scholarly journals Exposure to duloxetine during pregnancy and risk of congenital malformations and stillbirth: A nationwide cohort study in Denmark and Sweden

PLoS Medicine ◽  
2021 ◽  
Vol 18 (11) ◽  
pp. e1003851
Author(s):  
Mikkel Zöllner Ankarfeldt ◽  
Janne Petersen ◽  
Jon Trærup Andersen ◽  
Hu Li ◽  
Stephen Paul Motsko ◽  
...  
Keyword(s):  
Reuptake Inhibitor ◽  
Congenital Malformations ◽  
First Trimester ◽  
The United States ◽  
Population Based ◽  
Reproductive Age ◽  
Sensitivity Analyses ◽  
Selective Serotonin ◽  
Smoking During Pregnancy ◽  
Increased Risk

Background The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths. Methods and findings A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates. Conclusions Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.

Smoking during Pregnancy and Adverse Birth and Maternal Outcomes in California, 2007 to 2016

2019 ◽  
Vol 37 (13) ◽  
pp. 1364-1376
Author(s):  
Anura W.G. Ratnasiri ◽  
Lauren Gordon ◽  
Ronald A. Dieckmann ◽  
Henry C. Lee ◽  
Steven S. Parry ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pregnancy Outcomes ◽  
Retrospective Cohort ◽  
First Trimester ◽  
Population Based ◽  
Maternal Outcomes ◽  
Smoking During Pregnancy ◽  
Maternal Risk ◽  
Maternal Cigarette Smoking ◽  
Increased Risk

Abstract Objective This study aimed to determine associations between maternal cigarette smoking and adverse birth and maternal outcomes. Study Design This is a 10-year population-based retrospective cohort study including 4,971,896 resident births in California. Pregnancy outcomes of maternal smokers were compared with those of nonsmokers. The outcomes of women who stopped smoking before or during various stages of pregnancy were also investigated. Results Infants of women who smoked during pregnancy were twice as likely to have low birth weight (LBW) and be small for gestational age (SGA), 57% more likely to have very LBW (VLBW) or be a preterm birth (PTB), and 59% more likely to have a very PTB compared with infants of nonsmokers. During the study period, a significant widening of gaps developed in both rates of LBW and PTB and the percentage of SGA between infants of maternal smokers and nonsmokers. Conclusion Smoking during pregnancy is associated with a significantly increased risk of adverse birth and maternal outcomes, and differences in rates of LBW, PTB, and SGA between infants of maternal smokers and nonsmokers increased during this period. Stopping smoking before pregnancy or even during the first trimester significantly decreased the infant risks of LBW, PTB, SGA, and the maternal risk for cesarean delivery.

scholarly journals Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study

BMJ ◽  
2020 ◽  
pp. m1494 ◽  
Author(s):  
Yanmin Zhu ◽  
Brian T Bateman ◽  
Kathryn J Gray ◽  
Sonia Hernandez-Diaz ◽  
Helen Mogun ◽  
...  
Keyword(s):  
Cohort Study ◽  
Congenital Malformations ◽  
First Trimester ◽  
The United States ◽  
Population Based ◽  
Adjusted Relative Risk ◽  
Oral Clefts ◽  
Oral Fluconazole ◽  
Conotruncal Malformations ◽  
First Trimester Of Pregnancy

AbstractObjectiveTo examine the risk of congenital malformations associated with exposure to oral fluconazole at commonly used doses in the first trimester of pregnancy for the treatment of vulvovaginal candidiasis.DesignPopulation based cohort study.SettingA cohort of pregnancies publicly insured in the United States, with data from the nationwide Medicaid Analytic eXtract 2000-14.ParticipantsPregnancies of women enrolled in Medicaid from three or more months before the last menstrual period to one month after delivery, and infants enrolled for three or more months after birth.InterventionsUse of fluconazole and topical azoles was established by requiring one or more prescriptions during the first trimester of pregnancy.Main outcome measuresRisk of musculoskeletal malformations, conotruncal malformations, and oral clefts (primary outcomes), associated with exposure to oral fluconazole, diagnosed during the first 90 days after delivery, were examined.ResultsThe study cohort of 1 969 954 pregnancies included 37 650 (1.9%) pregnancies exposed to oral fluconazole and 82 090 (4.2%) pregnancies exposed to topical azoles during the first trimester. The risk of musculoskeletal malformations was 52.1 (95% confidence interval 44.8 to 59.3) per 10 000 pregnancies exposed to fluconazole versus 37.3 (33.1 to 41.4) per 10 000 pregnancies exposed to topical azoles. The risks of conotruncal malformations were 9.6 (6.4 to 12.7) versus 8.3 (6.3 to 10.3) per 10 000 pregnancies exposed to fluconazole and topical azoles, respectively; risks of oral clefts were 9.3 (6.2 to 12.4) versus 10.6 (8.4 to 12.8) per 10 000 pregnancies, respectively. The adjusted relative risk after fine stratification of the propensity score was 1.30 (1.09 to 1.56) for musculoskeletal malformations, 1.04 (0.70 to 1.55) for conotruncal malformations, and 0.91 (0.61 to 1.35) for oral clefts overall. Based on cumulative doses of fluconazole, the adjusted relative risks for musculoskeletal malformations, conotruncal malformations, and oral clefts overall were 1.29 (1.05 to 1.58), 1.12 (0.71 to 1.77), and 0.88 (0.55 to 1.40) for 150 mg of fluconazole; 1.24 (0.93 to 1.66), 0.61 (0.26 to 1.39), and 1.08 (0.58 to 2.04) for more than 150 mg up to 450 mg of fluconazole; and 1.98 (1.23 to 3.17), 2.30 (0.93 to 5.65), and 0.94 (0.23 to 3.82) for more than 450 mg of fluconazole, respectively.ConclusionsOral fluconazole use in the first trimester was not associated with oral clefts or conotruncal malformations, but an association with musculoskeletal malformations was found, corresponding to a small adjusted risk difference of about 12 incidents per 10 000 exposed pregnancies overall.

scholarly journals Second-generation antipsychotic use during pregnancy and risk of congenital malformations

2021 ◽  
Author(s):  
Maria Ellfolk ◽  
Maarit K. Leinonen ◽  
Mika Gissler ◽  
Sonja Kiuru-Kuhlefelt ◽  
Leena Saastamoinen ◽  
...  
Keyword(s):  
Congenital Malformations ◽  
Second Generation ◽  
First Trimester ◽  
Population Based ◽  
Birth Cohort Study ◽  
Sampling Frame ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Second Generation Antipsychotic ◽  
Major Congenital Malformations

Abstract Purpose To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM). Methods A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996–2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models. Results Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72–1.19) or to F-GA users (OR 0.82; 95% CI 0.56–1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19–3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35–10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results. Conclusions Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.

scholarly journals Pregabalin use early in pregnancy and the risk of major congenital malformations

Neurology ◽  
2017 ◽  
Vol 88 (21) ◽  
pp. 2020-2025 ◽  
Author(s):  
Elisabetta Patorno ◽  
Brian T. Bateman ◽  
Krista F. Huybrechts ◽  
Sarah C. MacDonald ◽  
Jacqueline M. Cohen ◽  
...  
Keyword(s):  
Propensity Score ◽  
Congenital Malformations ◽  
Linear Models ◽  
First Trimester ◽  
Sensitivity Analyses ◽  
Registry Study ◽  
Relative Risks ◽  
Increased Risk ◽  
Major Congenital Malformations ◽  
Propensity Score Adjustment

Objective:To assess whether first-trimester exposure to pregabalin is associated with an increased risk of major congenital malformations, as recently suggested in a pregnancy registry study.Methods:We performed a cohort study nested in the US Medicaid Analytic eXtract (MAX). The study population included 1,323,432 pregnancies resulting in a live-born infant between 2000 and 2010. We examined the risk of major congenital malformations among infants born to women exposed to pregabalin during the first trimester compared with women unexposed to anticonvulsants. We used propensity score fine stratification to control for >50 potential confounders, and we estimated relative risks (RRs) and 95% confidence intervals (CIs) in generalized linear models. The analyses were replicated in the Truven Health MarketScan Commercial Database (MarketScan). Pooled estimates based on the adjusted RR produced in MAX, MarketScan, and the previous registry study were calculated.Results:Of 477 infants exposed to pregabalin during the first trimester in MAX, 28 (5.9%) had malformations compared to 3.3% in nonexposed infants. The crude RR of major congenital malformations for pregabalin was 1.80 (95% CI 1.26–2.58). After propensity score adjustment, the RR moved to 1.16 (95% CI 0.81–1.67). Restriction to pregabalin monotherapy and sensitivity analyses produced similar results. The adjusted RR for major congenital malformations for the 174 infants exposed in MarketScan was 1.03 (95% CI 0.56–1.90). The pooled RR was 1.33 (95% CI 0.83–2.15) for pregabalin any use and 1.02 (95% CI 0.69–1.51) for pregabalin monotherapy.Conclusions:Findings did not confirm the suggested teratogenic effects of pregabalin, although they cannot rule out the possibility of a small effect.

scholarly journals Smoking during pregnancy reduces vitamin D levels in a Finnish birth register cohort

2019 ◽  
Vol 23 (7) ◽  
pp. 1273-1277 ◽  
Author(s):  
A Inkeri Lokki ◽  
Jenni Heikkinen-Eloranta ◽  
Hanna Öhman ◽  
Seppo Heinonen ◽  
Heljä-Marja Surcel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sun Exposure ◽  
First Trimester ◽  
Population Based ◽  
Control Group ◽  
Skeletal Health ◽  
Smoking During Pregnancy ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
Vitamin D Levels

AbstractObjectiveMaternal vitamin D level in pregnancy may have implications for both the mother and fetus. Deficiency of vitamin D has been linked to several pregnancy complications and fetal skeletal health. Smoking has been associated with reduced serum level of the vitamin D metabolite, 25-hydroxyvitamin D (25(OH)D).DesignA nested case–control study within the Finnish Maternity Cohort, a population-based cohort which includes first-trimester sera from 98 % of pregnancies in Finland since 1987. The selection consisted of women with uncomplicated pregnancies. We studied serum concentration of 25(OH)D in 313 non-smoking and forty-six self-reported smoking pregnant women.SettingWe hypothesize that pregnant smokers may have an increased risk of low 25(OH)D levels especially during winter months.ParticipantsA control group from an unpublished pregnancy complication study consisting of 359 uncomplicated pregnancies. Individuals who reported that they do not smoke were considered ‘non-smokers’ (n 313) and those who reported continued smoking after the first trimester of pregnancy were considered ‘smokers’ (n 46).ResultsSmokers had significantly lower levels of 25(OH)D irrespective of sampling time (P<0·0001). Furthermore, during the low sun-exposure season, only 14 % of smokers met the guideline level of 40 nmol/l for serum 25(OH)D in comparison with 31 % of non-smokers.ConclusionsExpectant mothers who smoke have an increased risk of vitamin D deficiency during low sun-exposure months in northern regions. Further studies are needed to assess the associated risks for maternal and fetal health as well as possible long-term implications for the infant.

Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study

2021 ◽  
pp. 1-25
Author(s):  
Qionggui Zhou ◽  
Xuejiao Liu ◽  
Yang Zhao ◽  
Pei Qin ◽  
Yongcheng Ren ◽  
...  
Keyword(s):  
Cohort Study ◽  
Population Based ◽  
Normal Weight ◽  
Sensitivity Analyses ◽  
Hypertension Status ◽  
Moderation Effect ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Chinese Cohort ◽  
The Impact

Abstract Objective: The impact of baseline hypertension status on the BMI–mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI–mortality association using a rural Chinese cohort. Design: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. Setting: Longitudinal population-based cohort Participants: 17,262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. Results: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the HRs (95% CI) for mortality in normotensive participants were 1.92 (1.23-3.00), 1.44 (1.01-2.05), 1.14 (0.82-1.58), 0.96 (0.70-1.31), 0.96 (0.65-1.43), 1.32 (0.81-2.14), and 1.32 (0.74-2.35) respectively, and in hypertensive participants were 1.85 (1.08-3.17), 1.67 (1.17-2.39), 1.29 (0.95-1.75), 1.20 (0.91-1.58), 1.10 (0.83-1.46), 1.10 (0.80-1.52), and 0.61 (0.40-0.94) respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity versus normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. Conclusions: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

Validation of self-reported incident cancer diagnoses in the U.S. Health and Retirement Study: A tool for population-based cancer and aging research.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 312-312
Author(s):  
Megan Mullins ◽  
Jasdeep Kler ◽  
Marissa Eastman ◽  
Mohammed Kabeto ◽  
Lauren P. Wallner ◽  
...  
Keyword(s):  
The United States ◽  
Population Based ◽  
Self Report ◽  
Sensitivity Analyses ◽  
Cancer Site ◽  
Fee For Service ◽  
Site Specific ◽  
Incident Cancer ◽  
Self Reports ◽  
Retirement Study

312 Background: Population aging and improving cancer survival rates are resulting in a growing population of older cancer survivors in the United States (US). As a result, there is an increasing need for longitudinal, population-representative data for interdisciplinary cancer research among older adults. The US Health Retirement Study (HRS) is an ongoing population-representative cohort of US adults over age 50 that contains rich interview and biomarker data on health during aging. Interviews have collected self-reported cancer diagnoses since 1998, but these self-reports have not been validated. We compared first incident cancer diagnoses self-reported in HRS interviews against diagnostic claims from linked Medicare records. Methods: We examined the validity of first incident cancer diagnoses self-reported in biennial HRS interviews from 2000 through 2016 against ICD-9 and ICD-10 diagnostic claim records among 8,242 HRS participants aged ≥65 with 90% continuous enrollment in fee-for-service Medicare, using the claim records as the gold standard. We calculated the sensitivity, specificity, and k for first incident cancer diagnoses (all cancers combined, excluding non-melanoma skin cancer, and each of bladder, breast, colorectal/anal, uterine, kidney/renal, lung/bronchus, and prostate cancers) cumulatively over the follow-up, and at each biennial study interview. Results: Self-reports of first incident cancer diagnosis (agnostic of site) between 2000 and 2016 had 73.2% sensitivity and 96.2% specificity against Medicare claims (k = 0.73). For site-specific self-reports, sensitivities ranged from 44.7% (kidney) to 75.0% (breast), and specificities ranged from 99.2% (prostate) to 99.9% (bladder, uterine, and kidney). Results were similar in sensitivity analyses restricting to individuals with 100% continuous fee-for-service Medicare enrollment and when restricting to individuals with at least 24 months of Medicare enrollment. Conclusions: Self-reported cancer diagnoses in the HRS have reasonable validity for population-based research on cancer and aging across cancer types. Apart from breast cancer, cancer site specific analyses will greatly benefit from the improved validity of self-report with Medicare claim linkage.

scholarly journals Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts

Gut ◽  
2018 ◽  
Vol 68 (6) ◽  
pp. 977-984 ◽  
Author(s):  
Ryan C Ungaro ◽  
Berkeley N Limketkai ◽  
Camilla Bjørn Jensen ◽  
Kristine Højgaard Allin ◽  
Manasi Agrawal ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
The United States ◽  
Health Claims ◽  
Sensitivity Analyses ◽  
Clinical Event ◽  
Clinical Events ◽  
Increased Risk ◽  
National Databases

ObjectiveThe benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA.DesignOur primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA.ResultsA total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF.ConclusionIn two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.

Sign in / Sign up

Export Citation Format

Share Document