Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters

The association between apical periodontitis and adverse pregnancy outcomes: a systematic review

BackgroundThe association between adverse pregnancy outcomes (APOs) and maternal apical periodontitis remains unclear as it has not been examined rigorously or reviewed systematically.ObjectiveTo systematically review and critically evaluate the available evidence on the association of maternal apical periodontitis with several APOs.MethodsA literature search was conducted using the following electronic databases: Clarivate Analytics’ Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL), from inception to 25 February 2021, with no language restrictions. Observational studies including longitudinal clinical trials, cohort, case–control and cross-sectional studies of prospective and retrospective design were included. Articles with duplicate or overlapping results, abstract-only papers, case reports, case series, animal studies and reviews were excluded. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The Newcastle–Ottawa Scale (NOS) and the adapted form of the NOS were used to assess the quality for case–control and cross-sectional studies, respectively.ResultsTwo case–control and one cross-sectional study were included in the current review. The included studies were published between 2015 and 2017, with a total of 1187 participating individuals with an approximate age range of 15 to 40 years. As the included studies reported different outcomes, the heterogeneity of data prevented a meta-analysis being undertaken. The overall quality of the evidence was ‘Fair’ for two out of three included studies, while one study was categorized as ‘Good’.DiscussionTwo out of three included primary studies had a substantial number of methodological inconsistencies and flaws, and therefore caution should be exercised in interpreting the results of this systematic review because several important covariates were not considered in the original investigations.ConclusionBased on a limited volume and ‘Fair’ and ‘Good’ quality of evidence, a positive association between maternal apical periodontitis and APOs was observed. However, more ‘Good’ quality clinical studies are needed to confirm the results of the current review

The association between apical periodontitis and adverse pregnancy outcomes: a systematic review

BackgroundThe association between adverse pregnancy outcomes (APOs) and maternal apical periodontitis remains unclear as it has not been examined rigorously or reviewed systematically.ObjectiveTo systematically review and critically evaluate the available evidence on the association of maternal apical periodontitis with several APOs.MethodsA literature search was conducted using the following electronic databases: Clarivate Analytics’ Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL), from inception to 25 February 2021, with no language restrictions. Observational studies including longitudinal clinical trials, cohort, case–control and cross-sectional studies of prospective and retrospective design were included. Articles with duplicate or overlapping results, abstract-only papers, case reports, case series, animal studies and reviews were excluded. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The Newcastle–Ottawa Scale (NOS) and the adapted form of the NOS were used to assess the quality for case–control and cross-sectional studies, respectively.ResultsTwo case–control and one cross-sectional study were included in the current review. The included studies were published between 2015 and 2017, with a total of 1187 participating individuals with an approximate age range of 15 to 40 years. As the included studies reported different outcomes, the heterogeneity of data prevented a meta-analysis being undertaken. The overall quality of the evidence was ‘Fair’ for two out of three included studies, while one study was categorized as ‘Good’.DiscussionTwo out of three included primary studies had a substantial number of methodological inconsistencies and flaws, and therefore caution should be exercised in interpreting the results of this systematic review because several important covariates were not considered in the original investigations.ConclusionBased on a limited volume and ‘Fair’ and ‘Good’ quality of evidence, a positive association between maternal apical periodontitis and APOs was observed. However, more ‘Good’ quality clinical studies are needed to confirm the results of the current review