Predictive factors of postoperative outcome in the elderly after resective epilepsy surgery.

OBJECTIVE: To evaluate the efficiency of resective epilepsy surgery (RES) in patients over 50 years and determine prognostic factors. RESULTS: Over the 147 patients over 50 years (54.9±3.8 years [50-69]) coming from 8 specialized French centres for epilepsy surgery, 72.1%, patients were seizure-free and 91.2% had a good outcome 12 months after RES. Seizure freedom was not associated with the age at surgery or duration of epilepsy. In multivariate analysis, seizure freedom was associated with MRI and neuropathological hippocampal sclerosis (HS) (P=0.009 and P=0.028 respectively), PET hypometabolism (P=0.013), temporal epilepsy (P=0.01). On the contrary, the need for intracranial exploration was associated with a poorer prognosis (P=0.001). Postoperative number of antiepileptic drugs was significantly lower in the seizure-free group (P=0.001). Neurological adverse event rate after surgery was 21.1% and 11.7% of patients had neuropsychological adverse effects overall transient. CONCLUSIONS: RES is effective procedure in the elderly. Even safe it remains at higher risk of complication and population should be carefully selected. Nevertheless, age should not be considered as a limiting factor, especially when good prognostic factors are identified.

Delayed-onset paraparesis in Lassa fever: A case report.

Lassa fever (LF) is an endemic viral hemorrhagic fever in West Africa. Among the serious complications of the disease are neurological manifestations whose spectrum is incompletely known. Here we report the case of a 61-year-old man who developed a delayed-onset paraparesis a few weeks after getting infected with Lassa virus, thereby suggesting a possible association between LF and spinal cord disorders.

Successful transcatheter pulmonary valve implantation in a dog: first clinical report.

Transcatheter pulmonary valve (TPV) implantation is a therapeutic approach approved by the United States Food and Drug Administration for human patients with failing pulmonary conduits in 2010 and for failing bioprosthetic surgical pulmonary valves in 2017. We report here the first successful transcatheter implantation of a stented valve in a pulmonary position in a dog with congenital pulmonary valve disease. A 3-year-old, 10.9 kg, client-owned Beagle dog was referred for a follow-up visit after a percutaneous balloon valvuloplasty performed 22 months before for treatment of a severe type A valvular pulmonary stenosis. The Doppler-derived peak pressure gradient was 348 mmHg before the procedure and 66 mmHg 24 h after. The dog was lethargic. Echocardiography revealed a mild pulmonary stenosis (pressure gradient-43 mmHg), severe pulmonary regurgitation, and secondary severe right ventricular and right atrial dilation. Worsening of right heart dilation was observed 2 months later despite medical therapy. A TPV implantation was performed using a prestented Melody bovine jugular bioprosthetic valve. The dog recovered uneventfully and was discharged 10 days after the procedure. Right heart dilation resolved within 15 days. The dog was doing well 7 months after valve implantation. This case demonstrates that TPV implantation with a stented valve is technically feasible in dogs with severe pulmonary valve disease. Stringent postoperative care, with particular attention to thrombosis and infectious endocarditis, and appropriate sizing and positioning of the valve stent are keys to the success of this procedure.

European survey on national training activities in clinical research.

BACKGROUND: Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists. METHODS: To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action. RESULTS: The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries. CONCLUSIONS: There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.

[Well-being in adulthood of patients with chronic conditions in childhood: The GEDEPAC-2 questionnaire]. / Bien-être à l'âge adulte des enfants atteints de maladies chroniques : le questionnaire GEDEPAC-2.

BACKGROUND: In France, chronic diseases affect 3 million children. In children with chronic conditions, long-term somatic outcome has been well described, but little is known about the psychosocial aspects of well-being. METHODS: Our aim was to build a self-administered questionnaire of global well-being in adults who had a chronic disease since or during childhood using a multidimensional and nonspecific approach. The questionnaire was constructed by a multidisciplinary group (epidemiologists, clinicians, sociologist, statistician). Items were built in compliance with reference data from the French general population (national surveys, free access) to allow comparative analysis adjusted for age and sex (and eventually other confounding factors) by indirect standardization (qualitative variables) or Z-scores (quantitative variables). RESULTS: The GEDEPAC-2 includes 108 items exploring 11 domains: education, employment, housing, material security, social links, civic engagement, leisure, environment, physical health/risky behavior, health-related quality of life and sex life. Factual questions and satisfaction scales jointly explore social well-being. Quality of life is analyzed in terms of physical quality of life, mental quality of life, fatigue and burden of treatment by 3 questionnaires validated in French (SF-12; MFI-20; Burden of Treatment Questionnaire). Experience of transition from pediatric to adult healthcare is described in 21 items. Paper and electronic versions were developed. CONCLUSION: Built in a multidimensional approach to well-being and in line with the available reference data, GEDEPAC-2 will facilitate the implementation of future studies on impact in adulthood of chronic disease in childhood.

[Vagus nerve stimulation for intractable epilepsy: A retrospective bicentric cohort study of 101 patients operated on between 1999 and 2010]. / La stimulation du nerf vague dans le traitement des épilepsies pharmacorésistantes : étude rétrospective bicentrique d'une cohorte de 101 patients implantés entre 1999 et 2010.

BACKGROUND: Vagus nerve stimulation is an adjunctive palliative therapy for refractory epilepsy. MATERIAL AND METHODS: We reviewed the clinical and surgical records of patients who had a VNS implantation for intractable epilepsy between the years 1999 and 2010 at two institutions, Bordeaux and Toulouse University Hospitals. RESULTS: A total of 101 patients were included of whom 57 were male. Median age at epilepsy onset was 7.5 years, inter quartile range (IQR) [2.5-12.5] and the median time between epilepsy onset and VNS implantation was 21.1 years, IQR [11.9-29.5]. At the end of the study, 85 patients were alive with a functional VNS. Survival probability of having a functional VNS at 1, 2 and 5 years were respectively: 99%, IC95% [97.1,100]; 96.49%, IC95% [92.7,100] and, 88.2%, IC95% [79.9,97.4]. Among the patients, 41.6% demonstrated a seizure decrease of more than 50%. The mean number of seizures was reduced by 5.7 per week. We failed to demonstrate any factor affecting the outcome. CONCLUSION: The VNS can decrease the seizure frequency but, also reduce their intensity and had a favourable effect on the patients mood. Morbidity is low and the therapeutic effect of the stimulation is sustainable. The indication of the VNS should be discussed earlier in the evolution of a nonsurgical and severe epilepsy.

Long-term impact of childhood-onset type 1 diabetes on social life, quality of life and sexuality.

AIM: This study describes the socio-professional outcomes, health-related quality of life (HRQOL) and sexuality of adults with childhood-onset type 1 diabetes (T1D). METHODS: The study participants (n=388), recruited from a nationwide registry (age: 28.5 ± 3.1 years; T1D duration: 17.0 ± 2.7 years), completed a questionnaire (198 items); the results were compared with the French general population using standardized incidence ratios (SIRs) and Z scores matched for age, gender and period with/without education levels and patterns of family life. Linear regression models also investigated correlates of SF-36 Physical (PCS) and Mental Composite Scores (MCS). RESULTS: Compared with the French general population, education levels of people with T1D were similar, with 68.6% having at least a high-school diploma or higher (SIR: 1.06, 95% CI: 0.93; 1.20), as were also their patterns of family life. Unemployment was higher in T1D women (15.3%, SIR: 1.50, 1.00; 2.05), but not in T1D men (8.6%, SIR: 0.96, 0.51; 1.57). Social discrimination was more common (SIR: 5.64, 4.64; 6.62), and frequency of daily alcohol consumption was higher (SIR: men, 3.34, 2.38; 4.54; women, 6.53, 4.57; 12.99). PCS and MCS were decreased moderately (mean ± SD: 52.0 ± 7.5; mean Z score: -0.2, 95% CI: -0.3; -0.1) and substantially (mean ± SD: 42.1 ± 12.4; mean Z score: -0.7, -0.8; -0.6), respectively. Fatigue and abandoning sports were predictive of a lower HRQOL. Both men and women were more frequently dissatisfied with their sex life. Prevalence of sexual problems was higher in women (SIR for: dysorgasmia, 1.91, 1.21-2.88; decreased/loss of desire: 2.11, 1.35-3.08), but similar in men. Participants with T1D-related complications had preserved social outcomes, but altered HRQOL. CONCLUSION: Young adults with T1D have satisfactory social participation. However, their higher alcohol consumption, lower MCS and frequent dissatisfaction with sexuality suggest a heavy impact of the disease on morale, especially in women. Improving the everyday well-being of these young adults represents a key challenge for diabetes healthcare.

[Ketoacidosis at time of diagnosis of type 1 diabetes in children and adolescents: effect of a national prevention campaign]. / Effet à un an de la campagne nationale de prévention de l'acidocétose au moment du diagnostic de diabète de type 1 chez l'enfant et l'adolescent.

The aim of the study was to evaluate, after the first year of a national information campaign, the effect on the frequency and severity of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in children and adolescents in France. The following data were collected during a 2-year period in people younger than 15 years of age at diagnosis of T1D, in 146 pediatric centers: age, sex, duration of symptoms, patient's previous care, clinical and biological signs, and family history of T1D. DKA was defined as pH<7.30 or bicarbonate<15mmol/L, severe DKA as pH<7.10 or bicarbonate <5mmol/L. During the 2nd year, an information campaign targeting health professionals and families was launched with the objective of reducing the time to diagnosis. Data were compared between the year before the campaign (year 0) and the first year of the campaign (year 1). The number of new cases of T1D was 1299 for year 0 and 1247 for year 1. Between year 0 and year 1, the rate of DKA decreased from 43.9% to 40.5% (P=0.08), exclusively due to the decrease of severe DKA from 14.8 to 11.4% (P=0.01). In the 0- to 5-year-old and 5- to 10-year-old age groups, the relative decrease in the rate of DKA was 13% and 15%, and 23% and 41% for severe DKA, respectively. In patients referred to the hospital by a pediatrician or who came at the family's initiative, the decrease was 34% and 7%, and 39% and 32% for severe DKA, respectively. No change was observed in the 10- to 15-year-old group or in those children who were referred by a general practitioner. In multivariate analyses, a higher DKA rate was associated with the young age of the child (<5 years), being hospitalized at the parents' initiative rather than being referred by a doctor, and the absence of a family history of T1D. A higher rate of severe DKA was associated with these last two factors but not with the child's age. The frequency of DKA at diagnosis of type 1 diabetes remains high in children and adolescents, but the first year of an information campaign decreased it. The results have also helped better define the strategy and targets of the continuing prevention campaign, to more efficiently reduce the morbidity and mortality of T1D at diagnosis in children and adolescents in France.

[Safety and efficacy of whole breast irradiation with a concomitant boost: analysis of 121 cases treated at the Institute of Cancerology of Lorraine]. / Efficacité et sécurité de la technique de radiothérapie mammaire avec complément d'irradiation concomitant : analyse de 121 cas traités à l'institut de cancérologie de Lorraine.

PURPOSE: To evaluate the safety and efficacy of whole breast irradiation with a concomitant boost. PATIENTS AND MATERIALS: This is a retrospective study of 121 patients with node negative T1-T2 breast tumors inferior to 3 cm in diameter, previously treated by conservative surgery without chemotherapy. A dose of 50 Gy was delivered to the whole breast in 2 Gy daily fractions with 5 weekly treatments. A concomitant boost to the lumpectomy site delivered a total of 10 Gy in 1 Gy fractions twice a week. This would result in an equivalent tumour bed dose (assuming an α/ß of 4) of approximately 65 Gy in 2 Gy fractions. RESULTS: Over 7 years, 121 patients were treated. The median age was 67 years (range, 46-86 years). Stage distribution was: 115 T1, 6 T2; 116 tumors had positive hormonal receptors, 6 grade SBR3. With a median follow-up of 6 years (range, 1.4-11.4 years), 5-year overall survival was 98.2% (95% confidence interval [CI] 0.95-1), disease-free survival was 100% and local recurrence-free survival 100%. The maximum acute skin toxicity by the end of treatment was grade 2. Cosmetic outcomes were good on the long term. One spontaneous rib fracture was observed 1 year after radiotherapy among 76 patients. CONCLUSIONS: The study shows that whole breast radiation therapy with a concomitant boost is safe and effective for selected patients with low risk of relapse, and gives excellent long term results. This protocol represents a good alternative to longer standard whole breast radiation therapy with sequential boost to the lumpectomy bed.

Ketoacidosis at diagnosis of type 1 diabetes in French children and adolescents.

OBJECTIVES: This study aimed to evaluate the frequency of diabetic ketoacidosis (DKA) and its associated factors at the diagnosis of type 1 diabetes (T1D) in French children and adolescents prior to launching a public-health campaign of information to prevent DKA. PATIENTS AND METHODS: Over a 1-year period, 1299 youngsters (aged < 15 years) were diagnosed with T1D at 146 paediatric centres in all regions of France. Age, gender, duration of symptoms, patient's pathway to diagnosis, clinical and biological signs, and family history of T1D were collected for each newly diagnosed patient. DKA was defined as pH < 7.30 or bicarbonate < 15 mmol/L, and severe DKA as pH < 7.10 or bicarbonate < 5 mmol/L. RESULTS: At the time of diagnosis, 26% of the children were aged 0-5 years, 34% were 5-10 years and 40% were 10-15 years. The overall prevalence of DKA was 43.9% (0-5 years: 54.2%; 5-10 years: 43.4%; and 10-15 years: 37.1%) and 14.8% for severe DKA (0-5 years: 16.6%; 5-10 years: 14.4%; and 10-15 years: 13.9%; < 2 years: 25.3%). Severe DKA was more frequent when the child was hospitalized at the family's behest (26.6%) than when referred by a general practitioner (7.6%) or paediatrician (5.1%; 30.6%, 53.7% and 9.2%, respectively, by patients' age group). The frequency of DKA decreased to 20.1% (severe DKA: 4.4%) in families with a history of T1D. Multivariate analysis showed that age, pathway to diagnosis, duration of polyuria/polydipsia (< 1 week) and family history of T1D were associated with the presence of DKA, while pathway to diagnosis and family history of T1D were associated with severe DKA. CONCLUSION: DKA at the time of T1D diagnosis in children and adolescents is frequent and often severe. Patients' age, pathway to hospitalization and family history of diabetes were the main factors associated with DKA. These data suggest that a public-health campaign to prevent DKA at diagnosis can help reduce the frequency of DKA and also provide baseline data for evaluating the efficacy of such a campaign.

[Epidemiology of diabetes mellitus in childhood]. / Épidémiologie des diabètes sucrés chez l'enfant.

Diabetes mellitus in childhood may correspond to different pathophysiological entities but type 1 diabetes is by far the most common form of diabetes in children. Its incidence has been increasing steadily over the past two decades. This trend is particularly important among younger children, leading to a youngest median age at the discovery of diabetes. Thus, approximately 25% of diagnoses of type 1 diabetes are in children under 5 years. In France, the type 2 diabetes in children is rare despite the rise in obesity. Investigations for the diagnosis are recommended in obese adolescents with a family history of type 2 diabetes. Monogenic diabetes are more common than type 2 diabetes in Europe. Their research depends on the analysis of family history and may lead to a specific therapeutic approach.

Diagnostic methods used to monitor an outbreak of babesiosis (Babesia bovis) in a herd of feral cattle in New Caledonia.

BACKGROUND: In December 2007, Babesia bovis was introduced to New Caledonia through the importation of cattle vaccinated with a live tick fever (babesiosis and anaplasmosis) vaccine. Medical measures, acaricide and antiprotozoal treatments, and quarantine restrictions were implemented with success on all the farms involved, but the disease spread to one of the neighbouring properties where feral cattle were present. To circumscribe and eliminate this outbreak, the authorities decided to slaughter all animals on the neighbouring property. OBJECTIVES: To monitor the spread of babesiosis in naïve cattle and to compare the usefulness of PCR, ELISA and brain smear for disease detection in monitoring this outbreak. METHODS: Blood and brain samples of slaughtered animals were analysed over time throughout the eradication campaign using serology, PCR and brain smears. In addition, field numbers of Rhipicephalus microplus tick larvae were assessed and Babesia infection of the larvae analysed using PCR. RESULTS: This study showed the natural spread of babesiosis in a naïve herd without pharmacological control measures. Prevalence reached 80% within a year of introduction. ELISA and PCR tests performed similarly in detecting disease in cattle and both were superior to brain smears. Nevertheless, specific tests or combinations of tests may be preferable, depending on the specific requirements of any future disease situation. CONCLUSIONS: In cattle, ELISA and PCR appear to be suitable tools for monitoring the evolution of a babesiosis outbreak, with brain smears as a useful adjunct. PCR was not suitable for detecting infection in tick larvae.

Sight-threatening phenylketonuric encephalopathy in a young adult, reversed by diet.

Phenylketonuria (PKU) leads to severe neurological disorders in childhood, shunned by the diet. The long-term prognosis after diet diversification at adolescence is uncertain. We report a case of cortical blindness in a young patient regressive 1 month after the diet was resumed.Mr M., 25 years old, had PKU detected at birth. He maintained good serum levels of Phenylalanine (Phe) (120-300 µmol/L) during childhood and got a normal intellectual development. During adolescence he diversified his diet but maintained low meat and fish intake; Phe was ~1,200 µmol/L with no symptoms. In 2009, the patient stopped the low-Phe amino acid substitutes due to weariness. On June 27, 2011, he consulted for a decrease of visual acuity progressing for 6 months. Ophthalmologic examination found that visual acuity was 2/10 in two eyes associated to a central visual field defect. The visual evoked potentials were altered. MRI showed bilateral and symmetric occipital FLAIR hyperintensities. On admission in the Nutrional Unit on June 29, 2011, blood pressure was 120/70 mmHg, there was no other neurological abnormality. Phe was at 1,512 µmol/L, and not responsive to BH4. He was then treated with a very low-Phe diet with an amino acid substitute, and he obtained Phe between 120 and 300 µmol/L. Visual acuity was suddenly restored on August 1, 2011, with a dramatic attenuation of the MRI hyperintensities.Our observation shows that the withdrawal of the diet and substitutes exposes to serious neurological complications in adults that may reverse with a fast nutritional support.

[Surgery and postoperative radiation therapy in primary retroperitoneal sarcomas: experience of the cancer centre Alexis-Vautrin]. / Intérêt de la radiothérapie postopératoire dans la prise en charge des sarcomes rétropéritonéaux primitifs : expérience du centre Alexis-Vautrin.

PURPOSE: Surgical resection remains the standard treatment for patients with resectable retroperitoneal sarcomas. The aim of this study was to retrospectively analyse the outcomes of patients with primary retroperitoneal sarcoma. PATIENTS AND METHODS: We analysed data of 50 patients with primary retroperitoneal sarcoma who underwent curative-intent resection from 1975 to 2008. External beam radiotherapy and chemotherapy were delivered postoperatively. Demographics, surgical, pathological variables and chemo/radiation therapy were analysed as prognosis factors. RESULTS: There were 22 males and 28 females (mean age 54 ± 13 years). Surgery required visceral resections in 30 patients. There were 16 leiomyosarcomas, 25 liposarcomas and eight other sub-types. Twenty-one patients had clear surgical margins. Twenty-eight patients received postoperative external beam radiotherapy (median 45 Gy) and 15 received chemotherapy. At the end of the follow-up (median 55 months), local recurrence occurred in 39% (n=14) among R0/R1 resection group (n=36). Postoperative external beam radiotherapy tends to increase the time of local recurrence from surgery (27 vs. 13 months, P=0.05). The overall survival rates were 81%, 55% and 46% at 1, 3 and 5 years, respectively. Although R0 resection (P=0.01), well tumour differentiation (P=0.004) and postoperative external beam radiotherapy (P=0.02) significantly influenced overall survival in univariate analysis, only R0 resection was an independent prognostic factor in a multivariate analysis. CONCLUSION: We confirm the pre-eminence of radical surgery with negative margins as major prognostic factor and the benefit of postoperative radiotherapy.

Extensive settlement of the invasive MEAM1 population of Bemisia tabaci (Hemiptera: Aleyrodidae) in the Caribbean and rare detection of indigenous populations.

Bemisia tabaci populations belonging to Middle East-Asia Minor one (MEAM1) and Mediterranean (MED) groups (formerly biotype B and Q, respectively) have spread throughout the world. Although the introduction of MEAM1 is documented from several Caribbean islands, it is generally not known whether MED has also been introduced; whether indigenous populations have survived; and if in the affirmative, to which group(s) they belonged. Whiteflies were collected from seven islands on various plant species. The prevalence of MEAM1 and non-MEAM1 individuals was assessed using a microsatellite approach validated with sequences of the mitochondrial cytochrome oxidase I (mtCOI) gene. Of the 262 samples tested, 247 exhibited the MEAM1 pattern, whereas none showed the MED pattern. The mtCOI gene was partially sequenced from a sample of individuals exhibiting MEAM1 (n = 15) and non-MEAM1 patterns (n = 8) and compared with type sequences. The 15 individuals exhibiting the MEAM1 pattern were confirmed to belong to MEAM1. Of the eight individuals representative of the six non-MEAM1 patterns, two belonged to the indigenous New World (NW) group of B. tabaci (NW), one belonged to a distinct species of Bemisia, and five belonged to MEAM1. One individual belonging to NW exhibited 99.9% nucleotide identity with a NW individual from Puerto Rico. The other was identified as the most divergent individual of the North and Central American genetic cluster. We conclude that a highly homogenous MEAM1 population has extensively settled in the Caribbean and that heterogeneous NW populations were still detectable although severely displaced.

Plasminogen activator inhibitor type-1 is an independent marker of metabolic disorders in young adults born small for gestational age.

BACKGROUND: Metabolic syndrome (MS) has been associated with being born small for gestational age (SGA). In epidemiological studies plasminogen activator inhibitor type-1 (PAI-1) levels have been associated with MS. Few studies have examined this association in subjects born SGA. PATIENTS AND METHODS: Five hundred and fifty-seven SGA adults (birth weight < 10th percentile) were compared with 671 subjects with a birth weight between the 25th and 75th percentiles (control group). MS was defined using the World Health Organization (WHO) definition. Active PAI-1 was measured on citrated plasma with bio-immunoassay. RESULTS: MS was more prevalent in the SGA group (8.7%) than in the control group (5.5%; P = 0.03). In both groups, PAI-1 concentrations were significantly correlated with waist circumference, plasma triglycerides, homeostatic model assessment-insulin resistance (HOMA-IR) and associated with male sex and MS. PAI-1 concentrations were significantly increased in the SGA group (12.2 ± 21.2 vs. 10.0 ± 13.5 IU mL⁻¹, P = 0.03) and this remained after adjustment of metabolic variables (P = 0.009). PAI-1 concentrations above 4.9 IU mL⁻¹ (= median of PAI-1 concentration in the control group) were present in 94% of the subjects with MS. Moreover, the adjusted odds ratio (OR) for having elevated PAI-1 was 1.48 (1.08; 1.95) in the SGA group in comparison with the control group (P = 0.005). CONCLUSIONS: PAI-1 plasma concentrations were significantly increased in SGA subjects independently of MS. These data suggest that elevation of PAI-1 concentrations might be an indication of an abnormal secretion at the level of the adipose tissue, endothelial cells or liver and implicated in metabolic disorders reported in SGA subjects.

Fertility is not altered in young adults born small for gestational age.

BACKGROUND: The intrauterine environment may have a lifelong impact on individuals' health. However, results on the relationship between birth size and gonadal function are conflicting, and it remains unknown whether reproductive function is altered in adults born small for gestational age (SGA). The aim of the present study was to compare the fertility of young adults from the general population, born either SGA or appropriate for gestational age (AGA). METHODS: There were 579 adults born SGA (birthweight under the 10th percentile) who were compared with 703 subjects of the same age (age 29.4 +/- 4.1 years) born AGA (birthweight between 25th and 75th percentiles). They fulfilled a questionnaire focusing on the first attempt to give birth, to have a measure of the time to pregnancy and an estimation of the fecundability (the monthly pregnancy probability), two relevant indicators of fertility at the couple level. Ratios of fecundability between AGA and SGA subjects were adjusted for known fertility factors (age, smoking, reproductive history) and for socioeconomic status. RESULTS: Time to pregnancy was comparable in the two groups: 5.7 +/- 8.0 versus 6.6 +/- 10.5 months in AGA and SGA, respectively (P = 0.31), in women and 5.1 +/- 7 versus 6.0 +/- 9 months in AGA and SGA, respectively, in men (P = 0.53). The adjusted ratios of fecundability comparing SGA to AGA subjects were not significant: HR = 0.91 [0.68;1.21] (P = 0.5) in women and HR = 0.95 [0.67;1.74] (P = 0.82) in men. CONCLUSION: When studied in young adults from the general population, fertility is not reduced in those born SGA.

11beta-hydroxysteroid dehydrogenase type 1 of the subcutaneous adipose tissue is dysregulated but not associated with metabolic disorders in adults born small for gestational age.

INTRODUCTION: The mechanisms relating being born small for gestational age (SGA) and the later risk of metabolic disorders are not yet fully understood. Adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity and expression have been positively associated with metabolic syndrome. In humans, no in vivo studies have explored 11beta-HSD1 activity and gene expression in sc adipose tissue of SGA subjects. SUBJECTS AND METHODS: Thirty-nine subjects SGA (birth weight<10th percentile) were matched on gender and age with 36 subjects born appropriate for gestational age (AGA) (25th percentile

Independent effects of weight gain and fetal programming on metabolic complications in adults born small for gestational age.

AIMS/HYPOTHESIS: Insulin resistance (IR) and the metabolic syndrome (MS) have been reported in adults as a consequence of being born small for gestational age (SGA). The process seems to be initiated early in life; however, little is known about the progression of MS and IR in young adults. We hypothesised that being born SGA would promote a greater progression over time of IR and MS, reflecting not only the gain in weight and fat mass but also the extension of the fetal programming process. METHODS: Participants were selected from a community-based cohort and born full-term either SGA (birthweight <10th percentile) or appropriate for gestational age (25th < birthweight < 75th percentile). A total of 1,308 individuals were prospectively followed between the ages of 22 and 30 years. RESULTS: At both ages, individuals born SGA were more insulin-resistant and showed a significantly higher prevalence of MS. Over the 8 year follow-up, the risk of developing MS was twofold higher in those SGA, after adjustment for gain in BMI, whereas the progression of IR was not significantly affected by the birth status. CONCLUSIONS/INTERPRETATION: Our data suggest that metabolic disorders in SGA individuals are amplified by the weight gain with time when adults, both probably resulting from fetal programming. Moreover, the modest increase in IR contrasts with the constant and much higher prevalence of MS.