Outcomes for patients with neonatal heart disease are affected by numerous noncardiac and genetic factors. These can include neonatal concerns, such as prematurity and low birth weight, and congenital anomalies, such as airway, pulmonary, gastrointestinal, and genitourinary anomalies, and genetic syndromes. This section will serve as a summary of these issues and how they may affect the evaluation and management of a neonate with heart disease. These noncardiac factors are heavily influenced by conditions common to neonatologists, making a strong argument for multidisciplinary care with neonatologists, cardiologists, surgeons, anesthesiologists, and cardiovascular intensivists. Through this section and this project, we aim to facilitate a comprehensive approach to the care of neonates with congenital heart disease.

In this section, we will focus on noncardiac contributors to outcomes in neonates with congenital heart disease (CHD). This will include common topics for NICU patients, including prematurity, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and congenital abnormalities of the airway, gastrointestinal (GI) tract, and genitourinary system. We will also address neonatal infections, hydrops, and other maternal factors.

The search strategy for this section included a review of peer-reviewed articles on neonatal/pediatric noncardiac comorbidities published in English since 2010. Additional studies were included on the personal knowledge of the writing group members according to their expertise (including publications before 2010). Nonfull text publications in languages other than English were excluded. After retrieval of the full-text publications, all writing group members independently reviewed the studies and suggested whether to include or exclude the study on the basis of the strength of the evidence.

Please refer to the executive committee introductory paper for discussion on Class of Recommendations and Level of Evidence (LOE), organization of the writing committees, and document review and approval.

Infants with CHD may be born at low birth weight (<2.5 kg), very low birth weight (VLBW; <1.5 kg), or extremely low birth weight (<1 kg). These neonates may be appropriate for gestational age (birth weight 10th–90th centile), small for gestational age (<10th centile), or large for gestational age (>90th centile).14 

The weight of the neonate at the time of cardiac surgery is an important predictor of morbidity and mortality. Various studies have assessed the correlation between weight and post-operative morbidity and mortality to determine the targeted weight for surgical intervention. Although many studies have revealed higher mortality in patients with low birth weight (<2.5 kg),57  it has been found that delaying surgery to achieve adequate weight has more detrimental effects on the hemodynamics of the heart, compared with the benefit. Therefore, early surgery can be performed, even in patients with a weight of <2.5 kg.815  However, other factors that may impact the prognosis should be evaluated and managed before proceeding to surgery. These may include prematurity, infection, congenital anomalies, and genetic abnormalities. Please refer to the article in this supplement on Surgical Readiness for an extensive discussion of these issues with regard to outcomes and timing of cardiovascular surgery.

Gestational age dating is determined by obstetrical ultrasound or last menstrual period. When there is no prenatal care or when there is a discrepancy between obstetrical dating estimate and infant examination at the time of birth, the Ballard examination can provide a postnatal gestational age estimate.16  Gestational age is an independent risk factor for morbidity and mortality. The authors of various studies who have investigated the association between gestational age and mortality have suggested that mortality is increased for any gestational age other than 39 to 40 weeks.1721  A study involving 971 neonates with critical CHD revealed that those born at 37 to 38 weeks’ gestation had 2.3-fold greater adjusted odds of in-hospital mortality when compared with a reference group born at 39 to 40 weeks.18  Another nationwide study revealed that the infant mortality rate due to CHD increased linearly with a decreasing gestational age <39 weeks.19  A multicenter study revealed that neonates born at 34 to 36 weeks of gestation (late preterm) and 37 to 38 weeks of gestation (early term) were associated with worse outcomes, higher rates of complication, and increased length of hospital stay when compared with those born at 39 weeks of gestation.17 

  1. Gestational age assessment of the infant is indicated to monitor for and address prematurity-related complications and to improve outcomes (Class I, LOE B-NR)

  2. Gestational age and weight must be considered in the timing of surgery requiring cardiopulmonary bypass in premature infants with CHD (Class IIa, LOE C-EO)

  3. The candidacy for surgery should be individualized for neonates with low birth weight or VLBW (Class IIa, LOE C-EO)

Insensible losses are greater for preterm infants whose epidermis is immature. A full term infant may require 40 to 60 mL/kg/d to cover losses on the first day of life. An extremely preterm infant may require 2 to 3-fold more fluid to cover insensible losses.22,23  Fluid goals depend on gestational age, birth weight, and whether the infant is housed in an enclosed incubator with heat and humidity regulation abilities.22  Close monitoring of serum sodium and chloride levels and urine output is necessary to direct fluid management of the preterm infant, particularly those born extremely preterm.

Patients with CHD may require closer monitoring of the fluid status on the basis of specific cardiopulmonary physiology. For example, those with left-to-right shunting may benefit from fluid restriction to decrease the volume overload on the heart and limit pulmonary over-circulation. Fluid restriction may need to be modified with the gestational age of the infant because pulmonary vascular resistance decreases with increasing age.

  1. Fluid management should be individualized for every patient with cardiac lesions, and strict input and output charting should be done for the neonates (Class IIa, LOE C-EO)

Both cold stress and elevated temperatures are associated with poorer outcomes for preterm infants. Infants born ≥1.5 kg may be able to maintain temperature but will expend calories to do so. Infants <1.5 kg typically cannot maintain their temperature without external heat sources. In addition, infants with CHD can have excessive perspiration and tachypnea, which can add to excessive water loss and insensible heat loss. This evaporative heat loss is ∼25% of the total body heat produced.24 

For each 1°C decrease below 36°C, there is an associated 28% increased risk of mortality for preterm infants. Therefore, a goal temperature of 36.5°C to 37.5°C is recommended for preterm infants.25  There are various methods of maintaining temperature. Skin-to-skin contact with their mother is appropriate for infants who are hemodynamically stable and do not require early respiratory support. The kangaroo method also may be used for preterm infants. Infants who are sick or hemodynamically unstable may be managed by using a radiant warmer or, if weight <1.5 kg, an incubator.26 

  1. Support thermoregulation in all neonates, especially VLBW infants, by targeting a temperature of 36.5°C to 37.5°C during cardiac interventional procedures and in the ICU to reduce mortality and morbidity (Class I, LOE B-NR)

There are numerous factors that have been associated with malnutrition and CHD. The cardiac lesion itself has varying effects on growth, depending on the lesion. The increased metabolic rate, in addition to inadequate caloric intake, in patients with CHD can cause malnutrition, which can affect growth and brain development. The decreased caloric intake may be secondary to loss of appetite, anoxia, acidosis, malabsorption, or a relative increase in nutrient requirements.27 

Oral intake also may be reduced because of heart failure, suck and swallow incoordination, postoperative vocal cord injury, and structural or functional neurologic abnormalities. Infants who cannot be safely orally fed may benefit from nasogastric or gastrostomy tube feeding. If growth velocity is suboptimal, fortifying the caloric density of expressed breast milk or infant formula may be necessary, including teaching parents how to properly mix formula. However, patients with CHD may develop GI complications such as gastroesophageal reflux, aspiration, osmotic diarrhea, constipation, and, rarely, necrotizing enterocolitis.28  Involving a dietitian or nutrition specialist in the hospital and outpatient care of neonates with heart disease can be helpful, particularly in patients needing any modification of feedings.29  For a more detailed discussion on nutritional challenges and needs in the neonatal cardiac population, please refer to the Nutritional article in this supplement.

  1. Dietitian/nutritional specialist involvement in the hospital and outpatient care of neonates with heart disease is beneficial given the potential risk of malnutrition (Class I, LOE C-EO)

RDS is an acute manifestation of surfactant deficiency apparent in the initial hours and days after birth.30  RDS manifests as increased work of breathing, hypoxemia, hypoventilation, and ground glass opacities on a chest radiograph.31  RDS may contribute to poor oxygenation in patients with CHD. Permissive hypercapnia may alter hemodynamics in a CHD patient. It is, therefore, important to prevent RDS by ensuring expectant mothers who threaten to deliver preterm receive antenatal corticosteroids.

Infants with RDS may be managed with invasive mechanical ventilation, noninvasive mechanical ventilation, and/or supplemental oxygen.33  Surfactant may be administered directly into the airway through an endotracheal tube, although investigators are exploring alternative minimally invasive mechanisms to administer surfactant.31,33  In addition to RDS, premature neonates are at risk for apnea of prematurity.

BPD is a chronic lung disease process that is a result of arrested alveolarization, often accompanied by abnormal pulmonary arterial development, and affected infants requirerespiratory support ranging from supplemental oxygen to invasive mechanical ventilation. BPD is 4 times more likely to occur in VLBW infants with CHD compared with infants without CHD, likely due to prolonged mechanical ventilation and pulmonary edema.34  BPD has a significant impact on the morbidity of neonates with CHD and those undergoing cardiac surgery, leading to prolonged ICU and hospital stays. Patients with single-ventricle physiology are at the highest risk.35  Clinicians need to evaluate these patients in detail and set appropriate goals of mechanical ventilation to avoid complications such as ventilator-associated lung injury.

  1. Administration of antenatal steroids to mothers is recommended before a preterm delivery to lower the risk of RDS (Class I, Level B-R)

  2. Surfactant administration in patients with RDS is indicated to reduce mortality and morbidity (Class I, LOE B-R)

Neurologic abnormalities are commonly present in preterm neonates because of hypoxia and injury during delivery36  and can present with seizures, hypotonia, and difficulty feeding. The risk of neurologic concerns is further increased in neonates with CHD. In these patients, white matter changes, periventricular leukomalacia, and hemorrhage can be seen on radiologic imaging such as MRI.3640  Periventricular leukomalacia is caused by injury to oligodendrocytes that are prone to ischemia in watershed areas and results in necrosis of the cerebral white matter around the ventricles.41  This can lead to long-term neurologic sequelae, such as developmental delay and attention-deficit/hyperactivity disorder.40  Intraventricular hemorrhages are graded from I to IV. Grades I to III are the result of the immature thin-walled vessels of the germinal matrix, which do not tolerate hemodynamic changes and do not have auto-regulatory capacity.42  Grade IV hemorrhage refers to periventricular hemorrhagic infarction within the brain parenchyma and occurs secondary to periventricular venous congestion. The risk of intraventricular hemorrhage in preterm infants is greatest in the first 3 days of life and drastically reduced after the first week.

The authors of various studies have investigated brain injury before and after cardiac surgery to assess the worsening of the injury after cardiac surgery. Although many of the studies indicate possible worsening of the neurologic abnormality after surgery, a meta-analysis performed in 2015 suggested that the abnormality in neurologic development may be due primarily to prenatal injury.43  In addition, neurodevelopmental anomalies have been noted in patients with HLHS undergoing Norwood and Fontan procedures.4448 

NEC, an inflammatory intestinal disease, is associated with prematurity and CHD. The incidence of NEC in patients with CHD has been reported to be from 3.3% to 13%, with the highest incidence seen in truncus arteriosus and hypoplastic left heart syndrome.49  Multiple studies have evaluated the impact of the concurrent presence of NEC and CHD on mortality and have found mixed results (Table 1). McElhinney et al reported no difference in overall mortality between CHD patients with and without NEC. In those that did develop NEC, patients with stage 3 NEC (hemodynamically significant with/without perforation) had higher mortality. The time of onset of NEC was not associated with an increased risk of death.50  Other studies have revealed an increased risk of mortality in CHD patients associated with NEC. Fischer et al reported 55% and 34% mortality in CHD patients with and without NEC respectively.51  A retrospective study revealed that the presence of CHD was not associated with the severity of NEC, surgical intervention, intestinal complication, or length of hospital stay, but, nonetheless, the overall mortality was higher in CHD patients.52  Early initiation of enteral feeding, including breast milk, when possible, has been shown to reduce the risk of NEC.53,54 

TABLE 1

Publications Reporting NEC in Neonates With CHD

StudyYearPatients% NECRisk FactorsOutcomes
McElhinney50  2000 643 neonates with CHD admitted to CVICU 3.3 Prematurity, HLHS, truncus arteriosus, episodes of poor systemic perfusion or shock No difference in hospital mortality between patients who developed NEC and controls. 
ElHassan89  2018 5720 infants with HLHS 6.10% LBW associated with mortality but not with NEC Overall mortality was 23.5%. Neither medical nor surgical NEC was a predictor of mortality. LBW was not a predictor for NEC. 
Fisher51  2015 1931 VLBW infants with significant CHD CHD: 13% Diagnosis of AV canal defect Mortality: CHD with NEC = 55%
CHD w/o NEC = 34% 
   Non-CHD: 9% CHD patients had a higher risk than non-CHD patients of perforation, need for surgery, strictures, need for a stoma, sepsis, and short bowel syndrome. 
Pickard90  2009 202 pts with NEC w/ or w/o CHD   CHD patients had higher risk than non-CHD patients for death from NEC, recurrent NEC, and need for peritoneal drainage. 
Dees et al91  2000 201 preterm and LBW infants CHD: 10% HLHS, patients with noncardiac congenital anomalies Mortality: CHD with NEC = 26%
CHD w/o NEC = 10% 
   Non-CHD: 6% 
Spinner49  2015 38 c770 neonates with major CHD Overall: 3.6% Prematurity, chromosomal anomalies Mortality w/ and w/o NEC by CHD diagnosis: 
  Highest in HLHS and truncus (6%)  TOF: 9.5%/18.1% (OR:1.6) 
    TGA: 5.8%/24% (OR 2.5) 
    Arch obstruction: 8.3%/20.1% (OR 1.8) 
    HLHS: 22.8%/28.7% (OR 1.3) 
     Truncus: 14.6%/18.6% (OR 0.7) 
StudyYearPatients% NECRisk FactorsOutcomes
McElhinney50  2000 643 neonates with CHD admitted to CVICU 3.3 Prematurity, HLHS, truncus arteriosus, episodes of poor systemic perfusion or shock No difference in hospital mortality between patients who developed NEC and controls. 
ElHassan89  2018 5720 infants with HLHS 6.10% LBW associated with mortality but not with NEC Overall mortality was 23.5%. Neither medical nor surgical NEC was a predictor of mortality. LBW was not a predictor for NEC. 
Fisher51  2015 1931 VLBW infants with significant CHD CHD: 13% Diagnosis of AV canal defect Mortality: CHD with NEC = 55%
CHD w/o NEC = 34% 
   Non-CHD: 9% CHD patients had a higher risk than non-CHD patients of perforation, need for surgery, strictures, need for a stoma, sepsis, and short bowel syndrome. 
Pickard90  2009 202 pts with NEC w/ or w/o CHD   CHD patients had higher risk than non-CHD patients for death from NEC, recurrent NEC, and need for peritoneal drainage. 
Dees et al91  2000 201 preterm and LBW infants CHD: 10% HLHS, patients with noncardiac congenital anomalies Mortality: CHD with NEC = 26%
CHD w/o NEC = 10% 
   Non-CHD: 6% 
Spinner49  2015 38 c770 neonates with major CHD Overall: 3.6% Prematurity, chromosomal anomalies Mortality w/ and w/o NEC by CHD diagnosis: 
  Highest in HLHS and truncus (6%)  TOF: 9.5%/18.1% (OR:1.6) 
    TGA: 5.8%/24% (OR 2.5) 
    Arch obstruction: 8.3%/20.1% (OR 1.8) 
    HLHS: 22.8%/28.7% (OR 1.3) 
     Truncus: 14.6%/18.6% (OR 0.7) 

AV, atrioventricular; CVICU, cardiovascular ICU; HLHS, hypoplastic left heart syndrome; LBW, low birth weight; OR, odds ratio; TGA, transposition of great arteries; TOF, tetralogy of Fallot.

  1. Early initiation of enteral feeding, when possible, reduces the risk of NEC (Class I, LOE B-NR)

Retinopathy of prematurity (ROP) is atypical retinal vasculature development that occurs after the initial arrest of vascular growth in premature infants. It has been postulated that arterial oxygen tension is involved in the pathogenesis of ROP.55  Various studies have looked for associations between ROP and CHD with mixed results. Some have revealed a positive correlation of ROP with CHD.5658  The worsening of ROP in children with CHD is due to alteration in retinal perfusion with a hypoxia-induced increase in vascular endothelial growth factor leading to potentially hazardous neovascularization.

Some studies have revealed that CHD may be a protective factor against ROP development,59  and some have revealed no association.60,61  For cyanotic heart diseases with right (nonoxygenated) to left (oxygenated) shunts, the oxygen concentration may be lowered, potentially explaining the protective mechanism against ROP.

The American Academy of Ophthalmology recommends screening infants born at ≤30 weeks’ gestation or ≤1.5 kg for ROP.62  Although the AAP recommends that the target saturation be 90% to 95% to reduce the risk of ROP, these recommendations are for premature infants, and they cannot be completely extrapolated to neonates with CHD because there has been no data specific to CHD. There is heterogeneity in the clinical presentation of CHD and variability of circulation that leads to a wide range of oxygen saturations for these patients, and thus, there is not a universal target oxygen saturation range for all types of CHD. However, CHD poses an increased risk of morbidity in preterm and premature infants.56,63  Therefore, ROP guidelines can be used for patients with CHD, but care must be individualized and catered to each clinical scenario with caution.

  1. In premature neonates with biventricular and nonductal-dependent physiology, it is indicated to target saturations between 90% to 95% to reduce the risk of developing ROP (Class I, LOE B-R)

  2. In infants born at ≤30 weeks’ gestation or ≤1.5kg in birth weight, ROP screening is recommended per existing guidelines (Class I, LOE B-R)

  3. Individualize target saturations for those with more complex CHD in consultation with the cardiology team.

Genetic syndromes play a significant role in the assessment, management, and outcomes of neonates with CHD.6469  In Table 2, we summarize genetic syndromes with their most common cardiac defects noted.

TABLE 2

Genetic Syndromes and Common Associated Cardiac Defects

Genetic SyndromeCommon Cardiac DefectComments
Down Syndrome VSD, AV canal, TOF, PDA, ASD Echocardiogram on all infants with Down Syndrome because 30%–50% have CHD 
22q11 Deletion Syndrome/Di George Syndrome Conotruncal anomalies (TOF, truncus, interrupted aortic arch type B, perimembraneous VSD, other isolated arch anomalies) 22q11 genetic testing 
Holt-Oram Syndrome ASD, VSD 75% of patients have CHD 
  Risk of progressing AV-conduction delay progressing to complete heart block 
William Syndrome Supravalvar aortic stenosis, supravalvar pulmonary stenosis Patients with ELN gene mutation can have similar findings 
Turner Syndrome Bicuspid aortic valve, coarctation of aorta, HLHS Bicuspid aortic valve may result in aortic stenosis 
Noonans Syndrome Pulmonary valve stenosis, ASD, hypertrophic cardiomyopathy 60% have CHD 
  Lymphedema 
Costello Syndrome Hypertrophic cardiomyopathy 60% have hypertrophic cardiomyopathy 
CHARGE Syndrome Conotruncal anomalies, arch anomalies, AV canal, isolated ASD, VSD CHD found in 80%–90% of patients with CHARGE Syndrome 
Alagille Syndrome PPS, pulmonary valve stenosis, TOF Typically right-sided heart lesions 
  Cholestatic jaundice secondary to biliary atresia 
Ellis Van Crevald Common atrium, isolated ASD, isolated VSD, PDA 50%–60% have CHD 
  Pulmonary disease evaluated carefully 
Rubenstein-Taybi Syndrome Isolated VSD, isolated ASD, PDA, bicuspid aortic valve/coarctation, pulmonary stenosis Characteristically broad thumb and first toe 
Trisomy 13 Poly-valvar disease, VSD, ASD, PDA, AV-canal, conotruncal (DORV, TOF) 80% have CHD 
Trisomy 18 ASD, VSD, polyvalvar disease with 2 or more valves thickened or dysplastic, conotruncal (DORV, TOF) 90% have CHD 
Genetic SyndromeCommon Cardiac DefectComments
Down Syndrome VSD, AV canal, TOF, PDA, ASD Echocardiogram on all infants with Down Syndrome because 30%–50% have CHD 
22q11 Deletion Syndrome/Di George Syndrome Conotruncal anomalies (TOF, truncus, interrupted aortic arch type B, perimembraneous VSD, other isolated arch anomalies) 22q11 genetic testing 
Holt-Oram Syndrome ASD, VSD 75% of patients have CHD 
  Risk of progressing AV-conduction delay progressing to complete heart block 
William Syndrome Supravalvar aortic stenosis, supravalvar pulmonary stenosis Patients with ELN gene mutation can have similar findings 
Turner Syndrome Bicuspid aortic valve, coarctation of aorta, HLHS Bicuspid aortic valve may result in aortic stenosis 
Noonans Syndrome Pulmonary valve stenosis, ASD, hypertrophic cardiomyopathy 60% have CHD 
  Lymphedema 
Costello Syndrome Hypertrophic cardiomyopathy 60% have hypertrophic cardiomyopathy 
CHARGE Syndrome Conotruncal anomalies, arch anomalies, AV canal, isolated ASD, VSD CHD found in 80%–90% of patients with CHARGE Syndrome 
Alagille Syndrome PPS, pulmonary valve stenosis, TOF Typically right-sided heart lesions 
  Cholestatic jaundice secondary to biliary atresia 
Ellis Van Crevald Common atrium, isolated ASD, isolated VSD, PDA 50%–60% have CHD 
  Pulmonary disease evaluated carefully 
Rubenstein-Taybi Syndrome Isolated VSD, isolated ASD, PDA, bicuspid aortic valve/coarctation, pulmonary stenosis Characteristically broad thumb and first toe 
Trisomy 13 Poly-valvar disease, VSD, ASD, PDA, AV-canal, conotruncal (DORV, TOF) 80% have CHD 
Trisomy 18 ASD, VSD, polyvalvar disease with 2 or more valves thickened or dysplastic, conotruncal (DORV, TOF) 90% have CHD 

ASD, atrial septal defect; AV, atrioventricular; DORV, double outlet right ventricle; ELN, elastin; HLHS, hypoplastic left heart syndrome; PDA, patent ductus arteriosus; PPS, peripheral pulmonary stenosis; TOF, tetralogy of Fallot; VSD, ventricular septal defect

The diagnosis of a particular genetic syndrome can have a significant effect on the outcomes of neonates with CHD.64  In some syndromes, the diagnosis allows for the assessment of other organs that may have dysfunction related to the genetic syndrome in question. In other syndromes, the diagnosis may allow for appropriate screening for future concerns in patients or to promote appropriate resources for patients. The need for testing a particular patient should be driven by the specific cardiac lesion, physical examination, and family history.56  For instance, neonates with d-transposition of the great arteries rarely have genetic syndromes identified in the absence of concerning extracardiac examination findings; however, it is recommended that all patients with conotruncal abnormalities, aortic aneurysm, or interrupted aortic arch be screened for 22 q11 deletion syndrome.64,69 

  1. In neonates with heart disease, testing for genetic syndromes is recommended on the basis of physical examination, family history, specific cardiac lesion involved, and testing findings (Class I, LOE B-NR)

Between 22% and 45% of patients with CHD have an associated chromosomal abnormality, genetic syndrome, or extracardiac abnormality (Table 3).6568,70 

TABLE 3

Congenital Anomalies in Patients With CHD

Anomaly TypeIncidence in Patients w/ CHDExamples of Defect
Brain — Periventricular leukomalacia, ischemic changes, and hemorrhage (before cardiac surgery) 
Tracheobronchial 5%–11%72  Tracheoesophageal fistula, tracheomalacia, and bronchmalacia 
Gastrointestinal 8%–15%78  Esophageal atresia, gastroschisis, and omphalocele 
Genitourinary 7.5%–12%86,92  Duplex and multiplex kidneys, renal agenesis, hydronephrosis, cystic kidney disease, vesicoureteric reflux, and posterior urethral valves 
Anomaly TypeIncidence in Patients w/ CHDExamples of Defect
Brain — Periventricular leukomalacia, ischemic changes, and hemorrhage (before cardiac surgery) 
Tracheobronchial 5%–11%72  Tracheoesophageal fistula, tracheomalacia, and bronchmalacia 
Gastrointestinal 8%–15%78  Esophageal atresia, gastroschisis, and omphalocele 
Genitourinary 7.5%–12%86,92  Duplex and multiplex kidneys, renal agenesis, hydronephrosis, cystic kidney disease, vesicoureteric reflux, and posterior urethral valves 

Various studies have revealed an increased frequency of tracheobronchial anomalies in patients with CHD.71,72  These anomalies also have been associated with a number of genetic syndromes,73  and higher mortality is reported in patients with CHD and tracheobronchial anomaly.74 

Common anomalies include tracheomalacia, bronchomalacia, pulmonary hypoplasia, and congenital diaphragmatic hernia (CDH). Tracheomalacia is a state of increased compliance of the airway that allows the airway to collapse under pressure (>50% narrowing). It may manifest as wheezing, prolonged expiration, difficulty weaning from respiratory support if intrathoracic, or inspiratory stridor if extrathoracic.75  Pulmonary hypoplasia often is diagnosed clinically by assessment of small lung fields on chest radiography in the context of the ability to oxygenate and ventilate. It is most often seen in certain subgroups of patients (newborns with a history of oligohydramnios or anhydramnios, skeletal dysplasia, renal anomalies, or CDH) and is often associated with pulmonary hypertension.76 

CDH is a defect of the diaphragm, most commonly posterolateral, which can also be associated with pulmonary hypoplasia and pulmonary hypertension.77  Repair of the defect is typically delayed beyond the initial days after birth because of the presence of or potential for pulmonary vasoreactivity and pulmonary hypertension. Extracorporeal membrane oxygenation may be required in some infants. The presence of concomitant CDH and CHD requires close multispecialty management and evaluation for candidacy for extracorporeal membrane oxygenation.

GI anomalies are common in neonates with CHD, with a reported prevalence of 8% to 15%.78  These anomalies may include esophageal atresia and tracheoesophageal fistula, gastroschisis, and omphalocele. These anomalies may be present as an isolated defect or as a manifestation of a chromosomal abnormality. Concomitant congenital heart disease with gastroschisis is rare.79  In contrast, chromosomal anomalies are found in one-third of children with omphalocele, including CHARGE syndrome and trisomies 13, 18, and 21.80  Patients with concurrent cardiac and GI anomalies have a higher risk of morbidity and mortality associated with congenital heart surgery81,82  or GI anomaly repair.75  This risk of mortality is higher in patients with ductal-dependent CHD.83  Thus, a thorough risk evaluation of postoperative outcomes is critical when preparing these patients for surgical repair and for informed consent. The timing of GI anomaly repair relative to cardiac intervention depends on the specific anomaly. In patients with esophageal atresia or tracheoesophageal fistula, repair of GI malformations is recommended before cardiac intervention.78  However, some patients with long segment esophageal atresia may require repair or palliation of CHD before correcting the GI anomaly.78,84 

Congenital anomalies of the kidney and urinary tract (CAKUT) in patients with CHD can include duplex and multiplex kidneys, renal agenesis, hydronephrosis, cystic kidney disease, vesicoureteral reflux, and posterior urethral valves and can be seen in patients with CHD. A study investigating the genetics of CAKUT and CHD found that 29% of the mutations causing CHD also were associated with renal anomalies, and a similar cooccurrence of renal anomalies was seen in 30% of the patients with CHD.85  CAKUT are more common in patients with CHD compared with non-CHD patients. Hydronephrosis was the most commonly observed anomaly, followed by vesicoureteral reflux and duplication of kidney and ureter.86 

  1. Airway evaluation is recommended for neonates with heart disease with wheezing, prolonged expiration, difficulty weaning from respiratory support, or inspiratory stridor (Class I, LOE C-EO)

  2. Repair esophageal atresia and tracheoesophageal fistula before cardiac surgery, when possible, to reduce complications related to GI anomalies in neonates with heart disease (Class IIa, LOE B-NR)

  3. Obtain a preoperative renal ultrasound in neonates with heart disease to detect CAKUT (Class IIa, LOE C-EO)

There are numerous maternal factors that carry an increased risk of various forms of CHD, which are listed in Table 4. These factors also may have effects on organs outside of the heart or affect the management of the neonate in other ways (ie, the need for blood sugar monitoring in neonates both to mothers with gestational diabetes). Established guidelines are available regarding the management of perinatal infections or exposures, and these should be followed similarly for any neonate with CHD.

TABLE 4

Maternal Factors Associated With CHD

Maternal DiseasesAssociated Congenital Heart Disease
Diabetes9395  TGA, VSD, AVSD, HLHS, PDA, and cardiomyopathy 
Lupus9698  ASD, VSD, and valve anomalies 
Anti SSA/Ro99,100  Transient fetal first-degree heart block, prolongation of QTc, sinus bradycardia, late-onset cardiomyopathy, endocardial fibroelastosis, and cardiac malformations 
Hyperthermia101  Conotruncal and obstructive defects 
Phenylketonuria102  VSD, PDA, TOF, and single-ventricle 
Infectious diseases 
 Rubella103  PDA, VSD, and pulmonary valve anomalies 
 Cytomegalovirus103  Aortic dilation, VSD, and hypertrophic cardiomyopathies 
Drugs used during pregnancy 
 Paroxetine104  ASD, VSD, and ventricular outflow tract obstruction 
 Bupropion105  Left ventricular outflow tract obstruction 
 Valproic acid ASD, VSD, TOF, PA, and HRHS 
 Lithium Ebstein anomaly, mitral atresia, and CAO 
 Nitrofurantoin HLHS and ASD 
 Cephalosporins ASD 
 Ibuprufen TGV, VSD, and bicuspid aortic valve 
 Indomethacin Premature closure of ductus arteriosus 
 Opioids106  VSD, TOF, ASD, and CAO 
 Vitamin A PS and outflow tract anomalies 
 Organic solvents Conotruncal defects, TOF, PS, HLHS, TAPVR, and CAO 
Maternal DiseasesAssociated Congenital Heart Disease
Diabetes9395  TGA, VSD, AVSD, HLHS, PDA, and cardiomyopathy 
Lupus9698  ASD, VSD, and valve anomalies 
Anti SSA/Ro99,100  Transient fetal first-degree heart block, prolongation of QTc, sinus bradycardia, late-onset cardiomyopathy, endocardial fibroelastosis, and cardiac malformations 
Hyperthermia101  Conotruncal and obstructive defects 
Phenylketonuria102  VSD, PDA, TOF, and single-ventricle 
Infectious diseases 
 Rubella103  PDA, VSD, and pulmonary valve anomalies 
 Cytomegalovirus103  Aortic dilation, VSD, and hypertrophic cardiomyopathies 
Drugs used during pregnancy 
 Paroxetine104  ASD, VSD, and ventricular outflow tract obstruction 
 Bupropion105  Left ventricular outflow tract obstruction 
 Valproic acid ASD, VSD, TOF, PA, and HRHS 
 Lithium Ebstein anomaly, mitral atresia, and CAO 
 Nitrofurantoin HLHS and ASD 
 Cephalosporins ASD 
 Ibuprufen TGV, VSD, and bicuspid aortic valve 
 Indomethacin Premature closure of ductus arteriosus 
 Opioids106  VSD, TOF, ASD, and CAO 
 Vitamin A PS and outflow tract anomalies 
 Organic solvents Conotruncal defects, TOF, PS, HLHS, TAPVR, and CAO 

COA, coarctation of aorta; ASD, atrial septal defect; AVSD, atrioventricular septal defect; HLHS, hypoplastic left heart syndrome; HRHS, hypoplastic right heart; PA, pulmonary atresia; PDA, patent ductus arteriosus; PS, pulmonary stenosis; QTc, corrected QT interval; TAPVR, total anomalous pulmonary venous return; TGA, transposition of great arteries; TOF, tetralogy of Fallot; VSD, ventricular septal defect

  1. Adhere to evaluation and treatment guidelines for perinatal infections or perinatal medication exposures for neonates with CHD to reduce the risk of transmission and long-term complications (Class I, LOE B-NR)

Hydrops fetalis may be related to immune (10%) or nonimmune etiologies, which include idiopathic, chromosomal, cardiac, and infectious causes.87  The common cardiac causes include structural cardiac anomalies, cardiac dysrhythmias, cardiac tumors, cardiomyopathy, and myocarditis.88  Elevated atrial pressure and volume overload, low cardiac output, and congestive heart failure are the proposed mechanisms. Although hydrops fetalis has a poor prognosis and high mortality, management can include ultrasound-guided pericardiocentesis and fetoamniotic shunting after diagnosis at 19 to 36 weeks of gestation.88 

All authors contributed equally to the conception, design, background research, analysis, data collection, writing, and editing of this document and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose.

The guidelines/recommendations in this article are not American Academy of Pediatrics policy, and publication herein does not imply endorsement.

     
  • BPD

    bronchopulmonary dysplasia

  •  
  • CAKUT

    congenital anomalies of the kidney and urinary tract

  •  
  • CDH

    congenital diaphragmatic hernia

  •  
  • CHD

    congenital heart disease

  •  
  • GI

    gastrointestinal

  •  
  • LOE

    Level of Evidence

  •  
  • NEC

    necrotizing enterocolitis

  •  
  • RDS

    respiratory distress syndrome

  •  
  • ROP

    retinopathy of prematurity

  •  
  • VLBW

    very low birth weight

1
Fenton
TR
,
Kim
JH
.
A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants
.
BMC Pediatr
.
2013
;
13
:
59
2
Centers for Disease Control and Prevention
.
WHO growth standards are recommended for use in the U.S. for infants and children 0 to 2 years of age
.
3
Olsen
IE
,
Groveman
SA
,
Lawson
ML
, et al
.
New intrauterine growth curves based on United States data
.
Pediatrics
.
2010
;
125
(
2
):
e214
e224
4
Fay
RA
,
Dey
PL
,
Saadie
CM
, et al
.
Ponderal index: a better definition of the ‘at risk’ group with intrauterine growth problems than birth-weight for gestational age in term infants
.
Aust N Z J Obstet Gynaecol
.
1991
;
31
(
1
):
17
19
5
Pawade
A
,
Waterson
K
,
Laussen
P
, et al
.
Cardiopulmonary bypass in neonates weighing less than 2.5 kg: analysis of the risk factors for early and late mortality
.
J Card Surg
.
1993
;
8
(
1
):
1
8
6
Curzon
CL
,
Milford-Beland
S
,
Li
JS
, et al
.
Cardiac surgery in infants with low birth weight is associated with increased mortality: analysis of the Society of Thoracic Surgeons Congenital Heart Database
.
J Thorac Cardiovasc Surg
.
2008
;
135
(
3
):
546
551
7
Lechner
E
,
Wiesinger-Eidenberger
G
,
Weissensteiner
M
, et al
.
Open-heart surgery in premature and low-birth-weight infants--a single-centre experience
.
Eur J Cardiothorac Surg
.
2009
;
36
(
6
):
986
991
8
Rossi
AF
,
Seiden
HS
,
Sadeghi
AM
, et al
.
The outcome of cardiac operations in infants weighing two kilograms or less
.
J Thorac Cardiovasc Surg
.
1998
;
116
(
1
):
28
35
9
Chang
AC
,
Hanley
FL
,
Lock
JE
, et al
.
Management and outcome of low birth weight neonates with congenital heart disease
.
J Pediatr
.
1994
;
124
(
3
):
461
466
10
Bové
T
,
François
K
,
De Groote
K
, et al
.
Outcome analysis of major cardiac operations in low weight neonates
.
Ann Thorac Surg
.
2004
;
78
(
1
):
181
187
11
Oppido
G
,
Pace Napoleone
C
,
Formigari
R
, et al
.
Outcome of cardiac surgery in low birth weight and premature infants
.
Eur J Cardiothorac Surg
.
2004
;
26
(
1
):
44
53
12
Reddy
VM
,
McElhinney
DB
,
Sagrado
T
, et al
.
Results of 102 cases of complete repair of congenital heart defects in patients weighing 700 to 2500 grams
.
J Thorac Cardiovasc Surg
.
1999
;
117
(
2
):
324
331
13
Roussin
R
,
Belli
E
,
Bruniaux
J
, et al
.
Surgery for transposition of the great arteries in neonates weighing less than 2,000 grams: a consecutive series of 25 patients
.
Ann Thorac Surg
.
2007
;
83
(
1
):
173
177
,
discussion 177–178
14
Pizarro
C
,
Davis
DA
,
Galantowicz
ME
, et al
.
Stage I palliation for hypoplastic left heart syndrome in low birth weight neonates: can we justify it?
Eur J Cardiothorac Surg
.
2002
;
21
(
4
):
716
720
15
Reddy
VM
,
Hanley
FL
.
Cardiac surgery in infants with very low birth weight
.
Semin Pediatr Surg
.
2000
;
9
(
2
):
91
95
16
Ballard
JL
,
Khoury
JC
,
Wedig
K
, et al
.
New Ballard Score, expanded to include extremely premature infants
.
J Pediatr
.
1991
;
119
(
3
):
417
423
17
Costello
JM
,
Pasquali
SK
,
Jacobs
JP
, et al
.
Gestational age at birth and outcomes after neonatal cardiac surgery: an analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database
.
Circulation
.
2014
;
129
(
24
):
2511
2517
18
Costello
JM
,
Polito
A
,
Brown
DW
, et al
.
Birth before 39 weeks’ gestation is associated with worse outcomes in neonates with heart disease
.
Pediatrics
.
2010
;
126
(
2
):
277
284
19
Cnota
JF
,
Gupta
R
,
Michelfelder
EC
,
Ittenbach
RF
.
Congenital heart disease infant death rates decrease as gestational age advances from 34 to 40 weeks
.
J Pediatr
.
2011
;
159
(
5
):
761
765
20
Goff
DA
,
Luan
X
,
Gerdes
M
, et al
.
Younger gestational age is associated with worse neurodevelopmental outcomes after cardiac surgery in infancy
.
J Thorac Cardiovasc Surg
.
2012
;
143
(
3
):
535
542
21
Steurer
MA
,
Baer
RJ
,
Keller
RL
, et al
.
Gestational age and outcomes in critical congenital heart disease
.
Pediatrics
.
2017
;
140
(
4
):
e20170999
22
Kjartansson
S
,
Arsan
S
,
Hammarlund
K
, et al
.
Water loss from the skin of term and preterm infants nursed under a radiant heater
.
Pediatr Res
.
1995
;
37
(
2
):
233
238
23
Agren
J
,
Sjörs
G
,
Sedin
G
.
Transepidermal water loss in infants born at 24 and 25 weeks of gestation
.
Acta Paediatr
.
1998
;
87
(
11
):
1185
1190
24
Puyau
FA
.
Evaporative heat losses of infants with congenital heart disease
.
Am J Clin Nutr
.
1969
;
22
(
11
):
1435
1443
25
Perlman
JM
,
Wyllie
J
,
Kattwinkel
J
, et al;
Neonatal Resuscitation Chapter Collaborators
.
Part 7: neonatal resuscitation: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations
.
Circulation
.
2015
;
132
(
16 Suppl 1
):
S204
S241
26
World Health Organization
.
Managing Newborn Problems: A Guide for Doctors, Nurses, and Midwives
.
Geneva, Switzerland
:
Integrated Management of Pregnancy and Childbirth
;
2003
27
Forchielli
ML
,
McColl
R
,
Walker
WA
,
Lo
C
.
Children with congenital heart disease: a nutrition challenge
.
Nutr Rev
.
1994
;
52
(
10
):
348
353
28
Lantin-Hermoso
MR
,
Berger
S
,
Bhatt
AB
, et al;
Section on Cardiology
;
Cardiac Surgery
.
The care of children with congenital heart disease in their primary medical home
.
Pediatrics
.
2017
;
140
(
5
):
e20172607
29
Medoff-Cooper
B
,
Ravishankar
C
.
Nutrition and growth in congenital heart disease: a challenge in children
.
Curr Opin Cardiol
.
2013
;
28
(
2
):
122
129
30
Stoll
BJ
,
Hansen
NI
,
Bell
EF
, et al;
Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
.
Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network
.
Pediatrics
.
2010
;
126
(
3
):
443
456
31
Reuter
S
,
Moser
C
,
Baack
M
.
Respiratory distress in the newborn
.
Pediatr Rev
.
2014
;
35
(
10
):
417
428
,
quiz 429
32
McGoldrick
E
,
Stewart
F
,
Parker
R
,
Dalziel
SR
.
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth
.
Cochrane Database Syst Rev
.
2020
;
12
:
CD004454
33
Sweet
DG
,
Carnielli
V
,
Greisen
G
, et al
.
European consensus guidelines on the management of respiratory distress syndrome - 2019 update
.
Neonatology
.
2019
;
115
(
4
):
432
450
34
Polito
A
,
Piga
S
,
Cogo
PE
, et al
.
Increased morbidity and mortality in very preterm/VLBW infants with congenital heart disease
.
Intensive Care Med
.
2013
;
39
(
6
):
1104
1112
35
McMahon
CJ
,
Penny
DJ
,
Nelson
DP
, et al
.
Preterm infants with congenital heart disease and bronchopulmonary dysplasia: postoperative course and outcome after cardiac surgery
.
Pediatrics
.
2005
;
116
(
2
):
423
430
36
McQuillen
PS
,
Barkovich
AJ
,
Hamrick
SE
, et al
.
Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects
.
Stroke
.
2007
;
38
(
2 Suppl
):
736
741
37
Dent
CL
,
Spaeth
JP
,
Jones
BV
, et al
.
Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion
.
J Thorac Cardiovasc Surg
.
2005
;
130
(
6
):
1523
1530
38
Mahle
WT
,
Tavani
F
,
Zimmerman
RA
, et al
.
An MRI study of neurological injury before and after congenital heart surgery
.
Circulation
.
2002
;
106
(
12 Suppl 1
):
I109
I114
39
Licht
DJ
,
Shera
DM
,
Clancy
RR
, et al
.
Brain maturation is delayed in infants with complex congenital heart defects
.
J Thorac Cardiovasc Surg
.
2009
;
137
(
3
):
529
536
,
discussion 536–537
40
Galli
KK
,
Zimmerman
RA
,
Jarvik
GP
, et al
.
Periventricular leukomalacia is common after neonatal cardiac surgery
.
J Thorac Cardiovasc Surg
.
2004
;
127
(
3
):
692
704
41
Volpe
JJ
.
Neurobiology of periventricular leukomalacia in the premature infant
.
Pediatr Res
.
2001
;
50
(
5
):
553
562
42
Papile
LA
,
Burstein
J
,
Burstein
R
,
Koffler
H
.
Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm
.
J Pediatr
.
1978
;
92
(
4
):
529
534
43
Li
Y
,
Yin
S
,
Fang
J
, et al
.
Neurodevelopmental delay with critical congenital heart disease is mainly from prenatal injury not infant cardiac surgery: current evidence based on a meta-analysis of functional magnetic resonance imaging
.
Ultrasound Obstet Gynecol
.
2015
;
45
(
6
):
639
648
44
Kern
JH
,
Hinton
VJ
,
Nereo
NE
, et al
.
Early developmental outcome after the Norwood procedure for hypoplastic left heart syndrome
.
Pediatrics
.
1998
;
102
(
5
):
1148
1152
45
Mahle
WT
,
Clancy
RR
,
Moss
EM
, et al
.
Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome
.
Pediatrics
.
2000
;
105
(
5
):
1082
1089
46
Rogers
BT
,
Msall
ME
,
Buck
GM
, et al
.
Neurodevelopmental outcome of infants with hypoplastic left heart syndrome
.
J Pediatr
.
1995
;
126
(
3
):
496
498
47
Wernovsky
G
,
Stiles
KM
,
Gauvreau
K
, et al
.
Cognitive development after the Fontan operation
.
Circulation
.
2000
;
102
(
8
):
883
889
48
Goldberg
CS
,
Schwartz
EM
,
Brunberg
JA
, et al
.
Neurodevelopmental outcome of patients after the Fontan operation: a comparison between children with hypoplastic left heart syndrome and other functional single ventricle lesions
.
J Pediatr
.
2000
;
137
(
5
):
646
652
49
Spinner
JA
,
Morris
SA
,
Nandi
D
, et al
.
Necrotizing enterocolitis and associated mortality in neonates with congenital heart disease: a multi-institutional study
.
Pediatr Crit Care Med
.
2020
;
21
(
3
):
228
234
50
McElhinney
DB
,
Hedrick
HL
,
Bush
DM
, et al
.
Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes
.
Pediatrics
.
2000
;
106
(
5
):
1080
1087
51
Fisher
JG
,
Bairdain
S
,
Sparks
EA
, et al
.
Serious congenital heart disease and necrotizing enterocolitis in very low birth weight neonates
.
J Am Coll Surg
.
2015
;
220
(
6
):
1018
1026.e14
52
Kessler
U
,
Hau
EM
,
Kordasz
M
, et al
.
Congenital heart disease increases mortality in neonates with necrotizing enterocolitis
.
Front Pediatr
.
2018
;
6
:
312
53
Patel
EU
,
Wilson
DA
,
Brennan
EA
, et al
.
Earlier re-initiation of enteral feeding after necrotizing enterocolitis decreases recurrence or stricture: a systematic review and meta-analysis
.
J Perinatol
.
2020
;
40
(
11
):
1679
1687
54
Good
M
,
Sodhi
CP
,
Egan
CE
, et al
.
Breast milk protects against the development of necrotizing enterocolitis through inhibition of toll-like receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor
.
Mucosal Immunol
.
2015
;
8
(
5
):
1166
1179
55
Kalina
RE
,
Hodson
WA
,
Morgan
BC
.
Retrolental fibroplasia in a cyanotic infant
.
Pediatrics
.
1972
;
50
(
5
):
765
768
56
Costello
JM
,
Kim
F
,
Polin
R
,
Krishnamurthy
G
.
Double jeopardy: prematurity and congenital heart disease-what’s known and why it’s important
.
World J Pediatr Congenit Heart Surg
.
2022
;
13
(
1
):
65
71
57
Bhatti
FN
,
Binenbaum
G
,
Tomlinson
L
, et al
.
Retinopathy of prematurity in infants with cardiovascular disease
.
Invest Ophthalmol Vis Sci
.
2020
;
61
(
7
):
2780
58
Johns
KJ
,
Johns
JA
,
Feman
SS
,
Dodd
DA
.
Retinopathy of prematurity in infants with cyanotic congenital heart disease
.
Am J Dis Child
.
1991
;
145
(
2
):
200
203
59
Yau
GSK
,
Lee
JWY
,
Tam
VTY
, et al
.
Risk factors for retinopathy of prematurity in extremely preterm Chinese infants
.
Medicine (Baltimore)
.
2014
;
93
(
28
):
e314
60
Cheung
PY
,
Hajihosseini
M
,
Dinu
IA
, et al
.
Outcomes of preterm infants with congenital heart defects after early surgery: defining risk factors at different time points during hospitalization
.
Front Pediatr
.
2021
;
8
:
616659
61
Norman
M
,
Håkansson
S
,
Kusuda
S
, et al;
International Network for Evaluation of Outcomes in Neonates (iNeo) Investigators
.
Neonatal outcomes in very preterm infants with severe congenital heart defects: an international cohort study
.
J Am Heart Assoc
.
2020
;
9
(
5
):
e015369
62
Fierson
WM
;
American Academy of Pediatrics Section on Ophthalmology
;
American Academy of Ophthalmology
;
American Association for Pediatric Ophthalmology and Strabismus
;
American Association of Certified Orthoptists
.
Screening examination of premature infants for retinopathy of prematurity
.
Pediatrics
.
2018
;
142
(
6
):
e20183061
63
Steurer
MA
,
Baer
RJ
,
Chambers
CD
, et al
.
Mortality and major neonatal morbidity in preterm infants with serious congenital heart disease
.
J Pediatr
.
2021
;
239
:
110
116.e3
64
Pierpont
ME
,
Basson
CT
,
Benson
DW
Jr
, et al;
American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young
.
Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics
.
Circulation
.
2007
;
115
(
23
):
3015
3038
65
Tennstedt
C
,
Chaoui
R
,
Körner
H
,
Dietel
M
.
Spectrum of congenital heart defects and extracardiac malformations associated with chromosomal abnormalities: results of a seven year necropsy study
.
Heart
.
1999
;
82
(
1
):
34
39
66
Meberg
A
,
Hals
J
,
Thaulow
E
.
Congenital heart defects--chromosomal anomalies, syndromes and extracardiac malformations
.
Acta Paediatr
.
2007
;
96
(
8
):
1142
1145
67
Gonzalez
JH
,
Shirali
GS
,
Atz
AM
, et al
.
Universal screening for extracardiac abnormalities in neonates with congenital heart disease
.
Pediatr Cardiol
.
2009
;
30
(
3
):
269
273
68
Baker
K
,
Sanchez-de-Toledo
J
,
Munoz
R
, et al
.
Critical congenital heart disease--utility of routine screening for chromosomal and other extracardiac malformations
.
Congenit Heart Dis
.
2012
;
7
(
2
):
145
150
69
Agergaard
P
,
Olesen
C
,
Østergaard
JR
, et al
.
The prevalence of chromosome 22q11.2 deletions in 2,478 children with cardiovascular malformations. A population-based study
.
Am J Med Genet A
.
2012
;
158A
(
3
):
498
508
70
Güçer
S
,
Ince
T
,
Kale
G
, et al
.
Noncardiac malformations in congenital heart disease: a retrospective analysis of 305 pediatric autopsies
.
Turk J Pediatr
.
2005
;
47
(
2
):
159
166
71
Chassagnon
G
,
Lefort
B
,
Meot
M
, et al
.
Association between tetralogy of Fallot and tracheobronchial branching abnormalities: a new clue for pathogenesis?
J Am Heart Assoc
.
2017
;
7
(
1
):
e006921
72
Noel
CV
,
Kovalchin
JP
,
Adler
B
,
Yates
AR
.
Incidence of tracheobronchial anomalies found with hypoplastic left heart syndrome
.
Congenit Heart Dis
.
2014
;
9
(
4
):
294
299
73
Landing
BH
.
Syndromes of congenital heart disease with tracheobronchial anomalies. Edward B. D. Neuhauser Lecture, 1974
.
Am J Roentgenol Radium Ther Nucl Med
.
1975
;
123
(
4
):
679
686
74
Lee
YS
,
Jeng
MJ
,
Tsao
PC
,
Soong
WJ
,
Chou
P
.
Prognosis and risk factors for congenital airway anomalies in children with congenital heart disease: a nationwide population-based study in Taiwan
.
PLoS One
.
2015
;
10
(
9
):
e0137437
75
Kamran
A
,
Jennings
RW
.
Tracheomalacia and tracheobronchomalacia in pediatrics: an overview of evaluation, medical management, and surgical treatment
.
Front Pediatr
.
2019
;
7
:
512
76
Delgado-Peña
YP
,
Torrent-Vernetta
A
, %
Sacoto
G
, et al
.
[Pulmonary hypoplasia: an analysis of cases over a 20-year period]
.
An Pediatr (Barc)
.
2016
;
85
(
2
):
70
76
77
Chandrasekharan
PK
,
Rawat
M
,
Madappa
R
, et al
.
Congenital diaphragmatic hernia - a review
.
Matern Health Neonatol Perinatol
.
2017
;
3
:
6
78
Mery
CM
,
De León
LE
,
Rodriguez
JR
, et al
.
Effect of gastrointestinal malformations on the outcomes of patients with congenital heart disease
.
Ann Thorac Surg
.
2017
;
104
(
5
):
1590
1596
79
Laje
P
,
Fraga
MV
,
Peranteau
WH
, et al
.
Complex gastroschisis: clinical spectrum and neonatal outcomes at a referral center
.
J Pediatr Surg
.
2018
;
53
(
10
):
1904
1907
80
Bauman
B
,
Stephens
D
,
Gershone
H
, et al
.
Management of giant omphaloceles: a systematic review of methods of staged surgical vs. nonoperative delayed closure
.
J Pediatr Surg
.
2016
;
51
(
10
):
1725
1730
81
Orün
UA
,
Bilici
M
,
Demirçeken
FG
, et al
.
Gastrointestinal system malformations in children are associated with congenital heart defects
.
Anadolu Kardiyol Derg
.
2011
;
11
(
2
):
146
149
82
David
TJ
,
O’Callaghan
SE
.
Cardiovascular malformations and oesophageal atresia
.
Br Heart J
.
1974
;
36
(
6
):
559
565
83
Diaz
LK
,
Akpek
EA
,
Dinavahi
R
,
Andropoulos
DB
.
Tracheoesophageal fistula and associated congenital heart disease: implications for anesthetic management and survival
.
Paediatr Anaesth
.
2005
;
15
(
10
):
862
869
84
Encinas
JL
,
Luis
AL
,
Avila
LF
, et al
.
Impact of preoperative diagnosis of congenital heart disease on the treatment of esophageal atresia
.
Pediatr Surg Int
.
2006
;
22
(
2
):
150
153
85
San Agustin
JT
,
Klena
N
,
Granath
K
, et al
.
Genetic link between renal birth defects and congenital heart disease
.
Nat Commun
.
2016
;
7
:
11103
86
Jiang
D
,
Wang
Q
,
Shi
Z
,
Sun
J
.
Congenital anomalies of the kidney and urinary tract in children with congenital heart defects
.
Kidney Blood Press Res
.
2020
;
45
(
2
):
307
313
87
Bellini
C
,
Hennekam
RC
.
Non-immune hydrops fetalis: a short review of etiology and pathophysiology
.
Am J Med Genet A
.
2012
;
158A
(
3
):
597
605
88
Yuan
SM
.
Cardiac etiologies of hydrops fetalis
.
Z Geburtshilfe Neonatol
.
2017
;
221
(
2
):
67
72
89
ElHassan
NO
,
Tang
X
,
Gossett
J
, et al
.
Necrotizing enterocolitis in infants with hypoplastic left heart syndrome following stage 1 palliation or heart transplant
.
Pediatr Cardiol
.
2018
;
39
(
4
):
774
785
90
Pickard
SS
,
Feinstein
JA
,
Popat
RA
, et al
.
Short- and long-term outcomes of necrotizing enterocolitis in infants with congenital heart disease
.
Pediatrics
.
2009
;
123
(
5
):
e901
e906
91
Dees
E
,
Lin
H
,
Cotton
RB
,
Graham
TP
,
Dodd
DA
.
Outcome of preterm infants with congenital heart disease
.
J Pediatr
.
2000
;
137
(
5
):
653
659
92
Cagli
C
,
Erdem
S
,
Atmis
B
, et al
.
P314 renal tract anomalies in children with congenital heart disease detected during the procedure of cardiac catheterization
.
Arch Dis Child
.
2017
;
102
(
Suppl 2
):
A155
93
Corrigan
N
,
Brazil
DP
,
McAuliffe
F
.
Fetal cardiac effects of maternal hyperglycemia during pregnancy
.
Birth Defects Res A Clin Mol Teratol
.
2009
;
85
(
6
):
523
530
94
Correa
A
,
Gilboa
SM
,
Besser
LM
, et al
.
Diabetes mellitus and birth defects
.
Am J Obstet Gynecol
.
2008
;
199
(
3
):
237.e1–9
95
Macintosh
MC
,
Fleming
KM
,
Bailey
JA
, et al
.
Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study
.
BMJ
.
2006
;
333
(
7560
):
177
96
Vinet
É
,
Pineau
CA
,
Scott
S
, et al
.
Increased congenital heart defects in children born to women with systemic lupus erythematosus: results from the offspring of Systemic Lupus Erythematosus Mothers Registry Study
.
Circulation
.
2015
;
131
(
2
):
149
156
97
Krishnan
AN
,
Sable
CA
,
Donofrio
MT
.
Spectrum of fetal echocardiographic findings in fetuses of women with clinical or serologic evidence of systemic lupus erythematosus
.
J Matern Fetal Neonatal Med
.
2008
;
21
(
11
):
776
782
98
Llanos
C
,
Friedman
DM
,
Saxena
A
, et al
.
Anatomical and pathological findings in hearts from fetuses and infants with cardiac manifestations of neonatal lupus
.
Rheumatology (Oxford)
.
2012
;
51
(
6
):
1086
1092
99
Costedoat-Chalumeau
N
,
Amoura
Z
,
Villain
E
, et al
.
Anti-SSA/Ro antibodies and the heart: more than complete congenital heart block? A review of electrocardiographic and myocardial abnormalities and of treatment options
.
Arthritis Res Ther
.
2005
;
7
(
2
):
69
73
100
Costedoat-Chalumeau
N
,
Georgin-Lavialle
S
,
Amoura
Z
,
Piette
JC
.
Anti-SSA/Ro and anti-SSB/La antibody-mediated congenital heart block
.
Lupus
.
2005
;
14
(
9
):
660
664
101
Shi
QY
,
Zhang
JB
,
Mi
YQ
, et al
.
Congenital heart defects and maternal fever: systematic review and meta-analysis
.
J Perinatol
.
2014
;
34
(
9
):
677
682
102
Rouse
B
,
Matalon
R
,
Koch
R
, et al
.
Maternal phenylketonuria syndrome: congenital heart defects, microcephaly, and developmental outcomes
.
J Pediatr
.
2000
;
136
(
1
):
57
61
103
Ye
Z
,
Wang
L
,
Yang
T
, et al
.
Maternal viral infection and risk of fetal congenital heart diseases: a meta-analysis of observational studies
.
J Am Heart Assoc
.
2019
;
8
(
9
):
e011264
104
Bérard
A
,
Iessa
N
,
Chaabane
S
, et al
.
The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis
.
Br J Clin Pharmacol
.
2016
;
81
(
4
):
589
604
105
Alwan
S
,
Reefhuis
J
,
Botto
LD
, et al
.
Maternal use of bupropion and risk for congenital heart defects
.
Am J Obstet Gynecol
.
2010
;
203
(
1
):
52.e1–6
106
Ramphul
K
,
Mejias
SG
,
Joynauth
J
.
In-utero exposure to opioid increases the risk of congenital heart defects
.
EXCLI J
.
2020
;
19
:
239
240