Introduction Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, affecting approximately 2% to 8% of pregnancies worldwide.1 Multifetal pregnancies are associated with a 2- to 3-fold increased risk of preeclampsia compared to singleton pregnancies.2 In twin pregnancies, severe preeclampsia tends to manifest earlier and progress more rapidly.3 Although the exact etiology and pathogenesis of preeclampsia remain incompletely understood, the only definitive treatment is delivery. As such, prolonging pregnancy to improve perinatal outcomes presents a major clinical challenge. In recent years, selective fetocide has emerged as a potential treatment option in complicated multifetal pregnancies, particularly those affected by severe preeclampsia. However, only a few case reports have documented the resolution of preeclampsia following selective reduction. Here, we present a case of severe preeclampsia in discordant twins that resolved after selective fetocide, successfully prolonging the pregnancy. Informed written consent was obtained from the patient for publication of this clinical observation. Case presentation A 32-year-old gravida 2, para 0 woman conceived a dichorionic diamniotic twin pregnancy through in vitro fertilisation and embryo transfer. She had well-controlled hypothyroidism (levothyroxine, daily) diagnosed in 2021. First-trimester preeclampsia screening at 12+3 weeks, incorporating maternal risk factors, mean arterial pressure and placental growth factor, identified a high risk for early-onset disease (< 34 weeks). Low-dose aspirin (100 mg daily) was initiated. Noninvasive prenatal testing performed the same day indicated a low risk of aneuploidy in both fetuses. Gestational diabetes mellitus was diagnosed at 24 weeks by oral glucose-tolerance testing. Routine anomaly scanning at 22+1 weeks demonstrated appropriate growth in twin A (estimated fetal weight 447 g) and severe growth restriction in twin B (300 g, < 1st percentile). Twin A also showed increased bowel echogenicity. A targeted ultrasound review confirmed these findings. Amniocentesis revealed normal karyotypes for both fetuses; amniotic‑fluid cytomegalovirus DNA PCR was negative. Follow‑up ultrasonography at 25+4 weeks showed minimal interval growth in twin B (427 g, < 1st percentile) and a shortened cervical length of 19.4 mm, signifying a high risk of preterm birth. Given the marked growth discordance, selective reduction was discussed. The patient and her family elected to defer a decision while considering the co‑twin's elevated risk of extreme prematurity. The patient had no personal or family history of hypertension, and her blood pressure and urinalysis were normal prior to 20 weeks. At 26+1 weeks, blood pressure increased to 160/90 mmHg and 24-hour urinary protein was 0.91 g. Dexamethasone (5 mg twice daily) was administered starting at 26+3 weeks. At 27+4 weeks, platelet count dropped to 72 × 109/L. Liver enzymes were mildly elevated: AST 49 IU/L (normal < 35 IU/L), LDH 308 IU/L (normal < 240 IU/L). Magnesium sulfate was administered for 48 hours. Antihypertensive treatment included oral labetalol (300 mg QID) and nifedipine (30 mg BID). Severe early-onset preeclampsia was diagnosed, and the prognosis was deemed poor. Concurrently, cervical length continued to shorten (see Supplementary Table S1, https://links.lww.com/MFM/A97). Given previous reports suggesting that selective fetocide might alleviate preeclampsia, the patient was counseled that twin B had minimal chances of survival. After thorough discussion and informed consent, selective fetocide of twin B was performed via intracardiac injection of potassium chloride without complications. In the days following the procedure, the patient's clinical status improved significantly. Blood pressure stabilized and showed a gradual decline; platelet counts improved steadily, although proteinuria persisted. Laboratory test results before and after selective fetocide are presented in Supplementary Table S2, https://links.lww.com/MFM/A97. At 28+3 weeks, ultrasound showed an estimated fetal weight of 1035 g (9.8th percentile) for the surviving twin. Notably, cervical length had increased, suggesting a reduced risk of preterm birth. At 29+3 weeks, ultrasound revealed an estimated fetal weight of 1058 g (1.4th percentile), elevated umbilical artery pulsatility index (UA PI = 1.4), and reduced middle cerebral artery PI (MCA PI = 1.44), resulting in a cerebroplacental ratio of 1.02. Non-stress testing showed reduced variability. Given intrauterine growth restriction and breech presentation, emergency cesarean delivery was performed. A male infant weighing 970 g was delivered with Apgar scores of 6 and 9 at 1 and 5 minutes, respectively. After a 61-day stay in the neonatal intensive care unit, the infant was discharged weighing 2030 g (< 3rd percentile). The patient's postpartum course was uneventful, and she was discharged four days later with oral nifedipine (30 mg BID). She was advised to maintain a low-sodium, high-protein diet and follow up regularly with a nephrologist. Discussion With the increasing use of ovulation-inducing agents and assisted reproductive technologies, the incidence of multiple pregnancies has risen significantly. Fetal reduction has traditionally been employed to mitigate the risks of preterm birth and other adverse perinatal outcomes in such pregnancies. In trichorionic triplet pregnancies, reduction to twins has been shown to prolong gestation by an average of three weeks.4 In dichorionic triamniotic triplets, reduction to a singleton similarly resulted in an increased median gestational age at delivery.5 Additionally, a retrospective cohort study reported that elective reduction in triplet pregnancies significantly reduced the incidence of preeclampsia compared with ongoing or spontaneously reduced triplet pregnancies.6 Multiple studies have demonstrated that fetal reduction can prolong gestation, increase neonatal birth weight, and reduce the incidence of preeclampsia and other complications.7 The elevated risk of preeclampsia in twin pregnancies may be attributed to the increased placental mass and the associated rise in anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1).8 We speculate that selective fetocide may contribute to the control of preeclampsia by reducing or halting the release of anti-angiogenic factors such as sFlt-1, thereby alleviating symptoms and prolonging the duration of pregnancy. In this article, we present a case involving a 32-year-old nulliparous woman with a dichorionic twin pregnancy complicated by early-onset preeclampsia. Following selective fetal reduction, the clinical manifestations of preeclampsia resolved for nearly two weeks. It is well recognized that both shortened cervical length and invasive procedures such as amniocentesis increase the risk of preterm premature rupture of membranes. In this case, the decision to perform amniocentesis with intracardiac injection of potassium chloride was further complicated by the presence of a short cervix. Notably, we observed a subsequent increase in cervical length following the fetal reduction, suggesting that the procedure may have alleviated intrauterine pressure associated with the twin pregnancy and potentially reduced the risk of preterm birth. To our knowledge, this is the first reported observation of such an effect, and we speculate that it may be related to a reduction in the overall pregnancy burden after selective reduction. We conducted a literature review and identified 11 publications reporting 13 cases in which selective fetocide was used as a therapeutic intervention for severe preeclampsia. The findings are summarized in Supplementary Table S3, https://links.lww.com/MFM/A97. Among the 13 cases, pregnancy was prolonged by approximately 2 to 21 weeks, and three patients delivered at term. Most cases involved dichorionic-diamniotic twin pregnancies. One case involved a triplet pregnancy with selective reduction of a monochorionic-diamniotic twin pair, while two cases involved triplet pregnancies that had spontaneously reduced to twins following intrauterine demise of one fetus during the first trimester. All reported cases of preeclampsia occurred prior to 34 weeks of gestation, with onset ranging from 18 to 31 weeks. Potassium chloride injection was the method of fetal reduction used in all cases. Following reduction, symptoms of preeclampsia improved in most patients within two weeks, with gestational prolongation ranging from 2 to 21 weeks. In two cases, resolution of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome was also documented. Most patients ultimately delivered a healthy surviving fetus. These findings suggest that selective fetocide may significantly alleviate maternal symptoms and improve perinatal outcomes in cases of early-onset preeclampsia. Conclusion Selective fetocide may be considered a therapeutic option for severe preeclampsia in discordant multifetal pregnancies. This intervention has the potential to prolong gestation and improve perinatal outcomes by reducing the release of anti-angiogenic or other pathogenic factors from the affected placenta. However, its application should be reserved for carefully selected cases and must be guided by comprehensive counseling and multidisciplinary management. Indications for selective fetocide should be strictly defined, primarily in cases of significant fetal growth discordance complicated by early-onset severe preeclampsia, where the prognosis for the smaller fetus is poor. In addition, the procedure should be subject to thorough ethical review, with particular attention to the psychological well-being of the patient and her family. Future research involving larger cohorts is needed to further elucidate the underlying mechanisms, as well as to assess the long-term efficacy and safety of this intervention. Funding The study was supported by National Natural Science Foundation of China (Grant No.82301910) and the National Key Research and Development Program (Grant No.2021YFC2701601). Conflicts of Interest None. Data Availability All data generated or analyzed during this study are included in this published article and its supplementary information files, https://links.lww.com/MFM/A97. Editor Note Huixia Yang is the Editor-in-Chief of Maternal-Fetal Medicine. The article was subject to the journal's standard procedures, with peer review handled independently of this editor and the associated research groups.
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