Oriol Coll

Maternal viral load and vertical transmission of HIV-1: an important factor but not the only one

OBJECTIVES To investigate the association between maternal RNA load, risk of vertical transmission of HIV-1, and other variables. METHODS Plasma or serum samples from mothers of 373 children, enrolled in the prospective European Collaborative Study, were collected around time of delivery, and HIV-RNA quantified using two types of commercial assay. Women and children were followed according to a standard protocol. Adjusted odds ratios (AOR) were calculated to estimate the effect of RNA load and other maternal factors on vertical transmission. RESULTS Maternal RNA levels, mode of delivery and gestational age were independently associated with transmission. Vertical transmission increased with increasing RNA levels, but there was no threshold below which transmission did not occur. The risk was more than double for women with RNA above the sample specific median [AOR 2.36 (1.23-4.52)]. Elective caesarean section was associated with a substantial and significant decrease in transmission [AOR 0.19 (0.06-0.55)], and delivery before 37 weeks gestation with an increased risk [AOR 2.67 (1.33-5.38)]. Elective caesarean section was effective in both subgroups defined by median RNA level [AORs 0.37 (0.08-1.71) and 0.15 (0.03-0.64) below and above median respectively]. The predicted rate of transmission in a woman with a low RNA load delivering by elective caesarean section or vaginally after 37 weeks is around 2%, and 11%, respectively. INTERPRETATION Mother-to-child transmission of HIV-1 is multi-factorial; high RNA load is an important determinant but clearly not the only one. Interventions that target risk factors other than maternal RNA load remain important.

Increased risk of pre-eclampsia and fetal death in Hiv-infected pregnant women receiving highly active antiretroviral therapy

Background:Pre-eclampsia and/or fetal death have increased sharply in HIV-infected pregnant women receiving HAART. Methods:The occurrence of pre-eclampsia or fetal death was analysed in women who delivered after at least 22 weeks of gestation for all women (January 2001 until July 2003) and for HIV-infected women (November 1985 until July 2003). Results:In 2001, 2002 and 2003, the rates per 1000 deliveries of pre-eclampsia and fetal death, respectively, remained stable in all pregnant women at 25.4, 31.9 and 27.7 (P = 0.48) and 4.8, 5.8, and 5.0 (P = 0.89) (n = 8768). In 1985–2000 (n = 390) to 2001–2003 (n = 82), rates per 1000 deliveries in HIV-infected women rose from 0.0 to 109.8 (P < 0.001) for pre-eclampsia and from 7.7 to 61.0 (P < 0.001) for fetal death. In all pregnant women, factors associated with pre-eclampsia or fetal death were multiple gestation [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI), 2.3–5.6; P < 0.001], HIV infection (adjusted OR, 4.9; 95% CI, 2.4–10.1; P < 0.001), multiparity (adjusted OR, 0.76; 95% CI, 0.58–0.98; P = 0.040) and tobacco smoking (adjusted OR, 0.65; 95% CI, 0.46–0.90; P = 0.010). The use of HAART prior to pregnancy (adjusted OR, 5.6; 95% CI, 1.7–18.1; P = 0.004) and tobacco smoking (adjusted OR, 0.183; 95% CI, 0.054–0.627; P = 0.007) were risk factors in HIV-infected women. Conclusions:HIV infection treated with HAART prior to pregnancy was associated with a significantly higher risk for pre-eclampsia and fetal death.

Uterine artery Doppler at 11–14 weeks of gestation to screen for hypertensive disorders and associated complications in an unselected population

To establish reference values for the first‐trimester uterine artery (UtA) pulsatility index (PI) and to investigate the role of UtA Doppler in the early prediction of hypertensive disorders and their associated complications in an unselected Mediterranean population.

Prevalence and Vertical Transmission of Trypanosoma cruzi Infection among Pregnant Latin American Women Attending 2 Maternity Clinics in Barcelona, Spain

We performed a prospective screening for Trypanosoma cruzi infection in 1350 Latin American pregnant women and their offspring in Barcelona, Spain. The rate of seroprevalence was 3.4%, and 7.3% of the newborns were infected. Routine screening and management programs in maternity wards may be warranted.

Sequential changes in uterine artery blood flow pattern between the first and second trimesters of gestation in relation to pregnancy outcome.

To describe sequential changes in uterine artery waveform between the first and second trimesters of gestation and to analyze their association with the subsequent risk of hypertensive disorders and fetal growth restriction (IUGR).

Customised birthweight standards accurately predict perinatal morbidity

Objective: Fetal growth restriction is associated with adverse perinatal outcome but is often not recognised antenatally, and low birthweight centiles based on population norms are used as a proxy instead. This study compared the association between neonatal morbidity and fetal growth status at birth as determined by customised birthweight centiles and currently used centiles based on population standards. Design: Retrospective cohort study. Setting: Referral hospital, Barcelona, Spain. Patients: A cohort of 13 661 non-malformed singleton deliveries. Interventions: Both population-based and customised standards for birth weight were applied to the study cohort. Customised weight centiles were calculated by adjusting for maternal height, booking weight, parity, ethnic origin, gestational age at delivery and fetal sex. Main outcome measures: Newborn morbidity and perinatal death. Results: The association between smallness for gestational age (SGA) and perinatal morbidity was stronger when birthweight limits were customised, and resulted in an additional 4.1% (n = 565) neonates being classified as SGA. Compared with non-SGA neonates, this newly identified group had an increased risk of perinatal mortality (OR 3.2; 95% CI 1.6 to 6.2), neurological morbidity (OR 3.2; 95% CI 1.7 to 6.1) and non-neurological morbidity (OR 8; 95% CI 4.8 to 13.6). Conclusion: Customised standards improve the prediction of adverse neonatal outcome. The association between SGA and adverse outcome is independent of the gestational age at delivery.

Triggering with human chorionic gonadotropin or a gonadotropin-releasing hormone agonist in gonadotropin-releasing hormone antagonist-treated oocyte donor cycles : findings of a large retrospective cohort study

OBJECTIVE To compare pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS) in donor stimulation cycles where final maturation of oocytes was induced with recombinant hCG or GnRH agonist. DESIGN Retrospective, cohort study. SETTING Private infertility clinic. PATIENT(S) A total of 1171 egg donors performing 2077 stimulation cycles. INTERVENTION(S) Controlled ovarian hyperstimulation of egg donors with GnRH antagonist protocol triggered with recombinant hCG (rhCG; 250 microg) or GnRH agonist (triptorelin 0.2 mg) based on the physicians decision. MAIN OUTCOME MEASURE(S) Proportion of mature and fertilized oocytes per donor cycle; clinical, ongoing pregnancy and implantation rate in recipients; and incidence of moderate/severe OHSS in oocyte donors. RESULT(S) The proportion of mature oocytes was comparable, whereas the difference in the fertilization rate reached statistical significance (65% vs. 69%). No significant differences were observed in the implantation rate or clinical and ongoing pregnancy rates per ET. The incidence of moderate/severe OHSS was 1.26% (13/1031; 95% confidence interval [CI], 0.74-2.15) and 0% (0/1046; 95% CI, 0.00-0.37) in the rhCG and GnRH agonist groups, respectively. CONCLUSION(S) Recipient outcome was not significantly different when using oocytes from GnRH antagonist-treated donor cycles triggered with hCG or GnRH agonist. However, GnRH agonist triggering was associated with a lower incidence of moderate/severe OHSS in egg donors.

Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles

A retrospective study was conducted in a private infertility centre to evaluate the rate of complications in a large oocyte donation programme. A total of 4052 oocyte retrievals were performed between January 2001 and October 2007. Altogether, 1238 cycles (30.6%) were stimulated with the use of gonadotrophin-releasing hormone (GnRH) agonists and in 2814 cycles (69.4%) the GnRH antagonist protocol was used. The GnRH antagonist treated cycles were triggered with human chorionic gonadotrophin (HCG) or a GnRH agonist in 1295 and 1519 cycles, respectively. Complications related to oocyte retrieval occurred in 17 patients (0.42%) (intra-abdominal bleeding: n = 14, severe pain: n = 2, ovarian torsion: n = 1). Fourteen of these were hospitalized (0.35%) and six donors (0.15%) required surgical intervention. Pelvic infections, injury to pelvic structures or anaesthesiological complications were not observed in this series. Moderate/severe ovarian hyperstimulation syndrome (OHSS) occurred in 22 donors; 11 required hospital admission and 11 were managed on an outpatient basis. All cases were related to HCG triggering (0.87%). Serious complications related to oocyte retrieval occurred at a low rate in healthy young donors. The risk of OHSS can be substantially reduced by specific stimulation protocols, which include GnRH agonist triggering. Prospective oocyte donors should be adequately counselled about the risks related to egg donation.

Guidelines on CMV congenital infection.

Abstract Congenital cytomegalovirus (CMV) infection occurs in 0.6–0.7% of all newborns and is the most prevalent infection-related cause of congenital neurological handicap. Vertical transmission occurs in around 30% of cases, but the fetus is not always affected. Symptomatic newborns at birth have a much higher risk of suffering severe neurological sequelae. Detection of specific IgG and IgM and IgG avidity seem to be the most reliable tests to identify a primary infection but interpretation in a clinical context may be difficult. If a seroconversion is documented or a fetal infection is suspected by ultrasound markers, an amniocentesis should be performed to confirm a vertical transmission. In the absence of a confirmed fetal infection with fetal structural anomalies, a pregnancy termination should be discouraged. Fetal prognosis is mainly correlated to the presence of brain damage. Despite promising results with the use of antiviral drugs and CMV hyperimmune globulin (HIG), results have to be interpreted with caution. Pregnant women should not be systematically tested for CMV during pregnancy. Managing CMV screening should be restricted to pregnancies where a primary infection is suspected or among women at high risk. The magnitude of congenital CMV disease and the value of interventions to prevent its transmission or to decrease the sequelae need to be established before implementing public health interventions. In this paper, aspects of CMV infection in the pregnant woman and her infant are reviewed.

Doppler assessment of the aortic isthmus and perinatal outcome in preterm fetuses with severe intrauterine growth restriction

To evaluate the characteristics and association with perinatal outcome of the aortic isthmus (AoI) circulation as assessed by Doppler imaging in preterm growth‐restricted fetuses with placental insufficiency.