activity of amniotic fluid
Although bacteria may occasionally be isolated from the AF of asymptomatic patients,385, 386 the rarity of infection following millions of amniocenteses during the second and third trimesters of pregnancy clearly suggests a protective mechanism against bacterial infection in AF. The implication was that AF has specific antibacterial activity. Some investigators have concluded that AF has some antibacterial activity,386, 387 whereas others maintain that it has none or that it actually provides a good culture medium.388, 389 A substance bactericidal for Bacillus subtilis was found in about 17 percent of AF samples in one study.390
Bacteriostatic effect
A number of studies have supported the original contention of antibacterial activity by demonstrating that AF contains a substance that suppresses or inhibits bacterial growth.391, 392 The first suggestion was lysozyme, an ubiquitous enzyme with lytic properties found in many tissues and secretions.393 Subsequent studies have suggested that zinc is an important component.312, 394 The antibacterial activity of zinc in AF seems to depend on a second, organic, component, which is heat stable and resists proteolytic digestion.261 AF contains a potent antimicrobial peptide (β‐defensin‐2), the concentration of which is increased in patients with microbial infection in the amniotic cavity.395 Phosphate seems to reverse the AF inhibitory activity, possibly by interfering with the organic component rather than with the inorganic zinc.261, 354 The antimicrobial effect and bacteriolytic activity of AF have been studied on several strains.223, 396 Both lysozyme and β‐lysin (a bactericidal substance) have been identified as early as the second trimester. Normal bacteriolytic activities have been found in pregnancies in which respiratory distress syndrome developed in the infants. On the other hand, lack of an antimicrobial effect of AF on anaerobic bacteria may be one reason for the high incidence of spontaneous abortions in those conditions. Several findings suggest that β2‐ microglobulin exhibits strong antibacterial activity and is upregulated in amniotic cells during bacterial infection.397
Other workershave concluded that AF inhibits Staphylococcus aureus throughout pregnancy, whereas clear inhibition of Escherichia coli and Streptococcus agalactiae appears during the third trimester.263 It is important to note the ineffectiveness of AF against group B streptococci, the frequently documented cases of congenital infections, and the early deleterious effects of Bacteroides fragilis, especially in the first trimester.398
The effect of AF on bacterial growth also has been stressed by Ismail et al.399 while Martius and Eschenbach400 reviewed the literature on bacteria as a cause of amnionitis associated with premature labor. Bacterial proteases and lipases could play a role in weakening fetal membranes and a genetic predisposition may have a role.
An inhibitory effect on HIV replication has been observed, and attributed at least in part to the cell‐free protein fraction of AF.401
Isolation of infectious agents
Charles and Edwards402 have isolated Bacteroides bivius, Eubacterium lentum, and Staphylococcus epidermidis from fluids obtained by amniocentesis after cervical cerclage during the second trimester. When performing prenatal diagnosis amniocentesis on patients who have had a cerclage in the preceding weeks, prophylactic antibiotic therapy may be indicated to prevent infectious complications. The isolation of Mycoplasma hominis and Ureaplasma urealyticum from AF during the second trimester has confirmed previous reports295 suggesting that contamination of AF may be responsible more often than expected for prematurity, fetal loss, and amnionitis.
Auger et al.229 demonstrated in vitro a stunted growth of Candida albicans in the presence of AF obtained during the second trimester. They suggested that the transferrin content is a factor in the growth‐inhibiting activity. There is a high incidence of C. albicans genital infection during pregnancy, and this should not be overlooked when CVS is used for prenatal diagnosis. Other studies by the same group383 revealed a specific fetal IgA response to C. albicans in AF, suggesting that this represents a more efficient defense than the maternally transmitted IgG.
The fetal origin of interferon has been suggested by Lebon et al.,403 who detected small quantities in AF obtained between the 16th and 20th weeks of pregnancy. The absence of interferon in maternal serum and its presence in AF under physiologic conditions suggest that interferon may play a regulatory role during fetal development and also may act as an antiviral agent.
The presence of specific IgM in fetal serum is not de facto evidence of fetal demise, nor is the recovery of rubella virus from placental tissue331, 404 evidence of fetal infection. However, an apparently unequivocal test for diagnosis of fetal rubella virus is provided by the polymerase chain reaction (PCR) (see also Chapter 34).405 Bosma et al.406 evaluated a reverse transcription‐nested PCR assay (RT‐PCR) for the diagnosis of congenitally acquired rubella in utero. The detection of rubella virus RNA by RT‐PCR and the culture of tissues for the identification of the rubella virus was successful but not in all tissues tested, including the AF and chorionic villus samples. In a study of preterm labor, interleukin‐6 (IL‐6) levels in AF were positively correlated with intra‐amniotic inflammation and fetal morbidity and mortality whether or not microbial 16S ribosomal DNA was also detected.407 Studies of bacterial 16S rRNA in meconium of preterm infants confirmed a relationship between amniotic inflammation, preterm delivery, and presence of rRNA from Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella.408
Pons and co‐workers409 identified a case of fetal varicella by AF viral culture and PCR analysis (see also Chapter 34). To evaluate the risk of embryofetopathy in maternal varicella occurring before 20 weeks of gestation, Dufour et al.410 studied 17 cases and noted no abnormality.
The discovery of rare or as yet unknown infectious organisms may be revealed in AF from women who experience intrauterine fetal demise. A novel bacterium was isolated411 and characterized from the AF of a woman who experienced intrauterine fetal demise in the second trimester of pregnancy. The bacterium was a slow‐growing, Gram‐negative anaerobic coccobacillus belonging to the genus Leptotrichia. The 1,493‐pb 16S ribosomal DNA sequence had only 96 percent homology with L. sanguinegens but L. amnionii is a distinct species and most closely related to L. sanguinegens.412
AF inhibits the growth of aerobic and anaerobic bacteria and fungi, but the antimicrobial factors increase toward term and are not very active during the second trimester.379 Furthermore, AF from patients with intra‐amniotic infection is significantly less inhibitory to E. coli.381 Cytomegalovirus can be isolated in culture from samples during the second trimester, and its presence is strongly indicative of a fetal infection.413 Tissue culture was suggested for the early prenatal diagnosis of toxoplasmosis.414 Haemophilus influenzae was ascertained as the cause of a post‐amniocentesis intra‐amniotic infection.415 Several real‐time and quantitative PCR assays are available to identify group B streptococci, cytomegalovirus, toxoplasma, herpes, and other infections in AF416–419 (see also Chapter 34).
Studies have been made on the half‐life and distribution of several antibiotics, particularly cephalosporins,
