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597: Clinical risk factors associated with mother-to-child transmission (MTCT) of hepatitis C virus (HCV)
Poster Session IV
Epidemiology, Infectious Disease, Intrapartum Fetal Assessment, Operative Obstetrics, Obstetric Quality & Safety, Public Health-Global Health
www.AJOG.org
598 Diagnosis of perinatal cytomegalovirus infection via serial daily rapid urine viral culture Natali Aziz1, Frances Guo2, Michal McDowell3, Ann Folkins4, Mary Norton1, William Benitz5, Benjamin Pinsky6 1 Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Stanford, CA, 2Stanford University School of Medicine, Pathology, Stanford, CA, 3Stanford University, Human Biology, Stanford, CA, 4Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Pathology, Stanford, CA, 5Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Neonatology, Stanford, CA, 6Stanford University School of Medicine, Pathology and Medicine-Infectious Diseases, Stanford, CA
597 Clinical risk factors associated with mother-tochild transmission (MTCT) of hepatitis C virus (HCV) Mona Prasad1, Jonathan Honegger2, Kara B. Markham3, Christopher Walker4 1
The Ohio State University, Maternal Fetal Medicine, Columbus, OH, Nationwide Children’s Hospital, Infectious Disease, Columbus, OH, 3The Ohio State University, Maternal Fetal Medicine, Columbus, OH, 4Nationwide Children’s Hospital, Center for Vaccines and Immunity, Columbus, OH 2
OBJECTIVE: To determine the association between viral load, chronicity of disease, and mode of delivery and MTCT of HCV. STUDY DESIGN: A prospective cohort of HCV mono-infected women, identified between 2006 and 2011, at The Ohio State University Medical Center. Women were included if they were HCV antibody positive with demonstrable viremia. Demographics, serotype, 3rd trimester viral load, and clinical outcomes were recorded. Infants were followed at Nationwide Children’s Hospital and blood samples were drawn at 3, 6, and 18 months of age. Infants were considered to be HCV infected if they were HCV-RNA positive at 3 or 6 months or if they had persistence of anti-HCV beyond 18 months of age. RESULTS: 19 HCV mono-infected women gave birth to 23 neonates during this time period. 52% were infected with serotype 1a,4.3% with 1b, 8.7% with 2, 8.7% 2a, 8.7% 2b and 17% 3a. The average viral load in the third trimester was 3,658,042 IU/ml and the average duration of disease in infected mothers was 7.3 years. 61% delivered vaginally, 30% delivered via c-section, 4.3% delivered via forceps-assist, and 4.3% delivered via successful vaginal birth after cesarean. Two neonates (8.7%) were confirmed positive for MTCT of HCV; both were delivered vaginally; maternal serotype was 1a for each. 3rd trimester viral load was significantly higher in affected infants (12,885,487 IU/ml vs 2,805,905 IU/ml, p⫽.003). There was no difference in chronicity of disease (8.7 yrs vs 1.25 years, p⫽0.25). Cesarean delivery did not significantly impact MTCT ( RR 0.42, 95% CI 0.02-7.8629). CONCLUSION: Our cohort substantiates current estimates of MTCT of HCV. Though limited by small sample size, the significance of high viral loads is clear. Threshold levels for transmission were not established by this study, and would require a much larger scale project to do so. Our data suggests a trend toward prevention of MTCT of HCV with cesarean delivery, but failed to achieve statistical significance. Further research is necessary to define optimal practice patterns to prevent MTCT of HCV.
S270
OBJECTIVE: Perinatal cytomegalovirus (CMV) infection affects an estimated 40,000 newborns annually. Accurate diagnosis of CMV in infants is critical in light of potential benefits of antiviral therapy. Data comparing different diagnostic strategies are limited, and evidence for the common practice of testing multiple samples from the same patient is lacking. We compared serial daily rapid shell vial culture (SVC) and routine viral culture (RVC) for the diagnosis of infant CMV infection. STUDY DESIGN: We conducted a retrospective study of all urine samples in infants ⬍100 days old sent for viral culture from January 1, 2001 to December 31, 2010 at an academic medical center clinical virology laboratory. Each sample was tested by both rapid SVC and RVC. We evaluated concordance of these two tests, and calculated the detection rate of a serial daily viral culture testing strategy. RESULTS: Between 1-7 (average 2.1) samples were sent for viral culture per infant. Of 862 infants tested, 40 (4.6%) had at least one positive sample. The serial daily detection rate was 87.5% (35/40) with one sample, 97.5% (39/40) with two samples, and 100% (40/40) with three samples. There were a total of 58 positive samples from these 40 infants. SVC and RVC were concordant in 49/58 samples, with all 9 discrepancies being SVC positive and RVC negative. 6 of 9 discrepant results were confirmed with concurrent positive CMV PCR (2/9) or positive SVC (4/9) on samples collected within 2 days of the discrepant sample. In 44/1837 (2.4%) samples, RVC was negative but SVC results were uninterpretable due to toxic interference, laboratory error, or unacceptable controls. CONCLUSION: These results confirm the efficacy of testing three urine samples on consecutive days for the detection of CMV in infant urine. Though SVC appeared more sensitive than RVC, the risk of SVC failure due to technical limitations supports the use of multi-modality testing to optimize detection. Further comparative studies are needed to evaluate the role of CMV PCR as an adjunct to the current testing strategy or as a replacement for RVC.
599 Differential responses to Toll-like receptor (TLR) ligands in Hofbauer cells (HBCs: placental macrophages), placental fibroblasts (FIBs) and human umbilical vein endothelial cells (HUVECs): implications for the genesis of fetal inflammatory response syndrome (FIRS) Omar Young1, Zhonghua Tang1, Tracy Niven-Fairchild1, Seth Guller1 1 Yale University School of Medicine, Obstetrics, Gynecology and Reproductive Sciences, New Haven, CT
OBJECTIVE: Acute chorioamnionitis and chronic inflammation have been implicated in dysfunctional neuronal migration, cerebral palsy and FIRS. Little is known as to how various cell types in the placental villus core and umbilical cord respond to a microbial challenge. The study aims to uncover the patterns of microbial-driven pro-inflammatory processes in HBCs, FIBs, and HUVECs so as to gain insight into the mechanism of FIRS. STUDY DESIGN: HBCs, FIBs and HUVECs were cultured in a medium containing 10% fetal bovine serum (FBS) or in a serum-free medium for 24h or 48h with and without lipopolysaccharide (LPS: a TLR-4 ligand), peptidoglycan (PG: a TLR-2 ligand), polyinosinic:polycyt-
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
Epidemiology, Infectious Disease, Intrapartum Fetal Assessment, Operative Obstetrics, Obstetric Quality & Safety, Public Health-Global Health
www.AJOG.org
598 Diagnosis of perinatal cytomegalovirus infection via serial daily rapid urine viral culture Natali Aziz1, Frances Guo2, Michal McDowell3, Ann Folkins4, Mary Norton1, William Benitz5, Benjamin Pinsky6 1 Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Stanford, CA, 2Stanford University School of Medicine, Pathology, Stanford, CA, 3Stanford University, Human Biology, Stanford, CA, 4Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Pathology, Stanford, CA, 5Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Neonatology, Stanford, CA, 6Stanford University School of Medicine, Pathology and Medicine-Infectious Diseases, Stanford, CA
597 Clinical risk factors associated with mother-tochild transmission (MTCT) of hepatitis C virus (HCV) Mona Prasad1, Jonathan Honegger2, Kara B. Markham3, Christopher Walker4 1
The Ohio State University, Maternal Fetal Medicine, Columbus, OH, Nationwide Children’s Hospital, Infectious Disease, Columbus, OH, 3The Ohio State University, Maternal Fetal Medicine, Columbus, OH, 4Nationwide Children’s Hospital, Center for Vaccines and Immunity, Columbus, OH 2
OBJECTIVE: To determine the association between viral load, chronicity of disease, and mode of delivery and MTCT of HCV. STUDY DESIGN: A prospective cohort of HCV mono-infected women, identified between 2006 and 2011, at The Ohio State University Medical Center. Women were included if they were HCV antibody positive with demonstrable viremia. Demographics, serotype, 3rd trimester viral load, and clinical outcomes were recorded. Infants were followed at Nationwide Children’s Hospital and blood samples were drawn at 3, 6, and 18 months of age. Infants were considered to be HCV infected if they were HCV-RNA positive at 3 or 6 months or if they had persistence of anti-HCV beyond 18 months of age. RESULTS: 19 HCV mono-infected women gave birth to 23 neonates during this time period. 52% were infected with serotype 1a,4.3% with 1b, 8.7% with 2, 8.7% 2a, 8.7% 2b and 17% 3a. The average viral load in the third trimester was 3,658,042 IU/ml and the average duration of disease in infected mothers was 7.3 years. 61% delivered vaginally, 30% delivered via c-section, 4.3% delivered via forceps-assist, and 4.3% delivered via successful vaginal birth after cesarean. Two neonates (8.7%) were confirmed positive for MTCT of HCV; both were delivered vaginally; maternal serotype was 1a for each. 3rd trimester viral load was significantly higher in affected infants (12,885,487 IU/ml vs 2,805,905 IU/ml, p⫽.003). There was no difference in chronicity of disease (8.7 yrs vs 1.25 years, p⫽0.25). Cesarean delivery did not significantly impact MTCT ( RR 0.42, 95% CI 0.02-7.8629). CONCLUSION: Our cohort substantiates current estimates of MTCT of HCV. Though limited by small sample size, the significance of high viral loads is clear. Threshold levels for transmission were not established by this study, and would require a much larger scale project to do so. Our data suggests a trend toward prevention of MTCT of HCV with cesarean delivery, but failed to achieve statistical significance. Further research is necessary to define optimal practice patterns to prevent MTCT of HCV.
S270
OBJECTIVE: Perinatal cytomegalovirus (CMV) infection affects an estimated 40,000 newborns annually. Accurate diagnosis of CMV in infants is critical in light of potential benefits of antiviral therapy. Data comparing different diagnostic strategies are limited, and evidence for the common practice of testing multiple samples from the same patient is lacking. We compared serial daily rapid shell vial culture (SVC) and routine viral culture (RVC) for the diagnosis of infant CMV infection. STUDY DESIGN: We conducted a retrospective study of all urine samples in infants ⬍100 days old sent for viral culture from January 1, 2001 to December 31, 2010 at an academic medical center clinical virology laboratory. Each sample was tested by both rapid SVC and RVC. We evaluated concordance of these two tests, and calculated the detection rate of a serial daily viral culture testing strategy. RESULTS: Between 1-7 (average 2.1) samples were sent for viral culture per infant. Of 862 infants tested, 40 (4.6%) had at least one positive sample. The serial daily detection rate was 87.5% (35/40) with one sample, 97.5% (39/40) with two samples, and 100% (40/40) with three samples. There were a total of 58 positive samples from these 40 infants. SVC and RVC were concordant in 49/58 samples, with all 9 discrepancies being SVC positive and RVC negative. 6 of 9 discrepant results were confirmed with concurrent positive CMV PCR (2/9) or positive SVC (4/9) on samples collected within 2 days of the discrepant sample. In 44/1837 (2.4%) samples, RVC was negative but SVC results were uninterpretable due to toxic interference, laboratory error, or unacceptable controls. CONCLUSION: These results confirm the efficacy of testing three urine samples on consecutive days for the detection of CMV in infant urine. Though SVC appeared more sensitive than RVC, the risk of SVC failure due to technical limitations supports the use of multi-modality testing to optimize detection. Further comparative studies are needed to evaluate the role of CMV PCR as an adjunct to the current testing strategy or as a replacement for RVC.
599 Differential responses to Toll-like receptor (TLR) ligands in Hofbauer cells (HBCs: placental macrophages), placental fibroblasts (FIBs) and human umbilical vein endothelial cells (HUVECs): implications for the genesis of fetal inflammatory response syndrome (FIRS) Omar Young1, Zhonghua Tang1, Tracy Niven-Fairchild1, Seth Guller1 1 Yale University School of Medicine, Obstetrics, Gynecology and Reproductive Sciences, New Haven, CT
OBJECTIVE: Acute chorioamnionitis and chronic inflammation have been implicated in dysfunctional neuronal migration, cerebral palsy and FIRS. Little is known as to how various cell types in the placental villus core and umbilical cord respond to a microbial challenge. The study aims to uncover the patterns of microbial-driven pro-inflammatory processes in HBCs, FIBs, and HUVECs so as to gain insight into the mechanism of FIRS. STUDY DESIGN: HBCs, FIBs and HUVECs were cultured in a medium containing 10% fetal bovine serum (FBS) or in a serum-free medium for 24h or 48h with and without lipopolysaccharide (LPS: a TLR-4 ligand), peptidoglycan (PG: a TLR-2 ligand), polyinosinic:polycyt-
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012