Maternal–Fetal Infections (Cytomegalovirus, Toxoplasma, Syphilis): Short-Term and Long-Term Neurodevelopmental Outcomes in Children Infected and Uninfected at Birth
Abstract
:1. Introduction
2. Materials and Methods
2.1. Definitions
2.2. Statistical Analysis
3. Results
Outcomes in Children with Congenital Infection
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Definitions | |
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Cytomegalovirus | Symptomatic infection Presence of one or more of these symptoms: thrombocytopenia, petechiae, hepatomegaly, splenomegaly, intrauterine growth restriction, hepatitis (raised transaminases or bilirubin), central nervous system involvement such as microcephaly, radiographic abnormalities consistent with cytomegalovirus central nervous system disease (ventriculomegaly, intracerebral calcifications, cortical or cerebellar malformations), abnormal cerebrospinal fluid indices for age, chorioretinitis, sensorineural hearing loss, the detection of cytomegalovirus DNA in cerebrospinal fluid isolated sensorineural hearing loss (≥21 decibels), and isolation of CMV or identification of viral DNA in urine or saliva or blood. Asymptomatic infection No apparent abnormalities to suggest congenital cytomegalovirus disease, normal hearing, and isolation of CMV or identification of viral DNA in urine or saliva or blood, and detection of specific CMV IgM in blood during the first 3 weeks of postnatal life, without overt clinical symptoms of the infection. |
Toxoplasmosis | Symptomatic infection Presence of the classic triad of clinical signs: chorioretinitis, intracranial calcifications, and hydrocephalus and or microcephaly, intracranial calcifications, chorioretinitis, cataracts, convulsions, nystagmus, jaundice, petechiae, anemia, prematurity and severe intrauterine growth restriction, and the presence of positive specific IgG and/or IgM antibodies against Toxoplasma gondii. Asymptomatic infection Intrauterine infection without obvious signs of toxoplasmosis at birth on routine examination, with positive specific IgG and IgM antibodies against Toxoplasma gondii, or with an increasing specific IgG serum level. |
Syphilis | Confirmed Proven or Highly Probable Congenital Syphilis Any neonate with • an abnormal physical examination that is consistent with congenital syphilis; • a serum quantitative nontreponemal serologic titer that is fourfold (or greater) higher than the mother’s titer at delivery (e.g., maternal titer = 1:2, neonatal titer ≥ 1:8 or maternal titer = 1:8, neonatal titer ≥ 1:32); • or a positive darkfield test or PCR of placenta, cord, lesions, or body fluids or a positive silver stain of the placenta or cord. Possible Congenital Syphilis Any neonate who has a normal physical examination and a serum quantitative nontreponemal serologic titer equal to or less than fourfold of the maternal titer at delivery (e.g., maternal titer = 1:8, neonatal titer ≤ 1:16) and one of the following: • The mother was not treated, was inadequately treated, or has no documentation of having received treatment. • The mother was treated with erythromycin or a regimen other than those recommended in these guidelines (i.e., a nonpenicillin G regimen). • The mother received the recommended regimen but treatment was initiated Congenital Syphilis Less Likely Any neonate who has a normal physical examination and a serum quantitative nontreponemal serologic titer equal or less than fourfold of the maternal titer at delivery (e.g., maternal titer = 1:8, neonatal titer ≤ 1:16) and both of the following are true: • The mother was treated during pregnancy, treatment was appropriate for the infection stage, and the treatment regimen was initiated ≥30 days before delivery. • The mother has no evidence of reinfection or relapse. Congenital Syphilis Unlikely Any neonate who has a normal physical examination and a serum quantitative nontreponemal serologic titer equal to or less than fourfold of the maternal titer at delivery and both of the following are true: • The mother’s treatment was adequate before pregnancy. • The mother’s nontreponemal serologic titer remained low and stable (i.e., serofast) before and during pregnancy and at delivery (e.g., VDRL ≤ 1:2 or RPR ≤ 1:4). |
Clinical Characteristics at Birth | Symptomatic Infected Infants (n = 37) | Asymptomatic Infected Infants (n = 82) | Uninfected Infants (n = 67) | p-Value |
---|---|---|---|---|
Gender (males), n (%) | 23 (62.2%) | 46 (56.1%) | 30 (44.8%) | NS |
Gestational age (week), mean ± SD | 37.39 ± 3.18 | 38.92 ± 2.04 | 38.86 ± 1.50 | 0.001 |
Birth weight (g), mean ± SD | 2684.51 ± 769.91 | 3149.04 ± 570.81 | 3146.95 ± 488.56 | 0.000 |
Birth weight small for gestational age, n (%) | 8 (21.6%) | 12 (14.6%) | 8 (11.9%) | 0.022 |
Head circumference (cm), mean ± SD | 32.45 ± 3.02 | 34.37 ± 1.32 | 34.07 ± 1.40 | 0.000 |
Head circumference small for gestational age, n (%) | 7 (18.9%) | 6 (7.3%) | 6 (9.0%) | 0.028 |
Microcephaly, n (%) | 5 (13.5%) | 3 (3.7%) | 3 (4.5%) | 0.004 |
Cesarean section, n (%) | 13 (35.1%) | 20 (24.4%) | 14 (20.9%) | NS |
Apgar 5′, median (IQR) | 9 (9–10) | 9 (9–10) | 9 (9–10) | 0.019 |
Normal Development in 119 Infected Patients | Abnormal Development in 119 Infected Patients | ||
---|---|---|---|
One Sequela | Sequelae > 2 | ||
T1 No. (%) | T1 No. (%) | T1 No. (%) | |
CMV (n = 84) | |||
Asymptomatic at birth (n = 55) | 49/55 (89.1) | 6/55 (10.9) | 0/55 (0) |
Symptomatic at birth (n = 29) | 13/29 (44.8) | 12/29 (41.4) | 4/29 (13.8) |
TOXOPLASMA (n = 18) | |||
Asymptomatic at birth (n = 12) | 11/12 (91.7) | 1/12 (8.3) | 0/12 (0.0) |
Symptomatic at birth (n = 6) | 3/6 (50.0) | 2/6 (33.3) | 1/6 (16.7) |
SYPHILIS (n = 17) | |||
Asymptomatic at birth (n = 15) | 14/15 (93.3) | 1/15 (6.7) | 0/15 (0.0) |
Symptomatic at birth (n = 2) | 0/2 (0.0) | 0/2 (0.0) | 2/2 (100.0) |
TOTAL (n = 119) | |||
Asymptomatic at birth (n = 82) | 74/82 (90.2) | 8/82 (9.8) | 0/82 (0.0) |
Symptomatic at birth (n = 37) | 16/37 (43.2) | 14/37 (37.8) | 7/37 (18.9) |
Type of Infection | Cognitive Delay (Score < 85) | Motor Impairment (Score < 85) | Mild SNHL | Severe SNHL | Mild Abnormal Vision | Severe Visual Impairment |
---|---|---|---|---|---|---|
CMV (n= 84) | 3 (3.6%) | 11 (13.1%) | 11 (13.1%) | 1 (1.2%) | 2 (2.4%) | 0 (0.0%) |
Toxoplasma (n = 18) | 1 (5.6%) | 3 (16.6%) | 1 (5.6%) | 0 (0.0%) | 1 (5.6%) | 1 (5.6%) |
Syphilis (n= 17) | 0 (0%) | 3 (17.6%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
Total (n= 119) | 4 (3.4%) | 17 (14.3%) | 12 (10.1%) | 1 (0.8%) | 3 (2.5%) | 1 (0.8%) |
Normal Development in 92 Infected Patients | Abnormal Development in 92 Infected Patients | ||
---|---|---|---|
One Sequela | Sequelae > 2 | ||
T2 No. (%) | T2 No. (%) | T2 No. (%) | |
CMV (n = 69) | |||
Asymptomatic at birth (n = 42) | 34/42 (81.0) | 8/42 (19.0) | 0/42 (0.0) |
Symptomatic at birth (n = 27) | 8/27 (29.6) | 14/27 (51.9) | 5/27 (18.5) |
TOXOPLASMA (n = 14) | |||
Asymptomatic at birth (n = 8) | 4/8 (50.0) | 4/8 (50.0) | 0/8 (0.0) |
Symptomatic at birth (n = 6) | 3/6 (50.0) | 1/6 (16.7) | 2/6 (33.3) |
SYPHILIS (n = 9) | |||
Asymptomatic at birth (n = 7) | 5/7 (71.4) | 2/7 (28.6) | 0/7 (0.0) |
Symptomatic at birth (n = 2) | 0/2 (0.0) | 0/2 (0.0) | 2/2 (100.0) |
TOTAL (n = 92) | |||
Asymptomatic at birth (n = 57) | 43/57 (75.4) | 14/57 (24.6) | 0/57 (0.0) |
Symptomatic at birth (N = 35) | 11/35 (31.4) | 15/35 (42.9) | 9/35 (25.7) |
Type of Infection | Cognitive Delay (Score < 85) | Motor Impairment (Score < 85) | Mild SNHL | Severe SNHL | Mild Abnormal Vision | Severe Visual Impairment | Language Delay |
---|---|---|---|---|---|---|---|
CMV (n = 69) | 4 (5.8%) | 4 (5.8%) | 9 (13.0%) | 1 (1.4%) | 2 (2.%) | 0 (0.0%) | 18 (26.1%) |
Toxoplasma (n = 14) | 2 (14.3%) | 2 (14.3%) | 0 (0.0%) | 0 (0.0%) | 1 (7.1%) | 1 (7.1%) | 5 (35.7%) |
Syphilis (n = 9) | 1 (11.1%) | 1 (11.1%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 3 (33.3%) |
Total (n = 92) | 7 (7.6%) | 7 (7.6%) | 9 (9.8%) | 1 (1.1%) | 3 (2.3%) | 1 (1.1%) | 26 (28.3%) |
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Auriti, C.; Bucci, S.; De Rose, D.U.; Coltella, L.; Santisi, A.; Martini, L.; Maddaloni, C.; Bersani, I.; Lozzi, S.; Campi, F.; et al. Maternal–Fetal Infections (Cytomegalovirus, Toxoplasma, Syphilis): Short-Term and Long-Term Neurodevelopmental Outcomes in Children Infected and Uninfected at Birth. Pathogens 2022, 11, 1278. https://doi.org/10.3390/pathogens11111278
Auriti C, Bucci S, De Rose DU, Coltella L, Santisi A, Martini L, Maddaloni C, Bersani I, Lozzi S, Campi F, et al. Maternal–Fetal Infections (Cytomegalovirus, Toxoplasma, Syphilis): Short-Term and Long-Term Neurodevelopmental Outcomes in Children Infected and Uninfected at Birth. Pathogens. 2022; 11(11):1278. https://doi.org/10.3390/pathogens11111278
Chicago/Turabian StyleAuriti, Cinzia, Silvia Bucci, Domenico Umberto De Rose, Luana Coltella, Alessandra Santisi, Ludovica Martini, Chiara Maddaloni, Iliana Bersani, Simona Lozzi, Francesca Campi, and et al. 2022. "Maternal–Fetal Infections (Cytomegalovirus, Toxoplasma, Syphilis): Short-Term and Long-Term Neurodevelopmental Outcomes in Children Infected and Uninfected at Birth" Pathogens 11, no. 11: 1278. https://doi.org/10.3390/pathogens11111278