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The risk for persistent pulmonary hypertension of the newborn was significantly increased in the analysis of exposure to selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor in any trimester (odds ratio, 1.82; 95% confidence interval, 1.31-2.54; I2 = 72%), as well as in analysis restricted to exposure week >20 (odds ratio, 2.08; 95% confidence interval, 1.44-3.01; I2 = 76%). Reference Achenbach, McConaughy and Howell35. This association was partially as a result of higher postnatal maternal depressive symptoms (Table 2). It is evident soon after birth, and symptoms can range in severity from mild respiratory distress to the most severe form, with hypoxia necessitating intensive medical care.5 Persistent pulmonary hypertension of the newborn has been defined as a final common pathway of a variety of risk factors and insults that can cause pulmonary underdevelopment, maldevelopment, or poor postnatal adaptation.6 In 2006, Health Canada and the US Food and Drug Administration issued advisories7 8 alerting clinicians to a potential association between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and persistent pulmonary hypertension of the newborn following a publication showing such an association. Psychopharmacology (Berl) 2011; 217 :2119. Reference Barbey and Roose1 Bringing together these findings, this book explores the evidence linking the role of early life events to long-term physical and psychological health outcomes. 2012. Selective Serotonin Reuptake Inhibitors and Persistent Pulmonary Hypertension of the Newborn: An Update Meta-Analysis. There are currently no book-length treatments of perinatal neurodevelopment. This book fills this gap by presenting a collection of chapters from leading experts in the field. Importance Selective serotonin reuptake inhibitor (SSRI) use among pregnant women is increasing, yet the association between prenatal SSRI exposure and fetal neurodevelopment is poorly understood. Finally, SSRIs are mainly prescribed to treat depression, thus the association between prenatal SSRI exposure and pervasive developmental problems could be explained by these residual depressive symptoms. Reference Constantino and Gruber29,Reference Constantino, Przybeck, Friesen and Todd30 And, when we used the ratings of the father only, we also observed that children exposed to SSRIs were more likely to have pervasive developmental problems. Long-term drug safety trials are needed before evidence-based recommendations are possible. To assess autistic traits, mothers filled out the adapted 18-item version of the SRS at age 6 years, which is a quantitative measure of autistic traits for children aged between 4 and 18 years. Reference Schetter36 That study12 found caesarean delivery before onset of labour to be associated with persistent pulmonary hypertension of the newborn (odds ratios 4.9, 95% confidence interval 1.7 to 14.0). "newCitedByModal": true, A direct comparison of the effect estimates of SSRI use and depressive symptoms without SSRI use showed a significant difference ( for comparison 0.10, 95% CI 0.02-0.18, P<0.01). Finally, we used the level of depressive symptoms as a continuous variable and the analyses showed that prenatal depressive symptoms were not associated with an increased risk for pervasive developmental problems (OR = 1.19, 95% CI 0.93-1.53, P = 0.16). Reference El Marroun, Jaddoe, Hudziak, Roza, Steegers and Hofman12 Gestational Exposure to Selective Serotonin Reuptake Inhibitors and Offspring Psychiatric Disorders: A National Register-Based Study. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. We calculated the LR+, which was equal to 28.68. "isUnsiloEnabled": true, Furthermore, the sensitivity analyses demonstrated an increased risk for pervasive developmental problems when exposed to SSRIs in the first trimester of pregnancy only (OR = 2.15, 95% CI 1.02-4.55, P = 0.047) and a trend for and increased risk when exposed to SSRIs in multiple trimesters (OR = 2.03, 95% CI 0.82-5.03, P = 0.13). The difference in definition of early versus late exposure among the studies was a further limitation. Two studies,2 12 for example, did exclude congenital malformations known to be associated with persistent pulmonary hypertension of the newborn, but they did not exclude all malformations. It is imperative that the mothers health be weighed heavily in treatment decisions; she and her family must be counselled on both the risks of exposing the fetus to antidepressant drugs and the risks of severe depressive illness. The non-responders were younger (28.1 years (s.d. This concern was first raised by Chambers and colleagues who reported an association between third-trimester use of fluoxetine (Prozac) an increased risk of neonatal complications and higher rates of admission to the special care nursery ( Chambers 1996 ). To examine the relationship of exposure to prenatal SSRI use or maternal depressive symptoms with pervasive developmental and affective problems as reported by the father, we used linear regression analyses. 2016. However, persistent pulmonary hypertension of the newborn has been reported to be more common in infants born at 34 weeks compared with those born at term (37 to 41 weeks).29 31 It is also important to note that preterm birth has been associated with both antidepressant use and maternal depression.28 32 The independent effects of preterm birth and exposure to SSRIs remain to be determined. The pervasive developmental problems subscale of the CBCL 1.5-5 has been shown to be a useful screening instrument to identify children with autism spectrum disorder when compared with the Autism Diagnostic Observation Schedule - Generic. Kohm, A.D. However, the possible long-term consequences of prenatal SSRI exposure on child neurodevelopment are uncertain. Complementing lengthier psychiatric references, this latest "Concise Guide" offers enduring value in a convenient pocket-size format with extensive tables and illustrations. Any time in pregnancyThe pooled odds ratio of the two eligible studies2 11 for exposure to SSRIs at any time and persistent pulmonary hypertension of the newborn was 1.55 (95% confidence interval 0.79 to 3.04; P=0.20). Published by Elsevier Inc. Jaddoe, Vincent W. V. Eight articles met the inclusion criteria, but one29 was excluded as it was based on the same cohort as a more recent study.1 Seven studies were included in the quantitative analysis (fig 1,30 see supplementary table1 2 3 10 11 12 13). Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects. Reference Rothman41 Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? Contributors: SG and LER conceptualised and designed the study. It is the first book to call attention to the drugs' catch-22: Although many people are ready to go off these drugs, they continue to take them because either the patient or the doctor mistakes antidepressant withdrawal for depressive Development of the 10-item Edinburgh Postnatal Depression Scale, Characteristics of the Edinburgh Post Natal Depression Scale in The Netherlands, New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study. The adjusted odds ratio in those women who used SSRIs in late pregnancy and had a history of admission to hospital for a psychiatric condition was even higher at 3.1 (95% confidence interval 1.9 to 4.9), suggesting that the combination of a psychiatric disorder and antidepressant use might confer a higher risk. Mean duration of benzodiazepine use was 49.9 days (1.6 months). The CIDI is a structured interview based on DSM-IV criteria. Verhulst, Frank C. Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis. The CBCL 1.5-5 is a standardised assessment instrument, which covers a broad age range. Scattoni, Maria Luisa Healy, D. An established norm cut-off score (above the 93rd percentile) was used that indicates clinically meaningful problems. This unique chemical is present in all living cells including plants and animals. This book will take us through a serene journey of the evolutionary history of serotonin and its role from man to mollusk. Head circumference was also measured directly after birth or at child healthcare centres at age 3 weeks (mean post-conception age: 42.9 weeks). McEachan, Rosie R.C. "metricsAbstractViews": false, Epigenetics and Dermatology explores the role of epigenetics in the pathogenesis of autoimmune-related skin diseases and skin cancer. In the late exposure analysis, the infants included were of either 33 or 34 weeks or more gestation, and thus we were unable to evaluate preterm birth as a source of heterogeneity as well. For the same subgroup we tested the BSIs ability to identify postpartum depression. Use of SSRIs before pregnancy only was recorded in 146 (2.4%) women; these individuals were excluded as a spillover effect cannot be ruled out. Seven (18%) out of these 40 were found to have a form of CHD. The primary outcome was risk for persistent pulmonary hypertension of the newborn after exposure to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy. Search key words included: "SSRI," "SNRI," "pregnancy," "risk," "new-born," and "pulmonary hypertension." Of the 3077 abstracts reviewed, 2339 were excluded on the basis of the title and abstract. In total, 8880 mothers were enrolled during pregnancy (delivery from April 2002 to January 2006). Fig 2 Exposure to selective serotonin reuptake inhibitors in early pregnancy and risk of persistent pulmonary hypertension of the newborn: meta-analysis of all studies, Exposure to selective serotonin reuptake inhibitors (SSRIs) and risk of persistent pulmonary hypertension of the newborn: results of meta-analyses. Reference Walter20 The human literature has been more mixed in terms of the associations of prenatal exposure to SSRI with brain and cognitive development. Higher trait scores of SSRI-exposed than of non-exposed children were observed in every domain of autism: social cognition ( = 0.13, 95% CI 0.03-0.23, P = 0.01), social communication ( = 0.17, 95% CI 0.09-0.25, P<0.001) and autistic mannerism ( = 0.12, 95% CI 0.05-0.20, P= 0.006, Table 3). Parker, Matthew O. However, it has been shown that the BSI is reliable and valid. Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review. It is essential to contrast any effect of prenatal SSRI exposure with the known long-term consequences of untreated prenatal depression on child development. which was in line with a previous animal study. Removing the study1 that included an earlier definition of late exposure (after the first antenatal visit which is generally after the first trimester although unknown when exactly) resulted in a marginally non-significant result. Reference Cox, Holden and Sagovsky25,Reference Pop, Komproe and van Son26 Boulle, F and This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. According to our findings, sertraline ranked as most likely to have the lowest risk for persistent pulmonary hypertension of the newborn compared to other selective serotonin reuptake inhibitors, suggesting it may have the best safety profile for use in pregnancy For exposure to SSRIs in early pregnancy, the odds ratio of 1.23 led to an absolute risk difference of 0.44/1000 live births and an NNTH of 2288 women (table 2). Context Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants and maternal depression both alter neonatal health, and distinguishing the effects of each influence remains challenging.. Betas (s) represent the increased or decreased risk for autistic traits as measured with the Social Responsiveness Scale (at 6 years) in the subgroups as compared with the reference group. Reference Achenbach and Rescorla28,Reference Nakamura, Ebesutani, Bernstein and Chorpita47 Homberg, Judith R Based on previous literature potential confounders were selected. Furthermore, some studies excluded cases with more or less severe complications (for example, congenital malformations, meconium aspiration, preterm delivery (34 weeks), neonatal pneumonia, or sepsis, see supplementary table), whereas others did not. US Food and Drug Administration. We utilised the following databases (from inception to 30 December 2012): Medline In-Process (Ovid), Medline (Ovid) to access current literature (searching for keywords only), PsycINFO (American Psychological Association; Ovid), Embase (Excerpta Medica, Elsevier; Ovid), CINAHL (Nursing; Allied Health), and Scopus (Elsevier) to access current literature (through searching for keywords only). Additional analyses accounting for the level of prenatal depressive symptoms and fetal head growth were performed. Gaikwad, Siddharth There have been various studies showing a number of adverse outcomes, including gestational hypertension, reduced birth weight, altered neonatal pain responses and persistent pulmonary hypertension of the newborn with exposure 2012. The primary outcome of interest for this meta-analysis was persistent pulmonary hypertension of the newborn, as defined by the authors of the original publications. The GEE procedure adjusts for within-participant correlation. and Significant heterogeneity was found across studies (Q2=9.00, P=0.01; table 1), in the high range (I2=77.8%). Despite our attempt to determine if an association exists between all antidepressants with persistent pulmonary hypertension of the newborn, we were only able to examine SSRIs because of the lack of data on the other antidepressant classes; future research should determine if other classes of antidepressants show similar associations. 2014 Jan 14;348:f6932. The results of our meta-analysis suggest that the risk for persistent pulmonary hypertension of the newborn is increased with exposure to selective serotonin reuptake inhibitors (SSRIs) in late pregnancy; we did not find an increased risk from exposure in early pregnancy. The strength of our work rests on the attention to potential confounding factors. This suggests that mothers with depressive symptoms particularly may overestimate the problems of their children. Burger, David M Depressive symptoms were assessed with the Brief Symptom Inventory (BSI) Dragioti E, Solmi M, Favaro A, Fusar-Poli P, Dazzan P, Thompson T, Stubbs B, Firth J, Fornaro M, Tsartsalis D, Carvalho AF, Vieta E, McGuire P, Young AH, Shin JI, Correll CU, Evangelou E. JAMA Psychiatry. Finally, no observational study can rule out residual confounding, i.e. The present study is embedded in an ongoing population-based cohort, the Generation R Study. Identifying longterm neurodevelopmental effects of prenatal SSRI exposure is challenging in humans due to difficulties in distinguishing the effect of the drug from mother's mood during pregnancy and everyday environment in which the child lives, all of which contribute to shaping emotional, cognitive, and social development long after birth. It has been proposed that this early brain overgrowth might be as a result of an excess of neurons resulting from cell-cycle dysregulation and/or failure of naturally occurring apoptosis. Diamond, David M. There is a marked increase in the use of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors in the last decade. In contrast, the effect of prenatal exposure to maternal depressive symptoms was not significant when analyses were based on the fathers ratings (OR = 1.63, 95% CI 0.93-2.88, P = 0.09). Selection of treatment is based on several factors, and antidepressant drugs may be necessary, especially in severe depressive episodes.45 Although the odds for persistent pulmonary hypertension of the newborn seem to be greater with the use of SSRIs later in pregnancy, despite the limitations of the original studies, the risk is still low. Although SSRI use usually occurs in the context of maternal depressive and anxiety disorders, only a few studies have adjusted for these factors, yielding conflicting results (5, 6, 8, 20, 21). Found insideMedical Neurobiology, Second Edition continues the work of Dr. Peggy Mason as one of the few single author textbooks available. We used an odds ratio of 0.001 for the non-zero odds ratio, as this gave a summary odds ratio that was the same with or without the study included. SG held a new investigator award in womens health research from Canadian Institutes of Health Research in partnership with the Ontario Womens Health Council (award NOW-88207). Although four studies did report data for women using any antidepressant,1 2 3 10 not enough comparable data were available to permit pooling of at least three studies, and thus we limited our quantitative analysis to use of selective serotonin reuptake inhibitors (SSRIs, as in the individual studys definitions). Network meta-analysis was conducted, incorporating direct and indirect comparisons among different selective serotonin reuptake inhibitors. Three studies reported data on exposure to SSRIs in early pregnancy,1 2 3 two on exposure at any time or any point in pregnancy,2 11 two on exposure for most or all of pregnancy,1 13 and five on exposure in late pregnancy.1 2 3 10 12 Five studies used a cohort study design1 3 10 11 13 and two a case-control study design.2 12 All of the studies were above our quality threshold, and as a result we did not perform subanalyses to examine the effect of study quality. Compr Physiol. The R Project for Statistical Computing. As persistent pulmonary hypertension of the newborn is a rare event we included adjusted or unadjusted odds ratios, prevalence, or relative risks in the analyses as estimates of odds ratios. a. SSRI, selective serotonin reuptake inhibitor. Model II was additionally adjusted for maternal depressive symptoms at 3 years. Again, consistent results were observed if father ratings of child affective problems were analysed (OR for SSRI exposure 1.04, 95% 0.39-2.76, P = 0.95). Second, we previously showed that prenatal SSRI exposure was associated with decreased fetal head growth, We estimate that we would have to treat 286 to 351 women with an SSRI in late gestation to see one additional case of persistent pulmonary hypertension of the newborn. and the subscales for syndromes derived from the CBCL 1.5-5 had good fit in 23 international studies across diverse societies. When we excluded the study by Reis and Klln1 the odds ratio remained within this range (odds ratio of 2.4) but was marginally non-significant (P=0.06). Thus, 5976 children formed the study population. SSRIs are prescribed for anxiety disorders, which are increasingly recognised as being common in pregnancy39 and are themselves associated with adverse birth outcomes.40 41 42. Email: Petersen, Irene Perinatal mental health: a review of progress and challenges. We estimated risk differences to facilitate interpretation of our results for clinical practice (table 2). = 5.8), range 57.7-108.9), we used the CBCL 1.5-5 (preschool version) for reasons of continuity. Although more research controlling for risk factors discussed in this study as well as others not reviewed here, is needed, pregnant women considering or using SSRIs and their families should be educated about persistent pulmonary hypertension of the newborn, how the symptoms can range in severity, what treatments are available for it at the institution where the birth will take place, and that it can typically be managed successfully if it does occur in the context of SSRI use. This is in agreement with studies demonstrating overgrowth of the brain in children with autism in the first 3 years of life. In network meta-analysis, sertraline was ranked most likely to have the lowest risk for persistent pulmonary hypertension of the newborn among the different selective serotonin reuptake inhibitors (P = .83). We compared the characteristics of the 5976 women included in the analyses of the CBCL to those of 2122 mothers not included. The investigators found an association between exposure to an SSRI during the first trimester and an increased risk of omphalocele (OR, 2.8). The strongest effect was observed with paroxetine, which accounted for 36% of all SSRI exposures and which was associated with an 8.1-fold increase in risk of omphalocele. 16 Recent investigations have focused on the possible association between maternal SSRI use during pregnancy and the increased risk of Another study10 had few cases of persistent pulmonary hypertension of the newborn and yet another study12 was underpowered. 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