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Intra-amniotic infection: diagnosis, nomenclature, clinical significance, management, and microbiologic tools used for the diagnosis.

SUMMARYIntra-amniotic infection is the main cause of spontaneous preterm birth and adverse maternal-fetal outcomes; therefore, rapid, robust, and accurate diagnosis remains a clinical priority. Conventional microbiological techniques, especially culture-based methods, are limited by long turnaround times and the inability to detect fastidious or unculturable organisms. This review summarizes the diagnosis, nomenclature, clinical significance, management, and laboratory approaches for diagnosing intra-amniotic infection. Targeted nucleic acid amplification methods, including species-specific polymerase chain reaction and broad-range 16S rRNA gene sequencing, have improved the detection of bacterial DNA and enabled the identification of organisms that evade routine culture in intra-amniotic infection. More recently, whole-genome sequencing and metagenomic next-generation sequencing have provided culture-independent strategies for comprehensive pathogen profiling, allowing simultaneous detection of bacteria, viruses, and fungi, as well as characterization of antimicrobial resistance determinants and virulence-associated genes. However, challenges remain, particularly in low-biomass samples such as amniotic fluid, where contamination, host DNA background, and data interpretation can compromise specificity. This review critically evaluates the advantages and limitations of each molecular modality and discusses pre-analytical, analytical, and bioinformatic considerations essential for reliable implementation. Integration of molecular diagnostics into clinical workflows holds promise for improving etiological diagnosis and guiding targeted therapy in intra-amniotic infection, thereby improving maternal and fetal outcomes.

Humans↗

Detection of intra-amniotic infection by gas-liquid chromatography.

The use of gas-liquid chromatography to detect short-chain organic acids in the amniotic fluid of patients with amnionitis has been previously described. Most of the studies describe patients in the early third trimester with such infections. The purpose of the current study was to confirm the correlation of infection with increased production of organic acids and to assess the effect of gestational age on the presence of these short-chain fatty acids in the amniotic fluid. Six patients with confirmed chorioamnionitis were used as positive control subjects. Seventy-two patients at various gestational ages from 18 to 42 weeks with negative Gram's stain and culture results from the amniotic fluid were used as negative control subjects. The data revealed an increased production of organic acids, particularly pyruvic, oxalic and succinic, in patients with amnionitis regardless of gestational age. Interestingly, patients with noninfected amniotic fluid also revealed an increase in the concentrations of volatile organic acids between 27 and 32 weeks' gestation. It appears from this study that previous results correlating chorioamnionitis with an increased production of organic acids in the amniotic fluid may have been confounded by gestational age.

Amniotic Fluid↗

[The significance of prostaglandin F2 alpha (PGFM)--and plasma oxytocin level in patients with premature labor].

In the present study, plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) concentrations were measured in 46 patients admitted for preterm labour. Gestational age ranged from 20-34 weeks. Samples were collected 12 hours before and after initiation of tocolysis. Patients with a premature rupture of the membranes and/or intra-amniotic infection were excluded in this study. There was a significant difference in the oxytocin (p = 0.05) and PGFM levels (p = 0.007, after 12 hours: p = 0.004) between a control group without preterm labour and women with preterm labour. No differences were seen between the successfully treated (delivery more than 5 days after start of tocolysis) and the failure group. There was no significantly different increase or decrease in PGFM and Oxytocin plasma levels between treatment failures and successfully treated patients.

Birth Weight↗

Comparison of the virulence of two isolates of porcine parvovirus in 72-day-old porcine fetuses.

Two strains of porcine parvovirus (PPV), designated Kresse and NADL-8, were compared for relative virulence in porcine fetuses. Strain Kresse was injected into the amniotic fluid of all fetuses of 1 uterine horn of each of 2 pregnant gilts at 72 days of gestation. Strain NADL-8 was administered similarly to fetuses of 4 other gilts at the same stage of gestation. All gilts were killed and necropsied 35 days later. Selected tissues of all fetuses were tested for infectious virus and viral antigen. Sera from live fetuses were tested for antibody to PPV. These tests confirmed that most fetuses exposed to PPV by intra-amniotic injection became infected. All of 11 fetuses exposed to strain Kresse by intra-amniotic injection were alive at the time of necropsy, and all appeared clinically normal. In contrast, 8 of 24 fetuses exposed similarly to strain NADL-8 were dead. Many of the fetuses from the uterine horns contralateral to the uterine horns inoculated with virus were infected after 72 days of gestational age by intrauterine spread of the virus. Four such fetuses, 3 infected with the NADL-8 strain and 1 infected with the Kresse strain, were dead at the time of necropsy. These findings were inconsistent with those of a previous report, which indicated that the Kresse strain of PPV was markedly more virulent than the NADL-8 strain of PPV for porcine fetuses. A possible reason for this apparent discrepancy is discussed.

Animals↗

Extraovular prostaglandin F2alpha for early midtrimester abortion.

Twenty patients who were 13 to 15 weeks pregnant received extraovular prostaglandin F2-alpha (PGF2a) in dosages of 3 mg. every 1 to 3 hours. Ninety-five per cent of the patients successfully aborted and 30 per cent of the patients had retained placental tissue. The mean abortion time was 17 3/4 hours and the average total dose used was 29.2 mg. The abortion time appeared to decrease with parity and had no relationship to weeks of gestation. Only one patient failed to abort after 31 hours of therapy. She required a curettage and was the only patient to develop a postabortion infection. The technique appears to compare favorably with the results of intra-amniotic PGF2a. Extraovular prostaglandin may therefore be of particular value in inducing abortion in patients who are in the early midtrimester of pregnancy, i.e., when intra-amniotic instillation is technically infeasible.

Abortion, Induced↗

Laminaria use in midtrimester abortions induced by intra-amniotic prostaglandin F2alpha with urea and intravenous oxytocin.

A laminaria tent was used as an adjunct during midtrimester abortion to attempt to shorten the injection-abortion interval without adversely affecting the frequency of infection, hemorrhage, failed abortion, or cervical laceration. Eighty patients, between 14 and 20 weeks' gestation and desiring pregnancy termination, were randomized into three groups. Abortion was initiated by an intra-amniotic infusion of 20 mg of prostaglandin F2alpha and 80 gm of hyperosmolar urea in Ringer's lactate (135 ml total volume), followed by oxytocin infused intravenously at 333 mU/min. Group I (N = 28) received no additional therapy; Group II (N = 23) had laminaria placed at the time of the abortifacient injection and removed 4 hours later; Group III (N = 29) had laminaria placed 4 hours prior to inejction and removed at the time of injection. The injection-abortion intervals in these three groups were 17.76, 20.80, and 12.96 hours, respectively. This study illustrates that a laminaria tent palced 4 hours prior to injection is significantly more effective than a laminaria tent placed at the time of injection, and produces a shorter mean injection-abortion interval than that in patients receiving no laminaria. Furthermore, laminaria augmentation results in no demonstrable increase in the frequency of serious complications.

Abortifacient Agents↗

Intrauterine extra-amniotic 15(s)-15-methyl prostaglandin f2 alpha for induction of early midtrimester abortion.

Twenty-six patients 13 to 15 weeks pregnant received extraovular 15(S)-15-methyl prostaglandin F2 alpha in a dosage of 1 mg every 18 to 24 hours for three doses. Twenty-five (96%) of the patients aborted; fifteen patients aborted incompletely. The mean induction-to-abortion time was 15.8 hours. A decrease in plasma progesterone levels could not be consistently correlated with abortifacient activity, and there was no statistically significant relationship between abortion time and parity or gestational age. One patient failed to abort after 36 hours of therapy and was aborted by curettage. She was the only patient who developed a postabortion uterine infection. Results with the extraovular technique appear to be similar to those with the intra-amniotic and the intramuscular prostaglandin techniques. Therefore, extraovular administration may be useful for inducing abortion in patients who are in the early midtrimester of pregnancy.

Abortion, Induced↗

Experimental group B streptococcal infection in the rhesus monkey. I. Disease production in the neonate.

Group B streptococci (GBS) are responsible for serious infections of newborn infants. An experimental model for GBS infection was developed in the newborn rhesus monkey in order to obtain more information concerning the pathogenesis of such infections. A series of 29 newborn monkeys were inoculated with either type Ic or type III GBS or sterile broth. Fatal neonatal meningitis without associated pneumonia was produced consistently following intracerebral inoculation with either type Ic or type III; intracerebral inoculation with sterile broth produced no apparent disease. Variable disease production followed intravenous or intra-amniotic GBS inoculation, and clinical manifestations ranged from no apparent disease to fatal meningitis and pneumonia. This monkey model may be useful for further investigation of treatment and prevention of neonatal GBS infection.

Animals↗

Intra-amniotic prostaglandin F2alpha and urea for midtrimester abortion.

Intra-amniotic prostaglandin F2alpha, in doses of 2.5 to 20 mg, combined with 80 gm of urea, was an effective, safe, simple, and economical midtrimester abortifacient in 115 patients. The mean abortal time, 15.8 hours, was significantly less than that in prior series in which intra-amniotic hypertonic saline or urea was administered together with constant, intravenous oxytocin infusion. The use of intracervical laminaria tents did not shorten the abortal time. Only eight patients had not aborted within 30 hours; only two had not aborted within 36 hours; and only six received a second intra-amniotic injection. Operative removal of the placenta, when necessary, was accomplished under intravenous sedation in a treatment room. The incidence of infection, nausea, vomiting, and other complications was low.

Abortion, Induced↗

Therapeutic midtrimester abortion by the intra-uterine administration of prostaglandins. Experience of Groote Schuur Hospital, 1974-1975.

During the period from 1 January 1974 to 31 December 1975, 71 therapeutic midtrimester abortions were performed at Groote Schuur Hospital by the intra-uterine administration of prostaglandins. Both the extra- and intra-amniotic routes of administration proved to be uniformly successful but the latter route was associated with fewer side-effects. The intra-amniotic administration of 30 mg prostaglandin F2alpha in combination with 60 g urea is the recommended method for achieving midtrimester abortion. If the method described is strictly adhered to, it provides a single-dose regimen which is uniformly successful and which is associated with few complications.

Abortion, Therapeutic↗

The efficacy of intramuscular 15 methyl prostaglandin E2 in second-trimester abortion. Coagulation and hormonal aspects.

Termination of pregnancy in the second trimester is sometimes associated with serious complications. This led to clinical investigation seeking methods superior to the traditional technique utilizing hypertonic saline. Intra-amniotic administration of naturally occurring prostaglandin F2-alpha has been developed and appears to be advantageous--especially in the area of coagulation stability. This study describes a technique for intramuscular administration of a prostaglandin analogue--15 methyl prostaglandin E2. This analogue is much more potent than the natural compound. Administration to 32 patients resulted in abortion in 28. The coagulation milieu remained completely intact and all other parameters were similar to previous published data for prostaglandin administration. There were no infections in this group of patients.

Abortifacient Agents↗

Prenatal immunization against experimental enteric colibacillosis in piglets.

To establish a model for the study of prenatal immunization against enteric colibacillosis a proportion of the litters of seven sows were immunized in utero 18 to 22 days before term by intra-amniotic and intramuscular injection of Escherichia coli antigen and the litters challenged at birth with either homologous or heterologous strains. Protection against homologous challenge was demonstrated in some but not all vaccinated piglets. The study was severely compromised by the occurrence of intrauterine death in a significant proportion of vaccinated piglets.

Amnion↗

Intra-amniotic urea and prostaglandin F2 alpha for midtrimester abortion: a modified regimen.

A study comparing intra-amniotic urea plus intravenous oxytocin and intra-amniotic urea with 10 mg. prostaglandin F2 alpha was completed. In addition, the results obtained with a further 150 patients receiving urea and prostaglandin are reported. Mean injection-abortion intervals ranged from 15.75 hours for urea-prostaglandin to 18.93 hours for urea-oxytocin. The advantages of urea-prostaglandin and suggested improvements are discussed. Over all, the method appears efficacious though incomplete abortions and cervical laceration are persistent problems.

Abortion, Induced↗

Intra-amniotic urea and prostaglandin F2alpha for midtrimester abortion: clinical and laboratory evaluation.

The clinical management of the elective midtrimester abortion continues to be unsatisfactory as judged by either national mortality or morbidity rates. This report documents the results of a randomized series of 19 midtrimester abortions induced by either intra-amniotic hyperosmolar urea and 5 mg. of prostaglandin F2alpha (PGF2alpha) or intra-amniotic hyperosmolar urea alone. Pertinent clinical characteristics and biochemical determinations were compared between these two groups. A series of 150 patients were then treated with urea and 5 mg. of PGF2alpha. The clinical results of this series of patients are presented and compared with a previous group who had urea and 10 mg. of PGF2alpha. These studies demonstrate that 5 mg. of PGF2alpha with 80 Gm. of urea achieves injection-abortion intervals that are less than 24 hours.

Abortion, Induced↗

The current status of prostaglandins as abortifacients.

The present use and potential uses of prostaglandins as abortifacients are summarized. Pertinent history, chemistry, prostaglandins' possible role in physiologic and pathologic processes and pharmacologic actions are discussed. The results of natural prostaglandins and their analogues by systemic and intrauterine administration for the purposes of postcoital contraception, menstrual regulation, first- and second-trimester abortion, preoperative dilation of the cervix, and delivery of patients with death in utero are presented. The only approved method of induction of abortion with prostaglandins, prostaglandin F2alpha by the intra-amniotic route for the induction of midtrimester abortion, is evaluated and compared to other methods of midtrimester abortion. It was concluded that: (1) the present use of prostaglandins is an important addition to the obstetrician's armamentarium, (2) more effective and/or convenient methods that are useful in patients over a wider gestational age appear to have been defined, and (3) the routine use of prostaglandins for postcoital contraception, menstrual regulation, and first-trimester abortion will require the development of analogues that are more specific as to their abortifacient actions than the natural prostaglandins and/or the development of improved delivery systems.

Abortifacient Agents↗

Intra-amniotic urea as a midtrimester abortifacient: clinical results and serum and urinary changes.

Seventy-four patients, from 16 to 20 weeks pregnant, received intra-amniotic urea (80 Gm.) and intravenous oxytocin for the purpose of inducing abortion. Seventy-one of the 74 patients were successfully aborted by the primary method with a mean injection-to-abortion interval of 18.33 hours. There were no serious side effects, and the mean hospital stay was 32 hours. Following urea injection, the mean serum urea nitrogen rose to 33 mg. per cent at 4 hours. Maximum changes in serum electrolytes occurred at 8 to 12 hours after injection and included a decrease in the mean concentrations of sodium, chloride, and carbon dioxide and an increase in serum potassium. An increase in the urinary excretion of urea began within 4 hours, but significant diuresis did not occur in the presence of intravenous oxytocin administration. There was a significant increase in the leukocyte concentration while hematocrit values remained unchanged. Beginning approximately 8 hours following urea injection, the mean plasma fibinogen concentrations decreased by approximately 15 per cent and the mean platelet count showed a drop of approximately 18 per cent. Fibrinogen-fibrin degradation products were significantly increased in 36 per cent of the patients studied.

Abortifacient Agents↗