Point-of-Care Intrapartum Group B Streptococcus Molecular Screening: Effectiveness and Costs.

OBJECTIVE: To assess outcomes and costs associated with around-the-clock point-of-care intrapartum group B streptococcus (GBS) polymerase chain reaction (PCR) screening. METHODS: Intrapartum PCR screening was implemented in 2010. Intrapartum PCR was compared with antenatal culture screening in an uncontrolled, single institution, preintervention and postintervention study. The study periods included 4 years before and 6 years after the intervention, commencing in 2006 and concluding in 2015. The primary outcome measure was rate of early-onset neonatal GBS disease. Secondary outcomes included length of stay, days of antibiotics, and costs. RESULTS: During the 4 years of antenatal culture screening, 11,226 deliveries were recorded compared with 18,835 in the 6 years of intrapartum GBS PCR screening, corresponding to 11,818 and 18,980 live births, respectively. During the antenatal culture period, 3.8% of term deliveries did not undergo GBS testing compared with 0.1% during the intrapartum PCR period (P<.001). Between the two periods, the rate of proven early-onset GBS disease cases decreased from 1.01/1,000 to 0.21/1,000 (P=.026) and probable early-onset GBS disease cases from 2.8/1,000 to 0.73/1,000 (P<.001); the risk ratio for both was 0.25, 95% CI (0.14-0.43). Total days of hospital and antibiotic therapy for early-onset GBS disease declined by 64% and 60%, respectively, with no significant difference for average length of stay or antibiotic duration preintervention and postintervention. The yearly cost of delivery and treatment of newborns with GBS infection was reduced from $41,875±6,823 to $11,945±10,303 (P<.001). The estimated extra cost to avoid one early-onset GBS disease was $5,819. CONCLUSION: Point-of-care intrapartum GBS PCR screening was associated with a significant decrease in the rate of early-onset GBS disease and antibiotic use in newborns. The additional PCR costs were offset in part by the reduction in early-onset GBS disease treatment costs.

Cost and effectiveness of intrapartum group B streptococcus polymerase chain reaction screening for term deliveries.

OBJECTIVE: To estimate the cost and consequences of intrapartum polymerase chain reaction (PCR) screening on early-onset group B streptococcal (GBS) disease compared with the antenatal lower vagina culture screening recommended in France. METHODS: This was a single-institution study comparing the intrapartum PCR screening strategy implemented in 2010 with antenatal culture strategy in place in 2009. Early-onset GBS disease in newborns was monitored exhaustively. We estimated direct costs, including screening test costs and hospital costs, for deliveries of healthy newborns compared with those infected with GBS. Costs in 2009 and 2010 were compared on an intention-to-treat basis. RESULTS: Term deliveries were 2,761 and 2,814 in 2009 and 2010, respectively. Among the screened mothers, the vaginal GBS colonization rate was 11.7% based on antenatal GBS culture screening in 2009 compared with 16.7% in 2010 using the intrapartum PCR testing. The overall probabilities of neonatal GBS disease were 0.9% compared with 0.5%, and the average total cost per delivery was $1,759±1,209 in 2009 compared with $1,754±842 in 2010 (P=.9) in antenatal and intrapartum screening strategies, respectively. The number and severity of cases of early-onset GBS disease and the resulting hospital costs were higher in 2009. CONCLUSION: Polymerase chain reaction intrapartum screening strategy was cost-neutral when compared with the 2009 antenatal lower vagina culture screening, with a significant decrease in early-onset GBS disease.

Diagnostic accuracy of a rapid real-time polymerase chain reaction assay for universal intrapartum group B streptococcus screening.

BACKGROUND: Intrapartum antibiotic prophylaxis is currently given to mothers who test positive for group B streptococcus (GBS) by antenatal culture-based screening, with a risk-based approach for cases with an unknown GBS status. A rapid real-time polymerase chain reaction (PCR) assay for the detection of GBS became available recently, making intrapartum screening possible. We aimed to assess its diagnostic accuracy and to compare it with antenatal screening. METHODS: We conducted a prospective study in a French hospital. All pregnant women giving birth at the maternity ward were considered for inclusion, except those with planned cesarean delivery, with delivery at <35 weeks gestation, and who received antibiotic therapy before admission. We performed GBS culture (the reference standard) and a molecular GBS test (Xpert GBS; Cepheid) on intrapartum specimens. Decisions about intrapartum antibiotic prophylaxis were based on the current GBS screening by culture at 35-37 weeks gestation. RESULTS: We prospectively enrolled 968 pregnant women from April 2007 through March 2008. The overall molecular GBS test yield was 89.2%. Among the 863 women with available results, the molecular GBS test had a sensitivity of 98.5%, specificity of 99.6%, positive predictive value of 97.8%, and negative predictive value of 99.7%. The positive predictive value of antenatal culture for identifying colonization status at delivery was low (58.3%), whereas the negative predictive value was imperfect (92.1%). CONCLUSIONS: This real-time PCR assay is a highly accurate test to identify intrapartum GBS carriers at point of care. This new tool could enhance the exact identification of candidates for intrapartum antibiotic prophylaxis, including women with preterm rupture of membranes or preterm labor.

Fetal RhD genotyping by maternal serum analysis: a two-year experience.

OBJECTIVE: The purpose of this study was to determine the accuracy of the none-invasive prenatal determination of polymerase chain reaction (PCR)-based fetal RhD genotyping. STUDY DESIGN: A prospective case series was undertaken on all RhD-negative pregnant women presenting for genetic counseling in our prenatal diagnosis center from January 2001 until December 2002. Results were compared with serologic RhD typing of the newborns. RESULTS: Among the 285 pregnant women who participated in the study, fetal RhD status could be determined for 283 patients. In 2 cases, the RhD-negative phenotype of the mother was not the result of a complete RHD gene deletion, and therefore, the status of the fetus could not be determined. Neither false-negative nor false-positive results were observed. CONCLUSION: The present report demonstrates that a reliable fetal RHD genotype determination can be achieved with 100% accuracy. It is therefore possible to consider that such an assay could be systematically proposed to all RhD-negative pregnant women in order to more effectively utilize RhD prophylaxis.

Placenta-specific INSL4 expression is mediated by a human endogenous retrovirus element.

The human insulin-family genes regulate cell growth, metabolism, and tissue-specific functions. Among these different members, only INSL4 gene shows a predominant placenta-specific expression. Here, we show that the human INSL4 gene is tightly clustered with three other members of the human insulin superfamily (RLN1, RLN2, and INSL6) within a 176-kilobase genomic segment on chromosome region 9p23.3-p24.1. We also report evidence that INSL4 is probably the only insulin-like growth factor gene to be primate-specific. We identified an unexpected human endogenous retrovirus (HERV) element inserted into the human INSL4 promoter with a sequence similar to that of env gene, flanked by two long terminal repeats(LTRs). The emergence of INSL4 gene and genomic insertion of HERV appear to have occurred after the divergence of New World and Old World monkeys ( approximately 45 million years ago). Transient transfection experiments showed that the placenta-specific expression of INSL4 is mediated by the 3' LTR of the HERV element, and that the latter may have a major role in INSL4 up-regulation during human cytotrophoblast differentiation into syncytiotrophoblast. Finally, we identified an INSL4 alternatively spliced mRNA species that encodes putative novel INSL4-like peptides. These data support the view that ancient retroviral infection may have been a major event in primate evolution, especially in the functional evolution of the human placenta.

Fetal RHD genotyping in maternal serum during the first trimester of pregnancy.

Fetal RHD genotype determination is useful in the management of sensitized RhD-negative pregnant women. It can be ascertained early during pregnancy by chorionic villus sampling (CVS) or amniocentesis. However, these procedures are invasive, resulting both in an increased risk of fetal loss and in an increased severity of immunization due to fetomaternal haemorrhage. A reliable determination of RHD genotype by fetal DNA analysis in maternal serum during the first trimester of pregnancy is reported in this study. One hundred and six sera from RhD-negative pregnant women were obtained during the first trimester of pregnancy. These sera were tested for the presence of RHD gene using a new real-time polymerase chain reaction assay and the results compared with those obtained later in pregnancy on amniotic fluid cells and by RHD serology of the new-born. All sera from women carrying a RhD-positive fetus (n = 62) gave positive results for RHD gene detection and sera from women carrying a RhD-negative fetus (n = 40) were negative. The high level of accuracy of fetal RHD genotyping obtained in this study could enable this technique to be offered on a routine basis for the management of RhD-negative patients during the first trimester of pregnancy.