Introduction: The term “congenital infections” refers to infections which can be transmitted from the mother to the fetus during pregnancy. Pregnant women have an increased risk of acquiring and transmitting infections because are likely to reside with young children and because experience immunological modifications. In case of in utero infection, several consequences can occur, ranging from embryonic death and resorption, abortion and stillbirth, premature delivery and, in case of term pregnancy, intrauterine growth restriction, and systemic or localized clinical manifestations. In most of cases infection may not be evident at birth and manifests later in childhood. Microorganisms involved in congenital infections are indicated by the acronym TORCHES CLAP. The present study focuses on the two most common congenital infections: Toxoplasmosis and congenital Cytomegalovirus (CMV) infection. Objectives: The objective of our study was to investigate the incidence of congenital infection in a cohort of newborns and to evaluate the neurological, ophthalmological and auditive sequelae in infected ones. Besides, the study proposed to correlate the infection rate and the symptomatic cases rate with gestational age of maternal seroconversion, prenatal treatment (as concerns toxoplasmosis) and postnatal management. Subjects, Materials and Methods: The first part of the study was conducted in a cohort of 220 patients admitted to three Hospitals of the area of Catania (Cannizzaro Hospital, Garibaldi Hospital and Policlinico Hospital) for suspicion for congenital toxoplasmosis from 1996 to 2020 [M 116 (52.7%), F 104 (47.2%); mean age at the enrollment: 1.28 months]. The patients were selected by prenatal screening in 217 cases (98.6%) or by a successive ophthalmological evaluation in three cases. The second part of the study was conducted in a cohort of 43 newborns from mothers with CMV infection during pregnancy consecutively admitted to Policlinico-San Marco University Hospital from 2017 to 2020 [M 16 (52%), F 15 (48%)]. All patients were selected by prenatal screening. In both groups, the parameters analyzed were: gestational history, neonatal anamnesis and short and long-term follow up. Results: As concerns congenital toxoplasmosis, we observed a mother-to-child transmission (MTCT) rate of 13.18% (29/220). No correlation between risk of fetal infection and maternal age (OR=0.33, p=0.124) was found, nor with type of prenatal treatment (spiramycin followed by pyrimethamine-sulphonamide versus spiramycin or pyrimethamine-sulphonamide alone) (OR=1.88, p=0.254). The analysis of correlation between MTCT rate and gestational age at maternal seroconversion showed a direct statistically significant interaction between the two parameters: rate of transmission of 5% at first trimester (OR=0.12), 23% at the second (OR=1.18) and 63% at the third trimester (OR=5.8; p<0.001). As regards congenital CMV infection, the MTCT rate observed was 72% (31/43). No differences among the three trimesters of gestational age at maternal seroconversion (I, II and III) in terms of risk of fetal infection were observed. As concerns the type of maternal infection (primary versus secondary), an increased MTCT rate after primary infection, if compared with secondary infection, was observed. Besides, among the 29 patients affected by congenital toxoplasmosis, we found a rate of symptomatic cases of 20% at birth and of 59% in a long-term follow up, with 10% manifesting microcephaly, 19% brain abnormalities at birth- ultrasound, 4% behavioral disturbances, 7% epilepsy and 7% psychomotor delay associated with behavioral disturbance. The 38.7% (n 12) of CMV congenitally infected children manifested neurological sequelae, in particular speech delay (58.3%), motor delay (50%), epilepsy (8.3%), microcephaly (8.3%) and behavior disorder (8.3%). Sensorineural hearing loss (SNHL) was diagnosed in 2 infants (7.5%). No correlation between gestational age at maternal seroconversion and clinical manifestation was observed, both in congenital toxoplasmosis and in congenital CMV infection. As regards the type of maternal infection, we observed no differences between primary and secondary CMV infection in causing symptomatic congenital disease in newborn/child. As concerns CMV infection, we investigated some neonatal findings as predictors of neurological and audiological outcome. The presence of a viral blood load in newborns correlates with symptomatic disease. No correlation between urine viral load and neurological and audiological outcome had been observed. Conclusions: prenatal serological screening is effective in selecting newborns who have to be submitted to follow up and treatment for congenital infections. The results of our study are in accordance with literature for some aspects (direct correlation between gestational age at maternal seroconversion and rate of MTCT in toxoplasmosis) and in contradiction for others (we did not find any correlation between gestational age at maternal seroconversion and rate of symptomatic cases). Further randomized controlled clinical trials would better clarify the evolution of the disease in prenatal and postnatal age and the contribution of each variables in the occurrence of the infection and of its manifestations.
Introduzione: il termine “infezioni congenite” si riferisce alle infezioni a trasmissione materno-fetale. Si stima che le gestanti abbiano un rischio di infezione superiore rispetto alla popolazione generale in quanto spesso caregivers di bambini in età prescolare. La trasmissione dell’infezione al feto è inoltre agevolata da modifiche della risposta immunologica tipiche della gestazione. Le conseguenze di una infezione fetale acquisita in utero sono numerose, da aborto e morte intrauterina del feto, a prematurità e, nei casi di gravidanza a termine, restrizione della crescita endouterina e manifestazioni postnatali sistemiche o localizzate. In molti casi l’infezione non è evidente alla nascita e si manifesta successivamente nel corso dell’infanzia. I microrganismi coinvolti nelle infezioni congenite vengono indicati con l’acronimo TORCHES CLAP. Questo studio si focalizza sulle due infezioni congenite di più comune riscontro: la toxoplasmosi congenita e l’infezione congenita da Cytomegalovirus (CMV). Obiettivi: l’obiettivo del nostro studio è quello di stimare l’incidenza delle infezioni congenite in una coorte di neonati e di valutare le manifestazioni a distanza di tipo neurologico, oculare ed uditivo tra gli infetti. Inoltre, lo studio si propone di correlare il tasso di trasmissione materno-fetale e l’incidenza di casi sintomatici con l’età gestazionale alla sieroconversione materna, con il trattamento prenatale (per quel che riguarda la toxoplasmosi) e postnatale. Soggetti, Materiali e Metodi: la prima parte dello studio è stata condotta in una coorte di 220 pazienti reclutati da 3 Ospedali della città di Catania (l’Ospedale Cannizzaro, l’Ospedale Garibaldi ed il Policlinico) per il sospetto di infezione congenita da Toxoplasma gondii dal 1996 al 2020 [M 116 (52.7%), F 104 (47.2%); età media di arruolamento: 1.28 mesi]. I pazienti sono stati selezionati tramite lo screening prenatale in 217 casi (98.6%) o a seguito di una visita oculistica di controllo in 3 casi. La seconda parte dello studio è stata condotta su una coorte di 43 neonati da madri affette da infezione da CMV in gravidanza reclutate dall’Ospedale Universitario Policlinico-San Marco dal 2017 al 2020 [M 16 (52%), F 15 (48%)]. Tutti i pazienti sono stati selezionati tramite lo screening prenatale. In entrambi i gruppi i parametri analizzati sono stati: anamnesi gestazionale, anamnesi neonatale e follow up a breve e a lungo termine. Risultati: per quel che riguarda la toxoplasmosi congenita, abbiamo osservato un tasso di trasmissione materno-fetale del 13.8% (29/220). Non è stata riscontrata alcuna correlazione tra il rischio di infezione fetale e l’età materna (OR=0.33, p=0.124), né con il tipo di trattamento prenatale (spiramicina seguita da pirimetamina-sulfadiazina versus spiramicina o pirimentamina-sulfadiazina in monoterapia) (OR=1.88, p=0.254). L’analisi della correlazione tra tasso di trasmissione materno-fetale ed età gestazionale alla sieroconversione materna ha mostrato una correlazione diretta statisticamente significativa tra i due parametri: tasso di trasmissione del 5% al primo trimestre (OR=0.12), 23% al secondo (OR=1.18) e 63% al terzo trimestre (OR=5.8; p<0.001). Per quel che riguarda l’infezione congenita da CMV, il tasso di trasmissione materno-fetale osservato è stato del 72% (31/43). Non è stata riscontrata alcuna differenza tra i tre trimestri di gestazione alla sieroconversione materna (I, II e III) in termini di infezione fetale. Per quel che concerne il tipo d’infezione materna (primaria versus secondaria), è stato osservato un incremento della trasmissione materno-fetale nelle infezioni primarie, rispetto alle secondarie. Inoltre, tra i 29 pazienti affetti da toxoplasmosi congenita, abbiamo osservato un tasso di casi sintomatici del 20% alla nascita e del 59% nel follow up a lungo termine, di cui il 10% manifestava microcefalia, il 19% anomalie cerebrali all’ecografia transfontanellare, il 4% anomalie del comportamento, il 7% epilessia ed il 7% ritardo psicomotorio associato a disturbo del comportamento. Il 38.7% (n 12) dei bambini con infezione congenita da CMV ha manifestato sequele neurologiche, in particolare ritardo del linguaggio (58.3%), ritardo motorio (50%), epilessia (8.3%), microcefalia (8.3%) e disturbo del comportamento (8.3%). La sordità neurosensoriale è stata diagnosticata in 2 lattanti (7.5%). Non è stata osservata alcuna correlazione tra l’età gestazionale alla sieroconversione materna e le manifestazioni cliniche, sia nella toxoplasmosi congenita che dalla infezione congenita da CMV. Per quanto riguarda il tipo di infezione materna, non abbiamo osservato alcuna differenza tra infezione primaria e infezione secondaria da CMV nel causare una infezione congenita sintomatica nel neonato/bambino. Per quanto riguarda l’infezione congenita da CMV, abbiamo indagato alcuni parametri neonatali quali predittori di outcome neurologico e uditivo. La presenza di DNA virale nel sangue del neonato correla con un aumentato rischio di malattia sintomatica. Non è stata osservata invece alcuna correlazione tra la carica virale urinaria e le manifestazioni neurologiche ed uditive. Conclusioni: lo screening sierologico prenatale è efficace nel selezionare i neonati che devono essere sottoposti al follow up ed al trattamento per infezioni congenite. I risultati del nostro studio sono in accordo con la letteratura per alcuni aspetti (correlazione diretta tra epoca di sieroconversione materna e tasso di trasmissione materno-fetale nella toxoplasmosi) ed in contraddizione per altri (non abbiamo osservato alcuna correlazione statisticamente significativa tra epoca gestazionale alla sieroconversione materna e tasso di casi sintomatici). Ulteriori studi randomizzati controllati potrebbero meglio chiarire l’evoluzione della patologia in epoca prenatale e postnatale ed il contributo di ciascuna variabile nel determinare l’infezione e le sue manifestazioni.
INFEZIONI CONGENITE: ESPERIENZA TRIENNALE DI UN SINGOLO CENTRO
GAROZZO, MARIA TERESA
2021
Abstract
Introduction: The term “congenital infections” refers to infections which can be transmitted from the mother to the fetus during pregnancy. Pregnant women have an increased risk of acquiring and transmitting infections because are likely to reside with young children and because experience immunological modifications. In case of in utero infection, several consequences can occur, ranging from embryonic death and resorption, abortion and stillbirth, premature delivery and, in case of term pregnancy, intrauterine growth restriction, and systemic or localized clinical manifestations. In most of cases infection may not be evident at birth and manifests later in childhood. Microorganisms involved in congenital infections are indicated by the acronym TORCHES CLAP. The present study focuses on the two most common congenital infections: Toxoplasmosis and congenital Cytomegalovirus (CMV) infection. Objectives: The objective of our study was to investigate the incidence of congenital infection in a cohort of newborns and to evaluate the neurological, ophthalmological and auditive sequelae in infected ones. Besides, the study proposed to correlate the infection rate and the symptomatic cases rate with gestational age of maternal seroconversion, prenatal treatment (as concerns toxoplasmosis) and postnatal management. Subjects, Materials and Methods: The first part of the study was conducted in a cohort of 220 patients admitted to three Hospitals of the area of Catania (Cannizzaro Hospital, Garibaldi Hospital and Policlinico Hospital) for suspicion for congenital toxoplasmosis from 1996 to 2020 [M 116 (52.7%), F 104 (47.2%); mean age at the enrollment: 1.28 months]. The patients were selected by prenatal screening in 217 cases (98.6%) or by a successive ophthalmological evaluation in three cases. The second part of the study was conducted in a cohort of 43 newborns from mothers with CMV infection during pregnancy consecutively admitted to Policlinico-San Marco University Hospital from 2017 to 2020 [M 16 (52%), F 15 (48%)]. All patients were selected by prenatal screening. In both groups, the parameters analyzed were: gestational history, neonatal anamnesis and short and long-term follow up. Results: As concerns congenital toxoplasmosis, we observed a mother-to-child transmission (MTCT) rate of 13.18% (29/220). No correlation between risk of fetal infection and maternal age (OR=0.33, p=0.124) was found, nor with type of prenatal treatment (spiramycin followed by pyrimethamine-sulphonamide versus spiramycin or pyrimethamine-sulphonamide alone) (OR=1.88, p=0.254). The analysis of correlation between MTCT rate and gestational age at maternal seroconversion showed a direct statistically significant interaction between the two parameters: rate of transmission of 5% at first trimester (OR=0.12), 23% at the second (OR=1.18) and 63% at the third trimester (OR=5.8; p<0.001). As regards congenital CMV infection, the MTCT rate observed was 72% (31/43). No differences among the three trimesters of gestational age at maternal seroconversion (I, II and III) in terms of risk of fetal infection were observed. As concerns the type of maternal infection (primary versus secondary), an increased MTCT rate after primary infection, if compared with secondary infection, was observed. Besides, among the 29 patients affected by congenital toxoplasmosis, we found a rate of symptomatic cases of 20% at birth and of 59% in a long-term follow up, with 10% manifesting microcephaly, 19% brain abnormalities at birth- ultrasound, 4% behavioral disturbances, 7% epilepsy and 7% psychomotor delay associated with behavioral disturbance. The 38.7% (n 12) of CMV congenitally infected children manifested neurological sequelae, in particular speech delay (58.3%), motor delay (50%), epilepsy (8.3%), microcephaly (8.3%) and behavior disorder (8.3%). Sensorineural hearing loss (SNHL) was diagnosed in 2 infants (7.5%). No correlation between gestational age at maternal seroconversion and clinical manifestation was observed, both in congenital toxoplasmosis and in congenital CMV infection. As regards the type of maternal infection, we observed no differences between primary and secondary CMV infection in causing symptomatic congenital disease in newborn/child. As concerns CMV infection, we investigated some neonatal findings as predictors of neurological and audiological outcome. The presence of a viral blood load in newborns correlates with symptomatic disease. No correlation between urine viral load and neurological and audiological outcome had been observed. Conclusions: prenatal serological screening is effective in selecting newborns who have to be submitted to follow up and treatment for congenital infections. The results of our study are in accordance with literature for some aspects (direct correlation between gestational age at maternal seroconversion and rate of MTCT in toxoplasmosis) and in contradiction for others (we did not find any correlation between gestational age at maternal seroconversion and rate of symptomatic cases). Further randomized controlled clinical trials would better clarify the evolution of the disease in prenatal and postnatal age and the contribution of each variables in the occurrence of the infection and of its manifestations.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/73220
URN:NBN:IT:UNICT-73220