Keywords
absent pulmonary valve syndrome - intrapartum fetal demise - high-risk pregnancy
Absent pulmonary valve syndrome (APVS) is a rare congenital condition of uncertain
etiology often associated with tetralogy of Fallot (TOF). First described by Cheevers
in 1847, malformations include an absent or dysplastic pulmonary valve, annular pulmonary
stenosis with regurgitation, and aneurysmatic dilation of the main pulmonary artery.
Historically, the majority of cases have been diagnosed postnatally as a result of
dilated pulmonary arteries compressing bronchial airways, with a risk of perinatal
death as high as 60%.[1]
[2] Few studies have followed the antenatal course of fetuses affected by APVS, and
no study to date has described intrapartum fetal death.
Case Reports
Our first case was a nulliparous 16-year-old woman with abnormal fetal cardiac findings
on an 18-week ultrasound. Fetal echocardiogram at 20 weeks visualized a nubbin-like
pulmonary valve with a small 2.5-mm annulus, mild pulmonary stenosis with severe pulmonary
regurgitation, enlarged main and branch pulmonary arteries (6 to 7 mm), mild right
ventricular hypertrophy (RVH) and dilation, and an absent ductus arteriosus (DA).
Subsequent echocardiograms displayed enlarging pulmonary arteries (9 to 11 mm), one
small perimembranous and one midmuscular ventricular septal defect (VSD), and normal
aortic architecture. Evaluation of the fetus included a normal karyotype (46, XX).
The patient had no significant past medical history, and the fetus had no extracardiac
abnormalities.
Labor was induced at 38 weeks and 6 days for intrauterine growth restriction [estimated
fetal weight (EFW) 2620 g (<10th percentile); 2 weeks prior the EFW = 2524 g (21st
percentile)]. Doppler studies and amniotic fluid index (AFI) were in the normal range.
Cervidil (Forest Pharmaceuticals, St. Louis, MO) (10 μg) was placed vaginally, followed
by a standard oxytocin infusion. Nubain (APP Pharmaceuticals, Schaumburg, IL; nalbuphine
hydrochloride) and promethazine were given for patient discomfort at midnight. After
the medications were administered, there was decreased fetal heart rate (FHR) variability
on the external fetal monitor (EFM) but no decelerations were noted, findings commonly
seen in the FHR after Nubain administration. At 2:50 am, the patient was disconnected from the EFM for 10 minutes to void. Upon reconnection,
no FHR could be detected. Ultrasound showed fetal cardiac asystole. The cervix was
1 to 2 cm dilated, 50% effaced. Fetal membranes were intact. There was no cord prolapse.
The patient had no vaginal bleeding or abdominal pain, and no contractions were palpable
or demonstrated on the monitor. An emergency cesarean delivery was performed under
general anesthesia, and a stillborn infant female was delivered. There was no nuchal
or body cord and no evidence of a placental abruption. The birth weight was 2650 g.
Cord arterial blood gas was pH 7.09/pco
2 79/po
2 21 and venous blood gas was pH 7.14/pco
2 65/po
2 26. The infant was intubated, ventilated, and aggressively resuscitated. The neonate
received eight doses of norepinephrine and bicarbonate. The Apgar score was zero from
1 until 20 minutes. Twenty-three minutes after birth, a heart tone and improved skin
color were detected (Apgar score of 3 at 25 minutes) and the infant was brought to
the neonatal intensive care unit and maintained on mechanical ventilation support.
Echocardiogram confirmed the absence of a pulmonary valve and the presence of a dilated
pulmonary artery that appeared to be compressing the trachea. The infant showed no
tone or reflexes on day 2. Although electrocardiogram showed normal sinus rhythm at
180 beats/min, electroencephalogram noted minimal cortical function with bilateral
basal ganglia infarctions seen on cranial magnetic resonance imaging on day 3. Ventilation
support was withdrawn on day 4 after extensive counseling, and the neonate died shortly
thereafter. The patient was medically stable during her postpartum course and on postoperative
day 4 was discharged home. The 430-g placenta (25th to 50th percentile) contained
three infarcts (<5% of the placental disc), and a three-vessel umbilical cord. Autopsy
showed a stenotic pulmonary valve annulus with minimal dysplastic tissue in the region
of the pulmonary valve, dilation of the main, right and left pulmonary arteries, two
VSDs, absence of a DA, an atrial septal defect secundum type, RVH, and bilateral lung
congestion with evidence of atelectasis. In addition, coagulative necrosis consistent
with ischemic injury was noted in the myocardium of the left and right ventricles
and right atrium.
Our second case was a nulliparous 24-year-old woman with abnormal fetal cardiac findings
on an 18-week ultrasound. A subsequent 25-week ultrasound showed a hypoplastic right
ventricle and possible tricuspid atresia. Initial fetal echocardiography at 26 weeks
showed a hypoplastic right ventricle, small pulmonary artery (2.7 mm), and small tricuspid
valve with antegrade flow and no regurgitation. Subsequent echocardiograms visualized
moderate pulmonary insufficiency with antegrade and retrograde flow through the hypoplastic
pulmonary artery and no evidence of the pulmonary valve, consistent with APVS. The
ascending aorta and aortic arch were dilated and a patent DA with retrograde flow
was visualized. No VSDs were noted. The patient had no significant past medical history,
and only mild polyhydramnios was noted on serial ultrasound examinations until the
day of admission. She had declined amniocentesis.
Labor was induced at 39 weeks and 1 day for a decrease in AFI from 17 to 6 cm over
a 1-week period. One dose of 25 μg of misoprostol was placed vaginally and repeated
4 hours later. This was followed by a standard oxytocin infusion. The FHR was reactive
at 3 am with a baseline of 140 seconds and moderate variability on the EFM. The tracing was
unremarkable until 3:23 am when the baseline appeared as a rapid, oscillatory pattern which lasted 30 seconds
followed by apparent loss of the FHR ([Fig. 1]). There were no contractions, abdominal pain, or vaginal bleeding. Fetal membranes
were intact. Bedside ultrasound showed a FHR in the 60s and the patient was brought
back to the operating room for an emergent cesarean delivery under general anesthesia.
A stillborn male infant was delivered in the vertex position. There was no nuchal
or body cord, and there was no evidence of an abruption. The birth weight was 3282 g.
Aggressive resuscitation was instituted but cardiac asystole persisted. Resuscitation
efforts were abandoned after 30 minutes. Cord venous blood gas was pH 7.31/pco
2 47/po
2 41. The 491-g placenta (75th to 90th percentile) contained intervillous fibrin deposition
and a three-vessel umbilical cord. Cytogenetic analysis detected normal male karyotype
46, XY. The patient desired no autopsy to be preformed.
Figure 1 Rapid oscillatory pattern of fetal heart rate immediately prior to sudden loss of
fetal heart rate.
Discussion
Improvements in obstetric ultrasound have allowed for earlier and more precise prenatal
diagnosis of APVS. Recent studies have diagnosed APVS at 11 to 13 weeks' gestation
and have found associations with an increased first-trimester nuchal translucency,
congenital diaphragmatic hernia, nonimmune hydrops, polyhydramnios, and the chromosomal
22q11 microdeletion.[2]
[3]
[4]
[5] Varying presentations of APVS have also been documented. APVS is most commonly associated
with TOF and often accompanying VSD. Regurgitant flow results in volume overload of
both ventricles, especially in fetuses with a patent DA. The severe chronic volume
overload makes this combination incompatible with fetal life. APVS with an absent
DA (10 to 20% of these patients) may allow the fetus to reach the second trimester.[2] In these fetuses, the pulmonary trunk and branches are often severely dilated, as
in our first case. The rarer variant is APVS with tricuspid atresia, an intact interventricular
septum, saclike dilation of the right ventricle, and a patent DA.[6] This variant, due to increased aortic flow, results in more aortic and less pulmonary
artery branch dilation. Some features of this condition are noted in our second case.
The detection of structural details by ultrasound has also been shown to have prognostic
significance. Fetuses with hydrops or larger right pulmonary artery volume and annulus
size have been linked with poorer prognosis.[7] Infants with an intact interventricular septum and/or diagnosed after 6 months of
life have a more benign prognosis than those with a VSD or who develop respiratory
symptoms in infancy.[8] The more frequent variant of APVS may also have slightly better outcomes than that
of the rare variant.[9] Consequently, precise sonographic evaluation of the fetal heart and vessels in APVS
may be of prognostic benefit, as suggested in a recent study on the use of three-
and four-dimensional ultrasonography in APVS.[10]
The intrapartum monitoring and clinical findings in our cases suggest acute fetal
cardiac events when the patients were in early labor. The cause may have been electrophysiological
as there were no findings to suggest progressive mechanical cardiac failure prior
to labor and no evidence to suggest other common causes of intrapartum fetal death,
such as abruption, cord accident, tetanic uterine contraction, or ongoing hypoxia/acidemia.
The advantages and timing of early amniotomy and fetal scalp electrode placement to
more accurately monitor and intervene in the labor of fetuses with APVS is a question
to consider.
Acute intrapartum fetal demise with APVS has not been previously reported and further
adds to the well-accepted poor prognosis of affected fetuses. Larger studies of the
intrapartum course of fetuses affected by APVS are needed to determine if factors
that may increase sudden fetal death exist. In the meantime, in-depth parental counseling
with maternal–fetal medicine and pediatric cardiology should include the possibility
of acute fetal cardiac events in labor and the still uncertain fetal benefit of emergency
cesarean delivery.
