Neonates With Critical Congenital Heart Disease

CHAPTER 31 Neonates With Critical Congenital Heart Disease: Delivery Room Management and Stabilization Before Transfer to the Cardiac Intensive Care Unit

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Jay D. Pruetz, Jodie K. Votava-Smith, and Linda Tesoriero • M  ost prenatally diagnosed congenital heart disease (CHD) does not require emergent neonatal care. • Critical forms of CHD require emergent stabilization and intervention in the first hours after delivery. • Critical forms of CHD can benefit most from active perinatal and delivery room management. • Risk stratification strategies for CHD can help guide neonatal management in cases of complex CHD. • Fetal echocardiography can be used to determine which critical CHD lesions will need emergent neonatal intervention. • Current areas of research include evaluation of fetal echocardiographic markers used for assessing CHD severity and fetal interventions to improve postnatal outcomes.

Introduction to Prenatal Evaluation of Congenital Heart Disease and the Definition of Critical Congenital Heart Disease The incidence of congenital heart disease (CHD) is estimated at about 8 per 1000 live births,1 while more severe forms of CHD affect about 3 out of 1000 live births.2 Severe forms of CHD include those which require early medical, surgical, or catheterization based interventions in the first postnatal days to weeks, generally in concert with multidisciplinary subspecialty care including pediatric cardiologists, cardiothoracic surgeons, neonatologists, and pediatric cardiac intensivists. Since the first reports of using ultrasound to prenatally diagnose CHD more than 3 decades ago,3 there have been remarkable advances in ultrasound technology allowing for high-resolution assessment of fetal cardiac anatomy, function, and rhythm. Transition at birth from fetal to postnatal circulation involves lung expansion and a drop in pulmonary vascular resistance, loss of the low-resistance placenta from the circulation with a resultant increase in systemic vascular resistance, loss of the fetal intracardiac shunts, and shift to reliance on oxygenation by the lungs rather than the placenta.4 CHD lesion types with inadequate aortic or pulmonary outflow are termed “ductal dependent,” given the need for flow through the ductus arteriosus to provide or augment either pulmonary or systemic blood flow. Postnatally, medical therapy with prostaglandin E1 (PGE1) is needed to maintain ductal patency, with the eventual need for surgical- or catheter-based intervention to provide a more stable 555

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source of pulmonary or systemic blood flow (see Chapter 32). The most critical forms of CHD have an additional element of instability with the perinatal transition. These can be grouped into four categories, including (1) lack of adequate pulmonary egress, found in obstructed total anomalous pulmonary venous return (TAPVR) and subtypes of hypoplastic left heart syndrome (HLHS) with intact or restrictive atrial septum; (2) inadequate intracardiac mixing of oxygenated blood to the systemic circulation in some cases of d-transposition of the great arteries (d-TGA) with restrictive atrial shunting; (3) an associated anomaly of the airway which compromises the ability to ventilate such as severe cases of Ebstein anomaly and tetralogy of Fallot (TOF) with absent pulmonary valve (APV); and (4) inadequate cardiac output in cases of severe fetal arrhythmias or diminished cardiac function either in isolation or in combination with CHD. These critical forms of CHD can be predicted with fetal echocardiographic findings, which then allows for careful planning of maternal care to optimize the delivery and provide targeted postnatal care. 

Perinatal Management Strategies to Optimize Postnatal Transition The goals of active prenatal planning and perinatal management for neonates with CHD are a well-coordinated transition from fetal life to postnatal care, minimizing mortality and morbidity, and ensuring a stable preoperative clinical status. Additional benefits include adequate time for parental education, expanded prenatal evaluation, and mobilization of psychosocial support systems. Action plans must take into account the underlying cardiac anatomy, anticipated physiologic changes during the transition from fetal to postnatal life, the speed at which patients may become critically unstable, and the need for emergent neonatal intervention. Risk stratification systems are designed for multiple levels of CHD severity and are used to select the appropriate medical center for delivery, mode of delivery (MOD), level of perinatology and neonatology services available, and capability for immediate access to cardiology and cardiothoracic surgery care. The transportation of infants with critical CHD to a higher-level cardiac care center for delivery and postnatal care has been shown to improve outcomes and is associated with lower overall health care costs.57 Of note is that it is not recommended to deliver patients with CHD prematurely, as prematurity and low birth weight can have a significant negative impact on outcomes.8-10 Given this data, the current recommendations are to deliver these patients at 39 weeks’ gestation. A prenatal diagnosis of CHD may alter the chosen MOD and has been shown to result in elevated rates of elective C-section for many forms of CHD.11-13 However, there is little evidence to show that altering MOD improves outcomes for CHD patients and studies have shown that vaginal birth is well tolerated in this population.13-15 Thus, changes in delivery timing and MOD should only be made in order to provide rapid postnatal stabilization and intervention in the most critical of cases. Active perinatal management of critical CHD is now practiced by many centers across the United States and Europe using similar risk stratifying schemes with recommended care plans.16-19 These classification systems are based on regional practice patterns and designed to identify patients that require specialized treatment in the delivery room (DR) and cardiac intervention in the first hours after delivery (Table 31.1 and 31.2). The cardiovascular disease severity scales are based on the anatomic severity of CHD, need for postnatal intervention, complexity of intervention, and overall prognosis. The level of care (LOC) is typically assigned first by the cardiologist, according to the CHD severity, and is then reviewed and agreed upon with the entire maternal fetal medicine team. Each LOC is linked with a specific coordinated action plan and detailed perinatal recommendations for delivery and DR management such as need for PGE, transport, and intervention. Risk stratification and management systems using LOC for neonates prenatally diagnosed with CHD have been shown to be highly accurate at predicting the postnatal care and need for emergent intervention at birth.18,20 These classification strategies have been highly reproducible, with the exception of d-TGA, due to the difficulty determining the risk

Table 31.1 DEFINITION OF LEVEL OF CARE ASSIGNMENT AND COORDINATED ACTION PLAN DR Recommendations

LOC

Definition

Example CHD

Prenatal Planning

Delivery

1

CHD without physiologic instability in first weeks of life CHD with physiologic stability in DR but requiring postnatal intervention/surgery before discharge

1. Shunt lesions (e.g., ASD, VSD, AVSD)

Arrange outpatient cardiology evaluation

Spontaneous vaginal delivery

Routine DR management

Create plan of care for DR stabilization and neonatal management by local hospital with transport to pediatric cardiac center

Spontaneous vaginal delivery versus induction near term

Neonatologist in DR; initiate PGE at low dose for ductaldependent lesions

Create plan of care to include specialized pediatric cardiology team in DR and interventional/ surgical team on standby

Planned induction usually at 39 weeks with “bailout” C/S if necessary for care coordination

Neonatologist and pediatric cardiology specialists in DR; stabilizing medications predetermined by care plan

2

CHD with expected instability requiring immediate specialty care in DR before anticipated stabilizing intervention/surgery

4

CHD with expected instability requiring immediate specialty care and urgent intervention/surgery in DR to improve chance of survival

2. Ductal-dependent lesions or lesions with complex physiology likely to require neonatal intervention/surgery (e.g., HLHS, PA/IVS, truncus arteriosus) 3. Nonsustained or controlled tachyarrhythmias 1. HLHS/RFO 2. d-TGA/RFO 3. Severe Ebstein anomaly with dilated right ventricle and low RV pressure 4. TOF/APV with RV and/or LV dysfunction and cardiac shift 5. Sustained tachyarrhythmias or CHB with heart failure 1. HLHS/IAS 2. d-TGA/severe RFO or IAS with abnormal DA flow 3. Severe Ebstein anomaly or TOF/APV with hydrops 4. Tachyarrhythmias/bradyarrhythmias with hydrops

Create multidisciplinary Planned C/S at a medical center plan of care to include with high-level obstetrical and delivery at medical center pediatric cardiac and other with high-level obstetrical pediatric subspecialty services and pediatric cardiac seravailable usually at 38–39 vices available and with weeks or sooner if there is specialized care team in evidence of fetal distress or DR and interventional/ hydrops; maternal risk detersurgical team ready mined by obstetrician (delivery of such cases at medical centers with high-level adult and complex pediatric services)

Specialized care team in DR Stabilizing medications/equipment predetermined by care plan

557

APV, Absent pulmonary valve; ASD, atrial septal defect; AVSD. atrioventricular septal defect; CHB, complete heart block; CHD, congenital heart disease; C/S, cesarean section; DR, delivery room; DA, ductus arteriosus; HLHS, hypoplastic left heart syndrome; LOC, level of care; LV, left ventricular; PA/IVS, pulmonary atresia with intact ventricular septum; PGE, prostaglandin E; RV, right ventricular; RFO, restrictive foramen ovale; TOF, tetralogy of Fallot; VSD, ventricular septal defect. From Donofrio, MT, Skurow-Todd, K, Berger JT, et al: Risk-stratified postnatal care of newborns with congenital heart disease determined by fetal echocardiography; J Amer Soc Echocardiogr 2015;28(11):1339–1349.

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1. Benign arrhythmias

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Table 31.2 LEVEL OF CARE ASSIGNMENT AND COORDINATING ACTION PLAN LOC

Definition

Example CHD

P

CHD in which palliative care is planned

CHD with severe/fatal chromosome abnormality or multisystem disease

1

CHD without VSD, AVSD. mild TOF predicted risk of hemodynamic instability in the DR or first days of life CHD with minimal Ductal-dependent lesions, risk of hemodyincluding HLHS, critical namic instability coarctation, severe AS, in DR but requirIAA, PA/IVS, severe ing postnatal TOF catheterization/ surgery CHD with likely d-TGA with concerning hemodynamic atrial septum primum instability in DR (note: it is reasonable requiring immedito consider all d-TGA ate specialty care fetuses without an ASD for stabilization at risk) Uncontrolled arrhythmias CHB with heart failure

E 2

3

4

CHD with expected hemodynamic instability with placental separation requiring immediate catheterization/ surgery in DR to improve chance of survival

5

CHD in which cardiac transplantation is planned

Delivery Recommendations Arrange for family support/palliative care services Normal delivery at local hospital Arrange cardiology consultation or outpatient evaluation Normal delivery at local hospital

DR Recommendations

Routine DR care Neonatal evaluation

Consider planned induc- Neonatologist in DR tion usually near term Routine DR care, initiDelivery at hospital with ate PGE if indicated neonatologist and Transport for cathaccessible cardiology eterization/ consultation surgery Planned induction at 38–39 weeks; consider C/S if necessary to coordinate services Delivery at hospital that can execute rapid care, including necessary stabilizing/lifesaving procedures C/S in cardiac facility with necessary specialists in the DR usually at 38–39 weeks

HLHS/severely RFO or IAS d-TGA/severely RFO or IAS and abnormal DA Obstructed TAPVR Ebstein anomaly with hydrops TOF with APV and severe airway obstruction Uncontrolled arrhythmias with hydrops CHB with low ventricular rate, EFE, and/or hydrops HLHS/IAS; CHD including List after 35 weeks of severe Ebstein anomaly; gestation C/S when CHD, or cardiomyopathy heart is available with severe ventricular dysfunction

Neonatologist and cardiac specialist in DR, including all necessary equipment Plan for intervention as indicated by diagnosis Plan for urgent transport if indicated Specialized cardiac care team in DR Plan for intervention as indicated by diagnosis; may include catheterization, surgery, or ECMO

Specialized cardiac care team in DR

APV, Absent pulmonary valve; AS, aortic stenosis; ASD, atrial septal defect; AVSD, atrioventricular septal defect; CHB, complete heart block; CHD, congenital heart disease; C/S, cesarean section; d-TGA, transposition of the great arteries, DA, ductus arteriosus; DR, delivery room; ECMO, extracorporeal membrane oxygenation; EFE, endocardial fibroelastosis; HLHS, hypoplastic left heart syndrome; IAA, interrupted aortic arch; IAS, intact atrial septum; LOC, level of care; PA/IVS, pulmonary atresia/intact ventricular septum; PGE, prostaglandin E; RFO, restrictive foramen ovale; TAPVR, total anomalous pulmonary venous return; TOF, tetralogy of Fallot; and VSD, ventricular septal defect. From Donofrio MT, Moon-Grady AJ, Hornberger LK, et al: Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation 129(21):2183–2242, 2014.

for postnatal atrial level restriction and the result was to upgrade all d-TGA cases to LOC 4 status.20 Table 31.3 shows a comparison of various published CHD risk stratification systems, while Table 31.4 depicts an example of one of the classification systems, which we have termed “Emergent Neonatal Cardiac Intervention” (ENCI) risk categories (see Table 31.4).19

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Table 31.3 COMPARISON CHART OF DIFFERENT PUBLISHED CONGENITAL HEART DISEASE RISK CLASSIFICATION SYSTEMS Characteristics of Various CHD Severity Scales and Coordinating Care Plans

Donofrio et al., 2004

Berkley et al., 2009

Davey et al.,a 2014

Pruetz et al., 2014

Slodki et al., 2016

Level description

LOC 1–4

Care plans 1–5

LOC 1–7

ENCI Level 1–4

LOC 1–5, palliative care (P)

Palliative care Delivery site Mode of delivery Prostaglandin E1 Neonatology care Multispecialty care team Level of instability Need for emergent intervention Need for transport/transfer

N Y Y Y Y Y Y Y

Y Y Y Y Y Y N Y

Y N N Y Y Y N N

N Y Y Y Y Y Y Y

Severest, severe, urgent, planned N N Y Y Y Y Y Y

N

N

N

N

N

Y

AHA Statement Donofrio et al., 2014

Y Y Y Y Y Y Y Y

aThis

is a Fetal Cardiovascular Disease Scale and does not include coordinating actions plans. AHA, American Heart Association; CHD, congenital heart disease; ENCI, emergent neonatal cardiac intervention; LOC, level of care.

Table 31.4 EMERGENT NEONATAL CARDIAC INTERVENTION CLASSIFICATION SYSTEM AND MANAGEMENT GUIDELINEa

PGE

Mode of Delivery an Issue

NICU Acuity Level

Neonatology Present in Delivery Room

Cardiology, CT Surgery, CTICU, OR/ Cath Lab on Standby

No

No

Low

No

No

No

No

No

Medium

Possibly

No

3

Possibly

Yes

Possibly

High

Yes

Possibly

4

Yes

Yes

Yes

High

Yes

Yes

ENCI Level

High Risk

1

No

2

Examples ASD, VSD, Mild PS CAVC, TOF/ PS, Truncus Arteriosus HLHS, d-TGA/ VSD, PA/IVS d-TGA/RAS, Obstructed TAPVR

aA

four-level classification system for prenatally diagnosed congenital heart disease that takes into consideration both the level of postnatal clinical acuity and need for emergent postnatal intervention. ASD, Atrial septal defect; CAVC, complete atrioventricular canal; Cath, catheterization; CT, cardiothoracic; CTICU, cardiothoracic intensive care unit; d-TGA, d-transposition of the great arteries; HLHS, hypoplastic left heart syndrome; NICU, neonatal intensive care unit; OR, operating room; PA/IVS, pulmonary atresia with intact ventricular septum; PGE, prostaglandin E; PS, pulmonary stenosis; RAS, restrictive atrial septum; TOF, tetralogy of Fallot; VSD, ventricular septal defect. From Pruetz JD, Carroll C, Trento LU, et al: Outcomes of critical congenital heart disease requiring emergent neonatal cardiac intervention, Prenat Diagn 34(12):1127–1132, 2014.

1. LEVEL ONE, Low Risk: The lowest LOC is for CHD that does not cause hemodynamic instability in the newborn and is not expected to require specialized care or intervention in the newborn period. These patients can deliver at a hospital capable of providing care for babies with mild forms of CHD. MOD is not an issue and no special care is needed in the DR. Examples include atrial septal defect (ASD), ventricular septal defect (VSD), and mild valve abnormalities. 2. LEVEL TWO, Intermediate Risk: These newborns have potential for hemodynamic instability and need for postnatal evaluation by subspecialists, but low risk

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for neonatal intervention. These patients should deliver at a facility with access to subspecialty consultation if needed and neonatology involvement at birth as needed. Thus delivery should occur in a facility in close proximity to a center with pediatric cardiology support and a Level III neonatal intensive care unit (NICU) with a regional transfer agreement with a children’s hospital. MOD may be an issue if signs of congestive heart failure or hydrops are present. Examples include complete atrioventricular septal defect, aortic arch obstruction, moderate valve abnormality, truncus arteriosus, and TOF with expected mild to moderate level of pulmonary stenosis. 3. LEVEL THREE, Moderate Risk: These patients require neonatal intervention in the first days to weeks after delivery and include all ductal dependent lesions. These deliveries should be highly coordinated and occur at or nearby tertiary care centers with a high level of neonatal and cardiac expertise. If early intervention is likely or there is increased risk for high acuity at birth, delivery by induction or scheduled C-section should be considered to provide a window of anticipated delivery. MOD must also take in to account any evidence of congestive heart failure or hydrops. The cardiac intensive care unit (ICU), cardiology, and cardiothoracic surgery should be made aware of the patient well in advance. The transport team should be notified and on standby, to expedite the transfer. Examples include d-TGA with VSD, HLHS without restrictive atrial septum (RAS), severe aortic or pulmonary valve abnormalities (including single ventricles), unobstructed TAPVR, TOF with APV without lobar emphysema, Ebstein anomaly without hydrops, and complete heart block (CHB) with adequate heart rate (HR) (>60 bpm). 4. LEVEL FOUR, High Risk: The highest level is reserved for patients requiring immediate or emergent intervention, within hours after birth, and in whom severe instability is anticipated. The perinatal care should be highly coordinated in order for all resources to be available at the time of birth. These patients should deliver via scheduled C-section to minimize time to treatment with the necessary subspecialists on standby to care for the newborn. Ideally the delivery could occur in a highly specialized labor and delivery unit in a children’s hospital for immediate intervention.18,21 However, few programs have this capability and most still rely on transfer of the newborn from a connected or nearby maternity hospital. If transfer is needed, the transport team should also be on standby at the delivery institution. The baby must be adequately stabilized and monitored for transport, but performance of procedures in the delivery room must be balanced with the need to get the baby to intervention with minimal delay. Cardiac ICU, cardiology, and cardiothoracic surgery should be notified again immediately upon confirmation of birth. The operating room and/or cardiac catheterization laboratory should be on standby. Examples include obstructed TAPVR, HLHS with RAS, d-TGA with RAS, TOF/APV with lobar emphysema, severe Ebstein anomaly with hydrops or uncontrolled arrhythmia and unstable CHB with very low ventricular rate (<50 bpm), decreased myocardial function, or hydrops fetalis. 

Delivery Room Management and Stabilization This section will review specific cardiac lesions detailing the recommended prenatal planning, perinatal recommendations, and DR management.

Ductal-Dependent Lesions (Pulmonary Atresia, Interrupted Aortic Arch, Aortic Coarctation, Hypoplastic Left Heart Syndrome with Atrial Septal Defect) Cardiac defects expected to be postnatally ductal dependent for pulmonary blood flow either can be isolated (pulmonary stenosis/atresia with intact ventricular septum), or can occur as a part of TOF or a complex single ventricle lesion. Prenatal prediction of postnatally ductal-dependent pulmonary blood flow includes evaluation for antegrade pulmonary blood flow, reversed flow in the ductus arteriosus

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(e.g., prenatally directed from the aorta to the pulmonary arteries), pulmonary valve size with z-score less than −3, and a pulmonary-to-aortic valve annulus ratio less than 0.6.22-24 Cardiac defects expected to be postnatally ductal dependent for ­systemic blood flow include severe aortic stenosis/atresia, interrupted aortic arch (IAA), hypoplastic aortic arch, and suspected coarctation of the aorta. These lesions can occur in isolation or in combination with single ventricle defects such as HLHS. Prenatal predictors of postnatally ductal-dependent systemic blood flow include systolic flow reversal in the transverse aortic arch, left-to-right atrial shunting across the foramen ovale, and hypoplasia of the distal transverse aortic arch.22,25-27 All of these lesions will require neonatal intervention, but are unlikely to require specialized DR care or emergent intervention in the first 24 hours of postnatal life. They should have neonatology involvement and require initiation of PGE after birth. Postnatal care for complex cardiac patients requires preparation of the DR resuscitation team, NICU, and ancillary services (diagnostic imaging) prior to the delivery. The use of established DR room guidelines and checklists ensures a consistent approach to the stabilization of cardiac patients pending transfer to a surgical center. Team leaders should conduct a predelivery meeting with staff to review the CHD diagnosis, plan of care, and assign team member roles for the resuscitation/ stabilization. Equipment, intravenous (IV) access devices, emergency medications, cardiac medication infusions (such as PGE), and IV fluids should be prepared. Many steps outlined here will recur in the postnatal management of neonates with different forms of CHD, with variations based on the underlying diagnosis. Delivery room management begins by following the basic steps of neonatal resuscitation to assess the infant’s respiratory effort, circulation, and color. ENCI Level-3 patients are not at high risk for respiratory decompensation due to their underlying cardiac lesion after delivery, so elective intubation based on the cardiac diagnosis alone is not recommended. As with any neonate, the decision to intubate should be based on the assessment of the clinical respiratory and circulatory status with the use of premedication (“rapid sequence intubation”) if the intervention is not required on an emergent basis. Pulse oximetry should be initiated immediately after birth to guide judicious oxygen use in the DR with the goal of establishing preductal saturations based on the diagnosis: greater than 94% in patients with coarctation versus 75% to 85% in patients with HLHS and open septum. Ongoing circulatory assessment includes evaluation of HR, color, pulses, and central capillary refill. Once the patient has been assessed and stabilized in the DR, further stabilization should take place in the NICU prior to transfer out of the unit or facility. Cardiovascular monitoring can be further facilitated by placing umbilical venous (UVC) and arterial catheters (UAC). A UAC is used to directly monitor arterial blood pressure (BP) and obtain arterial laboratory samples. A UVC provides a secure method of monitoring central venous pressure (CVP), infusing IV medications, and delivering nutrition. X-ray or ultrasound verification of the central line position must be performed prior to use or transfer to avoid complications of catheter malposition (extravasation, cardiac tamponade, hepatic injury, etc.). Once IV access is secured, an infusion of PGE concentrated to 20 μg/mL at a dose of 0.025 μg/kg/ min should be started in a central line (UVC) or peripheral IV placed in an upper extremity to optimize medication transfer to the ductal tissue. Apnea and hypotension are known side effects of PGE which can manifest early. If the patient becomes apneic, respiratory stabilization is required using elective intubation with premedication and radiographic confirmation of the endotracheal tube position. Circulatory monitoring should continue with close attention to BP, urine output, and lactate levels. Transient hypotension can be managed with isotonic saline boluses of 10 mL/kg that may be repeated. Further BP stabilization may require the use of inotropic-lusitropic or vasopressor-inotropic support, as appropriate, to avoid repetitive volume bolus administration leading to volume overload. Maintenance fluid goals initiated with 10% dextrose at a total fluid goal of 80 mL/kg/day provide a glucose infusion rate of 5.5 mg/kg/min, which should maintain euglycemia in most term neonates. Following stabilization, care can be endorsed to the receiving facility and the neonatal transport team contacted. 

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Hypoplastic Left Heart Syndrome With Restrictive or Intact Atrial Septum Restriction of the foramen ovale is a severe and often fatal complication of HLHS occurring in 6% to 20% of HLHS cases.28-30 Prenatal identification of this highrisk subset of HLHS fetuses is crucial in order to coordinate the delivery, such that intervention to create an adequate atrial communication, via either cardiac catheterization or surgical intervention, can be performed in the first few minutes to hours after delivery.18,31 Pulsed Doppler interrogation of fetal pulmonary venous flow with measurement of the forward-to-reverse velocity time integral (VTI) is the most sensitive predictor of critically restrictive foramen ovale in HLHS (Fig. 31.1).32 This measurement evaluates the magnitude of flow reversal during atrial systole and provides an estimate of left atrial hypertension. Risk stratification categorizes pulmonary vein Doppler forward-to-reverse VTI ratio greater than 5 as a low-risk group, between 3 and 5 as moderate risk, and less than 3 high risk, with likely need for urgent intervention after birth.19,20 Neonates at the highest risk require a well-organized plan and close cooperation between pre- and postnatal

E

RA

RV LA

LV

A

B Forward/Reverse VTI ratio = 1.6 VTI = 3.6 cm

C

VTI = 5.8 cm

Fig. 31.1  Fetal echocardiogram images demonstrating HLHS with highly restrictive atrial septum. (A) Twodimensional image showing thick atrial septum (arrow) bowing from left atrium (LA) to right atrium (RA). (B) Color Doppler image of tiny left to right foramen ovale shunt (red flow marked with arrow). (C) Pulmonary vein pulsed Doppler waveform of the same fetus demonstrating measurement of forward flow (green) and prominent atrial systolic reversal (blue), with forward/reverse velocity time integral (VTI) ratio of 1.6 indicating highly restrictive atrial septum. LV, Left ventricle; RV, right ventricle.

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caregivers. The perinatal plan should involve a highly coordinated delivery via scheduled C-section to minimize time to treatment with the necessary subspecialists on standby to care for the newborn. In some centers, the delivery takes place in a specialized labor and delivery unit within the children’s hospital for immediate intervention, but if transfer is needed, the transport team should be ready on standby and an operating room or cardiac catheterization laboratory prepped and ready to receive the patient. As previously noted, the postnatal care of complex cardiac patients requires preparation of the DR resuscitation team, NICU, and support services such as radiology and the neonatal transport team. Due to the high acuity of ENCI Level-4 patients, these services should be on standby in the NICU prior to the delivery in order to expedite patient handoff after the initial stabilization. A standardized approach to care with optimized communication and predelivery preparation are even more important in the early management of these high-risk patients. Of note, delayed umbilical cord clamping at present is not recommended in these patients, who are anticipated to require immediate resuscitation for respiratory and/or cardiac compromise at birth. Evaluation begins by assessing the infant’s HR, respiratory effort, circulation, and color. Early elective endotracheal intubation is recommended in these patients due to the high risk for respiratory decompensation within the first hour after delivery. Pulse oximetry should be initiated immediately after birth to guide judicious oxygen use in the DR, with the goal of establishing preductal saturations in the range of 75% to 85%. In the event of bradycardia or cardiac compromise, a low-lying UVC should be immediately placed for the administration of emergency medications and IV fluids. Once the patient has been assessed and stabilized in the DR, further stabilization including radiographic confirmation of endotracheal tube and/or line placement should take place in the NICU prior to transfer. Recommendations for vascular access, prostaglandin infusion, circulatory monitoring, and fluids are outlined in the section covering ductal-dependent lesions. Management strategies for these patients include maneuvers to promote rightto-left shunting across the PDA to facilitate systemic blood flow. Steps to keep pulmonary vascular resistance from dropping quickly include avoiding the excess use of oxygen by targeting preductal saturations in the range of 75% to 85%, avoiding systemic hypertension by targeting a mean BP equal to the weeks of gestation with a maximum of 5 to 10 points above this level, and maintaining the hematocrit greater than 40% to temper pulmonary blood flow through viscosity. Close circulatory monitoring of HR, BP, pulses, and capillary refill remains ongoing throughout stabilization. Other markers of systemic perfusion, such as pH, lactate levels, and urine output, should also be followed. Once stabilized, the patient should be transferred to a cardiac center in an expedited manner by a highly trained neonatal transport team. 

D-Transposition of the Great Artery With Restrictive Atrial Septum Neonates with d-TGA have pulmonary and systemic circulations in parallel rather than in series, causing them to rely on intracardiac mixing of oxygenated blood into the systemic circulation, generally at the level of the atrial septum. Neonates with d-TGA and inadequate mixing at the atrial septum can be profoundly hypoxemic, and may require an urgent balloon atrial septostomy (BAS) by an interventional cardiologist to open the atrial septum. Differentiating which fetuses with d-TGA will have postnatal restriction of the atrial septum can be challenging. Several studies have shown that fetal echocardiographic assessment of atrial septal movement and excursion can be useful to predict cases at risk for postnatal atrial septal restriction.33-35 The predictive factors include hypermobility of the septum primum and bowing into the left atrium by more than 50% (Fig. 31.2), as well as diminished mobility, with an angle of less than 30 degrees between the atrial septum and bowing septum primum.34-36 Abnormal ductus arteriosus shunting patterns in d-TGA, including constriction, bidirectional flow, and reversal (see Fig. 31.2), can predict profound

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postnatal pulmonary hypertension and risk for neonatal death.35,37 However, our predictive capabilities remain suboptimal, such that the recent American Heart Association guidelines state that given the current lack of reliable markers to determine postnatal instability with high specificity and sensitivity, all babies with d-TGA should be delivered in anticipation of needing urgent BAS.7,12,36 Perinatal planning should include discussions of transfer of care to a higher level center and delivery by C-section or induction to expedite the time to intervention. As in the case of other ENCI Level-4 patients, the resuscitation team, equipment, and medications should be prepared prior to delivery as stated in the previous sections. Radiology services and a neonatal transport team should be on standby in the NICU in order to expedite the patient’s initial stabilization and transfer. Again, delayed umbilical cord clamping is not recommended due to the need for expedited resuscitation that includes early elective intubation. Initial DR management begins with assessment of the infant’s respiratory effort, HR, circulation, and color. Pulse oximetry initiated immediately after birth should guide oxygen use with the goal of establishing preductal saturations in the range of 75% to 85%. Early elective intubation is recommended, as these patients are at high risk for respiratory decompensation in the first minutes to hours after delivery and also require airway stabilization

RA

RA

LA LA

A

B AO

PA

DA

C

Ao arch

D

Fig. 31.2  D-Transposition of the great arteries (d-TGA) with restrictive atrial septum. Fetal echocardiogram images of patient with d-TGA with findings concerning for postnatal atrial septal restriction. (A) and (B) show hypermobile atrial septum (marked with arrows) which flops between the right atrium (RA) in panel A and left atrium (LA) in panel B. (C) Two-dimensional image of aortic arch and ductus arteriosus (DA) in the same fetus; note that the aorta (Ao) is located anteriorly as it comes off the right ventricle and pulmonary artery (PA) posteriorly off the left ventricle. (D) Color Doppler shows antegrade aortic arch flow (blue) and retrograde DA flow (red) marked with arrow.

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prior to atrial septostomy. Detailed circulatory assessment should be ongoing during resuscitation and stabilization. In the event of bradycardia or cardiac compromise, an emergent low-lying UVC should be placed for the administration of emergency medications such as epinephrine and IV fluid boluses. A low-lying UVC offers emergency central access in seconds, and its vascular pathway can later be repurposed to facilitate access for a BAS if needed. Line placement must be verified by x-ray prior to further use or transfer to avoid complications of malpositioned catheters. Recommendations for PGE infusion, circulatory monitoring, administration of fluids, and following markers of systemic perfusion are outlined in the previous sections. Strategies to improve pulmonary blood flow and avoid persistent pulmonary hypertension include optimizing oxygenation while avoiding/treating factors that can cause pulmonary vasospasm: metabolic or respiratory acidosis, systemic hypotension, hyperviscosity, and pain or agitation. Ongoing communication between the neonatology team leader, pediatric cardiology, and the transportation team is vital in expediting the transfer of patient care following the initial stabilization phase. 

Congenital Heart Disease With Airway Compromise: Tetralogy of Fallot With Absent Pulmonary Valve Syndrome and Severe Ebstein Anomaly TOF with APV syndrome is characterized by the absence or severe dysplasia of the pulmonary valve leaflets with severe pulmonary valve insufficiency. There is generally some degree of valvar pulmonary stenosis, but the hallmark is free pulmonary insufficiency with resultant aneurysmal dilatation of the branch pulmonary arteries, sometimes to a massive degree. The dilated pulmonary arteries compress the bronchi, resulting in varying degrees of bronchomalacia. The ductus arteriosus is often absent in this syndrome, but it is not known whether this is part of the defect or a consequence of the fetal hemodynamics.4 There is a high risk for in utero demise, which is thought to be secondary to right ventricular and right atrial dilatation affecting ductus venosus and venous pressures imposing a risk for hydrops. Airway obstruction due to severely dilated branch pulmonary arteries can cause extrinsic compression of the bronchi leading to “hyperinflation” of the lungs and lobar emphysema due to fetal lung fluid trapping. This can be seen on prenatal ultrasound, as it causes a severe axis shift of the heart in the chest and cardiac displacement, and can also be seen by fetal magnetic resonance image (Fig. 31.3).38,39 Preparation for the postnatal care and expedited transfer of ENCI Level-4 patients with antenatal diagnosis of TOF with APV involves the steps previously outlined in the section on HLHS with RAS/IAS. Additional steps must also be taken

Left Lung

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Fig. 31.3  (A) Fetal magnetic resonance image demonstrating axial plane through fetal thorax in a patient with Tetralogy of Fallot with absent pulmonary valve syndrome. The branch pulmonary arteries are massively dilated and the bronchi were not visible. The cardiac apex is deviated leftward. (B) Chest radiography of the same patient taken postnatally, demonstrating visible bulge of dilated RPA (*), lung hyperinflation, and interstitial lung disease in the setting of severe bronchomalacia. LPA, Left pulmonary artery; RPA, right pulmonary artery,

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to prepare for these patients who may be hydropic with limited antegrade pulmonary blood flow and emphysematous lungs, making effective oxygenation and ventilation a challenge following delivery. Large pleural effusions or significant abdominal ascites can impinge upon lung expansion affecting alveolar ventilation and the appropriate establishment of functional residual capacity, which limits gas exchange in general and oxygenation in particular. Preparation in the DR should include a setup for pleurocentesis, paracentesis, pericardiocentesis, and chest tube placement. Again, delayed cord clamping is not recommended for reasons previously stated. Early intubation for hydropic patients is of great importance because the ability to establish effective respirations and systemic oxygenation will likely be further diminished by the presence of generalized edema, pleural effusions, and ascites. Assessment of perfusion and cardiac function should be followed as outlined previously in the section on HLHS with RAS/IAS. The resuscitation team must know the location and size of effusions prior to delivery and be prepared to evacuate the fluid if a limited response to endotracheal positive pressure ventilation is noted. The aspirated fluid should be sent for analysis (glucose, protein, cell count, culture). Pneumothorax is a known potential complication of pleurocentesis and should be considered in neonates with respiratory deterioration after the procedure. Pulse oximetry should be used to target pre-ductal oxygen saturations between 75% and 85%. In the event of bradycardia or poor perfusion, an emergency low-lying UVC should be placed for the administration of emergency medications such as epinephrine and IV volume boluses. After the initial stabilization, the patient should be moved to the NICU for further stabilization, including appropriate central line placement and optimized respiratory management. There is potential for difficulty with ventilation from both the airway anomalies and inadequate antegrade pulmonary perfusion. PGE is not typically useful, as most cases have an absent ductus arteriosus. Extracorporeal membrane oxygenation (ECMO) may be needed for stabilization in cases of severe hypoxemia. Ventilation strategies for patients with emphysematous lungs should focus on modalities that minimize gas trapping and positioning the patient to decrease bronchial impingement. A trial of conventional ventilation may be employed using a low normal respiratory rate (30 breaths/min), inspiratory time to expiratory time ratio of 1:1.15 to optimize oxygenation, higher positive inspiratory pressure (PIP, 25 to 30 cm H2O), and adequate peak end-expiratory pressure (7 to 8 cm H2O) to keep airways stented open during exhalation and prevent collapse or gas trapping. The patient can also be positioned prone to alleviate bronchial compression from the engorged branch pulmonary arteries. If conventional ventilation fails, appropriately used high-frequency oscillatory ventilation (HFOV) or, if available, high-frequency jet ventilation (HFJV) offers a more effective method of ventilation in cases complicated by gas trapping and air leaks, as compared with conventional ventilation. With the use of HFOV or HFJV, ventilation is optimized with the use of lower peak and mean airway pressures compared with conventional ventilation, allowing emphysematous lung tissue to decompress and heal.40 A study using HFJV has also reported a positive effect on cardiac output, which can be compromised by marked gas trapping, decreasing venous return to the heart.41 X-ray confirmation of the position of the endotracheal tube and umbilical lines, ongoing hemodynamic monitoring, and communication with the transport team should be carried out as described earlier. Ebstein anomaly involves displacement of the tricuspid valve deep into the right ventricular cavity leading to severe tricuspid regurgitation, right atrial enlargement, and ventricular dysfunction. These fetuses are at high risk for development of fetal heart failure and hydrops related to elevated CVP,42 as well as risk for atrial tachyarrhythmia. Severe tricuspid regurgitation can result in massive cardiomegaly, which can pose a risk for the development of pulmonary hypoplasia (Fig. 31.4). Prenatal echo findings can help identify risk factors for poor outcome such as pulmonary regurgitation and cardiac enlargement, but it is not able to accurately predict the highest risk cases in which rapid deterioration in the perinatal period can be anticipated (see Fig. 31.4).43 Preparing for the postnatal care of patients with severe Ebstein anomaly with hydrops should be carried out as described previously for ENCI Level-4 patients with the additional anticipated challenges to adequate ventilation

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Fig. 31.4  (A) Fetal magnetic resonance image demonstrating axial plane through fetal thorax in patient with severe Ebstein anomaly with massive right atrial dilatation (right atrium width marked with arrows) and resultant bilateral lung hypoplasia. (B) Chest radiograph of the same patient taken postnatally, demonstrating severe cardiomegaly with wall-to-wall cardiac silhouette. RV, Right ventricle; LV, left ventricle; RL, right lung; LL, left lung.

and oxygenation due to various severity of pulmonary hypoplasia, severe edema, effusions, decreased pulmonary blood flow, and compromised cardiac output due to ventricular dysfunction and tachyarrhythmias. Antiarrhythmic medications and infusions should be prepared prior to delivery if there is a known fetal arrhythmia, and a defibrillator equipped with neonatal pads should be readily available should the need for synchronized cardioversion or defibrillation arise. The published algorithms for the management of arrhythmias delineated by the Pediatric Advanced Life Support program should be followed in these cases.44 Cases in which pulmonary hypoplasia is suspected can be given a trial of gentle conventional ventilation that begins in the DR and focuses on using a low-moderate PIP during resuscitation up to 20 to 25 cm H2O, increasing respiratory rate to 40 to 60 breaths per minute with IT of 0.3 to 0.4 seconds. PIP should be adjusted based on the patient’s lung compliance and oxygen titration based on continuous pulse oximetry with pre-ductal saturation goals of 75% to 85%. The team should be prepared to evacuate any significant effusions via pleurocentesis or paracentesis in an attempt to improve oxygenation and ventilation as outlined previously. If the trial with conventional ventilation is unsuccessful due to hypoxemia, hypercapnia, or air leaks, then a transition to HFOV or HFJV is indicated. Cautious titration of the mean airway pressure with close radiographic follow-up should be used to avoid hyperinflation, which can lead to gas trapping, air leaks, decreased venous return to the heart, and decreased pulmonary blood flow. Strategies to improve oxygenation and perfusion in these patients include PGE infusion, decreasing pulmonary vascular resistance (see previous section and consider the use of inhaled nitric oxide), and adding vasopressor-inotropes and/or lusitropes (dopamine and milrinone). Caution should be used in the selection of vasoactive medications in patients with severe Ebstein anomaly because they are at risk for supraventricular tachyarrhythmias (SVT) that can potentially degenerate into life-threatening ventricular arrhythmias.45 As previously stated, central line placement, ongoing assessments of hemodynamic status, and radiographic confirmation of the position of the central lines and the endotracheal and chest tubes should be completed prior to the hand-off of patient care or facility transfer. 

Bradyarrhythmias: Complete Heart Block Immune-mediated, congenital CHB is prenatally diagnosed in mothers that test positive for SSA/SSB antibodies. These fetuses usually have normal anatomic structure of the heart, but are at risk of developing hydrops, fetal demise, and preterm delivery when the fetal HR drops too low for adequate oxygen delivery to the fetus. After delivery, these infants may need pacing depending on the resting HR and clinical status. However, many of these neonates will not require any immediate intervention

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or placement of a permanent pacer until later in life. Prenatal findings that denote an increased risk are fetal HR less than 50 bpm, signs of fetal heart failure, and hydrops.46 Preparing for the delivery of patients with CHB requires preparation prior to delivery as discussed previously. Additional elements to consider include preparation of cardiac medication infusions for vasopressor-inotropic and chronotropic support in cases presenting with bradycardia and hemodynamic instability. Initial DR assessment includes evaluation of the neonate’s respiratory effort, HR, circulation, and color. Pulse oximetry should be performed immediately after birth in order to guide oxygen use with the goal for preductal saturations in the 85% to 95% range by 10 minutes after delivery, as delineated in the NRP algorithms.47 Patients with a documented, long-standing baseline ventricular rate of 55 to 60 bpm or greater than 60 bpm who do not exhibit signs of respiratory or circulatory compromise do not require early elective intubation or chest compressions. However, they do require ongoing hemodynamic monitoring with close attention to systemic perfusion. After initial stabilization in the DR, further NICU evaluation of stable, term neonates includes a 12 Lead electrocardiogram, echocardiogram, and cardiology consultation within 24 hours of birth. Patients whose antenatal course is complicated by a HR less than 50 bpm, decreased heart function, or hydrops should be approached as ENCI Level-4 patients. Detailed preparations should be carried out in addition to arranging for expedited transfer to a facility with the ability to provide a higher LOC. Early elective intubation followed by the evacuation of any effusions impinging on ventilation or perfusion should be addressed as soon as possible following delivery. Assessments of respiratory and hemodynamic stability should be ongoing during expedited central line placement and confirmation of line and tube positions. Those with imminent need for pacing and/or pacemaker placement for HR less than 55 bpm, significant hemodynamic instability, or wide complex escape rate (QRS duration >120 ms) should be transferred immediately to a higher LOC.48 For profound bradycardia or hypotension, epinephrine infusion should be initiated at a starting dose of 0.01 μg/kg/min with titration of the dose to the desired effect. An alternative medication to consider would be isoproterenol at a starting dose of 0.02 to 0.05 μg/kg/min. Some unstable patients may require transcutaneous pacing under the guidance of a pediatric cardiologist, which can be accomplished with the use of neonatal defibrillator pads, connected to a manual external defibrillator. 

Consideration for Fetal Therapy/Intervention In the current era of fetal intervention/therapy there exists the potential for lessening the acuity at neonatal presentation of CHD and improving the preoperative clinical condition by altering the disease state prenatally. Although appropriately designed, controlled trials have not been performed yet and might not even be feasible; findings of large case series suggest that balloon valvuloplasty of the aortic valve in cases of critical aortic stenosis might prevent progression to HLHS, resulting in a more stable biventricular circulation at birth.49,50 These patients may go from being ductal dependent at birth to not requiring a PGE infusion and possibly avoiding neonatal surgery. HLHS with RAS can be stabilized with prenatal/ fetal intervention by the creation of an atrial communication using either balloon septostomy or interatrial stent placement in the fetus.51 This has the potential to improve the physiology, stabilize the newborn, and avoid the need for emergent surgical- or catheter-based septostomy in the first hours after delivery. Medical fetal therapy with digoxin for fetal congenital heart failure (CHF), antiarrhythmia drugs for fetal SVT, and fetal transfusion all have the potential to reverse hydrops and fetal CHF improving fetal status prior to delivery and resulting in improved neonatal outcomes.36 Emerging therapies such as implantable fetal pacemakers for congenital CHB may help carry a pregnancy to term or near term and reverse fetal hydrops, resulting in a better clinical status at birth prior to permanent pacemaker implantation.52,53 

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Summary/Conclusions Neonates with critical CHD are at increased risk of mortality and morbidity due to their underlying condition and the compromise that postnatally begins in the delivery room.18 While advancements in scanning technology and enhanced screening guidelines continue to increase prenatal detection rates and improve outcomes for patients with CHD, identifying which newborns are at greatest risk for needing emergent neonatal cardiac intervention still presents a challenge. Critical CHD requires a highly coordinated perinatal plan and DR management strategy for appropriate stabilization and immediate transfer to the cardiac care team. From the time of initial diagnosis of critical CHD, there should be a comprehensive care plan developed based on the anticipated postnatal acuity level and need for emergent intervention. Active perinatal strategies and DR protocols, as well as close multidisciplinary collaboration, hold the promise of improving the approach to complex CHD. In the future, innovative fetal therapies may alter outcomes of critical CHD, and allow for a less critical transition from fetal to postnatal life. However, until that is fully realized, the best possibility for a good outcome is a well-developed and executed perinatal plan. REFERENCES 1. Montana E, Khoury MJ, Cragan JD, et al.: Trends and outcomes after prenatal diagnosis of congenital cardiac malformations by fetal echocardiography in a well defined birth population, Atlanta, Georgia, 1990–1994, J Am Col Cardiol 28(7):1805–1809, 1996. 2. Hoffman JI, Kaplan S: The incidence of congenital heart disease, J Am Col Cardiol 39(12):1890– 1900, 2002. 3. Kleinman CS, Hobbins JC, Jaffe CC, et al.: Echocardiographic studies of the human fetus: prenatal diagnosis of congenital heart disease and cardiac dysrhythmias, Pediatrics 65(6):1059–1067, 1980. 4. Rudolph AM: Congenital Diseases of the Heart: Clinical-Physiological Considerations, ed 3, Chichester, UK; Hoboken, NJ, 2009, Wiley-Blackwell. 5. Anagnostou K, Messenger L, Yates R, et al.: Outcome of infants with prenatally diagnosed congenital heart disease delivered outside specialist paediatric cardiac centres, Arch Dis Child Fetal Neonatal Ed 98(3):F218–221, 2013. 6. Jegatheeswaran A, Oliveira C, Batsos C, et al.: Costs of prenatal detection of congenital heart disease, Am J Cardiol 108(12):1808–1814, 2011. 7. Morris SA, Ethen MK, Penny DJ, et al.: Prenatal diagnosis, birth location, surgical center, and neonatal mortality in infants with hypoplastic left heart syndrome, Circulation 129(3):285–292, 2014. 8. Costello JM, Polito A, Brown DW, et al.: Birth before 39 weeks’ gestation is associated with worse outcomes in neonates with heart disease, Pediatrics 126(2):277–284, 2010. 9. Cnota JF, Gupta R, Michelfelder EC, et al.: Congenital heart disease infant death rates decrease as gestational age advances from 34 to 40 weeks, J Pediatr 159(5):761–765, 2011. 10. Wertaschnigg D, Manlhiot C, Jaeggi M, et al.: Contemporary outcomes and factors associated with mortality after a fetal or neonatal diagnosis of ebstein anomaly and tricuspid valve disease, Can J Cardiol 32(12):1500–1506, 2016. 11. Trento LU, Pruetz JD, Chang RK, et al.: Prenatal diagnosis of congenital heart disease: impact of mode of delivery on neonatal outcome, Prenat Diagn 32(13):1250–1255, 2012. 12. Peterson AL, Quartermain MD, Ades A, et al.: Impact of mode of delivery on markers of perinatal hemodynamics in infants with hypoplastic left heart syndrome, J Pediatr 159(1):64–69, 2011. 13. Peyvandi S, Nguyen TA, Almeida-Jones M, et al.: Timing and mode of delivery in prenatally diagnosed congenital heart disease- an analysis of practices within the University of California Fetal Consortium (UCfC), Pediat Cardiol January 11, 2017. 14. Walsh CA, MacTiernan A, Farrell S, et al.: Mode of delivery in pregnancies complicated by major fetal congenital heart disease: a retrospective cohort study, J Perinatol 34(12):901–905, 2014. 15. Reis PM, Punch MR, Bove EL, et al.: Obstetric management of 219 infants with hypoplastic left heart syndrome, Am J Obstet Gynecol 179(5):1150–1154, 1998. 16. Berkley EM, Goens MB, Karr S, et al.: Utility of fetal echocardiography in postnatal management of infants with prenatally diagnosed congenital heart disease, Prenat Diagn 29(7):654–658, 2009. 17. Slodki M, Respondek-Liberska M, Pruetz JD, et al.: Fetal cardiology: changing the definition of critical heart disease in the newborn, J Perinatol 36(8):575–580, 2016. 18. 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Michelfelder E, Gomez C, Border W, et al.: Predictive value of fetal pulmonary venous flow patterns in identifying the need for atrial septoplasty in the newborn with hypoplastic left ventricle, Circulation 112(19):2974–2979, 2005. 33. Punn R, Silverman NH: Fetal predictors of urgent balloon atrial septostomy in neonates with complete transposition, J Am Soc Echocardiogr 24(4):425–430, 2011. 34. Maeno YV, Kamenir SA, Sinclair B, et al.: Prenatal features of ductus arteriosus constriction and restrictive foramen ovale in d-transposition of the great arteries, Circulation 99(9):1209–1214, 1999. 35. Jouannic JM, Gavard L, Fermont L, et al.: Sensitivity and specificity of prenatal features of physiological shunts to predict neonatal clinical status in transposition of the great arteries, Circulation 110(13):1743–1746, 2004. 36. Donofrio MT, Moon-Grady AJ, Hornberger LK, et al.: Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association, Circulation 129(21):2183–2242, 2014. 37. Talemal L, Donofrio MT: Hemodynamic consequences of a restrictive ductus arteriosus and foramen ovale in fetal transposition of the great arteries, J Neonatal Med 9(3):317–320, 2016. 38. Sun HY, Boe J, Rubesova E, et al.: Fetal MRI correlates with postnatal CT angiogram assessment of pulmonary anatomy in tetralogy of fallot with absent pulmonary valve, Congenit Heart Dis 9(4):E105–109, 2014. 39. Chelliah A, Berger JT, Blask A, et al.: Clinical utility of fetal magnetic resonance imaging in tetralogy of fallot with absent pulmonary valve, Circulation 12 127(6):757–759, 2013. 40. Keszler M, Donn SM, Bucciarelli RL, et al.: Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstitial emphysema, J Pediatr 119(1 Pt 1):85–93, 1991. 41. Carlon GC, Ray Jr C, Pierri MK, et al.: High-frequency jet ventilation: theoretical considerations and clinical observations, Chest 81(3):350–354, 1982. 42. Pruetz JD, Votava-Smith J, Miller DA: Clinical relevance of fetal hemodynamic monitoring: perinatal implications, Semin Fetal Neonatal Med 20(4):217–224, 2015. 43. Freud LR, Escobar-Diaz MC, Kalish BT, et al.: Outcomes and predictors of perinatal mortality in fetuses with ebstein anomaly or tricuspid valve dysplasia in the current era: a multicenter study, Circulation 132(6):481–489, 2015. 44. de Caen AR, Berg MD, Chameides L, et al.: Part 12: pediatric advanced life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care, Circulation 132(18 Suppl 2):S526–542, 2015. 45. Giamberti A, Chessa M. The tricuspid valve in congenital heart disease. 46. Eliasson H, Sonesson SE, Sharland G, et al.: Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients, Circulation 124(18):1919–1926, 2011. 47. Weiner GM, Zaichkin J, Kattwinkel J, et al.: Textbook of Neonatal Resuscitation. ed 7. 48. Glatz AC, Gaynor JW, Rhodes LA, et al.: Outcome of high-risk neonates with congenital complete heart block paced in the first 24 hours after birth, J Thorac Cardiovasc Surg 136(3):767–773, 2008. 49. Freud LR, McElhinney DB, Marshall AC, et al.: Fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome: postnatal outcomes of the first 100 patients, Circulation 130(8):638–645, 2014. 50. Moon-Grady AJ, Morris SA, Belfort M, et al.: International fetal cardiac intervention registry: a worldwide collaborative description and preliminary outcomes, J Am Col Cardiol 66(4):388–399, 2015. 51. Marshall AC, van der Velde ME, Tworetzky W, et al.: Creation of an atrial septal defect in utero for fetuses with hypoplastic left heart syndrome and intact or highly restrictive atrial septum, Circulation 110(3):253–258, 2004. 52. Zhou L, Vest AN, Chmait RH, et  al.: A percutaneously implantable fetal pacemaker. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society, Annual Conference 2014:4459–4463, 2014. 53. Bar-Cohen Y, Loeb GE, Pruetz JD, et al.: Preclinical testing and optimization of a novel fetal micropacemaker, Heart Rhythm 12(7):1683–1690, 2015.