Prospective evaluation of pregnancy outcomes after gestational exposure to prazosin.

AIMS: Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. The aim of this study was to assess the fetal and pregnancy safety associated with prazosin exposures in early pregnancy. METHODS: Subjects were 11 patients who took prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between 1 January 2000 and 31 December 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires. RESULTS: It was found that 6/11 (54.5%) subjects did not report any adverse outcomes and experienced uneventful pregnancies. There were two miscarriages. Birthweights were within the normal range for the remaining nine pregnancies. Adverse events reported were consistent with background population expectation, including: one postpartum haemorrhage, one case of preeclampsia, one preterm birth, two NICU admissions, and two caesarean sections. CONCLUSIONS: For these 11 subjects, pregnancy outcomes after exposure to prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to prazosin while pregnant. Therefore, this study contributes valuable data towards monitoring safety of prazosin in pregnancy.

Severe Generalized Bullous Fixed Drug Eruption Treated with Cyclosporine: A Case Report and Literature Review.

Generalized bullous fixed drug eruptions (GBFDEs) are rare in the paediatric population. We present the case of a 7-year-old girl with GBFDE believed to be secondary to oral ibuprofen, who experienced rapid resolution of lesions and cessation of blistering with a 3-week course of oral cyclosporine. To the best of our knowledge, this is the first report of a paediatric case of GBFDE treated with cyclosporine. In our report, we review published cases of GBFDE in children, and all adult cases managed with cyclosporine.

Adrenal Cushing Syndrome Diagnosed During Pregnancy: Successful Medical Management With Metyrapone.

Adrenal Cushing syndrome during pregnancy is rare, and there is limited information on the effect and safety of metyrapone treatment both for mother and fetus. We present a 24-year-old woman diagnosed with adrenal Cushing syndrome at the end of the second trimester. We elected treatment with metyrapone titrated to 250 mg 3 times daily, resulting in good clinical response and maternal serum and saliva cortisol levels in the upper half of the normal pregnancy range. A healthy male infant was born at 35 weeks' gestation, with no clinical signs of adrenal insufficiency, this despite a low cortisol of 5 nmol/L on the first day of life. We measured metyrapone in maternal and umbilical cord blood samples, demonstrating fetal venous metyrapone levels similar to maternal venous concentration, and a fetal arterial cord concentration at about 60% of the fetal venous cord concentration. This case demonstrates that salivary cortisol levels may be used to monitor the effect of metyrapone on adrenal Cushing syndrome during pregnancy. We show, for the first time in humans, that metyrapone does cross the placenta and may suppress fetal cortisol production without necessarily causing clinical signs of adrenal insufficiency.

Peripartum hyperhemolysis prophylaxis and management in sickle cell disease: A case report and narrative review.

BACKGROUND: Sickle cell disease (SCD) is associated with hematologic complications including delayed hemolytic transfusion reactions (DHTRs) and pregnancy-related morbidity and mortality. Hyperhemolysis syndrome (HS) is the most severe form of DHTR in patients with SCD, in which both transfused and native red blood cells are destroyed. Further transfusions are avoided after a history of HS. Immunosuppressive agents can be used as prophylaxis against life-threatening hemolysis when transfusion is necessary. There is a paucity of evidence for the use of HS prophylaxis before transfusions, the continuation of hydroxyurea (HU) in lieu of chronic transfusion, and the use of erythropoiesis-stimulating agents (ESA) in pregnant SCD patients. CASE REPORT: We present a case of a pregnant patient with SCD and a previous history of HS. HS prophylaxis was given before transfusion with corticosteroids, intravenous immunoglobulin, and rituximab. In addition, HU was continued during pregnancy to control SCD, along with the use of concomitant ESA to maintain adequate hemoglobin levels and avoid transfusion. We describe a multidisciplinary approach to pregnancy and delivery management including tailored anesthetic and obstetric planning. CONCLUSION: This is the first published case of HS prophylaxis in a pregnant SCD patient, with good maternal and fetal outcomes after transfusion. HU and ESAs were able to control SCD and mitigate anemia in lieu of prophylactic transfusions during pregnancy. Further prospective studies are necessary to elucidate the ideal management of pregnant SCD patients with a history of HS or other contraindications to chronic transfusion.

Sleep-promoting medications in children: physician prescribing habits in Southwestern Ontario, Canada.

BACKGROUND: Research indicates that physicians may frequently use pharmacotherapy to treat pediatric insomnia despite minimal safety data and very limited indications. Canadian data on the subject are lacking. This study aimed to determine physicians' views on and prescribing habits for sleep-promoting over-the-counter medication (OTCM) and prescription (RXM) medications for children. METHODS: A modified 26-item version of the 'Pediatric Sleep Medication Survey', originally developed by Judith Owens and colleagues, was sent to 100 pediatricians and a random sample of 421 family physicians in Southwestern Ontario, Canada. RESULTS: A total of 67 returned surveys were sufficiently complete for analysis. Sixty-one respondents indicated their specialty (28 pediatricians, 33 family physicians). In a typical 6-month period, 89% and 66% of respondents have recommended OTCM and RXM, respectively, for children with sleep problems. Only 20% have received any formal training on pediatric sleep disorders. The most common circumstances and sleep problems for which OTCM or RXM were recommended were mood disorders, developmental delay and attention deficit hyperactivity disorder (ADHD) (56, 40, and 39%, respectively), and insomnia, bedtime struggles/delayed sleep onset and circadian rhythm disorders (52, 48, and 28%, respectively). A total of 30% recommended OTCM or RXM to otherwise healthy children with sleep problems. Melatonin (73%), OTC antihistamines (41%), antidepressants (37%), and benzodiazepines (29%) were the most commonly recommended OTCM and RXM, respectively. CONCLUSIONS: Respondents in our sample frequently use pharmacotherapy to treat pediatric sleep problems; few have received any training in this area. Our findings indicate the need for evidence-based guidelines and regular physician training in the management of pediatric sleep disorders.

Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update.

During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester.

Intraurethral Lidocaine for Urethral Catheterization in Children: A Randomized Controlled Trial.

OBJECTIVES: To determine whether lidocaine is superior to nonanesthetic lubricant (NAL) for relieving pain in children undergoing urethral catheterization (UC). METHODS: Children 0 to 24 months requiring UC were randomized to NAL or topical and intraurethral 2% lidocaine gel. Primary outcome was facial grimacing in the pre to during drug administration and catheterization phases. Secondary outcome was caregiver satisfaction by using a Visual Analog Scale. RESULTS: There were 133 participants (n = 68 lidocaine, n = 65 NAL). There were no significant differences in mean (SD) scores during UC between lidocaine and NAL (86.4% [121.5%] vs 85.2% [126.6%]), respectively (Δ [confidence interval (CI)] = -1.2 [-21.0 to 49.0], P = .4). There was a significantly greater difference in mean (SD) scores during instillation of lidocaine versus NAL (61.8% [105.6%] vs 3.2% [84.9%]), respectively (Δ [CI] -58.6 [-95.0 to -32.0], P < .001). There were no significant differences in mean (SD) parental satisfaction scores between lidocaine and NAL (4.8 [3.2] vs 5.9 [2.9]), respectively (CI-0.1 to 2.2; P = .06). In the subgroup analysis, age, gender, and positive urine culture did not significantly influence between-group differences in facial grimacing. CONCLUSIONS: Compared with NAL, topical and intraurethral lidocaine is not associated with significant pain reduction during UC, but significantly greater pain during instillation. Therefore, clinicians may consider using noninvasive pain-reducing strategies for young children who require UC.

Ethics of studies of drugs in pregnancy.

Pregnant women with illness require efficacious and safe drug therapy during pregnancy; however, their treatment is often hindered by a lack of information regarding the use of medications during pregnancy. Ethical challenges are encountered in conducting drug trials in pregnant women, who are often excluded from participation due to fear of harm to the fetus. However, as the health of the fetus is ultimately affected by that of the pregnant woman, inclusion of pregnant women in studies of medications that they may require for their own benefit may also benefit the unborn child. The principle of autonomy argues for the pregnant woman being able to make an informed choice to take part in a clinical trial, and the principle of justice dictates that she not be denied the benefits of drug research.

Ethics of research in pediatric emergency medicine.

Clinical research in the pediatric emergency department (ED) has been rapidly growing in the past decade, and has resulted in some of the most important milestone studies in the pediatric medical literature. However, it presents a unique ethical goal and requires that additional challenges, such as the acute medical condition, fear and anxiety, unfamiliar physician(s), fatigue, and lack of time be addressed in addition to the standard ethical requirements. These may impair several fundamental elements of research, including the patient enrollment process, informed consent/assent, randomization, and others. Every possible attempt must be made to reduce or minimize the risks to which the children are exposed, and one must be cognizant of the special needs of children and their families in the ED. Nevertheless, we are also obliged to find ethical ways to include them in appropriate research endeavors that aim to improve treatments for conditions unique to the ED. This paper explores and overviews the most recent literature in order to characterize the nature of ethical challenges complicating clinical research in pediatric emergency medicine, and then suggests some ethically sound solutions such as deferred/waived consent, designated research staff, and alternative study designs. Finally, a few examples of prospective, blinded randomized trials involving drugs in pediatric emergency medicine are provided, with special emphasis on how the investigators are overcoming the obvious ethical challenges.

Maternal, pregnancy and fetal outcomes in de novo anti-glomerular basement membrane antibody disease in pregnancy: a systematic review.

BACKGROUND: Outside of pregnancy, anti-glomerular basement membrane (GBM) antibody disease is associated with significant morbidity and mortality. However, there is limited knowledge regarding de novo anti-GBM disease in pregnancy. METHODS: A systematic review was performed to identify maternal, pregnancy and fetal outcomes in de novo anti-GBM disease in pregnancy. Studies were selected from PubMed, EMBASE, Cochrane Library databases and conference proceedings, without language restriction. RESULTS: Data from eight patients were derived from seven case reports and one unpublished case. Most (6/8) patients presented after the first trimester. During pregnancy, acute kidney injury (5/8), anemia (5/8), hematuria (8/8) and proteinuria (8/8) were common. When hemodialysis was required antepartum (5/8), renal function recovery to independence of renal replacement was unlikely (2/5). While pulmonary involvement was common (5/8), no permanent damage was reported (0/8). The majority of cases ended in live births (6/8) although prematurity (6/6), intrauterine growth restriction (2/6), small for gestational age (4/6) and complications of prematurity (1/6) were common. When anti-GBM levels were tested in the living newborn, they were detectable (2/5), but no newborn renal or lung disease was reported (0/6). Complications in pregnancy included gestational diabetes (3/8), hyperemesis gravidarum (2/8) and preeclampsia (2/8). CONCLUSIONS: Live births can be achieved in de novo anti-GBM disease in pregnancy, but are commonly associated with adverse maternal, pregnancy and fetal outcomes. Only with awareness of common presentations, and management strategies can outcomes be optimized.

Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study.

OBJECTIVES: Our objectives were to 1) determine whether first-trimester use of gabapentin is associated with an increased risk for major malformations; 2) examine rates of spontaneous abortions, therapeutic abortions, stillbirths, mean birth weight and gestational age at delivery; and 3) examine rates of poor neonatal adaptation syndrome following late pregnancy exposure. METHODS: The study design was prospective. Women were included who initially contacted the services between 5 and 8 weeks with a comparison group of women exposed to nonteratogens, collected in a similar manner. RESULTS: We have data on 223 pregnancy outcomes exposed to gabapentin and 223 unexposed pregnancies. The rates of major malformations were similar in both groups (p = 0.845). There was a higher rate of preterm births (p = 0.019) and low birth weight <2,500 g (p = 0.033) in the gabapentin group. Among infants who were exposed to gabapentin up until delivery, 23 of 61 (38%) were admitted to either the neonatal intensive care unit or special care nursery for observation and/or treatment, vs 6 of 201 (2.9%) live births in the comparison group (p < 0.001). There were 2 cases of possible poor neonatal adaptation syndrome in neonates exposed to gabapentin close to delivery, compared with none in the comparison group, although it must be noted that these infants were concomitantly exposed to other psychotropic drugs. Among the women who took gabapentin, the major indications were pain (n = 90; 43%) and epilepsy (n = 71; 34%); the remainder were for other indications, mostly psychiatric. CONCLUSION: Our results suggest that although this sample size is not large enough to make any definitive conclusions, and there was no comparator group treated with other antiepileptic drugs, gabapentin use in pregnancy does not appear to increase the risk for major malformations. This finding and the increased risk for low birth weight and preterm birth require further investigation.

Anemia among Pediatric Critical Care Survivors: Prevalence and Resolution.

To determine the incidence of anemia among pediatric critical care survivors and to determine whether it resolves within 6 months of discharge. Design. A prospective observational study. Patients with anemia upon discharge from the pediatric critical care unit (PCCU) underwent in hospital and post hospital discharge followup (4-6 months) for hemoglobin (Hb) levels. Setting. A medical-surgical PCCU in a tertiary care center. Patients. Patients aged 28 days to 18 years who were treated in the PCCU for over 24 hours. Measurements and Main Results. 94 (24%) out of 392 eligible patients were anemic at time of discharge. Patients with anemia were older, median 8.0 yrs [(IQR 1.0-14.4) versus 3.2 yrs (IQR 0.65-9.9) (P < 0.001)], and had higher PeLOD [median 11 (IQR 10-12) versus 1.5 (1-4) (P < 0.001)], and PRISM [median 5 (IQR 2-11) versus 3 (IQR 0-6) (P < 0.001)] scores. The Hb level normalized in 32% of patients before discharge from hospital. Of the 28 patients who completed followup, all had normalization of their Hb in the absence of medical intervention. Conclusions. Anemia is not common among patients discharged from the PCCU and recovers spontaneously within 4-6 months.

Therapeutic drug monitoring in pregnancy.

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Adherence with drug therapy in pregnancy.

Available information suggests that nonadherence with medication is a common problem in pregnant women. Not taking prescribed drugs may have potentially negative consequences as patients may not achieve their therapeutic goal. In addition to the many factors that may influence medication-taking behaviour in the general population, unique challenges are encountered in pregnant women as both maternal health and fetal well-being must be considered. On the one hand, pregnant women may be motivated to keep their underlying disease under control, while, on the other hand, fear and anxiety regarding the potential harmful effects of their medication on their unborn child may result in poor adherence with needed medication. Providing evidence-based information, ideally preconceptually, regarding the effects of their medication during pregnancy may be important in avoiding misperceptions that lead to nonadherence.

Translational research in pediatrics: tissue sampling and biobanking.

Translational research is expanding and has become a focus of National Research funding agencies, touted as the primary avenue to improve health care practice. The use of human tissues for research on disease etiology is a pillar of translational research, particularly with innovations in research technologies to investigate the building blocks of disease. In pediatrics, translational research using human tissues has been hindered by the many practical and ethical considerations associated with tissue procurement from children and also by a limited population base for study, by the increasing complexities in conducting clinical research, and by a lack of dedicated child-health research funding. Given these obstacles, pediatric translational research can be enhanced by developing strategic and efficient biobanks that will provide scientists with quality tissue specimens to render accurate and reproducible research results. Indeed, tissue sampling and biobanking within pediatric academic settings has potential to impact child health by promoting bidirectional interaction between clinicians and scientists, helping to maximize research productivity, and providing a competitive edge for attracting and maintaining high-quality personnel. The authors of this review outline key issues and practical solutions to optimize pediatric tissue sampling and biobanking for translational research, activities that will ultimately reduce the burden of childhood disease.

Palatability, adherence and prescribing patterns of antiretroviral drugs for children with human immunodeficiency virus infection in Canada.

PURPOSE: To assess the impact of perceived palatability of antiretroviral drugs on adherence to therapy of children infected by human immunodeficiency virus and on prescribing patterns by their caring physicians. DESIGN: Two arms--retrospective chart review and a cross-sectional survey. SETTING: Tertiary-care pediatric human immunodeficiency virus clinic during a 17-year period. PARTICIPANTS: Children with human immunodeficiency virus infection and physicians actively caring for children with human immunodeficiency virus infection in seven provinces in Canada were surveyed regarding their perception of the palatability of 8-liquid and 15 non-liquid antiretroviral medications and its effect on drug selection. MAIN OUTCOME MEASURE: Effect of taste preferences of antiretroviral drugs on adherence to treatment by infected children and on drug selection by their caring physicians. RESULTS: Forty of 119 children (34%) refused at least once to an antiretroviral medication. In 5%, treatment was discontinued because of poor palatability. Ritonavir was the least palatable drug (50% of children; p = 0.01). Ritonavir use (OR 4.80 [95%CI 1.34-17.20]) and male gender (OR 7.25 [95%CI 2.30-22.90]) were independent predictors of drug discontinuation because of poor taste. Physicians also perceived liquid ritonavir as the least palatable (p = 0.01) and the most likely to be discontinued (p = 0.01). However, they commonly prescribed it as first-line therapy (p = 0.06). CONCLUSIONS: A third of children infected with human immunodeficiency virus fail to adhere to their treatment because of poor drug taste. Physicians are aware of that, but this does not prevent them from selecting the least palatable drugs as first-line therapy.