David C. Knoppert

Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy harmful to neonates

1Physicians were advised to taper the dosage of antidepressants in pregnant women during the last trimester so that the fetus receives no drug for at least 7–10 days before delivery. A month later, Health Canada followed suit; the Canadian advisory 2 similarly suggested that “Physicians may consider slowly decreasing the dose of these medications in the third trimester.” These advisories were based on “reports reveal[ing] that some newborns whose mothers took these medications during pregnancy have developed complications at birth.” 2 These complications were seen as consistent with withdrawal symptoms or a direct adverse effect by the antidepressant on the baby. We believe those recommendations are only partially evidence-based and may put the depressed mother-to-be and her baby at an unreasonable health risk. This paper presents a brief discussion of the pattern of neonatal symptoms observed after maternal use of selective serotonin or serotonin–norepinephrine reuptake inhibitors (SSRIs or SNRIs, respectively).

Enoxaparin for neonatal thrombosis: A call for a higher dose for neonates

INTRODUCTION Enoxaparin is the current anticoagulant of choice for neonatal thrombosis. Present neonatal treatment guidelines of 1.5 mg/kg every 12 hours (q12 h) are extrapolated primarily from an earlier study with 9 infants less than 2 months of age. More recent studies indicate an increased dose requirement for neonates. MATERIALS AND METHODS Relevant data from articles and abstracts were identified by searching MEDLINE and pediatric and hematology conference proceedings. RESULTS Publications between 1996 and 2007 included 8 papers, 4 abstracts and 1 review article with primary research documenting enoxaparin use in 240 neonates. The mean maintenance dose of enoxaparin ranged from 1.48 to 2.27 mg/kg q12 h for all infants, but was higher for preterm neonates at 1.9-2.27 mg/kg q12 h. The efficacy of enoxaparin, causing either complete or partial resolution was between 59 and 100%. Minor side effects were common and adverse events (major bleeding) occurred in 12 patients (0-19%). CONCLUSIONS Increased experience with enoxaparin use in neonates in the past decade has indicated higher doses to achieve accepted target anti-factor Xa values. The long-term use of indwelling catheters (Insuflon catheter) for enoxaparin administration may need to be reevaluated in ELBW infants. Suggested starting doses of enoxaparin are 1.7 mg/kg q12 h for term neonates and 2.0 mg/kg q12 h for preterm neonates if there is no considerable bleeding risk. However, further prospective studies are needed to validate an increased initial dose of enoxaparin.

Enoxaparin use in the neonatal intensive care unit: experience over 8 years.

Study Objective. To evaluate the effectiveness and safety of enoxaparin therapy in a neonatal intensive care unit (NICU).

Cystic fibrosis: enhanced theophylline metabolism may be linked to the disease

Theophylline disposition (5.5 mg/kg administered intravenously) was studied in 12 patients with cystic fibrosis (CF) and 16 healthy control volunteers. Dietary controls and logs were used to minimize the influence of food on theophylline metabolism. Control subjects were restudied in random order on two subsequent occasions after 2 weeks of either pancreatic enzymes or placebo. Theophylline and its three main metabolites, 1‐methyluric acid, 3‐methylxanthine, and 1,3‐dimethyluric acid, were analyzed in serum and urine by HPLC. The total body clearance, renal clearance, nonrenal clearance, and volume of distribution of theophylline were significantly greater (p < 0.05) in patients with CF than in control subjects. The increased nonrenal clearance was the result of increased biotransformation to each of the three main metabolites. Patients with CF exhibited enhanced N‐demethylation and 8‐hydroxylation of theophylline, pathways that appear to be mediated by two different families of P‐450 enzymes. Theophylline clearance after 2 weeks of pancreatic enzyme administration in the control subjects was the same as with placebo. Possible reasons for enhanced theophylline biotransformation in CF are discussed.

The Effect of Two Different Domperidone Doses on Maternal Milk Production

Background: The benefits of breast milk to the newborn infant are well established. The Canadian Paediatric Society recommends exclusive breastfeeding for the first 6 months of life for healthy, term infants. Mothers of premature newborns, however, may have difficulty providing an adequate supply of breast milk. Domperidone is officially used as a prokinetic agent. However, it is used widely around the world as a galactogogue. Despite its widespread use as a galactogogue, only a small number of investigators have studied domperidone for this indication. Aims: The purpose of this study was to determine an optimal dosage of domperidone as a galactogogue. Methods: Eligible subjects were randomized to receive domperidone 10 mg 3 times daily or domperidone 20 mg 3 times daily for 4 weeks. At week 5, the frequency was decreased to twice daily in both groups, and finally once daily for week 6. Results: Over the entire first 4-week period, there was a significant increase in daily milk volumes within each group (P < .01). The between-group difference over this period, although not statistically significant, was clinically significant. Additionally, there was no significant within- or between-group difference during weeks 5 and 6. Conclusion: A dose of domperidone of 20 mg, 3 times daily instead of 10 mg, 3 times daily was associated with a clinical, but not statistically significant, increase in milk production.

Myoclonus Associated with Lorazepam Therapy in Very-Low-Birth-Weight Infants

Lorazepam is being used with increasing frequency as a sedative in the newborn and the young infant. Concern has been raised with regard to the safety of lorazepam in this age group, especially in very-low-birth-weight (VLBW; < 1,500 g) infants. Three young infants, all of birth weight < 1,500 g, experienced myoclonus following the intravenous administration of lorazepam. The potential neurotoxic effects of the drug (and its vehicle) in this population are discussed. Injectable lorazepam should be used with caution in VLBW infants.

Domperidone for lactating women

Reason for posting: Domperidone has been widely used as a motility and antiemetic agent.[1][1] In oral form it is also used off label to improve lactation in breast-feeding women. Intravenous domperidone has been withdrawn from the market worldwide because of reports of cardiac arrhythmia and sudden

Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

OBJECTIVE:To describe the association between opioid administration in the newborn period and neurologic abnormalitiesSTUDY DESIGN:Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxoneRESULTS:The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration.CONCLUSION: Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

Enhancing Human Milk Production With Domperidone in Mothers of Preterm Infants.

Background: Mothers of preterm infants often are at risk of expressing an inadequate amount of milk for their infants and the use of galactogogues is often considered. Domperidone is a widely used galactogogue with little information available to guide clinicians regarding initiation, timing, and duration of treatment. Research aim: The primary objective of this study was to determine whether administration of domperidone within the first 21 days after delivery would lead to a higher proportion of mothers achieving a 50% increase in the volume of milk at the end of 14 days of treatment compared with mothers receiving placebo. Methods: Eligible mothers were randomized to one of two treatment arms: Group A—domperidone 10 mg orally three times daily for 28 days; or Group B—placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days. Results: A total of 90 mothers of infants ≤ 29 weeks gestation were randomized. Mean milk volumes at entry were similar for both groups. More mothers achieved a 50% increase in milk volume after 14 days in Group A (77.8%) compared with Group B (57.8%), odds ratio = 2.56, 95% confidence interval [1.02, 6.25], p = .04. Conclusion: A greater number of mothers experienced a 50% or more increase in human milk volume, but the absolute increase in milk volume was modest.

Does thiopentone delay recovery in children premedicated with midazolam

This prospective, randomized trial of paediatric surgical outpatients, premedicated with oral midazolam, was designed to determine if an intravenous thiopentone induction of anaesthesia prolongs postoperative recovery compared to an inhalation induction with halothane. One hundred children, one to ten years of age, undergoing ENT surgical procedures of 30–60 min duration received midazolam 0.5 mg·kg−1 with atropine 0.03 mg·kg−1 and were randomized to either halothane (Group 1, n=50) or a thiopentone induction (Group 2, n=50) technique, followed by a standardized anaesthetic‐protocol. Time to extubation was significantly greater in the thiopentone group (8.8±4 min vs 7.1±3 min, P<0.05). Patients receiving thiopentone were also more sedated than the halothane group on arrival in the PARR (3.9±1.5, 3.3±1.7, respectively P<0.05), but the differences disappeared after 30 min. Children premedicated with oral midazolam who receive an intravenous thiopentone induction have a slightly prolonged emergence from anesthesia compared to children induced with halothane.