Radu Vladareanu

The potential of 4D sonography in the assessment of fetal neurobehavior - multicentric study in high-risk pregnancies

Abstract Objective: An evolving challenge for obstetrician is to better define normal and abnormal fetal neurological function in utero in order to better predict antenatally which fetuses are at risk for adverse neurological outcome. Patients and methods: Prenatal neurological assessment in high-risk fetuses using four-dimensional ultrasound applying the recently developed Kurjak antenatal neurodevelopmental test (KANET). Postnatal neurological assessment was performed using Amiel Tisons neurological assessment at term (ATNAT) for all live-borns and general movement (GM) assessment for those with borderline and abnormal ATNAT. Results: Inclusion criteria were met by 288 pregnant women in four centers of whom 266 gave birth to a live-born baby. It was revealed that 234 fetuses were neurologically normal, 7 abnormal and 25 borderline. Out of 7 abnormal fetuses ATNAT was borderline in 5 and abnormal in 2, whereas GM assessment was abnormal in 5 and definitely abnormal in 2. Out of 25 KANET borderline fetuses, ATNAT was normal in 7, borderline in 17 and abnormal in 1, whereas the GM assessment was as follows: normal optimal in 4, normal suboptimal in 20, and abnormal in 1. In summary, out of 32 borderline and abnormal fetuses ATNAT was normal in 7, borderline in 22 and abnormal in 3; GM assessment was normal optimal in 4, normal suboptimal in 20, abnormal in 6 and definitely abnormal in 2. Conclusion: The sonographic test requires further studies before being recommended for wider clinical practice.

Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine administered according to an alternative dosing schedule compared with the standard dosing schedule in healthy women aged 15 to 25 years: results from a randomized study.

Background: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine is immunogenic, has a clinically acceptable safety profile, and prevents incident and persistent HPV-16/18 infection and cervical precancerous lesions. This study (NCT00552279) evaluated the vaccine when administered according to an alternative dosing schedule (0–1–12 months) compared with the standard dosing schedule (0–1–6 months). Methods: The study was of randomized open design and was conducted at multiple centers in Europe. Healthy women aged 15 to 25 years were randomized (1:1) to receive HPV-16/18 vaccine according to the standard schedule at months 0, 1, and 6 (n = 401) or an alternative schedule at months 0, 1, and 12 (n = 403). HPV-16 and -18 antibodies were measured by enzyme-linked immunosorbent assay at months 0, 2, and 7 or 13 (depending on group); noninferiority evaluation was performed sequentially for seroconversion rates and geometric mean antibody titers. Primary analysis of immunogenicity was based on the according-to-protocol cohort. Vaccine safety and reactogenicity were assessed on the total vaccinated cohort. Results: Predefined noninferiority criteria were met 1 month after the third vaccine dose when the HPV-16/18 vaccine was administered according to the 0–1–12 month schedule compared with the 0–1–6 month schedule in terms of seroconversion rates for HPV-16 (100% and 100%) and HPV-18 (99.7% and 100%) and geometric mean antibody titers for HPV-16 (11884.7 and 10311.9 ELISA units/mL) and HPV-18 (4501.3 and 3963.6 ELISA units/mL), respectively. The HPV-16/18 vaccine had a clinically acceptable safety profile when administered according to either schedule. Conclusions: The third dose of the HPV-16/18 vaccine can be administered any time between 6 and 12 months after the first dose, with adequate immunogenicity and a clinically acceptable safety profile.

Delivery mode for the extremely premature fetus: a statement of the prematurity working group of the World Association of Perinatal Medicine

Abstract Recent retrospective publications have suggested that cesarean delivery may be beneficial for the extremely premature fetus. This article displays the available evidence and discusses this issue, including many aspects such as the difficulty in deciding when delivery is imminent, the negative impact on maternal morbidity and mortality and the cost to society of such a policy. The available scientific evidence does not support a recommendation for cesarean delivery for improving survival or decreasing morbidity for the extremely premature fetus.

Type-specific herpes simplex virus-1 and herpes simplex virus-2 seroprevalence in Romania: comparison of prevalence and risk factors in women and men

OBJECTIVE To determine herpes simplex virus (HSV)-2 and HSV-1 seroprevalence in women and men in Romania. METHODS A cross-sectional seroprevalence survey was conducted between 2004 and 2005 on a total of 1058 women and men representative of the population of Bucharest. All participants were aged 15-44 years and completed a structured questionnaire. A blood sample was collected to detect IgG anti-HSV-1 and HSV-2 serum antibodies using the HerpeSelect ELISA (Focus Diagnostics). RESULTS A total of 761 women (median age 29 years) and 297 men (median age 29 years) were included. Overall, HSV-2 seroprevalence (15.2%) increased with age. Among women, HSV-2 seroprevalence increased from 11.0% in 15-19-year-olds to 38.3% in 40-44-year-olds. Among men, seroprevalence increased from 4.0% in 20-24-year-olds to 27.1% in 40-44-year-olds. HSV-2 seroprevalence was significantly higher among women than men (17.0% vs. 10.8%). HSV-1 seropositivity was high (87.2%) in all age groups, with no clear trend by age or by sex. In addition to older age and female sex, risk factors for HSV-2 included greater number of lifetime sexual partners, lower educational attainment, and history of genital vesicles. Lower educational level and rural residence were associated with a higher risk of HSV-1 seropositivity. CONCLUSIONS In Romania, HSV-2 seroprevalence was higher in women than men, and was within European limits and lower than that in Africa and the USA. In contrast, HSV-1 seroprevalence was generally higher than that previously recorded in similarly aged populations in Western Europe.

Seroprevalence and risk factors associated with herpes simplex virus infection among pregnant women

OBJECTIVES To estimate the type-specific seroprevalence and identify the risk factors associated with herpes simplex virus (HSV)-2 infection in pregnant women in Bucharest, Romania. METHODS A prospective survey was conducted in 452 subjects, aged 15-39 years, at the Elias Hospital, during the years 2004-2005. We evaluated serum IgG anti-bodies to HSV-1 and HSV-2 using the HerpeSelect ELISA test. All subjects completed an epidemiological questionnaire. RESULTS Seroprevalence was 87.3% and 15.1% for HSV-1 and HSV-2, respectively. The risk factors for HSV-2 infection were lower level of education and a greater number of sexual partners. Elementary school and high-school graduates were 6.28 and 2.26 times more exposed than University graduates. Having 2-3 partners and more than three partners was associated with 2.43 and 4.26 times the risk of acquiring HSV-2, compared with having one partner. CONCLUSIONS In pregnant women, HSV-1 seroprevalence was higher than in Western Europe but similar to that in Eastern Europe. HSV-2 seroprevalence was within European ranges. Both were lower than in the USA. Risk factors for HSV-2 infection may lead to prevention programs.

Multicentric studies of the fetal neurobehavior by KANET test

Abstract Assessment of fetal neurobehavior and detection of neurological impairment prenatally has been a great challenge in perinatal medicine. The evolution of four-dimensional (4D) ultrasound not only enabled a better visualization of fetal anatomy but also allowed the study of fetal behavior in real time. Kurjak Antenatal Neurodevelopmental Test (KANET) was developed for the assessment of fetal neurobehavior and the detection of neurological disorders, based on the assessment of the fetus by application of 4D ultrasound in the same way that a neonate is assessed postnatally. KANET is a method that has been applied for the past 10 years and studies show that it is a strong diagnostic tool and can be introduced into everyday clinical practice. We present all data from studies performed up to now on KANET.

Early pregnancy serum neopterin concentrations predict spontaneous preterm birth in asymptomatic pregnant women.

Abstract Objective: To investigate if early pregnancy serum neopterin concentrations (EPSN) could predict spontaneous preterm birth (SPB). Methods: EPSN was measured in 92 sera collected from 46 pregnant women with birth at term and 40 sera from 20 pregnant women with preterm birth. Two sera were collected for each case: in the first and early second trimester. Results: EPSN concentrations correlate with gestational age (ρ=0.275, P=0.001), a correlation which was present in both groups: term and preterm birth. EPSN were higher in pregnancies with SPB compared with normal pregnancies (6.27±1.03 vs. 6.04±0.15, P=0.039). Patients with SPB showed a considerable increase of EPSN in the second trimester compared with patients with birth at term (7.30±1.53 vs. 6.16±0.23, P=0.043). A sharper increase was found in the group with SPB before 32 weeks of pregnancy (wp) (9.83±4.36 vs. 6.16±0.23, P=0.016). Pregnant women with an early second trimester serum neopterin value of above 8 nmol/L are associated with a risk of SPB before 32 wp (odds ratio=14.4, P=0.01) and of SPB before 34 wp (odds ratio=3.6, P=0.05), respectively. Conclusions: EPSN increases with the gestational age and predicts SPB in asymptomatic pregnant women.