The Effect of Maternal Use of Macrolides, Antifungals, and Antivirals/ Antiretrovirals on Non-Syndromic Orofacial Clefts
: A Systematic Review and Meta-analysis

  • Zainab M Alsaffar

Student thesis: Doctoral ThesisDoctor of Dental Surgery (DDS)


To assess the risk of non-syndromic orofacial cleft after exposure to macrolides, antifungals,
and antivirals/ antiretrovirals during pregnancy.
Search Strategy:
MEDLINE, EMBASE, and the Cochrane library were searched up to April 30, 2019.
Search Criteria:
Relevant English language studies investigating foetal adverse outcomes after in utero
exposure to macrolides, antifungals, and antivirals/ antiretrovirals.
Data Collection and Analysis:
Studies were screened by two reviewers. Data was extracted, study quality was assessed,
and pooled estimates were calculated. A random effects meta-analysis was conducted to
estimate the effect of macrolides and antifungals on the risk of developing a cleft.
Antivirals/ antiretrovirals were not included in the meta-analysis as it was not possible to
extract the data from the papers identified.
Main Results:
Overall, nine case-control studies and eight cohort studies met the inclusion criteria. Eight of
the seventeen studies were included in the meta-analysis having excluded those pertaining
to antivirals/ antiretrovirals and limiting to those measures that were either an “Odds Ratio”
or “Prevalence Odds Ratio”. The data indicated that erythromycin and fluconazole exposure
during pregnancy is not associated with an increased risk of cleft lip and palate. For
antivirals and antiretrovirals, no conclusion could be reached due to the high level of
heterogeneity within the studies.
Exposure to macrolides and antifungals was not associated with an increased risk of oral
cleft. Further studies are required to investigate whether antivirals and antiretrovirals pose
a risk during pregnancy.
Date of Award26 Nov 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorJonathan Sandy (Supervisor) & Anthony J Ireland (Supervisor)

Cite this