[Guidelines for multivitamin administration in fortified human milk prepared for preterm infants]. / Protocole d'administration de l'Uvestérol ADEC® au prématuré nourri au lait de femme enrichi.

BACKGROUND: To reach nutritional standards, human milk has to have 2g/dL of protein. In 2013, Lafeber stated that when human milk is fortified up to 2g/dL, it may increase its osmolality up to 500 mOsm/kg. He also warned that care must be taken when adding a drug or vitamins to human milk. AIM: We studied, for the first time, the impact of adding multivitamins (ADEC) on human fortified milk osmolality. METHOD: The osmolality of 36 pasteurized, fortified human milk samples was measured. The amount of milk required as a solvent to maintain osmolality below 500 mOsm/kg was then determined. RESULTS: The osmolality of 2mL of fortified human milk reached up to 750 mOsm/kg when the multivitamins ADEC was added. The osmolality decreased proportionately as the solution was diluted and if vitamins are added in two half-doses each time. It is only with 20mL of milk that the osmolality lowers to its initial rate of 430 mOsm/kg. The stronger the milk's fortification is, the greater impact it has on the milk's osmolality. CONCLUSION: New nutritional recommendations for premature infants are needed. In the meantime, when the fortified milk intake is under 20mL, it is preferable to extend parenteral intakes with fat-soluble vitamins or reduce doses of vitamins in milk. Also, we should use enriched human milk as a fortifier and be cautious with indiscriminate fortification or when adding drugs and electrolyte solutions.

PP116. Circulating PlGF can help predict preeclampsia and adverse outcome in patients with suspected preeclampsia or fetal growth restriction.

INTRODUCTION: The circulating concentration of PlGF is reported to be lower in patients experiencing preeclampsia and patients delivering a small for gestational age (SGA) neonate. OBJECTIVES: To evaluate the predictive value of circulating PlGF for preeclampsia and adverse outcome in patients with suspected preeclampsia or fetal growth restriction. METHODS: We prospectively enrolled 96 women who were included after 22 weeks gestation (WG) for suspected preeclampsia or suspected SGA, and measured plasma levels of PlGF (Triage® PLGF, Alere©) at enrollment. We studied outcome until delivery and one week postpartum, and defined adverse outcome as severe preeclampsia, SGA neonate (<10th centile) or elective delivery for maternal or fetal complication. Severe adverse outcome was studied among patients included <34WG and defined as eclampsia, HELLP syndrome, very SGA (<3rd centile) or elective delivery <34WG. RESULTS: The mean logtransformed PlGF level was lower for women who experienced preeclampsia than for those who did not (2.9 vs 3.7, p=0.02), and was markedly lower for patients who experienced adverse outcome (2.9 vs 4.3, p<0.001). The odds of presenting an adverse outcome were higher for the lowest tertile of PlGF compared to the higher (OR=12 , 95% CI [3-46] ). Among patients included <34WG, the odds of experiencing a severe adverse outcome were, respectively, for the lowest and intermediate tertile as compared with the higher tertile: OR=132 , 95% CI [14-1273]; and OR=20, 95% CI [4-106] . When included <34 WG, patients with a PlGF level <12pg/ml experienced a severe adverse outcome in 96% of cases (24/25), and only 1 of 28 patients with a PlGF level >50pg/ml experienced a severe adverse outcome within 15 days (4%). Among women with suspected SGA who were enrolled <32WG and whose PlGF level was <12pg/ml, 89% had an elective delivery before 34 WG (17/19). CONCLUSION: Among women with suspected preeclampsia or SGA, PlGF circulating levels differ between women who will experience an adverse outcome and those who will not. It can therefore be of help in the management of these patients, especially for those for whom the diagnosis is suspected early in pregnancy.

[Drugs during preeclampsia. Fetal risks and pharmacology]. / Médicaments utilisés dans la prise en charge de la prééclampsie. Pharmacologie et risques foetaux.

During pregnancy, the maternal, placental and fetal physiological characteristics constantly evolve and thereby constantly alter drug bioavailability in the mother and feto-placental unit. Gastric emptying time is increased and bowel movements are reduced. Distribution in the maternal body is mainly influenced by body mass variations, water content and fat stores. Metabolic capacity of the liver appears unchanged but renal clearance of drugs is gradually increased. The placental transfer of most drugs mainly consists of passive diffusion between the maternal and fetal circulations, along their respective concentration gradients. Only the free, unbound and non-ionized fraction of the drug readily crosses the membranes. Four anti-hypertensive drugs have been granted a license for the treatment of PE since the year 2000: these are Clonidine (Catapressan), Nicardipine (Loxen+), Labetalol (Trandate), Dihydralazine (Nepressol). Dihydralazine, Labetalol and Nicardipine are not contraindicated in the breast feeding mother. The administration of a long acting Benzodiazepine during pregnancy can lead to new born intoxication of variable severity and duration. These symptoms may precede a withdrawal syndrome (hyper-excitability, tremor, gastro-intestinal upset, such as diarrhea or vomiting). Breast feeding by mothers using benzodiazepines (Nitrazepam and Midazolam) is not recommended. In France, the use of low molecular weight heparins is not recommended during pregnancy whereas in the United States, they are recommended as a prophylactic measure. Their high molecular weight prevents their diffusion across the placental membrane and therefore prevents any fetal or neonatal risk. Bromocriptine is used as an inhibitor of lactation. During the post-partum period, serious accidents have been described: these consist of systemic hypertension, fits, infarcts (cardiac and neurological). It is contraindicated in case of systemic hypertension.

Retrospective diagnosis of an adverse drug reaction in a breastfed neonate: liquid chromatography-tandem mass spectrometry quantification of dextropropoxyphene and norpropoxyphene in newborn and maternal hair.

Dextropropoxyphene (DP) and norpropoxyphene (NP) are commonly used in the treatment of postpartum pain. The drug is widely prescribed in Europe and Canada and has been recently approved for use in the U.S. Its safety during breastfeeding, however, has not been fully established. Very few reports on its effects on neonates have been published. We report here the case of a mother treated with DP (6 capsules a day for 10 days) while she was breastfeeding. On day 7, her baby was lethargic and had difficulties with breastfeeding, which led to early weaning. The correlation between side effects observed in the infant and DP was made retrospectively by measuring DP and NP hair concentrations in the mother-infant pair with liquid chromatography-tandem mass spectrometry. Breastfeeding mothers taking DP expose their infants to high doses of DP and NP. In agreement with previously published reports, these data indicate that acetaminophen and nonsteroidal antiinflammatories are preferable for analgesia during breastfeeding. Breastfeeding should be encouraged under most circumstances, and if the mother takes any treatment for pain, a commonly prescribed drug with pharmacologic data available must be used.

Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy.

Enoxaparin is frequently prescribed for pregnant women who are at high risk for thromboembolic complications. We conducted a population pharmacokinetics study with 75 pregnant women and 38 nonpregnant women as controls to evaluate enoxaparin pharmacokinetics during pregnancy and the postpartum period. Clearance of the drug was higher in the pregnant women throughout pregnancy when compared with nonpregnant women (0.78 +/- 0.03 l/h vs. 0.52 +/- 0.03 l/h, respectively P < 0.001) with the stage of the pregnancy having no influence. The volume of distribution was influenced by stage of the pregnancy, characterized by a two-step increase, with an initial rise paralleling the woman's increase in body weight during the first two trimesters, followed by an additional increase of 41% during the last 2 months of pregnancy, independent of changes in weight. Using enoxaparin pharmacokinetic parameters to simulate anti-Xa time profiles, we observed that the maintenance of the same doses throughout pregnancy resulted in a progressive reduction in mean and peak anti-Xa activities. We recommend the administration of doses normalized for body weight changes so as to counteract enoxaparin pharmacokinetic changes that accompany various stages of pregnancy.

Population pharmacokinetics of ciprofloxacin in pediatric and adolescent patients with acute infections.

The aim of the present study was to characterize the population pharmacokinetics of ciprofloxacin in patients with and without cystic fibrosis ranging in age from 1 day to 24 years and to propose a limited sampling strategy to estimate individual pharmacokinetic parameters. Patients were divided into four groups according to the treatment schedule. They received ciprofloxacin by intravenous infusion (30 min) or by the oral route. The number of samples collected from each patient ranged from 1 to 12. The population parameters were computed for an initial group of 37 patients. The data were analyzed by nonlinear mixed-effect modeling by use of a two-compartment structural model. The interindividual variability in clearance (CL) was partially explained by a dependence on age and the patient's clinical status. In addition, a significant relationship was found between weight and the initial volume of distribution. Eighteen additional patients were used for model validation and evaluation of limited sampling strategies. When ciprofloxacin was administered intravenously, sampling at a single point (12 h after the start of infusion) allowed the precise and accurate estimation of CL and the elimination half-life, as well as the ciprofloxacin concentration at the end of the infusion. It should be noted that to take into account the presence of a lag time after oral administration, a schedule based on two sampling times of 1 and 12 h is needed. The results of this study combine relationships between ciprofloxacin pharmacokinetic parameters and patient covariates that may be useful for dose adjustment and a convenient sampling procedure that can be used for further studies.

[Clinical study and prevalence of fetal alcohol syndrome in medico-social institutions of the Reunion Island]. / Etude clinique et prévalence du syndrome d'alcoolisation foetale pris en charge dans les établissements médicosociaux de l'île de la Réunion.

BACKGROUND: Fetal alcohol syndrome (FAS) is a major problem in the Reunion Island and the Public Health Authorities decided to determine its prevalence in their medico-social centers on 31 December 1996. MATERIAL AND METHODS: A questionnaire was established to identify affected patients in the 20 medico-social centers in charge of 1320 children. Eighty-eight children were selected and 87 could be analyzed. RESULTS: Sixty-four of 87 (76.3%) were FAS and 23 of 87 (23.7%) had closely alcohol-related diseases. The prevalence was between 7.1 and 14.1% and lower than expected from available data. CONCLUSION: The study allowed to precise the social and familial factors predisposing to alcohol addiction during pregnancy. A TV prevention message will be broadcasted after this study.

[Effect of acupuncture on radial artery hemodynamics. Two controlled studies in pre-exposed and naive healthy subjects]. / Effets de l'acupuncture sur l'hémodynamique de l'artère radiale. Deux essais contrôlés chez des patients pré-exposés et chez des sujets sains naïfs.

Palpation of the radial pulses is one of the most important techniques in traditional Chinese medicine. Two double-blind randomised trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitised subjects), and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform was measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-minute's acupuncture period. In sensitised patients, arterial diameter significantly increased during real acupuncture, compared to the sham group (+7.5 +/- 2.8% vs -2.9 +/- 2.7%, respectively; p < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time-course of blood pressure, radial artery distensibility and pressure waveform. Our results demonstrate that real acupuncture can determine an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.