Human Papillomavirus in Newborns L. Conde-Ferráez1, G. Quintal Bojórquez2, M. Pérez Lopez3, R.E. Suárez Allén1, G. Ayora-Talavera1, M.R. González-Losa1. 1CIR-Biomédicas,
Universidad Autónoma de Yucatán. Mexico.
[email protected]. 2Facultad de Química, Universidad Autónoma de Yucatán; 3 Hospital General “Agustín O’Horán” , Servicios de Salud de Yucatán. Secretaría de Salud, Mexico
INTRODUCTION
Table. Variables present in 372 newborns analysed for association with HPV positivity . P values < 0.05 are significant.
Maternal transmission of Human papillomavirus (HPV) has been described to occur mostly during vaginal delivery in women with condyloma acuminata, which is the main risk factor associated to the development of juvenile onset respiratory papillomatosis in the child. (1) Other risk factors associated to vertical transmission are adolescent mother, premature rupture of membranes (PROM), cephalic presentation of the product and prolonged labor. HPV transmission and prevalence in cesarean delivered neonates have been described, and some evidence have suggested other routes of transmission such as transplacental or ascendant infection. (2, 3) In this work we detected HPV in cervical uterus of pregnant women at the time of delivery, and in oral mucosa of their neonates, and studied epidemiological determinants associated to transmission.
OR (CI)
p value (X2 test test))
153 197
1.29 (0.50-3.29)
0.5646193
21 1
319 31
2.04 (0.28-42.08)
0.4841772
PROM • Yes • No
5 17
40 310
2.28 (0.69 - 7.06)
0.1149347
LABOR • Yes • No
13 9
211 139
0.95 (0.37 - 2.49)
0.9115685
4 18
32 318
2.21 (0.59 - 7.52)
0.1642377
3 19 0
8 341 1
6.73 (1.29 - 31.37)
0.0023461
• 16-19 yrs old
13
104
3.42 (1.32 - 8.98)
0.0039966
• > 20 yrs old
9
246
Frequencies
Variable
METHODS
HPV+
HPV HPV--
MODE OF DELIVERY • Vaginal • Cesarean
11 11
PRESENTATION • Cephalic • Other
MATERNAL HISTORY OF CONDYLOMA • Ever • Never
This project was approved by the bioethical committee from the Hospital General “Agustín O’Horán” in which the study was carried out, during 20102011 in Merida Yucatan (Southeast Mexico). Patients from this public facility are mostly low-income native Mexican. Molecular detection of HPV was performed using universal primers and nested PCR in the Virology Laboratory from CIRBiomédicas, UADY.
CONDYLOMA AT DELIVERY • Yes • No • No data MATERNAL AGE
Informed consent
MOTHERS (attending for delivery)
Interview and clinical file
NEONATES (within 24hr after birth)
Oral swab
Cervical sample Automatized DNA extraction
HPV and b-globin PCR
Data base SPSS
Statistical analyses (Odds ratio, X2 test)
RESULTS We processed 372 mother-newborn paired samples. Mothers’ age ranged between 16 to 41 years old (mean 23.4 years). Overall, HPV DNA was found in 8.9% (33/372) of the mothers’ cervical samples, and in 5.9% (22/372) of the newborns’ oral mucosa. This could represent a mother transmission rate of 66.6%.
DISCUSSION HPV in neonates was not related to the mode of delivery, and therefore mechanisms such as ascendant or transplacental infection might be involved. (2,3) Transmission was significantly associated to younger maternal age, and to condyloma in the mother at delivery. Our results suggest the possible HPV transmission to newborns from HPV+ mothers in 66.6% of cases. A high percentage of these women (68.3%) had never participated in the cervical cancer screening and therefore, the presence of cervical lesions at the time of sampling was unknown, and might be related to the high transmission rate. The complete genotyping of HPV positive samples in both mothers and newborns is underway using sequencing and specific PCR. The genotypes most frequently found as yet are 6, 11, and 31. However, preliminary results have shown disparities in mother-newborn genotypes. Low type concordance in mother-newborn pairs has been described elsewhere and have been attributed to technical issues, presence of multiple types, dynamic of infection adquisition-clearence during pregnancy, and/or other contacts soon after birth. (4,5,6) To our knowledge, this is the first study of HPV in neonates performed in Mexico. Longitudinal studies are required to investigate the clinical significance of these findings, and to identify transient and persistent infections in the infants.
AKNOWLEDGEMENTS:
Half of the HPV positive newborns were born by cesarean section (11/22). Vaginal delivery, PROM and cephalic presentation were not associated to the presence of HPV in the newborns. The analysis is shown on the table.
We thank A.E. Santamaría, M.A. Molano, J. Cámara and R. Robles for technical and logistical support. FUNDING: SEP-Promep, Mexico
Eleven out of 33 (33.33%) HPV+ mothers had condyloma at the time of delivery; and 3 of their respective neonates were HPV+, representing that 27% of condylomatosis cases had HPV transmission to the newborns. Interestingly, all of the later were born by cesarean delivery, as currently indicated in this Hospital. The remaining 19 HPV positive neonates were born from positive mothers who could course a subclinical or latent infection.
REFERENCES 1) 2) 3) 4) 5) 6)
Silverberg, M.J., Thorsen, P., Lindeberg, H., Grant, L.A., Shah, K.V. 2003. Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis. Obstetrics & Gynecology, 101(4):645-652. Rombaldi, R.L., Serafini, E.P., Mandelli, J., Zimmermann, E., Losquiavo, K.P. 2008. Trasnplacental transmission of Human Papillomavirus Virology Journal, 5:106 Rintala, M.A.M., Grénman, S.E., Puranen, M.H., Isolauri, E., Ekblad, U., Kero, P.O., Syrjanen, S. 2005. Transmission of High risk human papillomavirus between parents and infant: a prospective study of HPVB in families in Finland. Clin Microbiol 43(1): 376–381 Rombaldi R.L., Serafini, E.P., Mandelli, J., Zimmermann, E., Losquiavo, K.P. et al 2009. Perinatal transmission of human papilomavirus DNA. Virology Journal 6:83 Castellsagué X, Drudis T, Cañadas MP, Goncé A, Ros R, Pérez JM, Quintana MJ, Muñoz J, Albero G, de Sanjosé S, Bosch FX. Human Papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain. BMC Infect Dis. 2009 May 27;9:74. Smith EM, Ritchie JM, Yankowitz J, Swarnavel S, Wang D, Haugen TH, Turek LP. 2004. Human papillomavirus prevalence and types in newborns and parents: concordance and modes of transmission. Sex Transm Dis. Jan;31(1):57-62.