scholarly journals Pharmacokinetics and Safety of Single-Dose Tenofovir Disoproxil Fumarate and Emtricitabine in HIV-1-Infected Pregnant Women and Their Infants

2011 ◽  
Vol 55 (12) ◽  
pp. 5914-5922 ◽  
Author(s):  
Patricia M. Flynn ◽  
Mark Mirochnick ◽  
David E. Shapiro ◽  
Arlene Bardeguez ◽  
John Rodman ◽  
...  
Keyword(s):  
Single Dose ◽  
Cesarean Section ◽  
Cord Blood ◽  
Pregnant Women ◽  
Tenofovir Disoproxil Fumarate ◽  
Maternal Plasma ◽  
Time Curve ◽  
Blood Concentrations ◽  
Macaque Model ◽  
Immunodeficiency Virus

ABSTRACTTenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section. Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth. All regimens were safe and well tolerated. Maternal areas under the serum concentration-time curve (AUC) and concentrations at the end of sampling after 24 h (C24) were similar between the two doses of TDF; the maximum concentrations of the drugs in serum (Cmax) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally (P= 0.04 and 0.046, respectively). The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median TFV concentration of 12 ng/ml 12 h after birth. Following administration of a single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their infants, 600 mg of TDF is acceptable as a single dose during labor. Low concentrations at birth support infant dosing as soon after birth as possible. Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression.

scholarly journals Population Pharmacokinetics of Emtricitabine in Human Immunodeficiency Virus Type 1-Infected Pregnant Women and Their Neonates

2008 ◽  
Vol 53 (3) ◽  
pp. 1067-1073 ◽  
Author(s):  
Déborah Hirt ◽  
Saik Urien ◽  
Elisabeth Rey ◽  
Elise Arrivé ◽  
Didier K. Ekouévi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cord Blood ◽  
Pregnant Women ◽  
High Performance ◽  
Placental Transfer ◽  
Compartment Model ◽  
Effect Compartment ◽  
Maternal Circulation ◽  
Time Curve ◽  
Immunodeficiency Virus

ABSTRACT The objectives of this study were to evaluate emtricitabine (FTC) pharmacokinetics in pregnant women and their neonates and to determine the optimal prophylactic dose for neonates after birth to prevent mother-to-child transmission of human immunodeficiency virus (HIV). A total of 38 HIV-infected pregnant women were administered tenofovir disoproxyl fumarate (300 mg)-FTC (200 mg) tablets—two tablets at the initiation of labor and one daily for 7 days postpartum. By pair, 11 maternal, one cord blood, and two neonatal FTC concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry validated method and analyzed by a population approach. Model and mean estimates (interpatient variability) were a two-compartment model for mothers, with an absorption rate constant of 0.54 h−1 (61%), apparent elimination and intercompartmental clearances of 23.2 (17%) and 6.04 liters·h−1, and apparent central and peripheral volumes of 127 and 237 liters, respectively; an effect compartment linked to maternal circulation for cord blood and a neonatal compartment disconnected, after delivery, with a 10.6-h half-life (30%). After the 400-mg FTC administration, the median population area under the concentration-time curve and the minimal and maximal plasma FTC concentrations in pregnant women were 14.3 mg·liter−1·h and 1.68 and 0.076 mg/liter, respectively. At delivery, median (range) predicted maternal and cord blood FTC concentrations were, respectively, 1.16 (0.14 to 1.99) and 0.72 (0.05 to 1.19) mg·liter−1. We concluded that the 400-mg FTC administration in pregnant women produces higher exposition than does the 200-mg administration in other adults, at steady state. FTC was shown to have good placental transfer (80%). Administering 1 mg FTC/kg as soon as possible after birth or 2 mg/kg 12 h after birth should produce neonatal concentrations comparable to the concentrations observed in adults.

scholarly journals Single-Dose and Steady-State Pharmacokinetics of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Children

2004 ◽  
Vol 48 (1) ◽  
pp. 124-129 ◽  
Author(s):  
Rohan Hazra ◽  
Frank M. Balis ◽  
Antonella N. Tullio ◽  
Ellen DeCarlo ◽  
Carol J. Worrell ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Single Dose ◽  
Steady State ◽  
Antiretroviral Therapy ◽  
Tenofovir Disoproxil Fumarate ◽  
Geometric Mean ◽  
Transcriptase Inhibitor ◽  
Time Curve ◽  
Immunodeficiency Virus ◽  
Tenofovir Df

ABSTRACT Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m2; the median administered dose was 208 mg/m2. Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to ∞ (AUC0-∞) was 2,150 ng · h/ml and the geometric mean maximum concentration (C max) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng · h/ml and was significantly higher than the AUC0-∞ after the first dose (P = 0.0004). The geometric mean C max at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, ∼3,000 ng · h/ml; C max, ∼300 ng/ml) treated with tenofovir DF at 300 mg.

scholarly journals Anti-α4β7 monoclonal antibody–conjugated nanoparticles block integrin α4β7 on intravaginal T cells in rhesus macaques

2020 ◽  
Vol 6 (34) ◽  
pp. eabb9853
Author(s):  
Sidi Yang ◽  
Geraldine Arrode-Bruses ◽  
Ines Frank ◽  
Brooke Grasperge ◽  
James Blanchard ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Single Dose ◽  
Side Effects ◽  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Vaginal Infection ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Vaginal Tract

Intravenous administration of anti-α4β7 monoclonal antibody in macaques decreases simian immunodeficiency virus (SIV) vaginal infection and reduces gut SIV loads. Because of potential side effects of systemic administration, a prophylactic strategy based on mucosal administration of anti-α4β7 antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α4β7 monoclonal antibody–conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α4β7 gel). When intravaginally administered as a single dose in a rhesus macaque model, the formulation preferentially bound to CD4+ or CD3+ T cells expressing high levels of α4β7, and occupied ~40% of α4β7 expressed by these subsets and ~25% of all cells expressing α4β7. Blocking of the α4β7 was restricted to the vaginal tract without any changes detected systemically.

scholarly journals Maternal-Fetal Pharmacokinetics and Dynamics of a Single Intrapartum Dose of Maraviroc in Rhesus Macaques

2010 ◽  
Vol 54 (10) ◽  
pp. 4059-4063 ◽  
Author(s):  
Mark A. Winters ◽  
Koen K. A. Van Rompay ◽  
Angela D. M. Kashuba ◽  
Nancy S. Shulman ◽  
Mark Holodniy
Keyword(s):  
Single Dose ◽  
Rhesus Macaques ◽  
Subsequent Development ◽  
Receptor Occupancy ◽  
Pharmacokinetic Profile ◽  
Maternal Plasma ◽  
Maximum Plasma ◽  
Time Curve ◽  
Ccr5 Receptor ◽  
Single Dose Nevirapine

ABSTRACT Single-dose nevirapine (NVP) is effective in reducing mother-to-child transmission (MTCT) of HIV; however, the subsequent development of drug resistance is problematic. The pharmacokinetic profile of the HIV entry inhibitor maraviroc after a single intrapartum dose in rhesus macaques was studied to determine whether maraviroc could serve as an alternative to NVP in a single-dose strategy. Four pregnant macaques received an oral dose of maraviroc 2 h before delivery, and both infant and maternal plasma maraviroc concentrations and CCR5 receptor occupancy on CD4+ lymphocytes were measured over time. Maximum plasma maraviroc concentrations were found at delivery (2-h-postintrapartum dose) in both the mothers and infants, with median concentrations of 974 ng/ml (range, 86 to 2,830 ng/ml) and 22 ng/ml (range, 4 to 99 ng/ml), respectively. Maraviroc was detected in the plasma of mothers up to 48 h after dosing but only as long as 3.5 h in the infants. The median fetal-maternal area under the concentration-time curve (AUC) ratio was 0.009 (range, 0.000 to 0.015). Maraviroc receptor occupancy data showed evidence of unprotected CCR5 receptors on CD4+ cells in the mothers 24 to 48 h after dosing. Extremely low CCR5 expression on CD4+ cells of newborn macaques prevented determination of receptor occupancy in the infants. In rhesus macaques, maraviroc was poorly transferred across the placenta and was quickly cleared from the infants’ blood. The low concentrations of fetal maraviroc and short pharmacokinetic profile in infants suggest that a single maternal intrapartum dose of maraviroc would not be effective in reducing the risk of MTCT of HIV.

scholarly journals Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Bassam H. Rimawi ◽  
Erica Johnson ◽  
Augustine Rajakumar ◽  
Sijia Tao ◽  
Yong Jiang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Maternal Plasma ◽  
Fixed Dose ◽  
Pharmacokinetic Data ◽  
Combination Regimen ◽  
Fetal Circulation ◽  
Drug Concentrations ◽  
Hiv 1 ◽  
Concentration Ratios

ABSTRACT The integrase inhibitors elvitegravir (EVG) and dolutegravir (DTG) rapidly decrease the plasma HIV-1 viral load, a key factor in the prevention of maternal-to-fetal transmission of HIV-1. No data have been reported on the concentrations of these drugs in cord blood, maternal peripheral blood mononuclear cells (PBMCs), or placental tissue in pregnant women. We present in vivo pharmacokinetic data on antiretrovirals (ARV) within maternal and cord blood and within placentae from HIV-1-infected pregnant women. Maternal blood and cord blood were obtained from women receiving EVG, cobicistat, tenofovir disoproxil fumarate, and emtricitabine as a single fixed-dose combination formulation or DTG as part of a combination regimen. Plasma and PBMCs from maternal and cord blood were obtained along with villous placental samples. Drug concentrations were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Utilizing medians and ranges to interpret our data, we compared the drug concentration ratios between different matrices (maternal and cord blood plasma, PBMCs, and placenta). All five agents transferred from maternal into fetal circulation via the placenta. Concentration ratios for EVG, cobicistat, tenofovir, and emtricitabine (n = 10) and DTG (n = 3) were determined between cord plasma and placenta, cord and maternal plasma, and cord PBMCs and maternal PBMCs. TFV moves from maternal plasma through the placenta to the cord blood and then into cord PBMCs, where it is phosphorylated into its active forms (TFV diphosphate). These five ARVs were detected in each of the compartments, highlighting transfer of these agents from the maternal into the fetal circulation.

scholarly journals Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection.

1997 ◽  
Vol 41 (1) ◽  
pp. 169-174 ◽  
Author(s):  
G D Morse ◽  
M A Fischl ◽  
M J Shelton ◽  
S R Cox ◽  
M Driver ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Single Dose ◽  
Nucleoside Analogs ◽  
Concurrent Administration ◽  
Time Curve ◽  
Single Dose Study ◽  
Cd4 Cell Count ◽  
Immunodeficiency Virus ◽  
Delavirdine Mesylate

Delavirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 (HIV-1) that is currently being evaluated in combination regimens with various nucleoside analogs, including didanosine. Due to the pH-dependent solubility of delavirdine, the buffering agents in didanosine formulations may reduce delavirdine absorption. To evaluate the potential interaction between these agents, 12 HIV-infected patients (mean [+/- standard deviation] CD4+ cell count, 304 +/- 213/mm3) were enrolled in a three-way crossover single-dose study. Didanosine (125 to 200 mg given as buffered tablets) and delavirdine mesylate (400 mg) pharmacokinetics were evaluated when each drug was given alone (treatments A and B, respectively), when the two drugs were given concurrently (treatment C), and when didanosine was given 1 h after delavirdine (treatment D). Delavirdine exposure was reduced by concurrent administration of didanosine. The maximum drug concentration in serum (Cmax) was reduced from 7.22 +/- 4.0 to 3.51 +/- 1.9 microM, and the area under the concentration-time curve from 0 h to infinity (AUC0-->infinity) was reduced from 22.5 +/- 14 to 14 +/- 5.7 microM.h. The extent of N-dealkylation, as indicated by the ratio of the N-dealkylated delavirdine AUC0-->infinity to the delavirdine AUC0-->infinity, was unchanged across study treatments (P = 0.708). Reductions in didanosine exposure were observed during concurrent administration with delavirdine with a Cmax reduction from 4.65 +/- 2.0 to 3.22 +/- 0.59 microM and an AUC0-->infinity reduction from 7.93 +/- 3.9 to 6.54 +/- 2.3 microM.h. Thus, concurrent administration of delavirdine and didanosine may reduce the AUC0-->infinity of both drugs, although the clinical significance of this reduction is unknown. Administration of delavirdine 1 h before didanosine avoided the interaction. Due to the single-dose nature of this study, these findings require further evaluation at steady state.

scholarly journals Pharmacokinetics and Safety of Indinavir in Human Immunodeficiency Virus-Infected Pregnant Women

2006 ◽  
Vol 51 (2) ◽  
pp. 783-786 ◽  
Author(s):  
Jashvant D. Unadkat ◽  
Diane W. Wara ◽  
Michael D. Hughes ◽  
Anita A. Mathias ◽  
Diane T. Holland ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasma Concentration ◽  
Pregnant Women ◽  
Cyp3a Activity ◽  
Time Curve ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
Plasma Concentration Time Curve ◽  
Grade 3 ◽  
Experienced Grade

ABSTRACT Human immunodeficiency virus-infected women (n = 16) received indinavir (800 mg three times a day) plus zidovudine plus lamivudine from 14 to 28 weeks of gestation to 12 weeks postpartum. Two women and eight infants experienced grade 3 or 4 toxicities that were possibly treatment related. Indinavir area under the plasma concentration-time curve was 68% lower antepartum versus postpartum, suggesting increased intestinal and/or hepatic CYP3A activity during pregnancy.

scholarly journals Pregnancy Outcome, Antibodies and Placental Pathology in SARS-CoV-2 Infection during Early Pregnancy

2021 ◽  
Vol 18 (11) ◽  
pp. 5709
Author(s):  
Won-Kyu Jang ◽  
Su-Yeon Lee ◽  
Sunggyun Park ◽  
Nam Hee Ryoo ◽  
Ilseon Hwang ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Amniotic Fluid ◽  
Cord Blood ◽  
Pregnant Women ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Maternal Plasma ◽  
Placental Pathology ◽  
Chain Reaction ◽  
Polymerase Chain

There are reports that pregnant women infected with SARS-CoV-2 not only have increased morbidity but also increased complications and evidence of maternal and fetal vascular malperfusion on placental pathology. This was a retrospective study of pregnant women diagnosed with SARS-CoV-2 infection after March 2020. The results of reverse transcription polymerase chain reaction testing and IgM and IgG antibody testing of the amniotic fluid, cord blood, placenta, and maternal blood were confirmed at delivery. Placentas were evaluated histopathologically. The study included seven pregnant women diagnosed with SARS-CoV-2 infection during pregnancy at a mean gestational age of 14.5 weeks. Out of the seven women, five were infected during the first trimester. The mean gestational age at delivery was 38.4 weeks. The reverse transcription polymerase chain reaction results for maternal plasma, cord blood, placenta, and amniotic fluid were negative and IgG antibodies were detected in maternal plasma and cord blood. On placental pathology, maternal vascular malperfusion was found in only one case, fetal vascular malperfusion in four cases, and inflammatory changes were found in two cases. Pregnancy outcomes for women diagnosed with SARS-CoV-2 infection during early pregnancy are positive and it is likely that maternal antibodies are passed to the fetus, which results in a period of immunity.

scholarly journals Interaction Studies of Tipranavir-Ritonavir with Clarithromycin, Fluconazole, and Rifabutin in Healthy Volunteers

2008 ◽  
Vol 53 (1) ◽  
pp. 162-173 ◽  
Author(s):  
Charles J. L. la Porte ◽  
John P. Sabo ◽  
Mabrouk Elgadi ◽  
D. William Cameron
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Multiple Dose ◽  
Geometric Mean ◽  
Time Curve ◽  
Drug Levels ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
Historical Controls ◽  
Hiv Negative

ABSTRACT Three separate controlled, two-period studies with healthy volunteers assessed the pharmacokinetic interactions between tipranavir-ritonavir (TPV/r) in a 500/200-mg dose and 500 mg of clarithromycin (CLR), 100 mg of fluconazole (FCZ), or 150 mg of rifabutin (RFB). The CLR study was conducted with 24 subjects. The geometric mean ratios (GMR) and 90% confidence intervals (90% CI; given in parentheses) of the areas under the concentration-time curve (AUC), the maximum concentrations of the drugs in serum (C max), and the concentrations in serum at 12 h postdose (Cp12h) for multiple-dose TPV/r and multiple-dose CLR, indicating the effect of TPV/r on the CLR parameters, were 1.19 (1.04-1.37), 0.95 (0.83-1.09), and 1.68 (1.42-1.98), respectively. The formation of the metabolite 14-OH-CLR was decreased by 95% in the presence of TPV, and the TPV AUC increased 66% compared to that for human immunodeficiency virus (HIV)-negative historical controls. The FCZ study was conducted with 20 subjects. The GMR (and 90% CI) of the AUC, C max, and Cp24h, indicating the effect of multiple-dose TPV/r on the multiple-dose FCZ parameters, were 0.92 (0.88-0.95), 0.94 (0.91-0.98), and 0.89 (0.85-0.92), respectively. The TPV AUC increased by 50% compared to that for HIV-negative historical controls. The RFB study was conducted with 24 subjects. The GMR (and 90% CI) of the AUC, C max, and Cp12h for multiple-dose TPV/r and single-dose RFB, indicating the effect of TPV/r on the RFB parameters, were 2.90 (2.59-3.26), 1.70 (1.49-1.94), and 2.14 (1.90-2.41), respectively. The GMR (and 90% CI) of the AUC, C max, and Cp12h of TPV/r and RFB with 25-O-desacetyl-RFB were 4.33 (3.86-4.86), 1.86 (1.63-2.12), and 2.76 (2.44-3.12), respectively. Coadministration of TPV with a single dose of RFB resulted in a 16% increase in the TPV Cp12h compared to that for TPV alone. In the general population, no dose adjustments are necessary for the combination of TPV/r and CLR or FCZ. Combining TPV/r with RFB should be done with caution, while toxicity and RFB drug levels should be monitored. Study medications were generally well-tolerated in these studies.

Non Invasive Screening for Fetal RHD-Genotype in All D-Negative Women Is Reliable and Cost-Effective.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 556-556
Author(s):  
C. Ellen Van der Schoot ◽  
Aicha Ait Soussan ◽  
Gouke J. Bonsel ◽  
Masja de Haas
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Large Scale ◽  
Serological Test ◽  
Cost Effective ◽  
Maternal Plasma ◽  
Serological Tests ◽  
Non Invasive ◽  
Automated Assay ◽  
Cell Free Fetal Dna

Abstract About 40% of D-negative pregnant women receive antenatal anti-D despite a D-negative fetus. We have developed an automated assay for fetal genotyping using cell-free fetal DNA from maternal plasma to restrict antenatal prophylaxis to women carrying a D-positive fetus. This will save anti-D of which is worldwide shortage, and will prevent the unnecessary administration of a blood product. 1 ml of plasma is automatically presented (Tecan) to a DNA isolation-robot (Roche). The DNA-eluate is tested (after automatically pipetting) in triplicate in a real-time RHD exon7-PCR (ApplBios). Results Plasma from 2415 D-negative pregnant women, whose blood was sent in for 28–30th week antibody screening, has been tested. In 35 cases (1.44%) the women (10 weak D and 25 normal D-positive) were typed as D-positive by repeated serological tests, and excluded from the study. 1465 of the plasma’s (61.59%) were typed RhD positive and 915 RhD negative. Because the RHD exon7-PCR will give positive results in D-negative women carrying D-negative variant RHD genes such as RHDΨ, we determined the incidence of these genes in our studygroup. In all cases (n=39) with Ct values below 33.2 DNA was isolated from maternal leukocytes. Of the 19 cases with extremely low Ct values (<32), 6 women carried an RHDΨ gene, 5 an RHD variant type VI, 3 weak D (type 1, 11 and 17) and 1 RHDdel. The 24 other women did not carry RHD genes. To compare the plasma PCR results with cord blood serology, all women and obstetric caregivers were sent questionnaires on cord blood serology. 55% responded (n=1257). For cases with discrepant results(n=21) or incompleted questionnaires(n=31) the laboratory which performed the cord blood typing was contacted. Finally, concordant results were obtained in 1249 of the cases. In 3 cases the genotype suggests D-positivity while serology is D-negative. In 5 cases no RHD-sequences were detected in plasma but cord blood was typed D-positive. For the discrepant cases it cannot be concluded yet, which assay gave the correct phenotype. Conclusion This is the first large scale automated study demonstrating the feasibility of screening D-negative women to restrict antenatal anti-D to women carrying D-positive fetuses. For the recognition of women at risk for immunization, the plasma-PCR test seems to be at least as reliable as the serological test. Furthermore, postnatal prophylaxis could have been given directly after delivery in all women with a positive PCR-result, saving cord blood serology tests and possibly increasing the effectiveness of postnatal prophylaxis. An economic evaluation demonstrated that this screening policy is cost effective in the Netherlands.

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