer from residential radon exposure were pooled in the meta-analysis for 2341 never-smoker cases, 8967 never-smoker controls, 9937 ever-smoker cases and 12 463 ever-smoker controls. Adjusted excess relative risks (aERRs) per 100 Bq·m−3 of radon level were 0.15 (95% CI 0.06–0.25) for never-smokers and 0.09 (95% CI 0.03–0.16) for ever-smokers, and the difference between them was statistically insignificant (p=0.32). The aERR per 100 Bq·m−3was higher for men (0.46; 95% CI 0.15–0.76) than for women (0.09; 95% CI −0.02–0.20) among never-smokers (p=0.027). Conclusion This study provided quantified risk estimates for lung cancer from residential radon exposure among both never-smokers and ever-smokers. Among never-smokers in radon-prone areas, men were at higher risk of lung cancer than women.

ObjectiveSocioeconomic inequalities in child growth failure (CGF) remain one of the main challenges in Ethiopia. This study examined socioeconomic inequalities in CGF and determinants that contributed to these inequalities in Ethiopia.MethodsThe Ethiopia Demographic and Health Surveys 2000 and 2016 data were used in this study. A pooled unweighted sample of the two surveys yielded 21514 mother–child pairs (10873 in 2000 and 10641 in 2016). We assessed socioeconomic inequalities in CGF indicators using the concentration curve and concentration index (CI). We then decomposed the CI to identify percentage contribution of each determinant to inequalities.ResultsSocioeconomic inequalities in CGF have increased in Ethiopia between 2000 and 2016. The CI increased from −0.072 and −0.139 for stunting, −0.088 and −0.131 for underweight and −0.015 and −0.050 for wasting between 2000 and 2016, respectively. Factors that mainly contributed to inequalities in stunting included geographical region (49.43%), number of antenatal care visits (31.40%) and child age in months (22.20%) in 2000. While in 2016, inequality in stunting was contributed mainly by wealth quintile (46.16%) and geographical region (−13.70%). The main contributors to inequality in underweight were geographical regions (82.21%) and wealth quintile (27.21%) in 2000, while in 2016, wealth quintile (29.18%), handwashing (18.59%) and access to improved water facilities (−17.55%) were the main contributors. Inequality in wasting was mainly contributed to by maternal body mass index (−66.07%), wealth quintile (−45.68%), geographical region (36.88%) and paternal education (33.55%) in 2000, while in 2016, wealth quintile (52.87%) and urban areas of residence (-17.81%) were the main driving factors.ConclusionsThis study identified substantial socioeconomic inequalities in CGF, and factors that relatively contributed to the disparities. A plausible approach to tackling rising disparities may involve developing interventions on the identified predictors and prioritising actions for the most socioeconomically disadvantaged groups.

Introduction Poor access to water, sanitation, and handwashing (WASH) facilities frequently contribute to child growth failure. The role of access to WASH facilities on child growth outcomes in Ethiopia is largely unknown. The aim of this study was to determine individual and combined effects of access to WASH facilities on child growth outcomes. Methods Data for this analysis was sourced from the recent Ethiopia Demographic and Health Survey (EDHS) 2016. A multivariable logistic regression model was applied to identify the separate and combined association of access to WASH facilities with child growth outcomes. Odds ratio (OR) and 95% confidence interval (CI) were estimated. Statistical significance was declared at p < 0.05. Results Included in the analyses were data for children 0-59 months of age, which amounted to valid data for 9588 children with a height-for-age z-score (HAZ), 9752 children with a weight-for-age z-score (WAZ) and 9607 children with a weight-for-height z-score (WHZ). Children with access to improved combined sanitation with handwashing facilities had 29% lower odds of linear growth failure (stunting) (adjusted odds ratio (AOR) = 0.71; 95% CI: 0.51-0.99) compared with those with unimproved. Children with access to combined improved WASH facilities were 33% less likely to have linear growth failure (AOR = 0.67; 95% CI: 0.45-0.98). Access to improved handwashing alone reduced the odds of being underweight by 17% (AOR = 0.83; 95% CI: 0.71-0.98) compared with unimproved. Improved water and sanitation separately as well as combined WASH were not associated with decreased odds of underweight and wasting. Conclusions Combined access to improved water, sanitation and handwashing was associated with reduced child linear growth failure. Further research with robust methods is needed to examine whether combined WASH practices have synergistic effect on child growth outcomes.

BACKGROUND:Some epidemiological studies show associations between disinfection byproducts (DBPs) and adverse developmental outcomes. OBJECTIVES:We undertook a meta-analysis of epidemiological studies on maternal exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) and risk of small for gestational age (SGA) birth. METHODS:We identified forty-five publications including two reports and five theses via a 2020 literature search. Nineteen study populations from 16 publications met the inclusion criteria and were systematically evaluated. Effect measures were pooled using random effects meta-analytic methods along with cumulative, sub-group and meta-regression analyses to examine between-study heterogeneity and variation in risk across different DBP measures. RESULTS:We detected a small increased risk for SGA with exposure to the sum of four (i.e., THM4) THM4 (odds ratio (OR) = 1.07; 95%CI: 1.03, 1.11), chloroform (OR = 1.05; 95%CI: 1.01, 1.08), bromodichloromethane (OR = 1.08; 95%CI: 1.05, 1.11) and the sum of the brominated THM4 (OR = 1.05; 95%CI: 1.02, 1.09). Larger ORs were detected for the sum of five haloacetic acids (i.e., HAA5) (OR = 1.12; 95%CI: 1.01, 1.25), dichloroacetic acid (OR = 1.25; 95%CI: 1.01, 1.41) and trichloroacetic acid (OR = 1.21; 95%CI: 1.07, 1.37). We detected larger SGA risks for several THM4 among the prospective cohort and case-control studies compared to retrospective cohorts and for the SGA3/5% (vs. SGA10%) studies. The THM4 meta-regression showed associations between SGA and the total quality score based on categorical or continuous measures. For example, an OR of 1.03 (95%CI: 1.01, 1.06) was detected for each 10-point increase in the study quality score based on our systematic review. CONCLUSIONS:We detected a small increased risk of SGA based on 18 THM4 study populations that was comparable to a previous meta-analysis of eight THM4 study populations. We also found increased risks for other THM4 and HAA measures not previously examined; these results were robust after accounting for outliers, publication bias, type of SGA classification, different exposure windows, and other factors.