Pulmonary outflow tract obstruction in fetuses with complex congenital heart disease: predicting the need for neonatal intervention

Authors


Correspondence to: Dr M. Quartermain, Fetal Heart Program at Wake Forest University School of Medicine, Winston-Salem, NC 27006, USA (e-mail: mquarter@wakehealth.edu)

ABSTRACT

Objective

To identify prenatal echocardiographic markers that could predict the need for neonatal intervention in fetuses with right ventricular outflow tract obstruction.

Methods

This was a retrospective study of 52 fetuses with right ventricular outflow tract obstruction. Echocardiograms were evaluated for fetuses with either two-ventricle anatomy with a large ventricular septal defect or single-ventricle anatomy. Fetuses with pulmonary atresia were excluded. Parameters were compared between groups that did and did not require an intervention at age < 30 days.

Results

Fifty-two fetuses were studied; 20 (38%) underwent neonatal intervention and 32 (62%) did not. The most common diagnosis was tetralogy of Fallot (n = 32). Fetuses with two ventricles that required an intervention had lower pulmonary valve diameter Z-score (PV-Z-score) (−4.8 ± 2.1 vs −2.6 ± 1.1; P = 0.0002) and lower pulmonary valve to aortic valve annular diameter ratio (PV/AoV) (0.53 ± 0.15 vs 0.66 ± 0.1; P = 0.003). Using a PV/AoV ratio of < 0.6 or a PV-Z-score of < −3 at final echocardiographic examination was highly sensitive (92%) but poorly specific (50%), whereas classifying direction of flow in the ductus arteriosus as either normal (all pulmonary-to-aorta) or abnormal (aorta-to-pulmonary or bidirectional) was both highly sensitive (100%) and specific (95%) for predicting the need for a neonatal intervention. Parameters for the single-ventricle cohort did not reach statistical significance.

Conclusions

Analysis of the pulmonary outflow tract and ductus arteriosus flow in the fetus with complex congenital heart disease can aid in identifying those that will require a neonatal intervention to augment pulmonary blood flow. This has important implications for the planning of delivery strategies.

INTRODUCTION

Accurate prenatal diagnosis has led to advances in perinatal care for the fetus with complex congenital heart disease (CHD). Several studies have demonstrated that a prenatal diagnosis of critical CHD allows for improved clinical status after birth[1, 2]. Pulmonary outflow tract obstruction is often present in the fetus with both single and two-ventricle forms of complex CHD. Fetuses with severe pulmonary outflow tract obstruction may develop significant cyanosis after birth and require urgent intervention. In these situations, an accurate assessment of the adequacy of the outflow tract by fetal echocardiography can help to determine whether there will be a need for prostaglandin infusion after birth to maintain ductal patency.

Previous studies have supported the role of fetal echocardiographic markers such as reversed shunting in the ductus arteriosus as predictive of severe right heart obstructive lesions[3-5]. The characteristics of two-dimensional, pulsed-wave and color Doppler findings of the ductus arteriosus in severe right heart lesions have been described[6]. Assessments of pulmonary artery growth in utero with attempts at prediction of the severity of postnatal outflow tract obstruction have been performed in fetuses with tetralogy of Fallot (TOF)[7, 8]. Despite these efforts, models for predicting critical pulmonary outflow tract obstruction do not exist. The goal of this study was to identify prenatal echocardiographic markers that would allow accurate prediction of which fetuses with complex CHD and pulmonary outflow tract obstruction will have ductal-dependent physiology after birth and require a neonatal intervention.

METHODS

Study patients

A review of the echocardiographic database from The Fetal Heart Program at The Children's Hospital of Philadelphia between July 2004 and January 2008 was performed to identify all fetuses referred for evaluation of pulmonary outflow tract obstruction in the setting of single-ventricle anatomy or two-ventricle anatomy with a large ventricular septal defect (e.g. TOF). Fetuses with at least one fetal echocardiogram, a postnatal transthoracic echocardiogram, survival to birth and documentation of neonatal clinical outcome were included. In order to isolate the degree of pulmonary outflow tract obstruction and its effects on postnatal cyanosis, we excluded patients with isolated valvar pulmonary stenosis with intact ventricular septum and other forms of CHD that could lead to postnatal cyanosis (e.g. transposition of the great arteries). Fetuses with pulmonary atresia documented on the first fetal echocardiogram were also excluded, as neonatal intervention is always needed in these patients. The study was approved by the Institutional Review Board at The Children's Hospital of Philadelphia (CHOP IRB # 09-007176).

All fetuses underwent examinations including two-dimensional echocardiography with color flow and spectral Doppler utilizing standard guidelines from the American Society of Echocardiography[9]. This included the four-chamber view and long- and short-axis images of the intracardiac anatomy and great vessels. Imaging of the ductus arteriosus was enhanced by utilizing a low Nyquist limit, and direction of flow was confirmed with pulsed-wave and color Doppler techniques. Images were obtained using a Siemens Acuson Sequoia ultrasound system (Mountain View, CA, USA) with appropriate transducers for the mother's body habitus and fetal gestational age. Measurements were made offline using Siemens Syngo Dynamics workstation (Ann Arbor, MI, USA) and were performed by a single worker (M.Q.) blinded to clinical outcome. Each parameter was measured three times and an average value recorded. Gestational age was determined from date of the last menstrual period. Interobserver variability was assessed between two independent investigators on 15 randomly selected datasets.

Two-dimensional echocardiographic measurements included pulmonary valve (PV) and aortic valve (AoV) annular diameters, subpulmonary valve (SubPV) region, main pulmonary artery (MPA) and branch pulmonary artery diameters. Measurements were made of the internal diameter of the identified structure in systole with the semilunar valve open. Both short- and long-axis views were utilized and measurements were made from the view that provided the clearest internal diameter of the structure based on fetal position. Z-score transformation was performed for structures with published normal values as previously described[10]. Color and pulsed-Doppler echocardiography were used to assess the peak velocity at the level of the pulmonary valve and the direction of flow across the ductus arteriosus. Ductal flow was designated as normal when all systolic and diastolic flow was from pulmonary artery to aorta. Flow was considered abnormal when there was either exclusive flow from aorta to pulmonary artery or bidirectional flow with reversal occurring in any phase of the cardiac cycle (Figures 1-3). As a means of assessing the degree of great-vessel disproportion, ratios of PV to AoV annular diameters were calculated.

Figure 1.

(a) Short-axis echocardiographic image of the right ventricular outflow tract in a fetus with tetralogy of Fallot showing normal flow (blue) across ductus arteriosus (DA) from pulmonary artery (PA) to aorta. (b) Pulsed-wave Doppler signal, showing continuous antegrade flow with high systolic and low diastolic velocity. DAo, descending aorta; R-L, right to left; RPA, right pulmonary artery; Sp, spine.

Figure 2.

(a) Aortic arch (Ao Arch) echocardiographic image in a fetus with severe tetralogy of Fallot showing abnormal flow (blue) across the ductus arteriosus (DA) from aorta to pulmonary artery. (b) Pulsed-wave Doppler signal, showing continuous flow with high systolic and very low diastolic velocity. DAo, descending aorta; L-R, left to right.

Figure 3.

Pulsed-wave Doppler signal in a fetus with complex single-ventricle anatomy and pulmonary stenosis, showing bidirectional flow with high systolic and diastolic velocities. Above baseline is pulmonary artery-to-aorta flow in diastole; below baseline is reversal of flow in systole. DA, ductus arteriosus; R-L, right to left.

All postnatal diagnoses were confirmed by a complete transthoracic echocardiographic examination. The patients' medical records were reviewed to confirm interventions and clinical outcomes. Neonatal intervention was defined as transcatheter balloon dilation valvuloplasty or a surgical procedure to augment pulmonary blood flow performed within 30 days of birth. Management of patients with pulmonary outflow tract obstruction at our institution includes a review of the postnatal echocardiogram and assessment of the patient's clinical status without a trial of prostaglandin if deemed possible. If adequate oxygen saturation is maintained after ductal closure then patients are discharged and followed closely in the outpatient setting until they are electively referred for intervention.

Data analysis

Data collected and analyzed included echocardiographic measurements, postnatal diagnostic groupings and primary clinical outcome (need for neonatal intervention). All analysis was done separately based on diagnostic group (single- vs two-ventricle circulation). Descriptive statistics were used to summarize the data, using mean ± SD for normally distributed continuous variables, median (range) for skewed continuous variables and frequency (percentage of total) for categorical or dichotomous variables. Comparisons of variables based on the primary clinical outcome status were made using the independent t-test for normally distributed continuous variables, Wilcoxon rank-sum test for skewed continuous variables and Fisher's exact test or the chi-square test for categorical variables. Changes in fetal echocardiographic measurements over time were assessed by measuring the change in PV annular dimension between the first and last fetal echocardiograms and dividing by the time between studies to generate a rate of growth of the PV annulus in mm/week. Comparison of annular growth based on clinical outcome status was made using an independent t-test. STATA v10.0 (STATA Corp., College Station, TX, USA) software was used for statistical analysis, and P < 0.05 was considered to be statistically significant.

To assess the predictive accuracy of prenatal indices, sensitivity and specificity were calculated for ductal flow pattern, PV annulus Z-score and the ratio of PV annulus diameter to AoV annulus diameter (PV/AoV ratio). Using receiver–operating characteristics curve analysis, optimum cut-off points in the predictor variables were obtained by selecting a cut-off point that produced a minimum sensitivity of 90% in discriminating the observed resulting classifications. This standard was established a priori in order to define a prediction rule that would minimize the very high cost of a false negative (incorrectly predicting that a neonatal intervention would not be needed in a newborn with ductal-dependent pulmonary blood flow). Because no cut-off point for PV annulus Z-score or PV/AoV ratio individually performed with a sensitivity of more than 90%, these two variables were combined in an either/or fashion to increase sensitivity.

RESULTS

Study population and clinical outcomes

A total of 65 fetuses were identified from the database during the study period. Eight pregnancies associated with heterotaxy (n = 4), trisomy 21 (n = 2), Dandy–Walker malformation (n = 1) and multicystic kidney disease (n = 1) were electively terminated. Fetal demise occurred in four cases and was associated with 22q11 microdeletion (n = 2), cystic hygroma (n = 1) and multiple congenital anomalies (n = 1). One fetus with TOF with restriction of the ventricular septal defect was excluded, thus 52 fetuses were included in the final cohort. Forty-seven had serial imaging performed and a total of 144 studies were reviewed. The mean gestational age at the time of diagnosis was 25 ± 4.0 weeks. There were four sets of twin pregnancies and the remaining 48 were singleton. Diagnoses are shown in Table 1 and divided into two cohorts: two-ventricle defects (n = 39) and single-ventricle defects (n = 13).

Table 1. Diagnoses of congenital heart disease grouped according to type of defect present in the fetus
Type of defectn
  1. AVC, atrioventricular canal; DILV, double-inlet left ventricle; DORV, double-outlet right ventricle; MS, mitral stenosis; PS, pulmonary stenosis; TAPVC, total anomalous pulmonary venous connection; TOF, tetralogy of Fallot.

Two-ventricle group 
TOF33
DORV/PS6
Single-ventricle group 
Unbalanced AVC, DORV, PS3
Unbalanced AVC, TOF2
Unbalanced AVC, DORV, TAPVC4
DILV, PS2
DORV, MS, PS2

Clinical outcomes including birth weight and gestational age at delivery by group are presented in Table 2. Twenty of 52 subjects (38%) had critical pulmonary outflow tract obstruction and required a neonatal intervention at a median of 12 (range, 1–30) days of age to increase pulmonary blood flow. Of the two-ventricle cohort, 13 of 39 (33%) required a neonatal intervention, comprising complete surgical repair (n = 8), transcatheter balloon dilation valvuloplasty (n = 3) or placement of a surgical shunt (n = 2). Of the single-ventricle cohort, seven of 13 (54%) required a neonatal intervention, which included transcatheter balloon dilation valvuloplasty (n = 3) and placement of a surgical shunt (n = 4). Compared with two-ventricle patients, the single-ventricle cohort demonstrated an increased risk of requiring neonatal intervention, with an odds ratio of 2.3 (95% CI, 0.7–8.1), although this difference did not reach statistical significance (P = 0.2).

Table 2. Clinical outcomes in fetuses grouped by type of defect and time of intervention
OutcomeIntervention at:P
> 30 days< 30 days
  • *

    In months.

  • In days.

Two-ventricle group (n = 39)   
n (%)26 (66.7)13 (33.3) 
Gestational age at delivery (weeks, mean ± SD)37.7 ± 2.537.6 ± 2.70.9
Birth weight (g, mean ± SD)2974 ± 8322625 ± 8680.25
Prostaglandin use (n (%))4 (15.4)11 (84.6)0.0001
Age at intervention (median (range))2.9 (1.6–5.2)*8 (1–30)† 
Single-ventricle group (n = 13)   
n (%)6 (46.2)7 (53.8) 
Gestational age at delivery (weeks, mean ± SD)38.8 ± 1.838.5 ± 1.20.7
Birth weight (g, mean ± SD)3357 ± 9313190 ± 5450.7
Prostaglandin use (n (%))3 (50.0)6 (85.7)0.3
Age at intervention (median (range))4.2 (2.8–10)*14 (3–30) 

Two-dimensional echocardiographic measurements

Measurements of the PV, AoV, SubPV region, MPA and proximal branch pulmonary arteries are presented by group in Table 3. These measurements were obtained from the final fetal echocardiogram performed at a mean gestational age of 34 ± 2.7 weeks. In the two-ventricle cohort, all measurements of the pulmonary outflow tract were significantly smaller in fetuses that went on to require a neonatal intervention than in those that did not. In the single-ventricle cohort, there were trends towards smaller measurements in PV-Z-score and PV/AoV ratio, but statistical significance was not reached. In both groups, accurate measurements of the SubPV region and MPA were not obtainable in a significant number of subjects. Interobserver variability was assessed with the intraclass correlation coefficient, which was 0.98 for the AoV and 0.96 for the PV, suggesting excellent reproducibility of measurements.

Table 3. Fetal echocardiographic measurements in fetuses with pulmonary outflow tract obstruction and congenital heart defect grouped by type of defect and whether or not neonatal intervention was required
ParameternNo interventionInterventionP
  1. Data are given as mean ± SD. AoV, aortic valve; LPA, left pulmonary artery; MPA, main pulmonary artery; PV, pulmonary valve; RPA, right pulmonary artery; SubPV, subpulmonary valve.

Two-ventricle group    
PV (mm)395.3 ± 1.04.1 ± 1.10.0035
PV Z-score39−2.6 ± 1.1−4.8 ± 2.10.0002
AoV (mm)398.0 ± 1.27.9 ± 0.90.7
AoV Z-score392.6 ± 0.82.5 ± 1.00.7
SubPV region (mm)195.0 ± 1.13.8 ± 1.10.032
MPA (mm)245.7 ± 0.84.2 ± 0.80.0005
LPA (mm)333.6 ± 0.52.8 ± 0.550.0006
RPA (mm)353.7 ± 0.53.1 ± 0.40.0007
PV/AoV ratio390.66 ± 0.10.53 ± 0.150.003
Single-ventricle group    
PV (mm)135.0 ± 0.84.5 ± 1.10.38
PV Z-score13−3.4 ± 1.0−4.1 ± 2.40.5
AoV (mm)137.7 ± 0.98.0 ± 0.40.4
AoV Z-score132.0 ± 1.12.6 ± 0.40.23
SubPV region (mm)44.2 ± 0.98
MPA (mm)95.3 ± 1.05.1 ± 0.60.8
LPA (mm)123.45 ± 0.153.9 ± 0.90.29
RPA (mm)123.6 ± 0.43.9 ± 0.80.4
PV/AoV ratio130.65 ± 0.10.57 ± 0.150.27

For the two-ventricle cohort sensitivities and specificities were obtained for the presence of a PV-Z-score of < −3 or a PV/AoV ratio of < 0.6 for their ability to predict the need for neonatal intervention (Table 4). Using either threshold produced > 90% sensitivity, which was consistent among various gestational ages. As demonstrated in Figures 4–6, the PV-Z-scores and PV/AoV ratios were significantly smaller in fetuses that required a neonatal intervention over various gestational ages. The AoV-Z-scores were larger than normal in both groups in the majority of cases.

Table 4. Sensitivity and specificity for a pulmonary valve diameter (PV) Z-score of < −3 or a PV to aortic valve annular diameter (PV/AoV) ratio of < 0.6 and ductal flow patterns in the prediction of need for neonatal intervention in fetuses that had two-ventricle defects
ParameterSensitivity (%)Specificity (%)
  1. echo, echocardiographic examination.

PV-Z-score < −3 or PV/AoV ratio < 0.6  
Early-gestation (< 24 weeks)10050
Mid-gestation (24–32 weeks)10048
Final echo (mean age, 34 weeks)9250
Ductal flow pattern  
Early-gestation (< 24 weeks)75100
Mid-gestation (24–32 weeks)8894
Final echo (mean age, 34 weeks)10095
Figure 4.

Echocardiographic parameters in fetuses that did (blue) and did not (red) require neonatal intervention plotted against gestational age: (a) pulmonary valve annular diameter Z-score (dashed black line represents Z-score of −3); (b) ratio of pulmonary valve to aortic valve annular diameter (dashed black line represents ratio of 0.6); and (c) aortic valve annular diameter Z-score (dashed black line represents Z-score of +2).

Ductal flow patterns

In 30 of 39 (77%) of the two-ventricle fetuses an assessment of the ductal flow pattern was made on the final echocardiogram. An abnormal ductal pattern was observed in all nine that required a neonatal intervention, providing a sensitivity of 100%. Of the 21 remaining fetuses that did not require a neonatal intervention, the ductal flow pattern was normal in all but one, providing a specificity of 95% (Table 4). Ductal flow patterns were obtained in 11 of 13 (85%) of the single-ventricle fetuses. Of the six that required a neonatal intervention, flow was abnormal in all, providing a sensitivity of 100%. Of the remaining five fetuses that did not require a neonatal intervention ductal flow was normal in four, giving a specificity of 80%. In those fetuses in which ductal flow direction could be measured (n = 41), comparison was made of the echocardiographic measurements between those with normal ductal flow and those with abnormal ductal flow patterns (Table 5). Pulmonary valve size and PV/AoV ratios were significantly smaller and AoV size was larger in the group with an abnormal ductal flow pattern.

Table 5. Echocardiographic measurements in fetuses with normal vs abnormal ductus arteriosus (DA) flow patterns in those in which DA flow could be measured (n = 41)
ParameterNormal DA flow (n = 24)Abnormal DA flow (n = 17)P
  1. Data are given as mean ± SD. AoV, aortic valve annular diameter; PV, pulmonary valve annular diameter.

PV (mm)5.2 ± 0.984.3 ± 1.10.012
PV-Z-score−2.4 ± 1.6−4.4 ± 2.00.0001
AoV (mm)7.7 ± 1.08.3 ± 0.560.037
PV/AoV ratio0.67 ± 0.10.52 ± 0.130.0001

Pulmonary valve Doppler velocities

Velocities were obtained across the pulmonary outflow tract in all but two fetuses. In general, velocities were only minimally above published norms. In addition, there were no significant differences between the group that required a neonatal intervention (1.32 ± 0.37 m/s) and the group that did not (1.16 ± 0.28 m/s), P = 0.112.

Progression of pulmonary outflow tract obstruction with gestational age

Serial fetal echocardiography was available for 47 of 52 fetuses. One fetus with antegrade flow on an early fetal echocardiogram developed pulmonary atresia on subsequent imaging. Fetuses that required a newborn intervention demonstrated diminished growth of the pulmonary valve from early-gestation echocardiogram (< 24 weeks) to late-gestation echocardiogram (> 32 weeks). When all fetuses with both an early and a late study were included (n = 20), growth rates for the intervention and non-intervention groups were 0.6 and 0.9 mm/month, respectively (P = 0.05).

DISCUSSION

We reviewed our experience with a cohort of fetuses with outflow tract obstruction to determine prenatal echocardiographic markers that could identify those that required a neonatal intervention to augment pulmonary blood flow. We found that fetuses with two ventricles, a large ventricular septal defect and pulmonary outflow tract obstruction (e.g. TOF) that require a neonatal intervention had significantly smaller measurements of the pulmonary outflow tract on echocardiography. In addition, PV/AoV ratio was significantly smaller in the neonatal intervention group. When using a PV/AoV ratio of < 0.6 or a PV-Z-score of < −3 there was a greater than 90% sensitivity across gestational age for predicting the need for a neonatal intervention. The weaker specificity values are acceptable in this clinical setting where the cost of a false negative is high.

Ductal flow pattern as a single marker provided the best sensitivity and specificity for predicting the need for a neonatal intervention; all fetuses with abnormal ductal flow required a neonatal intervention. Nonetheless, there will always be some patients where reliable ductal flow patterns cannot be obtained owing to fetal position or maternal body habitus. In our series, when ductal flow could not be obtained, measurements of the PV-Z-score and PV/AoV ratio allowed for discrimination between those fetuses that did and those that did not require a neonatal intervention. These measurements could therefore act as surrogate markers for abnormal ductal flow and need for neonatal intervention. In addition, valvar annular measurements have the added benefit of being more readily obtainable, which allows for their use by a variety of medical care providers.

There is a paucity of data describing perinatal outcomes of fetuses with complex single ventricles with pulmonary outflow tract obstruction with respect to the timing of the intervention. Therefore we studied a second, smaller group of complex single-ventricle patients. Fetuses in this group that required a neonatal intervention also had smaller PV and lower PV/AoV ratio, although statistical significance was not obtained – a result that is possibly related to the smaller numbers in this cohort. Similarly to the two-ventricle cohort, an abnormal ductal flow pattern produced excellent sensitivities and specificities for predicting the need for neonatal intervention.

Progression of pulmonary outflow tract obstruction was observed in our cohort. This finding supports previous reports that focused on pulmonary artery growth in CHD[7]. In our cohort, we also demonstrated diminished growth velocity of the PV in fetuses that went on to require a neonatal intervention. These differences in growth velocity can aid in the identification of fetuses at risk for critical obstruction after birth, which highlights the need for serial imaging throughout pregnancy.

Previous studies attempting to predict the need for neonatal intervention were limited by sample size. A review of 25 fetuses with TOF was unable to correlate echocardiographic findings with timing of surgery[8]. A separate review of 47 fetuses with TOF-type anatomy demonstrated that lower PV-Z-scores were associated with the use of prostaglandin, but it was not clear how many actually had critical CHD and required a neonatal intervention[11]. The importance of reversed ductal shunting in critical right-sided obstructive lesions was initially reported by Berning et al.[3]. In this series, 15 fetuses survived to term and only three survived the neonatal period, leading the authors to conclude that reversed ductal shunting predicts severe disease and poor outcome. Our study expands on this literature with a larger cohort, more perinatal management details and outcome data in the current era. Our findings further highlight the importance of abnormal ductal shunting as a strong marker of the need for neonatal intervention, even when pulmonary atresia and more severe CHD are not present.

Prenatal identification of pulmonary outflow tract obstruction is clinically relevant. It allows for more accurate prenatal counseling and enables the development of a perinatal plan for delivery in a tertiary center when appropriate. Moreover, our measurements and ratios are relatively easy for physicians who are not fetal cardiologists to utilize, making them excellent screening tools for those who often perform initial prenatal evaluations.

Our study is limited in that it is a retrospective review with selection bias of fetuses evaluated at a large referral center. In addition, there were patients in whom we were unable to accurately measure subpulmonary regions and therefore we could have missed important obstruction. We chose not to assess valvar pulmonary stenosis alone, as our goal was to isolate a dimension of the pulmonary outflow tract that would correlate with postnatal cyanosis and ductal dependency. Newborns with critical pulmonary stenosis may be cyanotic for various reasons, including significant right ventricular hypertrophy with a smaller than normal cavity and poor compliance leading to right-to-left atrial-level shunting, thus making them a different cohort of patients when predicting postnatal physiology. Finally, owing to small numbers our study was not powered to draw significant conclusions in the single-ventricle cohort.

In conclusion, in fetuses with pulmonary outflow tract obstruction in the setting of two ventricles with a large ventricular septal defect (e.g. TOF), assessment of the outflow tract allows for good discrimination between those that will and those that will not require a neonatal intervention to augment pulmonary blood flow. The presence of reversed ductal shunting is both highly sensitive and specific for critical obstruction, and is the strongest single fetal echocardiographic marker to predict the need for a neonatal intervention. When the ductus arteriosus cannot be identified, measurements of the PV and PV/AoV ratio are highly sensitive markers of the need for neonatal intervention. Fetuses that required a neonatal intervention had diminished growth of the PV from early to late gestation, highlighting the importance of serial echocardiography in determining critical CHD. Single-ventricle fetuses are more complex, but ductal patterns also appear to be sensitive and specific for predicting the need for an intervention. These findings have important implications for family counseling, the planning of delivery strategies and immediate postnatal care for these patients.

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