Relationship Between Amoxicillin Use in Pregnancy and Congenital Anomalies: A Systematic Review

Page: [170 - 176] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Objective: Amoxicillin is among the most used antibiotics in the treatment of a wide spectrum of bacterial infections. Although amoxicillin is categorized as group B in pregnancy, the findings of studies regarding its effects on the fetus are controversial. The aim of this systematic review was to review the reported effects of amoxicillin administration in pregnancy on congenital anomalies.

Methods: Published articles in PubMed, Scopus, SID, and Magiran databases, as well as Google Scholar were searched till May 2021 based on a search strategy. Case-control and cohort studies in Persian or English language were included. Four studies, including two case-control and two cohort studies, with an overall sample size of 260491 pregnant mothers, were included in the review.

Results: A review of case-control studies revealed an increased risk for cleft palate in one study. Cohort studies did not reveal a significant relationship between amoxicillin use and major congenital anomalies.

Conclusion: The findings of this systematic review showed that although no major congenital anomaly was reported for the administration of amoxicillin consumption with or without clavulanic acid, there is a possibility that amoxicillin administration in pregnancy might be related to some anomalies, including cleft palate. Amoxicillin should be administered with caution during pregnancy till more evidence is provided regarding its safety.

Graphical Abstract

[1]
Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernández-Díaz S, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J obstet and gynecol 2011; 205(1): e1-8.
[2]
Muanda FT, Sheehy O, Bérard A. Use of antibiotics during pregnancy and the risk of major congenital malformations: A population based cohort study. Br J Clin Pharmacol 2017; 83(11): 2557-71.
[http://dx.doi.org/10.1111/bcp.13364] [PMID: 28722171]
[3]
Romøren M, Lindbaek M, Nordeng H. Pregnancy outcome after gestational exposure to erythromycin - a population-based register study from Norway. Br J Clin Pharmacol 2012; 74(6): 1053-62.
[http://dx.doi.org/10.1111/j.1365-2125.2012.04286.x] [PMID: 22463376]
[4]
Mensah KB, Opoku-Agyeman K, Ansah C. Antibiotic use during pregnancy: A retrospective study of prescription patterns and birth out-comes at an antenatal clinic in rural Ghana. J Pharm Policy Pract 2017; 10(1): 24.
[http://dx.doi.org/10.1186/s40545-017-0111-0] [PMID: 28808578]
[5]
Lamont HF, Blogg HJ, Lamont RF. Safety of antimicrobial treatment during pregnancy: a current review of resistance, immunomodulation and teratogenicity. Expert Opin Drug Saf 2014; 13(12): 1569-81.
[http://dx.doi.org/10.1517/14740338.2014.939580]
[6]
deLemos AS, Ghabril M, Rockey DC, et al. Amoxicillin–clavulanate-induced liver injury. Dig Dis Sci 2016; 61(8): 2406-16.
[http://dx.doi.org/10.1007/s10620-016-4121-6] [PMID: 27003146]
[7]
Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology 2011; 53(4): 1377-87.
[http://dx.doi.org/10.1002/hep.24229] [PMID: 21480339]
[8]
Lin KJ, Mitchell AA, Yau WP, Louik C, Hernández-Díaz S. Maternal exposure to amoxicillin and the risk of oral clefts. Epidemiology 2012; 23(5): 699-705.
[http://dx.doi.org/10.1097/EDE.0b013e318258cb05] [PMID: 22766750]
[9]
Robinson A, Atallah F, Weedon J, Chen YJA, Apostol R, Minkoff H. Effect of removal of pregnancy category on prescribing in pregnancy: A randomized [5OP]. Obstet Gynecol 2018; 131(1): 2S.
[http://dx.doi.org/10.1097/01.AOG.0000533293.16410.58]
[10]
de Marco BA, Natori JSH, Fanelli S, Tótoli EG, Salgado HRN. Characteristics, properties and analytical methods of amoxicillin: A review with green approach. Crit Rev Anal Chem 2017; 47(3): 267-77.
[http://dx.doi.org/10.1080/10408347.2017.1281097] [PMID: 28080135]
[11]
Eslami ST, Nassirian A, Nassirian H, Hatami E, Sobhani E, Najibpour R. Comparing performance of amoxicillin and intramuscular benzathine penicillin in relieving manifestations of Streptococcal pharyngitis in children. Ghana Med J 2015; 48(4): 185-8.
[http://dx.doi.org/10.4314/gmj.v48i4.3] [PMID: 25709132]
[12]
Daniel S, Doron M, Fishman B, Koren G, Lunenfeld E, Levy A. The safety of amoxicillin and clavulanic acid use during the first trimester of pregnancy. Br J Clin Pharmacol 2019; 85(12): 2856-63.
[http://dx.doi.org/10.1111/bcp.14118] [PMID: 31486528]
[13]
Jepsen P, Skriver MV, Floyd A, Lipworth L, Schønheyder HC, Sørensen HT. A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark. Br J Clin Pharmacol 2003; 55(2): 216-21.
[http://dx.doi.org/10.1046/j.1365-2125.2003.01750.x] [PMID: 12580995]
[14]
Zhang Y, Shi D, Abagyan R, Dai W, Dong M. Population scale retrospective analysis reveals potential risk of cholestasis in pregnant women taking omeprazole, lansoprazole, and amoxicillin. Interdiscip Sci 2019; 11(2): 273-81.
[http://dx.doi.org/10.1007/s12539-019-00335-w] [PMID: 31106388]
[15]
Tang BH, Wu YE, Kou C, et al. Population pharmacokinetics and dosing optimization of amoxicillin in neonates and young infants. Antimicrob Agents Chemother 2019; 63(2): e02336-18.
[http://dx.doi.org/10.1128/AAC.02336-18] [PMID: 30509939]
[16]
Nahum GG, Uhl K, Kennedy DL. Antibiotic use in pregnancy and lactation: What is and is not known about teratogenic and toxic risks. Obstet Gynecol 2006; 107(5): 1120-38.
[http://dx.doi.org/10.1097/01.AOG.0000216197.26783.b5] [PMID: 16648419]
[17]
Crossan E, Duane B. Is there an association between maternal smoking and oral clefts? Evid Based Dent 2018; 19(1): 24-5.
[http://dx.doi.org/10.1038/sj.ebd.6401292] [PMID: 29568024]
[18]
Panamonta O, Wiromrat P, Wongswadiwat Y, Chaikitpinyo A, Panamonta M, Wichajarn K. Maternal tobacco smoke exposure during pregnancy and the occurrence of orofacial clefts: A systematic review of reported meta-analyses. J Med Assoc Thai 2017; 100(6): S270-7.
[19]
Lasalita-Zapico F, Peńaflorida A, Aguilar CH, Laniton LJ, Palarpalar EG. Oro-facial clefting and associated risk factors in selected families in general Santos City, Philippines. Asian. J Biol and Life Sci 2014; 3(2)
[20]
Abou TF. Teratogenic and toxic effects of Hiconcil (amoxicillin) on mouse fetuses. 1994.
[21]
Rashad HI, Shahin MA. Histological and ultrastructural studies on the effect of amoxicillin on the liver of mice foetuses. Egypt J Histol 2020; 43(1): 255-66.
[22]
Nathanson S, Moreau E, Merlet-Benichou C, Gilbert T. In utero and in vitro exposure to β-lactams impair kidney development in the rat. J Am Soc Nephrol 2000; 11(5): 874-84.
[http://dx.doi.org/10.1681/ASN.V115874] [PMID: 10770965]
[23]
Miller JE, Wu C, Pedersen LH, de Klerk N, Olsen J, Burgner DP. Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: A population-based cohort study. Int J Epidemiol 2018; 47(2): 561-71.
[http://dx.doi.org/10.1093/ije/dyx272] [PMID: 29415232]
[24]
Milliken S, Allen RM, Lamont RF. The role of antimicrobial treatment during pregnancy on the neonatal gut microbiome and the development of atopy, asthma, allergy and obesity in childhood. Expert Opin Drug Saf 2019; 18(3): 173-85.
[http://dx.doi.org/10.1080/14740338.2019.1579795] [PMID: 30739516]
[25]
Bai L, Zhao D, Cheng Q, et al. Trimester-specific association between antibiotics exposure during pregnancy and childhood asthma or wheeze: The role of confounding. Ann Epidemiol 2019; 30: 1-8.
[http://dx.doi.org/10.1016/j.annepidem.2018.10.003] [PMID: 30448356]
[26]
Turi KN, Gebretsadik T, Ding T, et al. Dose, timing, and spectrum of prenatal antibiotic exposure and risk of childhood asthma. Clin Infect Dis 2021; 72(3): 455-62.
[http://dx.doi.org/10.1093/cid/ciaa085] [PMID: 31994697]
[27]
Lamont RF, Møller Luef B, Stener Jørgensen J. Childhood inflammatory and metabolic disease following exposure to antibiotics in pregnancy, antenatally, intrapartum and neonatally. F1000 Res 2020; 9: 144.
[http://dx.doi.org/10.12688/f1000research.19954.1] [PMID: 32148773]
[28]
Chen LW, Xu J, Soh SE, et al. Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation. Int J Obes 2020; 44(7): 1508-20.
[http://dx.doi.org/10.1038/s41366-020-0572-0] [PMID: 32321980]
[29]
Adamek K, Skonieczna-Żydecka K, Węgrzyn D, Łoniewska B. Prenatal and early childhood development of gut microbiota. Eur Rev Med Pharmacol Sci 2019; 23(21): 9667-80.
[PMID: 31773718]
[30]
Wang T, Chen L, Huang P, et al. Association of maternal gut microbiota and plasma metabolism with congenital heart disease in offspring: A multi-omic analysis. Sci Rep 2021; 11(1): 5339.
[http://dx.doi.org/10.1038/s41598-021-84901-7] [PMID: 33674681]