Showing papers by "Gideon Koren published in 2001"

Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis.

Abstract: Background. Cyclosporine (CsA) therapy must often be continued during pregnancy to maintain maternal health in such conditions as organ transplantation and autoimmune disease. This meta-analysis was performed to determine whether CsA exposure during pregnancy is associated with an increased risk of congenital malformations, preterm delivery, or low birthweight. Methods. Various health science databases were searched to identify relevant articles. Articles selected for inclusion in the study were required to be free of any apparent selection bias and report outcomes in at least 10 newborns exposed to CsA in utero, specifically commenting on the presence or absence of congenital malformations. Article selection and data extraction were performed by two independent reviewers, with adjudication in cases of disagreement. To assess risks of CsA exposure, a summary odds ratio was calculated. Prevalence of malformations was calculated as a rate for all cyclosporine-exposed live births and for the subgroups identified. Ninety-five percent confidence intervals were constructed for both the odds ratio and prevalence rates. Results. Fifteen studies (6 with control groups of transplant without use of cyclosporine; total patients: 410) met the inclusion criteria for major malformations, 10 for preterm delivery (4 with control groups; total patients: 379) and 5 for low birth weight (1 with control groups; total number of patients: 314). The calculated odds ratio of 3.83 for malformations did not achieve statistical significance (CI 0.75‐19.6). The overall prevalence of major malformations in the study population (4.1%) also did not vary substantially from that reported in the general population. OR for prematurity [1.52 (CI 1.00 ‐2.32)] did not reach statistical significance although the overall prevalence rate was 56.3%. The OR for low birth weight [1.5 (CI 0.95‐ 2.44 based on 1 study)]. Conclusions. CsA does not appear to be a major human teratogen. It may be associated with increased rates of prematurity. More research is needed to evaluate whether cyclosporine increases teratogenic risk.

Socio-economic disparities in preterm birth: causal pathways and mechanisms.

Abstract: Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.

Pregnancy Outcome Following Gestational Exposure to Venlafaxine: A Multicenter Prospective Controlled Study

Abstract: OBJECTIVE: Because there are no studies available on the safety of venlafaxine during pregnancy, the authors’ goal in this study was to determine whether venlafaxine increases the risk for major malformations. METHOD: Data on 150 women exposed to venlafaxine during pregnancy in seven pregnancy counseling centers were compared with data from studies of pregnant women who 1) received selective serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received nonteratogenic drugs (N=150). RESULTS: Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions, and seven had therapeutic abortions; two of the babies had major malformations. There were no significant differences between these women and the two comparison groups on any of the measures analyzed. CONCLUSIONS: These results suggest that the use of venlafaxine during pregnancy does not increase the rates of major malformations above the baseline rate of 1%–3%.

Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling.

Abstract: Objective: To assess the consequences to mother and baby of abruptly discontinuing antidepressant or benzodiazepine medication during pregnancy and to assess the impact of our counselling. Participants: All women who consulted the Motherisk Program between November 1996 and December 1997 and who stopped taking antidepressant or benzodiazepine medication when pregnancy was confirmed agreed to participate in the study. Design and interventions: Subjects were interviewed, received counselling, and completed a questionnaire 1 month after their initial call and after the birth of their baby. Results: Of 36 women who completed the study, 34 discontinued their medication abruptly for fear of harming the fetus, 28 on the advice of their physician; 26 (70.3%) women reported physical and psychological adverse effects, 11 reported psychological effects only, and 11 reported suicidal ideation (4 were admitted to hospital). After counselling, 22 of 36 (61.1%) women resumed taking their medication, and 4 found that they no longer required it. One woman had a therapeutic abortion and 2 experienced spontaneous abortions; there were therefore 35 healthy babies (including 2 sets of twins) born to 33 women; 14 of 21 mothers breast-fed their babies while taking their psychotropic medication, with no adverse effects reported. Conclusions: When assessing the risks and benefits of taking psychotropic medication during pregnancy, women and their physicians should be aware that the abrupt discontinuation of psychotropic drugs can lead to serious adverse effects. Counselling is effective in reassuring women to adhere to therapy. Objectif : Evaluer les repercussions sur la mere et le bebe d’une interruption soudaine de l’administration d’antidepresseurs ou de benzodiazepines pendant la grossesse et evaluer l’effet de nos conseils. Participantes : Toutes les femmes qui ont consulte le programme Motherisk entre novembre 1996 et decembre 1997 et qui ont cesse de prendre des antidepresseurs ou des benzodiazepines lorsque la grossesse a ete confirmee ont consenti a participer a l’etude. Conception et interventions : Les sujets ont ete interviewees, ont recu des conseils et ont rempli un questionnaire un mois apres l’appel initial et apres l’accouchement. Resultats : Sur 36 femmes qui ont participe a l’etude, 34 ont cesse soudainement

Neonatal paroxetine withdrawal syndrome

Abstract: Four term neonates presented with symptoms such as jitteriness and necrotising enterocolitis after paroxetine exposure in utero.

Randomized, double-blind, placebo-controlled trial of nicotine replacement therapy in pregnancy

Abstract: Background: Smoking in pregnancy is associated with increased perinatal risks, including intrauterine growth retardation, stillbirth, and the sudden infant death syndrome. Reducing maternal smoking using nicotine replacement therapy (NRT) is a possible way to decrease the risks to the fetus. Objective: The purpose of this study was to examine the efficacy of NRT in reducing smoking among pregnant women who were heavy smokers and who could not quit smoking during their first trimester. Methods: In this double-blind, placebo-controlled trial, pregnant women (12 to 24 weeks' gestation) who smoked ≥ 15 cigarettes per day were randomized to receive a daily, 18-hour patch of nicotine 15 mg for 8 weeks, 10 mg for an additional 2 weeks, and 5 mg for the last 2 weeks, or an identical placebo patch. At baseline and at 1, 4, and 8 weeks, women received counseling, and serum and salivary cotinine levels were measured. Results: Seventeen women received NRT and 13 received placebo. In the NRT group, 4 women (23.5%) successfully completed the program and quit smoking during their second trimester. None of the 13 women who received placebo and counseling completed the program or quit smoking. The difference in success rates was not statistically significant ( P = 0.11). Conclusions: The effectiveness of NRT beyond the first trimester in pregnant women who smoke heavily is questionable, but NRT may be helpful in a minority of these women.

Repeated Doses of Porcine Secretin in the Treatment of Autism: A Randomized, Placebo-Controlled Trial

Abstract: 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.

Factors associated with elective termination of pregnancy among Canadian and American women with nausea and vomiting of pregnancy.

Abstract: Case reports have associated severe nausea and vomiting of pregnancy (NVP) with elective termination of pregnancy. Therefore, our objective was to explore the determinants of consideration of termi...

Maternal-fetal toxicology : a clinician's guide

Abstract: Pharmacokinetic changes during pregnancy and their clinical relevance developmental risk assessments drugs in pregnancy teratogenic drugs and chemicals in humans treatment for epilepsy in pregnancy the safety of commonly used antidepressants inpregnancy benzodiazepine use in pregnancy and major malformations or oral cleft - meta-analysis of cohort and case-control studies drug and chemicals most commonly used by pregnant women periconceptional folate and neural tube defects theeffectiveness of preconceptional counselling on women's compliance with folic acid supplementation pregnancy outcome following maternal exposure to corticosteroids - a prospective controlled cohort study, and a meta-analysis of epidemiological studies use of the retinoid pregnancy prevention programme in Canada - patterns of contraception use in women treated with isotretinoin and etretinate drugs and breastfeeding poisoning in pregnancy carbon monoxide poisoning during pregnancy direct drugtoxicity to the foetus the approach to the mother on nonmedicinal and chemnical use in pregnancy maternal and obstetrical effects of prenatal drug exposure neonatal drug withdrawal syndromes current management of the neonatal abstinence syndrome - acritical analysis of the evidence foetal effects of cocaine - an updated meta-analysis pregnancy outcome and infant development following gestational cocaine use by social cocaine users in Toronto, Canada long-term neurodevelopmental risks in childrenexposed in utero to cocaine biological markers for intrauterine exposure to cocaine and cigarette smoking foetal alcohol syndrome moderate alcohol consumption during pregnancy and the incidence of foetal malformations - a meta-analysis.

The safety of higher than standard dose of doxylamine-pyridoxine (Diclectin) for nausea and vomiting of pregnancy.

Abstract: A delayed-release combination of doxylamine-pyridoxine (D-P) (Diclectin) is the only approved antiemetic medication for use in pregnancy in Canada. The standard recommended dose is up to 4 tablets a day, regardless of body weight or severity of symptoms. The objective of this study was to determine the incidence of adverse maternal and fetal effects and pregnancy outcome in 225 women taking Diclectin at the recommended (n = 123) or higher than recommended (n = 102) doses. In this observational, prospective study, one-third (33.6%) of women reported having adverse effects (sleepiness, tiredness, and/or drowsiness) temporally related to the medication. There was no association between the dose per kg and rates of reported maternal adverse effects with doses ranging from 0.1 mg/kg to 2.0 mg/kg (1-12 tablets). Nausea and vomiting of pregnancy (NVP) was reported as severe by the majority (75.8%) of women. Mean birth weight (BW) was 3,400 g and gestational age (GA) 39 weeks. Multivariate analysis revealed that only prepregnancy weight and GA predicted lower BW, not the dose of D-P or the severity of NVP. There were two pregnancies with major malformation, a finding that is consistent with the rates of birth defects in the general population. It was concluded that the higher than standard dose of Diclectin, when calculated per kg of body weight, does not affect either the incidence of maternal adverse effects or pregnancy outcome. If needed, Diclectin can be given at doses higher than 4 tablets/day to normalize for body weight or optimize efficacy.

Management of paracetamol overdose: current controversies.

Abstract: Paracetamol (acetaminophen) is one of the most frequently used analgesics, and is the most commonly used substance in self-poisoning in the US and UK Paracetamol toxicity is manifested primarily in the liver Treatment with N-acetyl-cysteine (NAC), if started within 10 hours from ingestion, can prevent hepatic damage in most cases Pharmacokinetic data relating plasma paracetamol concentration to time after ingestion have been used to generate a 'probable hepatoxicity line' to predict which cases of paracetamol overdose will result in hepatotoxicity and should be treated with NAC However, later studies use a 25% lower line as their 'possible hepatotoxicity line' Although adopting the original line may save considerable resources, further studies are needed to determine whether such an approach is safe On the basis of the metabolism of paracetamol, several risk factors for paracetamol toxicity have been proposed These risk factors include long term alcohol (ethanol) ingestion, fasting and treatment with drugs that induce the cytochrome P450 2E1 enzyme system Although some studies have suggested that these risk factors may be associated with worse prognosis, the data are inconclusive However, until further evidence is available, we suggest that the lower line should be used when risk factors are present In Canada and the UK, the intravenous regimen for NAC is used almost exclusively; in the US, an oral regimen is used Both regimens have been shown to be effective There is no large scale study with direct comparison between these 2 therapeutic protocols and controversy still exists as to which regimen is superior During the last few years there has been an increase in the number of reports of liver failure associated with prolonged paracetamol administration for therapeutic reasons The true incidence of this phenomenon is not known We suggest testing liver enzyme levels if a child has received more than 75 mg/kg/day of paracetamol for more than 24 hours during febrile illness, and to treat with NAC when transaminase levels are elevated Paracetamol overdose during pregnancy should be treated with either oral or intravenous NAC according to the regular protocols in order to prevent maternal, and potentially fetal, toxicity Unless severe maternal toxicity develops, paracetamol overdose does not appear to increase the risk for adverse pregnancy outcome

Piracetam therapy does not enhance cognitive functioning in children with down syndrome.

Abstract: Background Piracetam is widely used as a purported means of improving cognitive function in children with Down syndrome. Its efficacy, however, has not been rigorously assessed. Objective To determine whether 4 months of piracetam therapy (80-100 mg/kg per day) enhances cognitive function in children with Down syndrome. Design A randomized, double-blind, placebo-controlled crossover study. Participants and Methods Twenty-five children with Down syndrome (aged 6.5-13 years) and their caregivers participated. After undergoing a baseline cognitive assessment, children were randomly assigned to 1 of 2 treatment groups: piracetam-placebo or placebo-piracetam. Main Outcome Measure The difference in performance while taking piracetam vs while taking placebo on tests assessing a wide range of cognitive functions, including attention, learning, and memory. Results Eighteen children completed the study, 4 withdrew, and 3 were excluded at baseline. Piracetam therapy did not significantly improve cognitive performance over placebo use but was associated with central nervous system stimulatory effects in 7 children: aggressiveness (n = 4), agitation or irritability (n = 2), sexual arousal (n = 2), poor sleep (n = 1), and decreased appetite (n = 1). Conclusion Piracetam therapy did not enhance cognition or behavior but was associated with adverse effects.

Neurodevelopment of children exposed in utero to treatment of maternal malignancy.

Abstract: Cancer is the second most common cause of death during the reproductive years, complicating approximately 1/1000 pregnancies. The occurrence of cancer during gestation is likely to increase as a result of a woman's tendency to delay childbearing. Improved diagnostic techniques for malignancies increases detection of cancer during pregnancy. Malignant conditions during gestation are believed to be associated with an increase in poor perinatal and fetal outcomes that are often due to maternal treatment. Physicians should weigh the benefits of treatment against the risks of fetal exposure. To date, most reports have focused on morphologic observations made very close to the time of delivery with little data collected on children's long-term neurodevelopment following in utero exposure to malignancy and treatment. Because the brain differentiates throughout pregnancy and in early postnatal life, damage may occur even after first trimester exposure. The possible delayed effects of treatment on a child's neurological, intellectual and behavioural functioning have never been systematically evaluated. The goal of this report was to summarize all related issues into one review to facilitate both practitioners' and patients' access to known data on fetal risks and safety.

Safety and pharmacokinetics of EMLA in the treatment of postburn pruritus in pediatric patients: a pilot study.

Abstract: The purpose of this study was to determine the safety and pharmacokinetics of a eutectic mixture of local anesthetics (EMLA) used to ameliorate postburn pruritus after application onto newly formed, intact skin in children. EMLA was applied once to an itchy site where healed skin had formed. Serial blood samples were collected to measure lidocaine, prilocaine, o-toluidine, and methemoglobin. Maximal plasma concentration, minimal plasma concentration, time to achieve the maximal plasma concentration, elimination half-life, and area under the concentration-time curve were calculated. Vital signs, oxygen saturation, clinical signs of hypoxia, and itch intensity were measured. Five children had 15.7 +/- 2.54 g (+/- SD) of EMLA applied to a skin surface area of 93.0 +/- 37.0 cm2. Lidocaine and prilocaine concentrations were below toxic levels; o-toluidine was not detected. Methemoglobin remained between 1 and 3%; patients did not exhibit any clinical signs of hypoxia. Mean oxygen saturation was 98.9 +/- 0.01%. The mean number of pruritic episodes and antihistamine breakthrough doses were greater in the 2 prestudy control days compared with study day 3 (P = 0.01 and P = 0.03, respectively). Skin at the site of EMLA application remained anesthetized for 12 to 13 hours. In this small pilot study, EMLA seems to be a safe, novel treatment for postburn pruritus in burned children when applied to newly healed, intact skin.

Glutathione stability in whole blood: effects of various deproteinizing acids.

Abstract: High-performance liquid chromatography separation of reduced and oxidized glutathione (GSH and GSSG) in biologic samples using electrochemical detection offers the convenience of both simultaneous quantitation and simple sample preparation. Rapid acidification is required to prevent GSH autooxidation, GSH and GSSG degradation, and precipitate proteins that interfere with analysis. Currently, little consistency exists in the literature regarding acid selection or the feasibility of sample storage before analysis. The purpose of this work was to examine the effects of perchloric (PCA), trichloroacetic (TCA), metaphosphoric (MPA), and 5-sulfosalicylic (SSA) acids on the short-term stability of GSH and GSSG measurements in whole blood. Samples were collected from adult volunteers and treated with multiple concentrations of each acid. The samples were analyzed immediately and aliquots were stored at -80 degrees C for up to 28 days. The suitability of each acid was assessed by percentage change of GSH and GSSG from baseline, efficiency of protein removal, and alteration of chromatogram characteristics. In general, increasing the acid concentration improved sample stability. Nevertheless, SSA did not achieve acceptable sample stability at any concentration tested. MPA was found to leave substantial amounts of protein in the samples, and TCA may interfere with the peaks of interest. Based on these results, a final concentration of 15% PCA is suggested for analysis of glutathione in whole blood. Although immediate sample preparation is preferred, 15% PCA can maintain sample integrity for 4 weeks after storage at -80 degrees C.

Effects of antibacterials on the unborn child: what is known and how should this influence prescribing.

Abstract: Antibacterials are among the most commonly prescribed drugs worldwide. In general, infections occur in pregnant women at much the same rate as in the general population. However, as a result of physiological changes brought about by pregnancy, some infections, such as those of the urinary tract, may have an increased incidence. It is important to remember that almost every drug crosses the placenta, ensuring that the unborn fetus is also exposed. When prescribing an antibacterial agent to a pregnant woman, it is important that the mother is treated appropriately while at the same time protecting the unborn child. Certain factors need to be addressed, such as the possible teratogenic risk, changes in pharmacokinetics and the potential toxicity of the drug. In this paper we have reviewed various classes of antibacterials which are commonly used during pregnancy, including penicillins, beta-lactam inhibitors, cephalosporins, macrolides, aminoglycosides, tetracyclines, lincosamides, fluoroquinolones, sulfonamides, nitrofurans, and anti-tubercular agents. Some of these drugs have been on the market for many years, whereas others are relatively new and increasingly popular, despite the fact that the older drugs remain very effective. After reviewing the evidence-based information from epidemiological studies, it appears that most antibacterial agents can be used relatively safely during pregnancy. Women who are pregnant should not be denied appropriate antibacterial therapy because of a lack of information. It is possible to treat the mother, while protecting the unborn child, by prescribing an agent that the causative bacteria is sensitive to, rather than a perceived 'safer' option that may not effectively treat the infection and which may also add to the growing problem of bacterial resistance.

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

Abstract: Contexte : Dans les etudes publiees sur le developpement neurologique des enfants exposes a la cocaine in utero, on n'a pas separe les effets in utero des effets en-vironnementaux postnataux, car les meres qui consomment de la cocaine sont regroupees au bas de l'echelle socio-economique et presentent d'autres facteurs de risque. Methodes : Pour contrer cette limite, on a realise une etude afin d'evaluer les caracteristiques du developpement physique et neurologique de 52 enfants : 26 ont ete adoptes par des parents qui ont consulte le programme Motherisk a l'Universite de Toronto parce que l'enfant avait ete expose a la cocaine avant sa naissance, et 26 etaient des temoins jumeles en fonction du quotient intellectuel (QI) de la mere, de sa situation socio-economique et de l'âge de la grossesse. Principales mesures de resultats : Circonference du crâne, indice de cognition generale (ICG) de McCarthy, performance linguistique et resultats de tests de temperament. Resultats : Les enfants du groupe d'etude avaient le crâne plus petit (34 e percentile par rapport au 54 e , p = 0,009), des resultats ICG McCarthy plus faibles (102,8 contre 114,2, p = 0,02), une performance linguistique moins bonne sur le plan de la reception et de l'expression, indiquee par le test de Reynell; les tests de temperament indiquaient des niveaux d'activite plus eleves, une persistance moindre et un penchant plus prononce a se laisser distraire. L'analyse a variables multiples a revele un lien important (p = 0,001) entre l'exposition a la cocaine, un QI plus bas et un developpement linguistique moins avance, sans egard au retard de croissance intra-uterine et a d'autres facteurs possibles de confusion. Interpretation : En controlant les facteurs environnementaux postnataux, cette etude sur l'adoption decrit les risques associes a l'exposition a la cocaine pour le developpement intra-uterin. Le suivi au cours des annees scolaires est justifie pour evaluer l'ampleur de ces effets.

Effects of maternal occupational exposure to organic solvents on offspring visual functioning: a prospective controlled study.

Abstract: Background Previous studies in adults and animals with high level exposure to organic solvents suggested impairments in visual functioning. The objective of this pilot study was to examine the effects of maternal occupational exposure to organic solvents during pregnancy on offspring color vision and visual acuity, the development of which may be especially vulnerable to organic solvent exposure. Methods We conducted a prospective cohort study of 32 offspring of women who were exposed occupationally to organic solvents during pregnancy compared with 27 nonexposed children. Monocular and binocular color vision and visual acuity were assessed using the Minimalist Test and the Cardiff Cards, respectively. Children with known hereditary color vision loss were excluded. Results Solvent-exposed children had significantly higher error scores on red-green and blue-yellow color discrimination, as well as poorer visual acuity compared with the control group. Exposure index (an estimated measure of exposure intensity) was not significantly related to color discrimination or visual acuity score. Despite excluding all children with a known family history of color vision loss, clinical red-green color vision loss was found among 3 of the 32 exposed children compared with none of the matched controls. Conclusions These preliminary findings suggest that occupational exposure to organic solvents during pregnancy is associated with an increased risk of color vision and visual acuity impairment in offspring. The importance of routine visual function screening in risk assessment after prenatal exposure to chemicals warrants further attention. Teratology 64:134–141, 2001. © 2001 Wiley-Liss, Inc.

Alcohol and Breast Feeding: Calculation of Time to Zero Level in Milk

Abstract: Objective: To create a nomogram that will guide lactating women who drink socially on how to avoid neonatal exposure to ethanol through breast milk. Design: Pharmacokinetic modeling of ethanol elimination from milk based on reference values. Calculation of the time to zero alcohol in breast milk for a range of doses and body weights. Results: The elimination of alcohol and time-to-zero levels in breast milk are described in a nomogram as a function of the amount of alcohol consumed and the body weight of the woman. Conclusions: Careful planning of a breast feeding schedule, by storing milk before drinking and/or waiting for complete alcohol elimination from the breast milk, can ensure women that their babies are not exposed to any alcohol.

Evidence based information on drug use during pregnancy: a survey of community pharmacists in three countries.

Abstract: Objective: To evaluate whether community pharmacists provide evidence‐based information to women inquiring about specific drug use during pregnancy.Design: A trained female student posing as a surrogate shopper requested information about the relative safety/risks of medications during pregnancy in two scenarios. Forty randomly selected pharmacies were surveyed in the Netherlands, Canada and Iceland, and pharmacists' recommendations were noted. Main outcome measures included the type of information that was provided, its presentation, and the source of information used. Results: A relatively small proportion of pharmacists surveyed, provided evidence‐based information regarding the drugs in question. Only 14% referred to current medical literature, while 60% consulted the product monograph. Over 90% of pharmacists referred the client to a physician. Conclusions: Community pharmacists do not disseminate evidence‐based recommendations when counseling women on drug use in pregnancy, and need further education on resources concerning drugs in pregnancy that are currently available.

The role of the placenta in variability of fetal exposure to cocaine and cannabinoids: a twin study.

Abstract: There is wide variability in the reported adverse fetal effects of cocaine and cannabinoids. The causes of this variability are largely unknown. We hypothesized that variability in placental handli...

Young age and the risk for ifosfamide-induced nephrotoxicity: a critical review of two opposing studies

Abstract: Ifosfamide has been in use as an effective antineoplastic agent for solid tumors in both children and adults since the late 1960s. Although some adverse effects (e.g. hemorrhagic cystitis) can be overcome by the co-administration of 2-mercaptoethanesulfonate (MESNA), others such as nephrotoxicity cannot. There is a consensus that factors such as the cumulative dose of ifosfamide and concomitant cisplatin administration may influence not only the incidence but also the severity of ifosfamide-induced renal toxicity. Several preliminary studies suggested young age as a risk factor for nephrotoxicity; however, there is little agreement on this. The reasons for this uncertainty may include sample size, study design, dose and differences in renal function assessment. In this review we examine the two largest cohort studies conducted in pediatric patients. One study suggests that ifosfamide-induced renal toxicity is age- related, whereas analysis of the other failed to show age as an important predictor for ifosfamide-induced renal toxicity. The studies differed in design, end-points of toxicity and concomitant drug therapy. Due to the effectiveness of ifosfamide as an antineoplastic agent, it is important that an understanding of the factors that predispose pediatric patients to ifosfamide-induced nephrotoxicity be obtained.

Can herbal products be used safely during pregnancy? Focus on echinacea.

Abstract: QUESTION: Many of my patients are now using herbal medicines; some even use them during pregnancy. As we enter the "cold and flu" season, many are inquiring about use of the herb echinacea to prevent these ailments. Is there any evidence to suggest that use of echinacea during pregnancy is safe? ANSWER: Although herbal products have been used in the past during pregnancy and delivery, there is little evidence showing they are safe. Many authoritative reviews of echinacea report that its safety for use during pregnancy has not been established. A recent Motherisk study showed that use of echinacea during the first trimester of pregnancy was not associated with increased risk of major malformations.

Use of hair analysis for confirmation of self-reported cocaine use in users with negative urine tests.

Abstract: Introduction: Identification of cocaine use based on a urine test may miss many cases because of the short elimination half-life of the drug. Our objective was to verify the sensitivity of the cocaine hair test in admitted users.Patients and Methods: Admitted cocaine users (38), that were 18–70 years of age and reported to have refrained from using cocaine in the few days to months prior to the test, were compared to 10 controls who claimed never to have used cocaine. All had negative urine tests for cocaine and benzoylecgonine by thin-layer chromatography. Cocaine and benzoylecgonine were extracted from unwashed hair and tested by established immunoassays.Results: The hair test was positive in 37/38 cases (97%) and in none of the controls. There was significantly more cocaine in black hair than in brown or blonde hair per mg of cocaine dose reported to have been consumed, highlighting a potential bias when interpreting test results in individuals with dark hair. There was a statistically significant corr...

The role of acetaldehyde in pregnancy outcome after prenatal alcohol exposure.

Abstract: It is not known why some heavy-drinking women give birth to children with alcohol-related birth defects (ARBD) whereas others do not. The objective of this study was to determine whether the frequency of elevated maternal blood acetaldehyde levels among alcoholics is in the range of ARBD among alcoholic women. MEDLINE was searched from 1980 to 2000 using the key words acetaldehyde, pharmacokinetics, and alcoholism for controlled trials reporting blood or breath acetaldehyde levels in alcoholics and nonalcoholics. Separately, using the key words fetal alcohol syndrome, epidemiology, prevalence, incidence, and frequency, articles were identified reporting ARBD incidences among the offspring of heavy drinkers. Of 23 articles reporting acetaldehyde levels in alcoholics, four met the inclusion criteria. Forty-three studies reported on the rate of ARBD in heavy drinkers, and 14 were accepted. Thirty-four percent of heavy drinkers had a child with ARBD, and 43% of chronic alcoholics had high acetaldehyde levels. The similar frequencies of high acetaldehyde levels among alcoholics and the rates of ARBD among alcoholic women provide epidemiologic support to the hypothesis that acetaldehyde may play a major role in the cause of ARBD.