Maternal Depression Trajectories and Children's Behavior at Age 5 Years.

OBJECTIVE: To assess the relationship between trajectories of maternal depression from pregnancy to the child's age of 5 years and children's emotional and behavioral difficulties at age 5 years. STUDY DESIGN: Mother-child pairs (n = 1183) from the EDEN mother-child birth cohort study based in France were followed from 24 to 28 weeks of pregnancy to the child's fifth birthday. Children's behavior at age 5 years was assessed with the Strengths and Difficulties Questionnaire. Maternal depression was assessed repeatedly with the Center for Epidemiological Studies Depression questionnaire (pregnancy, 3, and 5 years of age) and the Edinburgh Postnatal Depression Scale (4, 8, and 12 months postpartum). Homogeneous latent trajectory groups of maternal depression were identified within the study population and correlated with Strengths and Difficulties Questionnaire scores by the use of multivariate linear regression analyzes. RESULTS: Five trajectories of maternal symptoms of depression were identified: no symptoms (62.0%); persistent intermediate-level depressive symptoms (25.3%); persistent high depressive symptoms (4.6%); high symptoms in pregnancy only (3.6%); and high symptoms in the child's preschool period only (4.6%). Children whose mothers had persistent depressive symptoms--either intermediate or high--had the greatest levels of emotional and behavioral difficulties at age 5 years. In addition, compared with children whose mothers were never depressed, those whose mothers had high symptoms in the preschool period also had increased levels of emotional symptoms, conduct problems, and peer problems. CONCLUSIONS: Maternal depression symptoms are related to children's emotional and behavioral problems, particularly if they are persistent (29.9%) or occur during early childhood (4.6%).

Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C.

UNLABELLED: In patients with chronic hepatitis C (CHC), cirrhosis is associated with age, gender, diabetes, alcohol abuse, and coinfection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV). The effect of these factors on the outcome of cirrhosis is unknown. This study in CHC patients with cirrhosis aimed to assess the influence of these factors on decompensation, liver transplantation, and death. Consecutive patients with CHC and cirrhosis hospitalized between January 1, 2006 and December 31, 2008 were followed up until death, transplantation, or study closure in March 2013. Gender, age, Model for End-Stage Liver Disease (MELD) score, diabetes, alcohol abuse, HIV, or HBV coinfection were collected at inclusion. The complications of cirrhosis, death, and liver transplantation were recorded at inclusion and during follow-up. The association between baseline factors and liver-related outcomes at inclusion and during follow-up were tested using logistic regression and Cox's model, respectively. A total of 348 patients with CHC and cirrhosis (68% men; median age: 59 years; median MELD: 10) were included. At baseline, 40% of the patients had diabetes, 29% alcohol abuse, and 6% HIV or HBV coinfection. Baseline MELD≥10 (P<0.001), diabetes (P=0.027), and HBV coinfection (P=0.001) were independently associated with transplantation-free survival. Baseline diabetes was independently associated with ascites (P=0.05), bacterial infections (P=0.001), and encephalopathy (P<0.001) at inclusion. Baseline diabetes was independently associated with development of ascites (P=0.057), renal dysfunction (P=0.004), bacterial infections (P=0.007), and hepatocellular carcinoma (P=0.016) during the follow-up. CONCLUSION: In patients with CHC and cirrhosis, diabetes is an independent prognostic factor. Improving diabetes control may improve the outcome of cirrhosis.

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas.

Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was >20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was >20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to > 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus.

Alternative Response Criteria (Choi, European association for the study of the liver, and modified Response Evaluation Criteria in Solid Tumors [RECIST]) Versus RECIST 1.1 in patients with advanced hepatocellular carcinoma treated with sorafenib.

INTRODUCTION: Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), may underestimate activity and does not predict survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib. This study assessed the value of alternative radiological criteria to evaluate response in HCC patients treated with sorafenib. PATIENTS AND METHODS: A retrospective blinded central analysis was performed of computed tomography (CT) scans from baseline and the first tumor evaluation in consecutive patients treated with sorafenib over a 2-year period in a single institution. Four different evaluation criteria were used: Choi, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), and RECIST 1.1. RESULTS: Among 82 HCC patients, 64 with Barcelona Clinic Liver Cancer stage B-C were evaluable with a median follow-up of 22 months. Median duration of sorafenib treatment was 5.7 months, and median overall survival was 12.8 months. At the time of the first CT scan, performed after a median of 2.1 months, Choi, EASL, mRECIST, and RECIST 1.1 identified 51%, 28%, 28%, and 3% objective responses, respectively. Responders by all criteria showed consistent overall survival >20 months. Among patients with stable disease according to RECIST 1.1, those identified as responders by Choi had significantly better overall survival than Choi nonresponders (22.4 vs. 10.6 months; hazard ratio: 0.43, 95% confidence interval: 0.15-0.86, p = .0097). CONCLUSION: Choi, EASL, and mRECIST criteria appear more appropriate than RECIST 1.1 to identify responders with long survival among advanced HCC patients benefiting from sorafenib.

Emergence of quinolone resistance in the microbiota of hospitalized patients treated or not with a fluoroquinolone.

BACKGROUND: Quinolone resistance is a major global clinical problem. It primarily emerges in microbiota under selective pressure. Studies evaluating the incidence and risk factors for carrying quinolone-resistant bacteria in hospitalized patients treated with fluoroquinolones (FQs) are lacking. METHODS: We prospectively included hospitalized patients treated with FQs. Nasal, throat and rectal swabs were performed before FQ treatment, at the end of FQ treatment and 30 days later. A 'reference group' of patients not receiving FQs was also included to determine the rates of quinolone resistance acquisition not linked to FQ treatment. Prevalence and incidence of quinolone-resistant strains of nasal coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, pharyngeal α-haemolytic streptococci and faecal Escherichia coli, and risk factors for emergence of quinolone resistance in FQ-treated patients were assessed. RESULTS: Four-hundred and fifty-one FQ-treated patients were included, as well as 119 subjects in the 'reference group'. Emergence of quinolone resistance occurred in 110/213 (51.6%), 50/336 (14.9%), 53/290 (18.3%) and 46/336 (13.7%) of FQ-treated patients for CoNS, S. aureus, α-haemolytic streptococci and E. coli, respectively, significantly more than for reference patients for CoNS (23/65; P < 0.05), S. aureus (5/91; P < 0.02) and E. coli (4/84; P < 0.05), but not for α-haemolytic streptococci (15/70; P = 0.55). Emergence of resistance was not associated with the type of FQ received, the duration of therapy or the duration of hospital stay, but was associated with host factors such as immunosuppression and altered performance status. CONCLUSIONS: FQs received during hospitalization account for high rates of emergence of resistance to FQs in clinically relevant bacteria from human microbiota, reflecting the important ecological impact of FQs. Host factors outweighed treatment or hospitalization characteristics as risk factors for carrying quinolone-resistant strains.

Air pollution during pregnancy and childhood cognitive and psychomotor development: six European birth cohorts.

BACKGROUND: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood. METHODS: We analyzed data from 6 European population-based birth cohorts-GENERATION R (The Netherlands), DUISBURG (Germany), EDEN (France), GASPII (Italy), RHEA (Greece), and INMA (Spain)-that recruited mother-infant pairs from 1997 to 2008. Air pollution levels-nitrogen oxides (NO2, NOx) in all regions and particulate matter (PM) with diameters of <2.5, <10, and 2.5-10 µm (PM2.5, PM10, and PMcoarse, respectively) and PM2.5 absorbance in a subgroup-at birth addresses were estimated by land-use regression models, based on monitoring campaigns performed primarily between 2008 and 2011. Levels were back-extrapolated to exact pregnancy periods using background monitoring sites. Cognitive and psychomotor development was assessed between 1 and 6 years of age. Adjusted region-specific effect estimates were combined using random-effects meta-analysis. RESULTS: A total of 9482 children were included. Air pollution exposure during pregnancy, particularly NO2, was associated with reduced psychomotor development (global psychomotor development score decreased by 0.68 points [95% confidence interval = -1.25 to -0.11] per increase of 10 µg/m in NO2). Similar trends were observed in most regions. No associations were found between any air pollutant and cognitive development. CONCLUSIONS: Air pollution exposure during pregnancy, particularly NO2 (for which motorized traffic is a major source), was associated with delayed psychomotor development during childhood. Due to the widespread nature of air pollution exposure, the public health impact of the small changes observed at an individual level could be considerable.

Type 2 diabetes mellitus as a risk factor for intestinal resection in patients with superior mesenteric vein thrombosis.

BACKGROUND & AIMS: The most serious complication of acute mesenteric vein thrombosis (MVT) is acute intestinal ischaemia requiring intestinal resection or causing death. Risk factors for this complication are unknown. To identify risk factors for severe intestinal ischaemia leading to intestinal resection in patients with acute MVT. METHODS: We retrospectively analysed consecutive patients seen between 2002 and 2012 with acute MVT in 2 specialized units. Patients with cirrhosis were excluded. We compared patients who required intestinal resection to patients who did not. RESULTS: Among 57 patients, a local risk factor was identified in 14 (24%) patients, oral contraceptive use in 16 (29%), and at least one or more other systemic prothrombotic condition in 25 (44%). Five (9%) patients had diabetes mellitus (DM), 33 (58%) had overweight or obesity, 9 (18%) had hypertriglyceridemia and 10 (19%) had arterial hypertension. Eleven patients (19%) underwent intestinal resection. DM was significantly associated with intestinal resection (P = 0.02) while local factors or prothrombotic conditions were not. Computed tomography (CT) scans performed at diagnosis found that occlusion of second order radicles of the superior mesenteric vein was more frequently observed in patients who underwent intestinal resection (P = 0.009). CONCLUSIONS: In acute MVT, patients with underlying DM have an increased risk of requiring intestinal resection. Neither local factors nor systemic prothrombotic conditions are associated with intestinal resection. When CT scan shows the preservation of second order radicles of the superior mesenteric vein, the risk of severe resection is low.

Glycemic instability of non-diabetic patients after spine surgery: a prospective cohort study.

PURPOSE: Blood glucose (BG) dysregulation is a well-known condition for patients sustaining medical adverse events, such as sepsis or myocardial infarction. However, it has never been described following spine surgery. Our purpose was to assess postoperative glycemic dysregulation of non-diabetic patients undergoing spine surgery and determine if this is related to any complications within a 3-month postoperative period. METHODS: All the non-diabetic patients undergoing spine surgery in our center were prospectively included over a 6-month period. BG capillary measures were collected from the preoperative fasting period to the end of postoperative Day 3, six times a day. Patients were followed for 3 months after surgery. RESULTS: Data collected from 75 patients were eventually analyzed. A significant increase of BG level was observed from the preoperative to the second postoperative hour (P < 0.0001), remaining significantly elevated until Day 3 (P < 0.0001). Significant correlations were found between perioperative factors (age, smoking, revision status, instrumentation, operation time, blood loss and transfusion) and glycemic parameters. Day 2 mean BG level was found significantly higher for patients surgically revised than those not revised (P = 0.04). CONCLUSIONS: Non-diabetic patients experience a statistically significant increase in BG levels in the first 3 days following a spine surgery. This increase in BG might be correlated with postsurgical complications.

Social withdrawal at 1 year is associated with emotional and behavioural problems at 3 and 5 years: the Eden mother-child cohort study.

The objective of the study was to examine how social withdrawal in infants aged 12 months predicted emotional and behavioural problems at ages 3 and 5 years. The sample included 1,586 infants from the French Eden Mother-Child Cohort Study who had a measure of social withdrawal with the Alarm Distress BaBy scale at age 1 year; among these children, emotional and behavioural difficulties were rated by mothers using the Strength and Difficulty Questionnaire (SDQ) at 3 years for 1,257 (79 %) children and at 5 years for 1,123 (72 %) children. Social withdrawal behaviour at age 1 year was significantly associated with the SDQ behavioural disorder scale at 3 years, independently of a host of familial and child temperament confounders. The association with the relational disorder, prosocial and total difficulty scales was close to significance at 3 years after taking into account familial and temperament confounders. Social withdrawal significantly predicted the three aforementioned scales when measured at 5 years. No significant predictivity of the emotional scale and hyperactivity scale was detected at any age. This study made with a large longitudinal sample confirms the negative effects on development of social withdrawal behaviour, shedding light on the unfolding of behavioural disorders and relational difficulties in children; this calls for early detection of sustained social withdrawal behaviour, as it seems to hamper emotional development.

Use of bispectral index to monitor the depth of sedation in mechanically ventilated patients in the prehospital setting.

BACKGROUND: Sedative drug administration is a challenging aspect of the management of mechanically ventilated patients in the out-of-hospital critical care medicine. We hypothesised that the bispectral index of the EEG (BIS) could be a helpful tool in evaluating the depth of sedation in this difficult environment. The main objective of the present study was to assess the agreement of BIS with the clinical scales in the out-of-hospital setting. METHODS: This prospective study included mechanically ventilated patients. BIS values were blindly recorded continuously. A Ramsay score was performed every 5 min. The main judgement criterion was the correlation between BIS values and the Ramsay score. RESULTS: 72 patients were included, mostly presenting with toxic coma (36%) or neurological coma (21%). The median (IQR) BIS value was 85 (84-86) when the Ramsay score was 3, 80 (76-84) when the Ramsay score was 4, 61 (55-80) when the Ramsay score was 5 and 45 (38-60) when the Ramsay score was 6. According to Receiver operating characteristic (ROC) curves, BIS was categorised into three classes (BIS<54 corresponding to Ramsay score 6, 54≤BIS<72 for Ramsay score 5 and BIS≥73 for Ramsay score ≤4). Based on these categories, the proportion of appropriate BIS values was 67% (217/323). The concordance correlation coefficient for repeated measurements was 0.54 (0.43-0.64). The agreement between BIS and the Ramsay score is moderate. CONCLUSIONS: Prehospital measured BIS values appear poorly correlated with clinical assessment of the depth of sedation. For this reason, the use of BIS to guide prehospital sedation cannot be recommended.

Cognitive impairment at age 5 years in very preterm infants born following premature rupture of membranes.

OBJECTIVE: To evaluate the relationship between preterm premature rupture of membranes (PPROM) and cognitive impairment in 5-year-old children born very preterm. STUDY DESIGN: The Etude Epidémiologique sur les Petits Ages Gestationnels Study is a population-based cohort of children followed up from birth to age 5 years recruited in 9 French regions in 1997. We analyzed data from singletons born between 24 and 32 weeks gestation categorized into 4 groups according to etiology of prematurity: infants born after PPROM, after idiopathic preterm labor, in a vascular context (Vasc), and to women with other complications (Other). Cognitive development at age 5 years was assessed using the Mental Processing Composite score of the Kaufman-Assessment Battery for Children. RESULTS: Among the 1051 children followed up to age 5 years, the mean Mental Processing Composite score was 93.6 ± 19.7, and 13.3% of the children (140 of 1051) had cognitive impairment. After adjustment for potential confounders, the risk of cognitive impairment among infants in the PPROM group was not significantly different than that in the idiopathic preterm labor group (OR, 1.09; 95% CI, 0.62-1.92) and the Other group (OR, 1.36; 95% CI, 0.75-2.47), but was lower than that in the Vasc group (OR, 1.86; 95% CI, 1.16-2.97). In the PPROM group, the risk of cognitive impairment was greater when the latency period (ie, time from rupture to delivery) was <3 days (OR, 2.32; 95% CI, 1.07-5.02). CONCLUSION: Preterm infants born after PPROM are not at increased risk for cognitive impairment in childhood, but the time between PPROM and birth may influence that risk.

Pretransplant fecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae and infection after liver transplant, France.

Extended-spectrum ß-lactamase-producing Enterobacteriaceae isolates (ESBLE) are emerging pathogens that confer resistance to antimicrobial drugs. We conducted a 10-year study in France (January 2001-April 2010) to investigate the incidence of and risk factors for ESBLE infections after liver transplant. Of 710 transplant patients screened preoperatively for ESBLE fecal carriage, 5.5% had ESBLE infection develop within 4 months after surgery; patients with pretransplant ESBLE fecal carriage were more likely to have infection develop than were noncarriers. Typing showed extensive genetic diversity, with a large predominance of CTX-M enzymes. Independent predictors of ESBLE infection were pretransplant fecal carriage, Model for End Stage Liver Disease score >25, and return to surgery. Our results indicate that the influx of preoperatively acquired ESBLE isolates into the hospital outweighs cross-transmission in the epidemiology of ESBLE infections after liver transplant. Transplant candidates should be systematically screened for carriage, and posttransplant infection in carriers should be treated with carbapenems.

Perinatal risk factors and social withdrawal behaviour.

The objectives of the study were (1) to assess prevalence of social withdrawal behaviour in infants aged 12 months included in the French Perinatal Risk Factor Study Eden; (2) To study the correlation between relational withdrawal and several perinatal and parental factors assessed in the EDEN study. A longitudinal study using the ADBB scale was conducted within the Eden Cohort in the year 2008. 1,586 infants were included in the study. Fourteen percent of the children who had an ADBB assessment had a score at 5 and over on the ADBB, a scale designed to assess social withdrawal behaviour at age 0-24 months. Social withdrawal at 12 months was associated with low birth weight, low gestational age and with intra uterine growth retardation. Social withdrawal was independently associated with several maternal and paternal risk factors. The level of social withdrawal behaviour increased with a score of maternal difficulties. This study on a large longitudinally followed volunteer sample demonstrate a clear association of social withdrawal behaviour at age one with low birth weight and preterm birth, possibly mediated by parental vulnerabilities. Social withdrawal behaviour seems to be an important alarm signal to detect early on particularly in premature and small for date babies.

Predictors of the risk of cognitive deficiency in very preterm infants: the EPIPAGE prospective cohort.

AIM: To assess cerebral lesions and other medical as well as social characteristics as predictors of risk of mild and severe cognitive deficiencies in very preterm infants. METHODS: As part of the EPIPAGE population-based prospective cohort study, perinatal data and cognitive outcome at 5 years of age were recorded for 1503 infants born before 33 weeks of gestation in nine regions of France in 1997. Mild cognitive deficiency was defined as a Mental Processing Composite score on the Kaufman Assessment Battery for Children test of between 70 and 84, and severe cognitive deficiency as a score of <70. RESULTS: After controlling for cerebral lesions and other medical as well as social factors, low parental socio-economic status and lack of breastfeeding were significant predictors of mild and severe cognitive deficiencies, whereas presence of cerebral lesions, being small for gestational age and having a large number of siblings were predictors of severe cognitive deficiency. CONCLUSION: Predictors of poor cognitive outcome in very preterm infants are low social status, lack of breastfeeding, presence of cerebral lesions on ultrasound scan, being born small for gestational age and having a high number of siblings. Social factors predicted both mild and severe cognitive deficiencies, whereas medical factors predicted mostly severe cognitive deficiencies.

Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients: an analysis of 259 episodes.

Bloodstream infections (BSIs) are a major cause of mortality in liver transplant recipients. The incidence, microbiology, and outcome of BSIs in the first year after liver transplantation were analyzed in 704 patients who underwent transplantation at a single center between 1997 and 2007. BSIs occurred in 205 (29.1%) of the 704 patients. Overall, 259 episodes were documented, and they resulted in an incidence rate of 36.8%. Of these episodes, 39.4%, 27.8%, 17%, and 15.8% occurred in the very early period (< or = 10 days after liver transplantation), the early period (days 11-30), the intermediate period (days 31-90), and the late period (days 91-365), respectively. The most frequent pathogens were Enterobacteriaceae members (41%), Staphylococcus aureus (19.8%), enterococci (13.1%), Pseudomonas aeruginosa (8.8%), and yeasts (7.1%). The median time of onset ranged from 7 days for methicillin-resistant S. aureus to 25 days for Enterobacteriaceae. Mortality at 15 days after BSIs was 16.2%. Kaplan-Meier survival curves showed that patients with BSIs had a significantly higher 1-year mortality rate than those without BSIs (28.3% versus 16.6%, P < 0.001 with the log-rank test). When the time of BSI onset was considered, 1-year mortality was significantly associated with very early and early episodes (P < 0.001) but not with intermediate and late episodes (P = 0.47). In conclusion, BSIs are frequent and early complications after liver transplantation and are mostly caused by gram-negative bacilli. A BSI in the first posttransplant month is a significant predictor of 1-year survival.

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study.

AIM: The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population-based cohort of very preterm infants. METHOD: As part of EPIPAGE, a population-based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. RESULTS: The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1367 g (SD 393 g; range 450-2645 g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7-10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1305 g (SD 386 g; range 500-2480 g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03-2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95-3.14) were predictors of the development of CP in very preterm infants. INTERPRETATION: Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.

Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study.

BACKGROUND: The increasing survival rates of children who are born very preterm raise issues about the risks of neurological disabilities and cognitive dysfunction. We aimed to investigate neurodevelopmental outcome and use of special health care at 5 years of age in a population-based cohort of very preterm children. METHODS: We included all 2901 livebirths between 22 and 32 completed weeks of gestation from nine regions in France in Jan 1-Dec 31, 1997, and a reference group of 667 children from the same regions born at 39-40 weeks of gestation. At 5 years of age, children had a medical examination and a cognitive assessment with the Kaufman assessment battery for children (K-ABC), with scores on the mental processing composite (MPC) scale recorded. Data for health-care use were collected from parents. Severe disability was defined as non-ambulatory cerebral palsy, MPC score less than 55, or severe visual or hearing deficiency; moderate deficiency as cerebral palsy walking with aid or MPC score of 55-69; and minor disability as cerebral palsy walking without aid, MPC score of 70-84, or visual deficit (<3/10 for one eye). FINDINGS: In total, 1817 (77%) of the 2357 surviving children born very preterm had a medical assessment at 5 years and 396 (60%) of 664 in the reference group. Cerebral palsy was diagnosed in 159 (9%) of children born very preterm. Scores for MPC were available for 1534 children born very preterm: 503 (32%) had an MPC score less than 85 and 182 (12%) had an MPC score less than 70. Of the 320 children in the reference group, the corresponding values were 37 (12%) and 11 (3%), respectively. In the very preterm group, 83 (5%) had severe disability, 155 (9%) moderate disability, and 398 (25%) minor disability. Disability was highest in children born at 24-28 completed weeks of gestation (195 children [49%]), but the absolute number of children with disabilities was higher for children born at 29-32 weeks (441 children [36%]). Special health-care resources were used by 188 (42%) of children born at 24-28 weeks and 424 (31%) born at 29-32 weeks, compared with only 63 (16%) of those born at 39-40 weeks. INTERPRETATION: In children who are born very preterm, cognitive and neuromotor impairments at 5 years of age increase with decreasing gestational age. Many of these children need a high level of specialised care. Prevention of the learning disabilities associated with cognitive deficiencies in this group is an important goal for modern perinatal care for children who are born very preterm and for their families.

Temozolomide: a safe and effective treatment for malignant digestive endocrine tumors.

BACKGROUND: Systemic chemotherapies are associated with limited response rates and significant toxicity in patients with malignant digestive endocrine tumors (DET). Preliminary studies have reported interesting results with temozolomide in patients with DET. AIM: It was the aim of this study to assess the efficacy and safety of temozolomide in patients with malignant DET. PATIENTS AND METHODS: Twenty-one patients, median age 61 years (range 56-77), with metastatic well-differentiated DET were retrospectively studied. All patients except 1 had received prior treatment (hepatic resection, chemotherapy). All patients had progressive disease in the 3 months prior to entry into the study. Temozolomide was administered at doses of 200 mg/m(2) daily for 5 days, every 28 days. Treatment was assessed for safety, progression-free and overall survival. RESULTS: The median number of temozolomide cycles was 5 (range 2-15). Grade 3 hematological toxicity occurred in 5 patients. There were no toxic deaths. According to the Response Evaluation Criteria in Solid Tumors criteria, partial response and stabilization were obtained in 1 (5%) and 17 patients (81%), respectively. The median time to progression was 9 months (range 3-26). The 1-year progression-free survival and overall survival were 42 and 77%, respectively. CONCLUSION: Temozolomide is a well-tolerated oral chemotherapy in patients with malignant DET, including those who have already received treatment. In patients with progressive disease, temozolomide controls tumor progression in 86% of cases.

Screening for risk factors of relational withdrawal behaviour in infants aged 14-18 months.

OBJECTIVES: The objectives of this study were (1) to evaluate the prevalence of relational withdrawal behaviour in infants aged 14-18 months attending a public health centre in Paris, (2) to check some identified risk factors for relational withdrawal behaviour in this population. METHODS: A cross-sectional study was conducted in infants aged 14-18 months attending a child health screening centre during the year 2005. RESULTS: A total of 640 children were included in the study. Thirteen percent of the 640 infants (n=83, 95% CI [10.4%; 15.6%]) had an ADBB score at 5 and over 5 on the ADBB. There was a clear relationship between withdrawal behavior and having psychological difficulties as reported by parents, and between withdrawal and developmental delay. Withdrawal was also significantly associated with being a boy, with living in risk conditions (e.g. child being in joint custody, or with living in a foster family), with being adopted, or with being a twin. More withdrawn infants were taken care of at home. CONCLUSION: Sustained relational withdrawal behaviour was linked with developmental disorders and psychopathology and not with SES, ethnical origin or rank of birth. The scale could be used in screening early psychopathology in infants aged 2-24 months of age.

Developmental milestones at one year for the offspring of mothers with congenital hypothyroidism: a population-based study

OBJECTIVE: Maternal thyroid dysfunction during pregnancy is associated with neurodevelopmental impairment in the offspring. No data are currently available for the offspring of patients treated early for congenital hypothyroidism (CH). The aim of this study was to investigate motor and language milestones at one year of age in a population-based registry of children born to young women with CH. DESIGN AND METHODS: We assessed 110 children born to mothers with CH, and 1367 children from the EDEN French population-based birth cohort study prospectively, at the age of one year, with identical questionnaires. Outcomes were assessed in terms of scores for childhood developmental milestones relating to mobility, motor coordination, communication, motricity and language skills. RESULTS: After adjustment for confounding factors, children born to mothers with CH were found to have a higher risk of poor motor coordination than those of the EDEN cohort (OR: 4.18, 95% CI: 2.52-6.93). No differences were identified for the other four domains investigated. Children born to mothers with gestational diabetes have a higher risk of low motor coordination score than their peers (OR: 2.10, 95% CI: 1.21-3.66). Children born to mothers with TSH ≥ 10 IU/L during the first six months of pregnancy were more likely to have low motricity or communication skills scores than those born to mothers with lower TSH concentrations (56% vs 21% for each score, P < 0.04). CONCLUSIONS: Maternal CH may have slight adverse effects on some developmental milestones in the child at one year of age, particularly for children born to mothers with uncontrolled hypothyroidism. However, it remains unclear whether these adverse effects modify subsequent neurodevelopment.