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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 tissue^{331, 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 AF^416–419 (see also Chapter 34).

Studies have been made on the half‐life and distribution of several antibiotics, particularly cephalosporins, in fetal tissues.^{420, 421} Among others, cefazolin has been studied and in one case found to be absent from the fetus during the first trimester and present in fetal serum, urine, and AF in low concentrations during the second trimester. Cefazolin clearance from AF does increase during pregnancy, and is greater with polyhydramnios.⁴²² The authors formulated dosing regimens to achieve appropriate AF concentrations of the antibiotic.