Fetal development in uncomplicated pregnancies occurs in the absence of amniotic fluid microbiota and offspring microbial colonization starts after uterine contractions and rupture of amniotic membrane, according to a study recently published in the American Journal of Obstetrics and Gynecology.
The human microbiome discovery has developed quickly in recent decades, suggesting the importance of a diverse and well-balanced maternal and infant microbiome for normal development of a child’s immune system. Furthermore, a dysbiotic maternal gut microbiome has been associated with disease development in offspring as well as with other immune-mediated diseases. Identifying the timing of the initial microbial colonization of the offspring could therefore be helpful in further understanding the development origin of health and disease.
Challenging earlier studies, it has recently been suggested that amniotic fluid has a microbiome of its own in term, uncomplicated pregnancies. This evidence of a unique placental microbiome questions the “sterile womb” hypothesis. However, the current evidence for a sterile intrauterine environment is inconclusive and the extent to which, if, and how maternal microbiome influences fetal immunologic development and the shaping of the infant microbiome is not settled. Therefore, this study investigated the presence of a microbiota in amniotic fluid in term uncomplicated pregnancies and determined the amniotic fluid bacterial load.
In a period of 22 months from December 2014 to October 2016, 2701 pregnant women were enrolled in the Preventing Atopic Dermatitis and Allergies (PreventADALL) study in Norway and Sweden. Amniotic fluid was randomly sampled during cesarean deliveries in pregnant women at 1 of 3 study sites included in the PreventADALL study. Of the 65 term pregnancies in which amniotic fluid was sampled successfully, 10 were selected from elective (planned, without ongoing labor) cesarean deliveries, and 14 women with prior rupture of membranes were included as positive controls. Amniotic fluid was analyzed by culture-dependent and culture-independent techniques.
The median concentration of prokaryotic DNA (16S rRNA gene copies/mL; digital droplet polymerase chain reaction) was low for the group with intact membranes (664), whereas levels in the rupture of amniotic membranes group were >10-fold higher (7700; P =.0001). In addition, bacteria were detected in 50% of the rupture of amniotic membranes samples by means of anaerobic culturing, but none of the samples from the intact membrane group demonstrated bacterial growth. Sanger sequencing of the rupture of amniotic membrane samples identified bacterial strains that are commonly part of the vaginal flora and/or associated with intrauterine infections, including Streptococcus agalactiae, Peptoniphilus harei/ asaccharolyticus, Lactobacillus reuteri/crispatus/vaginalis, and Prevotella amnii/bivia.
Overall, the study authors concluded that, “[a]mniotic fluid is sterile in uncomplicated pregnancies with intact amniotic membranes at term.”
Rehbinder EM, Lødrup Carlsen KC, Staff AC, et al. Is amniotic fluid of women with uncomplicated pregnancies free of bacteria? [published online May 28, 2018]. Am J Obstet Gynecol. doi: 10.1016/j.ajog.2018.05.028