Eric Lachassinne

European registry of babies born to mothers with antiphospholipid syndrome

Objectives This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the childs immunological profile with their mothers. Methods A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years. Results 134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β2 glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mothers antibodies before 6 months of age (p<0.05). Conclusion Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.

European register of babies born to mothers with antiphospholipid syndrome

This prospective multicentric register was initiated by the European Forum of Antiphospholipid Antibodies (APL) in 2003 after approval by local ethic committees. This register allows the investigation of infants after written informed parental consent. It collects mothers’ clinical pattern of antiphospholipid syndrome (APS), course and outcome of pregnancy, treatment and immunological status. For the babies, clinical and immunological examinations are performed at birth; neuro-developmental conditions followed up to five years. A re-evaluation of lupus anticoagulant (LA), anticardiolipin (ACL) or other antibodies will be done if they are positive at birth to follow their kinetics. A descriptive and a case control study of babies with versus without APL at birth will be possible after the inclusion of 300 cases.

Tuberculosis in adolescents: A French retrospective study of 52 cases.

Background: The only available data about tuberculosis (TB) among adolescents date back to the 1980s, although the incidence of tuberculosis has been increasing in this age group. Methods: Medical records were reviewed for all adolescents aged 12 to 18 years hospitalized with the diagnosis of TB in Avicenne/Jean Verdier Teaching hospital (Seine-Saint-Denis, suburb of Paris) between September 2000 and December 2004. Results: Of the 52 patients identified, 52% were female. Median age at diagnosis was 15 years (range, 12–18 years). The proportion of adolescents known to be born abroad was 90%. Diagnoses resulted from the examination of a sick child in 79% of cases, a case contact investigation of an adult suspected of having TB in 19% and routine tuberculin skin test in 2%. Twenty-seven of 52 patients (52%) had isolated pulmonary disease. Sixteen patients (31%) had pulmonary and extrapulmonary TB and 8 cases (17%) had exclusively extrapulmonary disease. The site of extrapulmonary TB included pleural (n = 8), meningitis (n = 4), lymph node (n = 4), peritoneal (n = 5), osteoarticular (n = 3) and genitourinary (n = 1). TB was confirmed by the isolation of Mycobacterium tuberculosis from sputum (n = 21), gastric aspirate (n = 8), bone (n = 1) or cerebrospinal fluid (n = 2). No case had a relapse or recurrence of disease in median 3.2 years of follow up. Conclusions: Our results indicate that demographic and clinical characteristics of adolescents with TB differed from adults and children. A specific approach to the prevention and treatment of TB in adolescents is absolutely necessary.

Autism spectrum disorders in babies born to mothers with antiphospholipid syndrome

OBJECTIVES To evaluate the outcomes of babies born to mothers with primary antiphospholipid syndrome and to compare to the outcomes of babies of mothers with systemic lupus erythematosus. METHODS A retrospective study from 2003 to 2010 assessing the clinical characteristics and psychomotor development, as well as the immunological data, of children born to mothers with antiphospholipid syndrome (APS) (group 1) and systemic lupus erythematosus (group 2). RESULTS Group 1 consisted of 36 children born to mothers (n = 26) with a primary APS. Autism spectrum disorders occurred in 3 children from group 1 and all of them had persistent anti-β2GP1 IgG antibodies. Group 2 consisted of 12 children born to mothers (n = 9) with lupus erythematosus. Three children experienced cutaneous neonatal lupus, but there were no neurodevelopmental disorders. Comparing children of groups 1 and 2, no significant difference was found with regard to the parameters at birth or during follow-up. The children in group 2 had antinuclear antibodies more frequently (p < 0.05). CONCLUSION Autism spectrum disorders could be observed in babies born to mothers with antiphospholipid syndrome, but there is no risk of thrombosis. KEY MESSAGES Neonatal lupus is well-known complication in children born to mothers with systemic lupus erythematosus, but there is no risk of thrombosis in APS-exposed children. In children of APS mothers the rate of prematurity and small-for-gestational age weight remain high even in treated pregnancy. The presence of several cases of autism spectrum disorders in APS-exposed children could be related to mothers antibodies exposition, but need to be confirmed.

Germline gain-of-function mutations of ALK disrupt central nervous system development†

Neuroblastoma (NB) is a frequent embryonal tumor of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain‐of‐function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harboring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain‐of‐function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity‐dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes. Hum Mutat 32:277–281, 2011.

Follow-up of babies born to mothers with antiphospholipid syndrome: Preliminary data from the European neonatal registry

In this review preliminary data on the follow-up of 141 babies born to mothers with antiphospholipid syndrome are reported. In spite of maternal treatment, the rate of both preterm delivery and low birth weight were 16 and 17%, respectively. At birth, no clinical evidence of perinatal thrombosis was observed. Placental transfer of antiphospholipid antibodies occurred in 20, 25 and 43% of cases for lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I antibodies, respectively. At 24 months of follow-up, four children showed behaviour abnormalities suggesting the possible need for long-term neurological evaluation in this clinical setting.

European registry of babies born to mothers with antiphospholipid syndrome: a result update.

The registry is a prospective, European, multicentric, longitudinal study, which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). It was started in 2003. In this report, we update the results obtained from the study of 110 mothers and 112 children (two twin births). Eighty per cent of the mothers (n = 86) had primary APS. Purely obstetrical, thrombotic and mixed (obstetrical and thrombotic) APS represent 65.5 %, 21.8 % and 12.7 % of the whole cohort respectively. Isolated antiphospholipid antibodies and isolated anticardiolipin antibodies positivity were present in 50 of 109 (46%) and in 34 of 109 (31%) of the pregnant women, respectively. In the babies, in spite of a high rate of prematurity (14.3%) with four (3.6%) of the premature babies born before 33 weeks of gestation and an increased number of newborns small for gestational age (17%), the large majority of the neonates were healthy. Thirty-one infants are now older than 24 months. Among them, three displayed behavioural abnormalities before 3 years of age. After completing data, there will be the possibility to evaluate the newborn status in relation to the mothers’ diseases, treatments and antibodies and to follow the neuropsychological development and immunological evolution of the babies during the next 5 years.

Immunization of preterm newborns

* Auteur correspondant. e-mail : Joel.gaudelus@jvr.aphp.fr Les enfants nés prématurément sont des enfants à haut risque de contracter des infections dont certaines peuvent être prévenues par la vaccination. La vulnérabilité particulière de ces enfants résulte essentiellement de leurs faibles taux d’anticorps d’origine maternelle. Leur taux à la naissance dépend directement de l’âge gestationnel. Les compétences immunitaires de l’enfant prématuré dépendent de la maturation prénatale et de la maturation post-natale qui débute dès l’exposition aux antigènes de l’environnement et se fait chez le prématuré à une vitesse comparable à celle observée chez l’enfant à terme. Les données fondamentales et les études de tolérance chez ces enfants sont à la base des travaux des 20 dernières années permettant de recommander de vacciner les enfants nés prématurément « au même âge chronologique que les enfants à terme et avec les mêmes doses de vaccin ». Un article précédemment publié dans cette revue [1] et une actualisation très récente effectuée par la commission fédérale pour la vaccination et la société suisse de néonatologie [2] permettent de disposer d’une bibliographie actualisée.

SFP-P018 – Pathologie infectieuse – Tuberculose de l’adolescent : étude rétrospective de 52 cas

Objectifs Aucune serie de tuberculose (TB) chez l’adolescent n’a ete rapportee jusqu’a maintenant alors que cette tranche d’âge est fortement touchee. Materiels et Methodes Nous avons analyse les donnees medicales de tous cas adolescents âges de 12 a 18 ans, hospitalises pour tuberculose dans le CHU Avicenne/Jean Verdier (Seine-Saint-Denis) entre 2000 et 2004. Resultats 52 cas ont ete inclus dans cette etude. Le sexe ratio est equilibre et la mediane d’âge au diagnostic etait de 15,2 ans. La proportion d’adolescents nes a l’etranger etait de 90 %. Le diagnostic de tuberculose a ete evoque sur la presence de signes cliniques dans 79 % des cas, suite a une enquete autour d’un cas dans 19 % des cas et 19 % et apres un test tuberculinique systematique dans 2 % des cas. Vingt cinq adolescents (48 %) presentent des signes extra-pulmonaires : pleuresie (n = 8), meningite (n = 4), adenopathie (n = 4), atteinte peritoneale (n = 5), atteinte osteo-articulaire (n = 3) et atteinte genito-urinaire (n = 1). M. Tuberculosis a ete isole des aspirations gastriques pour 54 % des adolescents. Aucun cas de rechute n’a ete signale avec un recul moyen de quatre ans. Conclusions Nos resultats montrent que les caracteristiques cliniques et demographiques des adolescents sont differentes de celles des adultes et des enfants. Aussi bien dans la prevention que pour le traitement, les infections a M. Tuberculosis, doivent etre adaptees a cette tranche d’âge.