scholarly journals Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study

BMJ ◽  
2020 ◽  
pp. m237 ◽  
Author(s):  
Krista F Huybrechts ◽  
Brian T Bateman ◽  
Ajinkya Pawar ◽  
Lily G Bessette ◽  
Helen Mogun ◽  
...  

Abstract Objective To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. Design Cohort study nested in the Medicaid Analytic eXtract for 2004-13. Setting Publicly insured pregnancies in the United States. Participants Pregnant women 18 to 55 years of age and their liveborn infants. Interventions Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. Main outcome measures Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. Results Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. Conclusions On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. Trial registration EUPAS 15946.

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e027344
Author(s):  
Yohannes Ejigu ◽  
Jeanette H Magnus ◽  
Johanne Sundby ◽  
Maria C Magnus

ObjectiveThe objective of the study was to compare pregnancy outcomes according to maternal antiretroviral treatment (ART) regimens.DesignA retrospective cohort study.Participants and settingsClinical data was extracted from ART exposed pregnancies of HIV-infected Ethiopian women attending antenatal care follow-up in public health facilities in Addis Ababa between February 2010 and October 2016.OutcomesThe primary outcomes evaluated were preterm birth, low birth weight and small-for-gestational-age.ResultsA total 1663 of pregnancies exposed to ART were included in the analyses. Of these pregnancies, 17% resulted in a preterm birth, 19% in low birth weight and 32% in a small-for-gestational-age baby. Compared with highly active antiretroviral therapy (HAART) initiated during pregnancy, zidovudine monotherapy was less likely to result in preterm birth (adjusted OR 0.35, 95% CI 0.19 to 0.64) and low birth weight (adjusted OR 0.48, 95% CI 0.24 to 0.94). We observed no differential risk of preterm birth, low birth weight and small-for-gestational-age, when comparing women who initiated HAART during pregnancy to women who initiated HAART before conception. The risk for preterm birth was higher in pregnancies exposed to nevirapine-based HAART (adjusted OR 1.44, 95% CI 1.06 to 1.96) compared with pregnancies exposed to efavirenz-based HAART. Comparing nevirapine-based HAART with efavirenz-based HAART indicated no strong evidence of increased risk of low birth weight or small-for-gestational-age.ConclusionsWe observed a higher risk of preterm birth among women who initiated HAART during pregnancy compared with zidovudine monotherapy. Pregnancies exposed to nevirapine-based HAART also had a greater risk of preterm births compared with efavirenz-based HAART.


BMJ ◽  
2020 ◽  
pp. m1007
Author(s):  
Liv G Kvalvik ◽  
Allen J Wilcox ◽  
Rolv Skjærven ◽  
Truls Østbye ◽  
Quaker E Harmon

AbstractObjectiveTo explore conditions and outcomes of a first delivery at term that might predict later preterm birth.DesignPopulation based, prospective register based study.SettingMedical Birth Registry of Norway, 1999-2015.Participants302 192 women giving birth (live or stillbirth) to a second singleton child between 1999 and 2015.Main outcome measuresMain outcome was the relative risk of preterm delivery (<37 gestational weeks) in the birth after a term first birth with pregnancy complications: pre-eclampsia, placental abruption, stillbirth, neonatal death, and small for gestational age.ResultsWomen with any of the five complications at term showed a substantially increased risk of preterm delivery in the next pregnancy. The absolute risks for preterm delivery in a second pregnancy were 3.1% with none of the five term complications (8202/265 043), 6.1% after term pre-eclampsia (688/11 225), 7.3% after term placental abruption (41/562), 13.1% after term stillbirth (72/551), 10.0% after term neonatal death (22/219), and 6.7% after term small for gestational age (463/6939). The unadjusted relative risk for preterm birth after term pre-eclampsia was 2.0 (95% confidence interval 1.8 to 2.1), after term placental abruption was 2.3 (1.7 to 3.1), after term stillbirth was 4.2 (3.4 to 5.2), after term neonatal death was 3.2 (2.2 to 4.8), and after term small for gestational age was 2.2 (2.0 to 2.4). On average, the risk of preterm birth was increased 2.0-fold (1.9-fold to 2.1-fold) with one term complication in the first pregnancy, and 3.5-fold (2.9-fold to 4.2-fold) with two or more complications. The associations persisted after excluding recurrence of the specific complication in the second pregnancy. These links between term complications and preterm delivery were also seen in the reverse direction: preterm birth in the first pregnancy predicted complications in second pregnancies delivered at term.ConclusionsPre-eclampsia, placental abruption, stillbirth, neonatal death, or small for gestational age experienced in a first term pregnancy are associated with a substantially increased risk of subsequent preterm delivery. Term complications seem to share important underlying causes with preterm delivery that persist from pregnancy to pregnancy, perhaps related to a mother’s predisposition to disorders of placental function.


2021 ◽  
Vol 10 (2) ◽  
pp. 179
Author(s):  
Emma Rasmark Roepke ◽  
Ole Bjarne Christiansen ◽  
Karin Källén ◽  
Stefan R. Hansson

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.


2021 ◽  
Vol 10 (4) ◽  
pp. 643
Author(s):  
Veronica Giorgione ◽  
Corey Briffa ◽  
Carolina Di Fabrizio ◽  
Rohan Bhate ◽  
Asma Khalil

Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts (p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e022220 ◽  
Author(s):  
Daphne N McRae ◽  
Patricia A Janssen ◽  
Saraswathi Vedam ◽  
Maureen Mayhew ◽  
Deborah Mpofu ◽  
...  

ObjectiveOur aim was to investigate if antenatal midwifery care was associated with lower odds of small-for-gestational-age (SGA) birth, preterm birth (PTB) or low birth weight (LBW) compared with general practitioner (GP) or obstetrician (OB) models of care for women of low socioeconomic position.SettingThis population-level, retrospective cohort study used province-wide maternity, medical billing and demographic data from British Columbia, Canada.ParticipantsOur study included 57 872 pregnant women, with low socioeconomic position, who: were residents of British Columbia, Canada, carried a singleton fetus, had low to moderate medical/obstetric risk, delivered between 2005 and 2012 and received medical insurance premium assistance.Primary and secondary outcome measuresWe report rates, adjusted ORs (aOR), and 95% CIs for the primary outcome, SGA birth (<the 10th percentile), and secondary outcomes, PTB (<37 weeks’ completed gestation) and LBW (<2500 g).ResultsOur sample included 4705 midwifery patients, 45 114 GP patients and 8053 OB patients. Odds of SGA birth were reduced for patients receiving antenatal midwifery versus GP (aOR 0.71, 95% CI 0.62 to 0.82) or OB care (aOR 0.59, 95% CI 0.50 to 0.69). Odds of PTB were lower for antenatal midwifery versus GP (aOR 0.74, 95% CI 0.63 to 0.86) or OB patients (aOR 0.53, 95% CI 0.45 to 0.62). Odds of LBW were reduced for midwifery versus GP (aOR 0.66, 95% CI 0.53 to 0.82) or OB patients (aOR 0.43, 95% CI 0.34 to 0.54).ConclusionAntenatal midwifery care in British Columbia, Canada, was associated with lower odds of SGA birth, PTB and LBW, for women of low socioeconomic position, compared with physician models of care. Results support the development of policy to ensure antenatal midwifery care is available and accessible for women of low socioeconomic position. Future research is needed to determine the underlying mechanisms linking midwifery care to better birth outcomes for women of low socioeconomic position.


2019 ◽  
Vol 37 (01) ◽  
pp. 008-013 ◽  
Author(s):  
Lydia L. Shook ◽  
Mark A. Clapp ◽  
Penelope S. Roberts ◽  
Sarah N. Bernstein ◽  
Ilona T. Goldfarb

Abstract Objective To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. Study Design This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th–95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Results A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant <fifth percentile, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.1–4.8, p = 0.039). There was no significant association between high FF and either preterm birth or hypertensive disorders of pregnancy. Conclusion Women with a high FF in the first trimester are at increased risk of delivering a small for gestational age infant <fifth percentile. Further investigation into the clinical implications of a high FF is warranted.


BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e023529 ◽  
Author(s):  
Enny S Paixão ◽  
Oona M Campbell ◽  
Maria Gloria Teixeira ◽  
Maria CN Costa ◽  
Katie Harron ◽  
...  

ObjectivesDengue is the most common viral mosquito-borne disease, and women of reproductive age who live in or travel to endemic areas are at risk. Little is known about the effects of dengue during pregnancy on birth outcomes. The objective of this study is to examine the effect of maternal dengue severity on live birth outcomes.Design and settingWe conducted a population-based cohort study using routinely collected Brazilian data from 2006 to 2012.ParticipatingWe linked birth registration records and dengue registration records to identify women with and without dengue during pregnancy. Using multinomial logistic regression and Firth method, we estimated risk and ORs for preterm birth (<37 weeks’ gestation), low birth weight (<2500 g) and small for gestational age (<10thcentile). We also investigated the effect of time between the onset of the disease and each outcome.ResultsWe included 16 738 000 live births. Dengue haemorrhagic fever was associated with preterm birth (OR=2.4; 95% CI 1.3 to 4.4) and low birth weight (OR=2.1; 95% CI 1.1 to 4.0), but there was no evidence of effect for small for gestational age (OR=2.1; 95% CI 0.4 to 12.2). The magnitude of the effects was higher in the acute disease period.ConclusionThis study showed an increased risk of adverse birth outcomes in women with severe dengue during pregnancy. Medical intervention to mitigate maternal risk during severe acute dengue episodes may improve outcomes for infants born to exposed mothers.


2019 ◽  
Vol 41 (16) ◽  
pp. 1542-1550 ◽  
Author(s):  
Casey Crump ◽  
Jan Sundquist ◽  
Kristina Sundquist

Abstract Aims Preterm birth has been associated with elevated blood pressure early in life; however, hypertension risks from childhood into adulthood remain unclear. We conducted a large population-based study to examine gestational age at birth in relation to hypertension risks from childhood into adulthood. Methods and results A national cohort study was conducted of all 4 193 069 singleton live births in Sweden during 1973–2014, who were followed up for hypertension identified from nationwide inpatient and outpatient (specialty and primary care) diagnoses from any health care encounters through 2015 (maximum age 43 years; median 22.5). Cox regression was used to examine gestational age at birth in relation to hypertension risk while adjusting for other perinatal and maternal factors, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and/or environmental) factors. In 86.8 million person-years of follow-up, 62 424 (1.5%) persons were identified with hypertension (median age 29.8 years at diagnosis). Adjusted hazard ratios for new-onset hypertension at ages 18–29 years associated with preterm (&lt;37 weeks) and extremely preterm (22–27 weeks) birth were 1.28 [95% confidence interval (CI), 1.21–1.36] and 2.45 (1.82–3.31), respectively, and at ages 30–43 years were 1.25 (1.18–1.31) and 1.68 (1.12–2.53), respectively, compared with full-term birth (39–41 weeks). These associations affected males and females similarly and appeared substantially related to shared genetic or environmental factors in families. Conclusions In this large national cohort, preterm birth was associated with increased risk of hypertension into early adulthood. Persons born prematurely may need early preventive evaluation and long-term monitoring for the development of hypertension.


2018 ◽  
Vol 108 (4) ◽  
pp. 814-820 ◽  
Author(s):  
A Mukhopadhyay ◽  
T Thomas ◽  
R J Bosch ◽  
P Dwarkanath ◽  
A Thomas ◽  
...  

Abstract Background Maternal macronutrient intake is likely to play a pivotal role in fetoplacental growth. Male fetuses grow faster and their growth is more responsive to maternal size. Objective We assessed the role of fetal sex in modifying the effect of maternal macronutrient intake on the risk of small-for-gestational-age (SGA) birth. Design This was a prospective, observational cohort study of 2035 births from an urban South Asian Indian population. Maternal intakes of total energy and macronutrients were recorded by validated food-frequency questionnaires. The interaction of trimester 1 macronutrient intake with fetal sex was tested on the outcome of SGA births. Results The prevalence of SGA was 28%. Trimester 1 macronutrient composition was high in carbohydrate and low in fat (means ± SDs—carbohydrate: 64.6% ± 5.1%; protein: 11.5% ± 1.1%; and fat: 23.9% ± 4.4% of energy). Higher carbohydrate and lower fat consumption were each associated with an increased risk of SGA [adjusted OR (AOR) per 5% of energy (95% CI): carbohydrate: 1.15 (1.01, 1.32); fat: 0.83 (0.71, 0.97)] specifically among male births (males: n = 1047; females: n = 988). Dietary intake of &gt;70% of energy from carbohydrate was also associated with increased risk (AOR: 1.67; 95% CI: 1.00, 2.78), whereas &gt;25% of energy from fat intake was associated with decreased risk (AOR: 0.61; 95% CI: 0.41, 0.90) of SGA in male births. Conclusions Higher carbohydrate and lower fat intakes early in pregnancy were associated with increased risk of male SGA births. Therefore, we speculate that fetal sex acts as a modifier of the role of maternal periconceptional nutrition in optimal fetoplacental growth.


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