A 32 year old nulliparous woman was referred at 28 weeks of gestation because of severe pre-eclampsia in a dichorionic twin pregnancy conceived naturally. Her pregnancy was uneventful until 22 weeks of gestation, when a routine ultrasound scan revealed severe intrauterine growth restriction and reversed umbilical blood flow in one twin, while the other had normal development. At 28 weeks of gestation, the woman developed pre-eclampsia, with a blood pressure greater than 160/100 mmHg, proteinuria, headache and oedema.
In our centre, ultrasound examination confirmed growth restriction (weight estimation: 570 g) and reversed umbilical flow with cerebral redistribution in one twin, with a normal co-twin (estimated weight: 1270 g). The woman's clinical state was stable using a calcium channel blocker (nicardipine 100 mg given intravenously per day) to control her blood pressure. The degree of proteinuria was 2.16 g per day. After discussion with the parents and because of the poor prognosis for the growth-restricted twin, expectant management was decided, in order to avoid prematurity in the co-twin. Her proteinuria increased (Fig. 1) and control of her blood pressure required the addition of labetalol (600 mg intravenously per day). At 32 weeks of gestation, her proteinuria was 6.5 g per day. Ultrasound examination did not show evidence of any growth of the restricted twin and confirmed severe Doppler abnormalities, while the co-twin's assessment was reassuring. After discussion with the parents and in accordance with French law, selective termination of the compromised twin was performed by the administration of an intracardiac injection of potassium chloride.
From this point, her symptoms of pre-eclampsia disappeared, the proteinuria started a dramatic decrease (Fig. 1) and her blood pressure remained normal with a low dose of oral nicardipine (60 mg per day). Close follow up was maintained and her pregnancy remained uneventful. The woman was discharged home at 34 weeks of gestation. At 38 weeks, a healthy baby girl weighing 2560 g was born by vaginal delivery and a stillborn boy weighing 330 g was delivered immediately after. Her postpartum course was uneventful. Macroscopic and histologic examination confirmed a dichorionic pregnancy, with two placentas separated by two amnions and chorions.
Pre-eclampsia is a disorder specific to pregnancy characterised by increased blood pressure and proteinuria. It affects 3–5% of pregnancies and is a major cause of maternal and perinatal mortality1. The cause of pre-eclampsia remains elusive in spite of many attempts to understand the mechanisms responsible for its pathogenesis. Studies over the past decades suggest several possible origins of pre-eclampsia2. The initiating event could be reduced uteroplacental perfusion due to abnormal trophoblastic invasion of the spiral arterioles3. However, recent findings are more suggestive of an inappropriate maternal inflammatory response4 that could involve a superantigen-like effect5. Some authors speculate that oxidative stress in the abnormal placenta could lead to an overload of debris by stimulating apoptosis. The continual clearance of these debris from the maternal circulation could cause a systemic inflammatory response that deteriorates into pre-eclampsia6. Although the aetiology and pathogenesis remain to be elucidated, the placenta undoubtedly is involved, as termination of pregnancy eradicates the disease and delivery of the placenta is the only known cure7.
Few cases of resolution of pre-eclampsia after spontaneous intrauterine death of one twin have been reported8,9. Hagay et al.9 hypothesise that genetic susceptibility to pre-eclampsia could be conferred by homozygosity for the same single recessive gene expressed by both mother and fetus.
To our knowledge, this is the first case describing resolution of pre-eclampsia after selective termination of a dichorionic pregnancy in the third trimester. Selective termination is usually performed for structural, chromosomal and Mendelian anomalies, and third trimester procedures, where legal, can be performed with a good outcome for the surviving fetus10. It appears to be a reasonable option when one fetus is found abnormal in a multifetal pregnancy with dichorionic placentation.
In this case, we speculated that termination of the compromised twin could help to control the pre-eclampsia by stopping fetal blood flow to the abnormal placenta. Heyborne and Chism11 described reversal of the Ballantyne ‘mirror’ syndrome, which is similar to pre-eclampsia, by selective second trimester fetal termination. In the same way, Duthie and Walkinshaw12 reported reversal of pre-eclampsia after in utero fetal transfusion in a case of associated fetal hydrops associated with Parvovirus infection. On the other hand, Nugent et al.13 describe the persistence of a partial molar placenta and severe pre-eclampsia after selective termination in a twin pregnancy.
This case emphasises the requirement for interaction between the placenta and the maternal organism for the maintenance of pre-eclampsia. Pre-eclampsia occurs in genetically predisposed women1 and is probably promoted by the continuous transfer of factors from the placenta, leading to widespread activation and dysfunction of the maternal vascular endothelium. This phenomenon could be due to placental ischaemia3 or excess oxidative stress1,6.
Further studies are needed for a better understanding of pre-eclampsia and identification of the placental factors responsible for persistence of the disease. Our case of selective termination in a twin pregnancy with pre-eclampsia allowed prolongation of the pregnancy. This case may give us a better understanding of the mechanisms involved in the development of pre-eclampsia.