Background
Methods
Study design
Definitions of exposures and outcomes
Outcomes
Clinical variables
Echocardiographic variables
Descriptive statistics
Univariable and multivariable analyses
Results
Patient selection
Echocardiographic characteristics of infants with late PH
Echocardiographic parameters | Infants with Late PH, n = 59 | Infants without Late PH, n = 497 | Odd ratio (95% CI) |
p - value |
---|---|---|---|---|
Timing of final echo Median (IQR) | 77 (13–136) | 41 (21–105) | 1.0 (1.0–1.0) | 0.39 |
Atrial septal defects | ||||
None/PFO | 43, 73% | 434, 87% | ref | |
PFO vs. ASD | 4, 7% | 24, 5% | 1.7 (0.6–5.1) | 0.68 |
ASD | 10, 17% | 22, 4% | 4.6 (2.0–10.3) | <0.01* |
Atrial shunt direction (n, %) | ||||
None or left-to-right | 29, 57% | 312, 87% | ref | |
Bidirectional/Right-to-Left | 22, 43% | 47, 13% | 5.0 (2.7–9.5) | <0.01* |
Patent Ductus Arteriosus | ||||
None | 16, 36% | 217, 54% | ref | |
Small | 11, 24% | 69, 17% | 2.2 (1.0–4.9) | 0.28 |
Moderate/Large | 18, 40% | 116, 29% | 2.1 (1.0–4.3) | 0.27 |
Patent ductus arteriosus shunt direction (n, %) | ||||
None or left-to-right | 12, 43% | 177, 99% | ref | |
Bidirectional/Right-to-Left | 16, 57% | 1, < 1% | 236.0 (29–1933) | <0.01* |
Tricuspid regurgitation jet velocity (n, %) | ||||
Normal, < 32 mmHg | 11, 19% | 474, 98% | ref | |
Mild, 32–44 mmHg | 23, 39% | 12, 2% | 83.0 (33–207) | < 0.01* |
Mod, 45–60 mmHg | 15, 25% | 0, 0% | ________ | ____ |
Severe, > 60 mmHg | 10, 17% | 0, 0% | ________ | ____ |
Septal flattening (n, %) | ||||
None | 1, 2% | 96, 43% | ref | |
Any | 48, 98% | 126, 57% | 36.6 (5.0–269.7) | < 0.01* |
Right ventricular dilation (n, %) | ||||
None | 25, 45% | 436, 92% | ref | |
Any | 31, 55% | 36, 8% | 15.0 (8.0–28.1) | < 0.01* |
Right ventricular hypertrophy (n, %) | ||||
None | 22, 44% | 427, 90% | ref | |
Any | 28, 56% | 50, 10% | 10.9 (5.8–20.4) | < 0.01* |
Right ventricular dysfunction (n, %) | ||||
None | 38, 67% | 472, 97% | ref | |
Any | 19, 33% | 14, 3% | 16.9 (7.8–36.2) | < 0.01* |
Ventricular Septal Defect | ||||
None/Small | 51, 96% | 421, 97% | ref | |
Mod/Large | 2, 4% | 11, 3% | 1.5 (0.3–6.9) | 0.60 |
Left ventricular dysfunction (n, %) | 7, 12% | 31, 6% | 2 (0.8–4.8) | 0.11 |
Associations between neonatal characteristics and late PH
Birth/early hospital characteristics | Infants with Late PH, n = 59 | Infants without Late PH, n = 497 | Odds ratio (95% CI) |
p - value |
---|---|---|---|---|
Apgar 1 min. Mean ± SD | 3.5 ± 2.8 | 4.1 ± 2.6 | 0.9 (0.8–1.0) | 0.10 |
Apgar 5 min. Mean ± SD | 6.3 ± 2.4 | 6.5 ± 2.2 | 1.0 (0.8–1.1) | 0.44 |
Birthweight (kg) Mean ± SD | 0.75 ± 0.24 | 0.83 ± 0.25 | 0.2 (0.1–0.7) | 0.02* |
Gestational age (wks) Mean ± SD | 26.1 ± 2.4 | 26.1 ± 2.2 | 1.0 (0.9–1.1) | 0.99 |
Mode of Delivery (n, %) | ||||
C/S | 44, 77% | 327, 66% | 1.7 (0.9–3.3) | 0.10 |
Vaginal | 13, 23% | 166, 34% | ref | |
Gender (n, %) | ||||
Male | 33, 56% | 289, 42% | 0.9 (0.5–1.6) | 0.71 |
Female | 26, 44% | 205, 42% | ref | |
Intrauterine growth restriction (n, %) | 10, 18% | 35, 7% | 2.9 (1.3–6.2) | < 0.01* |
Placental abruption (n, %) | 9, 16% | 49, 10% | 1.7 (0.8–3.7) | 0.17 |
Chorioamnionitis (n, %) | 3, 5% | 50, 10% | 0.5 (0.2–1.7) | 0.27 |
Maternal betamethasone (n, %) | ||||
2 or more doses | 27, 57% | 267, 62% | 0.8 (0.4–1.5) | 0.52 |
0–1 doses | 20, 43% | 162, 38% | ref | |
Race (n, %) | ||||
Black | 36, 61% | 290, 60% | 1.1 (0.6–1.8) | 0.84 |
White/Asian/Hispanic | 23, 39% | 196, 40% | ref | |
Illicit drug use (n, %) | 3, 6% | 41, 9% | 0.6 (0.2–2.2) | 0.47 |
Multiples (n, %) | 12, 21% | 91, 18% | 1.2 (0.6–2.3) | 0.68 |
Maternal drug use | 5, 10% | 39, 9% | 1.2 (0.4–3.1) | 0.76 |
Caffeine (n, %) | 29, 51% | 341, 69% | 0.5 (0.3–0.8) | < 0.01* |
Any respiratory support, 28 days (n, %) | 26, 44% | 212, 43% | 1.0 (0.6–1.8) | 0.87 |
Positive pressure ventilation, 28 days (n,%) | 26, 44% | 203, 41% | 1.1 (0.7–2.0) | 0.63 |
Any respiratory support, 36 weeks (n, %) | 26, 44% | 199, 40% | 1.2 (0.7–2.2) | 0.45 |
Sildenafil (n, %) | 11, 19% | 19, 4% | 5.8 (2.6–12.8) | < 0.01* |
Bosentan | 2, 3% | 0, 0% | __________ | _____ |
Birth/early hospital characteristics | Infants with multiple studies and late PH n = 32 | Infants with multiple studies without late PH n = 224 |
p - value |
---|---|---|---|
Apgar 1 min. Mean ± SD | 3.0 ± 2.4 | 4.3 ± 2.5 | 0.01* |
Apgar 5 min. Mean ± SD | 6.0 ± 2.3 | 6.5 ± 2.2 | 0.27 |
Birthweight (kg) Mean ± SD | 0.68 ± 0.19 | 0.80 ± 0.24 | <0.01* |
Gestational age (wks) Mean ± SD | 25.7 ± 2.3 | 25.9 ± 2.2 | 0.73 |
Mode of Delivery – C/S (n, %) | 23, 72% | 145, 65% | 0.44 |
Gender -- Male (n, %) | 16, 50% | 129, 58% | 0.42 |
Intrauterine growth restriction (n, %)#
| 7, 23% | 20, 9% | 0.03* |
Placental abruption (n, %)#
| 4, 13% | 24, 11% | 0.76 |
Chorioamnionitis (n, %)#
| 2, 6% | 22, 10% | 0.75 |
Maternal betamethasone (n, %) | 16, 59% | 122, 63% | 0.72 |
Multiples (n, %)#
| 3, 9% | 46, 21% | 0.16 |
Caffeine (n, %) | 20, 63% | 152, 68% | 0.55 |
Any respiratory support, 28 days (n, %) | 17, 53% | 113, 51% | 0.81 |
Any respiratory support, 36 weeks (n, %) | 21, 66% | 117, 52% | 0.35 |
Death (n, %) | 12, 20% | 86, 17% | 0.56 |
Day of life, death or discharge Mean ± SD | 113 ± 81 | 126 ± 74 | 0.61 |
Race (n, %) | 0.52 | ||
Black | 21, 66% | 132, 60% | |
Other | 11, 34% | 89, 40% | |
Atrial septal defects (n, %) | 9, 28% | 16, 7% | <0.001* |
Bidirectional/right-to-left atrial shunt (n, %) | 12, 46% | 18, 12% | <0.001* |
Patent Ductus Arteriosus (n, %) | |||
Moderate/Large#
| 4, 19% | 22, 14% | 0.51 |
Bidirectional/R-to-L#
| 4, 57% | 0, 0% | < 0.001* |
Septal flattening (n, %) | 29, 97% | 79, 53% | <0.001* |
Right ventricular dilation (n, %) | 20, 69% | 23, 11% | <0.001* |
Right ventricular hypertrophy (n, %) | 20, 74% | 36, 17% | <0.001* |
Right ventricular dysfunction (n, %) | 13, 42% | 11, 5% | <0.001* |
Ventricular Septal Defect – Mod/Lgt# (n, %) | 1, 4% | 2, 1% | 0.35 |
Left ventricular dysfunction (n, %)#
| 3, 9% | 16, 7% | 0.67 |
Multivariable model for the outcome of late PH
Variable | Odds ratio | 95% CI |
p-value |
---|---|---|---|
Overall multivariable model for the outcome of late PH | |||
Gestational age | 0.9 | 0.8–1.1 | 0.22 |
Atrial septal defect (ASD vs. None) | 2.9 | 1.4–6.1 | <0.01* |
Growth restriction | 2.7 | 1.2–6.3 | 0.02* |
Caffeine | 0.4 | 0.2–0.8 | 0.01* |
Positive-pressure ventilation | 1.5 | 0.8–2.9 | 0.16 |
Multivariable model for the outcome of late PH, among infants with multiple studies | |||
Gestational age | 0.9 | 0.7–1.1 | 0.18 |
Atrial septal defect (ASD vs. None) | 5.9 | 2.0–16.5 | <0.001* |
Growth restriction | 3.7 | 1.3–10.7 | 0.01* |
Caffeine | 0.8 | 0.3–1.8 | 0.53 |
Positive-pressure ventilation | 1.4 | 0.6–3.3 | 0.38 |