Safety of ginger use in pregnancy: results from a large population-based cohort study

Purpose

The objective of the study was to examine the safety of ginger use during pregnancy on congenital malformations and selected pregnancy outcomes.

Methods

The Norwegian Mother and Child Cohort study, a large population-based cohort, provided the data used in this study. Our study population consisted of 68,522 women. Data on ginger use and socio-demographic factors were retrieved from three self-administered questionnaires completed by the women during weeks 17 and 30 of the pregnancy and when their child was 6 months old. Data on pregnancy outcomes were provided by the Medical Birth Registry of Norway.

Results

Among the 68,522 women in the study, 1,020 (1.5 %) women reported using ginger during pregnancy. The use of ginger during pregnancy was not associated with any increased risk of congenital malformations. No increased risk for stillbirth/perinatal death, preterm birth, low birth weight, or low Apgar score was detected for the women exposed to ginger during pregnancy compared to women who had not been exposed.

Conclusion

Use of ginger during pregnancy does not seem to increase the risk of congenital malformations, stillbirth/perinatal death, preterm birth, low birth weight, or low Apgar score. This finding is clinically important for health care professionals giving advice to pregnant women with NPV.     

Exposure to phototoxic NSAIDs and quinolones is associated with an increased risk of melanoma

Purpose

Ultraviolet radiation exposure is the most important exogenous risk factor for cutaneous malignancies. It is possible that phototoxic drugs promote the development of cutaneous melanoma (CM) by intensifying the effect of ultraviolet light on the skin. We investigated the association between the use of common systemic phototoxic drugs and development of CM.

Methods

This study was a case–control study in a Dutch population-based cohort. The drug dispensing data was obtained from PHARMO, a Dutch drug dispensing and hospital admissions registry, and linked to PALGA, the nationwide pathology network of the Netherlands. The cases were patients diagnosed with pathologically confirmed primary CM between 1991 and 2004. Controls were sampled from the PHARMO population. Exposure to systemic phototoxic drugs was measured and included antimicrobial agents, diuretics, antipsychotic drugs, antidiabetic drugs, cardiac drugs, antimalarials and nonsteroidal anti-inflammatory drugs (NSAIDs). A multivariate conditional logistic regression analysis was performed to study the association between exposure to phototoxic drugs and CM.

Results

The study population included 1,318 cases and 6,786 controls. Any phototoxic drug during the study period was dispensed for 46 % of the cases and 43 % of the controls (p?=?0.012). The use of quinolones [odds ratio (OR) 1.33, 95 % confidence interval (CI) 1.01–1.76] and propionic acid derivative NSAIDs (OR 1.33, 95 % CI 1.14–1.54) had a positive association with CM.

Conclusions

Our study shows that the use of phototoxic drugs is associated with an increased risk of developing CM. Even a short-term use of phototoxic quinolones and propionic acid derivative NSAIDs may increase the risk for CM. Patient education to promote sun-protective behaviour is essential to avoid immediate adverse effects and possible long-term effects of phototoxic drugs.     

Pharmacologic evidence to support clinical decision making for peripartum methadone treatment

Rationale

Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum.

Objectives

Study goals were to (1) characterize changes in methadone dose across childbearing, (2) determine enantiomer-specific methadone withdrawal kinetics from steady state during late pregnancy, (3) assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and (4) explore relationships between CYP2B6, CYP2C19, and CYP3A4 single-nucleotide polymorphisms and maternal dose, plasma concentration, and L/D.

Methods

Methadone dose changes and timed plasma samples were obtained for women on methadone (n?=?25) followed prospectively from third trimester of pregnancy to 3 months postpartum.

Results

Participants were primarily white, Medicaid insured, and multiparous. All women increased their dose from first to end of second trimester (mean peak increase?=?23 mg/day); 71 % of women increased from second trimester to delivery (mean peak increase?=?19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7–24.9 h; S-methadone, 8.02–18.9 h) were about half of those reported in non-pregnant populations. In three women with weekly 24-h methadone levels after delivery, L/D increased within 1–2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum.

Conclusions

Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.     

Drug-induced adverse reactions via breastfeeding: a descriptive study in the French Pharmacovigilance Database

Purpose

Most drugs are excreted in maternal milk and may therefore be ingested by children during breastfeeding. Data concerning the safety of the use of drugs by breastfeeding women are patchy, and almost nothing is known about this issue for many drugs.

Methods

The aim of this study was to describe the adverse drug reactions of drugs transmitted in breast milk on the basis of the data collected in the French Pharmacovigilance Database. All spontaneous reports of adverse drug reactions (ADRs) in breastfed infants recorded in the National Pharmacovigilance Database by the 31 French regional pharmacovigilance centres between 1984 and June 2011 were investigated.

Results

Between January 1985 and June 2011, 276 adverse drug reactions in 174 breastfed children were notified to the French Pharmacovigilance Network. The most frequently reported adverse drug reactions were neurological (28.6 %) and gastrointestinal (20.3 %). Sixty-five of the adverse drug reactions recorded were considered to be serious (37.4 %). The results of our study confirm that certain drugs were frequently implicated in serious adverse drug reactions. Two cases of ADRs (1.1 %) had a ‘certain’ causality score (I4) and 13 (7.5 %) a ‘likely’ score (I3). The suspected drugs include antiepileptic drugs, opiate analgesics and benzodiazepines. These results also demonstrate that some drugs that were thought to be anodyne or for which no data were available, such as ketoprofen and hydroxyzine, may be implicated in adverse effects. Finally, these data show that certain drugs, like pseudoephedrine, which should not be used during breastfeeding, were nevertheless implicated in several of the adverse drug reactions recorded.

Conclusion

This study shows that ADR via breastfeeding are rarely reported due to low awareness or low occurrence of ADR via breast milk. These results highlight the need for additional pharmacokinetic, clinical and epidemiological studies, given the paucity of published data. They also demonstrate the need to improve information for the general public about drugs and self-medication during breastfeeding.     

Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes

Background

Montelukast (Singulair) is a selective leukotriene receptor antagonist (LTRA) indicated for the maintenance treatment of asthma. Currently, there are limited prospective, comparative studies in the literature examining the safety of montelukast use in pregnancy.

Objectives

The primary objective of this study was to determine whether exposure to montelukast during pregnancy increases the rate of major malformations above the 1–3% baseline risk or the rate of other adverse effects.

Methods

Pregnant women taking montelukast were enrolled in the study from six teratogen information services around the world. These women were compared to two other groups of women: (1) disease-matched, who used inhalers for a similar indication and (2) women not diagnosed with asthma and not exposed to any known teratogens. The primary outcome was major malformations and secondary endpoints included spontaneous abortion, fetal distress, gestational age at birth and birth weight.

Results

Out of 180 montelukast-exposed pregnancies, there were 160 live births including three sets of twins, 20 spontaneous abortions, 2 elective abortions and 1 major malformation reported. The mean birth weight was lower (3,214?±?685 g) compared to controls [3,356?±?657 (disease-matched) and 3,424?±?551 (exposed to non-teratogens), P?=?0.038] and the gestational age was shorter [37.8?±?3.1 weeks (montelukast) and 37.6?±?4.4 (disease-matched) versus 39.3?±?2.4 weeks (exposed to non-teratogens), P?=?0.045]. About 25% of the newborns had fetal distress, a higher rate than controls (P?=?0.007). However, upon sub-analysis of women who continued the drug until delivery, only birth-weight difference (304 g) remained significant.

Conclusions

Montelukast does not appear to increase the baseline rate of major malformations. The lower birth weight in both asthma groups is most likely associated with the severity of the maternal condition.     

Objective assessment of nonadherence and unknown co-medication in hospitalized patients

Purpose

The intake of medications (drugs) without the knowledge of the treating physician (unknown co-medication) and nonadherence strongly influence drug safety. The aim of our study was to objectively assess unknown co-medication and nonadherence in hospitalized patients by screening urine for a large number of drugs using highly sensitive full scan gas chromatograpy/mass spectrometry (GC/MS). Secondary objectives were to determine the relationship of co-medication and nonadherence to the number of drugs prescribed and to compare history-taking by a pharmacist versus a physician.

Methods

In 152 patients, the drug histories taken by physicians, patients’ self-reported adherence, and information compiled during as many as three structured interviews conducted by a trained pharmacist on days 1–2, 3–4, and 7–11 of the hospital stay were compared with the GC/MS results from urine samples collected after each interview.

Results

In the interviews performed by the pharmacist, 235 additional drugs were identified that were not documented in the chart. Of all the drugs indicated in any interview, 16.9% were identified only by the physician, 24.1% only by the pharmacist, and 59% by both. Overall, in 78% of the patients at least one additional drug was identified by urine screening. The findings suggest overall nonadherence to at least one drug in 13.0% of patients on admission and in 23.3% of patients at any time during hospitalization. Nonadherence was less frequent for critical dose drugs and correlated with the number of prescribed drugs.

Conclusions

The drug history among hospitalized patients is often incomplete, and nonadherence and unknown co-medication are alarmingly frequent. This lack of knowledge might impact the overall success of drug therapies in the hospital setting.     

Pattern of drug use during the first trimester among Chinese women: data from a population-based cohort study

Aim

To describe the pattern of drug use among Chinese women during the first trimester and to examine the impact of maternal diseases on the choice of drugs.

Method

This drug utilisation study of pregnant women was performed using data from the ABCD cohort study. A total of 4,290 women were enrolled in the analysis. Information was collected by self-completion questionnaire combined with the “Maternal health handbook”.

Results

Of the 4,290 women interviewed, 75.9% of women took at least one drug during the first trimester. Users took a mean number of 1.43 drugs. The most frequently used drugs were folic acid (65.2%), vitamins (14.6%), calcium (12.0%), minerals (11.1%), Chinese traditional patent medicine (CTPM; 10.1%) and anti-infectives (6.5%). Among the women having used CTPM, influenza/cold and threatened abortion were the most commonly reported indications. Logistic regression analysis of drug use (excluding nutritional and haematological drugs) shows that CTPM and Western medicine are both associated with the use of drugs for occasional diseases and against threatened abortion. Maternal chronic diseases were not associated with the use of CTPM.

Conclusion

This analysis of pregnant women showed that drugs were prescribed to most women, even when nutritional and haematological drugs were excluded. Our data reflect, except for drugs used for chronic diseases, a general reluctance among Chinese women to use Western medicine and resorting to CTPM during pregnancy