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      Antidepressant use during pregnancy and the risk of developing gestational hypertension: a retrospective cohort study

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          Abstract

          Background

          Prior studies reported that exposure to antidepressants during pregnancy may be associated with gestational hypertension. The aim of this study is to assess the association between the use of antidepressants during pregnancy and the risk of developing gestational hypertension.

          Methods

          A retrospective cohort study using the prescription database IADB.nl was conducted among nulliparous women with singleton pregnancies between 1994 and 2015 in the Netherlands. Logistic regression analysis was used to estimate odds ratios (OR), adjusted OR (aOR) and their corresponding 95% confidence intervals (95% CI). Gestational hypertension as main outcome measure was defined as at least one dispensed record of an antihypertensive drug (methyldopa, nifedipine, labetalol, ketanserin, nicardipine) after 20 weeks of gestation until 14 days after delivery. Sub-analyses were conducted for class of antidepressant, duration and amount of use of antidepressant (≤30, ≥30 Defined Daily Doses or DDDs), and maternal age. Sensitivity analyses to assess uncertainties were conducted.

          Results

          Twenty-eight thousand twenty women were included, of which 539 (1.92%) used antidepressants. The risk of gestational hypertension was doubled for women using antidepressant (aOR 2.00 95% CI 1.28–3.13). Significant associations were also found for the subgroup selective serotonin reuptake inhibitors (SSRIs) (aOR 2.07 95% CI 1.25–3.44), ≥30 DDDs (aOR 2.50 95% CI 1.55–3.99) and maternal age of 30–34 years (aOR 2.59 95% CI 1.35–4.98). Varying the theoretical gestational age showed comparable results.

          Conclusion

          Prolonged use of antidepressants during the first 20 weeks of gestation appeared to be associated with an increased risk of developing gestational hypertension. When balancing the benefits and risks of using these drugs during pregnancy, this should be taken into account.

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          Most cited references24

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          Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

          The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland. Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Pre-eclampsia

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              Perinatal risks of untreated depression during pregnancy.

              To review the literature on the perinatal risks involved in untreated depression during pregnancy. We searched Medline and medical texts for all studies pertaining to this area up to the end of April 2003. Key phrases entered were depression and pregnancy, depression and pregnancy outcome, and depression and untreated pregnancy. We did not include bipolar depression. While there is wide variability in reported effects, untreated depression during pregnancy appears to carry substantial perinatal risks. These may be direct risks to the fetus and infant or risks secondary to unhealthy maternal behaviours arising from the depression. Recent human data suggest that untreated postpartum depression, not treatment with antidepressants in pregnancy, results in adverse perinatal outcome. The biological dysregulation caused by gestational depression has not received appropriate attention: most studies focus on the potential but unproven risks of psychotropic medication. No in-depth discussion of the role of psychotherapy is available. Because they are not aware of the potentially catastrophic outcome of untreated maternal depression, this imbalance may lead women suffering from depression to fear teratogenic effects and refuse treatment.
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                Author and article information

                Contributors
                +31 50 363 8209 , n.zakiyah@rug.nl
                l.f.ter.heijne@student.rug.nl
                h.j.bos@rug.nl
                e.hak@rug.nl
                m.j.postma@rug.nl
                c.c.m.schuiling-veninga@rug.nl
                Journal
                BMC Pregnancy Childbirth
                BMC Pregnancy Childbirth
                BMC Pregnancy and Childbirth
                BioMed Central (London )
                1471-2393
                29 May 2018
                29 May 2018
                2018
                : 18
                : 187
                Affiliations
                [1 ]ISNI 0000 0004 0407 1981, GRID grid.4830.f, Unit of PharmacoTherapy, -Epidemiology & -Economics (PTEE), Department of Pharmacy, , University of Groningen, ; A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
                [2 ]Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
                [3 ]ISNI 0000 0000 9558 4598, GRID grid.4494.d, Institute of Science in Healthy Aging & healthcaRE (SHARE), , University Medical Center Groningen, ; 9713 GZ Groningen, The Netherlands
                Author information
                http://orcid.org/0000-0002-9630-5567
                Article
                1825
                10.1186/s12884-018-1825-y
                5975401
                29843629
                0db8de37-6e63-4352-b2e7-d320ccd3043f
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 September 2017
                : 14 May 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Obstetrics & Gynecology
                antidepressive agents,pregnancy,gestational hypertension,preeclampsia
                Obstetrics & Gynecology
                antidepressive agents, pregnancy, gestational hypertension, preeclampsia

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