Introduction

Preterm birth (PTB), defined as delivery occurring prior than 37 weeks of gestation, is the major determinant of infant mortality and morbidity worldwide. Preterm born babies often require long periods of hospitalizations and more frequently face adverse outcomes such as breathing and feeding difficulties, possible impairment in neurological development, necrotizing enterocolitis, visual and hearing problems and intraventricular haemorrhage. They also have higher risk of death both during the neonatal period and up to five years of age if compared to babies born at term. Despite much effort on researches focused on this condition, the rate of PTB has increased annually and actually ranges from 5% to 18% [1,2].

During the years different pessaries used for the treatment of uterine or vaginal prolapse, have also been sporadically used for prevention of PTB [3]. The Arabin pessary was introduced in the last century and even though many studies have evaluated its efficacy in preventing preterm birth in singleton and twin pregnancy, its role is still a matter of scientific debate. Its mechanism of action is realistically due to the inclination of the cervix that allows cervical elongation and increases the utero-cervical angle [4]. Its positioning could also prevent additional dilatation of the internal os [3]. Moreover, Arabin pessary probably protects the cervical mucus plug, which is an important barrier that protects intrauterine cavity from ascending infection [5]. Lastly it may diminish the Ferguson reflex, which is a positive feedback loop between cervix or vaginal walls and hypothalamus or pituitary glands, causing oxytocin release and start of contractions [6].  Traditionally, it is considered as a safe method to use in pregnancy and the risk of chorioamniotitis in patients with Arabin Pessary is estimated at 3% [7].

In this case report we describe the case of maternal sepsis in a woman treated with Arabin pessary during the second trimester of pregnancy because of threatened preterm labor. 

Case report

A 34-years-old black race woman gravida 3, para 0 with a single spontaneous pregnancy was referred to our clinic for threatened preterm labor at 24 2/7 weeks. Her medical history was significant for two spontaneous miscarriages in the first trimester, chronic B hepatitis and multiple node fibromatosis. At the admission she was asymptomatic, there were no uterine contractions and no signs/symptoms of infection but she had a cervical shortening of 18 mm. A single course of corticosteroids was administered. After performing cervical and vaginal swabs, which resulted negative, we decided to place an Arabin Pessary at 26 weeks. After 2 weeks she came back for a control. The pessary was well positioned at the speculum examination and she did not refer any side effect. Cervical length was stable at 18 mm but the cervix was 1 cm open.  She had regular biweekly controls until 35 5/7 weeks when she was newly admitted to hospital because of abdominal pain. At the gynaecological examination malodorous vaginal discharge was noted and laboratory findings revealed an augmented C-reactive protein value of 1.5 mg/dl (normal value < 0.5). Antibiotic therapy with Clindamycin was started and a rescue dose of corticosteroids was repeated. Furthermore, she developed mild preeclampsia with high blood pressure and proteinuria > 300 mg/24 h so she started antihypertensive therapy with an alpha-blocker. The pessary was finally removed. The patient finally underwent an emergency caesarean section at 36 3/7 weeks for acute fetal distress revealed by the cardiotocography during labor. She delivered a live baby of 3000 g, Apgar 4/8, pH 7.14, excess bases -8.1. Immediately after delivery she developed fever for almost a week. Antibiotic therapy was continued with the addition of metronidazole. Blood cultures, urine culture and chest X-ray were performed but all of these exams were negative. The histological examination of the placenta revealed a congested placenta, with several subchorionic and intervillous thrombi and acute chorioamnionitis. The patient was finally discharged after 15 days with a complete resolution of symptoms.

Discussion

The 50-70% of perinatal mortality is attributed to PTB, similarly premature delivery is the main cause of perinatal morbidity. PTB can result in short term sequelae due to respiratory immaturity, apnoea, intracranial haemorrhage, infections, temperature instability, necrotize enterocolitis, periventricular leukomalacia and in long-term sequelae which include intellectual impairment, cerebral palsy, chronic lung disease, deafness, and blindness [8,9]. (Table 1). So, prevention of spontaneous preterm birth (SPTB) remains one of the most important targets to achieve in obstetric care.  

Different preventive strategies have been proposed in the last decades. These, in particular, include supplemental vaginal progesterone, cervical cerclage and cervical pessary. Cervical cerclage is the mechanical method most frequently used for the prevention of preterm birth. This procedure is though associated with the risk of cervical injury, premature rupture of membranes, sepsis, anaesthesiologic complications and release of prostaglandins that could lead to labour induction [12]. On the contrary, the use of pessary for cervical insufficiency is a not invasive procedure with low costs and no need for anaesthesia, a lower risk of cervical injury, high efficacy, good safety profile and is suitable for an outpatient setting [13]. The efficacy of Arabin pessary in preventing preterm birth in single pregnancy with short cervix has been evaluated by different randomized controlled trials with discordant results. The PECEP trial by Goya et al. was one of the first studies comparing incidence of preterm birth (<34 weeks) in 385 women with short cervix divided into pessary and expectant management groups. He showed that the incidence of PTB was significantly higher in the expectant group rather than the pessary group (27% vs 6%) [14]. Opposite results are those published by of Huy SY et al and Nicolaides KH reporting no positive effect of the prophylactic use of Arabin pessary on the prevention of preterm birth. Also, Dugoff et al, in a study enrolling 122 patients at high risk for SPTB, did not found any association between pessary application and prevention of preterm birth [15,16,17].

Many are the causes of SPTB. This condition in fact may be related to uterine factors (uterine overdistension such as polyhydramnios and twin pregnancies), decidual membranes activation (bleeding or placental lesion; lower genital tract infection especially Mycoplasma/Ureaplasma infection with increase of cytokines and prostaglandins) and/or cervical ripening (congenital disorder of the connective tissue, traumatic damage to the structural integrity, previous cervical surgery) [18,19,20].

Chorioamnionitis is one of the most important causes of preterm labour and preterm premature rupture of membranes. It is associated with increased risk of adverse neonatal and maternal outcomes. It is diagnosed by the presence of maternal fever with two or more criteria among uterine tenderness, leukocytosis, maternal tachycardia, fetal tachycardia, foul smelling amniotic fluid [21]. Chorioamnionitis is inversely correlated with gestational age and birth weight [22]. It can occur in 20% of women with preterm prelabor rupture of membranes (PPROM) [23] and in 10% of women with preterm labor and intact membranes [24]. Preterm clinical chorioamnionitis can also take place in the absence of spontaneous preterm labor and birth [25]. There are few studies about preterm clinical chorioamnionitis. The systemic and local inflammation at term is well known, but this is not the same in preterm babies. Moreover, preterm delivery is associated with higher risk for maternal sepsis, compared with term one [26]. Possible risk factors for increased incidence of maternal sepsis are nulliparity, black race, older age at first pregnancy, obesity, insulin-dependent diabetes, multiple gestation [27]. Escherichia coli, group A and group B Streptococcus are the predominant pathogens involved but even staphylococci, Gram-negative and anaerobic bacteria can be found [28]. The origin of bacteria in the fetal membrane microbiome is debated. It has been correlated to the mode of delivery, co-existent maternal condition, colonies of non-pathogenic bacteria [29]. Hochney et al. founded that a greater bacterial load is associated with histological chorioamnionitis and inflammatory markers. This supports the evidence that bacteria act in a dose dependent manner [30].

Arabin Pessary is generally described as a safe method to be used in pregnancy even though its use in clinical practice is not still standardized. Many studies have evaluated its efficacy in both singleton and twin pregnancy also comparing it with other preventive methods such as cervical cerclage or progesterone [31]; anyway, there are not many cases described in literature reporting the event of maternal sepsis in women treated with Arabin pessary. B Martinez de Tejada [7] has reported one case of maternal sepsis occurring in a twin pregnant woman who received Arabin Pessary placement at 19 weeks because of a wide funnelling with normal length cervix and a history of one previous preterm birth at 24 weeks. Two weeks later the placement of Arabin Pessary the patient showed bulging membranes with an augmented PCR and immediately after she had premature rupture of membranes with fever and onset of spontaneous labour. In this case the pessary positioning was early and the bulging of the membranes overlapped the underlying presence of funnelling. This did not happen in our patient who received Arabin pessary placement later (at 26 weeks) and did not show bulging membranes. In our case chorionamnionitis and maternal sepsis developed even though the exams preliminary to the positioning of the cervical ring were unremarkable and despite the early setting of antibiotic therapy. We hypothesize that the presence of Arabin Pessary could have prolonged and delayed cervical dilatation and fetal expulsion thus facilitating the onset of sepsis. If the Pessary had not been placed probably the delivery would have happened faster and maternal sepsis avoided.

Definitely we recommend that clinicians should carefully follow pregnant women with high risk of infection with close follow up and that Arabin pessary should be removed at the first signs of infection in order to prevent serious complications.

Conclusions

Maternal sepsis is a possible, even though rare, complication of Arabin Pessary placement. Clinicians should keep in mind this possible risk and perform regular checks on their patients. Arabin Pessary should be promptly removed in case of possible infection in order to avoid worse complications.

Funding
The authors received no funding for this research.

Acknowledgments
We thank the patient for letting us share her case.

Ethical approval
Not applicable.

Conflicts of interest
The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Authors’ contributions

Dr. DEL NEGRO V gave substantial contributions to the concept and the design of the study, draft the manuscript, revised it critically for important intellectual content, approved the definitive version of the submitted manuscript.

Dr. BRUNO VECCHIO RC revised the paper critically for important intellectual content and approved the definite version of the submitted manuscript.

Dr. SAVASTANO G gave substantial contributions to the design of the study, reviewed literature and wrote the manuscript.

Dr. FARALLI I. reviewed literature and wrote the manuscript

Dr. GALOPPI P revised critically the paper

Dr. PERRONE G contributed critically reviewing the manuscript for important intellectual content and gave her contribution to the concept and the design of the study

Dr. PICCIONI MG gave her contribution to the concept and the design of the study contributed critically reviewing the manuscript for important intellectual content.