Béatrice Ducot

Maternal Personal Exposure to Airborne Benzene and Intrauterine Growth

Background Studies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight. Objective Our aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth. Methods We recruited pregnant women in two French maternity hospitals in 2005–2006 as part of the EDEN mother–child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth. Results Median benzene exposure was 1.8 μg/m3 (5th, 95th percentiles, 0.5, 7.5 μg/m3). Log-transformed benzene exposure was associated with a gestational age–adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), −135 to −1 g] and of 1.9 mm in mean head circumference at birth (95% CI, −3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 mm in head circumference assessed during the third trimester (95% CI, −4.0 to 0.3 mm) and of 1.5 mm in head circumference assessed at the end of the second trimester of pregnancy (95% CI, −3.1 to 0 mm). Conclusions Our prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants.

Embolization of spinal cord arteriovenous shunts: morphological and clinical follow-up and results--review of 69 consecutive cases.

OBJECTIVEWe sought to analyze the results of embolization in patients with intradural spinal cord arteriovenous shunts. METHODSThe clinical and radiological files of 69 of a population of 155 patients treated with embolization between 1981 and 1999 were reviewed retrospectively. The patients’ clinical status was evaluated according to Karnofsky Performance Scale score. Twenty-one (14%) of 155 patients were treated surgically because they were thought to be poor candidates for embolization. Twenty-four (15%) of 155 patients were considered untreatable with surgery or embolization; in these patients, follow-up was proposed, but only 8 of them were followed appropriately and remained stable after the first consultation. Forty-one (26%) of 155 patients consulted our group, but no follow-up could be obtained. In 69 (45%) of 155 patients, comprising 20 children and 49 adults, endovascular treatment was performed with the patients under general anesthesia and without provocative tests, mainly with acrylic glue, in 99% of these patients. RESULTSThe mean number of diagnostic and therapeutic sessions was 3.5 per patient, and the mean number of pure therapeutic sessions was 1.5 per patient. Follow-up ranged between 6 months and 18 years (mean, 5.6 yr). In 16% of patients, anatomic obliteration of spinal cord arteriovenous shunts was obtained. Embolization reduced more than 50% of the spinal cord arteriovenous shunts in 86% of cases. No recanalization was noted on follow-up angiograms. Good clinical outcomes were obtained in 83% of the patients: 15% of them were asymptomatic, 43% were improved, and 25% were stable. In 4% of patients, embolization failed to stabilize the disease. Transient deficits were seen after embolization in 14% of the patients, and permanent severe complications occurred in 4% of the patients (Karnofsky Performance Scale score ≤70). Mild worsening was seen in 9% of the patients (Karnofsky Performance Scale score, 80). No bleeding or rebleeding was seen after endovascular treatment was considered to have been completed. CONCLUSIONThis study proves that embolization with acrylic glue is a therapeutic option that compares favorably with surgery or embolization with other agents (particles, coils, or balloons). It offers stable long-term clinical results, despite not necessarily achieving total cure. Studies of larger series with longer follow-up are necessary to confirm these encouraging therapeutic data.

Prognostic Value of Endoscopy in Children With Biliary Atresia at Risk for Early Development of Varices and Bleeding

BACKGROUND & AIMS Biliary atresia is the most common cause of childhood cirrhosis. We investigated prospectively the development of portal hypertension in 139 children with biliary atresia, the risk of gastrointestinal (GI) bleeding in the first years of life, and associations between endoscopic patterns of varices and risk. METHODS Children with clinical or ultrasonographic signs of portal hypertension underwent upper GI endoscopy examinations (n = 125, median age of 13 months). Information was recorded about esophageal varices and grade, red wale markings on the variceal wall, gastric varices along the cardia, and portal hypertensive gastropathy. A second endoscopy examination was performed in 64 children after a mean interval of 51 months to study their progression or regression. RESULTS At the first endoscopy examination, 88 of 125 children had esophageal varices, including 74 who were younger than 2 years. Grade II and III varices, red markings, gastric varices, and signs of gastropathy were present in 29, 30, 24, and 27 children, respectively. At the second endoscopy examination, progression, stability, and regression of endoscopic signs were observed in 37, 18, and 9 of the 64 children, respectively. Twenty-eight children had GI bleeding at a median age of 17 months. Multivariate analysis showed that red markings, and most importantly gastric varices, were independent factors associated with bleeding. CONCLUSIONS Children with biliary atresia have a high risk of portal hypertension in the first years of life. Spontaneous regression of varices is rare. Children with a combination of esophageal varices and red markings and/or gastric varices along the cardia should receive primary prophylaxis of bleeding.

How would a decline in sperm concentration over time influence the probability of pregnancy

Background: Reports have suggested a decline in sperm concentration during the second half of the 20th century. The effect of this decline on fecundability (the monthly probability of pregnancy) could be detected in principle by a study of time to pregnancy. In practice, the amplitude of this expected effect is not well known and the statistical power of time-to-pregnancy studies to detect it has not been explored. Methods: We developed a nonparametric model to describe a temporal decline in sperm concentration using data on French semen donors. We then applied this model to 419 Danish couples planning a first pregnancy in 1992, to predict their time to pregnancy as if the pregnancy attempt had begun during earlier decades with higher sperm concentrations. Finally, we used bootstrap simulations to estimate the statistical power of prospective or retrospective studies that compared fecundability (estimated from time to pregnancy) across these time periods. We express the change in fecundability over time as a fecundability ratio (FR), with values less than 1 indicating decreased fecundability. Results: We estimate that the median sperm concentration decreased by 21% from 1977 to 1992 and by 47% from 1947 to 1992. The estimated decline in fecundability with those semen changes was 7% from 1977 to 1992 (FR = 0.93, adjusted) and 15% from 1947 to 1992 (FR = 0.85, adjusted). The total numbers of couples that would be needed in prospective studies of time to pregnancy to detect these changes in fecundability (with a power of 80%) were 12,000 when comparing 1977 to 1992, and 2000 when comparing 1947 to 1992. Retrospective studies of the same size that excluded childless couples had much lower statistical power and were biased toward the null. Conclusion: The effect of realistic declines in sperm concentration on time to pregnancy may be observed only with studies that include several thousand couples.

Feasibility of the Current-Duration Approach to Studying Human Fecundity

Approaches for monitoring time trends in couples’ fecundity and for studying its sensitivity to environmental factors are needed. Two approaches rely on the inclusion of a cross-sectional sample of couples currently “at risk” of pregnancy either with follow up (prevalent cohort) or without follow up (current-duration design). To illustrate the feasibility of the current-duration design, we contacted a random sample of 1204 French women age 18 to 44 years in 2004 and recruited those who were currently having unprotected sexual intercourse. The current duration since the beginning of unprotected intercourse was defined for 69 women (5.7%). An additional 15 women (1.2%) were planning to start trying to become pregnant within the next 6 months. Parametric methods allowed, based on current duration of unprotected intercourse, estimation of fecundity as if the couples had been followed prospectively. The estimated proportion of couples not pregnant after 12 months of unprotected intercourse was 34% (95% confidence interval [CI] = 15–54%). The accelerated-failure time model allows study of the influence of environmental factors on fecundity. As an illustration, tobacco smoking by the woman was associated with a doubling in the median duration of unprotected intercourse before pregnancy (adjusted time ratio = 2.4; 95% CI = 1.1–5.2). We quantified the influence of time trends in the prevalence of smoking on this estimate. We suggest ways to quantify or avoid other potential bias. In conclusion, it is possible to recruit a sample of couples currently having unprotected intercourse. The current-duration design appears feasible with approximately 5 times as many women eligible for study as for an incident cohort design.

Risk factors of inadequate pain relief during epidural analgesia for labour and delivery

PurposeTo determine the causes of failure of epidural analgesia during labour and delivery.MethodsDuring six months, pregnant patients receiving epidural analgesia and delivering vaginally were studied prospectively. Bupivacaine 0.125% was used for the initial bolus dose and subsequent continuous infusion. Top-ups of the same solution were used for inadequate pain relief assessed using a visual analogue pain score (VAPS) and/or by clinical examination. Inadequate pain relief was defined as the need for ≥ 2 top-ups in addition to epidural infusion and failure during delivery as VAPS ≥ 30 mm during the expulsion phase.Results1009 patients delivered during this period, 596 had epidural analgesia for vaginal delivery of a live infant and data were complete in 456. Inadequate pain relief during labour and during delivery were found in 5.3% and 19.7% of patients. Risk factors of inadequate pain relief included: inadequate analgesic efficacy of the first dose (Odds ratio: 3.5, P = 0.001) and posterior presentation (Odds ratio: 5.6, P = 0.001). Radicular pain during epidural placement was associated with failure during labour (Odds ratio: 3.9, P = 0.05). Duration of epidural analgesia > six hours (Odds ratio: 9.1, P = 0.001) was a risk factor for insufficient pain relief during labour whereas duration of epidural analgesia < one hour was associated with pain during delivery (Odds ratio: 18.3, P = 0.001).ConclusionSeveral obstetrical and epidural-related factors increase the risk of inadequate epidural analgesia. For some, simple changes of practice pattern may lead to improved pain relief.RésuméObjectifDéterminer les causes d’insuffisance de l’analgésie péridurale obstétricale.MéthodesPendant 6 mois, toutes les patientes en travail ayant reçu une analgésie péridurale ont été évaluées prospectivement. La bupivacaïne 0,125 % a été utilisée pour l’injection péridurale initiale et pour la perfusion continue de même que pour les réinjections qui ont suivi l’évaluation de la douleur par l’échelle visuelle analogique (EVA) et la vérification du bloc. Une insuffisance d’analgésie pendant le travail a été définie par le besoin d’au moins deux réinjections (en plus de la perfusion péridurale continue) et lors de l’accouchement par une EVA 30 mm.RésultatsParmi les 1009 patientes étudiées, 596 ont reçu une analgésie péridurale pour donner naissance à un enfant vivant par voie vaginale et les données étaient complètes pour 456 d’entre elles (76,5 %). Une insuffisance d’analgésie a été constatée pendant le travail chez 5,3 % des patientes et, lors de l’accouchement, chez 19,7 %. Plusieurs facteurs de risque d’insuffisance d’analgésie ont été communs aux phases de dilatation et d’expulsion: insuffisance analgésique du premier bolus (coefficient de risque CR: 3,5; P = 0,001) et présentation postérieure (CR: 5,6; P = 0,001). La survenue d’une radiculalgie pendant la ponction était associée à un risque d’analgésie insuffisante pendant le travail (CR: 3,9; P = 0,05). Une durée d’analgésie péridurale > 6 h (CR: 9,1; P = 0,001) était un facteur de risque d’insuffisance pendant le travail alors qu’une durée < I h était associée à un risque accru d’échec lors de l’expulsion (CR: 18,3; P = 0,001).ConclusionPlusieurs facteurs obstétricaux ou liés à la technique péridurale sont asssociés à un risque accru d’analgésie inadéquate. Pour certains facteurs techniques, des modifications simples des pratiques pourraient conduire à une amélioration notable de l’analgésie.

Feasibility and Diagnostic Accuracy of Supersonic Shear-Wave Elastography for the Assessment of Liver Stiffness and Liver Fibrosis in Children: A Pilot Study of 96 Patients

PURPOSE To evaluate the feasibility of using supersonic shear-wave elastography (SSWE) in children and normal values of liver stiffness with the use of control patients of different ages (from neonates to teenagers) and the diagnostic accuracy of supersonic shear wave elastography for assessing liver fibrosis by using the histologic scoring system as the reference method in patients with liver disease, with a special concern for early stages of fibrosis. MATERIALS AND METHODS The institutional review board approved this prospective study. Informed consent was obtained from parents and children older than 7 years. First, 51 healthy children (from neonate to 15 years) were analyzed as the control group, and univariate and multivariate comparisons were performed to study the effect of age, transducer, breathing condition, probe, and position on elasticity values. Next, 45 children (from 1 month to 17.2 years old) who underwent liver biopsy were analyzed. SSWE measurements were obtained in the same region of the liver as the biopsy specimens. Biopsy specimens were reviewed in a blinded manner by a pathologist with the use of METAVIR criteria. The areas under the receiver operating characteristics curve (AUCs) were calculated for patients with fibrosis stage F0 versus those with stage F1-F2, F2 or higher, F3 or higher, and F4 or higher. RESULTS A successful rate of SSWE measurement was 100% in 96 patients, including neonates. Liver stiffness values were significantly higher when an SC6-1 probe (Aixplorer; SuperSonic Imagine SA, Aix-enProvence, France) was used than when an SL15-4 probe (Aixplorer) was used (mean ± standard deviation, 6.94 kPa ± 1.42 vs 5.96 kPa ± 1.31; P = .006). There was no influence of sex, the location of measurement, or respiratory status on liver elasticity values (P = .41-.93), although the power to detect such a difference was low. According to the degree of liver fibrosis at liver biopsy, 88.5%-96.8% of patients were correctly classified, with AUCs of 0.90-0.98 (95% confidence interval [CI]: 0.8, 1.0). The AUC for patients with stage F0 versus stage F1-F2 was 0.93 (95% CI: 0.87, 0.99). CONCLUSION SSWE allows accurate assessment of liver fibrosis, even in children with early stage (F1-F2) disease, and the choice of transducer influences liver stiffness values.

Liver Disease Associated with ZZ α1-Antitrypsin Deficiency and Ursodeoxycholic Acid Therapy in Children

Objectives: To investigate the effect of ursodeoxycholic acid (UDCA) in children with liver disease associated with ZZ α1-antitrypsin (AAT) deficiency. Patients and Methods: A total of 42 affected children received UDCA (30 mg · kg−1 · day−1) and underwent clinical and biochemical follow-up at least yearly. Results: In group 1, 22 children whose mean initial γ-glutamyl-transpeptidase (GGT) was 7.4 × N normalized serum liver test results after a mean treatment of 2.6 years. In 16 of these children, UDCA was discontinued. Relapse was observed in 11 children, and liver test results returned to normal after UDCA resumption. In the other 5 children, liver test results remained normal during a mean period of 2.5 years. In group 2, 11 children (mean initial GGT 12.8 × N) had improved liver test results after a mean treatment of 2.3 years. In group 3, 9 children (mean initial GGT 33.8 × N) had no liver test result improvement and evolution toward cirrhosis, requiring liver transplantation in 7. Most of the children in group 1 had normal results of clinical examination after UDCA treatment, versus none in group 3 (P ≤ 0.00001). Initial GGT (P ≤ 0.002) and total bilirubin (P ≤ 0.05) levels were significantly lower in group 1 than in group 3. Combined initial values of GGT ≤5.5 × N and total bilirubin ≤66 μmol/L were associated with normalization of liver test results in 90% of children. Conclusions: UDCA may significantly improve clinical status and liver test results in some children with liver disease associated with ZZ AAT deficiency. No beneficial effect of UDCA was shown in children with the most severe liver involvement. Initial levels of GGT and total bilirubin may be of prognostic value for therapy effectiveness.

Progression to high-risk gastroesophageal varices in children with biliary atresia with low-risk signs at first endoscopy.

Objectives: Biliary atresia carries a risk of bleeding because of portal hypertension. Our goal was to define the factors associated with the emergence of endoscopic signs carrying a high risk of bleeding in children who did not display these signs at the first upper gastrointestinal endoscopy. Methods: From 1989 to 2013, a total of 225 children with low-risk signs at the first endoscopic examination underwent ≥2 upper gastrointestinal endoscopic examinations. The emergence of high-risk gastroesophageal varices was observed in 76 children in the 10 years following the first endoscopic examination. A survival study using the occurrence of high-risk varices as an event was performed to identify factors related to the emergence of these varices and to describe the probability of their emergence in 2 groups of children ages older than 18 months and 18 months or younger at the time of the first endoscopy. Results: High total serum bilirubin concentration, young age, and high number/grade of esophageal varices at the first endoscopy were significantly related to the emergence of high-risk varices. The probability of the emergence of high-risk signs was higher and these signs appeared faster in infants 12 months of age or younger and/or when the first endoscopic examination displayed >1 grade 1 or grade 2 varices. Progression to high-risk varices was also related to bilirubinemia in children older than 18 months at the first endoscopy. Conclusions: The results allow defining a program of repeat endoscopies to detect high-risk varices and to discuss endoscopic primary prophylaxis of bleeding or hasten liver transplantation when these signs are found.

Sexual behavior and smoking: risk factor for urethritis in men.

Two hundred men who had symptoms of urethritis and 207 controls were interviewed. Because 60% of the men were of foreign nationality, the analysis of risk factors for urethritis was undertaken separately for the French and foreign subpopulations. The risk factors for urethritis were different for the French and foreign men. For the French men who had smoked, the risk of infection was 2.9 times greater than that for men who had never smoked (95% confidence interval, 1.2-7.6), after taking type of sexual behavior into account. There is a significant increase in the risk of urethritis when the amount of tobacco consumed daily increases (P less than 0.02). This finding suggests that smoking is an independent risk factor.