Terbutaline-triggered fetal arrhythmia prior to neonatal diagnosis of Wolff-Parkinson-White syndrome: A case report.

INTRODUCTION: Short-term maternal administration of betamimetics is a common obstetric practice with uses including tocolysis during antenatal corticosteroid administration for fetal lung maturity, intrapartum tachysystole, and prior to external cephalic version. While previous research has demonstrated adverse effects of prolonged use of maternal betamimetics, no prior documentation exists of fetal tachyarrhythmias beyond sinus tachycardia after administration of terbutaline. CASE: This case documents a transient fetal tachyarrhythmia consistent with presumed atrial flutter after maternal administration of terbutaline for external cephalic version. On day of life 9, the neonate presented in supraventricular tachycardia with signs of heart failure and was subsequently diagnosed with Wolff-Parkinson-White syndrome.
CONCLUSION: Maternal administration of terbutaline may be associated with transient fetal tachyarrhythmia. In some fetuses, this cardiac arrhythmia may predate diagnosis of an underlying cardiac disorder, warranting close follow-up after delivery.

Introduction

Terbutaline has multiple applications within the practice of obstetrics. Historically, it has been used as a tocolytic to inhibit preterm uterine contractions and prevent preterm labor [1,2]. While the US Food and Drug Administration has issued warnings against prolonged use of terbutaline due to potential maternal and fetal adverse effects [3], its short-term use as a tocolytic is endorsed by the American College of Obstetricians and Gynecologists [2,4,5].

Terbutaline exerts inotropic and chronotropic effects on cardiac muscle by activation of beta-1 adrenergic receptors and activates beta-2 adrenergic receptors to relax smooth muscle [6,7]. Maternal and fetal sinus tachycardia have been documented in response to maternal administration of terbutaline [3,8,9]. To the authors' knowledge, a case report of fetal tachycardia with postpartum diagnosis of neonatal ventricular tachycardia observed after maternal exposure to terbutaline is the only existing documentation of a fetal arrhythmia, aside from fetal sinus tachycardia, following maternal administration of terbutaline [1,8].

This case report documents a transient fetal tachyarrhythmia consistent with presumed atrial flutter (AFl) after routine administration of terbutaline in preparation for external cephalic version (ECV). The fetus had no known cardiac abnormalities and had not previously had any documented issues with fetal heart rate (FHR). After birth, the neonate was diagnosed with Wolff-Parkinson-White syndrome.

Case presentation

A 35-year-old woman, G5P0040, presented at 37 weeks and 3 days of gestation for planned ECV for breech presentation. Pregnancy history included three prior first-trimester spontaneous abortions and one prior ectopic pregnancy managed with left salpingectomy. The current pregnancy was complicated by advanced maternal age, maternal antiphospholipid antibody syndrome and maternal hypothyroidism, treated with enoxaparin, aspirin, and levothyroxine. Thyroid labs, measured monthly during pregnancy, were maintained within normal limits with adjustments of levothyroxine per endocrinology. Diagnosis of antiphospholipid syndrome was established by elevated anticardiolipin antibodies on two occasions <12 weeks apart and history of three spontaneous pregnancy losses prior to 10 weeks of gestation. Growth ultrasounds and antenatal testing were reassuring, with an appropriately grown fetus with an estimated fetal weight of 3126 g (77 percentile) at 36 weeks and 1 day.

Upon presentation for ECV, electronic fetal monitoring (EFM) demonstrated a baseline of 140 beats per minute (BPM), moderate variability, accelerations, and no decelerations. At patient request, spinal anesthetic was administered prior to the procedure. Subcutaneous terbutaline, 25μg, was administered prior to the procedure. Maternal vitals after administration of the above medications demonstrated mild tachycardia (max 113 BPM) with regular rhythm lasting 30 min and transient hypotension with nadir 80/40 mmHg managed by anesthesia with phenylephrine with return to normotension (111/68 mmHg). Maternal vitals remained stable throughout the remainder of her care. Ultrasound guidance confirmed breech fetal position and reassuring FHR. After one attempted fetal rotation, bedside ultrasound demonstrated an abnormal, tachycardic FHR at 300 BPM (Fig. 1). External fetal monitoring displayed FHR in the 140 s, inconsistent with the visualized heart rate. Fetal tachyarrhythmia persisted despite maternal repositioning, intravenous fluids, and blood pressure monitoring.

Fig. 1

Fetal tachyarrhythmia following terbutaline administration. White arrows depict ventricular contractions with corresponding rate of 300 BPM. Black arrows depict atrial contractions.

Maternal Fetal Medicine was consulted. FHR was thought to be consistent with possible 2:1 atrial flutter vs. SVT; available images from bedside ultrasound displayed atrial and ventricular rates of 280–300, and atrial rates of 500–600 consistent with 2:1 AFl. Imaging of the atrial rate on M-mode was limited by gestational age and rate. Immediate medical management was deferred due to advanced gestational age and acute onset. Bedside ultrasound was without obvious congenital cardiac anomalies or signs of hydrops. The FHR converted spontaneously to normal rate and rhythm approximately 4 h after administration of the betamimetic. Continuous fetal monitoring overnight demonstrated reassuring FHR, confirmed intermittently with ultrasound and Doppler. Formal echocardiogram with pediatric cardiology was deferred given spontaneous conversion of rhythm and reassuring screening cardiac views. The patient was discharged home the following day with instructions to continue antenatal testing and regular prenatal visits; the remainder of her prenatal course was without evidence of recurrent fetal tachyarrhythmia.

The patient underwent uncomplicated primary low transverse cesarean delivery at 39 weeks and 3 days for breech presentation. The infant was vigorous at delivery with APGAR scores of 8 and 9. The FHR was within normal limits and vital signs were stable. Neonatal TSH was within normal limits. A newborn EKG obtained prior to discharge demonstrated peaked P waves in lead II, concerning for right atrial enlargement. An echocardiogram performed on day of life (DOL) 2 showed low-normal aortic arch and isthmus dimensions without evidence of obstruction, a mildly dilated ascending aorta, and persistent patent ductus arteriosus (PDA). A repeat echocardiogram was performed on DOL 3, redemonstrating low-normal aortic arch dimensions, without evidence of obstruction, and with interval closure of the PDA. A follow-up echocardiogram at 2–4 weeks after delivery was recommended.

On DOL 9, the newborn patient was brought to her primary care physician due to tachycardia noted by the parents. On presentation, the heart rate was 250 BPM with associated tachypnea; EKG demonstrated SVT with HR up to 297 BPM (Fig. 2). The patient was transferred to the children's emergency department (ED). Upon presentation to the ED, the newborn received adenosine and was cardioverted with transient pre-excitation noted upon return of sinus rhythm. She was started on propranolol on admission with no further episodes of tachyarrhythmia. Follow-up ECG showed preexcitation consistent with a left-sided accessory pathway (Fig. 3), yielding a diagnosis of Wolff-Parkinson-White syndrome. Transient secondary cardiomyopathy with moderately diminished systolic function was noted, but improvement was apparent on repeat imaging the following day. The patient was discharged home on propranolol with a cardiac event monitor.

Fig. 2

Initial ECG at presentation: Narrow complex tachycardia consistent with SVT at 280 BPM.

Fig. 3

Follow-up ECG in sinus rhythm showing preexcitation consistent with a left-sided WPW pathway. A positive delta wave is noted in leads V 1 to V 6 and is negative in leads 1 and aVl with a short PR segment.

Upon follow-up at 5 weeks of life, the previously documented tachycardia-mediated cardiomyopathy had resolved. The child was continued on propranolol with dose adjustments for breakthrough episodes of SVT related to increased weight. Repeat EKG at nine months of life demonstrated resolution of preexcitation and sinus bradycardia. Plans per pediatric cardiology included repeat EKG at 21 months of life, with plans to trial off propranolol.

Discussion

This case describes a pregnant patient who presented for external cephalic version at 37 weeks of gestation. Her fetus, with a previously normal targeted anatomic survey and cardiac evaluation, developed a tachyarrhythmia shortly after administration of terbutaline, which resolved spontaneously. Additional administered medications including spinal anesthesia are not associated with fetal tachycardia [11]. Neonatal evaluation demonstrated reassuring cardiac status until the neonate presented at DOL 9 with tachyarrhythmia and cardiomyopathy and was diagnosed with Wolff-Parkinson-White syndrome.

Terbutaline is a beta agonist with stimulatory effects on both B1 and B2 receptors [7]. The utility of terbutaline in obstetrics stems from B2 stimulation, leading to relaxation of smooth muscle. Historically, terbutaline and other betamimetics were administered for prolonged periods in the setting of preterm uterine contractions; however, emerging data demonstrates lack of efficacy beyond 48 h with no meaningful prolongation of pregnancy, as well as potential harm [1,2,7]. Current betamimetic use in pregnancy is limited to short-term prenatal administration for tocolysis to allow for steroid administration to aid fetal lung maturity (tocolysis in the steroid window [[1], [2], [3]]), prenatal administration to aid success of ECV [5], and intrapartum administration for maternal tachysystole [4,17].

Adverse maternal effects have been documented, including but not limited to maternal sinus and ventricular tachycardias, atrial fibrillation, pulmonary edema, and maternal SVT [1,3,7,[12], [13], [14], [15]]. Most documented adverse maternal effects occur after prolonged use of betamimetics; ritodrine has been removed from the US market and terbutaline has received an FDA warning against use for greater than 48 h due to concern for maternal cardiac safety and maternal death [3,16].

Limited data exists regarding the potential effects of betamimetics on the fetus or neonate [[18], [19], [20]]. Fetal sinus tachycardia is a known side-effect of betamimetics [1]; the B1 stimulatory effect of terbutaline has been leveraged for management of congenital fetal heartblock [10,18,19]. Review of the literature demonstrates one previous case report of a fetal tachycardia to 190 BPM after maternal administration of terbutaline with subsequent diagnosis of neonatal ventricular tachycardia [8] as well as a case report of congenital atrial flutter and hydrops fetalis following prolonged administration of ritodrine [20]. No other literature exists documenting fetal tachyarrhythmia or discovery of an underlying cardiac disorder after short-term administration of terbutaline.

To the authors' knowledge, this is the first reported case of terbutaline associated with a tachyarrhythmia from underlying fetal Wolff-Parkinson-White or any other cardiac syndrome. This case presents multiple salient learning points. Fetal tachyarrhythmias following administration of terbutaline may resolve spontaneously. If a tachyarrhythmia is noted following maternal administration of terbutaline in a previously healthy fetus without signs of cardiac compromise (hydrops or cardiomyopathy), expectant management may be appropriate. Transient, unexpected fetal tachyarrhythmias following administration of maternal terbutaline may be a harbinger of future neonatal cardiac arrhythmias, begging the question of whether follow-up is needed for neonates who had transient cardiac tachyarrhythmias in utero. If a tachyarrhythmia is persistent, a formal echocardiogram should be performed by the maternal fetal medicine or pediatric cardiology physician prior to delivery; this may be delayed until the postpartum period in fetuses nearing full term.

Future research may delve into the effects of betamimetics or tocolytics in fetuses with known cardiac conditions or the incidence of diagnosis of neonatal cardiac complications after documentation of fetal tachyarrhythmias with in-utero exposure to betamimetics.