Is the womb sterile in uncomplicated pregnancies?

Recent studies have challenged the century-old notion that the human fetal environment is sterile and that the neonate's microbiome is acquired during and after birth. A recent study published in the Journal of Science Translational Medicine reported the presence of unique commensal placental microbiome from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla.

Research has shown that seeding of healthy microbiome at birth is crucial for human health in later life. Another study published in September issue of American Journal of Obstetrics and Gynecology does not support the existence of microbiomes within the healthy fetal milieu, and this concept of ‘sterile womb’ have implications in the development of practices like ‘vaginal seeding’ after cesarean births.

The researchers from Norway and Sweden randomly sampled amniotic fluid from study cohort of uncomplicated pregnancies at term from 1 of the three sites included in the Preventing Atopic Dermatitis and Allergies in children (PreventADALL) study. The amniotic fluid from 65 pregnancies was collected under sterile conditions, ten samples were from women undergoing elective, planned cesarean section and 14 were from women who had prior rupture of membranes.

Women with ruptured membranes have more than 10-fold higher concentration of prokaryotic DNA (16S rRNA) gene copies/mL. More than 50% samples of amniotic fluid from ruptured membranes cohort showed bacterial growth in anaerobic cultures, while all samples from women who had intact membranes were sterile.

The bacteria identified on culture were vaginal commensals and/ or intrauterine pathogens including Streptococcus agalactiae, Peptoniphilus harei/ asaccharolyticus, Lactobacillus reuteri/crispatus/vaginalis, and Prevotella amnii/bivia.

The authors concluded that in uncomplicated pregnancies, fetal development occurs in a sterile environment and fetal microbiome is seeded following rupture of membranes. Understanding the timing of the first microbial colonization in fetus could help the researchers in a better understanding of the origin of many diseases.

Abstract

Ob/Gyn Updated Facebook page

Vaginal fluid Interleukin-6 seems to be a promising non-invasive marker for the prediction of inflammation in amniotic cavity in PPROM.

Preterm PROM complicates 3% of all pregnancies and is responsible for one third of preterm labors which leads to significant fetal morbidity and mortality. [1]Once the membrane ruptures the protective and sterile environment of the amniotic cavity is breeched linking it to bacterial cervicovaginal flora. This increases the risk of amniochorial infection which in turn is responsible for fetal inflammatory response syndrome.

Obstetricians have to weigh the benefits of prolonging the pregnancy at the risk of intrauterine infection. vs active induction of  labor. Numerous biomarkers have been studied in predicting the occurrence of infection and decide the clinical course of the pregnancy.

Maternal serum markers are not much useful in prediction of the fetal inflammatory response; hence researchers have studied various biomarkers from vaginal fluid like tumor necrosis factor-α, metalloproteinase-8 (MMP-8), soluble HLA-G (sHLA-G) and interleukin-6.

A recent paper published ahead of print in July issue of American Journal of Perinatology concluded that MMP-8, IL-6, glucose, and lactate concentrations in vaginal fluid did predict poor neonatal outcome but it was not reach statistical significance. Only increased levels of metalloproteinase-8 (MMP-8) were associated with poor neurological outcome. [2]

A recent study published in the forthcoming issue of American Journal of Obstetrics and Gynecology aimed to determine the diagnostic indices and predictive value of vaginal fluid interleukin-6 concentration as a point of care tool(POCT) in predicting microbial invasion of the amniotic cavity(MIAC), intra-amniotic inflammation, and microbial-associated intra-amniotic inflammation in patients with preterm PROM.[3]

The researchers also intended to know the relationship between vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously.

This prospective cohort study recruited 153 women with singleton pregnancy who had PROM at between 24+0 and 36+6 weeks. Preterm PROM was confirmed by examination with a sterile speculum to verify the pooling of amniotic fluid in the vagina.

Samples of vaginal and amniotic fluids were collected from posterior fornix and transabdominal. IL6 assessment was done in both fluids by lateral immunoassay.

The cut-off level to define Intra-amniotic inflammation for IL6 was ≥745 pg/mL.

Out of 153 women in the study, samples of vaginal fluid were obtained in 141 women. It was possible to predict the microbial invasion of the amniotic cavity, intra-amniotic inflammation or microbial-associated intra-amniotic inflammation by higher vaginal fluid interleukin-6 concentrations.

The levels of vaginal fluid IL-6 were higher than amniotic fluid IL-6 concentrations.

A IL6 level of ≥2500 pg/mL identified patients with MIAC, intra-amniotic inflammation, and microbial associated intra-amniotic inflammation. Levels of IL6 < 2500 pg/mL could 100 % exclude patients with microbial-associated intra-amniotic inflammation. These findings need future corroboration by larger studies and meta-analysis before a clinical recommendation is made.

This finding has very important clinical implications, because in future it can be used as triage, to decide the expectant vs active management of women with preterm PROM.

By using this easy, cheap, noninvasive and rapid method, women will be spared of the invasive procedure of amniocentesis to evaluate the intrauterine environment.

---

[1] http://www.aafp.org/afp/2006/0215/p659.html

[2] http://www.ncbi.nlm.nih.gov/pubmed/27120475

[3] http://www.ajog.org/article/S0002-9378(16)30439-2/abstract