Top

Published in:

Open Access 01-12-2018 | Research article

Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births

Authors: Shan-Yan Gao, Qi-Jun Wu, Ce Sun, Tie-Ning Zhang, Zi-Qi Shen, Cai-Xia Liu, Ting-Ting Gong, Xin Xu, Chao Ji, Dong-Hui Huang, Qing Chang, Yu-Hong Zhao

Published in: BMC Medicine | Issue 1/2018

Abstract

Background

In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.

Methods

The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).

Results

Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).

Conclusions

The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.

Available only for authorised users

Ornoy A, Koren G. Selective serotonin reuptake inhibitors in human pregnancy: on the way to resolving the controversy. Semin Fetal Neonatal Med. 2014;19(3):188–94.CrossRef

Berard A, Zhao J, Sheehy O. Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort. BMJ Open. 2017;7:e0133721.CrossRef

Jimenez-Solem E, Andersen JT, Petersen M, Broedbaek K, Andersen NL, Torp-Pedersen C, et al. Prevalence of antidepressant use during pregnancy in Denmark, a nation-wide cohort study. PLoS One. 2013;8(4):e63034.CrossRef

Taouk LH, Matteson KA, Stark LM, Schulkin J. Prenatal depression screening and antidepressant prescription: obstetrician-gynecologists’ practices, opinions, and interpretation of evidence. Arch Womens Ment Health. 2018;21(1):85–91.CrossRef

Liu Y, Zhou X, Zhu D, Chen J, Qin B, Zhang Y, et al. Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis. Hum Psychopharmacol. 2015;30(3):132–42.CrossRef

Hendrick V, Stowe ZN, Altshuler LL, Hwang S, Lee E, Haynes D. Placental passage of antidepressant medications. Am J Psychiatry. 2003;160(5):993–6.CrossRef

Laine K, Heikkinen T, Ekblad U, Kero P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry. 2003;60(7):720–6.CrossRef

Sadler TW. Selective serotonin reuptake inhibitors (SSRIs) and heart defects: potential mechanisms for the observed associations. Reprod Toxicol. 2011;32(4):484–9.CrossRef

U.S Food and Drug Administration (FDA). Public Health Advisory: Paroxetine. 2005. https://wayback.archive-it.org/7993/20170112033310/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm051731.htm. Accessed 27 Aug 2018.; 2018.

10.

Nembhard WN, Tang X, Hu Z, MacLeod S, Stowe Z, Webber D. Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study. BMJ. 2017;356:j832.CrossRef

11.

Kang HH, Ahn KH, Hong SC, Kwon BY, Lee EH, Lee JS, et al. Association of citalopram with congenital anomalies: a meta-analysis. Obstet Gynecol Sci. 2017;60(2):145–53.CrossRef

12.

Selmer R, Haglund B, Furu K, Andersen M, Nørgaard M, Zoëga H, et al. Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: the Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy. Pharmacoepidem DR S. 2016;25(10):1160–9.CrossRef

13.

Kowalik E, Ward K, Ye Y. SSRI use in pregnancy and congenital heart defects: a metaanalysis of population-based cohort studies. Pharmacotherapy. 2016;36(12):e302.

14.

Wang S, Yang L, Wang L, Gao L, Xu B, Xiong Y. Selective Serotonin Reuptake Inhibitors (SSRIs) and the Risk of Congenital Heart Defects: A Meta-Analysis of Prospective Cohort Studies. J Am Heart Assoc. 2015;4(5):e001681.

15.

Myles N, Newall H, Ward H, Large M. Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Aust NZ J Psychiat. 2013;47(11):1002–12.CrossRef

16.

Painuly N, Painuly R, Heun R, Sharan P. Risk of cardiovascular malformations after exposure to paroxetine in pregnancy: meta-analysis. Psychiatrist. 2013;37(6):198–203.CrossRef

17.

Riggin L, Frankel Z, Moretti M, Pupco A, Koren G. The fetal safety of fluoxetine: a systematic review and meta-analysis. Journal of obstetrics and gynaecology Canada. JOGC. 2013;35(4):362–9.PubMed

18.

Yan Y, Cheng Y, Crowe B, Chhabra-Khanna R, Camporeale A, Marangell L. First trimester fluoxetine use and major malformations: a meta-analysis of epidemiological studies. Pharmacoepidem DR S. 2013;22:168–9.CrossRef

19.

Nikfar S, Rahimi R, Hendoiee N, Abdollahi M. Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: a systematic review and updated meta-analysis. Daru. 2012;20:75.CrossRef

20.

Wurst KE, Poole C, Ephross SA, Olshan AF. First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: a meta-analysis of epidemiological studies. Birth Defects Res Part A Clin Mol Teratol. 2010;88(3):159–70.CrossRef

21.

O’Brien L, Einarson TR, Sarkar M, Einarson A, Koren G. Does paroxetine cause cardiac malformations? J Obstet Gynaecol Can. 2008;30(8):696–701.CrossRef

22.

Bar-Oz B, Einarson T, Einarson A, Boskovic R, O'Brien L, Malm H, et al. Paroxetine and congenital malformations: meta-analysis and consideration of potential confounding factors. Clin Ther. 2007;29(5):918–26.CrossRef

23.

Addis A, Koren G. Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies. Psychol Med. 2000;30(1):89–94.CrossRef

24.

Zhang TN, Gao SY, Shen ZQ, Li D, Liu CX, Lv HC, et al. Use of selective serotonin-reuptake inhibitors in the first trimester and risk of cardiovascular-related malformations: a meta-analysis of cohort studies. Sci Rep. 2017;7:43085.CrossRef

25.

Shen ZQ, Gao SY, Li SX, Zhang TN, Liu CX, Lv HC, et al. Sertraline use in the first trimester and risk of congenital anomalies: a systemic review and meta-analysis of cohort studies. Brit J Clin Pharmaco. 2017;83(4):909–22.CrossRef

26.

Gao SY, Wu QJ, Zhang TN, Shen ZQ, Liu CX, Xu X, et al. Fluoxetine and congenital malformations: a systematic review and meta-analysis of cohort studies. Brit J Clin Pharmaco. 2017;83(10):2134–47.CrossRef

27.

Bérard A, Iessa N, Chaabane S, Muanda FT, Boukhris T, Zhao JP. The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis. Brit J Clin Pharmaco. 2016;81(4):589–604.CrossRef

28.

Grigoriadis S, VonderPorten EH, Mamisashvili L, Roerecke M, Rehm J, Dennis CL, et al. Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence. J Clin Psychiat. 2013;74(4):e293–308.CrossRef

29.

Reefhuis J, Devine O, Friedman JM, Louik C, Honein MA. Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. BMJ-Brit Med J. 2015;351:h3190.CrossRef

30.

Nishigori H, Obara T, Nishigori T, Mizuno S, Metoki H, Hoshiai T, et al. Selective serotonin reuptake inhibitors and risk of major congenital anomalies for pregnancies in Japan: a nationwide birth cohort study of the Japan Environment and Children’s Study. Congenit Anom. 2017;57(3):72–8.CrossRef

31.

Jordan S, Morris JK, Davies GI, Tucker D, Thayer DS, Luteijn JM, et al. Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants in pregnancy and congenital anomalies: Analysis of linked databases in Wales, Norway and Funen, Denmark. Plos One. 2016;11(12):e0165122.CrossRef

32.

Petersen I, Evans SJ, Gilbert R, Marston L, Nazareth I. Selective serotonin reuptake inhibitors and congenital heart anomalies: comparative cohort studies of women treated before and during pregnancy and their children. J Clin Psychiat. 2016;77(1):e36–42.CrossRef

33.

Malm H, Sourander A, Gissler M, Gyllenberg D, Hinkka-Yli-Salomäki S, McKeague IW, et al. Pregnancy complications following prenatal exposure to SSRIs or maternal psychiatric disorders: results from population-based national register data. AM J Psychiat. 2015;172(12):1224–32.CrossRef

34.

Furu K, Kieler H, Haglund B, Engeland A, Selmer R, Stephansson O, et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ. 2015;350:h1798.CrossRef

35.

Knudsen TM, Hansen AV, Garne E, Andersen AMN. Increased risk of severe congenital heart defects in offspring exposed to selective serotonin-reuptake inhibitors in early pregnancy - an epidemiological study using validated EUROCAT data. BMC Pregnancy Childbirth. 2014;14(1):333.

36.

Margulis AV, Abou-Ali A, Strazzeri MM, Ding Y, Kuyateh F, Frimpong EY, et al. Use of selective serotonin reuptake inhibitors in pregnancy and cardiac malformations: a propensity-score matched cohort in CPRD. Pharmacoepidem DR S. 2013;22(9):942–51.

37.

Jimenez-Solem E, Andersen JT, Petersen M, Broedbaek K, Jensen JK, Afzal S, et al. Exposure to selective serotonin reuptake inhibitors and the risk of congenital malformations: A nationwide cohort study. BMJ Open. 2012;2(3):e001148.CrossRef

38.

Nordeng H, Van Gelder MMHJ, Spigset O, Koren G, Einarson A, Eberhard-Gran M. Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian mother and child cohort study. J Clin Psychopharm. 2012;32(2):186–94.CrossRef

39.

Malm H, Artama M, Gissler M, Ritvanen A. Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstet Gynecol. 2011;118(1):111–20.CrossRef

40.

Colvin L, Slack-Smith L, Stanley FJ, Bower C. Dispensing patterns and pregnancy outcomes for women dispensed selective serotonin reuptake inhibitors in pregnancy. Birth Defects Res Part A Clin Mol Teratol. 2011;91(4):268.CrossRef

41.

Petersen I, Gilbert R, Evans S, Marston L, Nazareth I. SSRI and risk of congenital cardiac abnormalities. Pharmacoepidem DR S. 2010;19:S211.CrossRef

42.

Kornum JB, Nielsen RB, Pedersen L, Mortensen PB, Norgaard M. Use of selective serotonin-reuptake inhibitors during early pregnancy and risk of congenital malformations: updated analysis. Clin Epidemiol. 2010;2:29–36.CrossRef

43.

Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH. Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study. BMJ. 2009;339:b3569.CrossRef

44.

Merlob P, Birk E, Sirota L, Linder N, Berant M, Stahl B, et al. Are selective serotonin reuptake inhibitors cardiac teratogens? Echocardiographic screening of newborns with persistent heart murmur. Birth Defects Res Part A Clin Mol Teratol. 2009;85(10):837–41.CrossRef

45.

Diav-Citrin O, Shechtman S, Weinbaum D, Wajnberg R, Avgil M, Di Gianantonio E, et al. Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study. Brit J Clin Pharmaco. 2008;66(5):695–705.

46.

Kallen BA, Otterblad OP. Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations. Birth Defects Res A Clin Mol Teratol. 2007;79(4):301–8.CrossRef

47.

Vial T, Cournot MP, Bernard N, Carlier P, Jonville-Bero AP, Jean-Pastor MJ, et al. Paroxetine and congenital malformations: a prospective comparative study. Drug Saf. 2006;29(10):970.CrossRef

48.

Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010;67(10):1012–24.CrossRef

49.

Szegda K, Markenson G, Bertone-Johnson ER, Chasan-Taber L. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27(9):960–7.CrossRef

50.

Ogunyemi D, Jovanovski A, Liu J, Friedman P, Sugiyama N, Creps J, et al. The contribution of untreated and treated anxiety and depression to prenatal, intrapartum, and neonatal outcomes. AJP Rep. 2018;8(3):e146–57.CrossRef

51.

Pedersen LH. The risks associated with prenatal antidepressant exposure: time for a precision medicine approach. Expert Opin Drug Saf. 2017;16(8):915–21.CrossRef

52.

Susser LC, Sansone SA, Hermann AD. Selective serotonin reuptake inhibitors for depression in pregnancy. Am J Obstet Gynecol. 2016;215(6):722–30.CrossRef

53.

Koren G, Nordeng H. Antidepressant use during pregnancy: the benefit-risk ratio. Am J Obstet Gynecol. 2012;207(3):157–63.CrossRef

54.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.CrossRef

55.

Huybrechts KF, Palmsten K, Avorn J, Cohen LS, Holmes LB, Franklin JM, et al. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014;370(25):2397–407.CrossRef

56.

Davis RL, Rubanowice D, McPhillips H, Raebel MA, Andrade SE, Smith D, et al. Risks of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy. Pharmacoepidemiol Drug Saf. 2007;16(10):1086–94.CrossRef

57.

Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes in pregnant women taking fluoxetine. N Engl J Med. 1996;335(14):1010–5.CrossRef

58.

Vasilakis-Scaramozza C, Aschengrau A, Cabral H, Jick SS. Antidepressant use during early pregnancy and the risk of congenital anomalies. Pharmacotherapy. 2013;33(7):693–700.CrossRef

59.

Klieger-Grossmann C, Weitzner B, Panchaud A, Pistelli A, Einarson T, Koren G, et al. Pregnancy outcomes following use of escitalopram: a prospective comparative cohort study. J Clin Pharmacol. 2012;52(5):766–70.CrossRef

60.

Einarson A, Choi J, Einarson TR, Koren G. Incidence of major malformations in infants following antidepressant exposure in pregnancy: results of a large prospective cohort study. Can J Psychiatr. 2009;54(4):242–6.CrossRef

61.

Oberlander TF, Warburton W, Misri S, Riggs W, Aghajanian J, Hertzman C. Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data. Birth Defects Res Part B Dev Reprod Toxicol. 2008;83(1):68–76.CrossRef

62.

Wells GA, Shea BJ, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle–Ottawa scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. Appl Eng Agric. 2014;18(6):727–34.

63.

Odutayo A, Wong CX, Hsiao AJ, Hopewell S, Altman DG, Emdin CA. Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis. BMJ. 2016;354:i4482.CrossRef

64.

Bérard A, Zhao JP, Sheehy O. Sertraline use during pregnancy and the risk of major malformations. Am J Obstet Gynecol. 2015;212(6):791–5.CrossRef

65.

Hamling J, Lee P, Weitkunat R, Ambuhl M. Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat Med. 2008;27(7):954–70.CrossRef

66.

Einarson A, Pistelli A, DeSantis M, Malm H, Paulus WD, Panchaud A, et al. Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. AM J Psychiat. 2008;165(6):749–52.CrossRef

67.

Rothman KJ. Development DD. Modern Epidemiology. 3rd ed; 2014.

68.

Dersimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177.CrossRef

69.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.CrossRef

70.

Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.CrossRef

71.

Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRef

72.

Ban L, Gibson JE, West J, Fiaschi L, Sokal R, Smeeth L, et al. Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study. Bjog-Int J Obstet GY. 2014;121(12):1471–81.CrossRef

73.

Sari Y, Zhou FC. Serotonin and its transporter on proliferation of fetal heart cells. Int J Dev Neurosci. 2003;21(8):417–24.CrossRef

74.

Sit DK, Perel JM, Helsel JC, Wisner KL. Changes in antidepressant metabolism and dosing across pregnancy and early postpartum. J Clin Psychiatry. 2008;69(4):652–8.CrossRef

75.

Yavarone MS, Shuey DL, Tamir H, Sadler TW, Lauder JM. Serotonin and cardiac morphogenesis in the mouse embryo. Teratology. 1993;47(6):573–84.CrossRef

76.

Choi DS, Kellermann O, Richard S, Colas JF, Bolanos-Jimenez F, Tournois C, et al. Mouse 5-HT2B receptor-mediated serotonin trophic functions. Ann N Y Acad Sci. 1998;861:67–73.CrossRef

77.

Gentile S. Early pregnancy exposure to selective serotonin reuptake inhibitors, risks of major structural malformations, and hypothesized teratogenic mechanisms. Expert Opin Drug Metab Toxicol. 2015;11(10):1585–97.CrossRef

78.

Carmi R, Gohar J, Meizner I, Katz M. Spontaneous abortion--high risk factor for neural tube defects in subsequent pregnancy. Am J Med Genet. 1994;51(2):93–7.CrossRef

79.

Bukowski R, Carpenter M, Conway D, Coustan D, Dudley DJ, Goldenberg RL, et al. Causes of death among stillbirths. Jama-J Am Med Assoc. 2011;306(22):2459–68.CrossRef

80.

Ehrenstein V, Sorensen HT, Bakketeig LS, Pedersen L. Medical databases in studies of drug teratogenicity: methodological issues. Clin Epidemiol. 2010;2:37–43.CrossRef

81.

Tuccori M, Montagnani S, Testi A, Ruggiero E, Mantarro S, Scollo C, et al. Use of selective serotonin reuptake inhibitors during pregnancy and risk of major and cardiovascular malformations: an update. Postgrad Med. 2010;122(4):49–65.CrossRef

82.

Alwan S, Friedman JM. Safety of selective serotonin reuptake inhibitors in pregnancy. CNS Drugs. 2009;23(6):493–509.CrossRef

83.

Alwan S, Friedman JM, Chambers C. Safety of selective serotonin reuptake inhibitors in pregnancy: a review of current evidence. CNS Drugs. 2016;30(6):499–515.CrossRef

84.

Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med. 2007;356(26):2684–92.CrossRef

Title: Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births
Authors: Shan-Yan Gao
Qi-Jun Wu
Ce Sun
Tie-Ning Zhang
Zi-Qi Shen
Cai-Xia Liu
Ting-Ting Gong
Xin Xu
Chao Ji
Dong-Hui Huang
Qing Chang
Yu-Hong Zhao
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2018
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-018-1193-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Correction to: Frailty, nutrition-related parameters, and mortality across the adult age spectrum

Are smokers who are regularly exposed to e-cigarette use by others more or less motivated to stop or to make a quit attempt? A cross-sectional and longitudinal survey

Small contribution of gold mines to the ongoing tuberculosis epidemic in South Africa: a modeling-based study

How does malaria in pregnancy impact malaria risk in infants?

Chronic hepatitis B virus infection and risk of chronic kidney disease: a population-based prospective cohort study of 0.5 million Chinese adults

Large-scale external validation and comparison of prognostic models: an application to chronic obstructive pulmonary disease