Study: Antibiotic therapy reduces intraamniotic inflammation in second trimester idiopathic bleeding

Antibiotic therapy leads to reduced intraamniotic inflammation among patients with idiopathic bleeding in the second trimester of pregnancy, according to a recent study published in the American Journal of Obstetrics & Gynecology.

Approximately ¼ of pregnancies are impacted by vaginal bleeding, which often presents in the first trimester. However, under 1% of pregnancies are impacted by vaginal bleeding during the second trimester.

If all major identifiable causes of bleeding are discounted, then bleeding is categorized as idiopathic or unexplained. Idiopathic and unexplained bleeding are associated with increased risk of adverse maternal and infant health risks such as preterm prelabor rupture of membranes, preterm labor, oligohydramnios, fetal growth restriction, small for gestational age, and stillbirth.

A change in local hemostasis in the decidua caused by infection or inflammation may explain certain cases of idiopathic bleeding. Antibiotic treatment can be used to manage intraamniotic inflammatory complications, but it is unclear whether this treatment is effective when utilized during the second trimester.

To evaluate the impact of antibiotic therapy on intraamniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy, investigators conducted a retrospective cohort study. Participants were patients aged 18 years or older with a singleton pregnancy, vaginal bleeding of uterine origin, gestational ages from 15+0 to 27+6 weeks, and written informed consent.

Exclusion criteria included signs of congenital structural or chromosomal abnormalities from the fetus, regular uterine activity, amniotic fluid leakage, placenta previa major, trauma of the introitus or the vagina, bleeding from the ectocervix, and systemic disorders.

First-trimester fetal biometry was used to determine gestational age, while a sterile speculum determined blood flow through the external os of the cervix to determine vaginal bleeding. Intraamniotic environment, including IL6 concentrations and microbial invasion of the amniotic cavity (MIAC), was evaluated among patients with second trimester idiopathic vaginal bleeding via amniocentesis.

During ultrasound at admission, approximately 3 mL of amniotic fluid was aspirated. Antibiotic treatment began when results of amniotic fluid IL6 were available and confirmed intraamniotic inflammation. Treatment included 2-g ceftriaxone every 24 hours, 500-mg metronidazole every 8 hours, and 500-mg clarithromycin every 12 hours.

Treatment efficacy was confirmed during a 7-day follow-up. The cobas e602 immunoanalyzer was used to measure IL6 concentration in amniotic fluid. A QIAamp DNA Mini Kit (QIAGEN, Hilden, Germany) was used to isolate DNA so that Ureaplasma spp, Mycoplasma hominis, and Chlamydia trachomatis could be detected.

Polymerase chain reaction testing was used to detect bacterial DNA, and amniotic fluid samples were cultured on Columbia agar. Two investigators reviewed neonatal medical records for data about short-term neonatal morbidity.

There were 36 patients included in the final analysis, 36% of whom had MIAC and 69% had intraamniotic inflammation. Ureaplasma spp was detected in the amniotic fluid of 11 patients during the initial amniocentesis, Rothia mucilaginosa in 1, and Streptococcus parasanguinis in 1. Of women, 36% had intraamniotic infection and 33% had sterile intraamniotic inflammation.

The highest rate of oligohydramnios at admission, shortest interval between admission and abortion or delivery, lowest gestational age at abortion or delivery, lowest birth weight, and lowest rate of placental findings consistent with maternal vascular malperfusion were observed among patients with intraamniotic infection.

The highest rate of deliveries at term, lowest rate of Apgar scores below 7 at 5 and 10 minutes, and placental findings consistent with acute inflammatory lesions were observed among patients without intraamniotic inflammation. Delivery more than 7 days after admission was reported in 74% of overall patients, 60% with intraamniotic inflammation, and 100% without intraamniotic inflammation.

IL6 concentrations in amniotic fluid were reduced in patients with intraamniotic inflammation receiving follow-up amniocentesis during follow-up amniocentesis compared to initial amniocentesis, with median interquartile ranges (IQRs) of 3457 pg/mL and 19,812 pg/mL, respectively. Decreasing IL6 concentrations were observed in 100% of patients and intraamniotic inflammation resolution in 50%.

Patients with intraamniotic infection also had reduced IL6 concentration in amniotic fluid during follow-up amniocentesis vs initial amniocentesis, with median IQRs of 12,424 pg/mL and 27,881 pg/mL, respectively. Reduced inflammation intensity and intraamniotic inflammation resolution were observed in 100% and 25% of these patients, respectively.

Ureaplasma spp DNA was found in 88% of these patients at baseline and follow-up. However, Ureaplasma spp DNA was reduced at follow-up compared to baseline.

IL6 concentrations were also reduced in the amniotic fluid of patients with idiopathic bleeding and sterile intraamniotic inflammation during follow-up amniocentesis vs initial amniocentesis, with IQRs of 2690 pg/mL and 16,209 pg/mL, respectively. Decreased inflammation intensity and intraamniotic inflammation resolution were observed in 100% and 86% of these patients, respectively.

These results indicated reduced or resolved intraamniotic inflammation following antibiotic treatment in patients with idiopathic bleeding in the second trimester of pregnancy. The treatment also reduced the amniotic fluid load of microorganisms in these patients.

Reference

Musilova I, Stranik J, Jacobsson B, et al. Antibiotic treatment reduces the intensity of intraamniotic inflammation in pregnancies with idiopathic vaginal bleeding in the second trimester of pregnancy. Am J Obstet Gynecol .2024;230:245.e1-14. doi:10.1016/j.ajog.2023.07.041