Keywords
Fetal anemia - fetal demise - Doppler velocimetry - twin–twin transfusion syndrome
Acute inter–twin hemorrhage in stage V twin–twin transfusion syndrome (TTTS) may be
diagnosed using middle cerebral artery (MCA) Doppler velocimetry.
Case Report
A 27-year-old gravida 3, para 1 at 23 weeks and 4 days of gestational age with a spontaneous
monochorionic, diamniotic twin gestation presented to our institution for threatened
preterm labor. Ultrasound evaluation upon admission revealed previously unknown stage
I TTTS in otherwise anatomically normal female fetuses. The donor twin was noted to
be a classic “stuck twin” without a measurable fluid pocket; the recipient showed
severe polyhydramnios with a deepest vertical pocket (DVP) of >13 cm. Over the course
of 9 days of hospitalization, three amnioreduction procedures were performed removing
900, 1400, and 1000 mL of amniotic fluid, respectively. The patient received magnesium
sulfate tocolysis and betamethasone for fetal lung maturation. Her preterm labor resolved,
and she was discharged home undelivered with close outpatient follow-up. Serial ultrasound
examinations were performed and noted no progression of TTTS by Quintero staging criteria.
However, the fluid discrepancy, particularly the amount of polyhydramnios, remained
significant with 1.6- to 1.9-cm pockets in the donor and 11- to 13-cm pockets in the
recipient twin. Five additional amnioreduction procedures were performed for maternal
symptomatic relief and improvement of the DVP in the donor to 6.5 to 6.8 cm was noted.
At 28 weeks and 6 days of gestation, 2 days following a routine ultrasound evaluation
that showed a DVP of 6.7 cm in the donor and 13 cm in the recipient twin as well as
normal umbilical artery Doppler with a systolic to diastolic (S/D) ratio of 2.0 in
the donor and 2.8 in the recipient, stage V TTTS was diagnosed with demise of the
donor twin. The surviving recipient twin was noted to have a mildly increased umbilical
artery S/D ratio of 4.9 with positive end-diastolic flow. Fetal heart rate tracing
revealed minimal variability with intermittent variable and rare late decelerations.
Repeat ultrasound evaluation after transfer to the labor and delivery unit included
a fetal MCA peak systolic velocity (PSV) measurement and showed a marked increase
to 2.27 multiples of the median (MoM) for gestational age.
Given the sudden progression and clinical symptoms of acute anemia in addition to
a worsening fetal heart rate tracing, the decision was made to proceed with urgent
repeat cesarean section. The demised donor twin A weighed 1206 g. The surviving twin
B weighed 1365 g with Apgar scores of 1 at 1 minute and 8 at 5 minutes (cord blood
gases: arterial pH 7.31; pCO
2 44.9 mm Hg; pO
2 13.6 mm Hg; HCO3 22.0 mmol/L; base excess -4; O2 saturation 14.2%; venous pH 7.38; pCO
2 39 mm Hg; pO
2 30.4 mm Hg; HCO3 22.3 mmol/L; base excess −3; O2 saturation 56.7%). The newborn was pale and immediate blood analysis confirmed acute
anemia with a hemoglobin of 8.1 g/dL and a hematocrit of 27.8%. She was intubated
and received 15 mL of type O-negative packed red blood cells. Maternal Kleihauer-Betke
test was negative for indices of fetomaternal hemorrhage. Placental pathology demonstrated
meconium-pigmented macrophages in the placental membranes, a velamentous cord insertion,
a false knot, and generalized pallor. Multiple small artery-to-vein anastomoses were
noted.
The infant's neonatal intensive care course was uncomplicated with the exception of
a few typical complications of prematurity: mild hyperbilirubinemia and a short course
of necrotizing enterocolitis were medically managed. At her 11-month follow-up, she
met all developmental milestones and had not required additional specialist care.
Discussion
TTTS complicates 10 to 15% of monochorionic twin pregnancies.[1] The underlying pathophysiology involves unbalanced blood flow through placental
vascular anastomoses. Stage V TTTS—defined as death of at least one twin—occurs in
32% of such pregnancies.[2] When not treated with laser ablation or another interventions, ~50% of surviving
twins die or experience permanent disabilities.[3] Such disabilities are likely due to acute hemorrhage from surviving twin to deceased
twin, resulting in severe anemia and ischemia-related damage, such as periventricular
leukomalacia.[4] These hemodynamic changes have been observed fetoscopically within 3 hours of initial
twin demise.[5] Morbidity and mortality associated with significant preterm birth—occurring in ~68%
of these cases—are difficult to distinguish from the sequelae of acute ischemia.[6] Given that the average gestational age at which death of the first twin occurs is
24 weeks,[7] management of the surviving twin poses an obstetric dilemma. In our case, elevated
fetal MCA Doppler PSV was used in the scenario of stage V TTTS to diagnose an acute
intertwin hemorrhage. This ultimately led to delivery of a 28-week fetus due to concerns
for impending fetal compromise and resulted in good long-term outcome.
TTTS in the lower stages is considered a chronic fetal condition that may be expectantly
managed with careful observation to avoid complications of prematurity.[1] Invasive procedures such as laser photocoagulation are not usually recommended for
treatment in stage I TTTS.[2] Sudden progression to a significantly higher stage is rare but associated with significant
morbidity and mortality.[1] In a very premature gestation as represented by our case, the decision to proceed
with delivery rather than continue with expectant management or treatment by fetal
transfusion must be carefully weighed. Because we could rely on a well-documented
normal ultrasound just 2 days prior to the sudden deterioration, we were able to use
the acute change manifested in the pathologically elevated fetal MCA Doppler measurement
as an indicator of fetal compromise and make the decision to deliver urgently. We
believe that despite the premature gestation, this rapid intervention and the subsequent
neonatal transfusion led to the ultimately good outcome. Fetal MCA PSV of 1.5 MoM
and greater has demonstrated 90% sensitivity and specificity for the prediction of
moderate or severe fetal anemia[5] ([Figs. 1] and [2]). The critically elevated value in this instance was likely due to reversal of blood
flow through the anastomoses to the demised twin leading to anemia, as has been described
previously in the literature.[4] A few prior reports have discussed similar cases and avoided premature delivery
by performing cordocentesis and rescue intrauterine transfusions.[8] We argue that urgent delivery was likely preferable in our scenario, given the mixed
reported results of such transfusions and the already compromised fetal heart rate
tracing. Although we will not always have the luxury to be able to evaluate a twin
pair with TTTS immediately at the time of demise of one twin to be able to intervene
quickly and prevent demise or damage of the survivor, we believe that our case demonstrates
how fetal MCA Doppler studies, even without corroboration by fetal blood sampling,
can provide valuable information and may be integrated into the management of this
rare but devastating complication. Physicians, sonographers, and parents of affected
pregnancies should be aware of this possible outcome and have an emergent treatment
plan in effect that should include immediate evaluation of the MCA Doppler PSV.
Figure 1 Example of a normal middle cerebral artery peak systolic velocity measurement of
40.9 cm/s or 1.27 multiples of the median by Doppler ultrasound at 25 weeks gestational
age.
Figure 2 Example of an abnormal middle cerebral artery peak systolic velocity measurement
of 83.5 cm/s or 2.06 multiples of the median by Doppler ultrasound at 30 weeks gestational
age indicating fetal anemia.
