Cheri Nickel

Pregnancy Outcome Following Prenatal Exposure to Triptan Medications: A Meta-Analysis

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.

Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta‐analysis

AIMS The objective of this meta-analysis was to determine whether gestational use of hydroxychloroquine (HCQ) for autoimmune disorders leads to an increase in the risk for adverse pregnancy outcomes. METHODS MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched from inception to November 21 2014. Studies which reported the outcomes of pregnant women after exposure to HCQ during pregnancy and including a control (unexposed) group were included. Two independent reviewers carried out the review and the quality assessment using the Methodological Index for Non-Randomized Studies (MINORS). A random effects method was used to calculate the odds ratios (OR) for the outcomes. RESULTS The meta-analysis reported no significant increases in rates of major congenital (OR 1.13, 95% confidence interval (CI) 0.59, 2.17), craniofacial (OR 0.62, 95% CI 0.13, 3.03), cardiovascular (OR 1.06, 95% CI 0.29, 3.86), genitourinary (OR 1.38, 95% CI 0.42, 4.53), nervous system malformations (OR 1.81, 95% CI 0.31, 10.52), stillbirth (OR 0.69, 95% CI 0.35, 1.34), low birth weight (OR 0.69, 95% CI 0.21, 2.27) or prematurity (OR 1.75, 95% CI 0.95, 3.24). The rate of spontaneous abortions, however, was found to be significantly increased in HCQ exposed pregnancies (OR 1.85, 95% CI 1.10, 3.13). No significant heterogeneity was detected among the studies for the evaluated outcomes except prematurity. CONCLUSIONS Prenatal exposure to HCQ for autoimmune diseases does not appear to increase the risk of adverse pregnancy outcomes except spontaneous abortion rate, which may be associated with the underlying disease activity (bias by indication) and needs further investigation.

Association Between Use of Oral Contraceptives and Folate Status: A Systematic Review and Meta-Analysis

OBJECTIVE To conduct a systematic review and meta-analysis of the effect of oral contraceptive use on plasma and red blood cell (RBC) folate concentrations. METHODS We searched Medline, EMBASE, Web of Science, and the Cochrane library for human studies published from inception to June 2013 evaluating oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. A random-effects model of outcomes was used for the meta-analysis. RESULTS A total of 2831 women in 17 studies were included in the analysis. In those whose plasma folate concentrations were available, there was a significant folate-lowering effect of oral contraceptives observed (mean reduction 1.27 µg/L; 95% CI 1.85 to 0.69, P < 0.001). Similarly, after analyzing data from 1389 women in 12 studies whose RBC folate concentrations were available, significantly lower folate status was observed among oral contraceptive users (mean reduction 59.32 µg/L; 95% CI 58.03 to 23.04, P < 0.001). CONCLUSION Because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is critical for women of childbearing age to continue folate supplementation during oral contraceptive use.

The Effectiveness of Folate-Fortified Oral Contraceptives in Maintaining Optimal Folate Levels to Protect Against Neural Tube Defects: A Systematic Review

OBJECTIVE To conduct a systematic review evaluating the effectiveness of a folate-fortified oral contraceptive preparation in increasing blood folate concentrations to levels providing optimal protection against neural tube defects (> 906 nmol/L). METHODS We searched Medline, EMBASE, Web of Science, and the Cochrane Library for human studies published from inception to June 2013 that evaluated oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. Efficacy and bioequivalence data were evaluated from included studies. RESULTS Overall, efficacy and bioequivalence data for the folate-fortified oral contraceptive show that it is at least as effective as folic acid alone in raising blood folate concentrations, and that the concomitant administration of folate with the oral contraceptive component does not affect its absorption or kinetics. CONCLUSION A folate-fortified oral contraceptive preparation provides an option for women to maintain blood folate levels, especially those who may be planning a family after the cessation of oral contraceptive therapy.

Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis

Evaluation of human data regarding the outcomes of topical‐retinoid‐exposed pregnancies is important in terms of counselling pregnant women with inadvertent exposure. The objective of this study was thus to determine whether exposure to topical retinoids leads to an increase in the risk of adverse pregnancy outcomes. We carried out a search using the Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases from inception to 4 December 2014. The selection, review and quality assessment of the studies were carried out by two independent reviewers according to predetermined inclusion criteria. Odds ratios (ORs) were calculated by the random effects method. This meta‐analysis, including a total of 654 pregnant women who were exposed to topical retinoids, and 1375 unexposed control pregnant women, did not detect significant increases in rates of major congenital malformations [OR 1·22, 95% confidence interval (CI) 0·65–2·29], spontaneous abortions (OR 1·02, 95% CI 0·64–1·63), stillbirth (OR 2·06, 95% CI 0·43–9·86), elective termination of pregnancy (OR 1·89, 95% CI 0·52–6·80), low birthweight (OR 1·01, 95% CI, 0·31–3·27) or prematurity (OR 0·69, 95% CI 0·39–1·23). No significant heterogeneity was detected among the studies for the evaluated outcomes. The present meta‐analysis ruled out a major increase in the rates of major congenital malformations, spontaneous abortions, low birthweight and prematurity. This result may be used primarily in reassuring women who were inadvertently exposed to topical retinoids during their pregnancy. However, the statistical power is not adequate to justify the use of topical retinoids during pregnancy.

Are statins teratogenic in humans? Addressing the safety of statins in light of potential benefits during pregnancy

HMG-CoA reductase inhibitors (statins) are increasingly being prescribed. Their safety during pregnancy has not been determined. Statins are contraindicated during pregnancy based on the overarching concept that their benefits do not outweigh potential fetal risks of exposure. The role of cholesterol during gestation, combined with teratogenic effects seen in animal testing of lovastatin has supported this contraindication. However, statins have become exceedingly popular, women are delaying pregnancy, and obesity and subsequent cardiovascular risk has increased. The time off of therapy may have detrimental effects to both the fetus and mother. Additionally, statins have been shown to have benefits not related to cholesterol lowering effects, known as pleiotropic effects. These indications may support use during pregnancy for obstetrical complications. This article will systematically review statin safety during pregnancy. Included, we present a meta-analysis of controlled studies in an attempt to provide...

Hyperosmolar metabolic acidosis in burn patients exposed to glycol based topical antimicrobials—A systematic review

BACKGROUND The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents. METHODS Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy. RESULTS A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap. CONCLUSION This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner.