Early exposure of pregnant women to non-steroidal anti-inflammatory drugs delivered outside hospitals and preterm birth risk: nationwide cohort study.

OBJECTIVE: To assess the risk of preterm birth associated with nonsteroidal anti-inflammatory drugs (NSAIDs), focusing on early exposure in the period from conception to 22 weeks of gestation (WG). DESIGN: National population-based retrospective cohort study. SETTING: The French National Health Insurance Database that includes hospital discharge data and health claims data. POPULATION: Singleton pregnancies (2012-2014) with a live birth occurring after 22WG from women between 15 and 45 years old and insured the year before the first day of gestation and during pregnancy were included. We excluded pregnancies for which anti-inflammatory medications were dispensed after 22WG. METHODS: The association between exposure and risk of preterm birth was evaluated with GEE models, adjusting on a large number of covariables, socio-demographic variables, maternal comorbidities, prescription drugs and pregnancy complications. MAIN OUTCOME MEASURES: Prematurity, defined as a birth that occurred before 37WG. RESULTS: Among our 1 598 330 singleton pregnancies, early exposure to non-selective NSAIDs was associated with a significantly increased risk of preterm birth, regardless of the severity of prematurity: adjusted odds ratio (aOR) = 1.76 (95% CI 1.54-2.00) for extreme prematurity (95% CI 22-27WG), 1.28 (95% CI 1.17-1.40) for moderate prematurity (28-31WG) and 1.08 (95% CI 1.05-1.11) for late prematurity (32-36WG), with non-overlapping confidence intervals. We identified five NSAIDs for which the risk of premature birth was significantly increased: ketoprofen, flurbiprofen, nabumetone, etodolac and indomethacin: for the latter, aOR = 1.92 (95% CI 1.37-2.70) with aOR = 9.33 (95% CI 3.75-23.22) for extreme prematurity. CONCLUSION: Overall, non-selective NSAID use (delivered outside hospitals) during the first 22WG was found to be associated with an increased risk of prematurity. However, the association differs among NSAIDs. TWEETABLE ABSTRACT: French study for which early exposure to non-selective NSAIDs was associated with increased risk of prematurity.

A Computer Prescribing Order Entry-Clinical Decision Support system designed for neonatal care: results of the 'preselected prescription' concept at the bedside.

WHAT IS KNOWN: The neonatal intensive care units (NICUs) are at the highest risk of drug dose error of all hospital wards. NICUs also have the most complicated prescription modalities. The computerization of the prescription process is currently recommended to decrease the risk of preventable adverse drug effects (pADEs) in NICUs. However, Computer Prescribing Order Entry-Clinical Decision Support (C.P.O.E./C.D.S.) systems have been poorly studied in NICUs, and their technical compatibility with neonatal specificities has been limited. OBJECTIVES: We set up a performance study of the preselected prescription of drugs for neonates, which limited the role of the prescriber to choosing the drugs and their indications. METHODS: A single 29 bed neonatal ward used this neonatal C.P.O.E./C.D.S. system for all prescriptions of all hospitalized newborns over an 18-month period. The preselected prescription of drugs was based on the indication, gestational age, body weight and post-natal age. The therapeutic protocols were provided by a formulary reference (330 drugs) that had been specifically designed for newborns. The preselected prescription also gave complete information about preparation and administration of drugs by nurses. The prescriber was allowed to modify the preselected prescription but alarms provided warning when the prescription was outside the recommended range. The main clinical characteristics and all items of each line of prescription were stored in a data warehouse, thus enabling this study to take place. RESULTS: Seven hundred and sixty successive newborns (from 24 to 42 weeks' gestation) were prescribed 52 392 lines of prescription corresponding to 65 drugs; About 30·4% of neonates had at least one out of licensed prescription; A prescription out of the recommended range for daily dose was recorded for 1·0% of all drug prescriptions. WHAT IS NEW?: The C.P.O.E./C.D.S. systems can currently provide a complete preselected prescription in NICUs according to dose rules, which are specific to newborns and also comply with local specificities (therapeutic protocols and formulation of drugs). The role of the prescriber is limited to the choice of drugs and their indications. The prescriber still retains the possibility of modifying each item of the prescription, with all other prescription items being calculated by the C.P.O.E. system. In these conditions, the prescribers rarely modified the preselected prescription and the rate of out of range prescription was low. A multicentric study is required to confirm and extend these observations. CONCLUSIONS: This study showed the feasibility of preselected prescription in NICUs and a low rate of out of range prescriptions. The preselected prescription could play a key role in lowering the dose error rate in NICUs.

Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study.

OBJECTIVE: The aim of this study was to evaluate the effect of hydroxychloroquine (HCQ) on fetal preterm delivery and intrauterine growth restriction (IUGR) in a cohort of pregnant women with systemic lupus erythematosus (SLE). METHODS: Over an 11-year period (January 1, 2001 to December 31, 2011), all women with SLE and admitted to deliver after 22 weeks of gestation to Bordeaux University Hospital (France), were retrospectively enrolled in the present study. The population was then split into two groups based on the treatment they received: HCQ exposed (HCQ+) versus HCQ non-exposed (HCQ-) group. RESULTS: 118 pregnancies were included, 41 in the HCQ+ group and 77 in the HCQ- group. The rate of adverse fetal outcome was significantly lower in the HCQ+ group (p = 0.001), particularly in terms of preterm delivery, 15.8% versus 44.2% (p = 0.006), and IUGR, 10.5% versus 28.6% (p = 0.03). No adverse outcomes were reported in the HCQ+ group. CONCLUSION: HCQ reduces neonatal morbidity in women with SLE by significantly decreasing the rate of prematurity and intrauterine growth restriction.

Frequency of dosage prescribing medication errors associated with manual prescriptions for very preterm infants.

WHAT IS KNOWN AND OBJECTIVE: The risk of dosage Prescription Medication Error (PME) among manually written prescriptions within 'mixed' prescribing system (computerized physician order entry (CPOE) + manual prescriptions) has not been previously assessed in neonatology. This study aimed to evaluate the rate of dosage PME related to manual prescriptions in the high-risk population of very preterm infants (GA < 33 weeks) in a mixed prescription system. METHODS: The study was based on a retrospective review of a random sample of manual daily prescriptions in two neonatal intensive care units (NICU) A and B, located in different French University hospitals (Dijon and La Reunion island). Daily prescription was defined as the set of all drugs manually prescribed on a single day for one patient. Dosage error was defined as a deviation of at least ±10% from the weight-appropriate recommended dose. RESULTS AND DISCUSSION: The analyses were based on the assessment of 676 manually prescribed drugs from NICU A (58 different drugs from 93 newborns and 240 daily prescriptions) and 354 manually prescribed drugs from NICU B (73 different drugs from 131 newborns and 241 daily prescriptions). The dosage error rate per 100 manually prescribed drugs was similar in both NICU: 3·8% (95% CI: 2·5-5·6%) in NICU A and 3·1% (95% CI: 1·6-5·5%) in NICU B (P = 0·54). Among all the 37 identified dosage errors, the over-dosing was almost as frequent as the under-dosing (17 and 20 errors, respectively). Potentially severe dosage errors occurred in a total of seven drug prescriptions. None of the dosage PME was recorded in the corresponding medical files and information on clinical outcome was not sufficient to identify clinical conditions related to dosage PME. Overall, 46·8% of manually prescribed drugs were off label or unlicensed, with no significant differences between prescriptions with or without dosage error. The risk of a dosage PME increased significantly if the drug was included in the CPOE system but was manually prescribed (OR = 3·3; 95% CI: 1·6-7·0, P < 0·001). WHAT IS NEW AND CONCLUSION: The presence of dosage PME in the manual prescriptions written within mixed prescription systems suggests that manual prescriptions should be totally avoided in neonatal units.

Respiratory morbidity of preterm infants of less than 33 weeks gestation without bronchopulmonary dysplasia: a 12-month follow-up of the CASTOR study cohort.

The aim of this study was to describe the incidence and risk factors for respiratory morbidity during the 12-month period following the first respiratory syncytial virus (RSV) season in 242 preterm infants [<33 weeks gestational age (GA)] without bronchopulmonary dysplasia and 201 full-term infants (39-41 weeks GA) from the French CASTOR study cohort. Preterm infants had increased respiratory morbidity during the follow-up period compared to full-terms; they were more likely to have wheezing (21% vs. 11%, P = 0·007) and recurrent wheezing episodes (4% vs. 1%, P = 0·049). The 17 infants (14 preterms, three full-terms) who had been hospitalized for RSV-confirmed bronchiolitis during their first RSV season had significantly more wheezing episodes during the follow-up period than subjects who had not been hospitalized for RSV-confirmed bronchiolitis (odds ratio 4·72, 95% confidence interval 1·71-13·08, P = 0·003). Male gender, birth weight <3330 g and hospitalization for RSV bronchiolitis during the infant's first RSV season were independent risk factors for the development of wheezing episodes during the subsequent 12-month follow-up period.

Economic analysis of the costs associated with prematurity from a literature review.

OBJECTIVES: To analyse published cost-of-illness studies that had assessed the cost of prematurity according to gestational age at birth. METHODS: A review of the literature was carried out in March 2011 using the following databases: Medline, ScienceDirect, The Cochrane Library, Econlit and Business Source Premier, and a French Public-Health database. Key-word sequences related to 'prematurity' and 'costs' were considered. Studies that assessed costs according to the gestational age (GA) at the premature birth (<37 weeks of gestation) in industrialized countries and during the last two decades were included. Variations in the reported costs were analysed using a check-list, which allowed the studies to be described according to several methodological and contextual criteria. RESULTS: A total of 18 studies published since 1990 were included. According to these studies, costs were assessed for different follow-up periods (short, medium or long-term), and for different degrees of prematurity (extreme, early, moderate and late). Results showed that whatever the follow-up period, costs correlated inversely with GA. They also showed considerable variability in costs within the same GA group. Differences between studies could be explained by the choices made, concerning i/the study populations, ii/contextual information, iii/and various economic criteria. Despite these variations, a global trend of costs was estimated in the short-term period using mean costs from four American studies that presented similar methodologies. Costs stand at over US$ 100,000 for extreme prematurity, between US$ 40,000 and US$ 100,000 for early prematurity, between US$ 10,000 and US$ 30,000 for moderate prematurity and below US$ 4500 for late prematurity. CONCLUSION: This review underlined not only the clear inverse relationship between costs and GA at birth, but also the difficulty to transfer the results to the French context. It suggests that studies specific to the French health system need to be carried out.

[Growth charts and intrauterine growth retardation]. / Les courbes de poids fœtales et néonatales et la restriction de croissance intra-utérine.

Intrauterine growth restriction indicates that a fetus is unable to achieve its growth potential. The individual growth potential is approximated by customization of growth charts. Neonatal growth charts rely on body weight measures at birth while fetal growth charts rely on body weight estimated from biometric measurements of the fetus. The neonatal and fetal growth charts are not equivalent and have different meanings for epidemiologists and clinicians. Fetal growth charts also assess fetal growth velocity, but individual assessment of fetal weight may be flawed by lack of precision. Neonatal charts are constructed based on data obtained in the whole population or in a subgroup without gestational diseases. The two types of neonatal charts markedly differ at low gestational ages as 30% of preterm infants present intrauterine growth restriction, usually due to maternal diseases. Even if intrauterine growth restriction is a risk factor of fetal mortality, neonatal mortality, and short- and long-term morbidity, the predictive value of the charts (whether or not they are customized) at an individual level is low and may be improved by additional investigations.

Comparison of the ability of alternative birthweight and fetal weight standards to identify preterm newborns at increased risk of perinatal death.

OBJECTIVE: To compare prediction of perinatal deaths among preterm infants based on fetal weight standards versus a new subpopulation-based birthweight standard. DESIGN: Population-based cohort study. SETTING: France. POPULATION: A total of 9100 preterm singletons, born between 24 and 36 weeks of gestation in 2000-09, in Burgundy (France). METHODS: We first classified all newborns as either small for gestational age (SGA) or not, based on alternative fetal weight or birthweight standards, including a new birthweight standard that excludes infants born to mothers with disease related to the weight of a fetus. Based on discrepancies between the different classifications, we then divided the newborns into four groups, and compared their risks of stillbirth and in-hospital death, using a generalised linear model with relative risks (RR). MAIN OUTCOME MEASURES: Perinatal deaths, including, in separate analyses, stillbirths and in-hospital deaths. RESULTS: The preterm infants classified as SGA by our new subpopulation-based birthweight standard but not by the conventional birthweight standard had a significantly higher risk of both stillbirth (RR = 2.6; 95% confidence interval [95% CI] = 1.9-3.6) and in-hospital death (RR = 2.8; 95% CI = 1.8-4.5). In contrast, no risk increase was found for infants classified as SGA by the fetal standard only (RR = 1.1; 95% CI = 0.7-1.7 for stillbirths, and RR = 0.5; 95% CI = 0.3-1.3 for in-hospital deaths). CONCLUSIONS: Our subpopulation-based birthweight standard identified a subgroup of preterm newborns who have significantly increased risks of perinatal death but are not classified as SGA by the conventional birthweight standard. In contrast, the subgroup classified as SGA by the fetal standards only, but not by our subpopulation-based birthweight standard, had no increased risk of mortality, compared with non-SGA infants.

Hospitalizations for respiratory syncytial virus bronchiolitis in preterm infants at <33 weeks gestation without bronchopulmonary dysplasia: the CASTOR study.

This study was conducted during the 2008-2009 respiratory syncytial virus (RSV) season in France to compare hospitalization rates for bronchiolitis (RSV-confirmed and all types) between very preterm infants (<33 weeks' gestational age, WGA) without bronchopulmonary dysplasia and full-term infants (39-41 WGA) matched for date of birth, gender and birth location, and to evaluate the country-specific risk factors for bronchiolitis hospitalization. Data on hospitalizations were collected both retrospectively and prospectively for 498 matched infants (249 per group) aged <6 months at the beginning of the RSV season. Compared to full-term infants, preterm infants had a fourfold [95% confidence interval (CI) 1·36-11·80] and a sevenfold (95% CI 2·79-17·57) higher risk of being hospitalized for bronchiolitis, RSV-confirmed and all types, respectively. Prematurity was the only factor that significantly increased the risk of being hospitalized for bronchiolitis. The risk of multiple hospitalizations for bronchiolitis in the same infant significantly increased with male gender and the presence of siblings aged ⩾2 years.

Advantages and limitations of using national administrative data on obstetric blood transfusions to estimate the frequency of obstetric hemorrhages.

BACKGROUND: Obstetric hemorrhages are a frequent cause of maternal death all over the world, but are not routinely monitored. Health systems administrative databases could be used for this purpose, but data quality needs to be assessed. OBJECTIVES: Using blood transfusion data recorded in administrative databases to estimate the frequency of obstetric hemorrhages. Research design A population-based study. Subjects Validation sub-sample: all mothers who gave birth in a French region in 2006-07 (35 123 pregnancies). Main study: all mothers who gave birth in France in 2006-07 (1 629 537 pregnancies). METHOD: Linkage and comparison of administrative data on blood transfusions with data from the French blood agency ('gold standard'), and, based on this validation, the construction of a multivariable regression model to correct the number of pregnant women identified as having received a transfusion in the national administrative database. RESULTS: The blood transfusion rate observed in the gold standard was 7.12‰. The sensitivity of the administrative data was estimated at 66.3% and the positive predictive value at 91.3%. The estimated total number of pregnant women who received blood transfusions in France in 2006-07 was 10 941 (6.71‰). CONCLUSIONS: The administrative data, available in most countries, can be used to estimate the frequency of obstetric hemorrhages.

[Medication errors in neonatal medicine: from prescription to administration]. / Prévention des erreurs médicamenteuses en néonatologie : de la prescription à l'administration.

Neonatal units have the highest incidence of medication errors (approximately 5%) compared to adult and pediatric wards. Medication errors include prescribing errors, transcription errors, dispensing errors, medication administration errors, and monitoring. Dosing error is the most common prescribing error. Prevention of medication error must be global. The implementation of a computerized physician order entry significantly reduces prescribing errors but other preventive measures remain necessary.

Neonatal problems of late and moderate preterm infants.

Late and moderate preterm infants account for >80% of premature births. These newborns experience considerable mortality and morbidity in comparison with full-term born infants. The purpose of this paper is to summarise the most common morbidities of late and moderate preterm infants in the neonatal period, their incidence, severity, risk factors and need for admission to the different levels of care. The recent findings on preventive strategies and management priorities for clinical care of these vulnerable babies are also reviewed.

Similarly increased congenital anomaly rates after intrauterine insemination and IVF technologies: a retrospective cohort study.

BACKGROUND: While intrauterine insemination (IUI), a simple, inexpensive and non-invasive technique, is the most used assisted reproduction technology (ART) worldwide, the risk of major birth defects following IUI is paradoxically not well documented. METHODS: Retrospective cohort study performed in Burgundy, France, over a 9-year period which consisted of the cross analysis of two prospective databases, the Burgundy perinatal network database and the database of the assisted conception units in Burgundy. A total of 1348 ART singletons [in vitro fertilization technologies (IVFT): n= 903; IUI: n= 445] matched with 4044 infants conceived naturally, 552 ART twins (IVFT: n= 362; IUI: n= 190) matched with 1656 twins who were conceived naturally. The major birth defects were categorized according to the European Surveillance of Congenital Anomalies classification EUROCAT. RESULTS: Compared with naturally conceived singletons, singletons born after IUI and IVFT had a higher prevalence of major congenital malformations, with adjusted odd ratios (AOR) of 2.0 [95% confidence interval (CI) 1.0-3.8] and 2.0 (CI 1.3-3.1); 3.6 and 4.2% of infants born, respectively. All twins and unlike-sex twins born after IVFT but not IUI, have an increased prevalence of major birth defects compared with naturally conceived twins; AOR of 3.0 (CI 1.6-5.6) and 3.7 (CI 1.1-16.9), respectively. When comparing IUI with IVFT, no differences were observed for singletons (AOR 1.0; CI 0.4-2.2), all twins (AOR 0.4; CI 0.1-1.2) and unlike-sex twins (AOR 0.3; CI 0.1-4.5). CONCLUSIONS: The risk of major birth defects in singletons conceived through IUI was increased over naturally conceived singletons. This risk was no different from that observed after IVFT.

Paediatric intensive care admissions for respiratory syncytial virus bronchiolitis in France: results of a retrospective survey and evaluation of the validity of a medical information system programme.

The purpose of this study was to describe the characteristics of patients with bronchiolitis admitted to a paediatric intensive care unit (PICU), and to evaluate a national registry of hospitalizations (Programme de Médicalisation des Systèmes d'Information; PMSI) as a potential source of epidemiological data. Of the 49 French PICUs invited to take part in a retrospective survey of children aged <2 years who were hospitalized during the 2005-2006 epidemic season, 24 agreed to participate. Overall, 467 children were enrolled: 75% were aged <2 months, 76% had positive respiratory syncytial virus (RSV) tests, 34·9% required non-invasive ventilation, 36·6% were mechanically ventilated, and six infants died. The main neonatal characteristics were: prematurity (31·9%), respiratory disease (16·5%), congenital heart disease (6·4%), receiving mechanical ventilation (11·6%), and bronchopulmonary dysplasia at day 28 (3·8%). For bronchiolitis episode, the kappa coefficient between the survey and PMSI data was good only for mechanical ventilation (0·63) and the death rate (0·86).

A Population-Based Study of Meconium Aspiration Syndrome in Neonates Born between 37 and 43 Weeks of Gestation.

The epidemiology of meconium aspiration syndrome (MAS) in term neonates is described in a population-based retrospective study of data recorded for all births from 2000 to 2007 in a French region (Burgundy). Of the 132 884 eligible term newborns, the rate of meconium-stained amniotic fluid (MSAF) was 7.93%. The prevalence of severe MAS was 0.067% in the overall population. MAS rate was 0.11% at 37-38 weeks of gestation (WG), 0.20% at 39-41 WG, and 0.49% at 42-43 WG. Factors independently associated with severe MAS were identified by a case-control study, that is, thick meconium amniotic fluid, fetal tachycardia, Apgar score ≤3 at 1 minute, and birth in a level III facility. Our results confirm the high prevalence of MSAF after 37 WG but also show the low frequency of severe MAS in a period corresponding to the new international recommendations on the management of birth with MSAF.

Hypoproteinemia on the first day of life and adverse outcome in very preterm infants admitted to the neonatal intensive care unit.

OBJECTIVE: We aimed to investigate the relationship between day-1 hypoproteinemia and severe adverse outcome (SAO) in very preterm infants admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: Retrospective study of all patients born from 24 to 31 weeks gestation and cared for in our NICU over an 8-year period. Infants were excluded if the serum protein value on the first day of life was not available. RESULT: A total of 913 patients were included. In all, 14.6% presented with SAO (death or severe neurological injury on cranial ultrasound). Hypoproteinemia (total protein level <40 g l(-1)) on day 1 of life occurred in 19.5 % of all patients. The rate of SAO was 33.7% in patients with hypoproteinemia and 9.9% in those with normoproteinemia (P<0.0001). Logistic and multiple regression analysis confirmed that the association hypoproteinemia-SAO remained significant after adjustment for the other major predictors of outcome present at baseline (odds ratio 3.4; 95% confidence interval 2.1-5.4; P<0.0001). CONCLUSION: Hypoproteinemia was highly associated with SAO in this cohort of critically ill preterm infants. We are unable to explain the link between hypoproteinemia and adverse outcome in our population. This investigation serves as a hypothesis-generating report of a large preterm infants sample, and suggests the need to assess the predictive accuracy for adverse outcome of hypoproteinemia in future prospective studies.

The effect of parenteral nitrogen and energy intake on electrolyte balance in the preterm infant.

BACKGROUND/OBJECTIVES: Recent guidelines for preterm parenteral nutrition (PN) recommend an earlier and higher intake of amino acids (AA) and energy to avoid postnatal catabolism and approximate normal fetal growth. Few investigations explored how early PN may affect electrolyte and water homeostasis. We performed a prospective observational trial to assess the effect of nutrient intake on electrolyte homeostasis and balance. SUBJECTS/METHODS: During 16 months, all infants ≤32 weeks were eligible. In the first week of life, we recorded the following daily: electrolytes (plasma and 8-h urine collection), nutritional intake, urine output, body weight, and we calculated sodium (Na) and potassium (K) balance. Infants were divided, for analysis, into three groups of AA intake: low <1.5 g/kg/day (LAA), medium 1.5-2 g/kg/day (MAA) and high >2 g/kg/day (HAA). RESULTS: A total of 154 infants were included. HAA group presented lower weight loss. Na balance was influenced by urine output and postnatal age, with little contribution of nutrition. Kalemia and K balance were mainly influenced by AA intake. K balance differed among groups: LAA, -2.3 mmol/kg/week; MAA, 1.1 mmol/kg/week; and HAA 2.6 mmol/kg/week (P<0.0001). In the HAA group, plasma and urine K were significantly lower and non-oliguric hyperkalemia was reduced. CONCLUSIONS: Na homeostasis was very slightly modified by early nutrition, suggesting that a negative Na balance is obligatory after birth. We showed that AA intake strongly affects K balance, minimize hyperkalemia and reduces weight loss. As K balance is strictly linked to cellular metabolism, we speculate that early nutrition may inhibit cellular catabolism and reduce the contraction of intracellular water compartment.

Fluid and electrolyte intake during the first week of life in preterm infants receiving parenteral nutrition according current guidelines.

There is growing evidence that early water and electrolyte homeostasis may be influenced by energy balance in preterm infants. Some fluid and electrolyte disturbances of postnatal life could be in part promoted by the catabolism due to withheld amino acid and energy supply after birth. According to current guidelines parenteral nutrition with relatively high protein and lipid needs is commenced on day one. By turning the nitrogen balance from negative to zero or even positive, amino acid administration could also minimize the occurrence of water and ions disturbances after birth especially in extremely preterm infants. Future researches are needed in order to further investigate the impact of amino acid and energy intake on early fluid balance in preterm infants.

Aquaporin-2 urinary excretion in preterm infants: relationship to diuresis and vasopressin.

AIMS: Few investigations have explored the urinary aquaporin-2 (u-AQP2) excretion pattern after birth in preterm infants with conflicting results regarding the correlation between u-AQP2, urinary osmolality and vasopressin. The aims of this study were to evaluate u-AQP2 excretion during the first week of life in preterm infants, to correlate u-AQP2 with other markers of renal function and to investigate the relationship between u-AQP2, urinary tonicity and arginine-vasopressin in the immature kidney. METHODS: In infants born less than 33 weeks daily diuresis, u-AQP2, urinary arginine-vasopressin, urine and plasma tonicity, creatinine and electrolytes were measured through the first 7 days of life. RESULTS: Fifty-five infants were evaluated. u-AQP2 excretion showed the following profile: the highest u-AQP2 levels were found on day 2 and values remained significantly higher until day 5 with respect to day 1. On day 6, u-AQP2 levels significantly decreased to values closer to those found on day 1. u-AQP2 excretion was not associated with arginine-vasopressin while significant, but weak association was found with urinary tonicity (r = -0.20; -0.32 < r < -0.11; P < 0.05). u-AQP2 excretion and creatinine clearance were significantly associated during the study period (r = 0.19; 0.08 < r < 0.29; P < 0.05). There was a strong association between totally u-AQP2 excretion and diuresis over the week (r = 0.72; 0.66 < r < 0.76; P < 0.0001). CONCLUSION: Significant variations occur in AQP2 expression levels during the first week of life in preterm infants. AQP2 does not seem to contribute to the urinary concentration ability after birth. Further investigations are required to elucidate the mechanisms underlying the strong association between diuresis and u-AQP2 excretion in early postnatal life.

[Variations in the prevalence of Down's syndrome in the French population between 1978 and 2005]. / Variations de prévalence de la trisomie 21 en population française entre 1978 et 2005.

OBJECTIVES: To evaluate the impact of maternal age and prenatal diagnosis on the prevalence of Down's syndrome at birth in French population sample. PATIENTS AND METHODS: Data concerning Down's syndrome from 1978 to 2005 were obtained from the REMERA registry of congenital malformations. The population surveyed was approximately 10% of French births. We studied total prevalence, live-birth prevalence and the prevalence of pregnancy termination after prenatal diagnosis. RESULTS: Mean maternal age has risen from 26 to 30 years over the study period. Total prevalence of Down's syndrome has increased from 14 per 10,000 in 1978 to 23 per 10,000 live-births in 2005. Termination of pregnancy after prenatal diagnosis of Down's syndrome gradually increased reaching 78% in 2005. Live-birth prevalence decreased from 14 per 10,000 in 1978 to 5.1 per 10,000 in 2005. CONCLUSION: This work shows the importance of continuing the epidemiological survey of Down's syndrome in France, especially because of the modification in population ageing as well in prenatal screening policies for Down's syndrome.