The outcome of isolated prenatal
ventricular size disproportion in the
absence of aortic coarctation
Outcome non-CoA cases
A.E.L van Nisselrooij#, L. Rozendaal†, I. Linskens*, S.A. Clur‡, J. Hruda‖, E. Pajkrt§, C.L. van Velzen*, N.A. Blom†, M.C. Haak#
# Department of Obstetrics and Fetal Medicine, Leiden University Medical Center, Leiden * Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam † Department of Pediatric Cardiology, Leiden University Medical Center, Leiden
‡ Department of Pediatric Cardiology, Emma Children’s Hospital, Academic Medical Center, Amsterdam § Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam
‖ Department of Pediatric Cardiology, VU University Medical Center, Amsterdam
Corresponding author: A.E.L. van Nisselrooij
Abstract
Objectives
Ventricular size disproportion is a marker for aortic coarctation (CoA) in fetal life, however
approximately 50% of fetuses do not develop CoA after birth. The aim of this study was to evaluate the postnatal outcome of cases with ventricular disproportion in the absence of CoA in this cohort.
Methods
All cases with prenatal isolated ventricular size disproportion in the period 2002-2015 were extracted from a prenatal congenital heart defects (CHD) registry of a regional cohort. Cases were assigned to a group without aortic arch anomalies (non-CoA) or to the group with CoA (CoA). Postnatal outcome of non-CoA cases was evaluated by assessing the presence of cardiac and other congenital malformations, genetic syndromes and other morbidity after birth. Non-CoA cases were subdivided in a group without morbidity (uncomplicated) and a group with pathology with moderate morbidity and/or conditions requiring follow-up visits beyond the age of 2 (moderate morbidity) and a group with severe morbidity, that comprised cases with multiple organ pathology, genetic syndromes or severe prenatally undetected congenital heart defects requiring surgery within the first year of life (severe morbidity).
Results
Conclusions
Introduction
Aortic coarctation (CoA) accounts for approximately 4-6% of all congenital heart defects and frequently requires surgery in the first year of life.1,2 A prenatal diagnosis of CoA is beneficial as timely management with prostaglandins after birth prevents clinical deterioration of the neonate before surgery, resulting in less mortality.3 Ventricular disproportion on fetal ultrasound, with a smaller left ventricle compared to the right ventricle, is known to be a predictor of CoA.4 Prenatal diagnosis of CoA remains, however, challenging given the moderate sensitivity and low specificity of this ultrasonographic sign. The low specificity can be attributed to the difficulty to differentiate between physiological enlargement of the right ventricle and pathological ventricular size disproportion.4-6
Over the past decade most studies have focussed on the improvement of the prenatal detection of CoA.6-9 Despite a false-positive rate of around 50% for the finding of fetal ventricular size
disproportion10,11, hardly any studies have assessed the postnatal course and long-term outcome of fetuses in whom aortic surgery was not required.
Methods
The three tertiary care centers Leiden University Medical Center, VU Medical Center and Academic Medical Center collaborate in the care for children with congenital heart defects (Center for Congenital Heart Defects Amsterdam Leiden, CAHAL). This area covers approximately 40% of all live births in the Netherlands, equal to 72 000 infants per year. Since 2002 all fetuses and infants diagnosed in CAHAL with a severe congenital heart defect (CHD) are registered. A severe CHD is defined as cases born with a CHD requiring a therapeutic cardiac intervention or cardiac surgery in the first year of life. The
prevalence of severe congenital heart defects in this registry is 2,0 per 1000 live births, which
corresponds with the generally accepted prevalence of severe CHDs.1,2 Data collection for this CAHAL regional cohort registry has been described before.5 All cases with fetal ventricular size disproportion, diagnosed between 2002 and 2015, were extracted from this cohort. In this study, cases diagnosed with ventricular size disproportion were included if parents were counselled about the possibility that the neonate might develop a CoA after birth and if subsequent postnatal intensive care admission to monitor ductal closure was initiated, as systematic measurements of the AV valves and ventricle size were not measured routinely in the early years of this cohort. We only included cases with isolated ventricular size disproportion, thus no other antenatal detected cardiac or non-cardiac defects were present. Cases with ventricular disproportion with persistent left superior vena cava (PLSVC) were included if it was decided prenatally to admit the neonate for ductal closure monitoring.10 Cases born before 36 weeks’ gestational age were excluded, as a distinction between morbidity due to prematurity and morbidity due to ventricular disproportion is difficult to make in these cases.
with severe morbidity. Cases with an uncomplicated course were not diagnosed with conditions that needed follow-up visits beyond the age of 2. Moderate morbidity was defined as the presence of a congenital defect or condition requiring follow-up visits beyond the age of 2, whereas the severe morbidity group comprised cases with multiple organ pathology, genetic syndromes or severe congenital heart defects requiring surgery within the first year of life, which were not detected prenatally.
Pediatric charts were assessed to retrieve data on postnatal outcome. We assessed baseline
characteristics such as age and sex in both the non-CoA and CoA group. To evaluate the outcome in the non-CoA group in particular, we assessed the postnatal presence of cardiac and extra-cardiac
(congenital) malformations, syndromes or other chromosomal anomalies, drug use, the number of interventions, number of admissions to the hospital, the presence of neonatal pulmonary hypertension in the first year of life. Pulmonary hypertension (PH) was defined as failure of the normal postnatal decline of pulmonary vascular resistance that may be associated with oxygenation failure or right ventricular dysfunction. The severity of the PH was based on the clinical impact and duration of the PH. PH was considered to be clinically relevant if infants received respiratory support, vasodilators or diuretics. The duration of PH was either scored as self-limiting (<=6 weeks) or persistent (>6 weeks). If PH developed in a later stage as the consequence of a cardiac malformation, rather than as a result of alterations in hemodynamics during transition, it was scored 0. The following grading system for PH was used: 0 = the absence of signs for PH; 1 = subclinical PH, self-limiting; 2 = subclinical PH, persistent (>6wks); 3 = clinical PH, self-limiting; 4 = clinical PH, persistent (>6wks).
Results
Between 1 January 2002 and 31 December 2015, 100 women were referred to one of the three centers because of a prenatally diagnosed ventricular left-right disproportion. Additional cardiac and non-cardiac abnormalities were present in 11 cases (non-isolated), disproportion normalized during pregnancy in 8 cases and a premature birth (<36 weeks) occurred in 4 cases. Thus, 23 cases were excluded, leaving 77 cases available for analysis (Figure 1).
CoA and non-CoA combined
All 77 cases with isolated prenatal ventricular size disproportion were initially admitted to the neonatal ward for observation upon ductal closure. Forty-six cases (60%) did not develop an aortic arch anomaly that required surgery (non-CoA group), whereas 31 cases (40%) required surgical intervention for aortic arch anomalies (CoA group). The prenatal presence of the findings PLSVC (12/77, 16%) and restricted or closed foramen ovale (9/77, 12%) did not differ significantly between both groups, as shown in Table 1. A significant difference was encountered in the incidence of postnatally diagnosed bicuspid aortic valve between the non-CoA (3/46, 7%) and CoA group (10/31, 32%), resulting in an odds ratio of 6,8 for CoA in the presence of a bicuspid aortic valve.
Non-CoA group
Non-CoA: Absent or mild morbidity
In the non-CoA group, 27 cases were allocated to the absent or mild morbidity group, of which 17 did not have structural cardiac anomalies (17 of all 46 non-CoA; 37%). The 10 cases with minor cardiac abnormalities were also allocated to this group, because of the absent need for long-term follow up (3 PLSVC, 1 small ventricular septal defect (VSD) together with PLSVC, 1 atrial septal defect type 2 (ASD-II) and 5 other anomalies, Table 2). All cases with PLSVC were prenatally identified.
hospital. Follow-up visits are ongoing in 4 under the age of 2 years and 23 cases did not have follow-up visits planned after the second year of life.
Non-CoA: Moderate morbidity
In the non-CoA group, 9 were allocated to moderate morbidity, comprising of 5 cases with minor cardiac abnormalities that were not detected on the prenatal scans (valve abnormalities such as a bicuspid or asymmetric aortic valve and a dysplastic pulmonary valve; Table 3) and 4 cases with miscellaneous pathology. Four cases received diuretics for the treatment of PH or (transient) increased left atrial pressure because of a borderline left ventricle. In this subcategory the mean duration of initial hospital admissions was 12 days, varying from a hospital stay of 2 to 37 days, and 8 readmissions occurred. Non-CoA: Severe morbidity
The description of the 10 cases with severe morbidity is outlined in Table 4. Five cases required cardiac surgery, including surgical correction of a total (TAPVR) or partial anomalous pulmonary venous return (PAPVR), aortic valve stenosis, mitral valve stenosis and multiple VSDs. Seven of these cases received medication, including ACE-inhibitors, diuretics and anticoagulants because of renal vein and sagittal sinus thrombi. The mean duration of initial hospital admission in this group was 37 days, varying from 2 to 189 days, and 21 readmissions occurred.
Combined pathology of the non-CoA cases
Genetic or syndromic features were seen in 4/46 cases; 1 case with Down syndrome (1/46), and 3 cases with dysmorphic features (3/46). Overall, 43% of all non-CoA children were still under surveillance at the end of the study period (December 2015).
Pulmonary hypertension
Discussion
This study shows that the prenatal counseling in cardiac left-right ventricular disproportion should include information regarding the significant risk of additional pathology, as 41% of the non-CoA group was diagnosed with undetected cardiac defects, genetic syndromes and other pathology. Previous studies mainly focus on the improvement of the identification of cases that require aortic arch surgery. 6-9,13-16
We encountered a relatively high incidence of prenatally undetected congenital malformations (22% severe, 20% moderate) amongst cases without CoA, which mainly comprised of cardiac defects. The association of left-right disproportion with both cardiac and extra-cardiac pathology has been reported before by Hornung et al.17 and Axt-Friedner et al.18, who found a considerable incidence of other CHDs, such as VSD, PLSVC and pulmonary or aortic valve stenosis, non-cardiac anomalies and chromosomal diseases in these patients. These studies, however, included both isolated and non-isolated cases with ventricular size disproportion, resulting in a considerably higher incidence of severe cardiac and extra-cardiac pathology, genetic syndromes and a correspondingly higher termination and mortality rate, compared to our findings. The presented frequency and severity of (additional) pathology encountered in this cohort, reports on the incidence of pathology amongst prenatally isolated cases only.
and tricuspid valve dysplasia, which are all known to be difficult to diagnose in the prenatal period or may be progressive with advancing gestation, but can have long-term consequences. Furthermore, this cohort showed that a prematurely closed or restrictive foramen ovale or PLSVC was found more often in non-CoA compared to CoA cases. A bicuspid aortic valve occurred in 32% of the CoA compared to 7% of the non-CoA group, which is in accordance with the known association between bicuspid aortic valve and aortic coarctation.4,15,19
Pulmonary pathology in general was also frequently encountered, varying from the need for respiratory support in the neonatal period to long-term obstructive lung disease. Respiratory support was needed in 30% of all non-CoA cases, including cases without a condition requiring long-term follow-up.
Furthermore 9% had long-term respiratory tract pathology, such as obstructive lung disease. PH in the neonatal period was present in 24% of all non-CoA cases, which did not have further clinical
consequences (11%) or clinical follow-up longer than 6 weeks (9%), leaving 4% with persistent PH receiving respiratory support or vasodilators in combination with diuretics. Even though the majority of infants were discharged from the hospital within 2 weeks, only 41% (of the non-CoA group) did not need any postnatal support or other clinical interventions during the neonatal observation. It is therefore recommended to alert parents of potential transition problems and the occurrence of other minor or major defects already in the prenatal counseling, as they may experience the transient need for pulmonary support to be a very stressful event.
the pulmonary vascular development during fetal life, potentially causing both short-term, in the transition phase from fetus to newborn, and long-term effects. This theory is supported by the rare situation in which a premature closed or restricted foramen ovale causes idiopathic pulmonary hypertension. 20,21 Uterine closure of this fetal shunt, results in a pulmonary overflow, which causes remodeling of pulmonary vasculature with vascular wall thickening and smooth muscle hypoplasia.22 Fetal ventricular disproportion also reflects an imbalance in pulmonary and aortic flow, possibly leading to comparable, but less severe symptoms. This hypothesis might explain the high percentage (33% of the non-CoA group) of pulmonary pathology and clinically relevant PH (13% of the non-CoA group) in this cohort, compared to a prevalence of 1,9 PPHN cases per 1000 live births.23,25
Finally, 35% of all cases with prenatal ventricular size disproportion had an uncomplicated course after observation without moderate to severe additional morbidity or follow-up visits beyond the second year of life. In this series, prenatal ventricular size disproportion, known to precede a postnatal diagnosis of CoA27, did not result in a coarctation after ductal closure in 60%. This false-positive rate of ventricular disproportion for CoA in this cohort is consistent with previous publications, reporting rates from 33% up to 65%. The range can be explained by the subjectivity of the finding and differences in in- and exclusion criteria.7,14,25-27 A limitation of this study was the lack of specific measurements, such as isthmus and ductal diameter, to calculate ratios or z-scores and define cases suspected for CoA more objectively. Alarge prospective cohort study, including the outcome of non-CoA cases, based on specific measurements, may be beneficial to support these findings with additional details.
References
1. Samánek M, Slavík Z, Zborilová B, Hrobonová V, Vorísková M, Skovránek J. Prevalence, treatment, and outcome of heart disease in live-born children: A prospective analysis of 91,823 live-born children. Pediatr
Cardiol 1989; 10 : 205-211.
2. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39 : 1890-900.
3. Franklin O, Burch M, Manning N, Sleeman K, Gould S, Archer N. Prenatal diagnosis of coarctation of the aorta improves survival and reduces morbidity. Heart 2002; 87 : 67–69.
4. Matsui H, Mellander M, Roughton M, Jicinska H, Gardiner HM. Morphological and physiological predictors of fetal aortic coarctation. Circulation 2008; 118 : 1793–1801.
5. van Velzen CL, Clur SA, Rijlaarsdam MEB, Bax CJ, Pajkrt E, Heymans MW, Bekker MN, Hruda J, de Groot CJM, Blom NA, Haak MC. Prenatal detection of congenital heart disease—results of a national screening programme. BJOG 2016; 123 : 400–407.
6. Buyens A, Gyselaers W, Coumans A, Al Nasiry S, Willekes C, Boshoff D, Frijns JP, Witters I.Difficult prenatal diagnosis: fetal coarctation. Facts Views Vis Obgyn 2012; 4 : 230–236.
7. Gabbay-Benziv R, Cetinkaya Demir B, Crimmins S, Esin S, Turan OM, Turan S. Retrospective case series examining the clinical significance of subjective fetal cardiac ventricular disproportion. Int J Gynaecol
Obstet 2016; 135 :28-32.
8. Quarello E, Stos B, Fermont L. Diagnostic prénatal dese coarctations de l’aorte. Gynecol Obstet Fertil 2011;
39 : 442–453.
9. Quartermain MD, Cohen MS, Dominguez TE, Tian Z, Donaghue DD, Rychik J. Left ventricle to right ventricle size discrepancy in the fetus: the presence of critical congenital heart disease can be reliably predicted. J Am Soc Echocardiogr 2009; 22 : 1296–1301.
10. Gómez-Montes E, Herraiz I, Mendoza A, Escribano D, Galindo A. Prediction of coarctation of the aorta in the second half of pregnancy. Ultrasound Obstet Gynecol 2013; 41 :298-305.
11. Weber RW, Ayala-Arnez R, Atiyah M, Etoom Y, Manlhiot C, McCrindle BW, Hickey EJ, Jaeggi ET, Nield LE. Foetal echocardiographic assessment of borderline small left ventricles can predict the need for postnatal intervention. Cardiol Young 2013 Feb; 23 : 99-107.
12. Pasquini L, Fichera A, Tan T, Ho SY, Gardiner H. Left superior caval vein: a powerful indicator of fetal coarctation. Heart 2005; 91 : 539-540.
13. Brown DL, Durfee SM, Hornberger LK. Ventricular discrepancy as a sonographic sign of coarctation of the fetal aorta: how reliable is it? J Ultrasound Med 1997; 16 : 95-9.
14. Allan LD, Chita SK, Anderson RH, Fagg N, Crawford DC, Tynan MJ. Coarctation of the aorta in prenatal life: an echocardiographic, anatomical, and functional study. Br Heart J 1988; 59 : 356-360.
15. Sivanandam S, Nyholm J, Wey A, Bass JL. Right Ventricular Enlargement In Utero: Is It Coarctation? Pediatr
Cardiol 2015; 36 : 1376-81.
16. Benacerraf BR1, Saltzman DH, Sanders SP. Sonographic sign suggesting the prenatal diagnosis of coarctation of the aorta. J Ultrasound Med 1989; 8 : 65-9.
17. Hornung TS, Heads A, Hunter AS. Right ventricular dilatation in the fetus: a study of associated features and outcome. Pediatr Cardiol 2001; 22 : 215-217.
18. Axt-Fliedner R, Hartge D, Krapp M, Berg C, Geipel A, Koester S, Noack F, Germer U, Gembruch U. Course and outcome of fetuses suspected of having coarctation of the aorta during gestation.
Ultraschall Med 2009; 30 : 269-276.
19. Durand I, Deverriere G, Thill C, Lety AS, Parrod C, David N, Barre E, Hazelzet T. Prenatal Detection of Coarctation of the Aorta in a Non-selected Population: A Prospective Analysis of 10 Years of Experience.
Pediatr Cardiol 2015; 36 : 1248-54.
20. Alano MA, Ngougmna E, Ostrea EM, Jr., Konduri GG. Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. Pediatrics 2001; 107 :
21. Levin DL, Mills LJ, Parkey M, Garriott J, Campbell W. Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe. J Pediatr 1979; 94 : 647–650.
22. Robin H Steinhorn, MD and Kathryn N Farrow, MD, PhD. Pulmonary hypertension in the neonate.
NeoReviews 2007; 8 : e14-e21.
23. Steurer MA, Jelliffe-Pawlowski LL, Baer RJ, Partridge JC, Rogers EE, Keller RL. Persistent Pulmonary Hypertension of the Newborn in Late Preterm and Term Infants in California. Pediatrics 2017; 139 :
e20161165.
24. Walsh-Sukys MC1, Tyson JE, Wright LL, Bauer CR, Korones SB, Stevenson DK, Verter J, Stoll BJ, Lemons JA, Papile LA, Shankaran S, Donovan EF, Oh W, Ehrenkranz RA, Fanaroff AA. Persistent pulmonary
hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 2000; 105 : 14-20.
25. Allan LD, Hornberger L, Sharland G. Textbook of Fetal Cardiology. Cambridge: Cambridge University Press; 2000. p. 596.
26. Head CE, Jowett VC, Sharland GK, Simpson JM. Timing of presentation and postnatal outcome of infants suspected of having coarctation of the aorta during fetal life. Heart 2005; 91 : 1070-1074.
Attachments
Conflict of interest
Tables
Table 1. Descriptives
Non-CoA CoA P (95% CI) OR (95% CI)
Numbers 46 (59,7) 31 (40,3) Sex, male 26 (56,5) 18 (58,0) 0,89 Age (yrs)# Mean 4,9 4,7 0,82 (-1,95;1,54) Median 4,2 2,8 Range 0,3-12,0 0,3-14,3 Additional prenatal findings Prematurely restricted or closed FO 6 (13,0) 3 (9,7) 0,65 0,74 (0,17;3,10) PLSVC 9 (19,6) 4 (12,9) 0,44 0,61 (0,17;2,19) Additional postnatal findings
Bicuspid aortic valve 3 (6,5) 10 (32,3) 0,003* 6,8 (1,7;27,5)
Data are given as n (%) or n. * p-value <0,05
#Age is given at time of the end of study period (December 2015)
Non-CoA: group without aortic arch anomalies pp, CoA: group with aortic arch anomalies pp, FO: foramen ovale, PLSVC: persistent left superior vena cava.
Table 2. Clinical outcome non-CoA – uncomplicated cases (n=27)
Diagnosis Hospital visits
No structural abnormalities 17 Number of admissions
PLSVC 3 Total 27#
VSD/PLSVC* 1
ASD-II 1 Postnatal duration of
admission (days)
Other
Narrow aortic arch † 1 Mean 4,9 [1-10]
Collateral vein/Coronary fistula 1 Total 131
Pulmonary vein stenosis 1
Bicuspid pulmonary valve 1
Pulmonary sequestration 1 Follow-up visits
PH Yes
Grade 0 24 Age ≤ 1 year 3
Grade 1 2 Age ≤ 2 years 1
Grade 2 0 No
Grade 3 1 Age ≤ 1 year 20
Grade 4 0 Age > 1 years - ≤ 2 years 3
Treatment
Postnatal respiratory support 8
Data are given as n or n [range] * spontaneously closure VSD
† narrow but not leading to clinical interventions
# no additional hospital admissions were reported after the observational period
Pulmonary hypertension (PH) was graded as stated before. Clinical is defined as desaturation requiring respiratory support, vasodilators or other drugs supporting cardiac function. Subclinical is defined as the absence of desaturation requiring treatment
Age is given at time of the end of study period (December 2015)
Abbreviations: ASDII atrial septal defect type II, PLSVC persistent left superior vena cava, VSD ventricular septal defect.
Table 3. Clinical outcome non-CoA - moderate morbidity (n=9)
Nr. PH Diagnosis Treatment Hospital visits
Adm.
(n) (days) Stay Follow-up Last visit 1 0 Asymmetric Aortic valve, ASDII Follow-up visits only 2 12 Yes yrs. 9
2 0 Bicuspid aortic valve, asthma Salbutamol,
fluticasone 2 4 Yes
7 yrs.
3 0 Bicuspid aortic valve with stable CoA Follow-up visits only 1 9 Yes mo. 9
4 0 Borderline LV with transient high LA pressure, normalized
within 2 months Diuretics 1 20 Yes
3 yrs.
5 1 Dysplastic tricuspid valve, TI and WPW Syndrome Catheter ablation 3 12 Yes yrs. 9
6 3 Isolated increased pulmonary pressure, hearing loss
Respiratory support,
diuretics 2 16 No yrs. 6
7 1 Isolated increased pulmonary pressure Diuretics 1 6 No yrs. 5
8 2
Obstructive lung disease with increased pulmonary pressure, syndactyly, undergrowth digit IV, VSD, ASDII
Surgical correction syndactyly and excision digit (II) Salbutamol, fluticasone
4 46 No yrs. 6
9 0 Bicuspid aortic valve, ASDII, humeral exostosis, small
head circumference (p2) Follow-up visits only 1 2 Yes
4 yrs.
Pulmonary hypertension (PH) was graded as stated before. Admissions (Adm.) is the total number of admissions to the hospital, Stay is the total number of days in the hospital including all admissions Last visit is the age at time of last follow-up visit given in months (mo.) or years (yrs.).
Abbreviations: LV left ventricle, LA left atrium, ASDII atrial septal defect type II, CoA aortic coarctation, VSD ventricular septal defect, PLSVC persistent left superior vena cava, WPW syndrome
Wolff-Parkinson-White Syndrome, TI tricuspid valve insufficiency.
Table 4. Clinical outcome non-CoA - severe morbidity (n=10)
Nr PH Diagnosis Treatment Hospital visits
Adm.
(n) (days) Stay Follow-up Last visit 1 3 TAPVR Intubation, surgical correction TAPVR and ASDII 2 39 Yes mo. 6
2 4 PAPVR, VSD Surgical correction PAPVR, ASD, VSDs, sildenafil, diuretics 1 47 Yes 3 yrs.
3 0 NCCM Heparine, enalapril, carvedilol, salbutamol 6 51 Yes 2 yrs.
4 0
Aortic valve stenosis, cardiac failure due to post-intervention aortic insufficiency
Balloon valvuloplasty, Ross procedure
Elanapril, diuretics 4 65 Yes 1 yr.
5 0* Mitral valve stenosis Mitral valve replacement, pacemaker implantation,
diuretics 4 87 Yes mo. 8 6 0* Multiple VSDs, persistent and recurrent vomiting, growth deficiency
Pulmonary artery banding Sildenafil, diuretics
Enteral tube feeding 4 76 Yes
4 mo. 7 4 Pulmonary hypertension, cor pulmonale, severe AITP and AIN
Diagnostic heart catheterization (NO)
Oxygen, bosentan, sildenafil, IVIG, filgrastim
2 190 Yes mo. 10
8 3 Down syndrome, pulmonary valve stenosis.
Postnatal respiratory support
Enteral tube feeding 1 24 Yes 5 yrs.
9 0 Genetic syndrome not specified, ASDII Follow-up visits only 2 11 No 1 yr.
10 0
RVT and CVST, Transient brachial plexus lesion,
Hypertension, Hearing loss, Delayed language development
Postnatal respiratory support Nephrectomy left kidney Tinzaparine, Elanapril Special educational needs
Pulmonary hypertension (PH) was graded as stated before: 0* = PH was not present in neonatal phase, but occurred at a later stage as a result of cardiac morbidity
Admissions (Adm.) is the total number of admissions to the hospital, Stay is the total number of days in the hospital all admissions included. Last visit is the age at time of last follow-up visit given in months (mo.) or years (yrs.).
Abbreviations: TAPVR total anomalous pulmonary venous return, PAPVR partial anomalous pulmonary venous return, NCCM non-compaction cardiomyopathy, VSD ventricular septal defect, AITP
autoimmune thrombocytopenia, AIN autoimmune neutropenia, RVT renal vein thrombosis, CVST cerebral venous sinus thrombosis, ASD atrial septal defect.
NO nitric oxide, IVIG Intravenous immunoglobulin
Legends for illustrations
Figure 1: Proportions mentioned are based on all included cases with isolated prenatal ventricular size
