Census tract-level social vulnerability and gonorrhea rates in central Ohio: results from the STD Surveillance Network, 2020-2021.

BACKGROUND: Gonorrhea remains a significant burden in central Ohio, particularly in socially disadvantaged communities. This study evaluates gonorrhea case rates and changes from 2020 to 2021, focusing on geographic patterns associated with social vulnerability. METHODS: We analyzed gonorrhea case data from the Columbus STD Surveillance Network (SSuN) for 2020 and 2021. Cases were linked to census tracts and categorized into low (0-0.66) or high (0.67-1.0) vulnerability groups based on the CDC/ATSDR social vulnerability index (SVI). We mapped gonorrhea case rates per 100,000 population, stratified by SVI group, and compared changes using Jenks natural breaks to determine cutpoints. High case rates were defined as ≥605 (2020) and ≥ 532 (2021). A change in case rates was defined as <154 (decrease/no change) or ≥ 154 (increase). Demographic factors were summarized for both years. RESULTS: In 2020 and 2021, nearly half of high SVI tracts had high gonorrhea rates, compared to about 4-7% of low SVI tracts. Median rates in high SVI tracts were approximately five times higher than in low SVI tracts, with rates 546 and 598 per 100,000 in 2020 and 2021, compared to 98 and 104 per 100,000, respectively. Gonorrhea rates increased in 23 (9%) of low SVI tracts and 37 (25%) of high SVI tracts. Demographic characteristics remained consistent between the two years. CONCLUSIONS: Gonorrhea rates increased in central Ohio between 2020 and 2021, with higher burdens in high SVI census tracts. Understanding the dynamics of social vulnerability at the community level is crucial for targeting limited STD resources effectively.

Acquisition of Gonococcal AniA-NorB Pathway by the Neisseria meningitidis Urethritis Clade Confers Denitrifying and Microaerobic Respiration Advantages for Urogenital Adaptation.

Neisseria meningitidis historically has been an infrequent and sporadic cause of urethritis and other urogenital infections. However, a nonencapsulated meningococcal clade belonging to the hyperinvasive clonal complex 11.2 lineage has recently emerged and caused clusters of urethritis cases in the United States and other countries. One of the genetic signatures of the emerging N. meningitidis urethritis clade (NmUC) is a chromosomal gene conversion event resulting in the acquisition of the Neisseria gonorrhoeae denitrification apparatus-the N. gonorrhoeae alleles encoding the nitrite reductase AniA, the nitric oxide (NO) reductase NorB, and the intergenic promoter region. The biological importance of the N. gonorrhoeae AniA-NorB for adaptation of the NmUC to a new environmental niche is investigated herein. We found that oxygen consumption, nitrite utilization, and NO production were significantly altered by the conversion event, resulting in different denitrifying aerobic and microaerobic growth of the clade. Further, transcription of aniA and norB in NmUC isolates differed from canonical N. meningitidis, and important polymorphisms within the intergenic region, which influenced aniA promoter activity of the NmUC, were identified. The contributions of three known meningococcal regulators (NsrR, FNR, and NarQP) in controlling the denitrification pathway and endogenous NO metabolism were distinct. Overall, transcription of aniA was dampened relative to canonical N. meningitidis, and this correlated with the lower NO accumulation in the clade. Denitrification and microaerobic respiration were bolstered, and protection against host-derived NO was likely enhanced. The acquisition of the N. gonorrhoeae denitrification pathway by the NmUC supports the clade's adaptation and survival in a microaerobic urogenital environment.

Infection With the US Neisseria meningitidis Urethritis Clade Does Not Lower Future Risk of Urethral Gonorrhea.

BACKGROUND: Cross-protective immunity between Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) may inform gonococcal vaccine development. Meningococcal serogroup B (MenB) outer membrane vesicle (OMV) vaccines confer modest protection against gonorrhea. However, whether urethral Nm infection protects against gonorrhea is unknown. We examined gonorrhea risk among men with US Nm urethritis clade (US_NmUC) infections. METHODS: We conducted a retrospective cohort study of men with urethral US_NmUC (n = 128) between January 2015 and April 2018. Using diagnosis date as the baseline visit, we examined Ng status at return visits to compute urethral Ng risk. We compared these data to 3 referent populations: men with urethral Ng (n = 253), urethral chlamydia (Ct) (n = 251), and no urethral Ng or Ct (n = 255). We conducted sensitivity analyses to assess varied approaches to censoring, missing data, and anatomical site of infection. We also compared sequences of protein antigens in the OMV-based MenB-4C vaccine, US_NmUC, and Ng. RESULTS: Participants were primarily Black (65%) and heterosexual (82%). Over follow-up, 91 men acquired urethral Ng. Men with urethral US_NmUC had similar Ng risk to men with prior urethral Ng (adjusted hazard ratio [aHR]: 1.27; 95% CI: .65-2.48). Men with urethral US_NmUC had nonsignificantly increased Ng risk compared with men with urethral Ct (aHR: 1.51; 95% CI: .79-2.88), and significantly increased Ng risk compared with men without urethral Ng or Ct (aHR: 3.55; 95% CI: 1.27-9.91). Most of the protein antigens analyzed shared high sequence similarity. CONCLUSIONS: Urethral US_NmUC infection did not protect against gonorrhea despite substantial sequence similarities in shared protein antigens.

Evaluation of Urethrotropic-Clade Meningococcal Infection by Urine Metagenomic Shotgun Sequencing.

Urethral infections caused by an emerging nongroupable (NG) urethrotropic clade of Neisseria meningitidis were first reported in the United States in 2015 (the "U.S. NmNG urethritis clade"). Here, we evaluate for the presence of other urethral pathogens in men with U.S. NmNG urethritis clade infection. We evaluated 129 urine specimens collected from men at a sexual health clinic, including 33 from patients with culture-confirmed or suspected urethral N. meningitidis infection and 96 specimens in which nucleic acid amplification test detected Neisseria gonorrhoeae, Chlamydia trachomatis, both pathogens, or neither pathogen. N. meningitidis was detected first by real-time PCR, followed by metagenomic shotgun sequencing of 91 specimens to identify coinfections. N. meningitidis genomes were sequenced following selective whole-genome amplification when possible. Metagenomic sequencing detected N. meningitidis in 16 of 17 specimens from culture-confirmed N. meningitidis cases, with no coinfection by other conventional urethral pathogens. Metagenomic sequencing also detected N. meningitidis in three C. trachomatis-positive specimens, one specimen positive for both N. gonorrhoeae and C. trachomatis, and nine specimens with negative N. gonorrhoeae and C. trachomatis results, eight of which had suspected Neisseria infections. N. meningitidis from culture-confirmed N. meningitidis cases belonged to the U.S. NmNG urethritis clade, while N. meningitidis identified in other specimens belonged to multiple clonal complexes. Additional urethral pathogens were predominant in non-N. meningitidis specimens, including N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, and herpes simplex virus 2. Coinfection with other conventional urethral pathogens is rare in men with culture-confirmed U.S. NmNG urethritis clade infection and points to the strong association of this clade with disease.

Emergence of a novel urogenital-tropic Neisseria meningitidis.

PURPOSE OF REVIEW: Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N. gonorrhoea (Ng), Nm can colonize urogenital and rectal mucosal surfaces and cause disease. First noted in 2015, but with origins in 2011, male urethritis clusters caused by a novel Nm clade were reported in the USA (the US_NmUC). This review describes research developments that characterize this urogenital-tropic Nm. RECENT FINDINGS: The US_NmUC evolved from encapsulated Nm serogroup C strains. Loss of capsule expression, lipooligosaccharide (LOS) sialylation, genetic acquisition of gonococcal alleles (including the gonococcal anaerobic growth aniA/norB cassette), antimicrobial peptide heteroresistance and high surface expression of a unique factor-H-binding protein, can contribute to the urethra-tropic phenotype. Loss-of-function mutations in mtrC are overrepresented in clade isolates. Similar to Ng, repeat US_NmUC urethritis episodes can occur. The US_NmUC is now circulating in the UK and Southeast Asia. Genomic sequencing has defined the clade and rapid diagnostic tests are being developed for surveillance. SUMMARY: The US_NmUC emerged as a cause of urethritis due to acquisition of gonococcal genetic determinants and phenotypic traits that facilitate urogenital tract infection. The epidemiology and pathogenesis of this urogenital-tropic pathogen continues to be defined.

Passage of abortion ban and women's accurate understanding of abortion legality.

BACKGROUND: Legislative and judicial procedures related to banning abortion after 6 weeks of gestation in Ohio occurred from November 2018 to July 2019. These activities could have increased the belief that abortion has become illegal even though the 6-week abortion ban has never been in effect to date. OBJECTIVE: We sought to determine the prevalence and correlates of holding the belief that abortion is illegal in Ohio and to evaluate whether this belief increased over the time in which the 6-week abortion ban was introduced, passed twice, and then blocked in Ohio. STUDY DESIGN: We analyzed data from the first wave of the Ohio Survey of Women, a population-based survey of adult, reproductive-aged Ohioan women conducted from October 2018 to June 2019. During each of the 8 survey months, a median of 240 women (range, 70-761) completed the survey, including the survey question "Based on what you know or have heard, is it legal to get an abortion in your state?" We used multivariable logistic regression to assess the prevalence and correlates of believing that abortion is illegal in the state of Ohio. In addition, we used multinomial logistic regression to evaluate whether this belief increased over the interval during which women completed the survey, which roughly corresponded to the interval marked by legislative and judicial activities surrounding the 6-week abortion ban. RESULTS: Most of the 2359 participants understood that abortion is legal in the state of Ohio (64.0%) with the remainder believing it to be illegal (9.8%) or being unsure (26.2%). Correlates of believing abortion to be illegal included younger age, lower socioeconomic status, never married or married status, and Black, non-Hispanic race and ethnicity. Being unsure about legality did not change over time; however, the proportion of women who believed that abortion is illegal increased from the first month (4.5%) to the last month (15.9%) of the study period. Each additional study month was associated with a 17% increase in the odds of believing abortion to be illegal, in both unadjusted and adjusted models (odds ratio, 1.17; 95% confidence interval, 1.08-1.27). CONCLUSION: Attempts to restrict abortion access could contribute to women mistakenly believing that abortion is illegal despite it being unsuccessful.

Role of temporal discounting in a conditional cash transfer (CCT) intervention to improve engagement in the prevention of mother-to-child transmission (PMTCT) cascade.

BACKGROUND: Temporal discounting, the tendency of individuals to discount future costs and benefits relative to the present, is often associated with greater engagement in risky behaviors. Incentives such as conditional cash transfers (CCTs) have the potential to counter the effects of high discount rates on health behaviors. METHODS: With data from a randomized trial of a CCT intervention among 434 HIV-positive pregnant women in the Democratic Republic of Congo, we used binomial models to assess interactions between discount rates (measured using a delay-discounting task) and the intervention. The analysis focused on two outcomes: 1) retention in HIV care, and 2) uptake of prevention of mother-to-child transmission (PMTCT) services. RESULTS: The effect of high discount rates on retention was small, and we did not observe evidence of interaction between high discount rates and CCT on retention. However, our findings suggest that CCT may mitigate the negative effect of high discount rates on uptake of PMTCT services (interaction contrast (IC): 0.18, 95% CI: - 0.09, 0.44). CONCLUSIONS: Our findings provide evidence to support the continued use of small, frequent incentives, to motivate improved uptake of PMTCT services, especially among women exhibiting high rates of temporal discounting. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01838005 , April 23, 2013.

Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operon.

Clusters of Neisseria meningitidis (Nm) urethritis among primarily heterosexual males in multiple US cities have been attributed to a unique non-encapsulated meningococcal clade (the US Nm urethritis clade, US_NmUC) within the hypervirulent clonal complex 11. Resistance to antimicrobial peptides (AMPs) is a key feature of urogenital pathogenesis of the closely related species, Neisseria gonorrhoeae. The US_NmUC isolates were found to be highly resistant to the model AMP, polymyxin B (PmB, MICs 64-256 µg ml-1 ). The isolates also demonstrated stable subpopulations of heteroresistant colonies that showed near total resistant to PmB (MICs 384-1024 µg ml-1 ) and colistin (MIC 256 µg ml-1 ) as well as enhanced LL-37 resistance. This is the first observation of heteroresistance in N. meningitidis. Consistent with previous findings, overall PmB resistance in US_NmUC isolates was due to active Mtr efflux and LptA-mediated lipid A modification. However, whole genome sequencing, variant analyses and directed mutagenesis revealed that the heteroresistance phenotypes and very high-level AMP resistance were the result of point mutations and IS1655 element movement in the pilMNOPQ operon, encoding the type IV pilin biogenesis apparatus. Cross-resistance to other classes of antibiotics was also observed in the heteroresistant colonies. High-level resistance to AMPs may contribute to the pathogenesis of US_NmUC.

In Vitro Exposure of Leukocytes to HIV Preexposure Prophylaxis Decreases Mitochondrial Function and Alters Gene Expression Profiles.

The use of antiretroviral therapy (ART) as preexposure prophylaxis (PrEP) is an effective strategy for preventing HIV acquisition. The cellular consequences of PrEP exposure, however, have not been sufficiently explored to determine potential effects on health in individuals without HIV. In this study, peripheral blood mononuclear cells (PBMCs) from people without HIV were exposed to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) overnight. Mitochondrial mass and function were measured by flow cytometry and an Agilent XFp analyzer. Monocyte-derived macrophages (MDMs) were differentiated in 20% autologous serum for 5 days in the presence or absence of TDF or FTC, and surface markers, lipid uptake, and efferocytosis were measured by flow cytometry. MDM gene expression was measured using transcriptome sequencing (RNA-seq). Plasma lipids were measured using mass spectrometry. PBMCs exposed to TDF or FTC had decreased maximal oxygen consumption rate (OCR) and reduced mitochondrial mass. Exposure to PrEP also increased reactive oxygen species (ROS) production from monocyte subsets. Compared to MDMs cultured in medium alone, cells differentiated in the presence of TDF (829 genes) or FTC (888 genes) had significant changes in gene expression. Further, PrEP-exposed MDMs had decreased mitochondrial mass and displayed increased lipid uptake and reduced efferocytosis. Plasma biomarkers and lipid levels were also altered in vivo in individuals receiving a PrEP regimen. In conclusion, exposure of leukocytes to TDF or FTC resulted in decreased mitochondrial function and altered functional and transcriptional profiles. These findings may have important implications for the metabolic and immunologic consequences of PrEP in populations at risk for HIV acquisition.

Reverse Sequence Syphilis Screening and Discordant Results in Pregnancy.

A "reverse sequence syphilis screening" algorithm is widely used for syphilis testing. This retrospective study showed that most (65%) pregnant women with discordant screening results (treponemal multiplex flow immunoassay IgG+/rapid plasma reagin-) had a nonreactive confirmatory Treponema pallidum-particle agglutination assay, likely indicative of a false-positive reaction.

An Assessment of Risk Factors for Herpes Simplex Virus Type 2 Infection in Malawian Women Using 2 Classifications for the HerpeSelect 2 Test.

BACKGROUND: The HerpeSelect 2 ELISA IgG test for herpes simplex virus type 2 (HSV-2) infection is widely used, convenient, and inexpensive. However, it has been shown to have lower specificity among populations in Sub-Saharan Africa compared with HSV-2 tests regarded as criterion standards. METHODS: In 2016, we collected blood and survey data from 248 women participating in a community-based cohort study in rural Malawi (the Umoyo wa Thanzi project). Using multinomial logistic regression accounting for village-level clustering, we examined unadjusted associations between select demographic and sexual risk factors and HSV-2 serostatus. Because increasing the index value cutpoint for a positive result improves specificity, we coded HSV-2 serostatus in 2 ways: the manufacturer's recommended cutpoints (<0.9, negative; 0.9-1.1, indeterminate; >1.1, positive) and modified cutpoints with improved specificity (<0.9, negative; 0.9-3.5, indeterminate; >3.5, positive). We aimed to investigate whether associations between select risk factors and HSV-2 serostatus varied under the 2 approaches. RESULTS: The prevalence of HSV-2 in this sample was 67% under the manufacturer's cutpoint and 22% under the modified cutpoint. Under both cutpoints, age, household size, number of marriages, and number of pregnancies were associated with HSV-2-positive serostatus. Using modified cutpoints, current bacterial vaginosis (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.35-7.47), partner concurrency (OR, 4.88; 95% CI, 2.54-9.37) and unsure about partner concurrency (OR, 1.91; 95% CI, 1.08-3.38) were associated with HSV-2 seropositivity. Household size, education, and marital status were the only variables significantly associated with indeterminate HSV-2 serostatus using the modified cutpoints. CONCLUSION: HSV-2-focused interventions informed by identifying individuals likely to have or acquire HSV-2 must be aware that different target populations may emerge depending on which cutpoints are adopted.

For Human Papillomavirus Self-Sampling, Stated Willingness Does Not Correspond With Subsequent Uptake by Rural Malawian Women.

BACKGROUND: Human papilloma virus (HPV), the causative agent for cervical cancer, can be tested for using self-collected vaginal samples. Self-collection is promising for HPV screening in hard-to-reach populations. To assess the relationship between willingness to self-collect and subsequent uptake of self-collection, we conducted a longitudinal study of reproductive-age women in rural Malawi. METHODS: At baseline, we asked women if they would be willing to self-collect a vaginal sample for HPV testing. At follow-up (12-18 months later), we offered the same women the opportunity to self-collect a sample for HPV testing. We examined unadjusted and adjusted associations between baseline willingness to self-collect a sample for HPV testing and uptake of self-collection at follow-up using log-binomial models. RESULTS: Among 122 women who, at baseline, indicated willingness to self-collect, n = 65 (53%) agreed to self-collect a sample at follow-up. Of 64 women who stated unwillingness at baseline to self-collect, n = 30 (47%) self-collected a sample for testing at follow-up. We observed no association between women's willingness at baseline and their observed self-collection decision at follow-up (unadjusted prevalence ratio, 1.14; 95% confidence interval, 0.83-1.55). The association remained null after adjustment for age, awareness of cervical cancer, and perceived behavioral control. CONCLUSIONS: Our results suggest that evaluation of acceptability of self-collection should go beyond simply asking women if they would be willing to self-collect a vaginal sample. Given that half of this study's participants agreed to self-collect a sample when the opportunity was offered, regardless of their previously stated preferences, self-collection should be offered to everyone.

Repeat Episodes of Symptomatic Urethritis Due to a Uropathogenic Meningococcal Clade.

In 2015, we identified a non-groupable clade of Neisseria meningitidis that causes urethritis in men (the US_NmUC). Because repeat infection is common with Neisseria gonorrhoeae, we examined whether reinfection also occurs with the US_NmUC. We provide evidence that men are susceptible to repeat episodes of urethritis from the US_NmUC.

Emergence of a new Neisseria meningitidis clonal complex 11 lineage 11.2 clade as an effective urogenital pathogen.

Neisseria meningitidis (Nm) clonal complex 11 (cc11) lineage is a hypervirulent pathogen responsible for outbreaks of invasive meningococcal disease, including among men who have sex with men, and is increasingly associated with urogenital infections. Recently, clusters of Nm urethritis have emerged primarily among heterosexual males in the United States. We determined that nonencapsulated meningococcal isolates from an ongoing Nm urethritis outbreak among epidemiologically unrelated men in Columbus, Ohio, are linked to increased Nm urethritis cases in multiple US cities, including Atlanta and Indianapolis, and that they form a unique clade (the US Nm urethritis clade, US_NmUC). The isolates belonged to the cc11 lineage 11.2/ET-15 with fine type of PorA P1.5-1, 10-8; FetA F3-6; PorB 2-2 and express a unique FHbp allele. A common molecular fingerprint of US_NmUC isolates was an IS1301 element in the intergenic region separating the capsule ctr-css operons and adjacent deletion of cssA/B/C and a part of csc, encoding the serogroup C capsule polymerase. This resulted in the loss of encapsulation and intrinsic lipooligosaccharide sialylation that may promote adherence to mucosal surfaces. Furthermore, we detected an IS1301-mediated inversion of an ∼20-kb sequence near the cps locus. Surprisingly, these isolates had acquired by gene conversion the complete gonococcal denitrification norB-aniA gene cassette, and strains grow well anaerobically. The cc11 US_NmUC isolates causing urethritis clusters in the United States may have adapted to a urogenital environment by loss of capsule and gene conversion of the Neisseria gonorrheae norB-aniA cassette promoting anaerobic growth.

Parental Perceptions and Behaviors Regarding Child Weight Status among Toddlers Born Preterm.

OBJECTIVE: Childhood obesity is a significant determinant of adult obesity. Among children born preterm, rapid "catch-up growth" in infancy increases the risk of later obesity. Parental perceptions of their child's weight status may compound the child's biologically heightened risk of obesity. STUDY DESIGN: We performed a secondary analysis of data on parental perceptions of child weight status from a randomized controlled trial (2012-2017, n = 331 toddlers born preterm). We used the Child Feeding Questionnaire (CFQ) to measure parental child feeding behaviors and beliefs. We calculated the prevalence of incorrect weight estimation, and used t-tests and chi-square tests to compare sample characteristics by correct versus incorrect weight estimation. We calculated odds ratios (ORs) for factors associated with parental underestimation of child weight status. RESULTS: Most (90%) children were of normal weight, whereas 3% were underweight and 7% were overweight. A majority (75%) of parents correctly estimated their child's weight status. Incorrect weight estimation was only associated with child's actual weight. Parents of overweight children were more likely to underestimate their child's weight status than parents of normal weight children (OR: 2.23, 95% confidence interval: 2.00-2.49). Mean CFQ scores differed by the child's actual weight status but not by the child's estimated weight status. CONCLUSION: Among these toddlers born preterm, significantly higher proportions of parents with underweight and overweight children incorrectly estimated their child's weight status relative to parents of normal weight children. Our findings suggest that weight underestimation could be a problem in this population, although it was not associated with changes in feeding practices.

Who Has Yet to Test? A Risk Score for Predicting Never Having Tested for Human Immunodeficiency Virus Among Women and Men in Rural Malawi.

BACKGROUND: Human immunodeficiency virus (HIV) status awareness is important for preventing onward HIV transmission, and is one of the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 goals. Efforts to scale up HIV testing have generally been successful, but identifying at-risk individuals who have never tested for HIV-a population necessary to reach improved HIV status awareness-remains challenging. METHODS: Using data from a community-based cohort of people living in rural central Malawi, we identified demographic, socioeconomic, and sexual health correlates of never having tested for HIV. Correlates were assigned values from the logistic regression model to develop a risk score that identified who had never tested for HIV. RESULTS: Among 1310 ever sexually active participants, 7% of the women and 13% of the men had never tested for HIV. Of those who had tested for HIV, about 30% had tested more than 12 months ago. For women, younger age and poorer sexual health knowledge were correlated with never having tested for HIV, and the c-statistic for the risk score was 0.83. For men, their partner having not tested for HIV, low socioeconomic status, and poor sexual health knowledge were correlated with never testing for HIV (c-statistic, 0.81). Among those with a score of 3 or greater, the sensitivity and specificity for never having tested for HIV were 81% and 77% for women, and 82% and 66% for men, respectively. CONCLUSIONS: About 10% of participants had never tested for HIV. This risk score could help health professionals to identify never testers to increase HIV status awareness in line with 90-90-90 goals.

Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

BACKGROUND: Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm. OBJECTIVES: The aim of the trial was to examine the effects of supplementing toddlers born preterm with DHA and arachidonic acid (AA) for 180 d on growth and adiposity. METHODS: Omega Tots, a randomized placebo-controlled trial, was conducted between April 2012 and March 2017. Children born at <35 wk gestation who were 10-16 mo in corrected age were assigned to receive daily oral supplements of DHA and AA (200 mg each, "DHA + AA") or corn oil (placebo) for 180 d. Prespecified secondary outcomes included weight, length, head circumference, mid-upper arm circumference, triceps and subscapular skinfolds, BMI, and their respective z scores, and body fat percentage, which were measured at baseline and trial completion. Mixed-effects regression was used to compare the change in outcomes between the DHA + AA and placebo groups, controlling for baseline values. RESULTS: Among 377 children included in the analysis (median corrected age = 15.7 mo, 48.3% female), 348 (92.3%) had growth or adiposity data at baseline and trial end. No statistically significant differences between the DHA + AA and placebo groups in growth or adiposity outcomes were observed. For instance, the change in weight-for-age z scores was 0.1 for the DHA + AA group and 0.0 for the placebo group (effect size = 0.01, P = 0.99). However, post-hoc subgroup analyses revealed a statistically significant interaction between treatment group and sex, suggesting somewhat slower linear growth for females assigned to the DHA + AA group compared with the placebo group. CONCLUSIONS: Among toddlers born preterm, daily supplementation with DHA + AA for 180 d resulted in no short-term differences in growth or adiposity compared with placebo. If DHA supplementation is implemented after the first year of life, it can be expected to have no effect on short-term growth or adiposity. This trial is registered with clinicaltrials.gov as NCT02199808.