R. Wimalasundera

Pre-eclampsia, antiretroviral therapy, and immune reconstitution

Antiretrovirals are standard treatment for HIV-1-positive women during pregnancy in the UK, but little is known about maternal or fetal safety. In our cohort study of 214 pregnant women with HIV-1 infection, those who received no antiretroviral therapy had a rate of pre-eclampsia significantly lower (none of 61) than those on triple antiretroviral therapy (8 of 76; odds ratio 15.3, 95% CI 0.9-270, p=0.0087). However, the rate of pre-eclampsia in HIV-1-positive women on treatment did not differ from that in uninfected controls (12 of 214; p=0.2). The association of HIV-1-related immune deficiency with a low rate of pre-eclampsia, and the restoration of this rate in women treated with triple antiretroviral therapy to the expected rate indicates a pivotal role of the immune system in the pathogenesis of pre-eclampsia. The clinical presentation of pre-eclampsia and toxic effects of antiretroviral therapy could overlap and complicate diagnosis and management in these patients.

Doppler for artery-artery anastomosis and stage-independent survival in twin-twin transfusion.

OBJECTIVE: Treatment selection in twin–twin transfusion syndrome is increasingly determined by disease severity. We investigated whether detection of arterio-arterial anastomoses predicts perinatal survival. METHODS: An artery–artery anastomosis was sought by Doppler and disease stage was determined in 105 cases of twin–twin transfusion syndrome at presentation, first treatment, and worst stage. Outcome measures were perinatal, double, and any (1 or more babies) survival rates. RESULTS: After exclusion of 10 noninformative pregnancies, perinatal, double, and any survival rates were 61%, 44%, and 77%, respectively. When an anastomosis was detected at each of the 3 time points, perinatal and double survival rates were higher than when one was not (at first treatment, perinatal survival 83% versus 53%, respectively, P = .003; double survival 78% versus 33%, P < .001). Perinatal and double survival (P ≤ .01) were poorer with more advanced stage, but any survival rates were not influenced by stage or anastomosis detection. Multiple logistic regression demonstrated that anastomosis detection at treatment increased the chance of perinatal (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.6, 15.9) and double survival (OR 19.3, 95% CI 2.7, 138), independently of stage. For stages I–III at treatment, anastomosis detection predicted better perinatal (100% versus 63%, 100% versus 59%, and 83% versus 44%, respectively) and double survival rates (100% versus 52%, 100% versus 46%, and 78% versus 26%). Stage III, with anastomoses detected, had better perinatal (83% versus 63%) and double survival (78% versus 52%) than did stage I without detection. CONCLUSION: Antenatal detection of artery-to-artery anastomosis predicts higher perinatal and double survival in twin–twin transfusion syndrome, independently of disease stage. LEVEL OF EVIDENCE: II-3

Reducing the incidence of twins and triplets

Multiple pregnancy rates remain high after assisted conception because of a misconceived assumption that transferring three or more embryos will maximize pregnancy rates. Maternal morbidity is sevenfold greater in multiple pregnancies than in singletons, perinatal mortality rates are fourfold higher for twins and sixfold higher for triplets, while cerebral palsy rates are 1-1.5% in twin and 7-8% in triplet pregnancies. Therefore, multiple pregnancies must be considered a serious adverse outcome of assisted reproductive techniques. Primary prevention of multiple pregnancies is the solution. The overwhelming evidence presented in this chapter demonstrates that limiting the embryo transfer in in vitro fertilization to two embryos would significantly reduce adverse maternal and perinatal outcomes by reducing the incidence of high order multiple pregnancies without reducing take-home-baby rates. Secondary prevention by multifetal pregnancy reduction is effective, but not acceptable to all patients. New developments in blastocyst culture, single embryo transfer, embryo cryopreservation and pre-implantation aneuploidy exclusion, should allow improvements in pregnancy rates without increasing multiple pregnancies.

Fetal ECG: A Novel Predictor of Atrioventricular Block in Anti-Ro Positive Pregnancies

Objective: Approximately 2.8% of pregnancies are Ro/La antibody positive. 3–15% of fetuses develop complete heart block (CHB). First-degree atrioventricular heart block (1° AVB) is reported in a third of Ro/La fetuses but as most have a normal postnatal ECG this may reflect inadequacies of Doppler measurement techniques. Methods: Comparison was made between mechanical (mPR) and electrical (ePR) intervals obtained prospectively using Doppler and non-invasive fetal ECG (fECG) in 52 consecutive Ro/La pregnancies in 46 women carrying 54 fetuses in an observational study at a fetal medicine unit. 121 mPR and 37 ePR intervals were recorded in 49 Ro/La fetuses. Five were referred with CHB and excluded. ePR was measured successfully in 35/37 (94%) and mPR was measured in all cases. 1° AVB was defined as PR >95% CI. Logistic regression predicted abnormal final fetal rhythm from first mPR or ePR. Results: The ePR model gave 66.7% sensitivity (6 of 8 final abnormal fetal rhythm cases were predicted correctly in fetuses >20 weeks) and 96.2% specificity. mPR gave 44.4% sensitivity (4 of 9 cases) and 88.5% specificity. Z scores for ePR (zPR) were calculated from 199 normal fetuses. The area under the receiver operator characteristic (ROC) curve was 0.88 (95% CI, 0.754 to 1.007). A cut-off of 1.65 gave a sensitivity of 87.5% and specificity of 95% for those with prolonged and normal ePR intervals, respectively. Conclusion: zPR is better than mPR at differentiating between normal and prolonged PR intervals, suggesting that fECG is the diagnostic tool of choice to investigate the natural history and therapy of conduction abnormalities in Ro/La pregnancies.

High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and cesarean delivery at 32 weeks' gestation

Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm.

Selective reduction and termination of multiple pregnancies.

The substantial increase in high order multiple pregnancies in the last two decades as a result of assisted reproductive techniques has necessitated the development of multifetal pregnancy reduction as a management tool to decrease fetal number and improve perinatal survival. The evidence in favour of reduction in pregnancies with more than four fetuses to twins is undisputed. Despite the recent improvements in expectant management of triplets with reasonable perinatal outcomes, the evidence suggests that reduction to twins significantly reduces the risk of preterm delivery without an increase in miscarriage rates. Recent advances in vascular-occlusive techniques have allowed the possibility of selective termination in monochorionic pregnancies in the presence of discordant anomalies or indeed multifetal reduction in non-trichorionic triplets, with radiofrequency ablation and cord occlusion appearing to be the most successful. However, the techniques vary in complexity and complication rates, which increase with gestation. Hence the need to refer these pregnancies early to specialist centres.

Radiofrequency ablation for selective reduction in complex monochorionic pregnancies

Please cite this paper as: Paramasivam G, Wimalasundera R, Wiechec M, Zhang E, Saeed F, Kumar S. Radiofrequency ablation for selective reduction in complex monochorionic pregnancies. BJOG 2010;117:1294–1298.

Transfusional fetal complications after single intrauterine death in monochorionic multiple pregnancy are reduced but not prevented by vascular occlusion

Objective  To document co‐twin death/pregnancy loss and brain injury after single intrauterine death (sIUD) in monochorionic pregnancies.

Interstitial laser therapy for fetal reduction in monochorionic multiple pregnancy: loss rate and association with aplasia cutis congenita.

To evaluate experience with interstitial laser therapy for intrafetal vascular ablation in monochorionic (MC) multiple pregnancy.

Prenatal ultrasound findings in complete trisomy 9

To report on the prenatal ultrasound findings associated with complete trisomy 9.