Mitochondrial DNA parameters in blood of infants receiving lopinavir/ritonavir or lamivudine prophylaxis to prevent breastfeeding transmission of HIV-1

Children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA) parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC) pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN) and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery (PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value, and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa (control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was not significantly different between the two prophylactic regimens. Poisson regressions showed that LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75 (CI95%: 1.15–2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00–2.37), p = 0.05). Moreover, the proportion of children with MDD was unexpectedly high before randomisation in both groups. Long-term health impacts of these mitochondrial DNA parameters should be investigated further for both CHEU and HIV-infected children receiving LPV/r- or 3TC- based regimens.http://www.mdpi.com/journal/jcmpm2021Paediatrics and Child Healt

Niveau d'anxiété et refus scolaire dans les troubles anxieux chez l'adolescent

International audienceObjectives: The primary objective was to compare the level of anxiety on the Multidimensional Anxiety Scale for Children in two groups of anxious secondary school children, one group out of school meeting the criteria of School Refusal and the other in school. The secondary objective was to compare these groups on other clinical, sociodemographic and therapeutic parameters. Patient and method: Retrospective observational study of 34 school-going anxious teenagers recruited at the University Hospital of Montpellier, compared with 55 out of school anxious teenagers meeting the criteria of Anxious School Refusal recruited in a multicentre study. Results: There was no significant intergroup difference in median scores on the Multidimensional Anxiety Scale for Children (P = 0.49), but a significant intergroup difference in median scores was found on the Behavioural Anxiety and Phobia Scale with higher total scores in the School Refusal group (151.5 [130.5; 169.0] vs. 125.0 [94.0; 139.0], P < 0.01). The School Refusal group was more likely to have a panel of anxiety disorders including agoraphobia, separation anxiety, depressive disorders, more impaired global functioning and more likely to receive psychotropic medication (P < 0.01). There were no significant intergroup differences in sociodemographic characteristics except age. Discussion: The absence of significant intergroup differences in the level of anxiety measured with the Multidimensional Anxiety Scale for Children could be related to a lower level of anxiety in the school refusal group due to school refusal. The higher anxiety score with the Behavioural Anxiety and Phobia Scale in the refusal group could be related to their better sensitivity. The clinical picture in the refusal group, both more severe and with co-morbidities, is comparable to what is described in the literature. Conclusion: A higher level of anxiety was not associated with school refusal according to main endpoints in teenagers with anxiety disorders. However, this group had other criteria of greater clinical severity that justify early identification

Impact of containment and mitigation measures on children and youth with SD during the COVID-19 pandemic: Report from the ELENA cohort

International audienceBackground: Containment, involving separation and restriction of movement of people due to the COVID-19 pandemic, and mitigation, also referred to as lockdown, involving closure of schools, universities and public venues, has had a profound impact on people's lives globally. The study focuses on the effects of containment and mitigation measures, on the behavior of children and youth (CaY) with Autism Spectrum Disorders (ASD). The study primary aim was to examine the impact of these urgent measures on the behaviors, communication, sleep, and nutritional status of the CaY. A secondary aim was to explore risk and protective factors on behavior change including sociodemographic variables, living conditions, ASD symptom severity and continuity of interventions. Methods: The study sample consisted of 239 ASD subjects, 2–21 years of age, enrolled in the ELENA cohort in France at Stage 3 confinement and mitigation measures announced on March 16, 2020. A parent informant completed the COVID-19 questionnaire. Results: Of the domains examined, challenging behaviors, communicative skills and sleep had the greatest impact; in terms of risk and protective factors, subject age, ASD severity, single parenthood, daily living skills, and intervention continuity were most likely to impact behaviors; living conditions were not linked to behavior change. Conclusions: The findings highlight the topography of behavioral change in CaY with ASD following institution of containment and mitigation measures during the COVID-19 pandemic and help identify risk and protective factors to help better address needs and tailor interventions in the future

Breastfeeding is not a risk factor for clinical severity in Autism spectrum disorder in children from the ELENA cohort

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder that results from a complex interaction between genes and environment. Breastfeeding (BF) is thought to promote healthy cognitive development, and a body of research has suggested that it may also protect against ASD. Our objectives were to identify the relationship between the initiation and duration of BF and the severity of clinical presentation in ASD. Data were collected from 243 children with a confirmed diagnosis of ASD followed in the ELENA cohort. Clinical severity was measured according to multiple dimensions using standardised tools. The frequency of the initiation of BF was comparable to that of the general population and the rate of children still being breastfed at six months of age was higher. Our results did not indicate a contribution of initiation or duration of BF to the prevention of clinical severity of ASD. We discuss our results in the light of possible methodological limitations of previous reports of an association between BF and ASD. Clinical Trial Registration: NCT02625116

Anxiety and depression in parents of children with autism spectrum disorder during the first COVID-19 lockdown: Report from the ELENA cohort

International audienceBackground: The Covid-19 pandemic had a strong impact on mental health in the general population. This study conducted during the first lockdown in France considered parents of children with Autism Spectrum Disorder (ASD) prospectively followed in the ELENA Cohort.Objectives: We aimed to (1) compare the Anxiety and Depression (AaD) levels during the lockdown between mothers and fathers, (2) compare the parent's AaD between the lockdown and the last ELENA follow-up visit, and (3) identify risk factors for parental AaD during lockdown among socio-demographic and children's clinical characteristics.Methods: The Hospital Anxiety and Depression Scale (HADS) was used to assess AaD in 134 parent's pairs. Parents also completed the Questionnaire about their living conditions during COVID-19, their child's interventions and perceived changes about their child's behaviors and sleep. Child's ASD severity, intellectual and socio-adaptive skills and parent's socio-demographic characteristics were collected from ELENA follow-up.Results: The parents' AaD levels were lower during the lockdown compared to the last ELENA visit that coincided in 96% with the child's ASD diagnosis. The AaD levels were more pronounced in mothers and significantly associated with the child's challenging behaviors, parents' teleworking and perceived knowledge about COVID-19. The perception of an insufficient knowledge was the only risk factor for mothers' AaD.Conclusion: Our findings highlighted the pertinence for an assessment of the mental health of main caregivers of children with ASD, consideration of their gender characteristics, and the importance of providing relevant information during pandemic. Future studies examining the pandemic long-term effects are needed

Psychoactive substances, alcohol and tobacco consumption in HIV-infected outpatients

International audienc

Screen time and associated risks in children and adolescents with autism spectrum disorders during a discrete COVID-19 lockdown period

International audienceBackground: The COVID-19 pandemic may affect the screen time of children and adolescents with Autism Spectrum Disorders (ASD). This study aimed to examine the screen time of children and adolescents with ASD during a discrete lockdown period in France and identify risk factors for excessive screen time. Methods: The study sample consisted of 249 ASD subjects, 3–17 years of age, enrolled in the ELENA cohort. Information about the screen time was collected using the COVID-19 questionnaire specially created for this study. The clinical, socio-demographic and familial characteristics were collected from the last ELENA follow-up visit. Results: More than one third of subjects exceeded recommended levels of screen time and almost half of parents reported that their child spent more time using screen since COVID-19 pandemic beginning. Excessive screen time was significantly related to age with higher screen time in adolescents. Risk factors for excessive screen time were high withdrawn behaviors and low socioeconomic status for children, and older age and male gender for adolescents. Conclusion: These results imply to adapt the recommendations already formulated in general population concerning the good use of screens in youth with ASD. Specific recommendations and suitable guidance are needed to help children and adolescents with ASD and their parents implement the more optimal use of screen time activities for educational, therapeutic and social goals. Trial registration number: NCT02625116. Copyrigh

Lopinavir/ritonavir initiated at 7 days of life impairs infant growth

International audienc

Human papillomavirus (HPV) shedding in breast milk from African women living with HIV

International audienceBackground: Little is known about human papillomavirus (HPV) shedding in human breast milk.Objective: To investigate HPV shedding in mature breast milk specimens collected from breastfeeding African women living with HIV-1 and not receiving antiretroviral treatment. Design: 62 African women enrolled in the ANRS 12174 trial participated in this study. 79 lactoserum specimens obtained from right and/or left breasts from 42 Zambian women as well as lactosera and cell pellets from 40 milk samples collected from right and left breasts among 20 Ugandan women were tested for HPV using the INNO-LiPA HPV Genotyping Extra II assay.Results: HPV DNA was detected in 9 (11.4%) lactoserum specimens collected from 8 (19.0%) Zambian women. Fourteen (17.5%) samples from 5 (25%) Ugandan women were positive for HPV detection. Differences in HPV type identification between the two breasts as well as between lactoserum and cell pellet were oberved. Overall, 13 (21.0%) of the 62 women included in this study had detectable HPV DNA in their breast milk, representing 11 HPV types, including high-risk, probable high-risk and low-risk types.Conclusion: This study confirms that HPV can be frequently detected in breast milk in HIV-infected women. Further studies are needed to understand the way by which maternal milk can shed HPV

Recurrent Severe Subclinical Mastitis and the Risk of HIV Transmission Through Breastfeeding

International audienceSubclinical mastitis (SCM) is an important risk factor of postnatal HIV-1 transmission that is still poorly understood. A longitudinal sub-study of the ANRS12174 trial including 270 breastfeeding mothers in Lusaka, Zambia measured sodium (Na + ) and potassium (K + ) in archived paired breast milk samples collected at week 14, 26 and 38 postpartum to determine cumulative incidence of SCM and the effects of recurrent severe SCM on HIV-1 shedding in breast milk. A nested retrospective cohort study including 112 mothers was also done to determine longitudinal effects of SCM on four pro-inflammatory cytokines; IL6, IL8, IP10 and RANTES. The cumulative incidence for any SCM (Na + /K + ratio &gt; 0.6) and severe SCM (Na + /K + ratio &gt; 1) were 58.6% (95%CI: 52.7 – 64.5) and 27.8% (95%CI: 22.5 – 33.1), respectively. In majority of affected mothers (51.4%) severe SCM was recurrent. Both breasts were involved in 11.1%, 33.3% and 70% of the mothers with a single episode, 2 and 3 episodes respectively. In affected breasts, an episode of severe SCM resulted in steep upregulation of the four cytokines considered (IL8, IP10, RANTES and IL6) compared to: before and after the episode; contralateral unaffected breasts; and SCM negative control mothers. Recurrent severe SCM significantly increased the odds of shedding cell-free HIV-1 in breast milk (OR: 5.2; 95%CI: 1.7 – 15.6) whereas single episode of severe SCM did not (OR: 1.8; 95%CI: 0.8 – 4.2). A Na + /K + ratio &gt; 1 indicative of severe SCM is an excellent indicator of breast inflammation characterized by a steep, localized and temporal upregulation of several pro-inflammatory cytokines that favor HIV-1 shedding in mature breast milk and may facilitate postnatal HIV-1 transmission through breastfeeding