Comprehensive human amniotic fluid metagenomics supports the sterile womb hypothesis.

As metagenomic approaches for detecting infectious agents have improved, each tissue that was once thought to be sterile has been found to harbor a variety of microorganisms. Controversy still exists over the status of amniotic fluid, which is part of an immunologically privileged zone that is required to prevent maternal immune system rejection of the fetus. Due to this privilege, the exclusion of microbes has been proposed to be mandatory, leading to the sterile womb hypothesis. Since nucleic acid yields from amniotic fluid are very low, contaminating nucleic acid found in water, reagents and the laboratory environment frequently confound attempts to address this hypothesis. Here we present metagenomic criteria for microorganism detection and a metagenomic method able to be performed with small volumes of starting material, while controlling for exogenous contamination, to circumvent these and other pitfalls. We use this method to show that human mid-gestational amniotic fluid has no detectable virome or microbiome, supporting the sterile womb hypothesis.

Steroid sulfatase deficiency and contiguous gene deletion syndrome amongst pregnant patients with low serum unconjugated estriols.

OBJECTIVE: To ascertain all prenatally diagnosed cases of Steroid Sulfatase (STS) deficiency in British Columbia between August 2002 and July 2007 to determine the incidence of this condition, the clinical and laboratory findings, and the risk of a contiguous gene deletion syndrome. METHODS: We reviewed the medical records of these patients to obtain detailed information about the maternal serum screening results, family history, investigations performed, and outcome of the pregnancy. RESULTS: Thirty pregnant patients were found to have a male fetus/infant with STS deficiency, giving a minimal estimated incidence of this condition of approximately 1 in 1513 males. In twenty nine cases, this condition was isolated. One patient was found to have a contiguous gene deletion syndrome. In cases of sporadic STS deficiency diagnosed prenatally, the frequency of contiguous gene deletion syndrome in this study was 1 out of 12 (8.3%). CONCLUSION: The clinical, cytogenetic and molecular data on this series of prenatally diagnosed cases of STS deficiency indicates that this is a common condition and in cases with no family history, the risk of contiguous gene deletion syndrome is significant, and warrants additional molecular genetic investigations of the mother and/or fetus.