Acceptability and Usability of Self-Sampling for the Detection of Sexually Transmitted Infections Among Transgender Women: The TransOdara Multicentric Study in Brazil.

BACKGROUND: The effective testing of sexually transmitted infections (STIs) requires sampling from potential infection sites. This study aimed to assess the choice, satisfaction, and performance of self-collected samples (SCS) from potential infection sites for STI testing among transgender women in Brazil. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study conducted in 5 Brazilian cities. Using respondent-driven sampling, 1317 transgender women 18 years or older were recruited. Participants completed interviewer-led questionnaires and provided swab samples from multiple sites (anorectal, oropharyngeal, genital) for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and human papillomavirus (HPV) testing. Participants were given a choice of SCS or provider-collected samples (PCS) at each site. RESULTS: Most participants selected SCS for anorectal (74.9%; 95% confidence interval [CI], 72.4-77.3) and genital (72.7%; 95% CI, 70.2-75.1) sites, whereas fewer chose for oropharyngeal samples (49.8%; 95% CI, 47.0-52.6). For future testing, most participants expressed a preference for SCS for genital (72.2%; 95% CI, 69.5-74.7) and anorectal (70.2%; 95% CI, 67.6-72.7) sites. There was no significant difference in the positive test results for CT and NG between SCS and PCS at anorectal and oropharyngeal sites, or for HPV at anorectal and genital (penile or neovaginal) sites. CONCLUSIONS: This study demonstrated a high level of acceptability and usability of self-sampling for STI testing among transgender women. A preference for SCS was evident at the anorectal and genital sites, and the results of SCS were comparable to those of PCS. The findings suggest that multisite STI testing utilizing self-collection methods as a provided option can be effectively integrated into sexual health services for transgender women.

Dengue Outbreak Response during COVID-19 Pandemic, Key Largo, Florida, USA, 2020.

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Hepatitis C virus prevalence among men who have sex with men: a cross-sectional study in 12 Brazilian cities.

BACKGROUND: Despite the preventive policies adopted, reduction in sexually transmitted infections (STIs) among men who have sex with men (MSM) has been limited. The risk of hepatitis C virus (HCV) infection has increased among the most vulnerable population groups, including MSM. The aim of this study was to estimate the prevalence of HCV infection and to assess risky practices among MSM from 12 Brazilian cities. METHODS: This study was carried out from June to December 2016 using respondent driven sampling (RDS). Participants completed a self-administered questionnaire to collect behavioral, socioeconomic, and demographic variables. In addition, the rapid diagnostic test (RDT) for HCV was offered. Positive results were sent to Instituto Adolfo Lutz for confirmation. RESULTS: A total of 4,176 participants were recruited and 23 samples were sent for confirmation. Of these, 16 were confirmed, resulting in a prevalence of 0.7% (95% CI: 0.3%-1.7%). The Southeast region showed a prevalence of 0.9% (95% CI: 0.3-2.6), followed by the South region, with 0.6% (95% CI: 0.2-2.1). The Northeast region had a prevalence of 0.3% (95% CI: 0.1-1.0) and the Midwest 0.1% (95% CI: 0.0-0.7). No positive cases were found in the North. Single men aged 40 years or older were the majority of participants exposed to HCV. High levels of alcohol consumption, illicit drug use, irregular condom use, in addition to infection with other STIs, were associated with exposure to HCV. CONCLUSIONS: STIs continue to be important health problems in Brazil and globally. Many STIs are inapparent for many years until they bring more serious consequences. Extra investment in HCV is also warranted, given that it can be eliminated. Relying solely on clinical data to provide information about inapparent infection, especially in stigmatized populations, will make that goal more difficult to achieve. Surveillance studies, such as the one reported here need to be repeated over time to demonstrate trends and to provide information for evaluation, program and policies. Investments in the most vulnerable populations are critical to achieve the World Health Organization global health goals including the elimination of viral hepatitis by 2030.

Perceived Risk of HIV Infection and Acceptability of PrEP among Men Who Have Sex with Men in Brazil.

The HIV epidemic affects men who have sex with men (MSM) disproportionally in Brazil, and pre-exposure prophylaxis (PrEP) is effective for preventing HIV in this population. However, low perceived risk of HIV may influence the acceptability and decision to use PrEP. This study estimated the association between self-perception of HIV risk and acceptability of daily oral PrEP among Brazilian MSM. Respondent-driven sampling (RDS) was used for behavioral and biological surveillance to recruit 4,176 MSM 18 years or over in 12 Brazilian cities in 2016. Results were weighted using Gile's estimator in RDS Analyst software. Adjusted odds rations (OR) with 95% confidence intervals were calculated using multivariate logistic regression. Acceptability of daily oral PrEP was high (69.7%) among the 3,544 MSM available for analysis. Most participants self-reported low or moderate risk of HIV infection (67.2%) and a small proportion (9.3%) reported high risk. A dose-response relationship was observed between acceptability of PrEP and self-reported risk: PrEP acceptability was 1.88 times higher (OR 1.8; 95% CI: 1.24-2.85) among MSM whose perceived risk of HIV infection was low or moderate, and 5 times higher (OR 5.68; 95% CI: 2.54-12.73) among those who self-reported high risk compared to MSM reporting no HIV risk. MSM with the highest risk perception of HIV reported higher rates of PrEP acceptability. Given the availability of daily oral PrEP in the public health care system in Brazil, we suggest emphasizing counseling about self-perception of HIV risk as part of routine HIV prevention services.

Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation.

Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to offspring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.

Factors associated with loss to follow up among HIV-exposed children: a historical cohort study from 2000 to 2017, in Porto Alegre, Brazil.

BACKGROUND: There are many inequalities in terms of prevention and treatment for pregnant women with HIV and exposed children in low and middle-income countries. The Brazilian protocol for prenatal care includes rapid diagnostic testing for HIV, compulsory notification, and monitoring by the epidemiological surveillance of children exposed to HIV until 18 months after delivery. The case is closed after HIV serology results are obtained. Lost to follow-up is defined as a child who was not located at the end of the case, and, therefore, did not have a laboratory diagnosis. Lost to follow-up is a current problem and has been documented in other countries. This study analyzed factors associated with loss to follow-up among HIV-exposed children, including sociodemographic, behavioral, and health variables of mothers of children lost to follow-up. METHODS: This historical cohort study included information on mothers of children exposed to HIV, born in Porto Alegre, from 2000 to 2017. The research outcome was the classification at the end of the child's follow-up (lost to follow-up or not). Factors associated with loss to follow-up were investigated using the Poisson regression model. Relative Risk calculations were performed. The significance level of 5% was adopted for variables in the adjusted model. RESULTS: Of 6,836 children exposed to HIV, 1,763 (25.8%) were classified as lost to follow-up. The factors associated were: maternal age of up to 22 years (aRR 1.25, 95% CI: 1.09-1.43), the mother's self-declared race/color being black or mixed (aRR 1.13, 95% CI: 1.03-1.25), up to three years of schooling (aRR 1.45, 95% CI: 1.26-1.67), between four and seven years of schooling (aRR 1.14, 95% CI: 1.02-1.28), intravenous drug use (aRR 1.29, 95% CI: 1.12-1.50), and HIV diagnosis during prenatal care or at delivery (aRR 1.37, 95% CI: 1.24-1.52). CONCLUSION: Variables related to individual vulnerability, such as race, age, schooling, and variables related to social and programmatic vulnerability, remain central to reducing loss to follow-up among HIV-exposed children.

RAPIDO: Promoting stroke awareness among Spanish speakers.

ABSTRACT: The mnemonic BE-FAST (Balance, Eyes, Face, Arm, Speech, Time) has been developed for the public to better remember and identify the warning signs of stroke. However, discrepancies may arise when translating stroke educational materials from English to Spanish. This article discusses the use of a culturally tailored tool, RAPIDO, to raise stroke awareness in Spanish-speaking populations.

Acceptability of HIV self-testing is low among men who have sex with men who have not tested for HIV: a study with respondent-driven sampling in Brazil.

BACKGROUND: Brazil has many people living with HIV (PLWH) who are unaware of their serostatus. The public health system has recently added HIV self-testing (HIVST) for key populations such as men who have sex with men (MSM). This study estimates HIVST acceptability among Brazilian MSM and explores factors associated with acceptability among MSM who have never tested for HIV or who had a previous negative result. METHODS: Respondent-driven sampling (RDS) was used to recruit 4176 MSM in 12 Brazilian cities in 2016 to this biological and behavioral surveillance study. We excluded from this analysis all MSM who were aware of their positive HIV serostatus. Descriptive, bivariate and multivariate analyses were conducted. Overall proportions were weighted with Gile's estimator in RDS Analyst software and 95% confidence intervals were calculated. The analyses of HIVST acceptability were stratified by prior HIV testing (never or one or more times). RESULTS: For this analysis, 3605 MSM were included. The acceptability of HIVST was 49.1%, lower among those who had never tested for HIV (42.7%) compared to those who had a previous HIV negative test (50.1%). In the subgroup of MSM who had never tested for HIV, those who reported discrimination or who had a medical appointment in the last 12 months reported higher HIVST acceptability. Among MSM who had a previous negative HIV test, only those reporting condomless receptive anal sex reported higher HIVST acceptability. In addition, we observed that high levels of knowledge of HIV/AIDS, taking part in lesbian, gay, bisexual, and transgender nongovernmental organizations (LGBT-NGO), or complete secondary or incomplete higher undergraduate education reported higher acceptability. CONCLUSIONS: The acceptability of HIVST was low among MSM, especially among those who never tested for HIV. Given access to HIVST in Brazil, we point to the need for programs that enhance promotion of testing addressed to MSM.

The use of a task through virtual reality in cerebral palsy using two different interaction devices (concrete and abstract) - a cross-sectional randomized study.

BACKGROUND: Cerebral Palsy (CP) is characterised by variable difficulties in muscular action, resulting in inability of the individual to perform functional movement. An option to provide functionality to the individual with CP is the use of computer innovation. The aim of this paper was to verify if there was any performance improvement in a task performed in a virtual environment and if there was transfer to the task performed in the real environment and vice versa in this population. METHODS: A computer program was developed comprising a motor task, but with two possibilities of user interaction: a) concrete interface (with physical contact): in which the individual touches the computer screen to finish the task and b) abstract interface (no physical contact): in which the individual performs a hand movement in front of the Kinect device. Participants were split into two groups. The experimental group consisted of 28 individuals with CP within the ages of 6 and 15 years old. The control group included 28 typically developing individuals mirroring the age and sex of the experimental group. RESULTS: Individuals from both groups were able to improve task performance and retain acquired information. The CP group presented worse performance than the control group in all phases of the study. Further findings showed that the CP group presented better performance in the abstract interface than in the concrete interface, whereas, in the control group, the opposite occurred: their best performance was in the concrete. CONCLUSIONS: Motor tasks performed by individuals with CP through an interface with a more virtual environment feature (abstract interface: Kinect) provided better performance when compared to an interface with a more real characteristic (concrete interface: Touchscreen). TRIAL REGISTRATION: ClinicalTrials.gov Identifier - NCT03352440; Date of registration - November 17, 2017.

Discrimination based on gender identity against transgender women and travestis in Brazil: a latent class analysis and associated factors.

OBJECTIVE: To identify groups of transgender women and travestis (TGW) with specific patterns of gender-based discrimination (GBD) and analyze the factors associated with GBD. METHODS: A cross-sectional study was conducted with TGW recruited through respondent-driven sampling in five Brazilian cities (2019-2021). Latent class analysis was used to characterize GBD (low, medium, and high) using 14 observable variables. Descriptive analysis was performed, and associations between predictor variables and GBD were estimated by adjusted odds ratios (aOR) using ordinal logistic regression. RESULTS: Out of a total of 1,317 TGW, 906 (68.8%) answered questions about GBD. Most were under 34 years old, single, and had a Brown race/skin color. GBD was classified as "low," "medium," and "high," with estimates of 41.7, 44.5, and 13.8%, respectively. Variables positively associated with higher intensity of GBD included living in Manaus compared to São Paulo, being ≤34 years old compared to >34, being homeless compared to living in one's own house or rented apartment, not having legally changed one's name compared to those who had, and reporting physical or sexual violence compared to those who did not report. Variables negatively associated with higher intensity of GBD included having a Brown or Asian race/skin color compared to White and a monthly income ≥1 minimum wage compared to ³1. CONCLUSION: A high proportion of GBD was observed in Brazilian TGW, with this outcome associated with more vulnerable sociodemographic characteristics and a history of violence.

Estimation of population age structure, daily survival rates, and potential to support dengue virus transmission for Florida Keys Aedes aegypti via transcriptional profiling.

Aedes aegypti is an important vector of dengue virus and other arboviruses that affect human health. After being ingested in an infectious bloodmeal, but before being transmitted from mosquito to human, dengue virus must disseminate from the vector midgut into the hemocoel and then the salivary glands. This process, the extrinsic incubation period, typically takes 6-14 days. Since older mosquitoes are responsible for transmission, understanding the age structure of vector populations is important. Transcriptional profiling can facilitate predictions of the age structures of mosquito populations, critical for estimating their potential for pathogen transmission. In this study, we utilized a two-gene transcript model to assess the age structure and daily survival rates of three populations (Key West, Marathon, and Key Largo) of Ae. aegypti from the Florida Keys, United States, where repeated outbreaks of autochthonous dengue transmission have recently occurred. We found that Key Largo had the youngest Ae. aegypti population with the lowest daily survival rate, while Key West had the oldest population and highest survival rate. Across sites, 22.67% of Ae. aegypti females were likely old enough to transmit dengue virus (at least 15 days post emergence). Computed estimates of the daily survival rate (0.8364 using loglinear and 0.8660 using non-linear regression), indicate that dengue vectors in the region experienced relatively low daily mortality. Collectively, our data suggest that Ae. aegypti populations across the Florida Keys harbor large numbers of older individuals, which likely contributes to the high risk of dengue transmission in the area.

Profile and experiences during the incarceration of transgender women and travestis (TGW) in Brazil: a cross-sectional study.

OBJECTIVE: The objective of the present study is to describe the sociodemographic and behavioral characteristics of a group of transgender women and travestis (TGW) with a history of incarceration and the institutional and social context of this experience in Brazil. METHODS: The analyzed data were derived from the TransOdara Study, a cross-sectional study conducted in five Brazilian capitals from December 2019 to July 2021. Participants were recruited using the Respondent-Driven Sampling (RDS) technique, in which, after an initial formative and exploratory stage, the first participants were identified; in turn, these participants recruited up to six other transgender women and travestis for the research. The study's outcome was the experience of incarceration throughout life, captured through the question: "Have you ever been arrested in your life?" RESULTS: A total of 1,245 TGW were interviewed, of which 20.3% (n=253) experienced incarceration. Incarceration was more frequent among those aged 33 to 42 years (35.6%), with lower level of education (45.5%, p<0.001), engaged in informal work (30.3%), without a partner (67.2%), and among those who reported illicit drug use (66.4%). The majority (60.9%) of TGW were incarcerated with cisgender men, and the most common reasons for imprisonment were drug trafficking (30.4%) followed by robbery (29.2%). Over a quarter of the interviewees (26.3%) experienced assault, and 13.8% reported experiencing sexual violence during incarceration. CONCLUSION: The results emphasize the high prevalence of incarceration among TGW. This incarceration takes place in male wards and in a context of high rates of physical and sexual violence.

Lifetime sexual violence among transgender women and travestis (TGW) in Brazil: Prevalence and associated factors.

OBJECTIVE: To describe the prevalence, characteristics, and factors associated with sexual violence in transgender women and travestis (TGW) in Brazil. METHODS: This cross-sectional study was conducted in five Brazilian cities (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo) between 2019 and 2021. Participants were recruited using the respondent-driven sampling (RDS) technique. The outcome of interest is the self-reported experience of sexual violence throughout the respondents' lifetime. We evaluated the actions taken by victims of sexual violence and how they dealt with the experience. Logistic regression analysis was employed to examine the associations between sociodemographic and behavioral factors (such as race, income, drug use, sex work, and access to healthcare) and the outcome. RESULTS: A total of 1,317 TGW were interviewed. Among them, 53% (n=698) reported experiencing sexual violence. For 64.4% (n=419) of the respondents, sexual violence occurred on more than one occasion. The majority of TGW did not seek health services (93.2%, n=648), disclose the violence (93.9%, n=653), nor seek support from family or friends (86.5%, n=601). A higher prevalence of sexual violence was associated with homelessness (adjusted prevalence ratio - aPR=1.69, 95% confidence interval - 95%CI 1.01-2.84), a history of engaging in sex work (aPR=2.04, 95%CI 1.46-2.85), self-reporting regular, bad, or very bad emotional health (aPR=1.67, 95%CI 1.28-2.19), and experiencing difficulties accessing health services in the previous year (aPR=2.78, 95%CI 1.74-4.43). CONCLUSION: The high prevalence of sexual violence, analyzed together with the actions of the victims, indicates a context of high vulnerability and low institutional support. In this scenario, violence can be exacerbated, resulting in severe health consequences.

A Cross-sectional Survey of Comprehension and Satisfaction of Spanish-Reading Adults Regarding RÁPIDO as a Stroke Awareness Acronym.

ABSTRACT: BACKGROUND: Delay time to hospital arrival may be influenced by lack of recognition of stroke signs and the necessity to seek emergency medical, which in turn is influenced by language barriers to, a modifiable risk factor, stroke awareness education. The objective was to determine the comprehension and satisfaction of a Spanish stroke awareness acronym, RÁPIDO, among community-living, Hispanic and Latino, Spanish-reading adults. METHODS: A 33-item survey was completed by 166 adults. Data on sociodemographics, language preferences, stroke education, and comprehension and satisfaction with RÁPIDO were collected. Descriptive characteristics were calculated. Fisher exact tests were performed to determine whether reading language (group 1, only or predominantly reads in Spanish; group 2, reads in Spanish and English equally or reads predominately in English) influenced survey responses. Responses to open-ended questions were categorized. RESULTS: Sixty-nine percent of the participants were born outside of the United States, 82% currently resided in the United States, 34% read only or predominately in Spanish, and 7% had a stroke. Most participants thought RÁPIDO was informative, eye-catching, and easily remembered. Significant differences were found between reading language preference groups for correctly identifying RÁPIDO images for facial drooping (group 1, 80%; group 2, 95%; P ≤ .001) and dizziness/loss of balance (group 1, 54%; group 2, 73%; P = .027). Eighty percent or more of all participants were able to correctly interpret RÁPIDO images for facial drooping, blurry vision, impaired speech, and call emergency services. Adding "911" to the RÁPIDO image of the clock was a common suggestion. CONCLUSIONS: RÁPIDO was well received among the participants. Modifications to RÁPIDO images representing dizziness/loss of balance and arm weakness, and the addition of "911" may improve its usefulness. Obtaining more extensive feedback across the United States and testing the effect of RÁPIDO on increasing knowledge of stroke signs and retention of that knowledge are necessary next steps.

TransOdara study: the challenge of integrating methods, settings and procedures during the COVID-19 pandemic in Brazil.

OBJECTIVE: Sexually transmitted infections (STIs) disproportionately affect transgender women and travestis (TGW), who often lack access to healthcare due to stigma and discrimination. We describe the approach and methodology of a study investigating the prevalence of syphilis, HIV, hepatitis A, B, and C, Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and human papillomavirus (HPV) among TGW, as well as their knowledge and perceptions regarding syphilis, to better inform policies to curb STIs among this vulnerable population. METHODS: TransOdara was a multicentric, cross-sectional study conducted among TGW in five capital cities from major Brazilian regions between December 2019 and July 2021. Self-identified transgender women and travestis aged >18 years were recruited using respondent-driven sampling after a qualitative formative phase, completed an interviewer-led questionnaire, were offered a physical examination, and were also asked to provide samples from multiple sites to detect various STIs, starting vaccination and treatment when indicated. RESULTS: A total of 1,317 participants were recruited from the five study locations: Campo Grande (n=181, 13.7%), Manaus (n=340, 25.8%), Porto Alegre (n=192, 14.6%), Salvador (n=201, 15.3%), and São Paulo (n=403, 30.6%). The recruitment period varied at each study location due to logistic constraints imposed by the COVID-19 pandemic. CONCLUSION: Despite the enormous challenges posed by the co-occurrence of the COVID-19 pandemic and field work targeting a vulnerable, elusive, and scattered population, the TransOdara project has been effectively implemented. Caveats did not preclude 1,300 TGW from being interviewed and tested, amid a significant epidemic that disrupted health services and research projects in Brazil and worldwide.

Increasing HIV prevalence rate among men who have sex with men: results of a comparison of two national surveys.

Our objective was to compare HIV prevalence between two national surveys among men who have sex with men in Brazil in 2009 and 2016. HIV prevalence was estimated stratifying by age and socioeconomic status. HIV prevalence increased from 11.9% [95% confidence interval (CI): 9.9-14.3], in 2009, to 19.1% (95% CI: 16.5 - 22.0), in 2016 [odds ratio (OR) = 1.8; 95% CI: 1.3-2.3] increasing 320% among Young MSM of low SES. Political leadership is needed to develop a scientifically sound and inclusive solution.

Correction: Influenza vaccination hesitancy in five countries of South America. Confidence, complacency and convenience as determinants of immunization rates.

[This corrects the article DOI: 10.1371/journal.pone.0243833.].

Hepatitis A, B and C prevalence among transgender women and travestis in five Brazilian capitals between 2019-2021.

OBJECTIVE: To estimate the prevalence and factors associated with hepatitis A, B, and C in transgender women and travestis's networks, in 5 regions of Brazil. METHODS: This cross-sectional study includedtransgender women and travestis in five Brazilian capitals (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo), between December/2019 and July/2021. All samples were subjected to detection of serological markers of hepatitis virus A (HAV), B (HBV), and C (HCV) infections through rapid tests and chemiluminescent microparticle immunoassays. Positive samples in the screening tests were submitted to detect HBV DNA and HCV-RNA by real-time PCR and genotyped by Sanger sequencing. RESULTS: Analysis of 1,317 samples showed network prevalence rates of 69.1%, 25.1%, and 1.5% for HAV, HBV, and HCV exposure, respectively. A high susceptibility rate to HBV infection (35.7%) and low prevalence of vaccine response markers (40%) were also observed. Age greater than 26 years, self-declared black/brown skin color, having only primary education, history of incarceration, and use of a condom in the last sexual intercourse with a casual partner were associated with total anti-HAV. Exposure to HBV was associated with age greater than 26 years, self-declared black/brown, history of being a sex worker, and incarceration. Age > 37 years, history of sexual abuse, and frequent alcohol consumption were associated with hepatitis C infection. CONCLUSION: The highest prevalence of HAV in this population was found in the North and Northeast regions, and the prevalence found was higher than that in the general population, suggesting greater vulnerability. The prevalence of HCV infection in our study was similar to that observed in the general population.

Analysis of the insulin-like growth factor 1 receptor gene in children born small for gestational age: in vitro characterization of a novel mutation (p.Arg511Trp).

BACKGROUND: Insulin-like growth factor 1 insensitivity caused by IGF1R mutations has been previously identified as one of the causes of growth impairment in children born small for gestational age (SGA). OBJECTIVE: To analyse the IGF1R in children born SGA. SUBJECTS: From an initial cohort of 54 sequential children born SGA, without catch-up growth, 25 children were selected for this IGF1R study due to the presence of serum IGF-1 values above the mean for their age and sex. METHODS: The proximal IGF1R promoter region, the entire coding region and the exon-intron boundaries were directly sequenced, and multiplex ligation-dependent probe amplification analysis was performed. Fibroblast cultures were developed from one patient with a mutation for the in vitro characterization of IGF-1 insensitivity. RESULTS: The copy number variation analysis did not identify deletions involving the IGF1R gene. We identified two children carrying heterozygous nucleotide substitutions in IGF1R: c.16G>A/p.Gly6Arg and c.1531C>T/p.Arg511Trp. The first variant (p.Gly6Arg) was identified in control subjects (0·3%) and in a relative with normal growth; thus, it was considered to be a rare benign allelic variation. The second variant (p.Arg511Trp) was not found in 306 alleles from control subjects, and it segregated with the growth impairment phenotype in the patient's family. Fibroblasts obtained from this patient had a significantly reduced proliferative response and AKT phosphorylation after IGF-1 stimulation compared with control fibroblasts. CONCLUSION: The identification of an inactivating IGF1R mutation in the present cohort should encourage further studies of larger series to establish the precise frequency of this molecular defect in children with growth impairment of a prenatal onset.