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Biomedical subjects

H Grandjean

Publications and source records attributed to H Grandjean.

At least 19 recordsLinked to original sources

Sensitivity of routine ultrasound screening of pregnancies in the Eurofetus database. The Eurofetus Team.

In this prospective study, we recorded details on 3,685 fetuses with congenital structural abnormalities from an unselected population of women who underwent routine ultrasound examinations during their pregnancies. Overall, 2,262 fetuses were diagnosed as being abnormal before birth (sensitivity = 61.4%). The total number of abnormalities was 4,615, of which 1,733 (37.5%) were major abnormalities. The overall number of detected abnormalities was 2,593 (sensitivity = 56.2%). If only major abnormalities were considered, the sensitivity rose to 73.7%, compared to only 45.7% for the minor abnormalities. Within each severity group, the accuracy of detection varied across systems. For the major abnormalities, it was higher for the central nervous system (88.3%) and urinary tract (84.8%), but lower for heart and great vessels (38.8%). Detection of minor abnormalities was also effective for the urinary tract (89.1%), but not for the heart and great vessels (20.8%) and the musculoskeletal system (18%).

Congenital Abnormalities

Sensitivity of fetal anomaly detection as a function of time.

In this paper, we show that the ratio of the number of fetal anomalies detected by ultrasounds (US) to the total number of cases is not a consistent estimator of the US sensitivity. As Eddy pointed out, when the disease evolves over time, the sensitivity of a test also varies over time according to the development of the disease. To assess correctly the detection capability of a test, it is therefore necessary to estimate a time continuous function (sensitivity function) instead of a single parameter. From a methodological point of view, by considering the "detectability" time of a fetal anomaly as a random variable and parametrizing its distribution function, we estimate the probability that an anomaly is detected conditional upon the precise timing of actually performed US during pregnancy. We fit this model with Eurofetus data (about 7,300 abnormal fetuses), and we compare estimations for different kinds of anomalies (classification based on the system involved and/or severity of the handicap). To allow for heterogeneity of anomalies regarding the detectability time, we generally adopt mixture models. For instance, we select a bi-gamma distribution for major malformations and estimate that 63% of such anomalies are detectable quite early in pregnancy (conditional mean: 15.2 weeks of amenorrhea (WA) +/- 4.2 WA), the others becoming detectable later (30.3 WA +/- 6.4 WA). Such results are then integrated in a cost-effectiveness analysis.

Congenital Abnormalities

Detection of chromosomal abnormalities, an outcome of ultrasound screening. The Eurofetus Team.

Chromosomal abnormalities were recorded from all the fetuses of women who benefited from sonographic examinations in the Eurofetus centers, excluding those for whom karyotyping was motivated by age or personal history. Among the 378 chromosomal abnormalities recorded, 210 were detected before birth (sensitivity = 55.6%). Down syndrome (trisomy 21) represented 197 cases, or which 68 were detected before birth (sensitivity = 34.5%). Eighty-two of the cases of Down syndrome had associated structural abnormalities; the sensitivity in these cases increased to 57%. Among the 115 cases of Down syndrome without structural abnormalities, 21 (18.3%) had associated abnormal ultrasound findings that led to prenatal detection. Sensitivity of prenatal detection was 58.1% for trisomy 13 and 79% for trisomy 18. For the abnormalities detected before birth, spontaneous fetal death occurred in 27% of cases, and an early termination of pregnancy was decided in 53% of cases.

Chromosome Aberrations

[Definition and prevalence of school-age multi-handicaps].

BACKGROUND: Regulations concerning services for handicapped children in France have defined the notion of multi-handicap. There are, however, divergences in the procedures for applying this definition, and differences in the prevalence in different areas. This study is aimed at clarifying these two points. POPULATION AND METHODS: A survey in three French departments provided data about disabled children born between 1975 and 1985 who received services from the departmental committee for special education or from day hospitals. The data was systematically collected by a physician using medical files. RESULTS: The results showed that the group of multi-handicapped children was heterogeneous. The most restrictive definition (motor disability with profound mental retardation, bed-ridden or restricted to a chair) resulted in a prevalence of 0.73%. A broader definition based on the concept of zero autonomy, but excluding mild or moderate mental retardation, resulted in a prevalence of 1.28%. CONCLUSION: The importance of specifying the objectives of a definition selected for operational reasons is stressed in order to improve the estimation of specific needs.

Adolescent

Visual impairment in children: prevalence, aetiology and care, 1976-85.

Visual impairment (corrected visual acuity in the best eye < 0.3) was evaluated in a retrospective study of 296 children born between 1976 and 1985 and recruited from three French departments. For children younger than 9 years, the overall prevalence was 0.80 per 1000 and that of blindness was 0.28 per 1000. No decrease in prevalence was noted over this decade. The most common aetiologies were antenatal factors (48%), which were observed mainly in the cases of poor vision, and perinatal factors (27%), which were more common in the cases of blindness. Fifty-six per cent of the children had an additional severe handicap. The most common association was with motor impairment and mental retardation. The mean age of first medical care (3.1 years) did not change over the decade: 2.0 years for children with an associated handicap, 2.9 years for cases of isolated blindness and 5.1 years for cases of isolated poor vision. Among children with isolated visual impairment, there was a significantly higher percentage of scholastic underachievers in those presenting after the age of 5 years (39.3% vs. 14.6%).

Achievement

Growth hormone, insulin-like growth factor-I and insulin-like growth factor binding protein-3 are regulated differently in small-for-gestational-age and appropriate-for-gestational-age neonates.

Growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were measured in 90 neonates during the first 5 days of life. Twenty-six small-for-gestational-age (SGA) neonates were compared with 64 appropriate-for-gestational-age (AGA) neonates. There were no differences in nutritional status between the 2 groups. Mean GH levels were significantly higher in the SGA group (53.4 +/- 30.8 vs. 39.9 +/- 23.3 microg/l; p < 0.05). In both groups GH levels correlated with birth weight (expressed as SDS) but not with gestational age. IGF-I levels were significantly lower in SGA neonates (6.6 +/- 4.0 vs. 11.7 +/- 8.2 ng/ml; p < 0.01). In SGA neonates with short stature, IGF-I levels were lower and GH levels were higher than in normal stature SGA neonates. IGFBP-3 levels were significantly lower in SGA neonates than in AGA neonates (0.72 +/- 0.40 vs. 0.98 +/- 0.43 microg/l; p < 0.01). IGF-I and IGFBP-3 correlated with gestational age in AGA but not in SGA neonates and there was no correlation with birth weight in either group. Our data provide evidence for a graduation in the severity of impact of fetal 'malnutrition' on the somatotropic axis and on intrauterine growth. The most severe state (SGA with short stature) was associated with a GH-resistance syndrome, characterized by very low IGF-I levels and high GH levels.

Body Height

Autism and associated medical disorders in a French epidemiological survey.

OBJECTIVE: To estimate the prevalence of autism, to assess the strength of its association with specific medical disorders, and to test for a secular increase in its incidence. METHOD: An epidemiological survey was conducted among 325,347 French children born between 1976 and 1985 and living in three different French départements. Diagnosis, educational level, and associated medical conditions were abstracted from the records of children known to local educational authorities. Data were also pooled with those from another similar survey. RESULTS: One hundred seventy-four children (mean age: 11.6 years) with autism were identified. The prevalence rate was 5.35/10,000 (16.3/10,000 if other pervasive developmental disorders are included), with no difference according to geographical area or social class. Rates of medical conditions were as follows: 1.1% for tuberous sclerosis, 2.9% for chromosomal abnormalities including fragile X, 2.9% for cerebral palsy, 4.6% for sensory impairments, 0.6% for neurofibromatosis, 0.6% for congenital rubella, and 1.7% for Down syndrome. In the combined sample of 328 children with autism, the level and pattern of medical correlates were comparable, with tuberous sclerosis having a consistently strong association with autism. Prevalence rates were similar in successive birth cohorts. CONCLUSION: Medical disorders (excluding epilepsy and sensory impairments) accounted for fewer than 10% of the cases of autism. No secular increase in the prevalence of autism was found.

Adolescent

Prevalence and time trends of disabilities in school-age children.

BACKGROUND: Although the evolution of the prevalence of cerebral palsy is now well documented, much less is known about the evolution of the prevalence of other disabilities such as mental retardation, sensorial defects, autism and psychosis. The aim of this paper is to determine those trends. METHODS: A population-based survey was carried out in 1992-1993 in three French 'départments'. All disabled children born between 1976 and 1985 and receiving a special education and/or financial assistance were systematically registered. RESULTS: The comparison of three cohorts of children born in 1976-1978, 1979-1981 and 1982-1984 using the test for trend in proportion showed a significant decrease (P = 0.03) in the prevalence of severe mental retardation, after exclusion of Down syndrome. This decrease was significant for severe mental retardation associated with psychosis. The time trend prevalence for cerebral palsy increased (P = 0.03) but was irregular. The time trend prevalence of other disabilities (other motor defects, severe sensorial disabilities, autism and psychosis) did not change significantly. A detailed analysis of severe mental retardation and cerebral palsy was performed by geographical area, age at first registration and type of disability. CONCLUSION: The increase in prevalence of cerebral palsy is possibly due to earlier registration of disabled children. The decrease in prevalence of severe mental retardation does not seem to be due to recruitment bias, but there is a possibility of classification bias.

Adolescent

Influence of maternal blood flow on the placental transfer of three opioids--fentanyl, alfentanil, sufentanil.

The placental transfer of three opioids used in peridural analgesia, fentanyl, alfentanil and sufentanil, and two reference substances, antipyrine and *H2O, was determined ex vivo in the human placental cotyledon system. (1) In the first set of experiments, the infusion rates were constant and fixed at physiological flow rates. Under these conditions, the magnitude of the materno-fetal transfer was in the following order: *H2O = antipyrine = fentanyl > alfentanil > sufentanil. No particular influence of molecular weight, lipophilia, pKa or the degree of ionization could be discerned. (2) In the second set of experiments, the influence of different flow rates, reflecting various pathophysiological conditions, was examined. There was a linear relationship between the maternal flow and the materno-fetal transfer of the three opioids. On the other hand, for antipyrine and tritiated water, the relationship was logarithmic, a difference attributed to the marked lipophilia of the opioids. (3) At high maternal flow rates, saturation was observed for all five substances due to the short duration of contact with the membrane. There were logarithmic relationships between the maternal flow and the materno-fetal transfer. (4) These findings emphasize the importance of the lipophilic and hydrophilic characteristics of drugs on placental transfer, especially in the event of fluctuations in maternal flow.

Alfentanil

Fall-related factors and risk of hip fracture: the EPIDOS prospective study.

BACKGROUND: Most hip fractures result from falls. However, the role of fall-related factors has seldom been examined. Comparison of the predictive value of these factors with that of bone mineral density (BMD) has important implications for the prevention of hip fractures. METHODS: We assessed femoral-neck BMD by dual-photon X-ray absorptiometry and potential fall-related risk factors, which included self-reported physical capacity, neuromuscular function, mobility, visual function, and use of medication in 7575 women, aged 75 years or older, with no history of hip fracture recruited at five centres in France. We followed up these women every 4 months to record incident hip fractures. During an average of 1.9 years of follow-up 154 women suffered a first hip fracture. FINDINGS: In age-adjusted multivariate analyses, we found four independent fall-related predictors of hip fracture: slower gait speed (relative risk = 1 . 4 for 1 SD decrease [95% Cl 1.1-1.6)]; difficulty in doing a tandem (heel-to-toe) walk (1.2 for 1 point on the difficulty score [1.0-1.5]); reduced visual acuity (2.0 for acuity < or = 2/10 [1.1-3.7]); and small calf circumference (1.5 [1.0-2.2]). After adjustment for femoral-neck BMD, neuromuscular impairment--gait speed, tandem walk--and poor vision remained significantly associated with an increased risk of subsequent hip fracture. With high risk defined as the top quartile of risk, the rate of hip fracture among women classified as high risk based on both a high fall-risk status and low BMD was 29 per 1000 women-years, compared with 11 per 1000 for women classified as high risk by either a high fall-risk status or low BMD; for women classified as low risk based on both criteria the rate was five per 1000. INTERPRETATION: We conclude that neuromuscular and visual impairments, as well as femoral-neck BMD, are significant and independent predictors of the risk of hip fracture in elderly mobile women, and that their combined assessment improves the prediction of hip fractures.

Absorptiometry, Photon

Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study.

Increased bone turnover has been suggested as a potential risk factor for osteoporotic fractures. We investigated this hypothesis in a prospective cohort study performed on 7598 healthy women more than 75 years of age. One hundred and twenty-six women (mean years 82.5) who sustained a hip fracture during a mean 22-month follow-up were age-matched with three controls who did not fracture. Baseline samples were collected prior to fracture for the measurement of two markers of bone formation and three urinary markers of bone resorption: type I collagen cross-linked N- (NTX) or C-telopeptide (CTX) and free deoxypyridinoline (free D-Pyr). Elderly women had increased bone formation and resorption compared with healthy premenopausal women. Urinary excretion of CTX and free D-Pyr, but not other markers, was higher in patients with hip fracture than in age-matched controls (p = 0.02 and 0.005, respectively). CTX and free D-Pyr excretion above the upper limit of the premenopausal range was associated with an increased hip fracture risk with an odds ratio (95% confidence interval) of 2.2 (1.3-3.6) and 1.9 (1.1-3.2), respectively, while markers of formation were not. Increased bone resorption predicted hip fracture independently of bone mass, i.e., after adjustment for femoral neck bone mineral density (BMD) and independently of mobility status assessed by the gait speed. Women with both a femoral BMD value of 2.5 SD or more below the mean of young adults and either high CTX or high free D-Pyr levels were at greater risk of hip fracture, with an odds ratio of 4.8 and 4.1, respectively, than those with only low BMD or high bone resorption. Elderly women are characterized by increased bone turnover, and some markers of bone resorption predict the subsequent risk of hip fracture independently of hip BMD. Combining the measurement of BMD and bone resorption may be useful to improve the assessment of the risk of hip fracture in elderly women.

Absorptiometry, Photon

[Outcome of blood gas parameters during the first 24 years after Exosurf administration].

BACKGROUND: There is now good evidence that the clinical course of infants with respiratory distress syndrome can be improved by treatment with exogenous surfactant. However, optimal methods of giving such a treatment are still debated. POPULATION AND METHODS: The arterial blood gases and the arterial/alveolar oxygen tension ratio (a/A) were recorded during the 24 hours following artificial surfactant (Exosurf) treatment in 400 newborns aged 25 to 42 gestational weeks. A positive response was defined by an a/A ratio > 0.22 or an increase in a/A ratio up to 25%. RESULTS: After administration of the first dose, a positive response was obtained in 63% of cases during the first 6 hours and 11% during the 6 following hours. The response after the second dose was favourable in 75% of cases. At 24 hours after treatment, 36% of the infants had obtained an a/A ratio > 0.22. CONCLUSION: Because of the 18% of infants who responded positively only after the second dose, administration of this dose seems justifiable even in case of non-response to the first dose. The quality of the response is related to the severity of the pulmonary illness but is independent of the gestational age.

Analysis of Variance

Prevalence, aetiology, and care of severe and profound hearing loss.

Severe and profound hearing loss (> 70 dB) were analysed in a retrospective study of 226 children, born between 1976 and 1985, and recruited from three French administrative departments. The prevalence was 0.54 per 1000 children under 9 years old, with no decrease over the study period. A hereditary origin was identified in 20.8% of cases and an infectious origin in 11.5%. Perinatal risk factors were present in 11.5%, while the aetiology was undetermined in more than half the cases. In 85.8% of the children there was no other severe impairment. Marked learning difficulties were observed: 36% of the children were two years behind their age group and 28% were more than two years behind. The age of initial care decreased over the study period but is still too advanced. Systematic neonatal screening would enable earlier care, which should limit the social and educational impact of hearing loss.

Adolescent

[Fetal growth from the AUDIPOG study. I. Establishment of reference curves].

The collection of nearly 100,000 births from 22 maternity hospitals in various French regions permitted to establish foetal growth curves for weight, height and head circumference. The 50th percentiles of weight at term obtained in this sample are not different from those given by Leroy and Lefort in the Paris region in 1971. However below 38 weeks of gestation, we found that 50th percentiles are 100 or 150 g less than those given by Leroy and Lefort. The discussion from international papers show large variations of the 10th percentile for weight in according to gestational age and sex, these variations are often related to the choice of different target populations.

Birth Weight

[Fetal growth from the AUDIPOG study. II. Application for the diagnosis of intrauterine growth retardation].

The identification of intrauterine growth retarded infants remains a problem. It is useful to distinguish between small for date which uses the reference of a statistical birthweight limit and intrauterine growth retardation. A study comprising nearly 100,000 births from many French regions allowed a definition of the limits of birthweights taking into account gestational age, sex, birth rank, maternal height and pregravid maternal weight. This new approach distinguished two groups of newborns, the "constitutionaly small" and those who are newly called "growth retarded". The validity of this new classification is discussed.

Adult

Femur/foot length ratio for detection of Down syndrome: results of a multicenter prospective study. The Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant Study Group.

OBJECTIVE: The aim was to determine the sensitivity and specificity of a short femur for detection of trisomy 21 in the second trimester. STUDY DESIGN: Thirty-six investigators in 12 centers measured biparietal diameter and femur and foot lengths in 3582 14- to 24-week-old fetuses in mothers undergoing amniocentesis for age, history of genetic disorder, or laboratory signs. RESULTS: Among the various ratios for evaluating femur shortening the femur/foot ratio appeared to be the most discriminatory. At an upper cutoff level of 0.88 a sensitivity of 35% was obtained for 4.6% false positives in normal infants. However, to only obtain 2.3% false positives, the cutoff limit had to be set at 0.85, giving a sensitivity of no more than 15%. CONCLUSION: Determination of the femur/foot ratio improves ultrasonographic detection of trisomy 21 in the second trimester, although for systematic use it would lead to an unacceptable number of unnecessary amniocenteses.

Amniocentesis

Sonographic measurement of nuchal skinfold thickness for detection of Down syndrome in the second-trimester fetus: a multicenter prospective study. The AFDPHE Study Group. Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant.

OBJECTIVE: To determine the sensitivity and specificity of soft-tissue nuchal-fold measurement in the second-trimester fetus for the detection of trisomy 21. METHOD: Thirty-six investigators in 12 centers measured nuchal skinfold thickness in 3308 fetuses of 14-24 weeks' gestation. All mothers were referred for amniocentesis because of age, history of genetic disorder, or laboratory findings. Those referred with an ultrasound indication for amniocentesis, including nuchal-fold thickening, were excluded. RESULTS: Overall, nuchal skinfold was 6 mm or more in 8.5% of chromosomally normal fetuses and in 38% of those with trisomy 21. A false-positive rate below 5% was obtained by 81% of the investigators. Raising the cutoff of normality to 7 mm after 18 weeks' gestation improved specificity. CONCLUSION: Although the diagnostic value of this sign in skilled hands could allow its use as an indication for genetic amniocentesis at the second trimester, the method does not appear suitable for population screening because of the high variability in the results among the investigators.

Analysis of Variance