Introduction
Patients and Methods
Case no. | Prenatal diagnoses | Gestational age, weight, length, and body surface area at delivery | Gestational age at start of maternal HO and days of HO before delivery | Left ventricular area (cm2/Z-score) | Mitral valve diameter (mm & Z-score) | Aortic valve diameter (mm & Z-score) | Ascending aorta diameter (mm & Z-score) | Isthmus diameter (mm & Z-score) | Doppler flow findings of interest | Postnatal diagnosis and treatment |
---|---|---|---|---|---|---|---|---|---|---|
Before HO | Before HO | Before HO | Before HO | Before HO | ||||||
First day of HO | First day of HO | First day of HO | First day of HO | First day of HO | ||||||
Last 1–2 days of HO | Last 1–2 days of HO | Last 1–2 days of HO | Last 1–2 days of HO | Last 1–2 days of HO | ||||||
First day of life | First day of life | First day of life | First day of life | First day of life | ||||||
1 | Left ventricular hypoplasia, mitral and aortic valve hypoplasia, tubular aortic arch hypoplasia | 39 + 6 w & d | 38 + 0 w & d | 2.4/−2.1 | 8/−3.1 | 4.4/−3.1 | 4/−4.6 | 2.3/−4.9 | Before and at end of HO, bidirectional Doppler flow pattern in aortic isthmus with larger retrograde flow portion; postnatally antegrade flow | Aortic isthmus shelf, tubular aortic arch hypoplasia |
3.1 kg | 13 | 2/−2.5 | 9/−2.2 | 4.7/−2.6 | 4.8/−3.4 | 2.9/−3.5 | Discharged home without surgery on day 5 | |||
50 cm | 3.4/−1.3 | 12/−0.4 | 6.5/−0.5 | 6.5/−1.5 | 3.5/−2.7 | |||||
0.21 m2
| 3.1/−1.6 | 10/−1.8 | 6.6/−0.4 | 6.2/−1.8 | 3.5/−2.7 | |||||
2 | Left ventricular hypoplasia, aortic valve stenosis, mitral valve hypoplasia, severe tubular aortic arch hypoplasia, ductus venosus agenesis | 38 + 5 w & d | 37 + 4 w & d | 1.1/−4 | 5.5/−5.8 | 3.9/−4 | 3.9/−4.7 | 1.8/−6.2 | Retrograde continuous coarctation–like aortic isthmus; Doppler flow signal (systolic maximum velocity 190 cm/s) at start of therapy | Left ventricular hypoplasia, moderate mitral valve hypoplasia, restrictive subaortic ventricular septal defect, aortic valve stenosis, severe tubular hypoplasia of aortic arch distal to truncus brachiocephalicus |
2.5 kg | 9 | 1.35/−3.5 | 7/−4 | 4.2/−3.3 | 4.9/−3 | No reliable measurement | ||||
45 cm | 2.5 cm2/−2.1 | 9/−2.4 | 5.7/−1.3 | 6.2/−1.5 | 2.8/−3.8 | Single–step biventricular repair with aortic arch patch reconstruction at day 13 | ||||
0.16 m2
| 2.5 cm2/−2.1 | 7.5/−3.7 | 5.5/−1.5 | 6/–1.8 | 2.4/−4.7 | Demasking of aortic valve stenosis by hyperoxygenation; maximum systolic velocity 70 cm/s before oxygen; ≤220 cm/s on oxygen | Further procedures during year 1 were required to achieve biventricular circulation: aortic valvuloplasty, aortic vavulotomy, Ross-Konno procedure | |||
3 | Left ventricular hypoplasia, mitral valve hypoplasia, dynamic left ventricular outflow tract obstruction (165 cm/s), ventricular septal defect, shelf and abnormal flow at aortic isthmus | 39 + 3 w & d | 37 + 1 w & d | 2.3 cm2/−2.1 | 7/−3.9 | 5.4/−1.3 | 5.2/−2.4 | 3.9/−1.5 | Antegrade flow with systolic maximum velocity 219 cm/s at aortic isthmus at beginning of therapy, which decreased to 170 cm/s by end of therapy | Normal left ventricle, moderate subaortic ventricular septal defect covered by tricuspid valve tissue, aortic isthmus shelf |
4.15 kg | 13 | 2.9 cm2/−1.2 | 8/−2.9 | 4.6/−2.5 | 5.2/−2.4 | 4.3/−0.9 | Discharged home without surgery on day 13 | |||
53.2 cm | 3.5 cm2/−0.8 | 10/−1.6 | 6/−0.9 | 6.7/−1 | 4/−1.7 | Coarctation repair by end-to-end anastomosis, ventricular septal defect closure at 3 months | ||||
0.24 m2
| 4.0 cm2/−.5 | 11/−0.9 | 6/−0.9 | 6/−1.8 | 5/−0.3 | |||||
4 | Left ventricular hypoplasia, apical ventricular septal defect with bidirectional shunt, posterior malalignment ventricular septal defect, tubular arch hypoplasia | 37 + 6 w & d | 35 + 3 w & d | 1.7 cm2/−2.7 | 6/−4.6 | 4/−3.1 | 5.3/−1.9 | 1.8/−5.8 | Antegrade flow with systolic maximum velocity 60 cm/s in aortic isthmus at beginning of therapy and similar velocity at end of therapy and after delivery | Moderate left ventricular hypoplasia, unrestrictive 4-mm ventricular septal defect with bidirectional shunt, 3-mm subaortic posterior malalignment ventricular septal defect, severe tubular arch hypoplasia at 37 + 1 weeks gestation |
1.77 kg | 14 | 1.6 cm2/−2.7 | 6.2/−4.4 | 4.2/−2.8 | 5.7/−1.3 | 2.4/−4.1 | ||||
43 cm | 2 cm2/−2.5 | 9/−2.1 | 5.4/−1.3 | 5.6/−2 | 2.2/−5 | Failed biventricular repair after aortic arch patch reconstruction; pulmonary artery banding; died at univentricular palliation attempt | ||||
0.11 m2
| 1.9 cm2/−2.5 | 8/−3 | 5.3/−1.5 | 5.2/−2.5 | 2.3/−4.7 | |||||
5 | Aortic valve hypoplasia, 2.5-mm subaortic ventricular septal defect with left-to- right shunt, tubular aortic arch hypoplasia | 40 + 0 w & d | 37 + 3 w & d | 2.9 cm2/−1.4 | 10/−1.3 | 4.5/−2.8 | 6.7/−0.6 | 2.9/−3.3 | Predominantly antegrade flow with systolic maximum velocity 150 cm/s in aortic isthmus at beginning of therapy, which decreased to 117 cm/s by end of therapy; 161 cm/s after delivery | Normal left ventricle, significant dysproportion between smaller left and much larger right ventricle, 2.5-mm subaortic ventricular septal defect with left-to-right shunt, aortic arch shelf with flow disturbance and increased velocity |
4.66 kg | 11 | 3.5 cm2/−0.6 | 10.5/−0.9 | 5.9/−0.7 | 7.9/0.6 | 3.8/−1.7 | Discharged home without surgery on day 13 | |||
56.5 cm | 3.4 cm2/−1 | 11/−0.9 | 7/0.3 | 8.8/1 | 5.5/0.2 | |||||
0.25 m2
| 3.7 cm2/−0.9 | 10/−1.6 | 7.3/0.6 | 8/0.3 | 5.3/0 | |||||
6 | Left ventricular hypoplasia, 4-mm subaortic ventricular septal defect, left-to-right ventricular/length ratio 0.85, severe aortic arch hypoplasia/interrupted aortic arch | 39 + 0 w & d | 36 + 3 w & d | 2.1 cm2/−2.1 | 6.1/−4.8 | 5.4/−1.1 | 6.1/−1.1 | 1.9/−5.7 | Retrograde flow at beginning and end of therapy in aortic isthmus | Left ventricular hypoplasia, unrestrictive 4-mm subaortic and additional 3-mm apical ventricular septal defect, coarctation, atrial septal defect |
3.12 kg | 17 | 2.3 cm2/−1.7 | 7/−3.7 | 6/−0.3 | 6.3/−0.8 | 2.1/−5.1 | ||||
50 cm | 2.2 cm2/−2.5 | 9/−2.4 | 6.5/−0.3 | 6.5/−1.2 | 2.5/−4.5 | Systolic maximum velocity decreased from 150 to 70 cm/s during the course of therapy | Underwent coarctation and ventricular septal defect repair at day 5; no patch augmentation of moderately hypoplastic arch required | |||
0.2 m2
| 1.9 cm2/−2.7 | 11/−0.9 | 6/−0.9 | 6.5/−1.2 | 2.5/−4.5 | |||||
7 | Left ventricular hypoplasia, apex forming right ventricle, severe tubular aortic arch hypoplasia, left superior caval vein to coronary sinus, no bridging vein, ductus venosus agenesis | 38 + 3 w & d | 35 + 5 w & d | 1.1 cm2/−3.8 | 6.1/−4.6 | 3.8/−3.6 | 5.5/−1.7 | 2/−5.2 | Retrograde flow across aortic isthmus with systolic maximum velocity 60 cm/s at beginning of therapy | Severe left ventricular hypoplasia, 5-mm perimembranous ventricular septal defect, nonrestrictive atrial septal defect, severe tubular hypoplasia of aortic arch, left superior caval vein to coronary sinus, no bridging vein, ductus venosus agenesis, left superior caval vein deflects pulmonary venous flow by way of atrial septal defect toward right heart; coronary sinus largely obstructs left ventricular inflow |
4.08 kg | 19 | 1.2 cm2/−3.7 | 5.3/−5.7 | 3.7/−3.8 | 6.2/−0.8 | 2.7/−3.4 | ||||
53 cm | 1.3 cm2/−3.6 | 6/−5.4 | 3.7/−4.6 | 5.5/−2.4 | 2/−5.8 | No adequate insonation angle for isthmus flow measurement on last day of therapy; postnatally retrograde flow | Underwent univentricular palliation by Norwood procedure | |||
0.25 m2
| 1.2 cm2/−3.5 | 6/−5.4 | 4/−4.1 | 8/0.5 | 1/−10 | |||||
8 | Intrauterine growth retardation, moderate left ventricular hypoplasia, mitral valve hypoplasia, moderate tubular hypoplasia of aortic arch, increased arterial cerebral media flow | 36 + 0 w & d | 34 + 0 w & d | 1.4 cm2/−2.8 | 6.1/−4.2 | 4.7/−1.5 | 5.5/−1.2 | 1.9/−5.2 | Retrograde flow in aortic isthmus with systolic maximum velocity 150 cm/s before therapy | Intrauterine growth retardation, normally sized left ventricle, dilated right ventricle |
1.75 kg | 14 | 1.6 cm2/−2.5 | 6.4/−3.8 | 4.1/−2.6 | 5.9/−0.7 | 1.9/−5.2 | Mild tubular hypoplasia of aortic arch with distal narrowing | |||
41.5 cm | 2 cm2/−2a
| 6.8/−3.6a
| 6.4/0.6a
| 6.3/−0.5a
| 2.9/−2.9a
| Discharged home without surgery on day 13 | ||||
0.11 m2
| 2.3 cm2/−1.9 | 7.3/−3.1 | 6/−0.1 | 6.5/−0.2 | 3.1/−2.5 | No flow disturbance in isthmus region postnatally | ||||
9 | Mitral valve hypoplasia, aortic valve hypoplasia and stenosis, moderate tubular aortic arch hypoplasia, coarctation, ductus venosus agenesis | 36 + 3 w & d | 34 + 3 w & d | 2.3 cm2/−1.7 | 7/−3.2 | 4.3/−2.3 | 5/−2 | 3/−2.5 | Aortic isthmus at start of therapy with antegrade flow with systolic maximum velocity 220 cm/s, which decreased to 180 cm/s until end of therapy | Normal left ventricle, dilated right ventricle, aortic valve stenosis, bicuspid aortic valve, normal aortic arch dimensions, paraductal shelf and increased flow velocity at aortic isthmus, ductus venosus agenesis |
3.9 kg | 14 (therapy aborted early for preterm delivery because of uteroplacental insufficiency) | 2.7 cm2/−0.9 | 8/−2.2 | 4.6/−1.8 | 6.4/−0.2 | 3.5/−1.6 | At ductal closure, development of clinically significant coarctation at shelf site; underwent surgery on day 7; on inspection, normal arch dimensions before coarctation site | |||
52.5 cm | 3.2 cm2/−0.6 | 10.8/−0.4 | 5.7/−0.7 | 7.3/0.3 | 4.2/−0.9 | Antegrade flow with systolic maximum velocity 180 cm/s postnatally | ||||
0.21 m2
| 3.3 cm2/−0.5 | 11.0/−0.3 | 5.5/−0.9 | 7.1/0.1 | 4.3/−0.7 | |||||
10 | Mitral valve hypoplasia with subvalvar and valvar aortic stenosis (235 cm/s), apex forming right ventricle, tubular aortic arch hypoplasia, shelf at isthmus | 38 + 4 w & d | 35 + 5 w & d | 2.3 cm2/−1.8 | 6.7/−3.9 | 3.7/−3.8 | 5.3/−1.9 | 2.5/−3.9 | Aortic isthmus flow at start of therapy antegrade with systolic maximum velocity 170 cm/s, which decreased to 134 cm/s until end of HO | Bicuspid aortic valve (13 mm Hg gradient), left ventricular outflow narrowing, mitral valve hypoplasia, circumscript coarctation, distal arch before coarctation of normal dimension |
4.03 kg | 20 | 1.8 cm2/−2.5 | 7.7/−2.8 | 3.4/−4.5 | 5.3/−1.9 | 2.8/−3.2 | After isthmus stent insertion, relief of coarctation; temporary congestive heart failure and pulmonary hypertension from small mitral valve | |||
59 cm | 2.9 cm2/−1.8 | No adequate measurement | 5.5/−1.5 | 7.0/−0.6 | 4/−1.6 | |||||
0.26 m2
| 3.0 cm2/−1.7 | 7.4/−3.8 | 5.3/−1.8 | 7/−0.6 | 4/−1.6 | Systolic flow velocity across aortic valve decreased from 235 cm/s before start of therapy to 180 cm/s at end of HO; postnatally, maximum systolic flow velocity across aortic valve was 130 cm/s | Discharged home on day 25 | |||
11 | Left ventricular hypoplasia, aortic and mitral valve hypoplasia and stenoses, apex forming right ventricle (LV/RV ratio = 0.8), abnormal ductus venosus | 36.6 weeks & days | 35 + 5 weeks & days | 1.2 cm2/−3.3 | 5.6/−5.2 | 3.1/−5.2 | 4.3/−3.5 | 2.3/−4.4 | At beginning and end of therapy, retrograde coarctation-like Doppler flow signal in aortic isthmus with maximum velocity 241 cm/s | Hypoplastic left heart complex, apex forming right ventricle, mitral valve hypoplasia and stenosis (mean gradient 10 mm Hg), bicuspid aortic valve/aortic valve stenosis (170 cm/s), narrow left ventricular outflow tract, coarctation |
Baseline MV Doppler | 2.76 kg | 8 | 1.6 cm2/−2.9 | 6.9/−3.7 | 3.9/−3.4 | 4/−4 | 2.4/−4.1 | Flow pattern within isthmus did not change during therapy; antegrade flow (160 cm/s) after delivery | Stent insertion into aortic isthmus | |
Day 1: E 94/A 158 cm/s | 52 cm | HO aborted early because of progressive thinning of uterine wall due to previous cesarean sections | 1.9 cm2/−0.5 | 7/−3.8 | No reliable measurement | 5.4/−2.1 | 2.2/−4.9 | Discharged on day 18 | ||
Day 7: E 131/A 190 cm/s | 0.2 m2
| 2.0 cm2/−2.4 | 6.9/−4 | 4.2/−3.2 | 5/−2.7 | 2.3/−4.6 | ||||
12 | Left ventricular hypoplasia, hypoplastic aortic valve, coarctation, complete oval foramen closure | 38 + 1 w & d | 36 + 1 w & d | 2 cm2/– 2.3 | 8.9/−1.8 | 5.8/−0.6 | 6.1/−1 | 2.9/−3.1 | Across isthmus antegrade flow with systolic maximum velocity 175 cm/s at beginning of therapy | Postnatally normal-sized left ventricle, two shelves within aortic arch: one after origin of brachiocephalic trunc, one at isthmus |
3.43 kg | 14 | 2.4 cm2/−1.7 | 8.8/−1.9 | 5.7/−0.6 | 6.3/−0.7 | 3/−2.9 | Postnatally across proximal shelf at brachio-cephalic trunc origin 140 cm/s and across aortic isthmus 2 m/s systolic maximum velocity | Discharged without surgery after 21 days of hospitalization; (prolonged treatment and surveillance for kidney problem) | ||
50 cm | 2.7 cm2/−0.7 | 9.5/−1.8 | 6/−0.7 | 7.2/−0.3 | 4.2/−1.2 | |||||
0.22 m2
| 3.0 cm2/−0.5 | 8.9/−2.3 | 5.8/−1 | 6.0/−1.6 | 4.1/−1.4 | |||||
13 | Normal-sized left heart but abnormally high flow velocity and turbulent flow at aortic arch coarctation site | 40 + 5 w & d | 36 + 4 w & d | 3.2 cm2/−0.6 | 9/−1.9 | 5.9/−0.4 | 7.7/−0.6 | 3.6/−1.9 | Before therapy, turbulent flow into descending aorta from coarctation shelf site with 220 cm/s maximum systolic flow velocity | Postnatally normal-sized left heart structures, normal aortic arch dimensions, distal shelf |
3.78 kg | 18 | 3.0 cm2/−1 | 8.4/−2.4 | 6.1/−0.2 | 7/−0.1 | 4.3/−0.8 | ||||
55 cm | 3.5 cm2/−1 | 9/−2.7 | 6.9/−0.1 | 7.7/−0.2 | 5.7/0.3 | After delivery, turbulent flow across shelf site into descending aorta with maximum systolic flow velocity 162 cm/s | Discharged home without surgery on day 5 | |||
0.24 m2
| 4.0 cm2/−1 | 9.3/−2.4 | 6.9/−0.1 | 8.8/0.8 | 5.8/0.4 | |||||
14 | Anatomically corrected transposition of great arteries, unrestrictive muscular ventricular septal defect, severe hypoplasia of anatomic right ventricle and tricuspid valve | 39 + 2 w & d | 33 + 5 w & d | 1.35 cm2/−2.8 | 5.2/−5.7 | 7.4/2.2 | 7/0.7 | 3.7/−1.1 | Markedly improved visibility of and filling across tricuspid valve during treatment | Anatomically corrected transposition of great arteries; unrestrictive 6-mm muscular ventricular septal defect with exclusively right-to-left shunt; hypoplasia of anatomic right ventricle and tricuspid valve; normal aortic arch dimensions; atrial septal defect |
3.51 kg | 33 | 1.53 cm2/−2.2 | 5.7/−5 | No adequate measurement | 7.6/1.3 | 5.3/1.1 | ||||
51 cm | No adequate measurement | 9.4/−2.9 | 9/2.2 | 8.4/0.67 | No adequate measurement | |||||
0.22 m2
| 1.59 cm2/–3.8 | 9/−3.3 | 10/3 | 8.4/0.6 | 5.5/0.2 | |||||
15 | Fallot tetralogy with severe valvar and subvalvar pulmonary stenosis, right aortic arch, retrograde flow into central pulmonary arteries by way of small aortopulmonary collaterals | 39 + 6 w & d | 36 + 6 w & d | 2/−11.4c
| 5/−3.9d
| 2/−4.1e
| Systolic maximum velocity across right ventricular outflow tract and pulmonary valve 4 m/s | On day 1, right ventricular outflow tract and pulmonary vessels could not be demonstrated adequately by transthoracic imaging that even the diagnosis of pulmonary atresia is being considered. The prenatal diagnosis of Fallot tetralogy with patent pulmonary valve that could be dilatated with a 5-mm balloon is finally confirmed during cardiac catheterization on day 6 | ||
3.04 kg | 16 | 1.9/−11.8 | No adequate measurement | 2.1/−3.8 | Before therapy, low-flow velocities with little pulsatility in central pulmonary arteries; notably improved lung flow with higher flow velocity and pulsatility by end of therapy | Fallot tetralogy with valvar and subvalvar pulmonary stenosis, hypertrophy of ventricular septum, right aortic arch; retrograde flow into central pulmonary arteries by way of small aortopulmonary collaterals; hypoplastic branch pulmonary arteries saturation without supplemental oxygen 50–60% | ||||
48 cm | 5.2/−4.1 | 7.2/−1.54 | 3.5/−1.4 | Microdeletion 22q11.2 | ||||||
0.2 m2
| No adequate measurement | No adequate measurement | No adequate measurement | Surgery on day 11; ventilation and catecholamine dependant until then |
Informed Consent and Treatment Protocol
Measurements
Measurements provided as | Baseline/during HO | ||||
---|---|---|---|---|---|
(21% O2)/(maternal \( {\text{Fi}}_{{{\text{O}}_{ 2} }} \) 40–50%) | |||||
Case no. | MV-E (cm/s) | MV-A (cm/s) | AoV (cm/s) | Pulmonary vein (mean velocity [cm/s]) | Color Doppler (lung flow increase) |
1 | 40/50 | 55/53 | No data | 16/31 | ++ to +++ |
2 | 45/47 | 66/67 | 62/200 | 27/36 | + to +++ |
3 | 49/– | 43/72 | 165/123 | 24/* | + to ++ |
4 | 34/34 | 46/64 | 81/77 | 14/19 | + to ++ |
5 | 56/50 | 64/80 | 82/101 | 34/39 | ++ to +++ |
6 | 29/53 | 35/61 | 110/124 | 13/20 | + to ++ |
7 | 52/74 | 76/74 | 92/95 | 14/* | ++ to +++ |
8 | 56/42 | 49/33 | 85/73 | 24/37 | + to +++ |
9 | 46/b
| 61/b
| 206/234 | 21/b
| + to ++ |
10 | 60/66 | 81/78 | 235/216 | 29/29 | ++ to +++ |
11 | 94/b
| 158/166 | 91/110 | 22/22 | + to ++ |
12 | b/30 | b/73 | b/94 | 15/20 | + to ++ |
13 | 38/46 | 46/55 | 70/84 | b/b | + to ++ |
14 | 50/54 | 56/78 | 103/b
| 14/22 | + to ++ |
15 | No data | No data | No data | 18/25 | + to ++ |
Available pairs | 10/15 | 12/15 | 11/15 | 11/15 | 15/15 |
Flow increase | 7/10 | 8/12 | 7/11 | 9/11 | 15/15 |
Flow decrease | 2/10 | 4/12 | 4/11 | – | – |
No change | 1/10 | – | – | 2/10 | – |
p
| 0.16 | 0.05 | 0.32 | <0.0007 | <0.0001 |