Vanishing twin syndrome

Vanishing twin syndrome is defined as the spontaneous reduction of a fetus while still in utero ¹⁾, which dissipates either partially or completely during gestation ²⁾. Vanishing twin syndrome is estimated to occur in 50% of pregnancies that start with three or more gestational sacs, and 36% of twin pregnancies ³⁾. In vanishing twin syndrome, there may be complete reabsorption of a fetus, formation of a fetus papyraceus (ie, a “mummified” or compressed fetus), or development of a subtle abnormality on the placenta such as a cyst, subchorionic fibrin, or amorphous material ⁴⁾. The timing of this event significantly affects the outcome of the viable twin and the maternal complications. For example, if the event occurs during the second half of pregnancy, the fetus could develop cerebral palsy or cutis aplasia, and the mother could develop preterm labor, infection, puerperal hemorrhage, consumptive coagulopathy, or obstruction of labor ⁵⁾.

Vanishing twin syndrome has also been demonstrated to alter the results of first trimester biochemistry testing that is used to screen for aneuploidy ⁶⁾. Additionally, vanishing twin syndrome was found to be associated with an increased risk for congenital anomalies ⁷⁾, malformations of cortical development in monochorionic twins ⁸⁾, vaginal bleeding ⁹⁾, and preterm premature rupture of membranes ¹⁰⁾, as compared with other types of gestation.

Conversely, there is no uniform consensus as to whether any detrimental perinatal outcome concerning infants delivered after vanishing twin syndrome exists at all ¹¹⁾. Moreover, another study that examined only IVF (in-vitro fertilization) pregnancies compared the outcomes of singletons, twins, and vanishing twin syndrome and found that indeed vanishing twin syndrome was associated with poorer outcome when compared with singletons, although a better outcome was noted when compared with twins ¹²⁾. Hence, there may be additional factors pertaining directly to the inherent underlying cause of infertile couples seeking treatment that can account for the adverse outcomes noted above, regardless of whether spontaneous fetal reduction or other potentially confounding factors have concomitantly occurred ¹³⁾.

In addition to its association with adverse maternal and neonatal outcome, vanishing twin syndrome was also found to be an independent risk factor for perinatal mortality. This finding confirms conclusions reached in previous studies, which showed that vanishing twin syndrome indeed posed a substantially higher risk for perinatal mortality ¹⁴⁾. One study even showed that vanishing twin syndrome more than tripled the risk for such an outcome, even after adjustment for maternal age and parity ¹⁵⁾. This last study was composed of 7,757 deliveries, all conceived through assisted reproductive technology (ART), whereas our study population is more than 32 times this value and is composed mainly of spontaneously conceived gestations. In contrast, other smaller studies demonstrated no increased risk of mortality or other adverse outcomes among the vanishing twin syndrome group ¹⁶⁾. The conflicting data noted above further emphasize the controversial views regarding the detrimental effects caused by vanishing twin syndrome.

With regard to IVF (in-vitro fertilization) or ICSI (Intracytoplasmic Sperm Injection) pregnancies, it is estimated to occur in 12–30% ¹⁷⁾. Furthermore, vanishing twin syndrome is associated with adverse pregnancy outcomes for the remaining survivor among both spontaneously conceived ¹⁸⁾ and assisted reproductive technology (ART) pregnancies ¹⁹⁾. Adverse outcomes include higher risk of low birth weight, preterm birth, small for gestational age (SGA) and birth defects ²⁰⁾.

Vanishing twin syndrome statistics

The frequency of multiple gestations is 3.3-5.4% at 8 weeks’ gestation ²¹⁾. Vanishing twin syndrome occurs in 21-30% of multifetal gestation ²²⁾.

Research from a European series of pregnancies associated with assisted reproductive technology (ART) show that 10-15% of singleton births were initially twin gestations.

What causes vanishing twin syndrome?

The cause of vanishing twin syndrome is frequently unknown; however, vanishing twin syndrome occurs more often in fetuses with genetic or chromosomal abnormalities ²³⁾. Improper cord implantation may also play a role in some cases.

Vanishing twin syndrome pathophysiology

Abnormalities that result in the disappearance of a fetus usually appear to be present from early in development rather than occurring from an acute insult. Placental or fetal analysis frequently reveals chromosome abnormalities. These abnormalities include diploidy, triploidy, and alternate sex chromosome results on placental pathology, skin biopsies, and chorionic villus sampling ²⁴⁾. Study findings of the viable twin chromosomes in these reports are normal. Therefore, it is thought that the vanished twin had a chromosomal abnormality resulting in disappearance.

Vanishing twin syndrome symptoms

Problems usually develop during the first trimester of pregnancy. The most common presenting complaints include bleeding, uterine cramps, and pelvic pain ²⁵⁾. When vanishing twin syndrome occurs during the first trimester, the mother is most likely to develop mild vaginal bleeding and cramping. If the event occurs later in the first trimester, morbidity may be similar to that of the second and third trimesters.

Maternal morbidity in the second and third trimesters

Maternal complications include premature labor, infection from a retained fetus, severe puerperal hemorrhage, consumptive coagulopathy, and obstruction of labor by a low-lying fetus papyraceus causing dystocia and leading to a cesarean delivery ²⁶⁾.

The diagnosis of vanishing twin in a pregnancy significantly increases both preterm (< 37 gestational weeks) and very preterm (< 32 gestational weeks) births ²⁷⁾.

Fetal morbidity and mortality

In addition to loss of a twin, the surviving fetus has an increased risk of cerebral palsy, particularly if vanishing twin syndrome occurred during the second half of pregnancy ²⁸⁾.

Other forms of morbidity reported in the surviving twin are aplasia cutis or areas of skin necrosis. In twins connected through vascular connection by placental anastomoses, temporary hypotension in the surviving twin at the time of fetal demise of the vanishing twin leads to poor perfusion and skin necrosis ²⁹⁾.

Vanishing twin syndrome complications

Prematurity

Singleton pregnancies that were reduced to singleton because of vanishing twin syndrome are more likely to be delivered preterm (35.1 vs 38.2 weeks). These rates of preterm delivery are similar to twin IVF pregnancies (23%) ³⁰⁾. In one series, singletons remaining after a vanishing twin event were associated with very premature birth (< 32 weeks estimated gestational age) ³¹⁾.

Low birth weight/small for gestational age

Singleton pregnancies that were reduced to singleton because of vanishing twin syndrome are at higher risk for growth restriction (32.6% vs 16.3% of control IVF singleton pregnancies) ³²⁾. Risks associated with intrauterine growth restriction include increased morbidity and mortality in the neonatal period and increased rates of hospitalization in the neonatal intensive care unit.

Cerebral palsy

Researchers proposed that vanishing twin syndrome could result in spastic cerebral palsy in the remaining twin. Cerebral palsy is the most common hypothesized pathological clinical sequela in the viable twin ³³⁾.

A possible mechanism is the transfusion of thromboplastic proteins from the vanishing twin to the surviving twin, leading to disseminated intravascular coagulation (DIC). Researchers hypothesize that disseminated intravascular coagulation (DIC) results from reverse blood flow from the macerated twin to the viable twin, thus carrying thromboplastins into the circulation. This large thromboplastin load is hypothesized to lead to a state of disseminated intravascular coagulation (DIC) in the viable twin, which then leads to intrauterine central nervous system damage ³⁴⁾.

Another proposed mechanism for central nervous system damage involves large amounts of blood loss from the surviving twin to the low resistance system of the vanishing twin through placental anastomoses. This transfusion could cause wide fluctuation in intravascular pressures, leading to intraventricular hemorrhage that results in cerebral palsy ³⁵⁾.

Cerebral impairment in the survivor has also been linked to confirmed cases of vanishing twin with impairment on the Griffiths Mental and Developmental Scales and Optimality score ³⁶⁾.

Associated congenital anomalies

A link in children with cerebral palsy and other congenital anomalies is possible. In one series, the relative risk for congenital malformations, including microcephaly, isolated hydrocephaly, eye, cleft lip/palate, and cardiac anomalies, increased over baseline from relative risk 3.1-116 depending on the specific defect ³⁷⁾. These anomalies are postulated to be due in part to perturbations in fetal flow in the surviving twin at the time of loss of the vanishing twin ³⁸⁾.

Cutis aplasia

The mechanism of development of cutis aplasia is most likely vascular. There is thought to be decreased perfusion to the affected area at the time of demise of the vanished twin. Most case reports include a fetus papyraceous as the vanished twin ³⁹⁾.

Other complications

Preterm birth of the surviving twin has been described with a 2.3-fold increased risk and a mortality rate that is 3-fold increased ⁴⁰⁾.

The surviving singleton infant after a twin vanishes has been shown to have a lower birth weight (mean difference, 368 g) than singleton pregnancies ⁴¹⁾.

Vanishing twin syndrome diagnosis

Recent vanishing twin has been shown to increase pregnancy associated plasma protein-A (PAPP-A) and free beta-hCG. This may affect risk assessment for aneuploidy in the surviving fetus ⁴²⁾.

Alpha-fetoprotein levels are elevated compared with values at similar junctures in both a singleton pregnancy and a normal twin pregnancy ⁴³⁾.

The rate of rise of beta-human chorionic gonadotropin is slower than in a normal twin pregnancy ⁴⁴⁾.

If vanishing twin syndrome is diagnosed at the time of nuchal translucency ultrasound, biochemical screening markers may not be as precise as in singleton-assisted reproductive technique pregnancies ⁴⁵⁾.

The use of biochemical markers may be indicated if, at the time of nuchal translucency, a vanishing twin is confirmed to have an empty gestational sac; however, if a dead fetus remains, biochemical markers are not accurate for screening ⁴⁶⁾.

Other tests

Amniocentesis after diagnosis of a vanishing twin by prior ultrasonography has been reported to detect an XY cell by both FISH and real-time PCR in the sustained XX 20 weeks’ gestation pregnancy. Take caution about interpretation of amniocentesis results because a vanishing twin fetus could lead to false-positive results ⁴⁷⁾.

Imaging Studies

Ultrasonography is used to confirm the diagnosis of early twin pregnancy. Follow-up ultrasonography reveals the pregnancy loss (vanishing twin) ⁴⁸⁾. In addition, after diagnosing first-trimester bleeding, using ultrasonography before dilation and curettage is important. This ensures that bleeding does not signal the loss of just one fetus.

Procedures

Chorionic villus sampling may be helpful if the placenta has a mosaic makeup and there is a singleton at birth.

Histologic Findings

Obtain histological samples of the placenta at birth since they may be the only evidence of vanishing twin syndrome with a reabsorbed fetus ⁴⁹⁾.

Vanishing twin syndrome management

Uncomplicated vanishing twin syndrome requires no special medical care.

If a fetus papyraceus remains, the pregnancy should be followed closely with serial ultrasonographic evaluation of the live fetus. Risks include premature labor, obstruction of labor, or death of the surviving fetus due to placental abruption or chorioamnionitis ⁵⁰⁾. This fetus is also at risk for low birth weight and small for gestational age (SGA) with increasing risk in the surviving twin for vanishing twin occurring later in gestation ⁵¹⁾.

Your doctor should watch carefully for infection and consumptive coagulopathy.

Instruct pregnant women to seek medical care for vaginal bleeding, cramping, and pelvic pain.

The viable twin should receive specialized medical care as indicated by initial physical examination and subsequent mental and physical development.

Anand et al ⁵²⁾ reported in 2007 that surviving cotwins had poorer scores on the Griffiths Mental and Development Scales when compared with singleton pregnancies.

Surgical Care

Only perform dilation and curettage after ultrasonographic confirmation that a viable embryo or fetus does not exist ⁵³⁾.