The reproductive effects of beta interferon therapy in pregnancy: a longitudinal cohort.

OBJECTIVE: To determine whether interferon therapy during human pregnancy increases reproductive risks in women. METHODS: This longitudinal, controlled cohort study consisted of three groups of women: an exposed group, a disease matched unexposed group, and a healthy comparative group. Subjects were selected from women contacting the Motherisk Program regarding maternal beta interferon exposure, mostly for multiple sclerosis during pregnancy, from 1997 to 2004. After delivery all of the women were re-contacted for a follow-up interview regarding maternal health, pregnancy outcome, and neonatal health. RESULTS: The study group (n = 16 women, 23 pregnancies) were exposed to interferon beta-1a (Avonex, Rebif) and interferon-1b (Betaseron). There was a decrease in mean birth weight in the exposed group (3,189 +/- 416 g) as compared to healthy controls (3,783 +/- 412 g, p = 0.002). Women exposed to beta interferon had a higher rate of miscarriages and stillbirths (39.1%) vs healthy controls (5%) (p = 0.03), even after correction for potential confounders. There were two major malformations (abnormality in the X chromosome, Down's syndrome) among exposed fetuses. CONCLUSIONS: Beta interferon therapy in the first trimester of pregnancy appears to be associated with an increased risk for fetal loss and low birth weight.

Neurodevelopment of adopted children exposed in utero to cocaine: the Toronto Adoption Study.

BACKGROUND: Published studies of children's neurodevelopment after in utero exposure to cocaine have not separated intrauterine from postnatal environmental effects as cocaine-using mothers cluster in low socioeconomic classes and have other risk factors. METHODS: To overcome this limitation, a study was done to assess physical and neurodevelopmental characteristics of 52 children: 26 were adopted by parents who sought counselling in the Motherisk Program at the University of Toronto for prenatal cocaine exposure, and 26 were controls matched for maternal intelligence quotient (IQ), socioeconomic status and gestational age. MAIN OUTCOME MEASURES: Head circumference, McCarthy General Cognitive Index (GCI) score, language performance and temperament tests. RESULTS: The children in the study group had smaller head circumferences (34th versus 54th percentiles p = 0.009), lower McCarthy GCI scores (102.8 versus 114.2, p = 0.02), poorer receptive and expressive language performance on the Reynell test, and higher activity levels, less persistence and increased distractibility on temperament tests. On multivariate analysis, cocaine exposure was significantly (p = 0.001) associated with lower IQ and poorer language development independent of intrauterine growth retardation and other potential confounders. INTERPRETATION: By controlling for postnatal environmental factors, this adoption study documents intrauterine developmental risks associated with cocaine exposure. Follow-up into school years is warranted to evaluate the extent of these effects.

Repeated doses of porcine secretin in the treatment of autism: a randomized, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: Anecdotal reports on the efficacy of secretin in autism raised great hopes for the treatment of children with this disorder. Initial single-dose, randomized, controlled trials failed to demonstrate any therapeutic effects of secretin. The present study is the first to test the outcome of repeated doses and to examine whether there is a subgroup of children who are more likely to achieve positive effects. METHOD: Sixty-four children with autism (ages 2-7 years; 55 boys and 9 girls) with a range of intelligence quotient and verbal ability were randomly assigned, in a double-blind manner, to secretin or placebo groups. Children received 2 doses of placebo or porcine secretin, 6 weeks apart. Assessments were performed at baseline and 3 weeks after each injection using several outcome measures. RESULTS: There were no group differences on formal measures of language, cognition, or autistic symptomatology. Subgroupings based on cognitive level, the presence or absence of diarrhea, or a history of regression failed to show any significant therapeutic effects of secretin. CONCLUSION: No evidence is provided for the efficacy of repeated doses of porcine secretin in the treatment of children with autism. The possible relationship between relief of biological symptoms and enhanced skill performance is discussed.

Determinants of the need for hospital care among women with nausea and vomiting of pregnancy.

OBJECTIVES: To characterize a cohort of pregnant women who required hospital care owing to nausea and vomiting of pregnancy (NVP) and to identify variables that could serve as predictors of the need for hospital care. DESIGN: A retrospective, observational study. METHODS: Between 1996 and 1997, women who suffered from NVP were invited to call the NVP Healthline at The Motherisk Program in Toronto. After obtaining verbal consent, callers were interviewed by trained counsellors through a structured questionnaire about their NVP experience in previous pregnancies. Univariate and multivariate analyses were used to identify factors that could predict the need for hospital care. RESULTS: In total, 3,201 women were recruited;1,348 (43.8%) needed hospital care (treatment in the emergency room, day unit or hospital ward). The following characteristics were significantly associated with the need for hospital care: severity of vomiting (more than 5 times a day), use of more than one antiemetic medication, being primigravid, feeling depressed, having had an obstetrician as the primary health care provider and feeling that NVP had affected the partner's daily life. CONCLUSIONS: Several factors, including the severity of physical symptoms of NVP and psychosocial factors, are associated with the need for hospital care. In addition to treatment of physical symptoms, it is important to address other factors associated with NVP.

Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children.

Ifosfamide is widely used in the treatment of pediatric solid tumors. Its main adverse effects are various forms of renal tubular and glomerular damage. The authors sought to determine factors that predict the risk for the development and severity of ifosfamide-induced nephrotoxicity in children and to examine the long-term outcome of this complication. A total of 174 children who had received ifosfamide for various cancers were studied. Nephrotoxicity was assessed by laboratory markers of glomerular and tubular function and a grading score (none, mild, moderate, severe). Patients were assessed 4 to 12 weeks after each ifosfamide course, 3 months after completion of chemotherapy, and 5 years later. Of 174 children, 72 (41.4%) developed tubular dysfunction, whereas only 11 (6.3%) demonstrated glomerular dysfunction; 40 (23.0%) demonstrated mild toxicity, 16 (9.2%) demonstrated moderate toxicity, and 16 (9.2%) developed severe nephrotoxicity. The four severity subgroups (none, mild, moderate, severe) received comparable doses/m2/cycle of ifosfamide and mesna. Children exhibiting severe toxicity were significantly younger compared to those with moderate, mild, or no nephrotoxicity (median age: 2.2, 7.0, 8.2, and 10.5 years, respectively; p < 0.001) and received significantly higher cumulative doses of ifosfamide (49.6 +/- 12.3, 46.0 +/- 13.1, 36.2 +/- 9.7, and 33.8 +/- 7.6 g/m2, respectively; p < 0.001). Cumulative doses of cisplatin were higher among children with severe nephrotoxicity compared to those with moderate, mild, or no toxicity, although this difference did not reach statistical significance. Of all risk factors analyzed by multiple regression analysis, age was the most significant predictor for the grade of nephrotoxicity (p < 0.001), followed by the cumulative dose of ifosfamide (p = 0.005). Seven out of 16 children (44.0%) with severe nephrotoxicity and 4 out of 16 children (25.0%) with moderate nephrotoxicity demonstrated severe chronic tubular toxicity over a follow-up period of 5 years. Since severe ifosfamide-induced renal toxicity tends to be chronic in a substantial number of treated children, it should be balanced carefully against efficacy. Cumulative ifosfamide doses of 45 g/m2 and above should be carefully considered, especially in children younger than age 3.

Neurodevelopment of children exposed in utero to antidepressant drugs.

BACKGROUND: Many women of reproductive age have depression, necessitating therapy with either a tricyclic antidepressant drug or a drug, such as fluoxetine, that inhibits the reuptake of serotonin. Whether these drugs affect fetal neurodevelopment is not known. METHODS: We studied the children of 80 mothers who had received a tricyclic antidepressant drug during pregnancy, 55 children whose mothers had received fluoxetine during pregnancy, and 84 children whose mothers had not been exposed during pregnancy to any agent known to affect the fetus adversely. The children's global IQ and language development were assessed between 16 and 86 months of postnatal age by age-appropriate Bayley Scales of Infant Development or the McCarthy Scales of Children's Abilities (for IQ) and the Reynell Developmental Language Scales. RESULTS: The mean (+/-SD) global IQ scores were 118+/-17 in the children of mothers who received a tricyclic antidepressant drug, 117+/-17 in those whose mothers received fluoxetine, and 115+/-14 in those in the control group. The language scores were similar in all three groups. The results were similar in children exposed to a tricyclic antidepressant drug or fluoxetine during the first trimester and those exposed throughout pregnancy. There were also no significant differences in temperament, mood, arousability, activity level, distractibility, or behavior problems in the three groups of children. CONCLUSIONS: In utero exposure to either tricyclic antidepressant drugs or fluoxetine does not affect global IQ, language development, or behavioral development in preschool children.

Golembiewski's phase model of psychological burnout: some issues.

The present investigation examined three issues relevant to Golembiewski's phase model of psychological burnout. These were use of the mean versus median in creating high and low subgroups on Maslach Burnout Inventory subscales, use of different item structures on Maslach subscales, and different sequences of Maslach subscales proposed by Golembiewski and Maslach in the development of psychological burnout. Use of mean versus median, or different item structures on Maslach subscales, made relatively little difference. Golembiewski's ordering of the subscales, compared to Maslach's, produced a more linear progression over the 8 phases, as well as on three antecedents and consequences, but both sequences were related to these three variables in an almost identical fashion.