No. 245-Alcohol Use and Pregnancy Consensus Clinical Guidelines.

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 Grey (unpublished) literature was identified through searching the websites of health technology assessment (HTA) and HTA-related agencies, national and international medical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: RECOMMENDATIONS.

Pregnancy Outcomes Following In Utero Exposure to Second-Generation Antipsychotics: A Systematic Review and Meta-Analysis.

Second-generation antipsychotics (SGAs) are increasingly used for a variety of mental illnesses; however, the data regarding the safety of these medications during pregnancy are inconclusive and contradictory. We examined the risk of adverse pregnancy outcomes associated with in utero exposure to SGAs by conducting a systematic review and meta-analysis. We searched the databases EMBASE and MEDLINE from January 1990 to December 2014. Eligible studies had to report pregnant women who took SGAs during pregnancy (first trimester exposure if analyzing congenital malformations), follow a healthy comparison group in a similar manner, and report data on pregnancy outcomes. There was no restriction on language, sample size, or publication date. The primary outcome analyzed was major congenital malformations, and secondary outcomes included miscarriages, stillbirths, preterm births, small or large for gestational age neonates, and differences in gestational ages and birth weights. A total of 12 studies met our inclusion criteria, totalling 1782 cases and 1,322,749 controls. The use of SGA during the first trimester of pregnancy was associated with a significant increased risk for major congenital malformations (odds ratio, 2.03; 95% confidence interval, 1.41-2.93); however, no specific pattern of malformations was found. An increased risk was also found for preterm births (odds ratio, 1.85; 95% CI, 1.20-2.86). The use of SGA during pregnancy was not found to be associated with an increased risk for secondary outcomes analyzed. The absence of a specific pattern of malformations makes it difficult to identify an explicit risk posed by SGAs, and therefore, further studies sufficiently controlling for confounding factors are needed to validate these findings.

Pregnancy outcome following prenatal exposure to triptan medications: a meta-analysis.

BACKGROUND: Migraine is a common disorder among women of childbearing age. Triptan medications are effective and commonly used to treat migraines in pregnancy. However, the reproductive safety of this group of drugs has not yet been confirmed. The aim of this study was to determine the reproductive safety of triptan medications by performing a literature review and a meta-analysis. METHODS: Available publications regarding pregnancy outcomes following prenatal exposure to triptans from 1991 to 2013 were identified and reviewed according to the inclusion criteria. A random-effects meta-analysis model was implemented to combine the available pregnancy outcome data for the exposed and comparison groups. RESULTS: One case-control study and 5 cohort studies met the inclusion criteria. The included studies provided information on duration of gestation, major congenital malformations, and spontaneous abortions of infants following prenatal triptan exposure. The 6 studies included 4208 infants of women who used sumatriptan or other triptan medications, and 1,466,994 children of women who did not use triptans during pregnancy. No significant increases in rates for major congenital malformations (MCMs), prematurity, or spontaneous abortions were found when comparing the triptan-exposed group to the migraine - no triptans control group (odds ratio [OR] = 0.84 [0.61-1.16]; OR = 0.90 [0.35-2.30]; OR = 1.27 [0.58-2.79], respectively). There were no increased rate of MCMs (OR = 1.18 [0.97-1.44]) or prematurity (OR = 1.16 (0.67-1.99) when the triptan-exposed group was compared with the healthy controls; however, there was a significant increase in the rates of spontaneous abortions (OR = 3.54 [2.24-5.59]). When the migraine no-triptan group was compared with healthy controls, a significant increase in the rates of MCMs was found (OR = 1.41 [1.11-1.80]). CONCLUSION: The use of triptans during pregnancy does not appear to increase the rates for MCMs or prematurity. The increased rates of spontaneous abortions in the triptan-exposed group and the increased rates of MCM in the migraine no-triptan group require further research.

P450 oxidoreductase *28 (POR*28) and tacrolimus disposition in pediatric kidney transplant recipients--a pilot study.

BACKGROUND: Both age and CYP3A5 genotype are important determinants of tacrolimus disposition in pediatric kidney transplant recipients. In a recent study in adults, POR*28 was associated with increased dosing requirements early after transplant of CYP3A5-expressing kidney transplant recipients. The authors aimed to evaluate the additional contribution of POR*28 to early tacrolimus disposition in pediatric kidney transplant recipients. METHODS: Retrospective data of 43 pediatric kidney transplant recipients up to 14 days posttransplant were evaluated on tacrolimus dose and tacrolimus predose blood concentrations. Recipient POR*28 and CYP3A5 genotype were determined. RESULTS: CYP3A5 expressers carrying at least 1 POR*28 allele had on average 18.3% lower tacrolimus predose concentrations and 20.2% lower concentration/dose ratios compared with CYP3A5 expressers with POR*1/*1 genotype (P = 0.002 and P = 0.001, respectively). In CYP3A5 nonexpressers, tacrolimus disposition did not significantly differ between POR genotypes. CONCLUSIONS: In this small cohort of pediatric kidney transplant recipients, POR*28 genotype seems to explain part of the variability found in tacrolimus disposition, in addition to age and CYP3A5 genotype. This finding should be validated in a larger population, and it would be worthwhile to evaluate the clinical impact of this genotype.

Gynecologic cancers in pregnancy: guidelines of a second international consensus meeting.

OBJECTIVES: This study aimed to provide timely and effective guidance for pregnant women and health care providers to optimize maternal treatment and fetal protection and to promote effective management of the mother, fetus, and neonate when administering potentially teratogenic medications. New insights and more experience were gained since the first consensus meeting 5 years ago. METHODS: Members of the European Society of Gynecological Oncology task force "Cancer in Pregnancy" in concert with other international experts reviewed the existing literature on their respective areas of expertise. The summaries were subsequently merged into a complete article that served as a basis for discussion during the consensus meeting. All participants approved the final article. RESULTS: In the experts' view, cancer can be successfully treated during pregnancy in collaboration with a multidisciplinary team, optimizing maternal treatment while considering fetal safety. To maximize the maternal outcome, cancer treatment should follow a standard treatment protocol as for nonpregnant patients. Iatrogenic prematurity should be avoided. Individualization of treatment and effective psychologic support is imperative to provide throughout the pregnancy period. Diagnostic procedures, including staging examinations and imaging, such as magnetic resonance imaging and sonography, are preferable. Pelvic surgery, either open or laparoscopic, as part of a treatment protocol, may reveal beneficial outcomes and is preferably performed by experts. Most standard regimens of chemotherapy can be administered from 14 weeks gestational age onward. Apart from cervical and vulvar cancer, as well as important vulvar scarring, the mode of delivery is determined by the obstetrician. Term delivery is aimed for. Breast-feeding should be considered based on individual drug safety and neonatologist-breast-feeding expert's consult. CONCLUSIONS: Despite limited evidence-based information, cancer treatment during pregnancy can succeed. State-of-the-art treatment should be provided for this vulnerable population to preserve maternal and fetal prognosis. SUPPLEMENTARY INFORMATION: Supplementary data on teratogenic effects, ionizing examinations, sentinel lymph node biopsy, tumor markers during pregnancy, as well as additional references and tables are available at the extended online version of this consensus article, go to http://links.lww.com/IGC/A197.

Safety of treatment of obsessive compulsive disorder in pregnancy and puerperium.

QUESTION: My patient is 3 weeks postpartum and has experienced repetitive checking and washing of her newborn as a result of obsessive concerns with the newborn's safety. Should I refer her for a psychiatric assessment to rule out obsessive compulsive disorder (OCD) or should I reassure her that her behaviour is normal? ANSWER: Current data suggest that pregnancy and the postpartum period are times of high risk of OCD onset and exacerbation. The presenting symptoms of OCD overlap with normal concerns and behaviour during the perinatal period; however, an undiagnosed or untreated disorder could have adverse consequences for both the mother and her newborn. Therefore, it is strongly recommended that this patient undergo screening and psychiatric assessment in order to be appropriately managed.

Acute olanzapine overdose in a toddler: a case report.

We describe a 17-month-old female presented with an acute overdose of olanzapine, an atypical antipsychotic. She displayed prolonged extrapyramidal symptoms as compared with that in previous reports and prolactin levels above the upper limits of normal ranges. This is the first report to measure serum prolactin levels in an olanzapine-overdosed toddler and the second to calculate olanzapine's elimination half-life.

RETIRED: Cancer chemotherapy and pregnancy.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation.

PURPOSE: In children, data on the combined impact of age, genotype, and disease severity on tacrolimus (TAC) disposition are scarce. The aim of this study was to evaluate the effect of these covariates on tacrolimus dose requirements in the immediate post-transplant period in pediatric kidney and liver recipients. METHODS: Data were retrospectively collected describing tacrolimus disposition, age, CYP3A5 and ABCB1 genotype, and pediatric risk of mortality (PRISM) scores for up to 14 days post-transplant in children receiving liver and renal transplants. Initial TAC dosing was equal in all patients and adjusted using therapeutic drug monitoring. We determined the relationship between covariates and tacrolimus disposition. RESULTS: Forty-eight kidney and 42 liver transplant recipients (median ages 11.5 and 1.5 years, ranges 1.5-17.7 and 0.05-14.8 years, respectively) received TAC post-transplant. In both transplant groups, younger children (<5 years) needed higher TAC doses than older children [kidney: 0.15 (0.07-0.35) vs. 0.09 (0.02-0.20) mg/kg/12h, p = 0.046, liver: 0.12 (0.04-0.32) vs. 0.09 (0.01-0.18) mg/kg/12h, p = 0.038]. In kidney but not liver transplants, CYP3A5 expressors needed significantly higher TAC doses than nonexpressors [0.15 (0.07-0.20) vs. 0.09 (0.02-0.35) mg/kg/12h, P = 0.001]. In these patients, age and CYP3A5 genotype were independently associated with TAC dosing requirement. In liver, but not kidney transplant patients, homozygous ABCB1 T-T-T haplotype carriers needed higher TAC doses than noncarriers [0.26 (0.15-0.32) vs. 0.11 (0.01-0.25) mg/kg/12h, p = 0.013]. CONCLUSION: CYP3A5 genotype may explain variation in tacrolimus disposition early after transplant in pediatric kidney recipients, independent of age-related variation. In contrast, in pediatric liver recipients, variation in tacrolimus disposition appears related to age and ABCB1 genotype. These findings illustrate the importance of the interplay among age, genotype, and transplant organ on tacrolimus disposition.

Diclectin for morning sickness: Long-term neurodevelopment.

Question A pregnant patient recently asked me whether using Diclectin for morning sickness might affect the development of her child. Answer Our recent large study does show such a trend, although the differences are not necessarily clinically significant.

Neurocognitive outcomes following fetal exposure to chemotherapy for gestational breast cancer: A Canadian multi-center cohort study.

BACKGROUND: Limited knowledge exists on outcomes of children exposed prenatally to chemotherapy for breast cancer (BC). The purpose of this study was to compare long-term neurocognitive, behavioral, developmental, growth, and health outcomes of children exposed in-utero to chemotherapy for BC. METHODS: This is a multi-center matched cross-sectional cohort study involving seven cancer centers across the region of Southern Ontario (Canada), and the Hospital for Sick Children (Toronto, Ontario). Using standardized psychological and behavioral tests, we compared cognitive and behavioral outcomes in children exposed to chemotherapy during pregnancy for BC to age-matched pairs exposed to known non-teratogens. RESULTS: We recruited 17 parent-child pairs and their matched controls. There were more preterm deliveries in the chemotherapy-exposed group compared to controls (p < 0.05). Full Scale IQ of children in the chemotherapy group was significantly confounded by maternal IQ and prematurity. Exposed children born at term were not different in cognitive outcomes. Children from both groups were similar in their developmental milestones, pediatric anthropometric measurements and health problems. There were no cases of autoimmune cytopenia. CONCLUSIONS: This is the first Canadian prospective comparative study designed to assess pediatric cognition following prenatal exposure to chemotherapy for BC. Chemotherapy was not found to be neurotoxic in this cohort and did not affect pediatric health. The decision to plan a preterm birth for initiating or continuing chemotherapy treatment must be taken into consideration in context of pediatric implications. While these results may assist in such decision making, replication with a larger sample is needed for more conclusive findings.

Universal screening for prenatal alcohol exposure: a progress report of a pilot study in the region of Grey Bruce, Ontario.

The main objective of this study is to evaluate the clinical utility of meconium analysis for fatty acid ethyl esters as a universal screening tool intended for the detection of newborns at risk for fetal alcohol spectrum disorder. This will be accomplished by assessing the rate of voluntary participation in a nonanonymous neonatal screening program and by determining the logistics of implementing the necessary follow-up and interventions as part of routine care. Additionally, this study will determine the predictive value of fatty acid ethyl ester-positive meconium with regard to neurodevelopmental delays. This is an ongoing prospective cohort study. Written informed consent is sought from all Grey Bruce women delivering at participating birthing sites. Collected meconium samples are tested for fatty acid ethyl esters by headspace-solid-phase microextraction followed by gas chromatography-mass spectrometry. Children with positive results are followed up through an existing public health program involving regular home visits and assessments of developmental milestones by a public health nurse. These children and matched control subjects also undergo neurodevelopmental testing at 3 and 18 months of age by a clinical psychologist using Bayley Scales of Infant and Toddler Development. If delays are detected, the child is referred to diagnostic services and appropriate intervention programs. This study has been granted ethics approval and enrollment began in November 2008 at St. Joseph's Health Care in London, Ontario. The first positive case has been identified and the follow-up is currently being conducted by the public health unit. The successful completing of this study will reveal the population's willingness to participate in a neonatal screening program for prenatal alcohol exposure and determine the costs, feasibility, and utility of implementing such programs in clinical practice.

Alcohol use and pregnancy consensus clinical guidelines.

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).

Paternal exposure to recreational drugs before conception and its effect on live-born offspring: A scoping review.

BACKGROUND: Men of reproductive age increasingly use recreational drugs. While many of these substances may reduce the quantity and quality of sperm, less is known about the effects of these exposures on their offspring. We performed a scoping review to summarize the available literature and identify areas for future research on the outcome of live-born offspring of fathers who were exposed to recreational drugs before conception. METHODS: A systematic search was conducted of the Medline, EMBASE, and Web of Science databases, which included keywords for the following substances: cannabis-related products, cocaine, heroin, hallucinogens, ecstasy and amphetamines. In total, 2,983 records were screened, and 129 publications were selected for full-text assessment. Publications were included if (a) the timing of exposure included the preconceptional period, and (b) if outcomes in live-born offspring were compared with an unexposed group. RESULTS: We included 30 publications, of which 15 animal studies and 15 human studies. Animal studies showed neurocognitive abnormalities, in particular in male offspring. Interestingly, these outcomes depend significantly on the method of exposure (i.e., fixed-dose administration vs. variable self-administration, which mimics addiction). Human studies were limited to specific congenital malformations and childhood cancers, which showed small increased odds ratios. CONCLUSIONS: While animal studies describe impaired neurocognitive outcomes following paternal exposure to recreational drugs, data in humans is currently lacking. Human studies require sound methodology in order to confirm findings on congenital malformations and childhood cancers. In addition, future neurocognitive studies require parental neurocognitive assessments to correct for confounding effects (i.e., role of genetics).

Long-term neurodevelopment of children exposed to maternal nausea and vomiting of pregnancy and diclectin.

OBJECTIVE: To determine the effects of nausea and vomiting of pregnancy (NVP) and its treatment with diclectin on child neurodevelopment. STUDY DESIGN: An observational cohort study of mother-child pairs ascertained via a pregnancy call-in center was conducted. Three groups of children were studied: 45 with NVP and diclectin, 47 with NVP no diclectin, and 29 with no NVP. Phone calls to mothers during pregnancy and 6 to 9 months after childbirth yielded information on pregnancy, birth, and early child development. Children aged 3 to 7 years received a comprehensive set of psychological tests. Mothers were assessed for IQ and socioeconomic status. RESULTS: All children scored in the normal range for IQ, with the NVP-exposed group scoring higher than the non-exposed group on Performance IQ (P < .02), NEPSY Verbal Fluency (P < .003) and Phonological Processing (P < .004), and McCarthy Numerical Memory (P < .004). Predictors of enhanced results were NVP severity and maternal IQ. CONCLUSIONS: NVP has an enhancing effect on later child outcome. Diclectin does not appear to adversely affect fetal brain development and can be used to control NVP when clinically indicated.

Both parental psychopathology and prenatal maternal alcohol dependency can predict the behavioral phenotype in children.

OBJECTIVE: To identify whether a child's behavior phenotype can be predicted by parental psychopathology and/or prenatal maternal alcohol dependency by using the Child Behavior List (CBCL) as a screening tool. METHODS: A retrospective cohort of four non-exclusive groups of children (aged 8-15 years) was studied: (i) children exposed to alcohol in utero (n = 25); (ii) children not exposed to alcohol in utero (n = 46); (iii) children exposed to parental psychopathology (n = 37); (iv) children not exposed to parental psychopathology (n = 34). To distinguish between the effects of alcohol and parental psychopathology, the children were further subdivided into groups with alcohol exposure in utero and parental psychopathology (n = 23), and psychopathology without alchohol exposure (n = 14). Each child was assessed with the CBCL. Subscale scores and selected subscale items were compared between the groups using t-tests and regression analysis. RESULTS: Children exposed to alcohol in utero scored significantly lower than unexposed children on school competency (p = 0.015). They were more likely to attend special classes (p = 0.048), repeat a grade (p = 0.011), and display more disobedience (p = 0.039) and vandalism (p = 0.033). For special classes and disobedience at school, gender proved to be a significant predictor, while maternal alcohol dependency was a significant predictor of vandalism and repeated grades. Children with parental psychopathology differed from children without parental psychopathology in the anxious/depressed (p = 0.04), social problems (p = 0.004), and attention problems (p = 0.04) subscales. The subscale items that were significantly different between the groups were nervousness (p = 0.002), self-consciousness (p = 0.019), feelings of worthlessness (p = 0.041), loneliness (p = 0.005), and difficulty with concentration (p = 0.02). Parental psychopathology was a significant predictor of all five items. Age and gender, however, were significant predictors only of difficulty with concentration. No significant differences were found when the groups with alcohol exposure in utero and parental psychopathology, and psychopathology without alcohol exposure were compared. In summary, parental psychopathology was a significant predictor of a child's internalizing behavior, as well as social problems, whereas alcohol exposure was more predictive of externalizing behaviour. CONCLUSION: Parental psychopathology and prenatal exposure to maternal alcohol can contribute to the child's behavioral phenotype as measured by the CBCL. Therefore, the CBCL can be used to screen for such behaviors.

Challenges to diagnosing colorectal cancer during pregnancy.

QUESTION: My patient is 13 weeks pregnant and has experienced rectal bleeding and vomiting. Should I send her for a colonoscopy to rule out colorectal malignancies or should I wait until after delivery? ANSWER: The data on colorectal cancer in pregnancy are scarce; however, as the presenting features of colorectal cancer overlap with those of pregnancy itself, there is a risk of development of advanced disease, with poorer prognosis at diagnosis. Therefore, it is strongly recommended that this patient, who is in her second trimester, undergo at least a flexible sigmoidoscopy, which is presumed safe during pregnancy, with or without a liver ultrasound and carcinoembryonic antigen detection based on pretest probability according to her other risk factors.

Guidelines for maternal codeine use during breastfeeding.

QUESTION: In light of the recent evidence of adverse events in infants whose mothers use codeine medication, we have been struggling with the issue of how to manage codeine analgesia in our postpartum patients. What are some guidelines for the safe use of codeine during breastfeeding? ANSWER: Motherisk has summarized recent scientific evidence into suggested guidelines for the safe use of codeine during breastfeeding.