Outcome following high-dose methotrexate in pregnancies misdiagnosed as ectopic.

OBJECTIVE: The objective of this study was to report the outcomes of intrauterine pregnancies misdiagnosed as ectopic and exposed to methotrexate, a major teratogen. STUDY DESIGN: We report the outcomes of all subjects who sought consultation after exposure to high-dose methotrexate to induce abortion in presumed ectopic pregnancies, which were later identified as viable intrauterine pregnancies by 3 North American Teratology Information Services between 2002 and 2010. RESULTS: Eight women with normal, desired pregnancies were administered high-dose methotrexate in the first trimester because of presumed, misdiagnosed ectopic pregnancies. All pregnancies resulted in catastrophic outcomes. Two pregnancies resulted in severely malformed newborns with methotrexate embryopathy; 3 women miscarried shortly after exposure, and in 3 the erroneous diagnosis led the physicians to advise and perform surgical termination. CONCLUSION: Erroneous diagnosis of intrauterine pregnancies as ectopic with subsequent first-trimester exposure to methotrexate may result in the birth of severely malformed babies or fetal demise.

Predisposition to epilepsy--does the ABCB1 gene play a role?

We performed a meta-analysis to evaluate the association between ABCB1 C3435T polymorphisms and the prevalence of epilepsy, including all relevant human studies (until June 2009), in which patients with or without epilepsy had undergone genotyping for the ABCB1 gene. Odds ratios (ORs) were calculated using a random effects model. We identified 9 case-control studies that included a total of 3,996 patients (2,454 with epilepsy and 1,542 nonepileptic subjects). No association was found between ABCB1 C3435T polymorphisms and the risk of having epilepsy (odds ratio 1.07, 95% confidence interval 0.76-1.51; p = 0.34). ABCB1 genotyping for epileptic patients is not warranted.

Is morphine exposure associated with acute chest syndrome in children with vaso-occlusive crisis of sickle cell disease? A 6-year case-crossover study.

BACKGROUND: Recurrent painful vaso-occlusive crises (VOC) are a hallmark of sickle cell disease (SCD), and narcotic analgesics are an effective component of therapy. However, the belief that these drugs can promote development of the acute chest syndrome (ACS) may lead to undertreatment of pain. OBJECTIVE: The aim of this study was to explore the potential association between a dose-response effect of morphine exposure and the development of ACS in children with SCD who presented with VOC. METHODS: A retrospective, self-matched, case-crossover design was used to study data from children with SCD who were treated with continuous-drip IV morphine (initial rate of 10 mug/kg . h) for VOC and subsequently developed ACS (index hospitalization) at a tertiary pediatric hospital in Toronto, Ontario, Canada, from April 1, 2000, to March 31, 2006. So that each child could serve as his or her own control for the analysis, a comparison hospitalization for VOC was identified for each child during which ACS did not develop (reference hospitalization). We determined the cumulative dose of morphine administered before ACS development (index interval) during the index hospitalization and the cumulative amount of morphine administered during the same time interval during the reference hospitalization (reference interval). RESULTS: Seventeen children (13 girls, 4 boys; index hospitalization: mean [SD] age, 8.9 [4.0] years; mean [SD] weight, 30.9 [15.2] kg; reference hospitalization: mean [SD] age, 8.6 [3.4] years; mean [SD] weight, 27.3 [11.2] kg) with SCD who met all inclusion criteria were identified. There was no significant difference in the cumulative morphine dose (mean [SD] amount, 1.24 [0.60] mg/kg) during the index interval compared with the amount administered during the reference interval (mean [SD] amount, 1.44 [0.84] mg/kg). CONCLUSION: Among these children with SCD who presented with VOC, the administration of morphine was not found to be associated with a dose-response effect on the risk for ACS.

Risky health behaviors among mothers-to-be: the impact of adverse childhood experiences.

OBJECTIVES: Adverse childhood experiences (ACEs) are risk factors for health problems later in life. This study aims to assess the influence of ACEs on risky health behaviors among mothers-to-be and determine whether a dose response occurs between ACEs and risky behaviors. METHODS: A prospective survey of women attending health centers was conducted at the first prenatal care visit, and at 3 and 11 months postpartum. Surveys obtained information on maternal sociodemographic and health characteristics, and 7 ACEs prior to age 16. Risky behaviors included smoking, alcohol use, marijuana use, and other illicit drug use during pregnancy. RESULTS: Our sample (N = 1476) consisted of low-income (mean annual personal income, $8272), young (mean age, 24 years), African American (71%), single (75%) women. Twenty-three percent of women reported smoking even after finding out they were pregnant, 7% reported alcohol use, and 7% reported illicit drug use during pregnancy. Nearly three fourths (72%) had one or more ACEs. There was a higher prevalence of each risky behavior among those exposed to each ACE than among those unexposed. The exception was alcohol use during pregnancy, where there was not an increased risk among those exposed when compared with those unexposed to witnessing a shooting or having a guardian in trouble with the law or in jail. The adjusted odds ratio for each risky behavior was >2.5 for those with >3 ACEs when compared with those without. CONCLUSIONS: ACEs were associated with risky health behaviors reported by mothers-to-be. Greater efforts should target the prevention of ACEs to lower the risk for adverse health behaviors that have serious consequences for adults and their children.

Clopidogrel use in children.

OBJECTIVES: To review a pediatric experience with the antiplatelet agent clopidogrel and suggest a dosage regimen. STUDY DESIGN: A retrospective chart review of all infants and children treated with clopidogrel at The Hospital for Sick Children, Toronto between January 2001 and April 2004. Clopidogrel dosages, duration of therapy, complications, and adverse effects in a pediatric population were explored. RESULTS: Fifteen infants and children with congenital and acquired heart disease were treated with clopidogrel (median age, 3.5 years; range, 6 weeks to 16 years). Dosages ranged from 1 to 6 mg/kg/day for periods between 1 month and 6 months. Although no thrombotic events were reported, 1 child had a bleeding complication (gastrointestinal) while on triple antithrombotic therapy. Other complications reported in adults, including rash and clinical thrombocytopenia, were not noted in this pediatric series. CONCLUSIONS: Clopidogrel was well tolerated. We suggest a starting dose of 1 mg/kg/day for children.