Impact of prenatal diagnosis of critical congenital heart disease on preoperative and postoperative outcomes

doi:10.21203/rs.3.rs-2762652/v1

Download PDF

Research Article

Impact of prenatal diagnosis of critical congenital heart disease on preoperative and postoperative outcomes

https://doi.org/10.21203/rs.3.rs-2762652/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 08 Jun, 2023

Read the published version in Pediatric Cardiology →

You are reading this latest preprint version

Objective: The objective of this study was to assess the relationship of prenatal diagnosis of critical congenital heart disease (CHD) to preoperative and postoperative patient findings.

Method: Retrospective analysis of neonates with critical CHD who underwent cardiothoracic surgery at one of four centers in North Carolina between 2008-2013. Surgical data collected by sites for submission to the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and the North Carolina CHD Lifespan Database were queried.

Results: There were 715 patients with STS records; 566 linked to the NC CHD database. Patients with prenatal diagnosis had a lower incidence of preoperative risk factors, including need for mechanical ventilation and presence of shock. However, prenatally diagnosed patients had worse short-term outcomes, including higher operative mortality, higher incidence of select postoperative complications, and longer LOS. There was no difference in one-year mortality.

Conclusion: Our findings are consistent with current literature which suggests that prenatal diagnosis of critical CHD is associated with a more optimized preoperative clinical status. However, we found that patients with prenatal diagnoses had less favorable postoperative outcomes. This needs to be investigated further, but may be secondary to patient-specific factors, such as CHD disease severity.

Congenital heart disease

prenatal diagnosis

preoperative outcomes

postoperative outcomes

Prenatal diagnosis of congenital heart disease (CHD) is associated with an optimized preoperative clinical status, but the impact on postoperative outcomes is inconclusive.

What does this study add?

In our analysis of a statewide surgical database over many years, we found that neonates with prenatally diagnosed CHD had less favorable short-term postoperative outcomes.
Longer-term outcomes were similar in neonates prenatally and postnatally diagnosed, likely reflecting excellent surgical and medical care available in the modern era.

Prenatal diagnosis of congenital heart disease (CHD) has become increasingly common.¹ Advances in fetal cardiac imaging have enabled not only increased prenatal recognition of cardiac defects, but also a detailed assessment of cardiac anatomy and physiology. Using disease-specific risk stratification metrics that predict postnatal physiology,² a level of care designation can be assigned to each fetus based on the anticipated risk for cardiorespiratory compromise in the delivery room and expected care needed for perinatal stabilization.^3–5 In those neonates with critical CHD with anticipated rapid clinical instability during perinatal transition,^6–8 a multidisciplinary team for disease-strategic delivery room resuscitation and stabilization can be coordinated such that the neonate can be expeditiously transferred to the cardiac intensive care unit in more stable condition for further care, which may include a life-saving specialized cardiac intervention.⁹

Thus, prenatal diagnosis and identification of the highest risk neonates with critical CHD enables coordinated, optimized perinatal management, such that these neonates can present to a specialized cardiac center earlier with less cardiorespiratory clinical compromise, improving preoperative hemodynamic status. Indeed, prior studies have shown that infants with prenatally diagnosed critical CHD and appropriate postnatal management have improved preoperative clinical status,^10–12 with less renal or hepatic dysfunction, lower likeliness of preoperative mechanical ventilatory or inotropic support, and a lower incidence of preoperative circulatory shock or cardiopulmonary resuscitation.¹⁰ Furthermore, it has been shown that there is an improvement in neonatal preoperative survival compared to those only postnatally diagnosed.¹³

However, despite this, there is a lack of consensus in the literature regarding whether prenatal diagnosis leads to improved postoperative outcomes. Several case studies have demonstrated decreased postoperative mortality rates with prenatal diagnosis of specific cardiac lesions, including hypoplastic left heart syndrome (HLHS)¹¹ and D-transposition of the great arteries (D-TGA).¹⁴ However, most studies have shown no difference in neonatal or infant survival.^15–18 One retrospective cohort study demonstrated worse surgical outcomes, including one-year mortality and postoperative length of stay in infants (less than one year of age at time of surgery) prenatally diagnosed. These outcomes persisted after controlling for covariates including weight, surgical severity, race, age at surgery, prematurity, and the presence or absence of genetic syndromes.¹⁹

The aim of our study was to determine if prenatal diagnosis of critical CHD impacts preoperative clinical status and postoperative outcomes, including postoperative complications, mortality, hospital length of stay, and readmission, in a cohort of neonates who underwent cardiothoracic surgery in the neonatal period. Given the well-described association between prenatal diagnosis and improved preoperative morbidity, yet the lack of consistent postoperative outcomes in the literature, we propose to leverage large, linked databases to better understand the impact of prenatal diagnosis in all phases of care.

Data Source and Study Design

This was a retrospective analysis of data extracted by four surgical sites in North Carolina (Carolinas Medical Center, Duke University, University of North Carolina, Wake Forest School of Medicine) for submission to the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD), as well as the North Carolina Congenital Heart Disease (NC CHD) Lifespan Database. The NC CHD Lifespan Database collects linked information from the infant birth certificate, electronic medical record, and surgical data prepared by sites for submission to STS-CHSD. Data from East Carolina University, the fifth center contributing data to the NC CHD database, was not included as this site did not report to the STS-CHSD. Data for the STS-CHSD included select preoperative factors, select complications, mortality (including operative mortality and 30-day postoperative mortality), hospital length of stay (LOS), and readmission rates within 30 days of discharge. Patients in the STS-CHSD files were linked to the NC CHD database using indirect identifiers (sex, date of birth, surgical center, and hospital admission and discharge dates) in order to assess longer-term outcomes, including readmission within 60 days of discharge and one-year postoperative mortality. This study was approved by all of the participating institutional review boards.

Patient Population

Included in the analysis were neonates diagnosed with critical congenital heart disease, defined as defects requiring cardiothoracic surgery with or without cardiopulmonary bypass in the neonatal period (≤ 30 days of age), who underwent surgery at one of four North Carolina surgical centers, which provide comprehensive care for patients with CHD, in the time period from 2008 to 2013. Cases were identified using International Classification of Disease (ICD), Ninth Revisions codes. Patients were categorized by antenatal diagnosis versus postnatal diagnosis based on documentation in the STS-CHSD. The diagnoses included in the analysis (primary and secondary diagnoses associated with the surgery) are detailed in Table 1.

Table 1

Types of complex congenital heart disease and diagnostic groupings
Diagnosis
Non-HLHS^† left heart disease
Aortic valve disease
Interrupted aortic arch
Right heart disease
Tetralogy of Fallot
Pulmonary atresia
Ebstein anomaly
RVOT^‡ obstruction and/or pulmonary stenosis
Single ventricle
Single ventricle
Hypoplastic left heart syndrome
Total anomalous pulmonary venous connection
D-transposition of the great arteries
Atrioventricular canal defect
Congenitally corrected transposition of the great arteries
Double outlet right ventricle
Coarctation of the aorta
Truncus arteriosus
^†HLHS hypoplastic left heart syndrome, ^‡RVOT right ventricular outflow tract

Specific diagnoses were then selected by consensus of the investigators and grouped for secondary analysis. The groupings were chosen based on cardiac lesions with similar physiology and comparable neonatal surgical interventions. Diagnostic groupings included non-HLHS left heart disease (aortic valve disease and interrupted aortic arch), right heart disease (Tetralogy of Fallot, pulmonary atresia, Ebstein anomaly, and RVOT obstruction and/or pulmonary stenosis), total anomalous pulmonary venous connection (TAPVC), D-transposition of the great arteries, and single ventricle defects (including hypoplastic left heart syndrome). Isolated coarctation of the aorta was excluded from the non-HLHS left heart disease group as the surgical repair and expected perioperative course is not typically as complex as other lesions in that subgroup.

Data Collection

The primary outcome evaluated in this study was mortality, including operative mortality as defined by the STS-CHSD as (1) all deaths occurring during the hospitalization in which the operation was performed, even if after 30 days, and (2) those deaths occurring after hospital discharge if within 30 days of the procedure.²⁰ The 30-day postoperative mortality in itself was also assessed. Secondary outcome measures obtained from the STS-CHSD were select preoperative factors, select postoperative complications, hospital length of stay (LOS), including preoperative and postoperative LOS, and readmission within 30 days of discharge (see Tables 4, 5 and 6 for full list of outcome measures analyzed). Additional secondary outcome measures obtained from the NC CHD database included longer-term outcomes, including readmission within 60 days of discharge and one-year postoperative mortality.

Statistical Analysis

Patient characteristics and outcomes were summarized as counts (percentages) for categorical variables and median (25th, 75th percentiles) for continuous variables in the overall cohort, and for patients with versus without antenatal diagnosis.

To evaluate the association between diagnosis timing and clinical factors of interest, the defined outcomes, including mortality, LOS, and readmission, as well as select preoperative factors and complications, were compared between groups. LOS was evaluated using the Wilcoxon rank sum test. Select preoperative factors were compared using chi-square tests due to low incidence of most factors. All other outcomes were assessed using unadjusted logistic regression, and odds ratios with 95% confidence intervals were presented. A secondary analysis was performed to evaluate associations between antenatal diagnosis and select complications, mortality, LOS, and readmission separately among the diagnostic groupings.

Missing data were excluded from denominators such that percentages were based on non-missing information. All analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC) by the Duke Clinical Research Institute (Durham, NC).

Study Population Characteristics and Antenatal Detection Rates

During the defined study period, there were 5,734 STS operative records that included our diagnoses of interest. Of these, 1,061 operative records met our age criterion of age ≤ 30 days at time of surgery, yielding 715 unique patients. For patients with more than one operative record, the first record was used for analysis. Of the 715 distinct patients with operative records within the STS, 566 were linked to the NC CHD database. Patients with missing data for antenatal diagnosis in the STS-CHSD were excluded (n = 12).

The demographic variables of the overall cohort using STS-CHSD data are shown in Table 2. Patients with prenatally diagnosed CHD had surgery earlier (mean 7.4 days vs. 9.4 days) than patients without a prenatal diagnosis. Compared to the postnatal diagnosis group, there was a higher incidence of prematurity (birth before 37 weeks of gestation) in the antenatal diagnosis group (16.3% vs. 13.9%, p = 0.24); however, this was not statistically significant. The remainder of the demographics variables were overall similar between the two groups.

Table 2

Patient demographics
Patient Characteristic	Antenatal Diagnosis (n = 381)	Postnatal Diagnosis (n = 334)
Age at surgery, days^†	7.4 ± 5.7	9.4 ± 6.8
Gender Male, %	54.7	62.6
Female, %	45.0	37.1
Race/Ethnicity Hispanic, %	10.1	12.3
Caucasian, %	63.4	62.9
African American, %	22.6	21.9
Other, %	12.4	13.5
Gestational age, weeks^†	38.06 ± 1.82	38.36 ± 2.21
Premature birth, %	16.3	13.9
Birth weight, kilograms*	3.06 ± 0.60	3.09 ± 0.64
Presence of at least one syndrome, %	14.6	17.3
Chromosomal abnormality, %	11.9	12.9
^†Values represent mean ± standard deviation

Patient diagnoses and antenatal detection rates in the overall cohort and by CHD diagnosis selected from the STS database are shown in Table 3. The overall reported antenatal detection rate was 53.3% (381/715). There was variation in antenatal detection among diagnoses, reflecting previous reports,²¹ with the highest detection rates for hypoplastic left heart syndrome (77.2%), single ventricle defects (77.6%), and congenitally corrected transposition of the great arteries (80%). The diagnosis with the lowest detection rate was total anomalous pulmonary venous connection (30.3%). When diagnoses were grouped for secondary analysis, the largest cohort was the single ventricle subgroup (n = 211), followed by the right heart disease (n = 118) and transposition subgroups (n = 112). TAPVC (n = 28) and non-HLHS left heart disease (n = 59) were the smallest subgroups.

Table 3

Antenatal diagnosis rates
Diagnosis	Overall (n = 715)	n with antenatal diagnosis = 381 (53.3%)
Congenitally corrected TGA^†	10	8 (80.0%)
Single ventricle	85	66 (77.6%)
Hypoplastic left heart syndrome	136	105 (77.2%)
Atrioventricular canal defect	30	22 (73.3%)
Ebstein anomaly	7	5 (71.4%)
DORV^‡	42	27 (64.3%)
Pulmonary atresia	85	53 (62.4%)
RVOT^§ obstruction and/or pulmonary stenosis	50	28 (56.0%)
Interrupted aortic arch	45	24 (53.3%)
Tetralogy of Fallot	35	18 (51.4%)
Truncus arteriosus	24	11 (45.8%)
Aortic valve disease	44	20 (45.5%)
Coarctation of the aorta	224	101 (45.1%)
D-transposition of the great arteries	124	48 (38.7%)
Total anomalous pulmonary venous connection	33	10 (30.3%)
^†TGA transposition of the great arteries, ^‡DORV double-outlet right ventricle, ^§RVOT right ventricular outflow tract
Values presented are counts (%) for categorical variables. Diagnoses are not mutually exclusive.

Preoperative Outcome Measures

The incidence of select preoperative risk factors was compared between patients with antenatal and postnatal diagnoses using STS-CHSD data (Table 4). As the majority of the preoperative factors selected had low event rates, only mechanical ventilation, shock (resolved at time of surgery), and cardiopulmonary resuscitation were compared between the two groups. Notably, need for mechanical ventilation (16.7% vs. 35.8%, p < 0.001) and the presence of shock, resolved at time of surgery (4.6% vs. 14.7%, p < 0.001) were found to be statistically significant when comparing the two groups, with a lower incidence of both of these preoperative risk factors in the antenatal diagnosis group. Need for cardiopulmonary resuscitation was not statistically significant (0.4% vs. 2.6%, p = 0.052); however, this may be due to the low event rate, with only one patient in the antenatal diagnosis group requiring preoperative cardiopulmonary resuscitation.

Table 4

Preoperative risk factors by antenatal diagnosis status, reported as percentages
Preoperative Risk Factor	Antenatal Diagnosis (n = 276)	Postnatal Diagnosis (n = 251)
Any risk factor identified	49.0	55.6
Mechanical ventilation	16.7	35.8
Shock, persistent at time of surgery	17.2	18.1
Other preoperative factors	16.7	12.5
Shock, resolved at time of surgery	4.6	14.7
Renal dysfunction	2.5	3.9
Cardiopulmonary resuscitation	0.4	2.6
Sepsis	1.3	1.7
Necrotizing enterocolitis, treated medically	0.8	1.7
Coagulation disorder, intrinsic hypocoagulable state	0.0	1.7
Stroke, CVA, or intracranial hemorrhage > grade 2	0.0	1.7
Hepatic dysfunction	0.0	1.3
Coagulation disorder, hypercoagulable state	0.4	0.4
Preoperative/preprocedural mechanical circulatory support	0.8	0.0
Factors are not mutually exclusive. Percentages are based on the number of unique patients with non-missing pre-operative information. Patients enrolled early on (versions 2.3 and 2.5 of the CRF) are excluded from this table as comprehensive data was not yet captured.

Postoperative Outcome Measures

Select postoperative complications were compared between patients with and without an antenatal diagnosis of CHD using STS-CHSD data (Table 5). There was a higher incidence of complications among the antenatal diagnosis group (OR 2.23, 95% CI 1.44–3.43, p < 0.001). Specifically, patients with antenatal diagnoses were more likely to require postoperative mechanical circulatory support (OR 1.72, 95% CI 1.01–2.93, p = 0.045), mechanical ventilation > 7 days (OR 1.59, 95% CI 1.09–2.32, p = 0.015), or have a postoperative wound infection (OR 2.64, 95% CI 1.03–6.75, p = 0.042).

When performing subgroup analysis, there was no meaningful difference in the rates of postoperative complications between those antenatally or postnatally diagnosed. The only subgroup found to have a higher incidence of a postoperative complication in the antenatal diagnosis group that met statistical significance was the right heart disease subgroup, with a higher likelihood of requiring mechanical ventilation > 7 days (OR 3.00, 95% CI 1.14–7.89, p = 0.026) and having postoperative wound infection (OR 8.46, 95% CI 1.03–69.34, p = 0.047). There was no difference in the incidence of postoperative complications between antenatal and postnatal subgroups in patients with non-HLHS left heart disease, TAPVC, transposition, or single ventricle defects.

Table 5

Select postoperative complications by antenatal diagnosis status
Complication	Antenatal Diagnosis (n = 345), %	Postnatal Diagnosis (n = 294), %	Odds Ratio (95% CI)	P-value
At least one complication	88.7	77.9	2.23 (1.44–3.43)	< .001
Intraoperative/intraprocedural death	0.0	0.3	--
Multi-system organ failure	1.7	1.4	1.28 (0.36–4.59)	0.701
Unexpected cardiac arrest	6.4	7.1	0.89 (0.48–1.64)	0.700
Unplanned cardiac reoperation	8.7	8.2	1.07 (0.61–1.88)	0.809
Bleeding requiring reoperation	4.9	3.4	1.47 (0.66–3.27)	0.342
Unplanned interventional cardiac catheterization	4.3	2.4	1.86 (0.75–4.63)	0.180
Postoperative mechanical circulatory support	12.8	7.8	1.72 (1.01–2.93)	0.045
Mechanical ventilation > 7 days	27.2	19.0	1.59 (1.09–2.32)	0.015
Reintubation	11.9	11.9	1.00 (0.62–1.61)	0.994
Arrhythmia requiring intervention	14.8	15.3	0.96 (0.62–1.48)	0.853
Pulmonary process	9.9	8.5	1.18 (0.68–2.02)	0.557
Renal failure requiring dialysis	2.9	0.3	8.74 (1.11–68.67)	0.039
Neurological deficit or IVH	4.1	3.4	1.20 (0.53–2.75)	0.664
Wound infection	5.2	2.0	2.64 (1.03–6.75)	0.042

Hospital Stay Metrics and Mortality

The primary outcome of mortality, as well as secondary outcomes including length of stay (LOS) and 30 day readmission, were compared between the antenatal and postnatal diagnosis groups using STS-CHSD data (Table 6). Operative mortality was higher in the antenatal diagnosis group when compared to the postnatal diagnosis group (OR 1.92, 95% CI 1.20–3.08, p = 0.007). However, there was no statistically significant difference in 30-day postoperative mortality between the two groups. Hospital LOS, including preoperative and postoperative LOS, was longer in the antenatal diagnosis group. There was no difference in readmission within 30 days of discharge between the two groups.

Table 6

Outcomes by antenatal diagnosis status
Outcome	Antenatal Diagnosis (n = 381)	Postnatal Diagnosis (n = 334)	Odds Ratio (95% CI)	P-value
Mortality
Operative	59/380 (15.5%)	29/332 (8.7%)	1.92 (1.20, 3.08)	0.007
30-day postoperative	31/380 (8.2%)	19/332 (5.7%)	1.46 (0.81, 2.64)	0.207
Length of stay (days)
Total hospitalization	31 (19, 54)	22 (14, 42)	--	< .001
Preoperative	6 (4, 8)	5 (3, 8)	--	0.003
Postoperative	26 (14, 48)	16 (9, 35)	--	< .001
Readmission
30-day readmission	44/313 (14.1%)	41/292 (14.0%)	1.00 (0.63, 1.58)	0.995
Length of stay values reported are median (25th, 75th percentiles).

In subgroup analysis, there was a similar trend toward higher rates of operative mortality and longer postoperative LOS in those with antenatal diagnoses in the majority of the diagnostic subgroups. Similar to the larger cohort, 30-day readmission was similar between those with and without antenatal diagnoses.

Long-term Outcome Measures

Secondary analysis was performed by linking STS-CHSD patients to records in the NC CHD database in order to evaluate longer-term outcomes, assessed by NC death certificates and hospital admissions within the health systems contributing data to NC CHD. As the longer-term analysis only included subjects linked to the NC CHD database, this cohort was smaller than the original, as all patients in the STS-CHSD were unable to be captured by NC CHD due to the unavailability of indirect identifiers used for linking. Although there was no difference in 30-day readmission between the antenatal and postnatal diagnosis groups using the STS-CHSD data, there was a significantly higher 60-day readmission rate in the antenatal diagnosis cohort using the NC CHD database (42.8% vs. 28.0%, OR 1.93, 95% CI 1.35–2.75, p < 0.001). There was no difference in one-year postoperative mortality between groups (13.2% vs. 8.7%, OR 1.60, 95% CI 0.92–2.77, p = 0.095).

Our cohort of patients was obtained from a statewide, large surgical database over many years, and is one of the largest studies to date specifically evaluating postoperative outcomes in the neonatal population. Additionally, by utilizing linked data from the NC CHD database that includes information from the electronic medical record, we were uniquely able to capture longer-term outcomes than can be assessed with the STS-CHSD database alone.

As previously reported,^10,14 we similarly found that neonates that had prenatally diagnosed CHD were more hemodynamically stable with less preoperative clinical risk factors. Specifically, we found that prenatally diagnosed neonates were less likely to require preoperative mechanical ventilation and were less likely to have preoperative circulatory shock. This may be secondary to perinatal care coordination of a neonate with prenatally diagnosed CHD including detailed delivery planning with early disease-strategic resuscitation, optimizing clinical stability in these neonates prior to cardiac intervention or surgery.^3–5

While a more stable preoperative clinical status in a neonate with prenatally diagnosed CHD should theoretically result in improved postoperative outcomes, there is lack of consensus in the literature supporting this, with the majority of studies demonstrating similar or even worse postoperative outcomes in neonates with an antenatal diagnosis. Our analysis also found that patients with prenatally diagnosed CHD had less favorable short-term postoperative outcomes, including a higher incidence of select postoperative complications, longer length of stay (LOS), and increased operative mortality. Across the diagnostic subgroups, the directionality of associations between postoperative outcomes and antenatal diagnosis were overall similar. However, the small sample size limits the ability to find statistically significant differences. In our cohort, there was no difference in the incidence of prematurity, presence of non-cardiac congenital anomalies, or genetic syndromes identified between the antenatal and postnatal groups, in terms of database searchable patient-specific factors that may have contributed to the postoperative outcomes captured.

Although our data and previous reports suggest an association between prenatally diagnosed CHD and less favorable postoperative outcomes, it is more important to note the limitations to all of the above reported findings. Our study was not able to account for and adjust for detailed patient-specific factors to isolate and understand the relationship between prenatal diagnosis and patient outcomes. We could not factor in variables such as the local resources available at the birth center of those postnatally diagnosed or the proximity to the specialized cardiac center, which could influence clinical outcomes. If a neonate presented with a postnatal CHD diagnosis but was already at the cardiac center or located at a resource-rich center in close proximity, there may be an increased incidence of preoperative clinical instability compared to a prenatally diagnosed neonate, but this may not be severe enough to lead to altered postoperative complications or mortality.²² Additionally, our patient cohorts were created based on broad cardiac diagnosis codes entered into STS-CHSD and therefore, we were unable to account for nuances in cardiac anatomic and physiologic disease severity. Prior investigators have suggested that fetuses prenatally diagnosed with CHD have a more severe disease phenotype.²³ For example, we analyzed all neonates with HLHS as a single cohort rather than being able to isolate those higher risk with a restrictive or intact atrial septum, which in itself carries a much poorer prognosis even with prenatal diagnosis and optimized perinatal care.²⁴

Finally, with access to the NC CHD database, our study uniquely examined longer-term outcome measures and found higher rates of readmission within 60 days of hospital discharge in the prenatal diagnosis group. However, we found no difference in one-year postoperative mortality between groups, consistent with prior work. A large, prospective, population-based cohort study in France evaluated the relationship between timing of diagnosis and risk of infant mortality for patients with four major congenital heart defects (functionally univentricular heart, D-transposition of the great arteries, tetralogy of Fallot, and coarctation of the aorta) and found no statistically significant association between prenatal diagnosis and infant (< 1 year) mortality.¹⁸ Additional studies evaluating for improvements in survival rates with prenatal diagnosis of CHD have yielded similar results.^15–17 The absence of a difference in survival may be related to recent advancements in cardiopulmonary bypass, surgical techniques, and perioperative clinical care, which has resulted in an overall improvement in surgical mortality and long-term survival for infants with even critical CHD.²⁵ Additionally, universal screening for critical CHD via pulse oximetry became recommended²⁶ and subsequently endorsed by the American Academy of Pediatrics²⁷ during our study period, which may have contributed to early identification of neonates with postnatally diagnosed CHD. Therefore, perhaps a postnatally diagnosed neonate may have a less stable preoperative clinical status, but if the neonate is still without significant morbidities to be a surgical candidate, may still have favorable long-term outcomes in the modern age of preoperative surgical and medical care compared to an antenatally diagnosed neonate.

The strengths of our study are the inclusion of patients across the entire state of North Carolina spanning many years that were entered in the STS-CHSD database, and access to the NC CHD database for longer-term outcome data. Our study limitations include those inherent to a retrospective analysis with collection from administrative databases in that our study centered on the accuracy of the data entered into the database by the cardiac centers. We were also unable to gather detailed patient-specific data as mentioned above, some of which can only be gathered from manual review of a patient’s electronic medical record which is challenging when studying a larger patient cohort with care across several centers. These factors include but are not limited to maternal health factors, distance from the birth to cardiac center or access to specialized resources at the birth center in those postnatally diagnosed, details on cardiac anatomic and physiologic disease severity, need for urgent intervention prior to surgical repair, or timing of definitive surgical repair – all of which can influence perioperative patient clinical status and mortality.

Most importantly, our study was unable to include neonates postnatally diagnosed with severe CHD who died prior to surgical repair or were too hemodynamically unstable to be surgical candidates and instead directed towards palliative care (preoperative mortality). It is known that infants with postnatally diagnosed CHD have a higher risk of preoperative mortality,^13,28 and so not accounting for preoperative mortality may mean that the postnatal neonates included in our cohort are selectively more hemodynamically stable for surgical intervention and therefore more likely to have favorable perioperative outcomes.

Finally, despite the larger size of our patient cohort, the incidence of preoperative and postoperative risk factors as well as perioperative death was overall low. This low event rate may have impacted the possibility of identifying statistical significance in our analysis. Additionally, as a result of the low event rate, we did not include any adjustment models in our analysis, which could result in confounding.

Neonates with prenatally diagnosed severe CHD are more hemodynamically stable with less preoperative clinical risk factors, which is likely secondary to consequent perinatal care coordination which may include a specialized delivery room care team for disease-specific proactive, expeditious resuscitation as needed for those at highest risk for cardiopulmonary compromise during perinatal transition. However, there was a higher incidence of postoperative complications and mortality in prenatally diagnosed neonates, which may be secondary to patient-specific factors that we were unable to account for. Longer-term outcomes such as one-year mortality is similar in neonates prenatally and postnatally diagnosed, likely reflecting excellent surgical and medical care available in the modern era.

Further work, including a prospective population based study with a larger sample size and a detailed analysis of maternal and patient-specific factors is needed to better understand the influence of prenatal diagnosis on patient outcomes.

Data availability statement:

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Conflict of interest:

The authors have no conflicts of interest to disclose.

Funding: N/A

Bakker MK, Bergman JEH, Krikov S, et al. Prenatal diagnosis and prevalence of critical congenital heart defects: an international retrospective cohort study. BMJ open vol. 9,7 e028139. 2 Jul. 2019, doi:10.1136/bmjopen-2018-028139.
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 vol. 129,21 (2014): 2183 – 242. doi:10.1161/01.cir.0000437597.44550.5d
Donofrio MT, Levy RJ, Schuette JJ, et al. Specialized delivery room planning for fetuses with critical congenital heart disease. The American journal of cardiology vol. 111,5 (2013): 737–47. doi:10.1016/j.amjcard.2012.11.029
Donofrio MT. Predicting the Future: Delivery Room Planning of Congenital Heart Disease Diagnosed by Fetal Echocardiography. American journal of perinatology vol. 35,6 (2018): 549–552. doi:10.1055/s-0038-1637764
Sanapo L, Pruetz JD, Slodki M, et al. Fetal echocardiography for planning perinatal and delivery room care of neonates with congenital heart disease. Echocardiography (Mount Kisco, N.Y.) vol. 34,12 (2017): 1804–1821. doi:10.1111/echo.13672
Divanović A, Hor K, Cnota J, et al. Prediction and perinatal management of severely restrictive atrial septum in fetuses with critical left heart obstruction: clinical experience using pulmonary venous Doppler analysis. The Journal of thoracic and cardiovascular surgery vol. 141,4 (2011): 988–94. doi:10.1016/j.jtcvs.2010.09.043
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 vol. 112,19 (2005): 2974–9. doi:10.1161/CIRCULATIONAHA.105.534180
Punn R, Silverman NH. Fetal predictors of urgent balloon atrial septostomy in neonates with complete transposition. Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography vol. 24,4 (2011): 425–30. doi:10.1016/j.echo.2010.12.020
Sethi N, Klugman D, Said M, et al. Standardized delivery room management for neonates with a prenatal diagnosis of congenital heart disease: A model for improving interdisciplinary delivery room care. Journal of neonatal-perinatal medicine vol. 14,3 (2021): 317–329. doi:10.3233/NPM-200626
Quartermain MD, Hill KD, Goldberg DJ, et al. Prenatal Diagnosis Influences Preoperative Status in Neonates with Congenital Heart Disease: An Analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Pediatric Cardiology, vol. 40, no. 3, 2018, pp. 489–496., doi:10.1007/s00246-018-1995-4.
Tworetzky W, McElhinney DB, Reddy VM, et al. Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome. Circulation, 103:1269–1273, 2001.
Kipps AK, Feuille C, Azakie A, et al. Prenatal diagnosis of hypoplastic left heart syndrome in current era. The American journal of cardiology vol. 108,3 (2011): 421–7. doi:10.1016/j.amjcard.2011.03.065
Holland BJ, Myers JA, Woods CR Jr. Prenatal diagnosis of critical congenital heart disease reduces risk of death from cardiovascular compromise prior to planned neonatal cardiac surgery: a meta-analysis. Ultrasound in Obstetrics & Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, vol. 45,6 (2015): 631–8. doi:10.1002/uog.14882
Bonnet D, Coltri A, Butera G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation vol. 99,7 (1999): 916–8. doi:10.1161/01.cir.99.7.916
Chakraborty A, Gorla SR, Swaminathan S. Impact of Prenatal Diagnosis of Complex Congenital Heart Disease on Neonatal and Infant Morbidity and Mortality. Prenatal Diagnosis, vol. 38, no. 12, 2018, pp. 958–963., doi:10.1002/pd.5351.
Cohen MS, Schultz AH, Tian ZY, et al. Heterotaxy Syndrome with Functional Single Ventricle: Does Prenatal Diagnosis Improve Survival? The Annals of Thoracic Surgery, vol. 82, no. 5, 2006, pp. 1629–1636., doi:10.1016/j.athoracsur.2006.05.039.
Brown DW, Cohen KE, O’Brien P, et al. Impact of Prenatal Diagnosis in Survivors of Initial Palliation of Single Ventricle Heart Disease. Pediatric Cardiology, vol. 36, no. 2, 2014, pp. 314–321., doi:10.1007/s00246-014-1005-4.
Khoshnood B, Lelong N, Houyel L, et al. Impact of Prenatal Diagnosis on Survival of Newborns with Four Congenital Heart Defects: a Prospective, Population-based Cohort Study in France (the EPICARD Study). BMJ Open, 2017; 7:e018285. doi:10.1136/bmjopen-2017-018285
Wright LK, Ehrlich A, Stauffer N, et al. Relation of Prenatal Diagnosis With One-Year Survival Rate for Infants With Congenital Heart Disease. The American Journal of Cardiology, vol. 113, no. 6, 2014, pp. 1041–1044., doi:10.1016/j.amjcard.2013.11.065.
The Society of Thoracic Surgeons. Performance Measures. Operative Mortality for Pediatric and Congenital Heart Surgery 2015. https://www.sts.org/quality-safety/performance-measures/descriptions. Accessed July 12, 2022.
Tegnander E, Williams W, Johansen OJ, et al. Prenatal detection of heart defects in a non-selected population of 30,149 fetuses–detection rates and outcome. Ultrasound in obstetrics & gynecology: the official journal of the International Society of Ultrasound in Obstetrics and Gynecology vol. 27,3 (2006): 252–65. doi:10.1002/uog.2710
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 vol. 129,3 (2014): 285–92. doi:10.1161/CIRCULATIONAHA.113.003711
McCandless RT, Puchalski MD, Minich LL, et al. Prenatally diagnosed coarctation: a more sinister disease?. Pediatric cardiology vol. 33,7 (2012): 1160-4. doi:10.1007/s00246-012-0275-y
Vlahos AP, Lock JE, McElhinney DB, et al. Hypoplastic left heart syndrome with intact or highly restrictive atrial septum: outcome after neonatal transcatheter atrial septostomy. Circulation vol. 109,19 (2004): 2326–30. doi:10.1161/01.CIR.0000128690.35860.C5
Spector LG, Menk JS, Knight JH, et al. Trends in Long-Term Mortality After Congenital Heart Surgery. Journal of the American College of Cardiology vol. 71,21 (2018): 2434–2446. doi:10.1016/j.jacc.2018.03.491
Mahle WT, Newburger JW, Matherne GP, et al. Role of pulse oximetry in examining newborns for congenital heart disease: a scientific statement from the American Heart Association and American Academy of Pediatrics. Circulation vol. 120,5 (2009): 447 – 58. doi:10.1161/CIRCULATIONAHA.109.192576
Mahle WT, Martin GR, Beekman RH 3rd, et al. Endorsement of Health and Human Services recommendation for pulse oximetry screening for critical congenital heart disease. Pediatrics vol. 129,1 (2012): 190–2. doi:10.1542/peds.2011-3211
Thakur V, Dutil N, Schwartz SM, et al. Impact of prenatal diagnosis on the management and early outcome of critical duct-dependent cardiac lesions. Cardiology in the young vol. 28,4 (2018): 548–553. doi:10.1017/S1047951117002682

No competing interests reported.

Download PDF

Journal Publication

published 08 Jun, 2023

Read the published version in Pediatric Cardiology →

Editorial decision: Major revision
04 May, 2023
Reviews received at journal
24 Apr, 2023
Reviewers agreed at journal
06 Apr, 2023
Reviewers invited by journal
02 Apr, 2023
Editor assigned by journal
01 Apr, 2023
Submission checks completed at journal
01 Apr, 2023
First submitted to journal
31 Mar, 2023

You are reading this latest preprint version

Impact of prenatal diagnosis of critical congenital heart disease on preoperative and postoperative outcomes

Status:

Journal Publication

Version 1

Abstract

What Is Already Known About This Topic?

Introduction

Methods

Data Source and Study Design

Patient Population

Data Collection

Statistical Analysis

Results

Study Population Characteristics and Antenatal Detection Rates

Preoperative Outcome Measures

Postoperative Outcome Measures

Hospital Stay Metrics and Mortality

Long-term Outcome Measures

Discussion

Conclusions

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1