Analysis of whole-body MRI artifacts in a pediatric population with a special emphasis on the effect of hands position.

PURPOSE: The purpose of this retrospective study was to determine the prevalence of artifacts on whole-body (WB) magnetic resonance imaging (MRI) examination in pediatric patients and identify their causes. MATERIALS AND METHODS: A total of 107 pediatric patients who underwent a total of 107 WB-MRI examinations, including short-tau inversion recovery (STIR) and T1-weighted sequences, were included. There were 62 girls and 45 boys with a mean age of 11 ± 3 (SD) years (age range: 2-16 years). WB-MRI examinations were analyzed for the presence of artifacts on STIR and T1-weighted sequences. Artifacts were further assigned to one of eight categories (motion, partial volume, cross-talk, phase sampling, susceptibility, equipment, noise, and "other") and 19 anatomical sites by a 4-year resident. Prevalence of artifacts were analyzed especially according to hands position during the examination for the upper limbs and patients' age. Age was expressed as a binary variable using median age (10 years) as the cut-off value. All qualitative variables were compared using chi-square test. RESULTS: A total of 3436 artifacts were found. The STIR sequences showed more "noise" artifacts (93/1038; 8.96%) and more "cross-talk" (102/1038; 9.83%) artifacts than T1-weighted sequences (12/1038 [1.16%] and 7/1038 [0.67%], respectively) (P < 0.001 for both). T1-weighted sequences showed more "equipment" (84/1038; 8.09%) and "stair-step" (a subset of "other") (41/1038; 3.95%) artifacts than the STIR sequences (39/1038 [3.76%] and 21/1038 [2.02%], respectively) (P < 0.001 and P = 0.01, respectively). T1-weighted sequences showed fewer artifacts on the wrists when the hands were under the bottom (P = 0.001). T1-weighted sequences showed less "equipment" artifacts when the hands were alongside the body (22/296; 7%) than on the abdomen (48/432; 11%) or under the bottom (14/128; 11%) (P < 0.001). STIR sequences showed more "motion" artifacts when the hands were on the abdomen (54/432; 13%) than alongside the body (30/296; 10%) or under the bottom (15/128; 12%) (P < 0.001). WB-MRI examinations had more "susceptibility" artifacts (38/960; 4%) and more "equipment" artifacts (81/960; 8.4%) in patients older than 10 years than in those under 10 years (23/752 [3.1%] and 42/752 [5.6%]) (P = 0.01 and P < 0.001, respectively). CONCLUSION: Artifacts on WB-MRI do not affect coronal STIR and T1-weighted sequences equally, so the use of both sequence types appears useful. Hands position should be considered with respect to both diagnostic benefit and safety.

Clinical course and cost assessment of infants with a first episode of acute bronchiolitis presenting to the emergency department: Data from the GUERANDE clinical trial.

INTRODUCTION: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED). METHODS: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority. RESULTS: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France. DISCUSSION: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.

Factors Associated With Being Overweight and Obesity in People Living With Human Immunodeficiency Virus on Antiretroviral Therapy: Socioclinical, Inflammation, and Metabolic Markers.

BACKGROUND: We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). METHODS: Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5-24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, <50 copies/mL) and maintained it through 36 months of treatment were selected. Clinical, immunovirological, and socioeconomic data and inflammation (high-sensitivity C-reactive protein, CXCL10, CXCL8, interleukin 6, soluble tumor necrosis factor receptors 1 and 2, soluble CD14, and soluble CD16) and serum metabolic (glucose, insulin, lipid profile, adiponectin, and leptin) markers were assessed. Factors associated with becoming overweight (BMI, 25-29.9) or obese (BMI, ≥30) at 36 months were assessed using multivariate logistic regression models. RESULTS: After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21-23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. CONCLUSION: Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

Abusive Head Trauma in Day Care Centers.

BACKGROUND: Abusive head trauma (AHT) warrants particular attention in terms of prevention. One of the key questions asked is how often AHT occurs in infant day care centers compared with private parental or nonparental homes. To investigate this, we studied the caretaking arrangement and child's location at the time of injury in a cohort of cases involving AHT from the courts. METHODS: This multicenter retrospective study covering an 18-year period included all medical and court records of 323 children (2.5 months to 3 years) with AHT, confirmed by the authors acting as medical experts. All markers for abuse and forensic written reports were analyzed by using a standardized data collection tool. The usual child care arrangement and the child's location at the time of injury were noted. The percentage of day care centers found in the study was compared to the expected rate in the French population (19.5%) by using the χ2 test. RESULTS: In 317 AHT cases (98.5%), the assault occurred in a private home (4 in other indoor settings and 1 with missing data). In only 1 case, shaking occurred in a day care center when the nurse was alone with the infant for a few minutes. In 317 cases (98.5%), the usual child care arrangement was by a single adult in charge of 1 or more children. CONCLUSIONS: The fact that AHT is an unusual occurrence in day care centers could help social service agencies make decisions in terms of prevention. Recent government policies regarding stay-at-home orders during a pandemic have given this issue new relevance.

pCLIF-SOFA is a reliable outcome prognostication score of critically ill children with cirrhosis: an ESPNIC multicentre study.

BACKGROUND AND AIMS: Data on outcome of critically ill children with cirrhosis are scarce. We aimed to evaluate the prognostic accuracy of sequential organs scoring systems in children with cirrhosis admitted to Paediatric Intensive Care Units (PICU). METHODS: We performed a multicentre retrospective analysis of children with cirrhosis admitted into four European PICUs between 2011 and 2016. Investigators were members of the ESPNIC liver failure and support working group. Paediatric End-Stage Liver Disease (PELD) and paediatric chronic liver failure sequential organ failure assessment score (pCLIF-SOFA) diagnostic accuracy for 28- and 60-day liver transplantation, 28-day mortality and 60-day composite outcome (ie. death or liver transplantation) were tested. RESULTS: One-hundred-and-thirty children were included. The main causes for PICU admission were acute-on-chronic liver failure (ACLF), gastrointestinal bleeding and sepsis. Twenty-nine percent died and 22.3% were transplanted by day-60 after PICU admission. On multivariable analysis, pCLIF-SOFA was the only predictor of mortality at day-28 and of composite outcome. Both pCLIF-SOFA and ACLF were independently associated with emergent liver transplantation. The pCLIF-SOFA score higher than 9 well predicted a 28-day mortality with a sensitivity of 87.8% and a specificity of 77.3%. A pCLIF-SOFA score higher than 7 was independently associated with liver transplantation on day-60. Stage 3 AKI assessed with KDIGO classification was significantly associated with 28-day mortality. CONCLUSIONS: Half of critically ill cirrhotic children admitted to PICU either died or were transplanted within the initial 28-day period. On admission pCLIF-SOFA score accurately identify patients transplanted at day-28 and day-60 to those alive without LT and is associated with 28-day mortality and composite outcome at day-60.

Classic Metaphyseal Lesions among Victims of Abuse.

OBJECTIVE: To use legal statements by perpetrators to gain new insights into the causative mechanism of classic metaphyseal lesion (CML). The CML, so called "corner fracture," is considered a highly specific marker for abuse in infants. However, the precise correlation between CMLs and abusive head trauma is still unknown. STUDY DESIGN: In this retrospective observational study, we selected 67 cases with at least 1 CML from a 15-year cohort of legally prosecuted child abuse cases. Their clinical, radiologic, and forensic records were analyzed. In 27 cases, the perpetrator confessed to abusing the child and described the events. Potential associations with subdural hematoma and with confession were evaluated using 2 separate binary logistic regression models. RESULTS: All 67 infants showed other signs of abuse. Median age was 3.4 months. Over 65% had multiple CMLs. Knees and ankles were predominantly involved (64%). Only CMLs of the shoulder were significantly associated with subdural hematoma (P = .03). Different-age fractures were more common in the nonsubdural hematoma group (P = .01). In the group with confessions, perpetrators admitted inflicting violent indirect skeletal forces (torsion, traction, compression, and forced movements). The most common circumstance was diapering (44%), reported by male perpetrators only (P = .03) followed by dressing/undressing (30%). The violence was habitual in 67% of cases. CONCLUSIONS: This unique forensic case series shows that CMLs are caused by violent acts inflicted most during physical care of infants. The frequency of habitual violence responsible for CMLs deserves greater attention.

Genomic Alterations and Complex Subclonal Architecture in Sporadic GH-Secreting Pituitary Adenomas.

Purpose: The molecular pathogenesis of growth hormone-secreting pituitary adenomas is not fully understood. Cytogenetic alterations might serve as alternative driver events in GNAS mutation-negative somatotroph tumors. Experimental Design: We performed cytogenetic profiling of pituitary adenomas obtained from 39 patients with acromegaly and four patients with sporadic gigantism by using array comparative genomic hybridization analysis. We explored intratumor DNA copy-number heterogeneity in two tumor samples by using DNA fluorescence in situ hybridization (FISH). Results: Based on copy-number profiles, we found two groups of adenomas: a low-copy-number alteration (CNA) group (<12% of genomic disruption, 63% of tumors) and a high-CNA group (24% to 45% of genomic disruption, 37% of tumors). Arm-level CNAs were the most common abnormalities. GNAS mutation-positive adenomas belonged exclusively to the low-CNA group, whereas a subgroup of GNAS mutation-negative adenomas had a high degree of genomic disruption. We detected chromothripsis-related CNA profiles in two adenoma samples from an AIP mutation-positive patient with acromegaly and a patient with sporadic gigantism. RNA sequencing of these two samples identified 17 fusion transcripts, most of which resulted from chromothripsis-related chromosomal rearrangements. DNA FISH analysis of these samples demonstrated a subclonal architecture with up to six distinct cell populations in each tumor. Conclusion: Somatotroph pituitary adenomas display substantial intertumor and intratumor DNA copy-number heterogeneity, as revealed by variable CNA profiles and complex subclonal architecture. The extensive cytogenetic burden in a subgroup of GNAS mutation-negative somatotroph adenomas points to an alternative tumorigenic pathway linked to genomic instability.

Polycystic Ovary Syndrome in Adolescents: Which MR Imaging-based Diagnostic Criteria?

Purpose To evaluate the validity and reproducibility of magnetic resonance (MR) imaging-based ovarian morphologic measurements for diagnosis of polycystic ovary syndrome (PCOS) in adolescents. Materials and Methods This case-control study included 110 adolescent girls (age range, 13-17 years) who underwent pelvic MR imaging in 2006-2015. The case group included girls with high (n = 40, hyperandrogenism and oligomenorrhea or amenorrhea), intermediate (n = 8, hyperandrogenism), or low (n = 7, oligomenorrhea or amenorrhea) suspicion of PCOS. Control subjects were 55 age-matched (± 2 years) girls with no clinical hyperandrogenism, oligomenorrhea, or amenorrhea. The validity (sensitivity, specificity, and area under the receiver operating characteristic curve [AUC]) of the number of follicles per ovary (FPO) measuring 9 mm or smaller (FPO-9) and FPO measuring 5 mm or smaller (FPO-5), ovarian volume (OV), sphericity index, peripheral distribution of follicles, and absence of a dominant follicle were determined, with girls who were highly suspected of having PCOS compared with control subjects as the reference. Two radiologists independently measured these criteria in 50 girls who were suspected of having PCOS to assess reproducibility (κ and intraclass correlation coefficients [ICCs]). Results All criteria except sphericity index and absence of a dominant follicle were significantly associated with the level of suspicion of PCOS (P ≤ .05). The AUCs for FPO-9 (0.78; 95% confidence interval [CI]: 0.68, 0.87), FPO-5 (0.73; 95% CI: 0.62, 0.83), and OV (0.77; 95% CI: 0.68, 0.87) were significantly greater than 0.5; that was not true for sphericity index (AUC, 0.58; 95% CI: 0.47, 0.70). Sensitivity and specificity for peripheral distribution of follicles were 33% (95% CI: 19%, 49%) and 95% (95% CI: 85%, 99%), respectively; for absence of a dominant follicle, they were 90% (95% CI: 76%, 97%) and 27% (95% CI: 16%, 41%), respectively. Reproducibility was almost perfect for OV (ICC, 0.89), substantial for absence of a dominant follicle (κ, 0.74), moderate for FPO-9 (ICC, 0.54) and FPO-5 (ICC, 0.61), and fair for peripheral distribution of follicles (κ, 0.37). Conclusion The most accurate MR imaging-based diagnostic criteria for PCOS were OV, FPO-9, and peripheral distribution of follicles; however, reproducibility of these measures was moderate, except that for OV (ICC, 0.89). © RSNA, 2017 Online supplemental material is available for this article.

Effect of Nebulized Hypertonic Saline Treatment in Emergency Departments on the Hospitalization Rate for Acute Bronchiolitis: A Randomized Clinical Trial.

Importance: Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED). Objective: To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis. Design, Setting, and Participants: The Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included. Interventions: Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart. Main Outcomes and Measures: Hospital admission rate in the 24 hours after enrollment. Results: Of the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, -3.2%; 95% CI, -8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (-3.1 [3.2]) than in the NS group (-2.4 [3.3]) (adjusted difference, -0.7; 95% CI, -1.2 to -0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events. Conclusions and Relevance: Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group. Trial Registration: clinicaltrials.gov Identifier: NCT01777347.

Pseudofeeders on fetal magnetic resonance imaging predict outcome in vein of Galen malformations.

OBJECTIVE: Although vein of Galen aneurysmal malformations (VGAM) can be diagnosed in the fetus, the challenge is predicting the occurrence of its 2 major complications: cardiopulmonary failure and encephalomalacia. This study attempts to determine which fetal brain magnetic resonance imaging (MRI) features might be used to predict the development of these complications at birth. METHODS: The cohort was extracted from a prospectively assembled database of VGAM cases managed at a single referral center from 2000 to 2014. Of 251 patients with VGAM, 83 cases were diagnosed prenatally. A total of 58 patient charts having at least 1 fetal MRI were reviewed. Patterns of brain parenchyma, hydrocephalus, and so-called middle cerebral artery (MCA) "pseudofeeders" were correlated with cardiac failure, pulmonary hypertension, and encephalomalacia at birth. RESULTS: The median gestational age at fetal MRI was 32.3 weeks of pregnancy (±2.3). Nine fetuses (16%) had encephalomalacia. Thirty-one fetuses (53%) had MCA pseudofeeders. Twenty-six fetuses (45%) had prenatal hydrocephalus. Prenatal MCA pseudofeeders were a risk factor for encephalomalacia at birth (p = 0.001). MCA pseudofeeders and hydrocephalus were risk factors for both severe cardiac failure (p = 0.01 and p = 0.04, respectively) and severe pulmonary hypertension (p = 0.014 and p = 0.05, respectively) at birth. INTERPRETATION: MCA pseudofeeders are the result of impaired cerebral blood flow, and are thus a risk factor for further brain melting at birth. Their presence can be used for informing parents and as an aid in management decisions. Ann Neurol 2017;81:278-286.

A Finger-Stick Whole-Blood HIV Self-Test as an HIV Screening Tool Adapted to the General Public.

BACKGROUND: In 2013, the French Health Authority approved the use of HIV self-tests in pharmacies for the general public. This screening tool will allow an increase in the number of screenings and a reduction in the delay between infection and diagnosis, thus reducing the risk of further infections. We previously compared 5 HIV-self test candidates (4 oral fluid and one whole blood) and demonstrated that the whole blood HIV test exhibited the optimal level of performance (sensitivity/specificity). We studied the practicability of an easy-to-use finger-stick whole blood HIV self-test "autotest VIH®", when used in the general public. METHODS AND MATERIALS: This multicenter cross-sectional study involved 411 participants from the Parisian region (AIDES and HF association) between April and July 2014 and was divided into 2 separate studies: one evaluating the capability of participants to obtain an interpretable result using only the information notice, and a second evaluating the interpretation of test results, using a provided chart. RESULTS: A total of 411 consenting participants, 264 in the first study and 147 in the second, were included. All participants were over 18 years of age. In the first study, 99.2% of the 264 participants correctly administered the auto-test, and 21.2% needed, upon their request, telephone assistance. Ninety-two percent of participants responded that the test was easy/very easy to perform, and 93.5% did not find any difficulty obtaining a sufficient good quantity of blood. In the second study, 98.1% of the 147 participants correctly interpreted the results. The reading/interpretation errors concerned the negative (2.1%) or the indeterminate (3.3%) auto-tests. CONCLUSIONS: The success rate of handling and interpretation of this self-test is very satisfactory, demonstrating its potential for use by the general public and its utility to increase the number of opportunities to detect HIV patients.

Does pregnancy affect the early response to cART?

OBJECTIVE: A part of women starting antiretroviral therapy during pregnancy fail to attain undetectable viral load by delivery. Here we studied whether pregnancy affects the early immunovirological response to combined antiretroviral therapy (cART), taking into account treatment duration and baseline characteristics. DESIGN: Antiretroviral-naive women initiating cART since 2004 and followed in three French ANRS multicenter HIV cohorts (French Perinatal Cohort, PRIMO and COPANA). METHODS: The early virological response (at 1, 3 and 6 months) and immunological increase after cART initiation were compared between women starting cART during (n = 708) and outside (n = 110) pregnancy. Relative risks were estimated in multivariate models adjusted for treatment duration, baseline viral load and CD4, sociodemographic factors and chronic hepatitis B. CD4 increases were compared by using mixed models. RESULTS: Only 63.8% of treated pregnant women attained a viral load less than 50 copies/ml by delivery. Similarly to nonpregnant women, nearly 90% of pregnant women reached a viral load less than 400 copies/ml at M3 [adjusted RR: 1.0 (95% confidence interval 0.7-1.4)], and nearly 100% at M6 following cART initiation [0.9 (0.4-1.9)]. viral load less than 50 copies/ml was attained by 61.5% of pregnant versus 67.9% of nonpregnant women at M3 (P = 0.26), and by 82.1 versus 87.0% at M6 (P = 0.48). CD4 recovery (both number and percentage) was similar in pregnant and nonpregnant women. Results were similar for the subset of women starting a boosted protease inhibitor-containing cART. CONCLUSION: Pregnancy does not affect the virological response to cART below 400 copies/ml, or CD4 increase. The main reason for pregnant women not achieving viral load less than 50 copies/ml at delivery appears to be a short duration of treatment.

Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost?

BACKGROUND: The association between combination antiretroviral (cARV) therapy use by human immunodeficiency virus (HIV)-infected women during pregnancy and risk of prematurity is still controversial. We explored this question, focusing on the initiation of ritonavir-boosted protease inhibitors (PIs) during pregnancy, which is now standard care. METHODS: Trends in prematurity (<37 gestational weeks) were studied among all singleton pregnancies in the Agence Nationale de Recherche sur le SIDA (ANRS) French Perinatal Cohort from 1990 through 2009 (n = 13 271). In-depth analysis was conducted in a more detailed substudy of the cohort, among women starting PI-based ARV therapy during pregnancy (n = 1253). Multivariable analysis adjusted for immunovirological status and known risk factors for prematurity. RESULTS: Prematurity increased from 9.2% during 1990-1993 (no therapy) and 9.6% during 1994-1996 (mostly zidovudine monotherapy) to 12.4% during 1997-1999 (dual-nucleoside analog therapy) and 14.3% during 2005-2009 (routine cARV therapy; P < .01). Prematurity was associated with cARV therapy, compared with zidovudine monotherapy, with an adjusted odds ratio of 1.69 (95% confidence interval [CI], 1.38-2.07; P < .01) when accounting for maternal age, intravenous drug use, geographic origin, and CD4 cell count. During 2005-2009, the prematurity rate was higher with boosted than with nonboosted PI therapy started during pregnancy (14.4% vs 9.1% [P = .05]; adjusted hazard ratio, 2.03 [95% CI, 1.06-3.89; P = .03] in multivariate analysis). The difference concerned mainly induced preterm delivery for maternal or fetal indications (5.6% vs 1.6%; P = .02), CONCLUSIONS: The prematurity rate among HIV-infected pregnant women was twice that in the general population in France; this was not entirely explained by sociodemographic characteristics. Prematurity was independently associated with cARV therapy and, particularly, with the initiation of ritonavir-boosted PI therapy during pregnancy.

No relation between in-utero exposure to HAART and intrauterine growth retardation.

BACKGROUND: The use of HAART during pregnancy is now standard care to prevent mother-to-child HIV transmission in developed countries. There is controversy about its impact on low birth weight. OBJECTIVE: To evaluate the impact of antiretroviral therapy during the pregnancy on birth weight, length and head circumference. METHODS: The study was performed in uninfected infants born to HIV-1-infected mothers, enrolled from 1990 to 2006 in the Agence Nationale de Recherche sur le SIDA French Perinatal Cohort CO1. We excluded mothers who used illicit drugs during pregnancy or had no prenatal care before the third trimester, twins and stillbirths. We used Z-scores adjusted for gestational age and sex. RESULTS: In 8192 mother-infant pairs, the mean birth weight Z-scores increased between 1990 and 1997 and then remained stable until 2006. There was no significant relation between the type of antiretroviral therapy and the proportion of small for gestational age (birth weight Z-score < or = -2SD), which was 4% overall. Infants exposed to HAART compared with monotherapy had a lower mean birth weight Z-scores (difference -0.09, 95% confidence interval -0.15 to -0.02); however, there was no difference between HAART exposure in 2005-2006 and monotherapy in 1999-2004, which corresponded to standard care during each period, respectively. Length or head circumference Z-scores were not associated with antiretroviral therapy exposure. Among pregnancies with HAART, there was no relation between the duration and type of therapy and the anthropometric parameters. CONCLUSION: Our findings in a large cohort suggest that HAART during pregnancy does not increase the incidence of infants who are small for gestational age.

Prevention of mother-to-child HIV transmission: similar access for sub-Sahara African immigrants and for French women?

OBJECTIVE: : To investigate whether mother-to-child transmission (MTCT) management and rate differed between African immigrants and French-born women delivering in France. METHODS: : MTCT strategies were studied among human immunodeficiency virus type 1-infected women delivering between 1984 and 2007 in the multicenter French Perinatal Cohort, according to geographical origin. RESULTS: : Among 9245 pregnancies (in 7090 women), the proportion of African mothers increased from 12% in 1984-1986 to 64% in 2003-2004. African women had later access to care than French women, even in recent years (1997-2004). They more often discovered their HIV infection during pregnancy (40.6 vs. 11.5%, P < 0.001), started prenatal care in the third trimester (14.1 vs. 9.8%, P < 0.001) and started antiretroviral therapy after 32 weeks gestation (7.6 vs. 4.1%, P < 0.001). The association with late treatment initiation disappeared when adjusted for late HIV diagnosis and prenatal care (adjusted odds ratio 1.0, 95% confidence interval 0.7-1.4). African and French women did not differ in terms of access to highly active antiretroviral therapy, nor for substandard management such as vaginal delivery with uncontrolled viral load, lack of intrapartum and postpartum treatment or breastfeeding. The MTCT rate was higher for African than for French women receiving antiretroviral therapy (1.8 vs. 0.8%, P = 0.02), but the difference was no longer significant after adjustment for main transmission risk factors (adjusted odds ratio = 1.7, 95% confidence interval 0.8-3.7, P = 0.17). MTCT did not differ among 2110 term deliveries with maternal viral load less than 400 copies/ml, (0.8 vs. 0.6%, P = 0.5). CONCLUSION: : African immigrants more often had late HIV screening in pregnancy than French-born women, but had similar access to MTCT prevention, once the infection was diagnosed.

Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS French Perinatal Cohort.

OBJECTIVE: To identify factors associated with mother-to-child HIV-1 transmission (MTCT) from mothers receiving antenatal antiretroviral therapy. DESIGN: The French Perinatal Cohort (EPF), a multicenter prospective cohort of HIV-infected pregnant women and their children. METHODS: Univariate analysis and logistic regression, with child HIV status as dependent variable, were conducted among 5271 mothers who received antiretroviral therapy during pregnancy, delivered between 1997 and 2004 and did not breastfeed. RESULTS: The MTCT rate was 1.3% [67/5271; 95% confidence interval (CI), 1.0-1.6]. It was as low as 0.4% (5/1338; 95% CI, 0.1-0.9) in term births with maternal HIV-1 RNA level at delivery below 50 copies/ml. MTCT increased with viral load, short duration of antiretroviral therapy, female gender and severe premature delivery: 6.6% before 33 weeks versus 1.2% at 37 weeks or more (P < 0.001). The type of antiretroviral therapy was not associated with transmission. Intrapartum therapy was associated with four-fold lower MTCT (P = 0.04) in case of virological failure (> 10 000 copies/ml). Elective cesarean section tended to be inversely associated with MTCT in the overall population, but not in mothers who delivered at term with viral load < 400 copies/ml [odds ratio (OR), 0.83; 95% CI, 0.29-2.39; P = 0.37]. Among them, only duration of antenatal therapy was associated with transmission (OR by week, 0.94; 95% CI, 0.90-0.99; P = 0.03). CONCLUSIONS: Low maternal plasma viral load is the key factor for preventing MTCT. Benefits in terms of MTCT reduction may be expected from early antiretroviral prophylaxis. The potential toxicity of prolonged antiretroviral use in pregnancy should be evaluated.

Change to a once-daily combination including boosted atazanavir in HIV-1-infected children.

BACKGROUND: Pediatric experience with atazanavir combined with antiretroviral drugs administered once daily is very limited. OBJECTIVE: The objective of this prospective, single-center observation study was to evaluate efficacy and tolerance of once-a-day ritonavir-boosted atazanavir, including treatment. RESULTS: Antiretroviral treatment of 23 children and adolescents with a median age of 16 years (range, 10-19 years) was changed to a single daily dose of a combination of ritonavir-boosted atazanavir and 2 other nucleoside or nonnucleoside analogs. The single daily dosing was expected to improve adherence to treatment. The mean follow-up period was 12 months (range, 6-17 months). At the time of the treatment switch, the previous treatment had been effective in 11 children (plasma viral load [pVL] <50 copies/mL) and not effective in 12 (pVL >50 copies/mL). None of the viral genotypes had resistance to atazanavir. The susceptibility score for the drugs used in combination with atazanavir (GSS) was at least 1.5 in 12 of 20 children. The atazanavir dose was 300 mg per day for children weighing more than 50 kg and 200 mg per day for children weighing 30 to 50 kg, in all cases associated with 100 mg ritonavir. During follow up, the mean atazanavir plasma concentration at 12 to 15 hours was 2.18 +/- 1.19 mg/L. Tolerance was good in most patients, but 4 children chose to stop treatment because of icterus (n = 2) or persistent nausea and vomiting (n = 2). In 6 of the 12 children in whom treatment was not virologically effective before the switch, pVL was below 50 copies/mL after 1 to 3 months of treatment. Poor compliance and virologic failure persisted in the other 6 children. Seven of the 11 children with good virologic control before the switch continued to have undetectable pVL but 4 experienced virologic failure after 1, 1, 3 or 12 months of treatment despite good compliance. Insufficient antiviral potency of associated drugs could have been the cause of 2 of these 4 unexpected virologic failures. CONCLUSION: In these children with extensive previous treatment, the change to a once-daily treatment, including ritonavir-boosted atazanavir, was associated with a significant risk of virologic failure.

Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years.

The pharmacokinetics of lopinavir were investigated by the use of a population approach performed with the nonlinear mixed effect modeling program NONMEM and 157 children ranging in age from 3 days to 18 years. The pharmacokinetics of lopinavir were well described by a one-compartment model in which the absorption and the elimination rate constants were equal. Typical population estimates of the apparent volume of distribution (V/F) and plasma clearance (CL/F) were 24.6 liters and 2.58 liters/h, respectively. The lopinavir V/F and CL/F were both related to body weight (BW), with an important increase in weight-normalized CL/F for the lowest BW. Combined treatment with lopinavir and nevirapine was found to increase the CL/F. The lopinavir CL/F was also age and sex related, as a 39% increase was observed after the age of 12 years for boys compared to the CL/F for girls. The consequences of these pharmacokinetic discrepancies and the necessity to modify the currently recommended dosage regimen should be further investigated.

Predictive factors of virologic success in HIV-1-infected children treated with lopinavir/ritonavir.

Predictive factors of the virologic success of the use of lopinavir/ritonavir (LPV/r) in HIV-infected children are unknown, especially in children who have been pretreated with protease inhibitors (PIs). This longitudinal, single-center, observational study included 69 children (21 PI-naive and 48 PI-experienced) who had received LPV/r for at least 3 months. The mean (+/- SD) age was 10.3 +/- 4.8 years, and the mean baseline of CD4 percentage and HIV-1 RNA was 14.9% +/- 9.8% and 4.8 +/- 1.05 log10 copies/mL, respectively. The mean duration of follow-up was 16.5 +/- 8.3 months. At 6, 12, and 18 months, 52%, 57%, and 49% of all children, respectively, had a viral load less than 50 copies/mL. The risk of virologic failure, defined as 2 consecutive viral loads greater than 1000 copies/mL, was significantly higher when the children were previously treated with PIs and when the baseline LPV mutation score exceeded 3 mutations. In the pretreated children, the ratio of the plasma LPV maximal concentration to the baseline LPV score mutation was also associated with failure, independently of resistance score. Finally, in children failing an LPV-containing regimen, accumulation of additional PI-associated resistance mutations was evidenced in viral isolates from children with prior PI treatment, even with viral replication levels less than 10,000 copies/mL. In pretreated children, LPV plasma levels should be optimized in an attempt to achieve sufficient drug concentrations to overcome the resistance level.

Maternal viral load and rate of disease progression among vertically HIV-1-infected children: an international meta-analysis.

OBJECTIVE: To evaluate whether maternal human immunodeficiency virus type 1 (HIV-1) RNA levels in the serum/plasma of mothers at or close to the time of delivery affects the rate of disease progression among vertically HIV-1-infected children and whether it correlates with other parameters affecting infant disease progression. METHODS: International meta-analysis of eight studies with 574 HIV-1 infected infants with available maternal HIV-1 RNA measurements at or close to delivery and clinical follow-up. The primary outcome was disease progression (stage C disease or death, n = 178). Cohort-stratified Cox models were used. RESULTS: Higher maternal HIV-1 RNA level at or close to delivery significantly increased disease progression risk [hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.04-1.52 per 1 log10 increase; P = 0.02) with a borderline effect on mortality (HR, 1.26; 95% CI, 0.96-1.65; P = 0.10]. The association with disease progression risk was strong in the first 6 months of life (HR, 1.77; 95% CI, 1.28-2.45; P = 0.001), but not subsequently (HR, 1.03; 95% CI, 0.81-1.30). Maternal HIV-1 RNA, early infant HIV-1 RNA (at 30-200 days after birth) and infant CD4 were independent predictors of disease progression in the first 6 months. Maternal HIV-1 RNA at or close to delivery correlated with early infant HIV-1 RNA (r = 0.26, P < 0.001). Effects were independent of maternal and infant treatment. CONCLUSIONS: Higher maternal HIV-1 RNA at or close to delivery strongly predicts disease progression for HIV-1-infected infants, especially in their first 6 months of life and correlates with the early peak of viremia in the infected child.