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.

Social Withdrawal Behaviour at One Year of Age Is Associated with Delays in Reaching Language Milestones in the EDEN Mother-Child Cohort Study.

OBJECTIVE: The aim of the study was to examine the relationship between social withdrawal behaviour at one year and motor and language milestones. MATERIALS AND METHODS: One-year old children from the EDEN French population-based birth cohort study (Study on the pre- and postnatal determinants of the child's development and prospective health Birth Cohort Study) were included. Social withdrawal at one year was assessed by trained midwives using the Alarm Distress BaBy (ADBB) scale. Midwives concurrently examined infants' motor and language milestones. Parents reported on child's psychomotor and language milestones, during the interview with the midwife. RESULTS: After adjusting for potential confounding factors, social withdrawal behaviour was significantly associated with concurrent delays in motor and language milestones assessed by the midwife or the parents. DISCUSSION: Higher scores on social withdrawal behaviour as assessed with the ADBB were associated with delays in reaching language milestones, and to a lesser extent with lower motor ability scores. Taking the contribution of social withdrawal behaviour into account may help understand the unfolding of developmental difficulties in children.

Reproductive disorders in hairdressers and cosmetologists: a meta-analytical approach.

OBJECTIVES: The aim of this study was to perform a systematic review and to use a meta-analytical approach to assess quantitatively the risk of adverse pregnancy outcomes in hairdressers and cosmetologists. METHODS: A systematic literature search up to 1 February 2012 was carried out using major bibliographic databases, grey literature, contacts with research teams working on the subject, review papers and reference lists of selected articles. Observational studies reporting measures of effects in relation with body care (hairdressers, cosmetologists, etc.) and reproductive disorders were included. Study quality was assessed by three reviewers. The estimated risk ratios (RR) from all studies reporting on identical outcomes were combined using an average of logarithm transformation of estimated RR weighted by their inverted variance. Statistical heterogeneity across studies was assessed using Cochran's Q test. To explore the sources of heterogeneity, several sensitivity analyses and subgroup analyses were conducted based on study quality, country, study period, alcohol consumption, smoking habit, jobs and control populations. RESULTS: Nineteen studies were selected and reviewed in-depth. The combined risk ratios (RRcs) of five reproductive outcomes were calculated and found to be significantly increased for four outcomes: time to pregnancy, which had an RRc of 1.11 (95% CI: 1.03-1.19); premature birth, which had an RRc of 1.05 (95% CI: 0.99-1.11); small for gestational age, which had an RRc of 1.24 (95 CI%: 1.10-1.41); low birth weight, which had an RRc of 1.21 (95% CI: 1.06-1.39); and embryonic and fetal losses, which had an RRc of 1.19 (95% CI: 1.03-1.38). CONCLUSIONS: This work confirms a weak increase in risk of some reproductive disorders in female hairdressers/cosmetologists. However, the evidence level is rather weak, and a causal association between job and reproductive outcomes cannot be asserted.

Developmental predictors of inattention-hyperactivity from pregnancy to early childhood.

OBJECTIVE: The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers. MATERIALS AND METHODS: Longitudinal data came from a French population based birth cohort study (EDEN; N = 1311 mother-child pairs followed from the pregnancy onwards). Inattention-hyperactivity symptoms were assessed with the Strengths and Difficulties Questionnaire when participating children were 3 years of age. Potential risk factors were classified in four domains (fetal exposures and child somatic characteristics, child temperament, child neurodevelopmental status, psychosocial environment) and four periods (before pregnancy, prenatal/birth, infancy, toddlerhood). Their role as potential moderator or mediator was tested with path analysis to determine the developmental sequence. RESULTS: A low family socioeconomic status before pregnancy was the main environmental risk factor for inattention-hyperactivity symptoms at 3 years, and its effect occurred via two pathways. The first was a risk pathway, where lower SES was associated with higher maternal depression and anxiety during pregnancy; then to higher maternal and child distress and dysregulation in infancy; and in turn to higher levels of inattention-hyperactivity at 3 years. The second was a protective pathway, where higher SES was associated with longer duration of breastfeeding during infancy; then to better child neurodevelopmental status in toddlerhood; and in turn to lower levels of inattention-hyperactivity at 3 years. DISCUSSION: This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood.

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%).

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.

Pregnancy outcomes and relationship to treatment adequacy in women treated early for congenital hypothyroidism: a longitudinal population-based study.

CONTEXT: Untreated hypothyroidism is associated with a higher risk of adverse obstetric and neonatal outcomes. Pregnancy complications have yet to be evaluated in patients treated early for congenital hypothyroidism (CH). OBJECTIVE: This study aimed to investigate pregnancy outcomes and their determinants in a population-based registry of young adult women with CH. SETTING AND DESIGN: In total, 1748 subjects were diagnosed with CH in the first 10 years after the introduction of neonatal screening in France; 1158 of these subjects completed a questionnaire on fecundity at a mean age of 25.3 years. We analyzed all declared singleton pregnancies ending after greater than 22 weeks of gestation before the initial survey (n = 207 pregnancies) and in the 3 years following the initial survey (prospective study, n = 174 pregnancies). The reference group comprised 7245 subjects from the French National Perinatal Survey. MAIN OUTCOME MEASURES: Pregnancy outcomes. Serum TSH concentrations and thyroid hormone requirements. RESULTS: In both the overall and prospective analyses, CH was associated with gestational hypertension, emergency cesarean delivery, induced labor for vaginal delivery, and prematurity. For the prospective population with CH, the adjusted odds ratios (aOR) (95% confidence interval [CI]) were 2.19 (1.26-3.81), 1.88 (1.17-3.02), 1.58 (1.12-2.24), and 1.85 (1.06-3.25), respectively. TSH concentrations at least 10 mIU/l during the first 3 or 6 months of pregnancy were associated with a higher risk of preterm delivery (aOR, 5.6; 95% CI, 1.6-20.0) and fetal macrosomia (aOR, 4.5; 95% CI, 1.03-20.1), respectively, whereas no such relationship was observed for TSH concentrations of 5.0-9.9 mIU/l. CONCLUSION: CH may result in adverse pregnancy outcomes. These nationwide data suggest that better thyroid disease management is required, particularly during the first two trimesters of pregnancy, together with vigilant monitoring.

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.

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.

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.

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.

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.

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.

Observational study of natural history of small sporadic nonfunctioning pancreatic neuroendocrine tumors.

CONTEXT: Asymptomatic sporadic nonfunctioning, well-differentiated pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis. OBJECTIVE: The objective of the study was to assess the natural history of asymptomatic sporadic NF-PNETs smaller than 2 cm in size and the risk-benefit balance of nonoperative management. EXPERIMENTAL DESIGN: From January 2000 to June 2011, 46 patients with proven asymptomatic sporadic NF-PNETs smaller than 2 cm in size were followed up for at least 18 months with serial imaging in tertiary referral centers. RESULTS: Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range 9-15). After a median follow-up of 34 months (range 24-52) and an average of four (range 3-6) serial imaging sessions, distant or nodal metastases appeared on the imaging in none of the patients. In six patients (13%), a 20% or greater increase in size was observed. Overall median tumor growth was 0.12 mm per year, and neither patients nor tumor characteristics were found to be significant predictors of tumor growth. Overall, eight patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range 27-58); all resected lesions were European Neuroendocrine Tumor Society T stage 1 (n = 7) or 2 (n = 1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion. CONCLUSIONS: In selected patients, nonoperative management of asymptomatic sporadic NF-PNETs smaller than 2 cm in size is safe. Larger and prospective multicentric studies with long-term follow-up are now needed to validate this wait-and-see policy.

Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants.

OBJECTIVE: To determine whether neonatal infections are associated with a higher risk of adverse neurodevelopment at 5 years of age in a population-based cohort of very preterm children. METHODS: We included all live births between 22 and 32 weeks of gestation, from 9 regions in France, in 1997 (EPIPAGE study). Of the 2665 live births, 2277 were eligible for a follow-up evaluation at 5 years of age: 1769 had a medical examination and 1495 underwent cognitive assessment. Cerebral palsy and cognitive impairment were studied as a function of early-onset sepsis (EOS) and late-onset sepsis (LOS), after adjustment for potential confounding factors, in multivariate logistic regression models. RESULTS: A total of 139 (5%) of the 2665 live births included in the study presented with EOS alone (without associated LOS), 752 (28%) had LOS alone (without associated EOS), and 64 (2%) displayed both EOS and LOS. At 5 years of age, the frequency of cerebral palsy was 9% (157 of 1769) and that of cognitive impairment was 12% (177 of 1495). The frequency of cerebral palsy was higher in infants with isolated EOS (odds ratio [OR]: 1.70 [95% confidence interval (CI): 0.84-3.45]) or isolated LOS (OR: 1.71 [95% CI: 1.14-2.56]) than in uninfected infants, and this risk was even higher in cases of combined EOS and LOS (OR: 2.33 [95% CI: 1.02-5.33]). There was no association between neonatal infection and cognitive impairment. CONCLUSIONS: Neonatal infections in these very preterm infants were associated with a higher risk of cerebral palsy at the age of 5 years, particularly in infants presenting with both EOS and LOS.

Brain injury in very preterm children and neurosensory and cognitive disabilities during childhood: the EPIPAGE cohort study.

OBJECTIVE: To investigate the association of motor and cognitive/learning deficiencies and overall disabilities in very preterm (VPT) children and their relations to gestational age (GA) and brain lesions. DESIGN SETTING AND PARTICIPANTS: EPIPAGE is a longitudinal population-based cohort study of children born before 33 weeks' gestation (WG) in 9 French regions in 1997-1998. Cumulating data from all follow up stages, neurodevelopmental outcomes were available for 90% of the 2480 VPT survivors at 8 years. Main outcomes were association of motor and cognitive deficiencies and existence of at least one deficiency (motor, cognitive, behavioral/psychiatric, epileptic, visual, and/or hearing deficiencies) in three GA groups (24-26, 27-28, and 29-32WG) and four groups of brain lesions (none, minor, moderate, or severe). RESULTS: VPT had high rates of motor (14%) and cognitive (31%) deficiencies. Only 6% had an isolated motor deficiency, 23% an isolated cognitive one and 8% both types. This rate reached 20% among extremely preterm. Psychiatric disorders and epilepsy were observed in 6% and 2% of children, respectively. The risks of at least one severe or moderate deficiency were 11 and 29%. These risks increased as GA decreased; only 36% of children born extremely preterm had no reported deficiency. Among children with major white matter injury (WMI), deficiency rates reached 71% at 24-26WG, 88% at 27-28WG, and 80% at 29-32WG; more than 40% had associated motor and cognitive deficiencies. By contrast, isolated cognitive deficiency was the most frequent problem among children without major lesions. CONCLUSIONS: In VPT, the lower the GA, the higher the neurodisability rate. Cerebral palsy is common. Impaired cognitive development is more frequent. Its occurrence in case without WMI or early motor disorders makes long-term follow up necessary. The strong association between motor impairments, when they exist, and later cognitive dysfunction supports the hypothesis of a common origin of these difficulties.

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.

Conservative management of bilateral vestibular schwannomas in neurofibromatosis type 2 patients: hearing and tumor growth results.

BACKGROUND: As new treatment modalities develop for the management of vestibular schwannomas (VS) in patients with neurofibromatosis type 2, it remains crucial to ascertain the natural history of the disease. OBJECTIVE: To determine the relationship between hearing and tumor growth in patients undergoing conservative VS management. METHODS: Patients harboring bilateral VS with at least 1 year of radiological follow-up were selected. Conservative management was proposed based on the small tumor size and/or serviceable hearing at presentation. Tumor size was calculated by using the 2-component box model and reported as mean tumor diameter. Hearing was evaluated by using pure-tone average and the American Academy of Otololaryngologists and Head and Neck Surgery classification. RESULTS: Forty-six patients harboring 92 VS were included. The mean clinical and radiological follow-up times were 6.0 and 4.2 years, respectively. The mean tumor diameter was 13 mm at presentation and 20 mm at the end of follow-up. Mean tumor growth rate was 1.8 mm/year. During follow-up, 17 patients (37%) underwent surgery for VS. Surgery-free rate for VS was 88% at 5 years. The number of patients with at least 1 serviceable ear was 39 (85%) at presentation and 34 (74%) at the end of follow-up, including 22 (66%) with binaural serviceable hearing maintained. There was no statistical correlation between tumor growth rate and preservation of serviceable hearing. Tumor growth rates and age at presentation were inversely correlated. CONCLUSION: This study illustrates the high variability among neurofibromatosis type 2 patients regarding hearing status and VS growth rate and justifies the choice of initial conservative management in selected cases. ABBREVIATIONS: : AAO-HNS, American Academy of Otololaryngologists and Head and Neck Surgery classificationMTD, mean tumor diameterNF2, neurofibromatosis type 2PTA, pure-tone averageSDS, speech discrimination scoreVS, vestibular schwannomas.