ÖZET
2019 yılında koronavirüslerin yol açtığı yeni tip bir viral solunum yolu enfeksiyonu tanımlanmış ve bu enfeksiyon Koronavirüs hastalığı-19 (COVİD-19) olarak isimlendirilmiştir. Gebe kadınların viral hastalıklara daha yatkın olmadıkları uzun zamandır bilinmektedir. Ancak gebelikte bağışıklık sisteminde meydana gelen değişiklikler, gebelerin bu hastalıkları daha ağır bulgularla geçirmelerine neden olabilir. Ağır COVİD-19 enfeksiyonu geçiren gebe olmayan kadınlarla karşılaştırıldıklarında gebe kadınlar, daha fazla risk altında gözükmemektedirler. Bugün için koronavirüslerin düşük, erken gebelik kaybı veya doğumsal defektlerle bir ilişkisi olduğuna dair kanıt yoktur. COVİD-19’un spesifik antiviral bir tedavisi bulunmamaktadır. COVİD-19 tanısı almış hastalarda tedavi seçenekleri son olarak, hidrosiklorokin ve/veya azitromisin, ağır pnömoni olgularında favipiravir olarak güncellenmiştir. Güncellenmiş COVİD-19 ulusal tedavi kılavuzuna göre, favipiravirin gebelerde ve emziren annelerde kullanımı önerilmemektedir. Lopinavir/ritonavir alternatif ya da kombine tedavi olarak diğer ilaçlara yanıt vermeyen gebelerde tercih edilebilir. Emzirme döneminde COVİD-19 ile ilgili yayınlanmış veriler sınırlıdır. Emzirmede esas risk, damlacık yoluyla hastalığı bulaştırabilecek anne ile bebeğin yakın temasıdır. COVİD-19 tedavisinde kullanılacak ilaçlar, fetus ve yenidoğana olası advers etkileri açısından dikkatle değerlendirilmelidir. Bu derleme gebelikte ve emzirme döneminde hidroksiklorokin, azitromisin ve lopinavir/ritonavir kullanımına ait literatür bilgisini sunmaktadır. Gebelikte ve emzirme döneminde hidroksiklorokin ve azitromisin kullanımının doğumsal kusur riskini artırması ya da yenidoğanda advers etkiye yol açması beklenmemektedir. Lopinavir/ritonavir tedavisi ile ilgili bilgilerimiz insan bağışıklık yetmezliği virüsü enfeksiyonu olan gebelere ait olmakla birlikte anne sağlığını tehdit eden durumlarda hem gebelikte hem emzirme döneminde bu ilaçlar kullanılabilir. Gebe veya emziren kadınlarda COVİD-19 enfeksiyonunu değerlendirmek zor olabilmekle birlikte ilaç seçimi konusunda özellikle dikkatli olunmalı ve hem anne hem bebek açısından ideal sonuçlar için en güncel bilgiler kullanılmalıdır.
References
1
T.C. Sağlık Bakanlığı. COVID-19 erişkin hasta yönetimi ve tedavisi, 2020. Last Accessed Date: 15.05.2020. Available from: https://covid19bilgi.saglik.gov.tr/depo/tedavi/COVID19-EriskinHastaTedavisi.pdf.
2
Gebelik, doğum ve lohusalık döneminde “Yeni koronavirüs enfeksiyonu 2019” (COVID-19) hakkında Türk Perinatoloji Derneği görüşü, 2020. Last Accessed Date: 15.05.2020. Available from: http://www.perinatoloji.org.tr/gebelik-dogum-ve-lohusalik-doneminde-yeni-koronavirus-enfeksiyonu-2019-covid-19-hakkinda-turk-perinatoloji-dernegi-gorusu.
3
Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in none pregnant women: A retrospective review of medical records. Lancet 2020;395:809-15.
4
Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr 2020;9:51-60.
5
Rodrigues C, Baía I, Domingues R, Barros H. Pregnancy and breastfeeding during COVID-19 pandemic: A systematic review of published pregnancy cases. Front Public Health 2020;8:558144.
6
Tırmıkçıoğlu Z. Drug use in pregnant women infected with COVID-19. Anatolian Clinic Journal of Medical Sciences 2020;25(Suppl 1):51-8.
7
Costedoat-Chalumeau N, Amoura Z, Duhaut P, Huong DL, Sebbough D, Wechsler B, et al Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum 2003;48:3207-11.
8
Motta M, Tincani A, Faden D, Zinzini E, Lojacono A, Marchesi A, et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol 2005;25:86-9.
9
Parke A, West B. Hydroxychloroquine in pregnant patients with systemic lupus erythematosus. J Rheumatol 1996;23:1715-8.
10
Hart CW, Naunton RF. The ototoxıcıty of chloroquıne phosphate. Arch Otolaryngol 1964;80:407-12.
11
Cimaz R, Brucato A, Meregalli E, Muscará M, Sergi P. Electroretinograms of children born from mothers treated with hydroxychloroquine (HCQ) during pregnancy and breast-feeding. Lupus 2004; 13: 755.
12
Klinger G, Morad Y, Westall CA, Laskin C, Spitzer KA, Koren G, et al. Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet 2001;358:813-4.
13
Osadchy A, Ratnapalan T, Koren G. Ocular toxicity in children exposed in utero to antimalarial drugs: review of the literature. J Rheumatol 2011;38:2504-8.
14
Sperber K, Hom C, Chao CP, Shapiro D, Ash J. Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases. Pediatr Rheumatol Online J 2009;7:9.
15
Kaplan YC, Ozarfati J, Nickel C, Koren G. Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: A systematic review and meta-analysis. Br J Clin Pharmacol 2015; 173: 1132-41.
16
Götestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016;75:795-810.
17
Centers for Disease Control and Prevention. CDC Yellow Book 2020: Health Information for International Travel. New York: Oxford University Press; 2019.
18
Cimaz R, Brucato A, Meregalli E, Muscará M, Sergi P. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Arthritis Rheum 2004;50:3056-7.
19
Motta M, Tincani A, Faden D, Zinzini E, Lojacono A, Marchesi A, et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol 2005;25:86-9.
20
Peng W, Liu R, Zhang L, Fu Q, Mei D, Du X. Breast milk concentration of hydroxychloroquine in Chinese lactating women with connective tissue diseases. Eur J Clin Pharmacol 2019;75:1547-53.
21
Costedoat-Chalumeau N, Amoura Z, Aymard G, Le TH, Wechsler B, Vauthier D, et al. Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum 2002;46:1123-4.
22
Kavanaugh A, Cush JJ, Ahmed MS, Bermas BL, Chakravarty E, Chambers C, et al. Proceedings from the American College of Rheumatology Reproductive Health Summit: The management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res (Hoboken) 2015;67:313-25.
23
Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016;55:1693-7.
24
Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al. 2020 American College of Rheumatology Guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 2020;72:529-56.
25
Centers for Disease Control and Prevention. CDC Yellow Book 2020: Health information for international travel. New York: Oxford University Press 2019.
26
Marzolini C, Rudin C, Decosterd LA, Telenti A, Schreyer A, Biollaz J, et al. Transplacental passage of protease inhibitors at delivery. AIDS 2002;16:889-93.
27
Ivanovic J, Nicastri E, Anceschi MM, Ascenzi P, Signore F, Pisani G, et al. Transplacental transfer of antiretroviral drugs and newborn birth weight in HIV-infected pregnant women. Curr HIV Res 2009;7:620-5.
28
Simon A, Warszawski J, Kariyawasam D, Le Chenadec J, Benhammou V, Czernichow P, et al. Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among uninfected infants of HIV-infected mothers. JAMA 2011;306:70-8.
29
Antiretroviral pregnancy registry Interim report for. 1 January 1989 -31 July 2020. Wilmington, NC: Registry Coordinating Center; 2019.
30
Sibiude J, Mandelbrot L, Blanche S, Le Chenadec J, Boullag-Bonnet N, Faye A, et al. Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the French perinatal cohort study (ANRS CO1/CO11). PLoS Med 2014;11:1001635.
31
Tookey PA, Thorne C, van Wyk J, Norton M. Maternal and foetal outcomes among 4118 women with HIV infection treated with lopinavir/ritonavir during pregnancy: analysis of population-based surveillance data from the national study of HIV in pregnancy and childhood in the United Kingdom and Ireland. BMC Infect Dis 2016;16:65.
32
Wang L, Zhao H, Cai W, Tao J, Zhao Q, Sun L, et al. Risk factors associated with preterm delivery and low delivery weight among HIV-exposed neonates in China. Int J Gynaecol Obstet 2018;142:300-7.
33
Guideline: Updates on HIV and Infant Feeding: The Duration of Breastfeeding, and Support from Health Services to Improve Feeding Practices Among Mothers Living with HIV. Geneva: World Health Organization; 2016.
34
Gandhi M, Mwesigwa J, Aweeka F, Plenty A, Charlebois E, Ruel TD, et al. Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding. J Acquir Immune Defic Syndr 2013;63:578-84.
35
Ramirez-Ramirez A, Sanchez-Serrano E, Loaiza-Flores G, Plazola- Camacho N, Rodriguez-Delgado RG, Figueroa-Damian R, et al. Simultaneous quantification of four antiretroviral drugs in breast milk samples from HIV-positive women by an ultra-high performance liquid chromatography tandem mass spectrometry (UPLCMS/ MS) method. PLoS One 2018;13:e0191236.
36
Oumar AA, Bagayoko-Maiga K, Bahachimi A, Maiga M, Cere MC, Diarra Z, et al. Efavirenz and lopinavir levels in HIV-infected women and their nursing infants, in mali. J Pharmacol Exp Ther 2018;366:479-84.
37
Heikkinen T, Laine K, Neuvonen PJ, Ekblad U. The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. BJOG 2000;107:770-5.
38
Savitcheva AM, Tchkhartishvili MG, Arzhanova O, Drobchenko SN. The course and outcome of pregnancy in women with chlamydial infection. J Perinat Med 2001;29(Suppl 1): 372.
39
Rahangdale L, Guerry S, Bauer HM, Packel L, Rhew M, Baxter R, et al. An observational cohort study of chlamydia trachomatis treatment in pregnancy. Sex Transm Dis 2006;33:106-10.
40
Cooper WO, Hernadez-Diaz S, Arbogast PG, Dudley JA, Dyer SM, Gideon PS, et al. Antibiotics potentially used in response to bioterrorism and major congenital malformations. Pharmaco Epidemiol Drug Saf 2006; 15(Suppl 1): S6- S7.
41
Bar-Oz B, Weber-Schoendorfer C, Berlin M, Clementi M, Di Gianantonio E, de Vries L, et al. The outcomes of pregnancy in women exposed to the new macrolides in the first trimester: A prospective, multicentre, observational study. Drug Saf 2012;35:589-98.
42
Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer SM, Gideon PS, et al. Antibiotics potentially used in response to bioterrorism and the risk of major congenital malformations. Paediatr Perinat Epidemiol 2009;23:18-28.
43
Muanda FT, Sheehy O, Bérard A. Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ 2017;189:625-33.
44
Kelsey JJ, Moser LR, Jennings JC, Munger MA. Presence of azithromycin breast milk concentrations: A case report. Am J Obstet Gynecol 1994;170:1375-6.
45
Sørensen HT, Skriver MV, Pedersen L, Larsen H, Ebbesen F, Schønheyder HC. Risk of infantile hypertrophic pyloric stenosis after maternal postnatal use of macrolides. Scand J Infect Dis 2003;35:104-6.
46
Lund M, Pasternak B, Davidsen RB, Feenstra B, Krogh C, Diaz LJ, et al. Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study. BMJ 2014;348:1908.
47
Goldstein LH, Berlin M, Tsur L, Bortnik O, Binyamini L, Berkovitch M. The safety of macrolides during lactation. Breastfeed Med 2009;4:197-200.
48
Sutton AL, Acosta EP, Larson KB, Kerstner-Wood CD, Tita AT, Biggio JR. Perinatal pharmacokinetics of azithromycin for cesarean prophylaxis. Am J Obstet Gynecol 2015;212:812.
49
Abdellatif M, Ghozy S, Kamel MG, Elawady SS, Ghorab MME, Attia AW, et al. Association between exposure to macrolides and the development of infantile hypertrophic pyloric stenosis: A systematic review and meta-analysis. Eur J Pediatr 2019;178:301-14.
50
Almaramhy HH, Al-Zalabani AH. The association of prenatal and postnatal macrolide exposure with subsequent development of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis. Ital J Pediatr 2019;45:20.
