Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial.

BACKGROUND: The efficacy of prophylaxis to prevent prenatal toxoplasmosis transmission is controversial, without any previous randomized clinical trial. In France, spiramycin is usually prescribed for maternal seroconversions. A more potent pyrimethamine + sulfadiazine regimen is used to treat congenital toxoplasmosis and is offered in some countries as prophylaxis. OBJECTIVE: We sought to compare the efficacy and tolerance of pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission. STUDY DESIGN: This was a randomized, open-label trial in 36 French centers, comparing pyrimethamine (50 mg qd) + sulfadiazine (1 g tid) with folinic acid vs spiramycin (1 g tid) following toxoplasmosis seroconversion. RESULTS: In all, 143 women were randomized from November 2010 through January 2014. An amniocentesis was later performed in 131 cases, with a positive Toxoplasma gondii polymerase chain reaction in 7/67 (10.4%) in the pyrimethamine + sulfadiazine group vs 13/64 (20.3%) in the spiramycin group. Cerebral ultrasound anomalies appeared in 0/73 fetuses in the pyrimethamine + sulfadiazine group, vs 6/70 in the spiramycin group (P = .01). Two of these pregnancies were terminated. Transmission rates, excluding 18 children with undefined status, were 12/65 in the pyrimethamine + sulfadiazine group (18.5%), vs 18/60 in the spiramycin group (30%, P = .147), equivalent to an odds ratio of 0.53 (95% confidence interval, 0.23-1.22) and which after adjustment tended to be stronger (P = .03 for interaction) when treatment started within 3 weeks of seroconversion (95% confidence interval, 0.00-1.63). Two women had severe rashes, both with pyrimethamine + sulfadiazine. CONCLUSION: There was a trend toward lower transmission with pyrimethamine + sulfadiazine, but it did not reach statistical significance, possibly for lack of statistical power because enrollment was discontinued. There were also no fetal cerebral toxoplasmosis lesions in the pyrimethamine + sulfadiazine group. These promising results encourage further research on chemoprophylaxis to prevent congenital toxoplasmosis.

Comparison of the Induction-to-Delivery Interval in Terminations of Pregnancy with or without Dilapan-S®.

OBJECTIVE: In France, terminations of pregnancy (TOP) for medical reasons beyond the second trimester use mifepristone and misoprostol. We sought to determine the effectiveness of Dilapan-S®, an osmotic cervical dilator, in shortening the induction-to-delivery interval (IDI). MATERIALS AND METHODS: This retrospective study of TOP in 2010-2012 compared the results from 2 hospitals with different TOP protocols starting at 16 weeks' gestation, one (164 women) with and one (106) without Dilapan-S®. The principal endpoint was the IDI. Results were analyzed according to 2 definitions of induction onset: definition 1, first dose of misoprostol in both centers, or definition 2, dilator placement if used, and otherwise first dose of misoprostol. RESULTS: With definition 1, the IDI was shorter with dilators (5 h 48 min vs. 10 h 18 min, p < 0.001); the rates of uterine evacuation within 12 and 24 h were higher (94.5 and 100 vs. 68.9 and 91.5%, p < 0.001), and the time between first misoprostol dose and amniotomy was shorter (0 h 47 min vs. 4 h 30 min, p < 0.001). Under definition 2, the IDI was longer with dilators (18 h 24 min vs. 10 h 18 min, p < 0.001), but the rate of evacuation within 24 h did not differ significantly. CONCLUSION: Dilapan-S® acts on cervical ripening and dilatation, thereby allowing early amniotomy. Assessing potential side effects and women's satisfaction requires prospective trials.

Hemodynamic impact of absent or reverse end-diastolic flow in the two umbilical arteries in growth-restricted fetuses.

OBJECTIVE: To determine if bilateral absent or reverse end-diastolic (ARED) flow in the two umbilical arteries (UAs) at the perivesical (PVC) segment represents a more severe degree of hemodynamic compromise than unilateral ARED flow at the PVC segment in singleton pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: This was a prospective observational study. One hundred nine fetuses with IUGR underwent a total of 225 ultrasound (US) examinations. We measured the pulsatility index (PI) from the two UAs at the PVC segment, UA in the free floating cord (FFC), middle cerebral artery (MCA), ductus venosus (DV) and the aortic isthmus blood flow index (IFI). Three groups were classified according to bilateral positive end-diastolic (PED) flow, unilateral ARED flow or bilateral ARED flow in the UAs at the PVC segment. RESULTS: The proportions of US examinations with PED flow, unilateral ARED flow and bilateral ARED flow in the UAs were 54.7%, 20.4%, and 24.9%, respectively. At the last US examination, the IFI z-scores were significantly lower in the bilateral ARED group (-6.28 ± 4.30) compared to the unilateral ARED group (-1.72 ± 3.18, p<0.05) and the bilateral PED group (-0.83 ± 2.36, p<0.05), the DV-PI z-scores were significantly higher in the bilateral ARED group (2.15 ± 3.79) compared to the bilateral PED group (0.64 ± 1.50, p<0.05). Before 32 weeks of gestation, the interval between US examination and delivery was significantly shorter in the bilateral ARED group (8.9 days ± 8.2) than the unilateral ARED group (15.9 days ± 13.4, p<0.05) and the bilateral PED group (30.3 days ± 25.7, p<0.05). CONCLUSION: There are significant differences in fetal blood fluxes between left and right UA. Doppler examination at the PVC segment significantly improves the comparability of UA-PI between two successive US examinations and allows a longitudinal and independent hemodynamic investigation of each UA. Examination of a single UA in free floating cord may miss a large fraction of unilateral ARED flow. In singleton IUGR fetuses, a bilateral ARED flow in the UAs at the PVC segment indicates more severe hemodynamic compromise and worse fetal conditions than unilateral ARED flow.

Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection in developed countries. OBJECTIVES: The objective of this study was to evaluate the impact of our prenatal CMV infection screening and counseling policy. STUDY DESIGN: Since 2005, all pregnant women in our obstetric center have been informed about CMV infection, and if they agree, given a serological test at around 12 weeks of gestation (WG). If this first test is negative, the women and their partners are given hygiene counseling on how to prevent CMV infection, and a second test is performed at around 36 WG. RESULTS: Among the 5312 women who had an unknown immune status, or were known to be seronegative when they had their first visit to our center for their current pregnancy, 97.4% agreed to CMV screening. Primary infection was detected in 11 women between 0 and 12 WG (0.42%), and seroconversion was diagnosed in five women between 12 and 36 WG (0.19%). CONCLUSIONS: These results suggest that if clear information is given on CMV infection during pregnancy, the rate of seroconversion is lower following counseling than before counseling.