Clinical Perinatal/Neonatal Case Presentation ⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢ Candida After Serial Therapeutic Amniocenteses: A Possible Association

Martha E. Rode, MD Case Report Mark A. Morgan, MD A 29-year-old healthy primigravida was referred at 16 weeks’ gestation Eduardo Ruchelli, MD for an increased risk of suggested by maternal serum Iraj Forouzan, MD testing. The was otherwise without complication. Specifi- cally, there was no history of intrauterine contraceptive device use, BACKGROUND: human immunodeficiency virus, or cervical cerclage. An ultrasono- Reduction is used in cases of severe to graphic anatomic survey of the demonstrated no structural decrease maternal discomfort and the risk of preterm labor. In a MED- abnormalities. Amniocentesis revealed a normal 46, XX karyotype. LINE search (1966 to present, English language, keywords: amniocente- Six weeks later, the patient presented for evaluation of uterine sis, chorioamnionitis), no report of Candida chorioamnionitis after size greater than gestational age. Ultrasonographic measurement of Ͼ 2 serial reduction amniocentesis exists. the index was 25 cm ( 95% for gestational age). Causes for polyhydramnios, including , Rh isoimmunization, CASE: and viral infection were not identified. A 29-year-old primigravida with a history of four therapeutic amniocen- At 25 weeks’ gestation, the patient experienced shortness of teses for idiopathic polyhydramnios developed preterm labor at 30 and breath, uterine contractions, and severe discomfort secondary to uter- 5/7 weeks’ gestation, , and Candida albicans ine distention. A therapeutic amniocentesis was performed. Recurrent chorioamnionitis. Despite aggressive therapy with amphotericin B, the symptoms required additional reduction amniocenteses at 27 and 29 neonate succumbed to overwhelming systemic candidiasis. weeks’ gestation. At each, 2000 to 3000 ml of amniotic fluid was re- moved, with the goal of a maximum vertical pocket of Ͻ8 cm. The CONCLUSION: ranged between 40 and 55 cm before the proce- Serial amniocentesis may place patients at elevated risk for Candida dure to between 22 and 26 cm after completion of the amnioreduc- chorioamnionitis and subsequent preterm delivery. Clinicians should tion. Because it was felt the patient was at high risk for preterm deliv- consider early diagnostic amniocentesis in patients in preterm labor with ery, a single course of betamethasone (12 mg intramuscularly, a history of prior amniocentesis, and the routine Gram stain and culture repeated at 24 hours) was administered at 25 weeks’ gestation. of amniotic fluid. At 30 and 5/7 weeks’ gestation, she presented complaining of Journal of Perinatology 2000; 5:335–337. shortness of breath and discomfort. Vital signs were normal. The patient’s abdomen was markedly distended. The amniotic fluid index was elevated at 47 cm. The cervical examination was changed from a stable fingertip of dilation without effacement first detected at 25 Intraamniotic infection is recognized as an important etiologic weeks’ gestation to 3 cm of dilation and complete effacement with factor for preterm delivery.1 Organisms involved are usually com- engagement of the fetal head. Uterine contractions were every 3 min- mon inhabitants of the lower genital tract. Although Candida utes. species are frequently recovered from the vagina during pregnancy Magnesium sulfate tocolysis was started. A fourth reduction am- and are associated with preterm labor, antenatal fetal infections niocentesis was performed to decrease amniotic fluid volume to aid in with this group of organisms are rare.1 We report a case of chorio- terminating preterm labor. To rule out the possibility of an infectious amnionitis and congenital candidiasis after serial amniocenteses etiology, amniotic fluid was sent for Gram stain and culture. for symptomatic polyhydramnios. Hours later, the Gram stain returned positive for yeast with no bacteria or white cells, and the patient experienced spontaneous Division of Maternal-Fetal Medicine (M. E. R., M. A. M., I. F.), Department of and rupture of membranes. Tocolysis was discontinued and pitocin aug- Gynecology, The University of Pennsylvania Health System, Philadelphia, PA; and Depart- mentation begun. Amphotericin B was given for coverage of probable ment of Pathology (E. R.), The Children’s Hospital of Philadelphia, Philadelphia, PA. Candida albicans. The fetal rate pattern became non-reassur- Address correspondence and reprint requests to Martha E. Rode, MD, Department of Obstet- rics and Gynecology, University of Pennsylvania Health System, 3400 Spruce Street, 2000 ing with repetitive late decelerations, and an emergent cesarean was Courtyard, Philadelphia, PA 19104. E-mail address: [email protected] performed.

Journal of Perinatology 2000; 5:335–337 © 2000 Nature America Inc. All rights reserved. 0743–8346/00 $15 www.nature.com/jp 335 Rode et al. Possible Association Between Candidiasis and Serial Amniocenteses

frequently. We believe ours is the first report of such after serial thera- peutic amniocenteses. Despite the high frequency of maternal vaginal candidal coloni- zation (ϳ34%),3 the rarity of monilial chorioamnionitis (6.5% of women in preterm labor with intact membranes and positive amni- otic fluid cultures)1 implies that factors beyond the presence of the fungus favor the initiation of placental and/or fetal infection. Four possible explanations have been proposed for Candida reaching the upper genital tract and causing chorioamnionitis: (1) direct invasion from the vagina after premature rupture of membranes, (2) sealed ruptures of the amnion, (3) migration across an intact amnion, and (4) a foreign body in the genital tract, such as an intrauterine contra- ceptive device or cerclage.4 Cases of neonatal and placental candidia- sis have been noted after premature rupture of the membranes with 1,5 Figure 1 Umbilical cord with scattered pale yellow plaques characteristic of Can- and without clinical “sealing.” C. albicans has the ability to cross dida funisitis. the amniotic membranes and cause degeneration of membrane epi- thelium in vitro.6 Case series and individual reports have highlighted the possible etiologic role of the retained intrauterine contraceptive A 1390-gm female infant was delivered with Apgar scores of 6 and 3 8 at 1 and 5 minutes, respectively. Umbilical cord blood gases were device and cervical cerclage. In a prior case report of congenital mucocutaneous candidiasis after amniocentesis performed to assess compatible with respiratory acidemia. Physical examination of the 7 neonate was remarkable for an erythematous rash with raised lesions fetal lung maturity, it was conjectured that Candida could be intro- over the face, chest, and abdomen. Early onset respiratory distress duced into the by the use of contaminated instruments, required endotracheal intubation and ventilation. After cultures were colonization of maternal skin, or puncture of fetal membranes allow- obtained, ampicillin, gentamicin, and amphotericin were adminis- ing entry of ascending vaginal organisms. In the present case, infec- tered. The initial white blood cell count was consistent with over- tion related to repetitive amniocenteses may be an addition to the whelming sepsis at 1400/␮l. At 13 hours of age, intense cyanosis, above list. Once amniotic fluid invasion by Candida has occurred, chorio- hypotension, and bradycardia developed. Volume expansion, inotropic 8 therapy, and cardiopulmonary resuscitation failed to revive the infant. amnionitis, funisitis, and fetal infection may follow. As in the current Shortly before demise, pulmonary hemorrhage was diagnosed as the case, invasion of the interstitium of the lungs or lumen of the bowel may occur in severe infections, with dissemination of disease. Neona- probable etiology for acute decompensation. Subsequently, blood and 4 urine cultures returned no growth. tal outcome remains dependent on gestational age and birth weight. The maternal postoperative course was complicated by endome- Although overall mortality is 33%, commonly due to pneumonitis, it Ͻ 1 tritis treated with intravenous, followed by oral, fluconazole for a total is significantly increased among infants weighing 2000 gm (as in of 14 days. As in the first trimester, human immunodeficiency virus this case). Early aggressive treatment with amphotericin B has been status was negative. Final amniotic fluid culture results were positive associated with improved survival. for moderate growth of C. albicans. Several unanswered questions remain regarding this case. Amni- Autopsy findings were consistent with severe in utero systemic otic fluid was not evaluated for evidence of infection until the last candidiasis. The placenta revealed acute inflammation of the mem- reduction amniocentesis; therefore, we can only speculate regarding branes with numerous yeast spores and hyphal forms typical of fungal the timing of infection. However, as Candida is usually slow-growing, chorioamnionitis. Small, 0.1-cm yellow-white plaques covering the the infection likely had been present for some time to produce the umbilical cord corresponded microscopically to Candida abscesses severe sepsis seen at delivery. The patient’s preterm cervical change, within Wharton’s jelly (Figure 1). The erythematous rash revealed although initially minimal, may have facilitated an ascending infec- multiple intraepidermal microabscesses containing yeast spores. tion. Also, no etiology for polyhydramnios was determined. Polyhy- dramnios has been associated with an increased risk of chorioamnio- There was fulminant fungal pneumonia with acute inflammation, 9 , numerous fungal hyphae and spores, and candidal invasion nitis at term, but no data exist on preterm gestations. Glucocorticoids of the interstitium. Postmortem cultures of the blood, spleen, and have not been linked to Candida chorioamnionitis; it is doubtful that lung were positive for C. albicans. The remainder of the examination the course administered at 25 weeks’ gestation was associated with was unremarkable and appropriate for gestational age. this dismal outcome. It is our recommendation that patients undergoing serial amnio- Comment centeses have amniotic fluid sent for Gram stain and culture, espe- With the increased use of diagnostic amniocentesis in preterm labor, cially in the setting of severe polyhydramnios of unknown etiology. the antepartum diagnosis of candidal chorioamnionitis is made more Antenatal detection of candidal chorioamnionitis may alter perinatal

336 Journal of Perinatology 2000; 5:335–337 Possible Association Between Candidiasis and Serial Amniocenteses Rode et al.

management, allowing prompt treatment of affected neonates and a 5. Albarracin NS, Patterson WS, Haust MD. Candida albicans infection of the resulting increase in survival. placenta and fetus. Obstet Gynecol 1967;30:838–41. 6. Gurgan T, Diker KS, Haziroglu R, Urman B, Akan M. In vitro infection of human References fetal membranes with Candida species. Gynecol Obstet Invest 1994;37:164–7. 1. Chaim W, Mazor M, Wiznitzer A. The prevalence and clinical significance of intraamniotic infection with Candida species in women with preterm labor. 7. Delaplane D, Wiringa KS, Shulman ST, Yogev R. Congenital mucocutaneous Arch Gynecol Obstet 1992;251:9–15. candidiasis following diagnostic amniocentesis. Am J Obstet Gynecol 1983;147: 342–3. 2. Moore TR, Cayle JE. The amniotic fluid index in normal human pregnancy. Am J Obstet Gynecol 1990;162:1168–73. 8. Sonnenschein H, Tascholjian CL, Clark DH. Congenital cutaneous candidiasis. 3. Whyte RK, Hussain Z, deSa D. Antenatal infections with Candida species. Arch Am J Dis Child 1964;107:2606. Dis Child 1982;57:528–35. 9. Maymon E, Ghezzi R, Shoham-Vardi I, et al. Isolated hydramnios at term gesta- 4. Morgan MA, Pippitt CH, Thurnau GR. Antenatal diagnosis of Candida chorio- tion and the occurrence of peripartum complications. Eur J Obstet Gynecol Re- amnionitis. South Med J 1989;82:276. prod Biol 1998;77:157–61.

Journal of Perinatology 2000; 5:335–337 337