American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity.

Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6 variability. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for codeine based on CYP2D6 genotype. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2D6 genotype and codeine therapy.

/pdf/clinical-pharmacogenetics-implementation-consortium-34u28qousw.pdf

Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update

Background: Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies. Aims of the Study: The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Methods and Findings: Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p,0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. Conclusions: The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research.

/pdf/toxoplasmosis-a-global-threat-correlation-of-latent-51kbfh1eag.pdf

Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries

The management of psychiatric disorders during the perinatal period can be difficult; psychiatric decompensation during pregnancy can affect not only the mother but also the fetus and neonate. It is imperative that psychiatric providers proactively discuss pregnancy planning, and be able to thoughtfully weigh the risks of untreated psychiatric illness and psychotropic medications in pregnancy and breast-feeding. With the exception of valproate and carbamazepine, several mood stabilizers and antipsychotics can be utilized during pregnancy with minimal risk to the fetus and neonate in terms of major malformations; there is a growing body of evidence regarding the risk profile of use of these medications in pregnancy. Key Points Preconception planning is very helpful when it can be done; consider discussion and documentation of risks at time of administration of psychotropic medications for any reproductive-aged women, regardless of plans for conception. Continued psychiatric stability through the perinatal period is imperative; the risks of an untreated psychiatric disorder are just as important, if not more so important, than the risks of psychotropic medication exposure. Exposure to one psychotropic medication is safer than exposure to multiple medications. Utilize lowest effective dose of medication; most risks are not dose dependent, therefore would typically prefer higher dose of medication, rather than emergence of psychiatric symptoms, in order to avoid exposure of the fetus to both psychotropic medications and psychiatric symptoms. General recommendations are to avoid valproate and carbamazepine in reproductive-aged women. With close monitoring, lithium can be safely utilized in pregnancy. Preliminary data regarding use of atypical antipsychotics is reassuring in regards to major malformations; however, larger numbers of participants are needed to provide more complete reproductive safety data with this class. Clearly document risks of an untreated psychiatric illness as well as risks of psychotropic medication management to the mother and developing fetus/neonate.

Managing Your Own Mood Lability: Use of Mood Stabilizers and Antipsychotics in Pregnancy

Background
There is evidence that certain antiepileptic drugs (AEDs) are teratogenic and are associated with an increased risk of congenital malformation. The majority of women with epilepsy continue taking AEDs throughout pregnancy; therefore it is important that comprehensive information on the potential risks associated with AED treatment is available.

Objectives
To assess the effects of prenatal exposure to AEDs on the prevalence of congenital malformations in the child.

Search methods
We searched the Cochrane Epilepsy Group Specialized Register (September 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 11), MEDLINE (via Ovid) (1946 to September 2015), EMBASE (1974 to September 2015), Pharmline (1978 to September 2015), Reprotox (1983 to September 2015) and conference abstracts (2010-2015) without language restriction.

Selection criteria
We included prospective cohort controlled studies, cohort studies set within pregnancy registries and randomised controlled trials. Participants were women with epilepsy taking AEDs; the two control groups were women without epilepsy and women with epilepsy who were not taking AEDs during pregnancy.

Data collection and analysis
Three authors independently selected studies for inclusion. Five authors completed data extraction and risk of bias assessments. The primary outcome was the presence of a major congenital malformation. Secondary outcomes included specific types of major congenital malformations. Where meta-analysis was not possible, we reviewed included studies narratively.

Main results
We included 50 studies, with 31 contributing to meta-analysis. Study quality varied, and given the observational design, all were at high risk of certain biases. However, biases were balanced across the AEDs investigated and we believe that the results are not explained by these biases.

Children exposed to carbamazepine (CBZ) were at a higher risk of malformation than children born to women without epilepsy (N = 1367 vs 2146, risk ratio (RR) 2.01, 95% confidence interval (CI) 1.20 to 3.36) and women with untreated epilepsy (N = 3058 vs 1287, RR 1.50, 95% CI 1.03 to 2.19). Children exposed to phenobarbital (PB) were at a higher risk of malformation than children born to women without epilepsy (N = 345 vs 1591, RR 2.84, 95% CI 1.57 to 5.13). Children exposed to phenytoin (PHT) were at an increased risk of malformation compared with children born to women without epilepsy (N = 477 vs 987, RR 2.38, 95% CI 1.12 to 5.03) and to women with untreated epilepsy (N = 640 vs 1256, RR 2.40, 95% CI 1.42 to 4.08). Children exposed to topiramate (TPM) were at an increased risk of malformation compared with children born to women without epilepsy (N = 359 vs 442, RR 3.69, 95% CI 1.36 to 10.07). The children exposed to valproate (VPA) were at a higher risk of malformation compared with children born to women without epilepsy (N = 467 vs 1936, RR 5.69, 95% CI 3.33 to 9.73) and to women with untreated epilepsy (N = 1923 vs 1259, RR 3.13, 95% CI 2.16 to 4.54). There was no increased risk for major malformation for lamotrigine (LTG). Gabapentin (GBP), levetiracetam (LEV), oxcarbazepine (OXC), primidone (PRM) or zonisamide (ZNS) were not associated with an increased risk, however, there were substantially fewer data for these medications.

For AED comparisons, children exposed to VPA had the greatest risk of malformation (10.93%, 95% CI 8.91 to 13.13). Children exposed to VPA were at an increased risk of malformation compared with children exposed to CBZ (N = 2529 vs 4549, RR 2.44, 95% CI 2.00 to 2.94), GBP (N = 1814 vs 190, RR 6.21, 95% CI 1.91 to 20.23), LEV (N = 1814 vs 817, RR 5.82, 95% CI 3.13 to 10.81), LTG (N = 2021 vs 4164, RR 3.56, 95% CI 2.77 to 4.58), TPM (N = 1814 vs 473, RR 2.35, 95% CI 1.40 to 3.95), OXC (N = 676 vs 238, RR 3.71, 95% CI 1.65 to 8.33), PB (N = 1137 vs 626, RR 1.59, 95% CI 1.11 to 2.29, PHT (N = 2319 vs 1137, RR 2.00, 95% CI 1.48 to 2.71) or ZNS (N = 323 vs 90, RR 17.13, 95% CI 1.06 to 277.48). Children exposed to CBZ were at a higher risk of malformation than those exposed to LEV (N = 3051 vs 817, RR 1.84, 95% CI 1.03 to 3.29) and children exposed to LTG (N = 3385 vs 4164, RR 1.34, 95% CI 1.01 to 1.76). Children exposed to PB were at a higher risk of malformation compared with children exposed to GBP (N = 204 vs 159, RR 8.33, 95% CI 1.04 to 50.00), LEV (N = 204 vs 513, RR 2.33, 95% CI 1.04 to 5.00) or LTG (N = 282 vs 1959, RR 3.13, 95% CI 1.64 to 5.88). Children exposed to PHT had a higher risk of malformation than children exposed to LTG (N = 624 vs 4082, RR 1.89, 95% CI 1.19 to 2.94) or to LEV (N = 566 vs 817, RR 2.04, 95% CI 1.09 to 3.85); however, the comparison to LEV was not significant in the random-effects model. Children exposed to TPM were at a higher risk of malformation than children exposed to LEV (N = 473 vs 817, RR 2.00, 95% CI 1.03 to 3.85) or LTG (N = 473 vs 3975, RR 1.79, 95% CI 1.06 to 2.94). There were no other significant differences, or comparisons were limited to a single study.

We found significantly higher rates of specific malformations associating PB exposure with cardiac malformations and VPA exposure with neural tube, cardiac, oro-facial/craniofacial, and skeletal and limb malformations in comparison to other AEDs. Dose of exposure mediated the risk of malformation following VPA exposure; a potential dose-response association for the other AEDs remained less clear.

Authors' conclusions
Exposure in the womb to certain AEDs carried an increased risk of malformation in the foetus and may be associated with specific patterns of malformation. Based on current evidence, LEV and LTG exposure carried the lowest risk of overall malformation; however, data pertaining to specific malformations are lacking. Physicians should discuss both the risks and treatment efficacy with the patient prior to commencing treatment.

Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child

Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine screening for Toxoplasma gondii infection during pregnancy not available for most Canadians?

Answer Low prevalence of the infection, high cost associated with testing, low sensitivity of screening tests, false-positive test results, and limitations of treatment effectiveness are all cited as reasons for not routinely screening for T gondii infection in Canada. Currently, screening for the detection of T gondii is only performed in Nunavik and other parts of northern Quebec owing to the high prevalence of infection in this region. Congenital toxoplasmosis causes neurologic or ocular disease (leading to blindness), as well as cardiac and cerebral anomalies.

https://www.cfp.ca/content/cfp/60/4/334.full.pdf

Toxoplasmosis and pregnancy

Listeriosis is a rare foodborne illness caused by Listeria monocytogenes It can be transmitted by consuming contaminated ready-to-eat food, long shelf-life products, deli meats, and soft cheeses Listeria has a predilection to affect immunocompromised patients, elderly people, pregnant women and neonates In particular, pregnant women are at ~18 times greater risk of infection than general population due to specific pregnancy-related suppressed cell-mediated immunity and placental tropism of L monocytogenes The purpose of this review is to summarize the current knowledge regarding listeriosis during pregnancy A literature search on Medline and Embase was done for articles about listeriosis during pregnancy A detailed review of published data on epidemiology, pathogenesis, diagnosis, treatment and prevention of listeriosis during pregnancy was performed Listeriosis during pregnancy encompasses maternal, fetal and neonatal disease Maternal listeriosis during pregnancy usually presents as a mild febrile illness Fetal listeriosis has a high mortality rate of 25–35%, depending on the gestational age at the time of infection Neonatal listeriosis may present as sepsis or meningitis with severe sequels and high case fatality rate of 20% Adequate treatment of maternal listeriosis prevents and treats fetal disease and it is of imminence importance in the treatment of the neonates Amoxicillin or ampicillin are the first line of treatment alone or in combination with gentamicin, followed by trimethoprim/sulfamethoxazole Pregnancy-associated listeriosis should be considered as a cause of fever during pregnancy and appropriate treatment should be initiated preemptively Prevention remains the best way to control listeriosis and should be reinforced among patients, health care professionals, and regulatory agencies

Listeriosis during pregnancy

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.

https://www.cfp.ca/content/cfp/61/7/607.full.pdf

Hepatitis E infection during pregnancy

First trimester exposure to topiramate and the risk of oral clefts in the offspring: A systematic review and meta-analysis

Background
Neonates are commonly exposed to maternal codeine through breast milk. Central Nervous System (CNS) depression has been reported in up to 24% of nurslings following codeine exposure. In 2009, we developed guidelines to improve the safety of codeine use during breastfeeding based on previously established pharmacogenetic and clinical risk factors. The primary objective of this study was to prospectively evaluate the effectiveness of these guidelines in ensuring neonatal safety.

https://e-lactancia.org/media/papers/CodeinaBF-2013_1.pdf

Shahnaz A. Chaudhry

Papers

Toxoplasmosis and pregnancy

Listeriosis during pregnancy

Hepatitis E infection during pregnancy

First trimester exposure to topiramate and the risk of oral clefts in the offspring: A systematic review and meta-analysis

A clinical tool for reducing central nervous system depression among neonates exposed to codeine through breast milk.