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.

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.

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.

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.

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.

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.

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.

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).

Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I.

The oral-facial-digital syndrome type I (OFD I) is characterized by multiple congenital malformations of the face, oral cavity and digits. A polycystic kidney disease (PKD) is found in about one-third of patients but long-term outcome and complications are not well described in the international literature. Renal findings have been retrospectively collected in a cohort of 34 females all carrying a pathogenic mutation in the OFD1 gene with ages ranging from 1 to 65 years. Twelve patients presented with PKD - 11/16 (69%) if only adults were considered -with a median age at diagnosis of 29 years [IQR (interquartile range) = (23.5-38)]. Among them, 10 also presented with renal impairment and 6 were grafted (median age = 38 years [IQR = (25-48)]. One grafted patient under immunosuppressive treatment died from a tumor originated from a native kidney. The probability to develop renal failure was estimated to be more than 50% after the age of 36 years. Besides, neither genotype-phenotype correlation nor clinical predictive association with renal failure could be evidenced. These data reveal an unsuspected high incidence rate of the renal impairment outcome in OFD I syndrome. A systematic ultrasound (US) and renal function follow-up is therefore highly recommended for all OFD I patients.

[Evolution of the number of rotavirus and respiratory syncytial virus infections in children hospitalised in a French university hospital between 1998 and 2005]. / Évolution du nombre d'infections àRotavirus et à virus respiratoire syncytial chez les enfants hospitalisés au CHU de Dijon entre 1998 et 2005.

AIM: Respiratory syncytial virus (RSV) and Rotavirus infections represent up to 30% of cross infections in pediatric units. As they are a major public health problem, we studied their evolution and distribution at the Dijon University Hospital. POPULATION AND METHODS: This exhaustive retrospective study included children under 15 with a new Rotavirus or RSV infection who were hospitalised at the Dijon University Hospital between 1998 and 2005. The general trend was determined by using moving averages, and the Spearman correlation coefficient r(s) was calculated. RESULTS: From 1998 to 2005, 1886 new RSV (n=981) or Rotavirus (n=905) infections were identified in hospitalised children. The number of the infections decreased significantly, both for RSV (r(s)=-0.71 ; p<0.0001) and for Rotavirus (r(s)=-0.77 ; p<0.0001). Almost half of Rotavirus infections were nosocomial (46.3%) vs 5.3% of RSV infections, p<0.0001. There was no significant difference in the proportion of RSV nosocomial infections between the epidemic and non-epidemic period (4.9% of nosocomial infections vs 7.1% respectively, p=0.25). Rotavirus nosocomial infections were less frequent in epidemic period (41.6%) than in non-epidemic period (54.6%); p=0.0002. CONCLUSION: RSV and Rotavirus infections significantly decreased between 1998 and 2005. Proportion of RSV or Rotavirus infections didn't increase in epidemic period, which could be explained both by an increased attention from healthcare professionals and by the effectiveness of hygiene measures taken.

[Stroke in neonates and children]. / Les accidents vasculaires cérébraux du nouveau-né et de l'enfant.

The clinical presentation, risk factors, causes, vital or functional prognosis, and acute management options for stroke occurring in neonates and children are specific, differing from those observed in young adults. Compared with the adult population, less is known about the epidemiology of stroke in the under-18 population where the disease could become more frequent because of advances in both neonatal resuscitation techniques for cerebral disorders and neuroimaging techniques enabling the diagnosis of small lesions. Clinical features are often delayed, especially in neonates, and unlike epilepsy or dystonia of the affected limb, which are frequent complications, aphasia is rather rare. The most frequent causes of stroke at the beginning of life are cardiac embolism, for ischemic stroke, and arteriovenous malformations, for intracerebral hemorrhage. Acute management at this age is specific. This article reviews the literature on the epidemiological and clinical features, the main causes, and the acute management guidelines of stroke occurring in newborn infants and children and highlights the need for neurologists to have comprehensive knowledge of this disease.

[Severe delayed apnea in neonates and Prader-Willi syndrome: 2 case studies]. / Apnées sévères différées en période néonatale et syndrome de Prader-Willi: à propos de 2 cas.

We report 2 cases of severe apnea in newborns presenting with Prader-Willi syndrome. They required transient mechanical ventilation and finally returned to spontaneous breathing. Clinical progression was then usual for the syndrome. Respiratory failure appearing after a few days of life could be a new neonatal clinical feature for the diagnosis of Prader-Willi syndrome. It is not related to poor outcome.

Clinical relevance of prevention of respiratory syncytial virus lower respiratory tract infection in preterm infants born between 33 and 35 weeks gestational age.

Premature infants are vulnerable to severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) resulting in hospitalisation and the potential for longer-term respiratory morbidity. Whilst the severity and consequence of RSV LRTI are generally accepted and recognised in infants born

[Liveborn birth-weight of single and uncomplicated pregnancies between 28 and 42 weeks of gestation from Burgundy perinatal network]. / Poids des nouveau-nés issus de grossesses uniques et non compliquées entre 28 et 42 semaines d'aménorrhée à partir des données du réseau périnatal de la région Bourgogne.

OBJECTIVES: To build a reference chart for birth weight according to gestational age based on a newborn population from single uncomplicated pregnancies. MATERIALS AND METHODS: We have used data from the Burgundy perinatal network for the years 2000 to 2005. We can exclude, with a validate linkage procedure of all mother-newborn couples, the whole of newborns from pregnancies complicated by mellitus diabetes or pre eclampsia. After statistical validation, the birth weights were modelled and graphically represented. RESULTS: We have used 105,665 data from the "healthy" sample to construct a birth weight distribution according to gestational age at 28 to 42 weeks'. Results are also represented adjusted for sex. CONCLUSION: We present an original birth weight distribution according to gestational age from a recent French population sample. Exclusion of maternal conditions which may affect fetal growth modify the data distribution, mainly for low birth weights and premature deliveries. Used in clinical practice, it could lead to better identify newborns with increased risk of postnatal complications.

[What are the neonatal risks in low-risk pregnancies: implications for the organization of birth centers]. / Quel risque néonatal pour les grossesses à bas risque: implications pédiatriques pour l'organisation des maisons de naissance?

AIM: This study was designed to identify pregnant women at low risk for severe neonatal morbidity. This population should apply for delivery in birth centers. POPULATION AND METHODS: This study was retrospective and included all livebirths in Burgundy over a 4-year period. Fifteen obstetric criteria recorded in the regional perinatal database were used to select pregnant women at low risk for severe neonatal morbidity. Incidence of severe neonatal morbidity in the low and high risk groups was assessed from the following markers: postnatal death; severe neurological conditions (ischemic encephalopathy, seizures, meningitis, intraventricular hemorrhage stage 3-4 and cystic periventricular leukomalacia in preterm infants); tracheal intubation; hospitalization in neonatal intensive care unit. RESULTS: The incidence of severe neonatal morbidity was significantly different (P<0.0001) in the low risk group (0.34% [IC 95%: 0.29-0.40]; N=46345) as compared with the high risk group (5.6% [IC 95%: 5.3-5.9]; N=24961). The main neonatal diseases in the low risk group were: respiratory diseases (29.8%); congenital heart diseases (17.9%) and perinatal asphyxia (15.3%). CONCLUSION: Even though the low risk criteria were associated with a low incidence of severe neonatal morbidity, residual morbidity should be considered in organization of birth centers in France.

[Metabolism of potassium in preterm infants]. / Métabolisme du potassium chez le prématuré

UNLABELLED: During the first days of life, hyperkalemia can affect 30 to 60% of very low birth weight infants free of acute renal insufficiency (i.e. nonoliguric hyperkalemia). The place of the kidney in the regulation of the potassium homeostasis of VLBW remains badly specified. OBJECTIVE: To evaluate the rate and the mechanisms of hyperkalemia in infants born at less than 32 weeks' gestation. METHODS: A prospective study was conducted in 33 preterm infants (BW=1289+/-382 g; GA=28.8+/-1.7 weeks). Fifteen consecutive 8-hour urine collections were performed for each infant from the 8th hour of life (495 periods). A plasma sample was obtained at the end of each urine collection. Sodium, potassium and creatinine were measured in urine and blood samples as often as possible. RESULTS: Plasma potassium concentrations varied significantly over the 15 successive periods with an initial value (P1) of 4.55+/-0.80 mmol/l, a peak on P3 (4.94+/-0.81 mmol/l) and the lowest value on P13 (3.88+/-0.42 mmol/l). Hyperkalemia (plasma potassium>6.0 mmol/l) was observed in 4 infants (12%) and in 1.2% of the periods. The cumulative potassium balance (output-input) was negative over the first 7 periods (-1.97 mmol/kg), and afterwards became positive (from P8 to P15:+1.57 mmol/kg). Over the first 3 days, plasma potassium concentrations were positively correlated (p<0.01) with urinary excretion of potassium, clearance of potassium, fractional excretion of potassium, and negatively with endogenous creatinine clearance. CONCLUSION: In the first days of life, very low birth weight infants present an increase in kalemia associated with a negative potassium balance indicating a intracellular to extracellular potassium shift rather than a lower renal potassium excretion.

Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Patent ductus arteriosus is a common complication of prematurity that frequently requires surgical or medical treatment. The benefit of prophylactic treatment by indometacin, a cyclo-oxygenase inhibitor, remains uncertain compared with curative treatment. This benefit could be improved with ibuprofen, another cyclo-oxygenase inhibitor with fewer adverse effects than indometacin on renal, mesenteric, and cerebral perfusion. We aimed to compare prophylactic and curative ibuprofen in the treatment of this abnormality in very premature infants. METHODS: We did a randomised controlled trial in infants younger than 28 weeks of gestation, who were randomly assigned to receive either three doses of ibuprofen or placebo within 6 h of birth. After day 3, symptomatic patent ductus arteriosus was treated first by open curative ibuprofen, then back-up indometacin, surgery, or both. The primary endpoint was need for surgical ligation. Analysis was per protocol. FINDINGS: The study was stopped prematurely after 135 enrollments because of three cases of severe pulmonary hypertension in the prophylactic group. 65 infants received prophylactic ibuprofen, and 66 received placebo. Prophylaxis reduced the need for surgical ligation from six (9%) to zero (p=0.03), and decreased the rate of severe intraventricular haemorrhage from 15 (23%) to seven (11%) (p=0.10). However, survival was not improved (47 [71%] placebo vs 47 [72%] treatment, p=1.00), because of high frequency of adverse respiratory, renal, and digestive events. INTERPRETATION: In premature infants, prophylactic ibuprofen reduces the need for surgical ligation of patent ductus arteriosus, but does not reduce mortality or morbidity. Therefore, it should not be preferred to early curative ibuprofen.