Neurocognitive development of children following in-utero exposure to labetalol for maternal hypertension: a cohort study using a prospectively collected database.

OBJECTIVE: To identify the effect of prenatal labetalol exposure on children's long-term neurodevelopment. DESIGN: A cohort study with matched controls using a prospectively collected database. METHODS: Participants were women counseled for hypertension in pregnancy at the Motherisk Program at The Hospital for Sick Children, and The Sunnybrook Health Sciences Centre, Toronto, Canada and their children. Mother-child pairs were divided into groups based on in-utero exposure to labetalol (n = 32), non-teratogenic substances (n = 42), and methyldopa (n = 25). The main outcome measures were children's Full-Scale IQ, Performance IQ and Verbal IQ assessed with the Wechsler Preschool and Primary Scale of Intelligence. RESULTS: There were no statistically significant differences in scores on Full-Scale IQ, Performance IQ, or Verbal IQ between children exposed in utero to labetalol and to non-teratogenic substances (Full-Scale IQ: 109.60 +/- 8.20 vs. 111.90 +/- 11.39, p = 0.647; Performance IQ: 104.80 +/- 8.69 vs. 110.19 +/- 12.91, p = 0.186; Verbal IQ: 112.27 +/- 11.05 vs. 11.21 +/- 11.98, p = 0.922, respectively). Children in the methyldopa group achieved lower scores on measures of Full-Scale IQ and Performance IQ when compared to children exposed to non-teratogenic substances (Full-Scale IQ: 105.24 +/- 12.46 vs. 111.90 +/- 11.39, p = 0.043; Performance IQ: 98.80 +/- 16.16 vs. 110.19 +/- 12.91, p = 0.002, respectively). Linear regression analysis revealed that maternal Full Scale IQ was a significant predictor of children's Full-Scale IQ (p = 0.020, beta = 0.229). Maternal Performance IQ and duration of treatment with methyldopa were significant predictors of children's Performance IQ (p = 0.028, beta = 0.232; p = 0.16, beta = -0.255, respectively). CONCLUSION: In-utero exposure to labetalol does not appear to adversely affect the neurocognitive development of young children. These reassuring results may aid disease management for pregnant women with hypertension.

Safety of glyburide for gestational diabetes: a meta-analysis of pregnancy outcomes.

BACKGROUND: Gestational diabetes mellitus affects approximately 4% of all pregnancies. As with other oral hypoglycemics, the use of glyburide in pregnancy has been limited by fears of neonatal hypoglycemia following fetal exposure. Recent experimental and clinical studies have suggested, however, that the drug is not detectable in umbilical blood. OBJECTIVE: To determine the safety of glyburide use in pregnancy in the treatment of gestational diabetes compared with insulin therapy by analyzing all available human studies. METHODS: We conducted a systematic review and meta-analysis of all randomized and cohort studies that reported on the perinatal complications among women with gestational diabetes who received glyburide versus insulin. MEDLINE, EMBASE, and biological abstracts using BIOSIS previews were searched from inception of these databases through October 2006. The following outcomes were included: macrosomia, birthweight, gestational age, neonatal hypoglycemia, and intensive care unit (ICU) admissions. Odds ratios were calculated by the random effects method using Cochrane's Review Manager version 4.3. RESULTS: Nine studies met the inclusion criteria, including a total of 745 glyburideexposed pregnancies and 637 insulin-exposed pregnancies, with each adverse perinatal outcome reported by 4-7 studies. The use of glyburide was not associated with risk of macrosomia (OR 1.07; 95% CI 0.78 to 1.47), differences in birth weight (weighted mean difference [WMD] OR 20.46 g; 95% CI -34.90 to 75.82), rate of large for gestational age (OR 1.04; 95% CI 0.75 to 1.43), differences in gestational age at birth (WMD 0.02 wk; 95% CI -0.23 to 0.26), ICU admission (OR 0.95; 95% CI 0.43 to 2.09), or increased risk of neonatal hypoglycemia (OR 1.24; 95% CI 0.91 to 1.69). CONCLUSIONS: The data shown here do not suggest increased perinatal risks with glyburide. The effectiveness and safety of glyburide require further evaluation, as most studies to date were not randomized.

Generalized seizures following topical lidocaine administration during circumcision: establishing causation.

We report a case of neonatal seizures after lidocaine administration for circumcision. A 3-month-old male infant received an overdose as evidenced by toxic lidocaine levels and developed generalized seizures shortly after. Back extrapolation of the serum lidocaine concentration to time zero was used to determine the administered dose. The Naranjo scale was used to determine causation; probable causation was defined. Particular care must be taken to administer an appropriate dose of local anesthetics in infants to avoid life-threatening seizures.

Does vitamin K prophylaxis prevent bleeding in neonates exposed to enzyme-inducing antiepileptic drugs in utero?

QUESTION: One of my epileptic patients takes carbamazepine. She is 36 weeks pregnant and has asked me whether she should start vitamin K to prevent neonatal bleeding. Does current evidence support this practice? ANSWER: Recent evidence does not support the notion that newborns of women treated with enzyme-inducing anticonvulsant drugs are at increased risk of hemorrhagic disease. Antenatal vitamin K can be prescribed on an individualized basis in certain circumstances, such as imminent premature delivery.

Cocaine toxicity after laryngoscopy in an infant.

Iatrogenic cocaine toxicity was observed in a 5.5-month-old male who received intranasal cocaine as a topical anesthetic for laryngoscopy. He became agitated, diaphoretic, tachycardic, and hypertensive shortly following the procedure. To control his signs and symptoms, he required 3 doses of IV lorazepam. Systemic absorption and toxicity can vary amongst individuals, making it difficult to determine appropriate dosing. The maximum dose of 1 mg/kg in children has not been validated and toxicity may appear at a much lower dose in certain individuals. Pediatric patients receiving topical cocaine as an anesthetic must be given the lowest possible dose, and then carefully monitored for signs of systemic absorption.

Pregnancy outcome after exposure to injectable ribavirin during embryogenesis.

We describe normal pregnancy outcome in a case of first trimester exposure to injectable ribavirin in a 36-year-old pregnant woman who received three intramuscular injections of ribavirin for suspected SARS. She delivered at 40 weeks of gestation a healthy baby girl. In pediatric follow up at 8 month of age, physical examination and neurodevelopmental milestones were normal.

Exposure to alcohol-containing medications during pregnancy.

QUESTION: A pregnant patient consulted her physician after discovering that a diphenhydramine preparation (Benadryl elixir) she used for allergy symptoms during the first trimester of her pregnancy contained 15% alcohol. Should she be concerned about fetal alcohol spectrum disorder in her baby? ANSWER: Most ethanol-containing medical preparations are safe during pregnancy. Adult doses of some elixirs with high ethanol concentrations might produce blood levels similar to those achieved by drinking 1 alcoholic beverage. Caution is advisable when prescribing ethanol-containing elixirs to pregnant women, as is informing them about the alcohol content.

Group A streptococcal meningitis as a complication of an infected capillary haemangioma.

UNLABELLED: We report a case of group A streptococcal meningitis in an infant resulting from an infected capillary haemangioma. The child suffered significant morbidity including cerebral infarction, epilepsy, and developmental delay. Treatment of infected capillary haemangiomas remains controversial and inconsistent. CONCLUSION: Our experience of this infant, resulting in profound neurological morbidity suggests that group A Streptococcus can be a virulent organism in the young child and that capillary haemangiomas must be treated aggressively at the first sign of infection.