MAMA

Background

The global rate of Caesarean section (CS) is 21.1 % (2021) and is rising worldwide. CS presents the third highest cumulative incidence for surgical site infections (SSI). Maternal infections around the time of childbirth account for 1 out of 10 maternal deaths worldwide. Therefore, perioperative antibiotic prophylaxis (PAP) during CS is common standard of care and part of numerous recommendations from expert bodies such as the World Health Organization (WHO) and different national gynecological professional associations. According to these, first and second generation cephalosporins like cefuroxime are the agents of choice for this indication. In fact, the use of PAP significantly reduces maternal morbidity and mortality rates. Whereas the side effect of this measure on the microbiome of the newborn has been the subject of repeated clinical studies, data on specific and especially long-term effects on the gut microbiome of the mothers are still lacking. MAMA is the first study to specifically and systematically investigate this question.

Methods

This multicenter, two-arm, non-interventional, observational study analyzes the qualitative and quantitative changes in the gut microbiome of mothers at birth due to antibiotic prophylaxis with cefuroxime. We recruited pregnant women from two perinatal centers in Germany, from outpatient facilities and via social media channels. Women with C-section were recruited for the study group, women with vaginal birth and without use of antibiotics as control. Participants gave their informed consent to participate in the study after a detailed consultation with the study coordinator. Each women submitted three stool samples (T0, T1, T2) for microbiome analysis. Stool samples were collected by the participant following a detailed description and using “DNA/RNA ShieldTM Fecal Collection Tube – DX” by Zymo Research to prevent quality loss during postal transport. Collection took place at home or (in case of prolonged inpatient treatment after delivery) at the hospital. Required metadata was collected via questionnaires. Stool samples and questionnaires were then sent back to the study coordinator. Thus, no additional on-site visits were required.

The taxonomic identification and quantification of the microbiome is performed by sequencing the 16S rRNA gene (V3/V4). The biostatistical analysis includes taxonomic annotation, OTU clustering and determination of α- and β-diversity. The changes in the microbiome (diversity, frequency, variance) of the study groups will show whether and which permanent (> 3 months) changes in the intestinal microbiome are caused by PAP with cefuroxime in mothers at birth. In particular, the (new) occurrence of potentially pathogenic species (induced dysbiosis) and changes in the physiological flora will be investigated, as women towards the end of pregnancy have an especially vulnerable microbiome. Permanent dysbiosis can be a risk factor for gestational diabetes in subsequent pregnancies.

Upcoming evaluation

The two-year recruitment phase has been concluded.

We will first determine a baseline microbiome prior to delivery (time point T0) and then analyze as well as compare its changes due to delivery (control group) or to antibiotic prophylaxis (CS group).

We expect the occurrence of induced dysbiosis in the CS group at time point T1, i.e. reduced α-diversity, decrease of beneficial gut bacteria, possible (new) emergence of potentially pathogenic species, including Clostridioides, increase of Enterobacteriaceae such as Enterococcus species. For the first time, however, we will be able to observe this effect specifically in women in the peripartum period and also to precisely describe it quantitatively and qualitatively by comparison with the control group. The latter is also crucial for the assessment of recolonization at time point T2. We will show for the first time whether and which long-term consequences the single shot antibiotic prophylaxis with cefuroxime causes in women giving birth.