Fetal Arrhythmia with a Myriad of Complications

A 22-year-old primigravida’s medical history is suggestive of hypothyroidism detected incidentally 3 years ago, which was controlled on tablet thyroxine 50 µg once a day. Previous ultrasonography scans performed until 18 weeks documented a fetal heart rate of 140 beats/min, with no obvious fetal anomaly. Subsequently, she is lost to follow-up until 39 weeks’ gestation. Ultrasonography performed at 39 weeks’ postmenstrual age shows a decreased fetal heart rate of 55 beats/min with fetal growth restriction (estimated fetal weight 2,139±321 g, <3rd percentile), oligohydramnios (amniotic fluid index of 5.5 cm), and Doppler showing pathologic cerebroplacental ratio of 0.9 (1.60±0.58). (1) No fetal echocardiography findings are available. A decision is made to proceed with delivery for fetal bradycardia because of the increased risk of fetal stillbirth. A male neonate weighing 2,030 g is born via emergency cesarean delivery at 39 weeks’ gestation and does not cry at birth, thus requiring intubation. Given the heart rate of less than 60 beats/min after successful intubation emergency line placement, chest compression and epinephrine are initiated in the delivery room.Despite resuscitation, the neonate continues to have bradycardia with a heart rate of 45 beats/min, along with hemodynamic instability and poor perfusion.Further examination shows no signs of dysmorphisms or hydrops fetalis. Anthropometrically, the neonate is small for gestational age with a birthweight of 2,030 g, length of 46 cm, and head circumference of 29 cm (all <10th percentile; modified Fenton growth chart). On cardiovascular examination, the neonate has a pansystolic murmur of grade IV/VI with normal heart sounds, and the liver is palpable 3 cm below the right subcostal margin.Fetal cardiac conduction defect (eg, heart block)Prolonged intrauterine hypoxiaCongenital heart diseaseDilated cardiomyopathyEndocardial fibroelastosisFetal anemiaFetal inflammatory response secondary to infectionAt admission to the NICU, the neonate had a heart rate of 45 beats/min. Chest radiography performed at admission showed cardiomegaly with a cardiothoracic ratio of 0.73. Electrocardiography showed right axis deviation with a heart rate of 40 beats/min, with complete dissociation of P and QRS waves with regular P-P and R-R intervals. The atrial rate was 140 beats/min, and the ventricular rate was 45 beats/min. There were no ventricular arrhythmias or escape rhythm, and QRS complexes were normal (Fig 1). Echocardiography showed severe biventricular dysfunction with an ejection fraction of 20%. There was also evidence of mild pulmonary hypertension with tricuspid regurgitation in a structurally normal heart.Given the aforementioned findings in the neonate, a detailed history from the mother was elicited. She had recurrent low-grade fever for 8 to 12 months, hair loss, oral sicca symptoms (dry mouth, difficulty in swallowing), and arthralgia in ankles and knees bilaterally with Raynaud phenomena.The differential diagnosis at this point was narrowed down to congenital heart block secondary to maternal autoimmune disease. Further evaluation of the mother and neonate are summarized in Tables 1 and 2.The neonate received mechanical ventilation at settings of 16/6/50% (peak inspiratory pressure/peak end expiratory pressure/FiO2) and required multiple inotropic support for cardiogenic shock with poor cardiac contractility. However, the neonate continued to have hemodynamic instability with a ventricular rate of 45 beats/min. Hence, temporary pacing via a transvenous approach was performed for the infant 24 hours after birth. The pacing was performed via a 5F umbilical venous catheter, which was exchanged over a 0.21” Terumo wire, and a 4F, 11-cm Terumo sheath was placed at the inferior vena cava-right atrium junction (Fig 2). Right ventricular pacing was started after positioning the pacing wire to achieve a threshold of 2 mV. Pacing was kept in the ventricular pacing and sensing (VVI) mode at 120 beats/min with an output of 8 mV. The neonate was monitored every 6 hours for pacemaker threshold, cardiac output, and complications of pacemaker insertion such as pericardial effusion, infection at the insertion site, and pacing failure. After the procedure, bedside functional echocardiography showed improvement in parameters (Table 3).On day 2, the neonate had sclerema. Sepsis evaluation conducted at that time showed a total leukocyte count of 26,400/µL (26.4 × 109/L; reference range: 5,000–25,000/µL [5–25 × 109/L]), C-reactive protein of 8.95 mg/dL (89.5 mg/L; reference range: 0–1 mg/dL [0–10 mg/L]), and sterile blood culture. The neonate was initiated on piperacillin-tazobactam injections (150 mg/kg per day). He also developed acute kidney injury in the form of increased creatinine (1.82 mg/dL [138.78 µmol/L]) and anuria, requiring 21 cycles of peritoneal dialysis to establish appropriate urine output. On day 4, echocardiography was performed, which showed dilated chambers of the heart with thin ventricular walls, suggesting dilated cardiomyopathy.The neonate underwent permanent pacemaker implantation as the definitive treatment on day 8 after birth after being hemodynamically stable for 24 to 48 hours. The Medtronic Vitatron Q20A2 single chamber pacemaker lead was sutured over the right ventricle and fixed to a pulse generator implanted in the peritoneum (Fig 3). The temporary pacemaker was removed after confirming that the permanent pacemaker was pacing at 140 beats/min. One hour postprocedure venous blood gas measurement (Table 2) showed low ionic calcium, for which calcium gluconate correction is added.However, the neonate died suddenly 6 hours after the permanent pacemaker was placed. Causes ascertained for sudden death were: 1) sudden acid-base balance or electrolyte disturbances, 2) malfunctioning of permanent pacemaker (however, interrogator did not show any change in impedance), 3) pericardial effusion or tamponade (ruled out), or 4) thromboembolism. The neonate’s parents did not consent to autopsy of the neonate to confirm the exact cause of death. The mother was counseled to continue treatment for Sjogren disease and is being followed up by the genetics and obstetrics team.The final diagnosis was autoimmune congenital heart block in a mother with Sjogren syndrome and hypothyroidism with dilated cardiomyopathy.Congenital complete heart block affects 1 in 15,000 infants. (2) Etiologies include transplacental transfer of Ro or La antibodies (60%–90%) seen in those born to mothers with autoimmune diseases, such as systemic lupus erythematosus (SLE) and Sjogren syndrome, and neonates with congenital heart disease (25%–33%) such as L-transposition of great arteries. (2)The mother in our case had nonspecific symptoms, but her true diagnosis was made only after she delivered a neonate with congenital complete heart block, similar to a study conducted on 49 congenital complete heart block cases, in which 64% to 78% of mothers were indirectly diagnosed with positive anti-Ro and anti-La antibodies due to Sjogren disease after delivery. (3)(4) Often, SLE is diagnosed in mothers and Sjogren syndrome is missed, with a ninefold risk for delivering a child with congenital complete heart block in those with an associated hypothyroidism. (5)In the case of suspected fetal congenital heart block, serial echocardiography and obstetric ultrasonography should be performed weekly from 16 weeks of gestation. (6) Options for antenatal treatment include fluorinated steroids, hydroxychloroquine, intravenous immunoglobulin, and plasma exchanges. These treatments may reverse or stabilize incomplete atrioventricular (AV) block only if given before deterioration of the cardiovascular profile score. (7) There is no definitive evidence that our neonate's heart block could have been reversed with antenatal diagnosis. (3)(7).Pacemaker implantation is indicated for congenital third-degree AV block in an infant with a ventricular rate of less than 55 beats/min without congenital heart disease. (8)(9) In a study by Glatz et al, early placement of a temporary pacemaker was recommended for severely affected newborns (coexistence of significant structural heart disease, extreme prematurity, low birthweight, in utero hydrops, or ventricular dysfunction) as a bridge to permanent pacemaker. (10) The index patient received a temporary pacemaker at the end of 24 hours and a permanent pacemaker after he was hemodynamically stable, which was similar to the aforementioned study wherein 54% received pacing in the first 24 hours. (10)Identified factors for poor prognosis despite pacing include hydrops fetalis, heart rate less than 50 to 55 beats/min, dilated cardiomyopathy, valvular dysfunction, low birthweight, male sex, delivery before 34 weeks of gestation, or complications from prematurity or neonatal lupus. (10) Poor prognostic markers in our neonate were low ventricular rate, severe cardiac dysfunction, and dilated cardiomyopathy, where mortality exceeds 80%. (10)Temporary and permanent pacemakers require aggressive short- and long-term follow-up, and yet certain groups have poor prognoses.Antenatal diagnosis of congenital complete heart block plays an important role in neonatal resuscitation and postpartum treatment of affected neonates.In neonates presenting with congenital complete heart block, especially if unknown antenatally, it is imperative to meticulously investigate gaps in the maternal medical history and promptly address them.