Abstract
Prenatal diagnosis of congenital heart disease (CHD) is increasingly common. However, the current impact of prenatal diagnosis on neonatal outcomes is unclear. Between January 2004 and January 2008, a retrospective chart review of infants who underwent surgical repair of CHD before discharge at our institution was conducted. Obstetric and perioperative variables were recorded. Of 439 neonates, 294 (67%) were diagnosed prenatally (PREdx). Infants with PREdx had a lower mean birth weight (3.0 ± 0.6 vs. 3.1 ± 0.6 kg, p = 0.002) and gestational age (37.9 ± 2.1 vs. 38.6 ± 2.4 wk, p < 0.001) than those with postnatal diagnosis (POSTdx). Severe lesions were more likely to be PREdx: Neonates with single-ventricle (SV) physiology (n = 130 patients [31.2%]) had increased odds of PREdx (n = 113/130, odds ratio [OR] 4.7; 95% confidence interval [CI] 2.7–8.2, p < 0.001). PREdx was associated with decreased preoperative intubation (OR 0.62; 95% CI 0.42–0.95, p = 0.033), administration of antibiotics (OR 0.23; 95% CI 0.15–0.36, p < 0.001), cardiac catheterization (OR 0.54; 95% CI 0.34–0.85, p = 0.01), and emergency surgery (OR 0.18; 95% CI 0.06–0.5, p < 0.001) compared with POSTdx infants. There was no difference in APGAR scores, preoperative pH, day of life of surgery, operative complications, hospital length of stay, or overall mortality in the PREdx versus POSTdx groups, even when controlling for lesion severity. PREdx was not independently associated with neonatal mortality, despite having included more severe cardiac lesions. PREdx was significantly associated with decreased neonatal morbidity in terms of decreased use of preoperative ventilator, administration of antibiotics, cardiac catheterization, and emergency surgery.
Keywords: Congenital, Diagnosis, Echocardiography, Heart defects, Surgery
Congenital malformations are a leading cause of infant mortality in the United States [6]. Heart defects comprise one quarter to one-third of all birth defects and are a large contributor to infant mortality. Prenatal diagnosis of congenital heart disease (CHD) by way of fetal echocardiography is increasingly common. Tworetsky et al. reported that from 1992 to 1999, 37% of hypoplastic left heart syndrome (HLHS) infants treated at Boston Children's Hospital were prenatally diagnosed (PREdx) [15], and Sivarajan et al., at the Royal Children's Hospital of Melbourne, reported that from 2001 and 2005, 77% of HLHS infants were PREdx [14].
Many infants with complex CHD require surgical intervention before hospital discharge. Previous studies investigating whether prenatal diagnosis of CHD favorably impacts survival have demonstrated inconsistent findings [9, 15]. Likewise, the impact on morbidity has been variably reported [3, 4, 16]. In light of these mixed reports, and with the knowledge that prenatal diagnosis is now more common than postnatal diagnosis, we sought to reassess the relations between prenatal diagnosis and various neonatal outcomes. First, we evaluated the effect of prenatal diagnosis on birth characteristics, such as gestational age (GA) and birth weight (BW). Second, the differences in anatomic cardiac diagnoses between PREdx and postnatally diagnosed (POSTdx) infants were investigated. Third, we assessed the impact of prenatal diagnosis on neonatal morbidity, including the need for more aggressive preoperative measures, day of life (DOL) of surgery, and hospital length of stay (LOS). Fourth, the effect of prenatal diagnosis on mortality was determined. Finally, we investigated the trends in prenatal diagnosis and the impact of prenatal diagnosis on DOL of surgery and hospital LOS at our institution during the course of the study period.
Methods
Study Design and Procedures
A retrospective chart review of infants who underwent repair of CHD before hospital discharge between January 1, 2004 and January 1, 2008 at the Morgan Stanley Children's Hospital of New York (MSCHONY), a tertiary care center with a level IV neonatal intensive care unit, was conducted using the pediatric cardiothoracic surgical database and the Center for Prenatal Pediatrics database. Institutional Review Board approval was obtained. Patient data recorded included timing of diagnosis, type of congenital heart defect, BW, GA, and DOL of surgery. In addition, preoperative information such as use of antibiotics, pressor support, or mechanical ventilator, as well as cardiac catheterization and MRI was collected. Operative and postoperative information including DOL of surgery, bypass and cross-clamp time, and hospital LOS was also recorded. Lesions were categorized based on the surgical severity score described and validated by Jenkins et al., which ranks cardiac diagnoses based on the surgical repair performed before hospital discharge [7].
Univariate descriptive statistics are summarized as means and SDs for normal distributions and as medians and interquartile ranges (IQR) for nonparametric distributions. Differences in proportions between groups were analyzed using 2 × 2 tables and Pearson's χ2 test statistic. Univariate relations were explored using Kaplan–Meier, and differences in medians were assessed using the log-rank test. In an effort to evaluate more fully the associations between prenatal diagnosis and DOL of surgery, hospital LOS, and neonatal mortality, multivariate models were constructed using both binary logistic regression and the Cox Proportional Hazards technique. Subject characteristics that showed a univariable association with DOL of surgery, hospital LOS, and mortality at the 0.1 level were eligible for inclusion in the multivariable models. All other alpha values were set at 0.05.
Results
During the 4-year study period, 439 infants underwent neonatal cardiothoracic surgery. Characteristics of the cohort are listed in Table 1. Prenatal diagnosis was made in 294 (67%) infants. Median DOL of surgery was 7 days (IQR 5–9), and median length of hospital stay was 17 days (IQR 12–28). Postoperative mortality was 5% in the entire series.
Table 1.
Information on total cohort (total n = 439)
| Variables | ||
|---|---|---|
| Characteristic | n (%) | |
| Catagoric variables | ||
| PREdx | 294 (67) | |
| Born at MSCHONY | 244 (55.6) | |
| Preoperative MRI | 26 (5.9) | |
| Preoperative cardiac catheterization | 100 (22.8) | |
| Preoperative antibiotics | 250 (56.9) | |
| Preoperative mechanical ventilation | 105 (23.9) | |
| Preoperative ECMO | 3 (0.7) | |
| Preoperative pressor support | 158 (36) | |
| Severity score of surgery performed | ||
| 1 | 0 (0) | |
| 2 | 32 (7.3) | |
| 3 | 169 (38.5) | |
| 4 | 135 (30.8) | |
| 5 | 7 (1.6) | |
| 6 | 96 (21.9) | |
| Surgery performed as emergency | 18 (4.1) | |
| Surgery postponed | 84 (19) | |
| Postoperative hospital mortality | 22 (5) | |
| Open chest | 65 (14.8) | |
| Characteristic | Mean ± SD | Median (IQR) |
| Continuous variables | ||
| Maternal age (y) | 30.3 ± 6.3 | |
| GA (wk) | 38.1 ± 2.1 | |
| BW (kg) | 3.04 ± 0.6 | |
| Apgar score at 1 min | 7.8 ± 1.5 | |
| Apgar score at 5 min | 8.6 ± 0.8 | |
| WBC count (109/L) | 16.3 ± 6 | |
| Highest arterial lactate (mM/l) | 4.2 ± 2.8 | |
| Arterial pH DOL 1 | 7.34 ± 0.1 | |
| Arterial pH DOL 2 | 7.34 ± 0.4 | |
| Arterial pH DOL 3 | 7.37 ± 0.1 | |
| Arterial pH DOL 4 | 7.38 ± 0.1 | |
| DOL postnatal diagnosis | 1.9 ± 2.2 | |
| DOL preoperative cardiac catheterization | 2.7 ± 2.9 | |
| DOL preoperative MRI | 5.4 ± 4.1 | |
| DOL at surgery | 7 (5–9) | |
| LOS | 17 (12–18) | |
ECMO extracorporeal membrane oxygenation
Birth Characteristics
Differences between the prenatal and postnatal diagnosis group are listed in Tables 2, 3. The prenatal diagnosis group had a lower mean GA (37.9 ± 2.1 vs. 38.6 ± 2.4 wk, p < 0.001) and BW (3.0 ± 0.6 vs. 3.1 ± 0.6 kg, p = 0.002) and were more likely to be born at our tertiary care center where the surgery was performed (OR 156.7; 95% CI 55.6–441.8, p < 0.001) compared with infants diagnosed after birth.
Table 2.
Catagoric variables
| Perinatal characteristics | No. prenatal diagnosis (%) | No. postnatal diagnosis (%) | OR | 95% CI | p |
|---|---|---|---|---|---|
| Total | 294 | 145 | |||
| Born at MSCHONY | 240 (81.6) | 4 (2.7) | 156.7 | 56–442 | <0.001 |
| Preoperative MRI | 15 (5.1) | 11 (7.6) | 0.7 | 0.3–1.5 | 0.30 |
| Preoperative cardiac catheterization | 56 (19) | 44 (30) | 0.5 | 0.3–0.9 | 0.008 |
| Preoperative antibiotics | 136 (46) | 114 (78.6) | 0.2 | 0.1–0.4 | <0.001 |
| Preoperative mechanical ventilation | 105 (35.7) | 68 (46.9) | 0.6 | 0.4–0.9 | 0.025 |
| Preoperative ECMO | 3 (1) | 0 (0%) | 0.22 | ||
| Preoperative pressor support | 102 (34.7) | 56 (38.6) | 0.8 | 0.6–1.3 | 0.42 |
| Preoperative positive blood culture | 11 (3.7) | 5 (3.4) | 1.1 | 0.4–3.2 | 0.87 |
| Severity score of surgery performed | – | – | <0.001 | ||
| 2 | 16 (5.4) | 16 (11) | |||
| 3 | 112 (38.1) | 57 (39.3) | |||
| 4 | 80 (27.2) | 55 (37.9) | |||
| 5 | 3 (1.0) | 4 (2.8) | |||
| 6 | 83 (28.2) | 13 (9.0) | |||
| Surgery performed as emergency | 5 (1.7) | 13 (9) | 0.2 | 0.1–0.5 | <0.001 |
| Surgery postponed | 67 (22.8) | 17 (11.7) | 2 | 1.3–3.3 | 0.006 |
| Postoperative hospital mortality | 18 (6.1) | 4 (2.8) | 2.3 | 0.7–6.9 | 0.129 |
| Patients with open chest | 44 (15) | 21 (14.5) | 1.0 | 0.6–1.8 | 0.89 |
ECMO extracorporeal membrane oxygenation
Table 3.
Continuous variables
| Perinatal characteristics | PREdx (mean ± SD)a | POSTdx (mean ± SD)a | p |
|---|---|---|---|
| Maternal age (y) | 30.6 ± 6.2 | 29.5 ± 6.5 | 0.098 |
| GA (wk) | 37.9 ± 2 | 38.6 ± 2 | <0.001 |
| BW (kg) | 3 ± 0.6 | 3.1 ± 0.6 | 0.002 |
| Apgar score at 1 min | 7.8 ± 1.5 | 7.9 ± 1.6 | 0.47 |
| Apgar score at 5 min | 8.6 ± 0.7 | 8.6 ± 1.1 | 0.97 |
| Highest arterial lactate (mM/l) | 4.1 ± 2.5 | 4.5 ± 3.5 | 0.20 |
| Arterial pH DOL 1 | 7.34 ± 0.07 | 7.33 ± 0.1 | 0.82 |
| Arterial pH DOL 2 | 7.34 ± 0.45 | 7.37 ± 0.07 | 0.57 |
| Arterial pH DOL 3 | 7.37 ± 0.06 | 7.38 ± 0.07 | 0.16 |
| Arterial pH DOL 4 | 7.37 ± 0.08 | 7.39 ± 0.06 | 0.08 |
| DOL of surgery (median) | 7 (5–8) | 6 (5–9) | 0.88 |
| Bypass time (min) | 126.8 ± 46.1 | 119 ± 40.6 | 0.096 |
| Cross-clamp time (min) | 56 ± 29.6 | 54.6 ± 26.6 | 0.67 |
| Circulatory arrest (min) | 38.6 ± 19.0 | 31.2 ± 19.6 | 0.003 |
| LOS (median d) | 20 (13–33) | 15 (11–25) | 0.001 |
Unless otherwise noted
Cardiac Diagnosis Breakdown
The prenatal diagnosis group had higher surgical severity scores (p < 0.001) compared with the postnatal group in accordance with the higher prevalence of more severe forms of CHD among the prenatal group (Table 4). Infants with HLHS were more likely to be PREdx (OR 4.1; 95% CI 1.9–8.9), whereas infants with transposition of the great arteries (TGA) were less likely to have a prenatal diagnosis (OR 0.4; 95% CI 0.3–0.7). Infants with total anomalous pulmonary venous return (TAPVR) were also less likely to be diagnosed before birth (OR 0.02; 95% CI 0.0–0.1).
Table 4.
Diagnosis breakdown: PREdx versus POSTdx
| Diagnosis | Total | No. PREdx (%) | No. POSTdx (%) | OR | 95% CI | p |
|---|---|---|---|---|---|---|
| Total | 439 | 294 (67) | 145 (33) | |||
| SV (total) | 135 | 118 (87.4) | 17 (12.6) | 5.0 | 2.9–8.8 | <0.001 |
| HLHS | 65 | 57 (89) | 8 (11) | 4.1 | 1.9–8.9 | <0.001 |
| Complex SV | 60 | 53 (88) | 7 (12) | 4.3 | 1.9–9.8 | <0.001 |
| Heterotaxy | 10 | 8 (80) | 2 (20) | 2 | 0.4–9.5 | 0.38 |
| d–TGA (total) | 89 | 46 (51.8) | 43 (48.2) | 0.4 | 0.3–0.7 | 0.001 |
| d–TGA/IVS | 51 | 22 (43.1) | 29 (56.9) | 0.3 | 0.2–0.6 | <0.001 |
| d–TGA/VSD | 25 | 16 (64) | 9 (36) | 0.9 | 0.4–2.0 | 0.45 |
| d–TGA/complex | 13 | 8 (61.5) | 5 (38.5) | 0.8 | 0.3–2.4 | 0.44 |
| Pulmonary atresia (non-SV) | 10 | 7 (70) | 3 (30) | 1.2 | 0.3–4.5 | 0.84 |
| DORV/MPGV | 18 | 14 (77.8) | 4 (22.2) | 1.9 | 0.6–5.8 | 0.19 |
| DORV, other | 8 | 8 (100) | 0 | – | – | 0.04 |
| Tetralogy of Fallot | 31 | 21 (67.8) | 10 (32.2) | 1.0 | 0.5–2.3 | 0.55 |
| TAPVR, isolated | 26 | 1 (3.8) | 25 (96.2) | 0.02 | 0.0–0.1 | <0.001 |
| IAA | 16 | 10 (62.5) | 6 (37.5) | 0.8 | 0.3–2.3 | 0.44 |
| Truncus arteriosus/IAA | 4 | 1 (25) | 3 (75) | 0.2 | 0.0–1.6 | 1.1 |
| Truncus arteriosus | 11 | 7 (63.6) | 4 (36.4) | 0.9 | 0.2–3 | 0.52 |
| Arch anomaly + intracardiac anomaly | 41 | 32 (78) | 9 (22) | 1.8 | 0.9–4 | 0.076 |
| Isolated arch anomaly | 29 | 18 (62) | 11 (38) | 0.8 | 0.4–1.7 | 0.35 |
| Intracardiac mass | 7 | 5 (71) | 2 (29) | 1.2 | 0.2–6.5 | 0.58 |
| Other | 14 | 6 (42.8) | 8 (57.2) | 0.36 | 0.1–1.0 | 0.05 |
DORV/MPGV double–outlet right ventricle/malposed great vessels, TAPVR total anomalous pulmonary venous return, IAA interrupted aortic arch, SV single ventricle, d–TGA (total) dextro-TGA of the great arteries, d–TGA/IVS dextro-TGA of the great arteries/intact ventricular septum, d–TGA/VSD dextro-TGA of the great arteries/ventricular septal defect
Neonatal Mortality
Prenatal diagnosis did not impact neonatal mortality. Independent factors associated with mortality are listed in Tables 5, 6. SV morphology (p < 0.001), surgical severity score (p = 0.002), postoperative open chest (p < 0.001), 1-min Apgar score (p = 0.05), and bypass time (p < 0.001) were significantly associated with mortality. Multivariate analysis demonstrated that postoperative open chest (OR 1.9; 95% CI, p = 0.12) was the only independent factor associated with mortality.
Table 5.
Univariate associations with mortality
| Catagoric variables | Total (n) | Mortality (n) | OR | 95% CI | p |
|---|---|---|---|---|---|
| Timing of diagnosis | 2.3 | 0.7–6.9 | 0.13 | ||
| Prenatal | 294 | 18 | |||
| Postnatal | 145 | 4 | |||
| Born at MSCHONY | 0.96 | 0.4–2.2 | 0.92 | ||
| Yes | 244 | 12 | |||
| No | 195 | 10 | |||
| SV anatomy | 4.5 | 1.9–11.1 | <0.001 | ||
| Yes | 135 | 14 | |||
| No | 304 | 8 | |||
| Other fetal anomalies | 1.8 | 0.58–5.5 | 0.304 | ||
| Yes | 50 | 4 | |||
| No | 389 | 18 | |||
| Preoperative pressor support | 2.23 | 0.94–5.3 | 0.063 | ||
| Yes | 158 | 12 | |||
| No | 281 | 10 | |||
| Preoperative antibiotic use | 1.1 | 0.46–2.6 | 0.85 | ||
| Yes | 250 | 13 | |||
| No | 188 | 9 | |||
| Preoperative positive blood culture | 1.2 | 0.16–9.7 | 0.84 | ||
| Yes | 16 | 1 | |||
| No | 409 | 21 | |||
| Preoperative ventilation | 1.8 | 0.7–4.4 | 0.20 | ||
| Yes | 173 | 11 | |||
| No | 246 | 9 | |||
| Severity of surgery performed | – | – | 0.002 | ||
| 2 | 32 | 0 | |||
| 3 | 169 | 1 | |||
| 4 | 135 | 11 | |||
| 5 | 7 | 1 | |||
| 6 | 96 | 9 | |||
| Emergency surgery | 1.1 | 0.14–8.8 | 0.91 | ||
| Yes | 18 | 1 | |||
| No | 421 | 21 | |||
| Postoperative open chest | 4.46 | 1.8–10.9 | <0.001 | ||
| Yes | 65 | 9 | |||
| No | 374 | 13 |
Table 6.
Continuous variables associated with mortality
| Variable | Mortality | No mortality | p |
|---|---|---|---|
| GA at birth (wk) | 37.5 (n = 22) | 38.1 (n = 410) | 0.19 |
| BW (kg) | 2.842 ± 0.67 (n = 21) | 3.045 ± 0.62 (n = 407) | 0.15 |
| Apgar score at 1 min | 7.2 ± 1.6 (n = 20) | 7.9 ± 1.5 (n = 389) | 0.05 |
| Apgar score at 5 min | 8.4 ± 0.7 (n = 20) | 8.6 ± 0.8 (n = 389) | 0.27 |
| Highest arterial preoperative lactate (mM/L) | 3.5 ± 1.4 (n = 17) | 4.3 ± 2.8 (n = 299) | 0.29 |
| DOL at surgery | 6 (5–9) (n = 22) | 7 (5–9) (n = 417) | 0.86 |
| Bypass time (min) | 168 ± 40.9 (n = 15) | 122 ± 43.7 (n = 353) | <0.001 |
All data reported as means with SD, except for DOL at surgery, which is reported as median with interquartile range
Preoperative Morbidity
PREdx infants were less likely to receive preoperative mechanical ventilation (OR 0.6; 95% CI 0.4–0.9), antibiotics (OR 0.2; 95% CI 0.1–0.4), cardiac catheterization (OR 0.5; 95% CI 0.3–0.9), or emergent surgery (OR 0.2; 95% CI 0.1–0.5) compared with POSTdx infants (Tables 2, 3).
DOL of Surgery
Prenatal diagnosis did not impact DOL of surgery (median DOL of surgery 7 days [IQR 5–8] for prenatal diagnosis vs. 6 days [IQR 5–9] for postnatal diagnosis, p = 0.9). There was no difference in DOL of surgery among groups even when stratified by cardiac lesion (Table 7). Univariate associations between subject characteristics and DOL of surgery are listed in Table 8. Multivariate Cox-proportional hazard modeling demonstrated that the use of preoperative antibiotics (hazard ratio [HR] 0.7; 95% CI 0.6–0.9, p = 0.002) and additional fetal anomalies (HR 0.5; 95% CI 0.4–0.7, p < 0.001) were independently associated with a longer time to surgery when controlling for timing of diagnosis, prematurity, and low BW.
Table 7.
Median DOL of surgery by cardiac diagnosis and diagnosis timing
| Lesion | PREdx | POSTdx | p |
|---|---|---|---|
| SV | 7 (5–8) | 8 (5–15) | 0.17 |
| HLHS | 7 (5–8) | 5 (5–7) | 0.6 |
| d–TGA | 7 (5–8) | 6 (4–7) | 0.07 |
d–TGA dextro-TPA of the great arteries
Data reported as medians with interquartile ranges
Table 8.
Univariate associations with DOL at surgery
| Variable | Total (n) | Median DOL | IQR | p |
|---|---|---|---|---|
| Timing of diagnosis | 0.88 | |||
| Prenatal | 294 | 7 | 5–8 | |
| Postnatal | 145 | 6 | 5–9 | |
| Born at MSCHONY | 0.43 | |||
| Yes | 244 | 6 | 4–8 | |
| No | 195 | 7 | 5–9 | |
| SV anatomy | 0.19 | |||
| Yes | 135 | 7 | 5–9 | |
| No | 304 | 6 | 4–9 | |
| Other fetal anomalies | <0.001 | |||
| Yes | 50 | 9 | 6–16 | |
| No | 389 | 6 | 4–8 | |
| Prematurea | 0.003 | |||
| Yes | 139 | 7 | 5–9 | |
| No | 300 | 6 | 4–8 | |
| Low BWb | 0.001 | |||
| Yes | 84 | 8 | 6–10 | |
| No | 355 | 6 | 4–8 | |
| Peak preoperative arterial lactate (mM/l) | 0.125 | |||
| ≤2.6 | 89 | 7 | 5–8 | |
| 2.7–3.5 | 73 | 6 | 5–8 | |
| 3.6–5.1 | 73 | 6 | 4–8 | |
| >5.1 | 77 | 6 | 4–10 | |
| Preoperative pressor support | 0.053 | |||
| Yes | 158 | 7 | 5–9 | |
| No | 281 | 6 | 4–8 | |
| Preoperative antibiotic use | 0.001 | |||
| Yes | 250 | 7 | 5–9 | |
| No | 188 | 6 | 4–8 | |
| Preoperative positive blood culture | <0.001 | |||
| Yes | 16 | 13 | 8–16 | |
| No | 409 | 6 | 5–8 | |
| Preoperative cardiac catheterization | 0.25 | |||
| Yes | 100 | 7 | 5–9 | |
| No | 339 | 6 | 4–9 | |
| Preoperative MRI | 0.12 | |||
| Yes | 26 | 8 | 7–10 | |
| No | 413 | 6 | 4–9 | |
| Preoperative ventilation | 0.71 | |||
| Yes | 173 | 6 | 4–9 | |
| No | 246 | 7 | 5–9 | |
| Severity of surgery performed | 0.22 | |||
| 2 | 32 | 7 | 4–10 | |
| 3 | 169 | 7 | 5–10 | |
| 4 | 135 | 6 | 4–8 | |
| 5 | 7 | 6 | 5–8 | |
| 6 | 96 | 7 | 5–8 | |
| Surgery postponed | <0.001 | |||
| Yes | 84 | 11 | 8–16 | |
| No | 355 | 6 | 4–8 | |
| Emergent surgery | <0.001 | |||
| Yes | 18 | 2 | 2–2 | |
| No | 421 | 7 | 5–9 |
GA <38 weeks
BW <2,500 g
Hospital LOS
Univariate associations between subject characteristics and hospital LOS are listed in Table 9. The prenatal diagnosis group had longer median hospital LOS (20 [range 13–33] vs. 15 days [range 11–25], p = 0.001) than the postnatal diagnosis group. Multivariate Cox-proportional hazard modeling demonstrated that surgical severity score (HR 0.9; 95% CI 0.8–0.9, p < 0.001), other fetal anomalies (HR 0.7; 95% CI 0.5–0.9, p = 0.03), prematurity (HR 0.8; 95% CI 0.6–0.9, p = 0.036), and DOL of surgery (HR 0.9; 95% CI 09–1, p < 0.001) were independently associated with a longer hospital LOS when controlling for prenatal diagnosis and low BW. Prenatal diagnosis was not associated with hospital LOS in this multivariate model.
Table 9.
Univariate associations with LOS
| Variable | Total (n) | Median LOS | IQR | p |
|---|---|---|---|---|
| Timing of diagnosis | 0.001 | |||
| Prenatal | 294 | 20 | 13–33 | |
| Postnatal | 145 | 15 | 11–25 | |
| Born at MSCHONY | <0.001 | |||
| Yes | 244 | 20 | 13–34 | |
| No | 195 | 15 | 11–25 | |
| SV anatomy | <0.001 | |||
| Yes | 135 | 22 | 14–39 | |
| No | 304 | 16 | 12–26 | |
| Other fetal anomalies | <0.001 | |||
| Yes | 50 | 28 | 18–45 | |
| No | 389 | 16 | 12–27 | |
| Prematurea | 0.007 | |||
| Yes | 139 | 21 | 14–34 | |
| No | 300 | 16 | 12–27 | |
| Low BWb | 0.087 | |||
| Yes | 84 | 21 | 14–30 | |
| No | 355 | 17 | 12–28 | |
| Peak preoperative arterial lactate (mM/l) | 0.030 | |||
| ≤2.6 | 89 | 17 | 12–34 | |
| 2.7–3.5 | 73 | 16 | 12–22 | |
| 3.6–5.1 | 73 | 20 | 12–28 | |
| >5.1 | 77 | 19 | 13–33 | |
| Preoperative pressor support | 0.47 | |||
| Yes | 158 | 18 | 12–32 | |
| No | 281 | 17 | 12–28 | |
| Preoperative antibiotic use | 0.99 | |||
| Yes | 250 | 17 | 13–28 | |
| No | 188 | 18 | 11–30 | |
| Preoperative positive blood culture | 0.31 | |||
| Yes | 15 | 20 | 16–45 | |
| No | 409 | 17 | 12–28 | |
| Preoperative cardiac catheterization | 0.18 | |||
| Yes | 100 | 16 | 11–26 | |
| No | 339 | 18 | 12–29 | |
| Preoperative MRI | 0.86 | |||
| Yes | 26 | 22 | 14–32 | |
| No | 413 | 17 | 12–28 | |
| Preoperative ventilation | 0.47 | |||
| Yes | 173 | 18 | 12–31 | |
| No | 246 | 17 | 12–28 | |
| Severity of surgery performed | 0.072 | |||
| 2 | 32 | 14 | 9–25 | |
| 3 | 169 | 17 | 12–26 | |
| 4 | 135 | 16 | 12–27 | |
| 5 | 7 | 22 | 8–59 | |
| 6 | 96 | 25 | 14–39 | |
| Surgery postponed | <0.001 | |||
| Yes | 84 | 26 | 16–45 | |
| No | 355 | 16 | 12–26 | |
| Emergent surgery | <0.001 | |||
| Yes | 18 | 11 | 10–14 | |
| No | 421 | 18 | 12–29 | |
| Surgery at DOL < 7 | <0.001 | |||
| Yes | 216 | 14 | 10–22 | |
| No | 223 | 22 | 15–37 | |
| Open chest | 0.002 | |||
| Yes | 65 | 28 | 17–39 | |
| No | 374 | 16 | 12–26 |
GA <38 weeks
BW <2,500 g
Prenatal Diagnosis Trends
Trends in prenatal diagnosis, DOL of surgery, and hospital LOS across the 4-year study period are listed in Table 10. Although there was no significant difference in the rate of prenatal diagnosis, median DOL of surgery and hospital LOS decreased significantly from 2004 to 2007.
Table 10.
Outcomes over the years
| Timing of diagnosis | Year of surgery (% total) | ||||
|---|---|---|---|---|---|
| 2004 (n = 107) | 2005 (n = 101) | 2006 (n = 123) | 2007 (n = 108) | p comparing 2004 and 2007 | |
| Prenatal | 70 (65.4) | 63 (62.4) | 80 (65) | 81 (75) | 0.166 |
| DOL at surgery (median) | |||||
| Prenatal | 8 (5–9) | 7 (5–9) | 6 (5–8) | 6 (4–8) | 0.036 |
| Postnatal | 6 (5–8) | 7 (4–12) | 7 (6–9) | 6 (4–9) | |
| All patients | 7 (5–9) | 7 (5–10) | 6 (5–8) | 6 (4–8) | |
| LOS (median d) | |||||
| Prenatal | 21 (15–35) | 22 (15–43) | 17 (12–26) | 17 (10–17) | 0.002 |
| Postnatal | 16 (12–28) | 15 (12–26) | 15 (11–27) | 14 (12–28) | |
| All patients | 20 (14–34) | 20 (13–34) | 16 (12–27) | 16 (11–26) | |
Discussion
This study demonstrates that the prevalence of prenatal diagnosis of CHD in the current era is higher than previously reported, reaching as high as 88% for certain defects at our center. There are various explanations for the increase in prenatal detection of CHD. First, standard of care of obstetrical screening for fetal anomalies has expanded to include first-trimester nuchal fold measurements. Abnormalities in these early scans typically result in referral for fetal echocardiography. Second, modern technology has improved image resolution, thus making it easier to detect anomalies during routine obstetric ultrasound screening.
Our study demonstrated an association between prenatal diagnosis and lower GA and BW. This has been reported previously [3]. This finding may be explained in part by institutional practices of scheduling delivery, especially among women who live far from the medical center, to assure availability of maximal neonatal medical support. The differences in BW and GA are small and are unlikely to be of clinical significance, as evidenced by the decrease in neonatal morbidity among the prenatal diagnosis group.
We found that the more severe cardiac anatomic lesions are likely to be PREdx. This finding has been reported previously [3] and can be explained by advances in obstetrical screening methods. The most common indication for referral for fetal echocardiography is a cardiac abnormality seen on the routine obstetrical anatomic scan [5, 12]. Guidelines from the American Institute of Ultrasound in Medicine recommend a complete second-trimester anatomic scan of the fetal chest, including a four-chamber view of the fetal heart and, if technically feasible, views of the two outflow tracts [1]. Therefore, the more grossly abnormal the appearance of the heart in the four-chamber view, the more likely the lesion is to be recognized on routine ultrasound. Conversely, lesions such as TAPVR and TGA that do not significantly change the appearance of the four-chamber view are more likely to be missed. TGA is likely to be overlooked because views of the outflow tracts are not always obtained. The same is true for anomalous pulmonary venous connections because pulmonary veins are not often discerned on fetal studies.
Our study did not demonstrate an association between prenatal diagnosis and surgical mortality. Other studies similarly did not demonstrate a positive impact of prenatal diagnosis on the survival of infants with HLHS and other forms of CHD [8–11]. In 2001, Tworetsky et al. demonstrated a survival advantage to prenatal diagnosis among HLHS infants. In this study, 37.5% of the HLHS infants were PREdx, whereas in our study 88% of HLHS infants were PREdx and 88% survived neonatal surgery. This change in the prevalence of prenatal diagnosis and in the prevalence of survival may partially explain the differences in findings. Although it is true that for some infants prenatal diagnosis is life saving, there are others for whom immediate delivery of targeted cardiac support may not be as crucial. If 88% of HLHS infants are PREdx indiscriminately, which includes a mix of the above phenotypes, then the association between prenatal diagnosis and survival may be difficult to discern.
We have demonstrated that prenatal diagnosis improves certain measures of neonatal morbidity. Others have reported that prenatal diagnosis decreases neonatal metabolic acidosis [2, 4, 13, 16]. Although we found no statistically significant impact of prenatal diagnosis on neonatal acid–base status, we did see decreased use of ventilators, antibiotics, and cardiac catheterization, and fewer emergent surgeries among the prenatal diagnosis group. These findings can be attributed in part to the anticipation of medical needs of patients with a fetal diagnosis of CHD and the institution of medical support before clinical status deterioration, avoiding the poor status that is the usual presentation of the POSTdx infant. The majority of our PREdx cohort (82%) was born at our institution, thus allowing the immediate delivery of medical support, including prostaglandin, which is vital for the maintenance of ductal patency in a ductal-dependent lesion. In addition, the development of cyanosis and respiratory distress in an infant without a prenatal CHD diagnosis often prompts intubation and a sepsis workup, further explaining the higher prevalence of these findings in the postnatal diagnosis group. Furthermore, infants born at outside institutions may have been intubated for the purposes of transportation to our center. The decreased use of cardiac catheterization in the prenatal diagnosis group may be accounted for by the high proportion of POSTdx infants with TGA, who often require balloon atrial septostomy, and those with TAPVR, who may undergo diagnostic cardiac catheterizations to delineate the anatomic pathways of the anomalous pulmonary veins. Similarly, the association with emergent surgery may be explained by the TAPVR anatomic subgroup, many of whom present in distress and are urgently repaired.
We found no association between prenatal diagnosis and DOL of surgery or hospital LOS, even when controlling for lesion severity. Although median hospital LOS was longer in the prenatal diagnosis group in a univariate analysis, the association was no longer significant in multivariate analysis. Copel et al. demonstrated that prenatal diagnosis was associated with an overall increase in neonatal hospital LOS and hospital expenses for live-born infants and postulated that this might be due to increased illness severity in the PREdx cohort [3].
Limitations
Our study consisted of a retrospective review of data. Only infants who survived to cardiac surgery were captured in this analysis; therefore, the effect of prenatal diagnosis on overall neonatal mortality cannot be assessed with the present data. In addition, our sample does not include pregnancies that were terminated. It has been our experience that few fetuses with a prenatal diagnosis of CHD seen at our institution are terminated, which is likely due to selection bias: patients who have decided to continue the pregnancy seek care at a tertiary-level referral center, whereas patients wishing to terminate the pregnancy may do so locally. One could postulate that prenatal diagnosis of CHD may lead to increased terminations of pregnancy, especially among fetuses with more severe lesions and with additional significant anomalies. All of these factors may confound our ability to establish a causal relation between prenatal diagnosis and neonatal outcomes.
Conclusion
Prenatal diagnosis of complex CHD is now more common than postnatal diagnosis; levels were as high as 75% overall in the final year of our study. Prenatal diagnosis is more likely to occur in lesions of higher severity. Despite representing more severe lesions, prenatal diagnosis was associated with decreased neonatal morbidity, including decreased use of mechanical ventilation, antibiotics, and emergent surgery. Prenatal diagnosis did not impact DOL of surgery, hospital LOS, or mortality. Further investigation into the impact of prenatal diagnosis on DOL of surgery and hospital LOS is needed. The positive economic impact of more efficient management of these patients is also an important consideration. Advanced prenatal knowledge of an indication for cardiac surgery may allow for the optimization of factors beyond immediate neonatal resuscitation that affect neonate survival, including labor, delivery, and operative repair.
Acknowledgments
I. A. Williams received support from Grant No. KL2 RR024157 from the National Center for Research Resources, a component of the National Institutes of Health and the National Institutes of Health Roadmap for Medical Research. The contents herein are solely the responsibility of the authors and do not necessarily represent the official view of National Centre for Research Resources or National Institutes of Health. Information on National Centre for Research Resources is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from www. http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.
Contributor Information
Allison Levey, Email: ap465@columbia.edu, Division of Cardiology, Department of Pediatrics and the Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Julie S. Glickstein, Division of Cardiology, Department of Pediatrics and the Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY, USA
Charles S. Kleinman, Division of Cardiology, Department of Pediatrics and the Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY, USA
Stephanie M. Levasseur, Division of Cardiology, Department of Pediatrics and the Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY, USA
Jonathan Chen, Division of Pediatric Cardiothoracic Surgery, Department of Cardiothoracic Surgery, Morgan Stanley Children's Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Welton M. Gersony, Division of Cardiology, Department of Pediatrics and the Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY, USA
Ismee A. Williams, Division of Cardiology, Department of Pediatrics and the Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY, USA
References
- 1.American Institute of Ultrasound in Medicine. American Institute of Ultrasound in Medicine; Laurel: 2000. [3 Feb 2010]. Clinical safety. Official statement. http://www.aium.org. [Google Scholar]
- 2.Bonnet D, Coltri A, Butera G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation. 1999;99:916–918. doi: 10.1161/01.cir.99.7.916. [DOI] [PubMed] [Google Scholar]
- 3.Copel JA, Tan AS, Kleinman CS. Does a prenatal diagnosis of congenital heart disease alter short-term outcome? Ultrasound Obstet Gynecol. 1997;10:237–241. doi: 10.1046/j.1469-0705.1997.10040237.x. [DOI] [PubMed] [Google Scholar]
- 4.Eapen RS, Rowland DG, Franklin WH. Effect of prenatal diagnosis of critical left heart obstruction on perinatal morbidity and mortality. Am J Perinatol. 1998;15:237–242. doi: 10.1055/s-2007-993934. [DOI] [PubMed] [Google Scholar]
- 5.Friedberg M, Silverman N. Changing indications for fetal echocardiography in a university center population. Prenat Diagn. 2004;24:781–786. doi: 10.1002/pd.981. [DOI] [PubMed] [Google Scholar]
- 6.Hoyert DL, Mathews TJ, Menacker F, Strobino DM, Guyer B. Annual summary of vital statistics: 2004. Pediatrics. 2006;117:168–183. doi: 10.1542/peds.2005-2587. [DOI] [PubMed] [Google Scholar]
- 7.Jenkins K, Gauvreau K, Newburger J, Spray T, Moller J, Iezzoni L. Consensus-based method for risk adjustment for surgery for congenital heart disease. J Thorac Cardiovasc Surg. 2002;123:110–118. doi: 10.1067/mtc.2002.119064. [DOI] [PubMed] [Google Scholar]
- 8.Kumar RK, Newburger JW, Gauvreau K, Kamenir SA, Hornberger LK. Comparison of outcome when hypoplastic left heart syndrome and transposition of the great arteries are diagnosed prenatally versus when diagnosis of these two conditions is made only postnatally. Am J Cardiol. 1999;83:1649–1653. doi: 10.1016/s0002-9149(99)00172-1. [DOI] [PubMed] [Google Scholar]
- 9.Mahle WT, Clancy RR, McGaurn SP, Goin JE, Clark BJ. Impact of prenatal diagnosis on survival and early neurologic morbidity in neonates with the hypoplastic left heart syndrome. Pediatrics. 2001;107:1277–1282. doi: 10.1542/peds.107.6.1277. [DOI] [PubMed] [Google Scholar]
- 10.Montana E, Khoury MJ, Cragan JD, Sharma S, Dhar P, Fyfe D. Trends and outcomes after prenatal diagnosis of congenital cardiac malformations by fetal echocardiography in a well defined birth population, Atlanta, Georgia, 1990–1994. J Am Coll Cardiol. 1996;28:1805–1809. doi: 10.1016/S0735-1097(96)00381-6. [DOI] [PubMed] [Google Scholar]
- 11.Munn MB, Brumfield CG, Lau Y, Colvin EV. Prenatally diagnosed hypoplastic left heart syndromēoutcomes after postnatal surgery. J Matern Fetal Med. 1999;8:147–150. doi: 10.1002/(SICI)1520-6661(199907/08)8:4<147::AID-MFM1>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
- 12.Russo M, Paladini D, Pacileo G, Ricci C, Di Salvo G, Felicetti M, et al. Changing spectrum and outcome of 705 fetal congenital heart disease cases: 12 years' experience in a third-level center. J Cardiovasc Med. 2008;9:910–915. doi: 10.2459/JCM.0b013e32830212cf. [DOI] [PubMed] [Google Scholar]
- 13.Satomi G, Yasukochi S, Shimizu T, Takigiku K, Ishii T. Has fetal echocardiography improved the prognosis of congenital heart disease? Comparison of patients with hypoplastic left heart syndrome with and without prenatal diagnosis. Pediatr Int. 1999;41:728–732. doi: 10.1046/j.1442-200x.1999.01154.x. [DOI] [PubMed] [Google Scholar]
- 14.Sivarajan V, Penny DJ, Filan P, Brizard C, Shekerdemian LS. Impact of antenatal diagnosis of hypoplastic left heart syndrome on the clinical presentation and surgical outcomes: the Australian experience. J Paediatr Child Health. 2009;45:112–127. doi: 10.1111/j.1440-1754.2008.01438.x. [DOI] [PubMed] [Google Scholar]
- 15.Tworetzky W, McElhinney DB, Reddy VM, Brook MM, Hanley FL, Silverman NH. Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome. Circulation. 2001;103:1269–1273. doi: 10.1161/01.cir.103.9.1269. [DOI] [PubMed] [Google Scholar]
- 16.Verheijen PM, Lisowski LA, Stoutenbeek P, Hitchcock JF, Brenner JI, Copel JA, et al. Prenatal diagnosis of congenital heart disease affects preoperative acidosis in the newborn patient. J Thorac Cardiovasc Surg. 2001;121:798–803. doi: 10.1067/mtc.2001.112825. [DOI] [PubMed] [Google Scholar]