Journal of Perinatology (2010) 30, 231–232 r 2010 Nature Publishing Group All rights reserved. 0743-8346/10 $32 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION Delayed onset of severe neonatal

D Al-Hamod1, C Vauloup2, M Goulet1, V Zupan-Simunek1, C Castel1 and P Boileau1 1Service de Pe´diatrie et Re´animation Ne´onatales, Hoˆpital Antoine-Becle`re, Clamart, France and 2Laboratoire de Microbiologie Immunologie biologique, Hoˆpital Antoine-Be´cle`re, Univ. Paris-Sud, Clamart, France

Case We report a case of severe neonatal infection on day 6 of life due to TG was a 6-day-old male admitted to our neonatal intensive mimicking septic syndrome associated with care unit with a diagnosis of suspected syndrome. multiple organ failure such as acute respiratory distress syndrome with The was a 17-year-old primigravida with no past medical persistent pulmonary hypertension, neurological distress, history, and who did not have any prenatal follow-up. She with disseminated intravascular coagulopathy and transaminitis. Clinicians presented in active labor and TG was delivered vaginally without facing an unexplained life-threatening condition in the first week of life any complication, weighing 2510 g and with Apgar scores of 10 and should take into consideration the possibility of neonatal toxoplasmosis. 10 at 1 and 5 min, having a cord venous blood pH of 7.31. He was Journal of Perinatology (2010) 30, 231–232; doi:10.1038/jp.2009.184 admitted to the maternity unit with an estimated gestational age of Keywords: toxoplasmosis; neonatal; thrombocytopenia; persistent 35 weeks being tonic, active, with all reflexes present and normal pulmonary hypertension; septic shock fontanels in size and shape. He had a normal respiratory rate of 50 breaths per min and normal cardiopulmonary auscultation. The liver was palpable for 2 cm and no malformations were noticed. Maternal serological results for toxoplasmosis showed positive immunoglobulin G at 44 IU mlÀ1 (Access Beckman Coulter, Introduction Fullerton, CA, USA), positive immunoglobulin M at high level (103 born with congenital toxoplasmosis are usually E/VS; Access Beckman Coulter) and a very low avidity index at 3% at birth and may thereafter develop sequelae such as (Vidas bioMe´rieux, Marcy l’Etoile, France), suggesting a recent mental retardation and impaired vision. As clinical benefit can be maternal primary infection. Further serological investigations of achieved by an appropriate treatment, the diagnosis of neonatal the mother confirmed that primary infection occurred in the last 6 infection is crucial. Congenital Toxoplasma infection may present weeks of . On day 6, the results of newborn serological as intrauterine growth restriction, prematurity, thrombocytopenia, screening came back positive for Toxoplasma at a very high level hepatomegaly, and convulsions, along with the (immunoglobulin M index at 12 (ISAgA)). Treatment with classical triad of , hydrocephalus and cerebral pyrimethamine and sulfadiazine was unfortunately not initiated calcifications.1 The risk of mother-to-child increases because of a cardio-respiratory arrest that occurred on that day. with gestational age at maternal seroconversion, whereas the risk He required full cardiopulmonary with of clinical manifestations in infected infants decreases.2 Without endotracheal intubation, two intravenous injections of epinephrine, characteristic clinical findings, the diagnosis of congenital sodium bicarbonate and a volume supplementation with toxoplasmosis relies on the presence of specific antitoxoplasmic normal saline. immunoglobulin M in the serum obtained from infants. After stabilization, he was transferred to the neonatal intensive Congenital toxoplasmosis affects approximately 6% of 800 000 care unit. His physical exam showed the following: rectal newborns per year in France;3 10 to 25% develop intracranial temperature of 34.5 1C, of 120 beat per min, refill calcifications, hydrocephalus and/or chorioretinitis and 1 to 2% die capillary time over 5 s, median blood pressure of 45 mmHg, during the perinatal period. We report an unusual case of severe hepatomegaly for 6 cm and generalized . Thereafter, he neonatal toxoplasmosis with a delayed onset after maternal showed a massive pulmonary hemorrhage with pulmonary primary infection in the last weeks of pregnancy. hypertension confirmed by echocardiography. He was mechanically ventilated with positive inspiratory pressure up to 30 cm H2O and a Correspondence: Professor P Boileau, Service de Pe´diatrie et Re´animation Ne´onatales, positive end expiratory pressure of þ 4, using 100% FiO2 resulting Hoˆpital Antoine Be´cle`re, 157 rue de la Porte de Trivaux, Clamart 92141, France. E-mail: [email protected] in an oxygenation index of 44. Inhaled nitric oxide was introduced Received 30 July 2009; revised 29 August 2009; accepted 1 October 2009 at 10 p.p.m. Severe neonatal toxoplasmosis D Al-Hamod et al 232

Laboratory investigations showed severe (venous blood Discussion À1 gas: pH 6.69, PCO2 7.85 kPa, bicarbonate 6.7 mmol l ) with lactic We have presented a severe case of neonatal toxoplasmosis that led À1 acidemia at 22 mmol l , (white blood count to a life-threatening condition and multiple organ failure. À3 6500 mm with neutrophils 12%), disseminated intravascular Maternal serological results indicated that toxoplasmosis infection coagulopathy with hypofibrinogenemia and thrombocytopenia was acquired late in pregnancy, but it was not treated because this À3 (platelet count 12 000 mm ), a marked transaminitis (alanine pregnancy was not followed up as usual. Current evidence is À1 aminotransferase 259 IU l , aspartate aminotransferase insufficient to confirm that treating who seroconvert À1 1169 IU l ) with an unconjugated hyperbilirubinemia during pregnancy prevents fetal infection. Nevertheless, a positive À1 (140 mmol l ), a normal renal function and a C-reactive protein diagnosis of toxoplasmosis has implications for subsequent À1 level of 16 mg l . He was treated with ampicillin, cefotaxime and treatment and follow-up. amikacin for a direct Gram stain of Gram-negative bacilli and We could not find a causative for his septic shock Gram-positive cocci in gastric aspirate. Blood, tracheal secretions other than Toxoplasma gondii, and we did not suspect at the and urine culture were all negative for . Lumbar puncture beginning that it could be toxoplasmosis because of its unusual was postponed due to thrombocytopenia. was found presentation and it being oriented to a neonatal infection with in gastric aspirate culture leading to the diagnosis of septic shock E. coli. Although the diagnosis of neonatal toxoplasmosis was due to a neonatal infection. However, even with a well-adjusted confirmed by laboratory investigations (blood and treatment, his C-reactive protein was uncontrolled, increasing to Toxoplasma gondii PCR), organ involvement could be a result of À1 90 mg l at day 8, in addition to the persistence of a disseminated a ‘near miss’ syndrome. However, the rapid improvement of the intravascular coagulopathy with thrombocytopenia (requiring patient’s clinical and biological condition after beginning the transfusion of fresh frozen plasma and platelets) and the occurrence antitoxoplasmic treatment confirms that Toxoplasma gondii was of a confirmed by an electroencephalography. TG was truly the pathogen in this case. Acute disseminated toxoplasmosis is reevaluated: tracheal secretions PCR of enterovirus and influenza a rare event in immunocompetent individuals, and occurs most À1 virus negative, plasma interferon-a <3 IU ml (normal <2) and frequently in immunosuppressed patients; disseminated urine cytomegalovirus PCR negative. Confirmation of a highly toxoplasmosis with a clinical and evolutionary course similar to À1 positive Toxoplasma serology immunoglobulin G 75.2 IU ml has been reported in these patients as well. Two reports have À1 (positive >6 IU ml ; Access Beckman Coulter), immunoglobulin described congenital toxoplasmosis and the acute occurrence of M 97.52 E/VS (Access Beckman Coulter) and positive blood PCR for septic shock4,5 immediately after birth, leading to death in one À1 Toxoplasam gondii (70 copies ml ) was obtained. We revised our case,4 although in this case clinical symptoms were delayed for diagnosis to severe infection due to congenital toxoplasmosis 6 days before the acute onset occurred. Such a delay makes this associated with multiple organ failure. Following these results, clinical presentation unusual in neonatal toxoplasmosis and Toxoplasma gondii PCR was undertaken on the placenta and septic shock. seemed to be positive. This observation suggests that any infant who presents with Drug was initiated at day 24 by pyrimethamine septic shock associated with severe multiple organ failure with À1 À1 À1 À1 1mgkg day , sulfadiazine 100 mg kg day and folic acid, complete negative bacterial and viral cultures should be screened being adjusted later on with corticosteroids for a positive for congenital Toxoplasma infection. ophthalmological examination of active chorioretinitis on the left side. Brain magnetic resonance imaging was performed after Conflict of interest stabilization of his general condition and after 8 days of treatment The authors declare no conflict of interest. with antitoxoplasmic agents on T2 hypodense lesions of the cortex associated with an intracranial calcification. References After 20 days of treatment with antitoxoplasmic agents, we noticed an improvement in liver function (alanine 1 Remington JS, Macleod R, Thulliez P, Desmonts G. Toxoplasmosis. In: Remington JS, aminotransferase 200 IU lÀ1, aspartate aminotransferase Klein JO (eds). Infectious Diseases of the Fetus and Newborn Infant, 6th edn. Elsevier- À1 À3 Saunders: Philadelphia, PA, 2006, pp 947–1091. 356 IU l ) and platelet count (343 000 mm ). The patient 2 Thiebaut R, and The SYROCOT (Systematic Review on Congenital Toxoplasmosis) study required 35 days of and 19 days of group. Effectiveness of prenatal treatment for congenital toxoplasmosis: inhaled nitric oxide because of persistent pulmonary hypertension. a meta-analysis of individual patients’ data. Lancet 2007; 369: 115–122. He was extubated on day 40 of life, tolerating spontaneous 3 Papoz L, Simondon F, Saurin W, Sarmini H. A simple model relevant to toxoplasmosis ventilation well and was transferred to the pediatric unit at applied to epidemiologic results in France. Am J Epidemiol 1986; 123: 154–161. 4 Cneude F, Deliege R, Barbier C, Durand-Joly I, Bourlet A, Sonna M et al. Septic shock day 43. He was discharged home at day 66 of life, weighing due to congenital disseminated toxoplasmosis? Arch Pediatr 2002; 10: 326–328. 3150 g, to complete his antitoxoplasmic treatment for a period 5 Armstrong L, Isaacs D, Evans N. Severe neonatal toxoplasmosis after third trimester of 6 months. maternal infection. Pediatr Infect Dis J 2004; 23: 968–969.

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