By Jakob Stokholm, MD, PhD
Chairman: Freddy Karup Pedersen
Opponent: Agnes Wold
Opponent: Niels Frimodt Møller
The commensal flora consists of non-pathogenic microbiota found on all body surfaces maintaining a well-balanced host-microbial symbiotic state.
The vaginal microbiota represents a microbial ecosystem. A low pH level is maintained by acid producing bacteria, most often dominated by Lactobacillus. The low pH level is together with the host immunity responsible for protection of the vagina. A vast number of other bacterial species are represented in the vaginal commensal microbiota and among these both Staphylococcus and E. coli are often found. Skewing of the vaginal commensal flora with a following increase in pH level can lead to an overgrowth of certain microbiota resulting in bacterial vaginosis or vaginal candidiasis.
Humans are continuously exposed to a large amount of environmental factors providing a possible influence on their microbial ecology. Antibiotic administration is one of the factors with the ability to promote such changes. Household pets are another contributor which can potentially affect the microbiota of the owner.
The aim of this PhD thesis was to investigate the factors affecting the antibiotic usage and vaginal microbiota in pregnant women from the COPSAC2010 pregnancy cohort.
In study I, we described the usage of antibiotics; (1) in pregnancy as oral antibiotics subdivided into groups; urinary tract infection (UTI) antibiotics, beta-lactams and other antibiotics, and (2) during birth as intrapartum antibiotics. Furthermore we examined whether the usage of both oral antibiotics during pregnancy and intrapartum antibiotics was associated to social and lifestyle-factors. The prevalence of oral antibiotic administration during pregnancywas higher than a decade ago with more than one-third of pregnant women being treated. Oral antibiotic administration as well as multiple antibiotic treatments was increased in the lower educated women. Younger women and smokers had an increased usage of UTI antibiotics and asthmatic women had an increased usage of beta-lactams. Administration of intrapartum antibiotics was increased in smokers, in women giving birth at a lower gestational age, and in women with a lower parity. These predictors for antibiotic administration may be used as general health indicators.
In study II, we analyzed the effect of antibiotic administration during pregnancy on the commensal vaginal microbiota. Vaginal samples were cultured at 36th week of pregnancy and described at genus level. Most dominating genus was Staphylococcus spp. which colonized 79% of the women. Oral antibiotic usage both at any time-point during pregnancy and during third pregnancy trimester was associated to an increased rate of vaginal colonization by Staphylococcus spp. These bacteriological changes were associated to treatment with UTI antibiotics. Women treated in the third trimester of pregnancy were more often colonized by E. coli. This change was associated to beta-lactam treatment. We did not observe any significant changes in vaginal group B Streptococcus (GBS) following antibiotic treatment in pregnancy.A changed vaginal flora in pregnant women may lead to infections with potential morbidity to woman and fetus.
In study III, we studied the associations between exposure to cat and dog during pregnancy and the vaginal bacterial flora at 36th week of pregnancy, antibiotic usage, and self-reported infections in pregnancy. We aimed to examine whether living with a cat or a dog was able to affect the vaginal flora, and prevalence of infections. Living with cat or dog in the home was significantly associated to increased vaginal colonization with E. coli, increased administration of antibiotics and increased prevalence of UTI in pregnancy. All estimates were adjusted for environmental and social factors. We suggest that transmission of bacteria from pet to owner is responsible for the associations to vaginal E. coli, oral antibiotic use, and UTI. Our study suggests a clinically important transmission of pathogenic bacteria from pet to owner.
In conclusion, we have found that Danish women present a high intake of antibiotics during pregnancy, and that both oral antibiotic usage during pregnancy and intrapartum antibiotic administration is influenced by social and lifestyle related factors. Antibiotic usage during pregnancy and especially in third trimester has the ability to cause alterations in the vaginal ecology at 36th week of pregnancy. Furthermore, both the vaginal flora and antibiotic usage during pregnancy is affected by having a cat or dog at home. A changed vaginal flora in pregnant women may potentially lead to intrauterine infection, UTI, preterm birth, neonatal infection and effects on theearly microbial colonization of the neonate. Likewise, it is suggested, that a transmission of pathogenic bacteria from pet to owner poses a clinical important threat, which can lead to infection in pregnant women.