Pharmacists' Experiences of Using Knowledge Bases on Medicines in Pregnancy and Breastfeeding.

Knowledge bases on medicines during pregnancy and breastfeeding integrated into a clinical decision support system are valuable tools for pharmacists. The information facilitates counseling, is time-saving and improves patient safety.

Neonatal morbidity after fetal exposure to antipsychotics: a national register-based study.

OBJECTIVE: To investigate the admission rate to neonatal care and neonatal morbidity after maternal use of antipsychotics during pregnancy. DESIGN: A population-based register study. SETTING: Information on all singleton births between July 2006 and December 2017 in Sweden including data on prescription drugs, deliveries and infants' health was obtained from the Swedish Medical Birth Register, the Prescribed Drug Register and the Swedish Neonatal Quality Register. Exposed infants were compared with unexposed infants and with infants to mothers treated with antipsychotics before or after but not during pregnancy. PARTICIPANTS: The cohort comprised a total of 1 307 487 infants, of whom 2677 (0.2%) were exposed to antipsychotics during pregnancy and 34 492 (2.6%) had mothers who were treated before/after the pregnancy. OUTCOME MEASURES: The primary outcome was admission rate to neonatal care. Secondary outcomes were the separate neonatal morbidities. RESULTS: Of the exposed infants, 516 (19.3%) were admitted to neonatal care compared with 98 976 (7.8%) of the unexposed infants (adjusted risk ratio (aRR): 1.7; 95% CI: 1.6 to 1.8), with a further increased risk after exposure in late pregnancy. The highest relative risks were seen for withdrawal symptoms (aRR: 17.7; 95% CI: 9.6 to 32.6), neurological disorders (aRR: 3.4; 95% CI: 2.4 to 5.7) and persistent pulmonary hypertension (aRR: 2.1; 95% CI: 1.4 to 3.1) when compared with unexposed infants. The absolute risks for these outcomes were however low among the exposed infants, 1.3%, 1.8% and 1.0%, respectively, and the relative risks were lower when compared with infants to mothers treated before/after the pregnancy. CONCLUSION: Fetal exposure to antipsychotics was associated with an increased risk of neonatal morbidity. The effects in the exposed infants seem transient and predominantly mild, and these findings do not warrant discontinuation of a necessary treatment but rather increased monitoring of these infants. The increased risk of persistent pulmonary hypertension requires further studies.

Antipsychotic Use During Pregnancy and Risk for Gestational Diabetes: A National Register-Based Cohort Study in Sweden.

OBJECTIVE: We aimed to study whether antipsychotic use during pregnancy is associated with gestational diabetes. METHODS: This was a Swedish national register-based cohort study on the Medical Birth Register and the Prescribed Drug Register including all 1,307,487 singleton births between July 2006 and December 2017. Antipsychotics were divided into first-generation antipsychotics (n = 728), high-risk metabolic second-generation antipsychotics including olanzapine, clozapine and quetiapine (n = 1710), and other second-generation antipsychotics (n = 541). The risks for gestational diabetes, foetal growth disturbances, pre-eclampsia, caesarean section and preterm labour were assessed. Women treated during pregnancy were compared to women not treated during pregnancy and to women who used antipsychotics before/after but not during pregnancy. RESULTS: The crude risk ratio for gestational diabetes for women treated with high-risk metabolic second-generation antipsychotics during pregnancy was 2.2 (95% confidence interval [CI] 1.6-2.9) compared to untreated pregnant women (n = 1,296,539) and 1.8 (95% CI 1.4-2.5) compared to women treated before/after pregnancy (n = 34,492). After adjustment for maternal factors including body mass index, the risk ratios were 1.8 (95% CI 1.3-2.4) and 1.6 (95% CI 1.2-2.1). Exposed infants had an increased risk of being large for gestational age: adjusted risk ratios 1.6 (95% CI 1.3-1.9) and 1.3 (95% CI 1.1-1.6) compared to no maternal antipsychotic use during pregnancy and maternal use before/after the pregnancy. Other antipsychotics were not associated with metabolic risks. CONCLUSIONS: Olanzapine, clozapine and quetiapine used during pregnancy were associated with increased risks for gestational diabetes and the infant being large for gestational age. Enhanced metabolic monitoring should be considered for pregnant women using these drugs.

The use of second-generation antipsychotics amongst pregnant women is increasing. The side effects of these drugs, for example weight gain and increased blood sugar, are well described for the general population. In particular, olanzapine, quetiapine and clozapine are known to cause these effects. Studies on their effects on blood sugar control in pregnant women have however been conflicting. Pregnancy itself also imposes a risk for increased blood sugar levels and gestational diabetes. The purpose of this study was to evaluate the risk of gestational diabetes connected to the use of antipsychotics during pregnancy. The study was nationwide and register based including 1.3 million births in Sweden between July 2006 and December 2017. The rates of gestational diabetes and the infants being small for gestational age or large for gestational age amongst women treated with antipsychotics were compared to the rates in pregnant women who did not receive antipsychotics and to rates in a control group of women treated with antipsychotics before/after but not during pregnancy. Antipsychotics were divided into three groups: (i) first-generation antipsychotics, (ii) high-risk second-generation antipsychotics including olanzapine, quetiapine and clozapine, and (iii) other second-generation antipsychotics. Women treated with high-risk second-generation antipsychotics were found to have an increased risk of gestational diabetes and giving birth to an infant being large for gestational age, both when compared with untreated pregnant women and with the control group. Other antipsychotics were not connected to increased risks of these outcomes. Hence, pregnant women treated with olanzapine, quetiapine or clozapine should be monitored regarding blood sugar levels.

Prenatal exposure to nitrofurantoin and risk of childhood leukaemia: a registry-based cohort study in four Nordic countries.

BACKGROUND: Studies have suggested increased risks of childhood leukaemia after prenatal exposure to antibiotics, particularly nitrofurantoin. However, these findings may be related to the underlying maternal infection. This multinational study aimed to investigate the association between prenatal nitrofurantoin exposure and childhood leukaemia while accounting for maternal infection. METHODS: In a population-based cohort study of children born in Denmark, Finland, Norway or Sweden from 1997 to 2013, prenatal exposure to nitrofurantoin or pivmecillinam (active comparator) was ascertained from national Prescription Registries. Childhood leukaemia was identified by linkage to national Cancer Registries. Poisson regression was used to estimate incidence rate ratios (IRRs) and incidence rate differences (IRDs) with inverse probability of treatment weights applied to account for confounding. RESULTS: We included 44 091 children prenatally exposed to nitrofurantoin and 247 306 children prenatally exposed to pivmecillinam. The children were followed for 9.3 years on average (standard deviation 4.1). There were 161 cases of childhood leukaemia. The weighted IRR for prenatal nitrofurantoin exposure when compared with pivmecillinam was 1.34 (95% confidence interval 0.88, 2.06), corresponding to an IRD of 15 per million person-years. Higher point estimates were seen for first- and third-trimester exposure. There was no evidence of a dose-response relationship. CONCLUSIONS: Prenatal exposure to nitrofurantoin was not substantially associated with childhood leukaemia, although a slightly elevated IRR with confidence intervals including the null was observed, corresponding to a small absolute risk. The lack of a dose-response relationship and a clear biological mechanism to explain the findings suggests against a causal association.

Online information discrepancies regarding safety of medicine use during pregnancy and lactation: an IMI ConcePTION study.

Background: Inconsistencies in information on safety of medicine use during pregnancy and lactation can result in sub-optimal treatment for pregnant and lactating women, risks to the fetus or child and unnecessary weaning off breastfeeding. The objective of this study was to analyze information discrepancies regarding medicine use during pregnancy and lactation between on-line sources for patients and health care professionals (HCPs) in four European languages.Research design and methods: The medicines analyzed were ibuprofen, ondansetron, olanzapine, fingolimod, methylphenidate and adalimumab. Recommendations were classified into different data source categories, for patients and for HCPs, and compared between the data source categories for each medicine and language.Results: For patients, 11/24 (46%) and 4/24 (17%) comparisons of the pregnancy and lactation recommendations, respectively, were consistent between all sources. The corresponding figures for HCP-sources were 13/24 (54%) and 5/24 (21%). Regulatory sources had generally more restrictive recommendations. Teratology Information Services (TIS) centers' recommendations for medicine use during pregnancy and lactation were consistent in 25/27 (93%) and 15/22 (68%) of cases respectively.Conclusion: Discrepancies between online information sources regarding medicine use during pregnancy and lactation are common, especially for lactation. TIS centers recommendations were more aligned. Additional work is needed to harmonize information within and between countries to avoid conflicting messages.

Midwives' Perception of Using a Knowledge Base on Fetal Impact of Drugs.

A non-commercial knowledge base providing assessments of fetal risks of medicinal drugs is a useful tool in the everyday work of midwives. The information is freely available on the internet, and according to a questionnaire study, nearly 95% of the midwives are familiar with the database, 30% use the information weekly, and 80% express that it affects their medical decisions. A vast majority of the midwives also state that it is time-saving.

Perinatal Outcomes After Treatment With ADHD Medication During Pregnancy.

OBJECTIVES: To analyze perinatal outcomes after maternal use of attention-deficit/hyperactivity disorder (ADHD) medication during pregnancy. METHODS: The study included singletons born between 2006 and 2014 in Sweden. Data on prescription drug use, pregnancies, deliveries, and the newborn infants' health were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We compared infants exposed to ADHD medication during pregnancy with infants whose mothers never used these drugs and infants whose mothers used ADHD medication before or after pregnancy. Analyses were performed with logistic regression. RESULTS: Among 964 734 infants, 1591 (0.2%) were exposed to ADHD medication during pregnancy and 9475 (1.0%) had mothers treated before or after pregnancy. Exposure during pregnancy increased the risk for admission to a NICU compared with both no use and use before or after pregnancy (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.3-1.7; and aOR, 1.2; 95% CI, 1.1-1.4, respectively). Infants exposed during pregnancy had more often central nervous system-related disorders (aOR, 1.9; 95% CI, 1.1-3.1) and were more often moderately preterm (aOR, 1.3; 95% CI, 1.1-1.6) than nonexposed infants. There was no increased risk for congenital malformations or perinatal death. CONCLUSIONS: Treatment with ADHD medication during pregnancy was associated with a higher risk for neonatal morbidity, especially central nervous system-related disorders such as seizures. Because of large differences in background characteristics between treated women and controls, it is uncertain to what extent this can be explained by the ADHD medication per se.

Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy.

OBJECTIVES: To estimate the rate of admissions to NICUs, as well as infants' morbidity and neonatal interventions, after exposure to antidepressant drugs in utero. METHODS: Data on pregnancies, deliveries, prescription drug use, and health status of the newborn infants were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We included 741 040 singletons, born between July 1, 2006, and December 31, 2012. Of the infants, 17 736 (2.4%) had mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Infants exposed to an SSRI were compared with nonexposed infants, and infants exposed during late pregnancy were compared with those exposed during early pregnancy only. The results were analyzed with logistic regression analysis. RESULTS: After maternal use of an SSRI, 13.7% of the infants were admitted to the NICU compared with 8.2% in the population (adjusted odds ratio: 1.5 [95% confidence interval: 1.4-1.5]). The admission rate to the NICU after treatment during late pregnancy was 16.5% compared with 10.8% after treatment during early pregnancy only (adjusted odds ratio: 1.6 [95% confidence interval: 1.5-1.8]). Respiratory and central nervous system disorders and hypoglycemia were more common after maternal use of an SSRI. Infants exposed to SSRIs in late pregnancy compared with early pregnancy had a higher risk of persistent pulmonary hypertension (number needed to harm: 285). CONCLUSIONS: Maternal use of antidepressants during pregnancy was associated with increased neonatal morbidity and a higher rate of admissions to the NICU. The absolute risk for severe disease was low, however.

Pregnant women's view on the Swedish internet resource Drugs and Birth Defects intended for health care professionals.

INTRODUCTION: Pregnant women often have questions concerning fetal effects of drugs but there is limited reliable information specifically intended for them. This study investigated how pregnant women perceive and value the scientific resource Drugs and Birth Defects (www.janusinfo.se/fosterpaverkan) and compared their opinions with those of health care professionals. MATERIAL AND METHODS: Electronic questionnaire study. Pregnant women were recruited at their regular visits, and health care professionals via e-mail, at 10 antenatal clinics. Altogether, 275 pregnant women, 38 midwives and 30 physicians participated. RESULTS: Among the pregnant women, 81% found the information valuable, 70% that it was easy to understand, and 92% that it strengthened information from the staff. Concerning anxiety for negative fetal effects, 68% of the women answered that the anxiety decreased or was not influenced by the texts and 22% that it increased. Among physicians and midwives, 44% saw risks associated with pregnant women reading the texts and 24% answered that they would fully recommend them to use the database. The corresponding figures among pregnant women were 17 and 65%, respectively (P < 0.001). The professionals preferred, to a greater extent than pregnant women did, lay people to use a special edition. CONCLUSIONS: The majority of pregnant women seem to benefit from using a scientific resource on fetal impact of drugs intended for health care professionals. Some women are more worried after having read the information, but most of them still find it valuable. It is important that pregnant women who use the database can reach a medical professional to discuss the contents.

Drugs and Birth Defects: a knowledge database providing risk assessments based on national health registers.

PURPOSE: To present concept, methods and use of a knowledge database providing assessments of potential fetal risks for all drugs on the Swedish market. METHODS: Assessments of fetal risks are made primarily by analyzing prospective epidemiological data from the Swedish Medical Birth Register on drug intake in relation to birth outcome. This is complemented by evaluation of the scientific literature. Following standardized working procedures, a statement is compiled for each substance, which is also classified into one of three categories depending on the estimated risk level. The final documents include drug product names on the market, via linkage to a medicinal products register. The information is free and published on the website www.janusinfo.se . It can also be used as an integrated part of electronic health records. RESULTS: The database covers assessments of fetal risks for close to 1,250 medicinal drug substances on the Swedish market. Each year, 96,000 searches are made, which might be compared to the around 100,000 children born in Sweden yearly. Apart from the Swedish Physicians' Desk Reference (Fass), the database is the most commonly used resource among specialists within gynaecology and perinatal medicine for information on drugs during pregnancy. CONCLUSIONS: A non-commercial knowledge base with assessments of fetal risk of different drugs is valued by health care professionals and is used extensively in Sweden. Based on analyses of national health registers, the database provides unique information on teratogenic drug risks.