The Role of Ureaplasma urealytkum in Adverse Pregnancy Outcome

EDITORIAL COMMENT: We accepted this paper for publication because it gives important information about the frequency of colonization of the lower and upper genital tract of pregnant women with Ureaplasma urealyticum. Although the authors discuss adverse pregnancy outcome they did not mention perinatal mortality or morbidity due to infection with Ureaplasma urealyticum although they note that there were 4 of the 16 preterm deliveries where there was evidence of chorioamnionitis. We have previously published a paper from the Toowoomba Base Hospital group on Ureaplasma urealyticum chorioamnionitis associated with 2 perinatal deaths and 1 case of severe chorioamnionitis where the infant survived (A). We refer readers to the Editorial Comment that accompanied this paper.
Summary: We investigated Ureaplasma urealyticum genital tract colonization rates in an Australian population to determine whether colonization was associated with adverse pregnancy outcome. Women attending an antenatal clinic were evaluated for lower genital tract colonization at their first antenatal visit (162 women) and at 28 weeks' gestation (120 women). Placentas from 92 women were cultured. U. urealyticum was the predominant isolate from the lower (57.4%) and upper (17.4%) genital tract in this population of pregnant women. U. urealyticum was a persistent colonizer during mid-trimester of pregnancy (in 88% of women colonized) whereas M. hominis, G. vaginalis, and Group B streptococcus were present as transient flora of the lower genital tract. Lower genital tract colonization during pregnancy was not directly associated with adverse pregnancy outcome. However preterm delivery in afebrile, asymptomatic women, could possibly be associated with chorioamnionitis (4 of 16 preterm births). Screening of women with a history of preterm birth may prevent upper genital tract infections and preterm delivery.     

High-density vaginal Ureaplasma urealyticum colonization as a risk factor for chorioamnionitis and preterm delivery

BACKGROUND: The aim of this case control study was to investigate the influence of genital Ureaplasma urealyticum colonization on pregnancy outcome. METHODS: One hundred and seventy-two women colonized with Ureaplasma urealyticum without co-existing other infections and 123 women with negative cultures for Ureaplasma urealyticum were enrolled. In a multivariate analysis the influence of quantitative Ureaplasma urealyticum colonization level was determined. RESULTS: Compared to the negative women increasing colonization with Ureaplasma urealyticum was associated with a significant decrease of birth weight (p<0.0001) and gestational age (p<0.0001) and with a significant increase of chorioamnionitis (p<0.0001) and preterm delivery (p<0.001). In a multivariate analysis high-density Ureaplasma urealyticum colonization was an independent risk factor for chorioamnionitis and preterm delivery, whereas low colonization levels had no effect on an adverse outcome of pregnancy. CONCLUSIONS: The degree of colonization with Ureaplasma urealyticum correlates strongly with an adverse effect on pregnancy outcome.     

First trimester chorionic villus sampling versus mid-trimester genetic amniocentesis--preliminary results of a controlled prospective trial

This controlled prospective study assesses the relative risks of first trimester chorionic villus sampling (CVS) versus mid-trimester gentic amniocentesis (GA). CVS subjects and amniocentesis controls were comparable with regard to several confounding variables which might influence the risk of pregnancy loss including maternal age, smoking, alcohol consumption, gestational age at study entry, and history of vaginal bleeding or poor prior reproductive outcome. The most common indication for prenatal diagnosis was advanced maternal age (n = 511). In this subgroup, spontaneous abortion (less than 24 weeks) occurred in 2.9 per cent of CVS subjects versus 4.3 per cent of amniocentesis controls. The sum of spontaneous and therapeutic abortions (less than 24 weeks) was identical (5.3 per cent) in both groups. Therefore, intervention in the CVS group (i.e., therapeutic abortion for cytogenetic abnormalities) did not influence the observed risk of pregnancy loss. Overall perinatal mortality rates were also similar in both groups. No significant differences were identified for a number of pregnancy outcome parameters including 5 min Apgar score, birth weight, body length, head circumference, gestational age at delivery, preterm delivery, fetal growth retardation, congenital malformations, and neonatal complications. Preliminary results of this controlled prospective study suggest that chorionic villus sampling carries a low and acceptable risk.     

Spontaneous abortion after amniocentesis in women with a history of spontaneous abortion

The incidence of spontaneous abortion after amniocentesis (19 to 28 weeks gestation) in women who have had previous spontaneous abortions is compared with the rate in women who have not had previous spontaneous abortions. The outcome of the pregnancy after amniocentesis and the previous history of spontaneous abortion is reported for 691 pregnancies. The rate of spontaneous abortion after amniocentesis was found to be significantly higher in women who had one or more previous spontaneous abortions, 12/238 (5 per cent), than in women who did not, 6/453 (1.3 per cent). In women who reported two or more previous spontaneous abortions, the rate was 7/81 (8.6 per cent). No statistically significant effect of maternal age or gravidity was detected. The incidence of spontaneous abortion after amniocentesis was greater in the three weeks following the procedure (three for each of the three weeks) than in the subsequent seven weeks (nine for seven weeks).     

Eradication of Ureaplasma urealyticum from the amniotic fluid with transplacental antibiotic treatment.

Ureaplasma urealyticum was isolated from the amniotic fluid of a patient with preterm premature rupture of membranes at 24 weeks. A second amniocentesis performed 48 hours later indicated an increase in the number of neutrophils in the amniotic fluid. Treatment with erythromycin, ampicillin, gentamicin, and clindamycin was instituted for a period of 6 days. Amniotic fluid analysis from a third amniocentesis performed 24 hours after discontinuation of antibiotic treatment revealed only a few white blood cells and was negative for microorganisms. The pregnancy continued for 22 days after admission, at which time spontaneous labor began. The neonate survived with no sequelae and had negative blood cultures. Antibiotic treatment was associated with eradication of Ureaplasma urealyticum from the amniotic cavity, pregnancy prolongation, and neonatal survival.     

Clinically silent polymicrobial amnionitis and intrauterine fetal death associated with a Cu-7 intrauterine contraceptive device

This article presents a case of silent polymicrobial amnionitis with subsequent intrauterine fetal death in a 34-year old woman who conceived with a Cu-7 IUD in place. There were no apparent pregnancy complications or symptoms of uterine infection during early pregnancy. At 16 weeks gestation, the patient underwent amniocentesis for cytogenetic studies. 5 different microorganisms--Corynebacterium, Staphylococcus warneri, Staphylococcus epidermidis, Streptococcus mitis, and Ureaplasma urealyticum--were isolated from the amniotic fluid. 2 week later, intrauterine fetal death was detected. U. urealyticum was at this point isolated from the cervix and placental and fetal tissues. This organism, which has been associated with chorioamnionitis, spontaneous abortion, and neonatal death, is suspected to have contributed to the fetal death in this case. U. urealyticum can invade the amniotic sac with fetal membranes intact and persist for 8 weeks without overt effects. This case illustrates the risks associated with nonremoval of an IUD after contraceptive failure.     

Postpartum bacteremia and placental colonization with genital mycoplasmas and pregnancy outcome

The influence of placental colonization and postpartum bacteremia with genital mycoplasmas on the course of delivery and the immediate postpartum period was evaluated in 511 women who gave birth to live infants of at least 26 weeks' gestation. Genital mycoplasmas were isolated from the placenta in 153 patients (29.9%) and from blood in four patients (0.8%). These four isolates were all Ureaplasma urealyticum. Patients with genital mycoplasmas isolated from the placenta were delivered of infants with birth weights and gestational ages similar to those of infants of patients who did not have genital mycoplasmas in the placenta (3260 gm and 39.2 weeks versus 3272 gm and 39.3 weeks). No adverse effects of maternal postpartum bacteremia with genital mycoplasmas were observed, either in the mother or in the baby. We conclude that, whereas genital mycoplasmas frequently can be isolated from the placenta, there is no evident relationship between the presence of genital mycoplasmas and pregnancy outcome. In a few instances U. urealyticum has been isolated from the blood of afebrile postpartum women. In these women the presence of this bacteria is probably related to the birth process. This bacteremia does not precede an infectious complication.     

Genital mycoplasmas and birth weight in offspring of primigravid women.

The relationship between colonization of pregnant women by Ureaplasma and Mycoplasma and the outcome of pregnancy in a study of 104 women is reported. There were eight abortions but no multiple births or stillbirths. Excluding abortions, the mean gestational length was 39.6 weeks and the corrected mean birth weight was 3.28 kilograms. There was no relationship between maternal colonization by genital mycoplasmas and reduction in birth weight of the offspring, but five of the eight women who aborted harbored Ureaplasma, suggesting an increased trend toward abortion in women harboring Ureaplasma.     

Genital mycoplasma colonization in neonatal girls

Specimens obtained from the genital tract of 90 pairs of mothers and their female infants were cultured for Ureaplasma urealyticum (Ureaplasma) and Mycoplasma hominis (M.hominis). Ureaplasma and M.hominis were isolated from 80% and 17% of pregnant women, and 41% and 4.4% of female infants, respectively. Fifty nine per cent of infants were positive for Ureaplasma when they were borne per vaginam by Ureaplasma-positive mothers. However, Ureaplasma was not isolated from any of 11 infants delivered by cesarean section before rupture of the fetal membranes, in spite of positive colonization by Ureaplasma in the mothers. Quantitation of Ureaplasma revealed that neonatal colonization was closely associated with the colonization number of this microorganism in the cervical canal of mothers. Prolonged interval between rupture of fetal membranes and delivery caused a slightly increased frequency of isolation of this organism, but it was less significant. A study of mean birth weight revealed that there was no correlation between maternal or neonatal colonization by Ureaplasma and low birth weight.     

A randomized placebo-controlled trial of erythromycin for the treatment of Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and Prematurity Study Group

Ureaplasma urealyticum has been associated with low birth weight and histologic chorioamnionitis and it is a frequent isolate from the chorioamnion of patients who are delivered prematurely. In prior clinical trials using antibiotics active against U. urealyticum, antibiotic treatment was associated with reduced prematurity and increased mean birth weight. In this multicenter, randomized, double-blind clinical trial, pregnant women with U. urealyticum were treated with 333 mg of erythromycin base or placebo three times daily, starting between 26 and 30 weeks' gestation and continuing through 35 completed weeks of pregnancy. Women with urinary tract infection or Neisseria gonorrhoeae infection were excluded from the trial, and women with Chlamydia trachomatis or group B streptococci were excluded from these analyses. Erythromycin did not eliminate U. urealyticum from the lower genital tract. There were no significant differences between erythromycin- and placebo-treated women in infant birth weight or gestational age at delivery, in frequency of premature rupture of membranes, or in neonatal outcome.     

Outcome of subsequent pregnancies following antibiotic therapy after primary or multiple spontaneous abortions

The course of the subsequent pregnancy and the maternal and fetal complications were evaluated in 254 couples who were seen in an infertility clinic after primary or multiple spontaneous abortions. The 100 couples who were treated with antibiotics after pregnancy loss showed a significantly better chance of achieving a subsequent pregnancy. The outcome of pregnancy was significantly better in the antibiotic treated group and the rate of spontaneous abortion recurrence was significantly lower (10 versus 38 per cent). The number of maternal complications was significantly less in the treated group--premature rupture of membranes, three (4 per cent) versus 30 (46 per cent), and postpartum fever, three (4 per cent) versus 23 (35 per cent), respectively. The untreated group experienced a significantly lower percentage of vaginal delivery (56 versus 69 per cent) (p less than 0.001). In the antibiotic treated group, there were significantly lower rates of fetal complications, including fetal distress, meconium, respiratory distress syndrome, neonatal infection and hyperbilirubinemia. The mean birth weight of infants in the antibiotic treated group was significantly higher (3,529 versus 3,090 grams; p less than 0.001). Prematurity and postdatism were significantly less frequent in the antibiotic treated group, and the corresponding Apgar scores were significantly better. We, thus, postulate that certain spontaneous abortions may be caused by bacteria present in the genital tract at the time of conception. These bacteria may have an adverse effect on the course of pregnancy and result in increased maternal and fetal complications.     

Genetic amniocentesis at 7-14 weeks of gestation.

Genetic amniocentesis performed at 7-14 weeks of gestation was studied in a series of 138 patients of whom 50 wanted termination of pregnancy (less than or equal to 12 weeks). The material for analysis consisted of 132 samples due to two sampling failures and four samples being handled incorrectly. Forty-eight samples (36 per cent) were taken at 7-12 weeks of gestation, mainly transvaginally (36/48: 75 per cent). The success rate of culture and karyotyping increased with the duration of pregnancy, but was only satisfactory from week 11 onwards. The time until harvest was then 14-15 days. The transvaginal approach is easy to perform and was accepted by the women, but we experienced bacterial or fungal overgrowth in 17 per cent of these samples, whereas no infection occurred in the samples taken transabdominally (n = 96). We conclude that genetic amniocentesis is feasible from week 11, but further studies concerning side effects, especially focusing on the procedure-related abortion risk, should be carried out before early amniocentesis is routinely applied.     

Prenatal diagnosis in multiple gestation: 20 years' experience with amniocentesis

Three hundred and thirty-nine cases of multiple gestation underwent prenatal diagnosis by amniocentesis. The spontaneous abortion rate (to 28 weeks) in this group was 3.57 per cent compared with our singleton abortion rate of 0.60 per cent. The perinatal mortality rate (PMR) and prematurity rate were not different from the singletons, and compared favourably with the PMR reported in the literature for multiple gestations which did not undergo any intervention during pregnancy. This increased abortion rate following amniocentesis may only represent the increased natural loss rate in multiple gestations, and not indicate any increased risk added by the procedure.     

Antepartum cultures for Ureaplasma urealyticum are not useful in predicting pregnancy outcome. The Vaginal Infections and Prematurity Study Group

To test the hypothesis that genital colonization with Ureaplasma urealyticum would predict adverse pregnancy outcome, 4934 women from five medical centers were evaluated for vaginal colonization with U. urealyticum between 23 and 26 weeks' gestation and followed up to delivery. U. urealyticum colonization was associated with maternal age, parity, racial-ethnic group, martial status, income, education, smoking, number of sexual partners, and colonization with Trichomonas vaginalis, Mycoplasma hominis, and bacterial vaginosis. After adjustment for medical and sociodemographic factors in a multivariate analysis, there was no difference in the mean birth weight or proportion of low-birth-weight infants delivered by women who carried U. urealyticum and those who did not. U. urealyticum colonization at 23 to 26 weeks was not associated with preterm rupture of membranes, preterm labor, or preterm delivery. A positive vaginal culture for U. urealyticum in midgestation does not predict those women at risk for preterm labor, preterm delivery, preterm premature rupture of membranes, or delivery of a low-birth-weight infant.     

Chronic Ureaplasma urealyticum amnionitis associated with abruptio placentae

Ureaplasma urealyticum is a common inhabitant of the lower genital tract of women. It is unclear whether or not the microorganism plays a role in provoking spontaneous abortion. Reported is a U urealyticum infection of placenta and amniotic fluid in an immunologically competent host resulting in abruptio placentae and spontaneous abortion during the second trimester of pregnancy. U urealyticum was isolated from peripheral maternal blood twice. Immunologic alterations, namely a transiently reversed OKT4/OKT8 rate and a decrease in immunoglobulin G levels, were detected in the patient. U urealyticum must be considered as a pathogen able to interfere with normal fetal development.     

Biovar diversity of Ureaplasma urealyticum in amniotic fluid: distribution,intrauterine inflammatory response and pregnancy outcomes

OBJECTIVE: The objective of this study was to determine the distribution of two biovars of Ureaplasma urealyticum (parvo and T960) in human amniotic fluid and to examine whether the magnitude of the intrauterine inflammatory response and pregnancy outcomes are different between patients with microbial invasion of the amniotic cavity with "parvo biovar" and those with "T960 biovar". STUDY DESIGN: This cohort included 77 preterm singleton pregnancies (gestational age < 37 weeks) in whom U. urealyticum was detected from amniotic fluid using the polymerase chain reaction (PCR). Amniotic fluid was obtained by transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. U. urealyticum was biotyped by PCR methods. Amniotic fluid inflammatory response was determined by amniotic fluid white blood cell count and interleukin-6 concentration. RESULTS: 1) The "parvo biovar" was detected in 82% (63/77) and "T960 biovar" was in 18% (14/77) of cases; 2) U. urealyticum was isolated by conventional culture method from amniotic fluid in 56% (35/63) of cases with positive for "parvo biovar" and in 50% (7/14) of cases with positive for "T960 biovar"; 3) There were no significant differences in the median gestational age at amniocentesis, gestational age at delivery, birth weight, amniotic fluid white blood cell count, amniotic fluid interleukin-6 concentration and the rates of clinical chorioamnionitis, histologic chorioamnionitis, funisitis and neonatal morbidity between patients in the two biovar groups. CONCLUSIONS: 1) The "parvo biovar" is more frequently isolated from amniotic fluid of preterm gestations than the "T960 biovar"; 2) Biovar diversity of U. urealyticum in amniotic fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.     

Pregnancy outcome and nuchal translucency measurements in fetuses with a normal karyotype

The aim of this study was to examine the relationship between nuchal translucency thickness and pregnancy and fetal outcome in fetuses with a normal karyotype and without structural malformations. Fetal nuchal translucency measurements were performed in 2088 chromosomally and structurally normal fetuses. In all fetuses the karyotype and pregnancy outcome were known. Likelihood ratios for different outcome measures were calculated. Spontaneous abortion, intra-uterine and neonatal death occurred in 2.4, 1.1 and 0.5 per cent respectively. The incidence of immature delivery was 1.1 per cent and of premature delivery 6.0 per cent. The only adverse pregnancy outcome recorded that was associated with increased nuchal translucency was spontaneous abortion. The likelihood ratio for the occurrence of a spontaneous abortion was 3.1 for measurements between 3.0 and 3.9 mm, and 6.8 for measurements>/=4 mm. Increased lethality in fetuses with enlarged nuchal translucency and normal chromosomes may provide evidence that the same insult causing excessive fluid collection in the nuchal region may also be responsible for fetal demise.     

Elevated concentrations of interleukin-6 in intra-amniotic infection with Ureaplasma urealyticum in asymptomatic women during genetic amniocentesis.

BACKGROUND: Intra-amniotic infection is an important cause of preterm delivery and interleukin-6 (IL-6) determination was recently applied for identification of microbial invasion of the amniotic cavity. Our aim was to determine the levels of IL-6 in culture-positive amniotic fluids at genetic amniocentesis and to evaluate their significance in relation to pregnancy outcome. METHODS: Seven culture-positive and 23 culture-negative amniotic fluids, obtained at 17-19 weeks of gestation, were analyzed for IL-6 levels by an immunoassay (ELISA). Pregnancy outcomes of all 30 women were obtained from the medical charts. RESULTS: The mean level of IL-6 in the culture-negative amniotic fluids was 78+/-206 pg/ml. Among the seven culture-positive, high levels of IL-6 were found only in three amniotic fluids that were culture-positive for Ureaplasma urealyticum (1834, 1342 and 2832 pg/ml). Low levels of IL-6, ranging from zero to 60 pg/ml, were found in four AFs that were culture-positive for Staphylococcus epidermidis (n=3) and Bacillus Gram-positive (n= 1). Adverse pregnancy outcome occurred in the three women who had intra-amniotic infection with U. urealyticum accompanied by high levels of IL-6 (two fetal loss and one preterm delivery at 28 weeks of gestation). The four women with culture-positive but IL-6 negative amniotic fluids, had normal pregnancy outcome and term delivery. Two of the 23 women with culture-negative had preterm delivery, one with high (1000 pg/ml) and one with low (80 pg/ml) levels of IL-6. CONCLUSION: High levels of IL-6 are suggestive of a genuine intra-amniotic infection with urea-plasmas resulting in adverse pregnancy outcome, while culture-positive amniotic fluids with normal IL-6 levels, may suggest a state of contamination.     

Comparison of transabdominal and transcervical CVS and amniocentesis: sampling success and risk.

A total of 2931 women randomized to either transabdominal CVS, transcervical CVS, or amniocentesis were studied. Unless intended or unintended abortion had occurred, they had completed up to 28 weeks of pregnancy. No significant difference was seen between total fetal loss in the transabdominal CVS group and the amniocentesis group (6.5 and 6.8 per cent, respectively, SE difference = 0.92 per cent, p = 0.01). The total fetal loss in the transcervical CVS group was 10.1 per cent. After pooling our data with data from the Canadian randomized study and the American non-randomized study, the difference in risk between transcervical CVS and amniocentesis was 1.8 per cent (SE difference = 0.64 per cent, p = 0.8). When the number of failed procedures and those cases evaluated as unfeasible for the assigned method--for anatomical reasons--are compared, the overall sampling efficacy is poorer transcervically than transabdominally.     

Incidence of abortion after genetic amniocentesis in twin pregnancies.

Fetal outcome after genetic amniocentesis (AC) in viable twin pregnancies was analysed in a retrospective study at three centres in order to estimate the rate of fetal loss after AC. The maternal age ranged from 33 to 45 years (mean 36.7 years). The gestational age varied between 15 and 20 weeks of gestation (mean 17.1). In 98 viable twin pregnancies with complete follow-up, spontaneous abortion of both fetuses occurred within 28 completed weeks of gestation in eight pregnancies and six women aborted within 20 completed weeks of gestation after AC, corresponding to a rate of fetal loss of 8.1 and 6.1 per cent, respectively (excluding the loss of five twins with viable outcome of the co-twin in five pregnancies).