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Hypothalamic-Pituitary-Adrenal (HPA) axis activity is related to negative mental health outcomes, including depression. Most developmental research uses salivary cortisol to index HPA activity; however, hair cortisol concentrations (HCCs) reflect cortisol production over extended periods of time. While HCCs have been linked to adult depression, their relationship to the development of children's depressive symptoms is unclear. We assessed HCCs in 60 seven-year-old community-dwelling girls who were followed up one year later. In broader models, girls' age 7 HCCs were positively associated with age 8 depressive symptoms at a trend level, indicating that HCCs may be related to mental health early in development.

Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine ( P < .05). As well, doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores. [ABSTRACT FROM AUTHOR]

Background: The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity. Methods: This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed. Results: Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359). Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch), 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer. Significance/Conclusion: These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users. [ABSTRACT FROM AUTHOR]

Background Meconium analysis for fatty acid ethyl esters ( FAEEs) is a validated method for identifying heavy prenatal ethanol (EtOH) exposure. This study investigated whether delayed sample collection can result in false-positive test results for FAEEs because of collection of samples potentially contaminated with postnatally produced stool. Methods Serial excretions were prospectively collected from neonates born to nondrinking mothers to capture the transition from meconium to postnatal stool. These were analyzed for FAEEs using headspace-solid phase microextraction and gas chromatography-mass spectrometry. Experiments involving incubation of samples with glucose or EtOH were performed to explore a potential mechanism of FAEE elevation. Results A total of 136 samples were collected from 30 neonates during their first few days of life (median of 4 samples/baby over a mean period of 68.5 hours postpartum). Although the first-collected meconium sample tested negative for FAEEs in all babies, later samples tested above the 2 nmol/g positive cutoff in 19 of 30 babies. Median time to appearance of FAEE-positive samples was 59.2 hours postpartum. In vitro experiments demonstrated that FAEE levels can be further increased in late samples (likely containing postnatal stool) after incubation with glucose, and that FAEEs are readily formed in meconium in the presence of EtOH. Conclusions Collection of samples excreted later in the postpartum period can lead to false-positive test results for FAEEs, which could be because of contamination with dietary components of postnatally produced stool and EtOH-producing microorganisms. Clinically, it is critical to collect the earliest possible excretion for determination of FAEEs to ensure that the FAEE content is representative of in utero EtOH exposure. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Teratology Information Services (TIS) provide health care professionals and the public with information regarding the safety and/or risk of exposures during pregnancy and lactation, mainly via telephone consultations. An international comparison of clinical practices at TIS has never been conducted. The survey objective was to compare international TIS to North American TIS, with an aim to identify strengths and challenges that can lead to service improvement. Methods Twenty-two international TIS were approached for participation during an international conference. TIS were surveyed on information in six categories: services, staffing, operations, data collection, knowledge transfer activities and additional information. Data were summarized using descriptive statistics. Statistical tests were conducted using SPSS®. Results Sixteen TIS from 12 countries participated. Survey results were compared with previously reported results from a similar survey of North American TIS (16 US, two Canadian). TIS exist in a variety of departments and settings, but most commonly are in university hospitals. Pregnant women were the most commonly counselled group worldwide. International TIS spent significantly more time fielding inquiries regarding medications, while North American TIS had a wider variety of inquiry categories. All TIS could improve budget tracking. Conclusions Overall, service practices and goals were similar, although international TIS conducted more follow-up with service users than North American TIS. This report offers TIS the first ever opportunity to compare practices. Increased dialogue between TIS encourages sharing of best practices and improves the ability of these important public health programmes to support women and health care providers. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: It has been estimated that between 7% and 55% of expectant mothers use herbal medicines or other types of natural health products (NHPs). Unfortunately, the safety and efficacy of NHPs during pregnancy and lactation is largely unknown. The Motherisk Program, at the Hospital for Sick Children, Toronto, Ontario, Canada, the is the major Canadian group to counsel and monitor outcomes of women using medications or NHPs, or of women exposed to chemicals, radiation or infection during pregnancy and lactation. Objective: To create a network for research on NHPs during pregnancy and lactation by forming longstanding collaborations among Canadian medical and complementary and alternative medicine (CAM) practitioners and scientists. Methodology: MotherNature Network members participated in three 2-day workshops and three conference calls throughout the length of this study. Each member was responsible to lead discussions surrounding one theme and address the following: initiation; development; presentation; and synthesis of comments of all members on the designated theme. Results: We prioritized areas in high need for future research and collaborative means to conduct such research. NHPs were prioritized for their importance for future study. Areas for the prospective collection of data on NHP use in pregnancy and lactation were identified. A research and business plan was developed for the long-term sustainability of the Network. Conclusions: The MotherNature Network is well-situated to create a new climate in Canada, where data are collected and interpreted on the effects and safety of NHPs during pregnancy and lactation. [ABSTRACT FROM AUTHOR]

Background: Glucosamine (GLS) is an endogenous aminomonosaccharide. It is used as a disease-modifying agent for the treatment of osteoarthritis. There is no information regarding its use in pregnancy. Our objective was to determine whether GLS treatment in pregnancy is associated with an increased risk of major malformations or other adverse outcomes. Methods: Pregnant women were recruited from The Motherisk Program at the Hospital for Sick Children, Toronto, Canada. Women exposed to GLS were compared with women exposed to nonteratogenic agents. They were matched for gestational age at time of call, maternal age, and cigarette and alcohol consumption. Rates of major malformations and other end points of interest were compared between the two groups. Results: We were able to ascertain the outcomes of 54 women who used GLS during pregnancy (34 during organogenesis). There were 50 live births (two sets of twins), 4 spontaneous abortions, 1 therapeutic abortion, and 1 stillbirth, with no major malformations. The mean birth weight was 3524 ± 482 g, and the median gestational age at birth was 39 weeks (range 37–40). Conclusions: These limited data suggest no increased risk for major malformations or other adverse fetal effects following the use of GLS during pregnancy. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Family Physician / Médecin de Famille Canadien is the property of College of Family Physicians of Canada and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The authors comment on a study which explores the association of the usage of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy with increased risk of spontaneous abortion. They note various limitations of the work including its failure to adjust for environmental exposure and application of difficult to interpret terms. Moreover, the authors cite the need for future research that include data relating to the use of prescription and over-the-counter NSAIDs.

The vast majority of drugs prescribed for children have not been approved by regulatory agencies for the pediatric age group and, in many cases, have not been studied appropriately. In July 2008, at a meeting of pediatric pharmacologists from over 30 countries and 5 continents in Toronto, ON, Canada, it became apparent that numerous pediatric drug studies are being conducted, often duplicating studies done elsewhere. This is also true for pharmacokinetic and pharmacodynamic studies, as well as for the development of pediatric formulations. Finding simple ways to inform the world about existing data may save time and facilitate efforts. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Family Physician / Médecin de Famille Canadien is the property of College of Family Physicians of Canada and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Family Physician / Médecin de Famille Canadien is the property of College of Family Physicians of Canada and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Focuses on the risk for malformations in infants of women taking isotretinoin. Characteristics of isotretinoin embryopathy; Discussion on the Pregnancy Prevention Program for women's awareness of teratogenicity of the drug; Introduction of generic isotretinoin in Canada.

Examines the folate status and obesity among schizophrenic patients treated with atypical antipyschotics in Canada. Risk of neural tube defects in infants due to adiposity in pregnant women; Correlation between serum folate levels and folate intake; Association of plasma folate level with fat intake.

Abstract: Background: There is a dearth of information on paternal drug exposure at the time of conception. The Motherisk Program, established in 1985, is a teratology information and clinical consultation service on drug safety during pregnancy and lactation, as well as paternal exposure (PEx). Here, we reviewed for the first time our experience with PEx. Methods: This was an observational retrospective cohort study using a prospectively collected database. Telephone counselling records from January 2002 to December 2007, inclusive, were screened to identify cases concerning PEx. Results: Of a total of 188,188 counselling requests over these 6 years, 301 (0.16%) pertained to PEx. Counselling was most frequently sought on methotrexate, finasteride, prednisone and azathioprine. For many drugs, limited or no information was available on PEx. Conclusions: Paternal exposure represents a small fraction of counselling requests to Motherisk. Our findings suggest that there is an ongoing need for information on paternal drug exposure. [Copyright &y& Elsevier]

Our study aimed to estimate the prevalence of heavy fetal alcohol exposure through the analysis of meconium FAEEs as an objective biomarker of fetal exposure. We conducted a study on meconium samples collected nationwide through the Maternal-Infant Research on Environmental Chemicals (MIREC) Study Group. FAEE in meconium was quantified by an established headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME GC-MS). Out of 1315 samples collected in 10 Canadian obstetric units coast to coast between 2008-2011, the estimated prevalence of positive meconium FAEE ranged between 1.16% and 2.40%, translating into at least 1800 new cases of FASD in Canada each year. Positive maternal self- reports of heavy alcohol use were tenfold lower (0.24%). Use of meconium FAEE revealed tenfold more cases of heavy exposure to maternal drinking than did maternal reports. The use of objective measures of maternal alcohol exposure is critical in accurately estimating risks and in monitoring effective prevention of FASD.

Objective: To review the existing data regarding varicella zoster virus infection (chickenpox) in pregnancy, interventions to reduce maternal complications and fetal infection, and antepartum and peripartum management ., Methods: The maternal and fetal outcomes in varicella zoster infection were reviewed, as well as the benefit of the different treatment modalities in altering maternal and fetal sequelae., Evidence: Medline was searched for articles and clinical guidelines published in English between January 1970 and November 2010., Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table)., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: To assess the percentage of women of childbearing age with suboptimal levels of folate for protecting against neural tube defects (&lt;906 nM), and assess folate status among the elderly., Methods: A total of 1,035 anonymous blood samples from a centralized clinical laboratory, with a catchment area across the Greater Toronto Area, were assessed for red blood cell (RBC) folate concentrations using a chemiluminescent immunoassay. Folate analysis was requested by physicians as part of clinical care. Available data included age, sex, and RBC folate concentration. Descriptive statistics were used to characterize the percent of women who had suboptimal blood folate concentrations, and a multiple regression was used to analyze determinants of folate status., Results: Our data from 2013 show that 7% of women of childbearing age (15-45 years) had RBC folate concentrations below 906 nM, a substantially lower percentage than in our 2006 study (40%). Results from the multiple regression showed that age is a significant positive predictor of higher RBC folate status (p &lt; 0.001)., Conclusion: Compared to our earlier data, we report a significant decrease in the suboptimal folate status among women of childbearing age. We also show that age is a predictor of higher RBC folate levels. Our data are limited due to a lack of information regarding patient or physician characteristics, and to the nature of our sample, yet our results are consistent with the continued increase in folate status observed among several population-level studies in the US and Canada post-fortification. Further research is needed to determine the reasons for and future implications of this continued increase in the elderly.

Question: Many of my patients are from Southeast Asia where hepatitis E virus (HEV) infection is quite common. What precautions can I suggest they take before traveling to these areas and what is the risk of contracting HEV during pregnancy?, Answer: Hepatitis E is a water-borne pathogen transmitted by the fecal-oral route. To reduce the risk of contracting HEV while traveling to endemic areas, it is important to maintain hygienic practices such as hand washing with safe water, particularly before handling food, avoiding drinking water or using ice cubes of unknown purity, and avoiding eating unpeeled fruits and vegetables. Currently there is no vaccine available in Canada for HEV. Hepatitis E infection during pregnancy, especially in the third trimester, is characterized by a more severe infection that sometimes results in fulminant hepatitis, increasing maternal and fetal mortality and morbidity., (Copyright© the College of Family Physicians of Canada.)

Importance: Suicide is the tenth leading cause of death in the United States, and its rate has risen by 16% in the past decade. Deliberate self-poisoning is the leading method of attempted suicide. Unlike more violent methods, which are almost universally fatal, survival following self-poisoning is common, providing an opportunity for secondary prevention. However, the long-term risk of suicide following a first episode of self-poisoning is unknown., Objective: To determine the risk of suicide and mortality from other causes following a first self-poisoning episode., Design, Setting, and Participants: Population-based cohort study using multiple linked health care databases. We identified all individuals with a first self-poisoning episode in Ontario, Canada, from April 1, 2002, through December 31, 2010, and followed up all surviving participants until December 31, 2011, or death, whichever occurred first. For each individual with a deliberate self-poisoning episode, we randomly selected 1 control from the same population with no such history, matched for age (within 3 months), sex, and calendar year., Main Outcomes and Measures: The primary analysis examined the risk of suicide following discharge after self-poisoning. The secondary analyses explored factors associated with suicide and examined the risk of death caused by accidents or any other cause., Results: We identified 65 784 patients (18 482 [28.1%] younger than 20 years) who were discharged after a first self-poisoning episode. During a median follow-up of 5.3 years (interquartile range, 3.1-7.6 years), 4176 died, including 976 (23.4%) by suicide. The risk of suicide following self-poisoning was markedly increased relative to controls (hazard ratio, 41.96; 95% CI, 27.75-63.44), corresponding to a suicide rate of 278 vs 7 per 100 000 person-years, respectively. The median time from hospital discharge to completed suicide was 585 days (interquartile range, 147-1301 days). Older age, male sex, multiple intervening self-poisoning episodes, higher socioeconomic status, depression, and recent psychiatric care were strongly associated with suicide. Patients with a self-poisoning episode were also more likely to die because of accidents (hazard ratio, 10.45; 95% CI, 8.10-13.47) and all causes combined (hazard ratio, 5.55; 95% CI, 5.12-6.02)., Conclusions and Relevance: A first self-poisoning episode is a strong predictor of subsequent suicide and premature death. Most suicides occur long after the index poisoning, emphasizing the importance of longitudinal, sustained secondary prevention initiatives.

Introduction: Labetalol is one of the most commonly used antihypertensive medications for the treatment of hypertension during pregnancy, an increasingly common and leading cause of maternal mortality and morbidity worldwide., Areas Covered: The literature reviewed included the 2014 Canadian national pregnancy hypertension guideline and its references. The additional published literature was retrieved through searches of Medline, CINAHL, and The Cochrane Library using appropriate controlled vocabulary (e.g., pregnancy, hypertension, pre-eclampsia, pregnancy toxemias) and key words (e.g., diagnosis, evaluation, classification, prediction, prevention, prognosis, treatment, and postpartum follow-up).Results were restricted to systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies published in French or English, Jan-Mar/14. The unpublished literature was identified by searching websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. We evaluated the impact of interventions on substantive clinical outcomes for mothers and babies., Expert Opinion: Labetalol is a reasonable choice for treatment of severe or non-severe hypertension in pregnancy. However, we should continue our search for other therapeutic options.

Question: I have learned that one of the manufacturers of prenatal vitamins has added omega-3 fatty acids and claims that they help support fetal cognitive health and brain function. Is this based on evidence?, Answer: The claim that polyunsaturated fatty acids help improve fetal brain and eye development has been made for more than a decade. Unfortunately it is not supported by evidence-based science. Long-term studies have failed to show such effects. Implying to women that using these products will improve the brain development of their children is unwarranted and misleading. Health Canada should clarify the contradictions in its statements about omega-3 fatty acids.

Objective: To investigate the effectiveness of Lactobacillus reuteri DSM 17938 for the treatment of infantile colic in breastfed Canadian infants, compared with placebo., Study Design: A randomized, double-blind, placebo-controlled trial was conducted involving 52 infants with colic, according to modified Wessel criteria, who were assigned at random to receive L reuteri DSM 17938 (10(8) colony-forming units) (n = 24) or placebo (n = 28) for 21 days. Daily crying and fussing times were recorded in a structured diary, and maternal questionnaires were completed to monitor changes in infant colic symptoms and adverse events., Results: Total average crying and fussing times throughout the study (from baseline to day 21) were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group (1719 ± 750 minutes [29 ± 13 hours] vs 2195 ± 764 minutes [37 ± 13 hours]; P = .028) (relative risk, 0.78; 95% CI, 0.58-0.98). Infants given L reuteri DSM 17938 showed a significant reduction in daily crying and fussing times at the end of treatment period compared with those receiving placebo (median, 60 minutes/day [IQR, 64 minutes/day] vs 102 minutes/day [IQR, 87 minutes/day]; P = .045). On day 21, a significantly higher proportion of infants in the L reuteri DSM 17938 group responded to treatment with a ≥50% crying time reduction compared with infants given placebo (17 vs 6, P = .035; relative risk, 3.3; 95% CI, 1.55-7.03)., Conclusion: Administration of L reuteri DSM 17938 significantly improved colic symptoms by reducing crying and fussing times in breastfed Canadian infants with colic., (Copyright © 2015 Elsevier Inc. All rights reserved.)

With children being largely orphaned from the benefits of drugs, and being managed mostly by medications unapproved by Health Canada, a landmark document was published in September 2014 by the Council of Canadian Academies (CCA) to serve as a blueprint to change this grim reality. The main findings of the panel included: 1. Children take medications, many of which have not been proven safe and effective for their use. 2. Children respond to medications differently from adults; thus, medicines must be studied in children and formulated for children. 3. Studying medicines in children is always possible and in their best interests. 4. In the United States and the European Union, pediatric medicines research is encouraged, required and monitored in ways that offer lessons for Canada. 5. Pediatric medicines research is a Canadian strength, but it requires reinforcement, sustained capacity and infrastructure to realize its full potential.

As part of the Canadian Association of Paediatric Health Centres Taskforce on FASD Screening commitment to further pilot, validate and evaluate the multiple components of the Canadian FASD Screening Tool Kit, it was deemed necessary that recent developments and/or improvements in FASD screening were identified and considered. In 2008 a literature review of methods for screening for FASD was published until 2006 and identified five tools which met pre-set criteria. A review of all new papers was published from the period January 2006 until July 1, 2013. Out of 1392 papers, two new screening methods met the inclusion criteria: Clarren et al's new norms for palpebral fissure length by age in Canada; and Breiner et al's extension of the Neurobehavioral Screening Test (NST) to age 4 years. Further work is needed to validate these methods in other settings.

Background: Cortisol level in hair is increasingly being used as a biomarker of chronic stress. Members of First Nation communities in Canada are experiencing stress related to a higher incidence of chronic diseases, socioeconomic factors, the state of their environment, and cultural oppression. This study aimed to investigate hair cortisol as a biomarker of stress in this population., Materials and Methods: Hair samples were collected from the posterior vertex of 55 Walpole Island First Nation (WIFN) volunteers and compared with white volunteers living in and around London, ON, Canada. An enzyme-linked immunosorbent assay technique was used to measure cortisol content in 1 cm of hair, considered to represent 1 month of growth. In parallel, the Perceived Stress Scale (PSS), which measures short-term stress, was also completed., Results: Median hair cortisol level (range) in WIFN volunteers was 177 (93-273) ng/g, significantly higher than the median hair cortisol in the healthy white controls of 116 (26-204) ng/g (P < 0.0001, Mann-Whitney U test). Hair cortisol correlated positively with gender, smoking status, and self-reported diabetes. Unlike hair cortisol, the Perceived Stress Scale did not differentiate between the First Nation and control population., Conclusions: The increased hair cortisol concentrations among WIFN volunteers compared with volunteers from a non-First Nation community suggests higher levels of chronic stress. The causes for this apparent increased stress are likely due to factors such as socioeconomic and poorer health and are worthy of further evaluation. The results highlight the difference between acute stress measured for short periods of time compared with chronic stress, measured by hair analysis.

Background: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health., Methods: Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the study's Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies., Results: Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada., Conclusions: The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals., (© 2013 John Wiley & Sons Ltd and Her Majesty the Queen in Right of Canada. Reproduced with the permission of the Minister of Health.)

Background: Most children with Fetal Alcohol Spectrum Disorder (FASD) do not display the typical facial changes, making the diagnosis much more challenging due to poor specificity of the brain dysfunction exhibited by these children. We have recently described and validated a behavioral phenotype of FASD using items from the Child Behavior Checklist (The Neurobehavioral Screening Test, NST). This tool has high sensitivity and specificity in separating children aged 6-13 yrs with FASD from those with ADHD and from healthy controls., Objectives: To test the validity of the NST for children aged 4-6 years in order to help facilitate diagnosis of FASD in young children., Methods: Children referred to Motherisk for FASD diagnosis are all tested using the Child Behavior Checklist. We compared the scores of children 4-6 yrs diagnosed with FASD to those referred but not receiving a diagnosis, as well as to normal healthy control children of the same age range.ResultsOut of the 10 items of NST used at age 6-13 years, 3 are not scored in children 4-6 years of age. Using the 7 remaining items, children with FASD endorsed significantly more items (6.7+/-1.3) than healthy controls ( 2.3+/-1.2 ), or alcohol- exposed children who were not given an FASD diagnosis (4.7+/- 1.9). Using a cut-off of 5 out of7 items, the NST had a 94% sensitivity and 96% specificity in identifying children with FASD. Nine of 19 children exposed to alcohol with whom an FASD diagnosis could not be confirmed, scored 5 or more on the NST., Conclusions: In this pilot study, the NST has shown very high sensitivity and specificity and can be used to identify children who are very likely to be diagnosed with FASD.

Objectives: This study compares the behavioral profile of children with fetal alcohol spectrum disorder (FASD) who were diagnosed using the Canadian Guidelines with children with prenatal alcohol exposure who did not meet criteria for a FASD diagnosis., Methods and Procedures: To accomplish this, we used caregiver and teacher questionnaires evaluating different aspects of behavior. Investigated were 170 children, 109 who received a diagnosis of FASD (Diagnosed Group) and 61 who did not (Non-Diagnosed Group). On the caregiver report, children in the Diagnosed Group had more internalizing and externalizing problems on the CBCL, more executive function difficulties on the BRIEF and more attention problems on the Conner's Rating Scale, compared to the Non-Diagnosed Group. On teacher report, children in the Diagnosed Group had more internalizing and externalizing problems on the TRF and more attention problems on the Conner's Rating Scale, compared to the Non-Diagnosed Group. For both informants, more children in the Diagnosed group had scores in the clinically elevated range., Conclusion: Overall, the present results identify key caregiver- and teacher-rated profiles of children with FASD diagnoses. These profiles will aid in better understanding, diagnosing and providing focused treatment approaches for children with FASD.

Question: While I usually prescribe doxylamine-pyridoxine for morning sickness, some of my patients with severe nausea and vomiting of pregnancy (NVP) receive ondansetron in hospital. I have read some new precautions recommended by the US Food and Drug Administration (FDA). Is ondansetron safe to use during pregnancy?, Answer: During the past decade ondansetron has been increasingly used in the United States for NVP, owing to the lack of an FDA-approved drug for this condition. While fetal safety data for doxylamine-pyridoxine are based on more than a quarter of a million pregnancies, the fetal safety data for ondansetron are based on fewer than 200 births. Moreover, a recent case-control study suggested there was an increased risk of cleft palate associated with ondansetron. Recently, the FDA issued a warning about potentially serious QT prolongation and torsade de pointes associated with ondansetron use; the warning included a list of precautions and tests that must be followed. The drug is not labeled for use in NVP in either the United States or Canada. Based on the data available today, ondansetron use cannot be assumed to be safe during pregnancy.

Question: I often prescribe domperidone to women as a galactagogue starting at a dose of 30 mg and increasing the dose as needed. In March of this year, Health Canada released an advisory warning of domperidone use and abnormal heart rhythms and sudden cardiac death. Should I cap doses at 30 mg or stop prescribing domperidone all together to these women?, Answer: The Health Canada warning is based on 2 studies. The results of the studies are not directly applicable to breastfeeding and should not change the way you normally manage otherwise healthy breastfeeding women.

Objective: To review the existing data regarding varicella zoster virus infection (chickenpox) in pregnancy, interventions to reduce maternal complications and fetal infection, and antepartum and peripartum management., Methods: The maternal and fetal outcomes in varicella zoster infection were reviewed, as well as the benefit of the different treatment modalities in altering maternal and fetal sequelae., Evidence: Medline was searched for articles and clinical guidelines published in English between January 1970 and November 2010., Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table)., Recommendations: 1. Varicella immunization is recommended for all non-immune women as part of pre-pregnancy and postpartum care. (II-3B) 2. Varicella vaccination should not be administered in pregnancy. However, termination of pregnancy should not be advised because of inadvertent vaccination during pregnancy. (II-3D) 3. The antenatal varicella immunity status of all pregnant women should be documented by history of previous infection, varicella vaccination, or varicella zoster immunoglobulin G serology. (III-C) 4. All non-immune pregnant women should be informed of the risk of varicella infection to themselves and their fetuses. They should be instructed to seek medical help following any contact with a person who may have been contagious. (II-3B) 5. In the case of a possible exposure to varicella in a pregnant woman with unknown immune status, serum testing should be performed. If the serum results are negative or unavailable within 96 hours from exposure, varicella zoster immunoglobulin should be administered. (III-C) 6. Women who develop varicella infection in pregnancy need to be made aware of the potential adverse maternal and fetal sequelae, the risk of transmission to the fetus, and the options available for prenatal diagnosis. (II-3C) 7. Detailed ultrasound and appropriate follow-up is recommended for all women who develop varicella in pregnancy to screen for fetal consequences of infection. (III-B) 8. Women with significant (e.g., pneumonitis) varicella infection in pregnancy should be treated with oral antiviral agents (e.g., acyclovir 800 mg 5 times daily). In cases of progression to varicella pneumonitis, maternal admission to hospital should be seriously considered. Intravenous acyclovir can be considered for severe complications in pregnancy (oral forms have poor bioavailability). The dose is usually 10 to 15 mg/kg of BW or 500 mg/m² IV every 8 h for 5 to 10 days for varicella pneumonitis, and it should be started within 24 to 72 h of the onset of rash. (III-C) 9. Neonatal health care providers should be informed of peripartum varicella exposure in order to optimize early neonatal care with varicella zoster immunoglobulin and immunization. (III-C) Varicella zoster immunoglobulin should be administered to neonates whenever the onset of maternal disease is between 5 days before and 2 days after delivery. (III-C).

Objective: To examine the health and well-being of children residing in residences where drug production is occurring., Study Design: Starting in January 2006, children identified by police and the Children's Aids Society in the York region of Ontario, Canada, were referred to the Motherisk Program at the Hospital for Sick Children for pediatric assessment of their general health and well-being, with specific focus on illicit-drug exposure. We used a standard protocol to collect all available medical and environmental history, conducted physical and neurologic examinations, and collected hair for analysis of illicit drugs., Results: In total, 75 children, at the mean age of 6.5 years, were referred to us after being removed from homes where marijuana was grown (80%) or other operations linked to drug production were occurring (20%). Overall, rates of health issues in this cohort fell below reference values for Canadian children. Of the hair tests, 32% were positive for illicit substances. In the majority there were no clinical symptoms related to these drugs., Conclusion: The majority of children removed from drug-producing homes were healthy and drug free. Comprehensive evaluations should be performed on a case-by-case basis in order to determine what is ultimately in the best interest of the child., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Introduction: Most biomarker studies of the effects of maternal smoking on fetal growth have been based on a single blood or urinary cotinine value, which is inadequate in capturing maternal tobacco exposure over the entire pregnancy. We used hair biomarkers to compare the associations of maternal self-reported smoking, hair nicotine, and hair cotinine with birth weight for gestational age (BW for GA) among active and passive smokers during pregnancy., Methods: We collected maternal hair in the immediate postpartum period and measured nicotine and cotinine concentrations averaged over the pregnancy in 444 term controls drawn from 5,337 participants in a multicenter nested case-control study of preterm birth. BW for GA Z-score and small for gestational age (SGA) were based on Canadian population-based standards., Results: The addition of hair nicotine to multiple linear regression models containing self-reported active smoking, hair cotinine, or both explained significantly more variance in the BW for GA Z-score (p = .01, .03 and .04, respectively). Similarly, women with hair nicotine, but not cotinine, at or above the median value had a significant increase in the risk of SGA birth (odds ratio: 3.07, 95% CI: 1.25-7.52). No significant association was observed between maternal passive smoking and BW for GA based on hair biomarkers., Conclusions: Hair nicotine is a better predictor of reductions in BW for GA than either hair cotinine or self-report. Our negative results for passive smoking suggest that previously reported small but significant effects may be explained by misclassification of active smokers as passive smokers based on self-report.

Objective: During the H1N1 influenza pandemic in 2009, The Motherisk Program, a counselling service providing teratology information, received many calls from pregnant women inquiring about the safety of the H1N1 vaccine. We wished to explore pregnant women's perception of risk and the factors associated with deciding whether or not to receive the vaccine., Methods: Pregnant women who called Motherisk between October 1 and November 30, 2009, requesting counselling regarding the safety of the H1N1 vaccine, and who had not yet received the vaccine, were contacted for follow-up using a structured questionnaire., Results: One hundred thirty women completed the questionnaire; 104 (80%) had received the H1N1 vaccination following their call to Motherisk, and 26 (20%) had not. More than 70% of the women cited confusing and frightening information in the media as a trigger for their concern, prompting them to call Motherisk. Sixty percent stated that information from their primary health care providers or Motherisk contributed to their decision making., Conclusion: The H1N1 vaccination rate in pregnant women who contacted Motherisk was higher than the rate in the general population, as many followed Motherisk's recommendation to receive the vaccine. During this period, the media appeared to provide pregnant women with confusing information. In any future pandemic scare, accessibility to primary health care providers or specialized information services such as Motherisk will be key to providing guidance for pregnant women.

Background: Diclectin, composed of 10 mg doxylamine succinate (DOX) and 10 mg pyridoxine hydrochloride, is the drug combination of choice for the management of nausea and vomiting during pregnancy in Canada. However, there is large variability in its onset and duration of action among women. To understand and improve its effectiveness, the variability in the pharmacokinetics of the ingredients in this doxylamine succinate/pyridoxine hydrochloride combination must be studied., Objectives: To determine the pharmacokinetics of DOX and pyridoxine after oral administration of two tablets of this drug combination in the form of Diclectin and to calculate their respective relative bioavailability by comparison with intravenous administration in another population., Methods: Eighteen nonpregnant, nonlactating, healthy females between 18 and 45 years of age were administered two tablets of Diclectin with 240 mL of water under empty stomach conditions. Blood samples were analyzed for DOX and pyridoxine along with its four active metabolites: pyridoxal, pyridoxal-5'-phosphate (PLP), pyridoxamine, and pyridoxamine-5'-phosphate using tandem mass spectrometry. For the purpose of this study, pharmacokinetic values for DOX and PLP were adjusted for body weight., Results: The mean DOX-AUC0→∞ was calculated to be 3137.22 ± 633.57 ng·hr/mL (range, 2056.59-4376.06 ng·hr/mL). The mean PLP-AUC0→∞ was calculated to be 5513.10 ± 2362.35 ng·hr/mL (range, 1572.56-10,153.77 ng·hr/mL). Based on literature values of the PLP-AUC0→∞ after intravenous administration and data from the current study, the relative bioavailability of pyridoxine in Diclectin was calculated at 100%., Conclusion: There was a 2.1-fold variability in the DOX-AUC0→∞ and 6.5-fold variability in the PLP-AUC0→∞ after oral administration of 20 mg Diclectin. Using literature values and data from the current study, we estimated the oral bioavailability of pyridoxine to be 100%. Therefore, interindividual differences in metabolism, and not in bioavailability, may be important sources of variability that need to be addressed in dosing guidelines.

The Canadian Association of Pediatric Health Centres, working in partnership with the Public Health Agency of Canada has recently published a toolkit to guide screening for identification of risk of FAS/FASD. One of the tools highlighted is the testing of meconium for fatty acid ethyl esters to identify high risk pregnancies and to support associated prevention programs. This paper describes the conclusions of a workshop held in Prince Edward Island in September 2011 to discuss key issues surrounding the wider deployment of meconium testing for assessment of population risk for FAS/FASD.

Background: In Canada the incidences of Fetal Alcohol Spectrum Disorder (FASD) is estimated to be in 1 in 100 live births caused by prenatal exposure to alcohol, the disorder is the leading cause of developmental and cognitive disabilities among Canadian children and its effects are life lasting. No research has attempted to describe the experience of living with FASD from the perspective of Canadian children., Purpose: The main purpose of this study was to describe the children's experience of living with FASD., Methods: A qualitative method was used to examine the children's experiences. Twenty-two (22) children, aged 6 to 18 years, living in urban and rural communities across Canada participated in an unstructured in-depth interview. Data was analysed using Colaizzi's qualitative method., Results: For all children in this study, living day-to-day with FASD meant feeling different. Within this construct knowing the disability; feeling alone-feeling supported, and overcoming the disability were dominant themes which emerged., Conclusion: Implications for practice and research have been described., Keywords: Fetal Alcohol Spectrum Disorder, children's experience, qualitative research.

It typically takes many years before an association of a drug with a rare, serious adverse reaction is established. As related to pediatric drug use, evidence is even more erratic, as most drugs are used off labels. To enhance child safety, there is an urgent need to develop robust and rapid methods to identify such associations in as timely a manner as possible. In this chapter, several novel methods, both clinically based pharmacoepidemiological approaches and laboratory-based methods, are described.

We report on the first Helpline for pharmacists dealing with the safety of medications in pregnancy and during breastfeeding. Pharmacists from all parts of Canada participated in this pilot, receiving guidance in approximately 90% of cases. There were 472 inquiries relating to 598 products with regards to safety in pregnancy and 197 calls relating to 249 products regarding exposure in breastfeeding. All callers who were surveyed found the service helpful in counseling both patients and physicians.

A new approach to the educational aspects of FASD will help educational experts to be better prepared for students affected by this challenging condition.

Background: Alcohol consumption in pregnancy may result in serious adverse fetal outcome. Non- or low alcoholic wines and beers may be a risk-reduction strategy to help alcohol-dependent individuals to prevent or limit ethanol consumption. The objective of this study was to quantify ethanol concentrations in Canadian beverages claiming to contain no or low alcohol content., Methods: Forty-five different beverages claiming to contain no or low alcohol content in the Canadian market were tested for ethanol concentration using gas chromatography., Results: Thirteen (29%) of the beverages contained ethanol levels higher than the declared concentration on their label. Six beverages claiming to contain no alcohol were found to contain greater than 1% ethanol., Conclusion: Pregnant women seeking replacement to alcoholic beverages may be misled by these labels, unknowingly exposing themselves and their unborn babies to ethanol.

Juxtaposing clinical pharmacology with human genetics, pharmacogenomics utilizes a patient's genetic information to identify genetic variants that have the potential to provide clinically relevant predictions of toxicity and efficacy. The goal is to develop personalized and genetic-based predictions of an individual's drug response and likelihood of experiencing an adverse drug reaction. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) has implemented active adverse drug reaction surveillance to monitor and discover genetic markers related to serious adverse drug reactions in the pediatric population. Evidence-based pharmacogenomics research will inform public policy and influence drug benefit-risk decision-making. Regulatory processes and future challenges in pharmacogenomics research will be discussed.

Objective: to establish national standards of care for the screening and recording of alcohol use and counselling on alcohol use of women of child-bearing age and pregnant women based on the most up-to-date evidence., Evidence: published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library in May 2009 using appropriate controlled vocabulary (e.g., pregnancy complications, alcohol drinking, prenatal care) and key words (e.g., pregnancy, alcohol consumption, risk reduction). Results were restricted to literature published in the last five years with the following research designs: systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment (HTA) and HTA-related agencies, national and international medical specialty societies, clinical practice guideline collections, and clinical trial registries. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was evaluated and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care., Values: the quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1)., Sponsor: the Public Health Agency of Canada and the Society of Obstetricians and Gynaecologists of Canada., Endorsement: these consensus guidelines have been endorsed by the Association of Obstetricians and Gynecologists of Quebec; the Canadian Association of Midwives; the Canadian Association of Perinatal, Women's Health and Neonatal Nurses (CAPWHN); the College of Family Physicians of Canada; the Federation of Medical Women of Canada; the Society of Rural Physicians of Canada; and Motherisk. SUMMARY STATEMENTS: 1. There is evidence that alcohol consumption in pregnancy can cause fetal harm. (II-2) There is insufficient evidence regarding fetal safety or harm at low levels of alcohol consumption in pregnancy. (III) 2. There is insufficient evidence to define any threshold for low-level drinking in pregnancy. (III) 3. Abstinence is the prudent choice for a woman who is or might become pregnant. (III) 4. Intensive culture-, gender-, and family-appropriate interventions need to be available and accessible for women with problematic drinking and/or alcohol dependence. (II-2)., Recommendations: 1. Universal screening for alcohol consumption should be done periodically for all pregnant women and women of child-bearing age. Ideally, at-risk drinking could be identified before pregnancy, allowing for change. (II-2B) 2. Health care providers should create a safe environment for women to report alcohol consumption. (III-A) 3. The public should be informed that alcohol screening and support for women at risk is part of routine women's health care. (III-A) 4. Health care providers should be aware of the risk factors associated with alcohol use in women of reproductive age. (III-B) 5. Brief interventions are effective and should be provided by health care providers for women with at-risk drinking. (II-2B) 6. If a woman continues to use alcohol during pregnancy, harm reduction/treatment strategies should be encouraged. (II-2B) 7. Pregnant women should be given priority access to withdrawal management and treatment. (III-A) 8. Health care providers should advise women that low-level consumption of alcohol in early pregnancy is not an indication for termination of pregnancy. (II-2A).

Objective: To study hair mercury concentrations among women of reproductive age in relation to fish intake in Ontario, Canada., Study Design: Three groups were studied: 22 women who had called the Motherisk Program for information on the reproductive safety of consuming fish during pregnancy, a group of Japanese residing in Toronto (n=23) consuming much larger amounts of fish, and a group of Canadian women of reproductive age (n=20) not seeking advice, were studied. Mercury concentrations in hair samples were measured using inductively coupled plasma mass spectrometry. Seafood consumption habits were recorded for each participant. Based on the types of fish consumed and consumption frequencies, the estimated monthly intake of mercury was calculated. Hair mercury concentrations were correlated to both the number of monthly seafood servings and the estimated ingested mercury dose., Results: There were significant correlations between fish servings and hair mercury (Spearman r=0.73, P<.0001) and between amounts of consumed mercury and hair mercury concentrations (Spearman r=0.81, P<.0001). Nearly two thirds of the Motherisk callers, all of the Japanese women, and 15% of the Canadian women of reproductive age had hair mercury above 0.3 microg/g, which was shown recently to be the lowest observable adverse effect level in a large systematic review of all perinatal studies., Conclusions: Because of very wide variability, general recommendations for a safe number of fish servings may not be sufficient to protect the fetus. Analysis of hair mercury may be warranted before pregnancy in selected groups of women consuming more than 12 ounces of fish per week, as dietary modification can decrease body burden and ensure fetal safety., (Copyright (c) 2010. Published by Mosby, Inc.)

Background: Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADRs and matched control patients., Summary: ADRs represent a significant unmet medical problem with significant morbidity and mortality, and Canadian Pharmacogenomics Network for Drug Safety is a nation-wide network in Canada that seeks to identify genetic factors responsible for interindividual differences in susceptibility to serious ADRs., Conclusions: Active ADR surveillance is necessary to identify and recruit patients who suffer from serious ADRs. National and international collaborations are required to recruit sufficient patients for these studies. Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future.

A woman's alcohol use during pregnancy is one of the top preventable causes of birth defects and developmental disabilities that are known as fetal alcohol spectrum disorders (FASD). The social and economic burden of FASD is substantial. Lifetime direct tangible costs per individual related to health care, education and social services in Canada have been estimated to be $1.4 million. Screening women of child-bearing age and pregnant women and recording their alcohol consumption is a practical process to identify and evaluate women at-risk and to identify potentially exposed infants. The FASD Advisory Workgroup proposes the following three levels of screenings which should be done on consenting women: Level I screening involves practice-based approaches that can be used by health care providers when talking to women about alcohol use, such as motivational interviewing and supportive dialogue. Level II screening includes a number of structured questionnaires that can be used with direct questioning (TLFB) or indirect /masked screening (AUDIT, BMAST / SMAST, CAGE, CRAFFT, T-ACE, TWEAK). Level III screening includes laboratory-based tools that can be used to confirm the presence of a drug, its level of exposure and determine the presence of multiple drugs. There are challenges and limitations in the use of the screening and assessment tools outlined. For example, the single question about alcohol use and the various questionnaires rely on a woman to provide details about her alcohol use. There is no consensus on the appropriate screening to use across Canada as each provincial / territorial jurisdiction, health care organization and healthcare provider uses a variety of formal and informal screening tool. In addition, there are inconsistent processes across Canada for the recording of the alcohol use in a woman's chart and the transfer of the information to the infant and the child's health records. The FASD Advisory Workgroup proposes eleven recommendations to improve the screening and recording processes for alcohol use in women of child-bearing age and pregnant women.

Background: Hair testing is commonly used to confirm potential drug exposure in children living with drug users, as well as abstinence in their caregivers., Objective: To examine differences across pediatric age groups in the relationship between caregiver use of cocaine and cocaine exposure in children., Methods: We determined concentrations of cocaine and its metabolite, benzoylecgonine, in the hair of 19 child-caregiver pairs to estimate the pattern of exposure of the children according to age; concentrations in the caregivers' hair were used as a surrogate marker for the intensity of environmental exposure. Cocaine and benzoylecgonine concentrations in hair were determined by immunoassay., Results: A significant correlation was observed between cocaine concentrations in the hair of infants and their caregivers (Spearman rho = 0.87; p = 0.005; n = 8), and the absence of a correlation in older children. These results suggest that environmental exposure plays an important role in the accumulation of cocaine in the hair of infants., Conclusion: Measurement of cocaine hair concentrations can allow estimation of the degree of environmental drug exposure in young children. Infants seem to have a disproportionately increased risk for systemic exposure, compared with older children.