Preterm birth risk linked to diversity of microbes in amniotic fluid

Preterm birth risk linked to diversity of microbes in amniotic fluid

US researchers have discovered a significant link between the number and range of bacteria or fungi in a mother's amniotic fluid and the degree to which her baby is born premature and sick.

Scientists at Stanford University Medical School in California, and colleagues from other establishments, published their findings in the 26th August issue of the open access online journal PLoS One.

About 12 per cent of all births in the US are premature and the figure is going up, wrote the researchers, who were led by research associate Dr Dan DiGiulio, in the lab of senior author Dr David Relman. They found that previously unrecognized and unidentified infections of amniotic fluid may account for a significant number of these births:

"If we could prevent these infections in the first place, or detect them sooner, we might one day be able to prevent some of these premature births," said DiGiulio.

DiGiulio and Relman worked with colleagues at Wayne State University in Detroit, the Detroit Medical Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development and analyzed amniotic fluid from women in preterm labour. They found that 15 per cent of the fluid samples contained bacteria and fungi. This figure is considerably more than the amount given in previous estimates.

The researchers also found that the more diverse the range of microbes (the "burden" of potentially infectious agents), the more likely the women were to give birth earlier and also to have sicker babies.

Relman, who is professor of infectious disease and also of microbiology and immunology at Stanford University Medical School, said they were shocked to find that:

"This amniotic compartment, which we have traditionally viewed as somewhat sacrosanct, is infected significantly more often than we thought."

Previous studies using a more conventional sampling method had estimated the infection rate at around 10 per cent.

For the study DiGiulio and colleagues examined the amniotic fluid of 166 women who went into preterm labour at the Detroit Medical Center between October 1998 and December 2002. 113 of the women actually went on to have preterm babies.

They used a modern technique called PCR, short for polymerase chain reaction, which is more sensitive than the conventional method to detect microbes like bacteria, fungi and other living organisms, which relied on taking a sample of amniotic fluid with a needle inserted into the amniotic cavity and then culturing and growing them in the lab. But this rather "rough" technique did not pick up the full range of microbes in the samples.

DiGiulio said scientists have become very good at cultivating some of the "weeds" of the microbial world but many species of micro-organisms don't respond to culturing. PCR uses scraps of DNA that encode portions of ribosomal RNA (rRNA) to detect the full range of individual species present, including those that don't respond to being cultured.

By using a mix of PCR and lab cultures, they estimated around 25 per cent of the 166 samples taken from the women who went into premature labour were infected with bacteria or fungi. The total range of micro-organisms they found spanned 17 different bacteria and one fungal species, considerably more than the 11 found by conventional means. These included some known species that scientists did not realize played a role in preterm delivery and one completely new one not seen before.

DiGiulio and Relman also discovered that:

  • All the women whose samples were positive by either PCR or by culture had their babies prematurely.
  • All those who were positive by both methods had their babies within one day of the initial fluid collection.
  • 68 percent of those that were positive by only one, but not the other, method delivered within the same time period.
  • 27 percent of samples from infected women who delivered their infants before 25 weeks gestation were positive only by PCR.
  • What was interesting was that using the culture method alone, failed to show that these samples were infected.
This last statistic is important because only 30 per cent of preterm babies in this age group (born before 25 weeks of gestation) survive. The scientists said it was very important to be able to diagnose infection accurately in these women.

DiGiulio and colleagues also found that the babies arrived earlier when the burden of infection increased. Thus the greater the number and range of bacteria and fungi, as detected by rRNA, in the amniotic fluid sample, the more likely the mother was to be delivered of a very young and very sick baby.

Speculating on their results, the researchers suggested that infected amniotic fluid may contribute to preterm birth because it triggers an inflammatory response in the pregnant mother. The microbes either travel from the vagina into the amniotic sac, or get into the mother's bloodstream from other parts of the body like the mouth. Other studies have linked gum disease and bacterial vaginosis to increased risk of early delivery.

"Microbial Prevalence, Diversity and Abundance in Amniotic Fluid During Preterm Labor: A Molecular and Culture-Based Investigation."

DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, et al.

PLoS ONE 3(8), 26 August 2008, e3056.


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Sources: Journal Article.

Preterm labor | Reproductive system physiology | NCLEX-RN | Khan Academy (Video Medical And Professional 2020).

Section Issues On Medicine: Women health