Peripartum Management of Pregnant Women With Congenital Heart Disease

Abstract

Background: The average maternal age at delivery, and thus the associated maternal risk are increasing including in women with congenital heart disease (CHD). A comprehensive management approach is therefore required for pregnant women with CHD. The present study aimed to investigate the factors determining peripartum safety in women with CHD.

Methods and Results: We retrospectively collected multicenter data for 217 pregnant women with CHD (age at delivery: 31.4±5.6 years; NYHA classifications I and II: 88.9% and 7.4%, respectively). CHD severity was classified according to the American College of Cardiology/American Heart Association guidelines as simple (n=116), moderate complexity (n=69), or great complexity (n=32). Cardiovascular (CV) events (heart failure: n=24, arrhythmia: n=9) occurred in 30 women during the peripartum period. Moderate or great complexity CHD was associated with more CV events during gestation than simple CHD. CV events occurred earlier in women with moderate or great complexity compared with simple CHD. Number of deliveries (multiparity), NYHA functional class, and severity of CHD were predictors of CV events.

Conclusions: This study identified not only the severity of CHD according to the ACC/AHA and NYHA classifications, but also the number of deliveries, as important predictive factors of CV events in women with CHD. This information should be made available to women with CHD and medical personnel to promote safe deliveries.

Advancements in medical technology have led to a rapid increase in the number of surviving adults with congenital heart disease (CHD), and many women with CHD now reach childbearing age.^1–3 Although the outcomes of pregnancy and delivery in women with CHD and preserved cardiac function are usually favorable, long-term residual lesions after repair and uncorrected cardiac defects may have adverse effects on both maternal and neonatal health.⁴ The average maternal age at delivery in the general population in Japan is continuing to increase in line with social progress.⁵ This social phenomenon is also reflected in the maternal age of women with CHD; a study published in 1994 reported that the median maternal age of women with CHD was 24 years, compared with an average age of 27.7 years in 2005, and >30 years in 2015 (median 32 years).^6–8 The peripartum risks are therefore likely to be increased in women with CHD and as CHD deteriorates with age, the circulatory overload during pregnancy thus becomes more serious in older women with CHD.^9,10 Cardiac, obstetric, and neonatal complications are therefore increasing among women with CHD in the current social environment.^7,11,12

Several studies have performed risk stratification of pregnant women with CHD to predict cardiac, obstetric, and neonatal complications.^6,13,14 Risk stratification includes assessing the detailed cardiac, surgical, and obstetric histories, oxygen saturation values, ECG and transthoracic echocardiography findings, and maternal functional status (e.g., exercise stress testing and stress ECG). Multicenter registries and meta-analyses also provide useful estimations of the risks associated with pregnancy and delivery for a given type of CHD. Risk classification systems proposed to evaluate pregnant women with CHD¹⁵ include the CARdiac disease in PREGnancy (CARPREG) risk score,¹⁶ modified World Health Organization (WHO) classification,¹⁷ ZAHARA score,¹⁸ and the clinical stratification of the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines.¹⁹ According to these risk assessments, pregnant women with CHD of moderate or great complexity according to the ACC/AHA guidelines should receive peripartum management at institutions that satisfy the criteria for a specialized facility equipped to manage pregnancy and childbirth in women with heart disease.²⁰ However, the CARPREG risk score, modified WHO classification, and ZAHARA score are relatively specialized and complicated scores that may be difficult for physicians and obstetricians to use. Therefore, in this study, we used the simple classification proposed by the ACC/AHA guidelines.

Japanese medical administration and peripartum checkup systems are well developed and differ from those in other countries, leading to low maternal and fetal death rates in the general population.⁵ The risk stratification of women with CHD in Japan should thus be evaluated in this specific social environment.

The present study focused on the peripartum management of pregnant women with CHD who were able to continue their pregnancy until delivery. Longitudinal multicenter data for both mothers and newborns from pregnancy to the postnatal period were analyzed to identify the problems encountered in the management of these cases, and to evaluate the peripartum risks. This is the first multicenter study involving pregnant women with moderate and great complexity CHD.

Methods

Subjects

This retrospective multicenter cohort study was conducted from January 2009 to March 2016. After excluding pregnant women with chromosomal aberrations and those who had experienced miscarriage, stillbirth, multiple births, and/or had been transferred between hospitals during their pregnancy, a total of 217 pregnant women with CHD were enrolled.

The participating facilities included Kyushu University Hospital, Japan Community Healthcare Organization Kyushu Hospital, Department of Perinatology and Gynecology of the National Cerebral and Cardiovascular Center, and the Cardiovascular Center of St. Luke’s International University Hospital. This study was conducted after giving an explanation of participation in this study, including an opt-out option, to the patients using the institutes’ homepage. The institutional review board or ethics committee at each of the 4 centers approved the study protocol (approval nos. 28-314, 381, M28-057, and 16-R131, respectively).

Data Collection

Qualified medical professionals retrospectively obtained data from the medical records, including baseline demographic characteristics, detailed cardiac, surgical, and obstetric histories, physical examination findings, cardiovascular (CV) parameters such as type of CHD, New York Heart Association (NYHA) functional classification, severity of CHD, types of surgery performed for CHD, and medications taken before and during pregnancy. The collected peripartum data included the maternal ages at the 1st and last deliveries, obstetric history, mode of delivery (vaginal or cesarean section), volume of intrapartum hemorrhage at the last delivery, and neonatal clinical information including gestational age, birth weight, and adverse events (including preterm delivery, low birth weight, and existence of CHD). We followed up the participants from the peripartum period to 1 year after delivery, and obtained information on the clinical status of both the mothers and their 1-year-old children at the 1-year health checkup.

Definitions

We defined the severity of CHD in accordance with the ACC/AHA guidelines for the management of adults with CHD,¹⁹ and defined CV events as heart failure, thrombosis, and arrhythmia requiring treatment during the peripartum period. Regarding adverse events experienced by the neonates, preterm delivery was defined as delivery at <37 weeks of gestation, and low birth weight was defined as a birthweight of <2,500 g. The feeding methods were surveyed at 1 month after delivery and were categorized as breast-feeding, bottle feeding, or mixed feeding (i.e., both breast and artificial milk). We defined 1st pregnancy trimester as <16 weeks of gestation, 2nd trimester as 16–27 weeks+6 days, and 3rd trimester as >28 weeks to delivery, according to the WHO. The preterm period was defined as <36 weeks+6 days, and the postpartum period as the period from preterm delivery to 1 year after delivery.

Statistical Analysis

The data are presented as mean±standard deviation, number, and percentage, number of events (number of patients), or odds ratio and 95% confidence interval. We analyzed differences between 2 groups using Student’s t-test or the Mann-Whitney U test after Kolmogorov-Smirnov testing. For categorical data, we compared intergroup differences using the χ² test. We assessed the possible predictors of CV events in pregnant women with CHD by logistic regression analysis using 3 models: Model 1: age at last delivery, number of deliveries, and NYHA functional class; Model 2: Model 1+severity of CHD; and Model 3: Model 2+medications before and during pregnancy. All statistical analyses were completed using SPSS version 25.0 (IBM, Inc., Chicago, IL, USA). Two-sided P values <0.05 were considered to indicate significant differences.

Results

Clinical Characteristics

The clinical characteristics of the 217 pregnant women with CHD are listed in Table 1. None of the women had a NYHA functional classification ≥III. The main medications taken before and during pregnancy were β-blockers, antiplatelet drugs, and digoxin. Most women had simple CHD (53.5%), followed by moderate complexity (31.8%), and great complexity CHD (14.7%). The most prominent types of CHD were ventricular septal defect in women with simple CHD, tetralogy of Fallot after repair in women with moderate complexity CHD, and complete transposition of the great arteries after repair in women with great complexity CHD.

Table 1. Clinical Characteristics of the 217 Pregnant Women With CHD

Age at last delivery in years, mean±SD	31.4±5.6
No. of deliveries, mean±SD	1.5±0.7
1, n (%)	129 (59.4)
2, n (%)	68 (31.3)
≥3, n (%)	20 (9.2)
History of smoking, n (%)	17 (7.8)
NYHA functional class
Class I, n (%)	193 (88.9)
Class II, n (%)	16 (7.4)
Unknown, n (%)	8 (3.7)
Medications before and during pregnancy, n (%)	36 (16.6)
β-blockers, n (%)	17 (7.8)
ACEI/ARB, n (%)	6 (2.8)
Digoxin, n (%)	11 (5.1)
Diuretics, n (%)	6 (2.8)
Antiplatelet drugs, n (%)	17 (7.8)
Antiarrhythmic drugs, n (%)	3 (1.4)
Severity of CHD*
Simple, n (%)	116 (53.5)
Moderate complexity, n (%)	69 (31.8)
Great complexity, n (%)	32 (14.7)
Type of CHD, n (unrepaired/repaired)
Simple CHD	116 (75/41)
VSD	50 (34/16)
ASD	36 (16/20)
Aortic valve disease	12 (12/0)
Mitral valve disease	8 (8/0)
Patent ductus arteriosus	4 (2/2)
ASD and VSD	3 (1/2)
Pulmonary valve disease	2 (2/0)
Patent foramen ovale	1 (0/1)
Moderate complexity CHD	69 (8/61)
Tetralogy of Fallot	21 (0/21)
Severe valvular disease	14 (2/12)
Complicated VSD	7 (0/7)
Atrioventricular septal defect	7 (0/7)
Coarctation of the aorta	6 (0/6)
Ebstein anomaly	6 (4/2)
PAPVR	4 (1/3)
TAPVR	3 (1/2)
Bland-White-Garland syndrome	1 (0/1)
Great complexity CHD	32 (1/31)
D-TGA	12 (0/12)
C-TGA	6 (1/5)
Pulmonary atresia	5 (0/5)
Double outlet right ventricle	4 (0/4)
Tricuspid atresia	3 (0/3)
Single ventricle	2 (0/2)

*American College of Cardiology criteria were used to assess the severity of CHD.¹⁷ ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blockers; ASD, atrial septal defect; CHD, congenital heart disease; C-TGA, corrected transposition of the great arteries; D-TGA, complete transposition of the great arteries; NYHA, New York Heart Association; PAPVR, partial anomalous pulmonary venous return; SD, standard deviation; n, number of patients; TAPVR, total anomalous pulmonary venous return; VSD, ventricular septal defect.

CV Events

The 33 CV events comprised 9 arrhythmia events (4.1%) and 24 heart failure events (11.1%) in 30 women (13.8%); 3 women experienced both arrhythmia and heart failure. The arrhythmia events comprised 3 cases of supraventricular arrhythmia (paroxysmal supraventricular tachycardia, atrial tachycardia, paroxysmal atrial fibrillation), 5 of ventricular arrhythmia (frequent non-sustained ventricular tachycardia), and 1 of sick sinus syndrome (bradycardia and tachycardia type). Supraventricular arrhythmia was managed by the administration of verapamil hydrochloride and β-blockers, ventricular arrhythmia by mexiletine hydrochloride and β-blockers, paroxysmal atrial fibrillation by cardioversion, and sick sinus syndrome by pacemaker implantation. The 16 heart failure events comprised general edema and exacerbation of pulmonary hypertension; 5 episodes involved pulmonary congestion and 3 involved both general edema and pulmonary congestion. Diuretics were used to treat all heart failure events, and cardiotonic drugs were added in cases of pulmonary congestion. One case of bicuspid aortic valve (moderate complexity) resulted in heart failure because of continuous tachyarrhythmia. Two women with great complexity CHD (complete transposition of the great arteries and pulmonary atresia with intact ventricular septum) who experienced arrhythmia events during early pregnancy developed heart failure at delivery.

All the women had recovered to predelivery status at their medical checkup 1 year after delivery, and the medical records revealed no reports of abnormal development in the offspring.

Maternal and Neonatal Outcomes in Women With CHD With and Without CV Events

The maternal and neonatal outcomes in women with CHD with and without CV events are summarized in Table 2. Overall, vaginal delivery was more common than cesarean section (65% vs. 35%, P<0.001) and was associated with less intrapartum hemorrhage than cesarean section (P=0.08). However, cesarean section was more common in participants with CV events than in those without CV events (P=0.064). Among the 15 women with CV events who underwent cesarean section, sections were planned in 3 women (corrected transposition of the great arteries; double-switch surgery, complete transposition of the great arteries; APC Fontan surgery, tricuspid atresia; lateral tunnel Fontan surgery) because of the severity of their CHD. Sections were performed because of pregnancy hypertension or preeclampsia in 1 and depression in 1, and the other 10 women delivered their babies by cesarean section because of obstetrical indications such as premature delivery (n=3) and obstructed labor (n=2). There was no significant difference in intrapartum hemorrhage between the women with CHD with and without CV events. However, women with CV events had a lower tendency to breast-feed (P=0.092) than those without CV events, and the incidences of preterm delivery and low birth weight neonates were significantly higher among women with CV events.

Table 2. Maternal and Neonatal Outcomes in Women With CHD With and Without CV Events

	Total (n=217)	CV events (n=30)	No CV events (n=187)	P value
Maternal outcomes
Delivery method, n (%)
Vaginal	141 (65.0)†	15 (50.0)	126 (67.4)	0.064
Cesarean section	76 (35.0)†	15 (50.0)	61 (32.6)
Intrapartum hemorrhage (g)
Vaginal delivery (n=139)	572±362††	541±333	575±366	0.73
Cesarean section (n=76)	663±362††	634±402	670±354	0.74
Unknown (n=2)	–	–	–	–
Neonatal outcomes
Gestational age (days), mean±SD (range)	269±16 (178–292)	261±20	270±15	0.003
Birth weight (g), mean±SD (range)	2,755±535 (486–4,062)	2,462±562	2,800±517	0.001
Infant nutrition, n (%)
Breast-feeding	84 (38.7)	9 (30.0)	75 (40.1)	0.092
Bottle feeding	21 (9.7)	6 (20.0)	15 (8.0)
Mixed feeding	89 (41.0)	11 (8.7)	78 (41.7)
Unknown	23 (10.6)	4 (13.3)	19 (10.2)
Neonatal events, n (%)
Preterm delivery*	29 (13.4)	10 (33.3)	19 (10.2)	0.001
Low birth weight**	54 (24.9)	14 (46.7)	40 (21.4)	0.003
Congenital heart disease***	14 (6.5)	1 (3.3)	13 (7.0)	0.45

^†P<0.001, ^††P=0.08. *Preterm delivery: <37 weeks of gestation. **Low birth weight: <2,500 g. ***CHD included ventricular septal defect, atrial septal defect, tricuspid regurgitation, and truncus arteriosus communis. CHD, congenital heart disease; CV, cardiovascular; SD, standard deviation.

Women with CHD and CV events had a significantly shorter gestation period and a higher incidence of preterm births than women without CV events (P=0.003, 0.001, respectively), as well as delivering neonates with a lower birth weight and neonates diagnosed as low birth weight (P=0.001, 0.003, respectively). However, there was no significant difference between the 2 groups in terms of the existence of CHD in the neonates.

Characteristics and Manifestations of Pregnant Women With Simple vs. Moderate/Great Complexity CHD

The clinical characteristics of women with simple (n=116) vs. moderate or great complexity CHD (n=101) are listed in Table 3. Women with simple CHD were significantly older at both the last (P=0.03) and first deliveries (P=0.03) compared with women with moderate/great complexity CHD. NYHA functional classifications were also significantly higher in women with moderate/great complexity CHD than in those with simple CHD (P=0.01). Medications were more commonly administered and CV events occurred significantly more frequently in women with moderate/great complexity compared with simple CHD (P=0.009 for arrhythmia, P<0.001 for heart failure).

Table 3. Characteristics and Manifestations in Pregnant Women With Simple vs. Moderate/Great Complexity CHD

	Simple CHD (n=116)	Moderate/great complexity CHD (n=101)	P value
Maternal
Age at last delivery (years), mean±SD	32.2±5.8	30.5±5.1	0.03
No. of deliveries	1.5±0.7	1.5±0.8	0.56
NYHA functional class			–
I, n (%)	112 (96.6)	81 (80.1)	0.01
II, n (%)	4 (3.4)	12 (11.9)
Unknown	0 (0)	8 (7.9)
Medications before and during pregnancy (n=36)	5 (4.3)	31 (30.7)	–
β-blockers, n (%)	2 (1.7)	15 (14.9)	<0.001
ACEI/ARB, n (%)	0 (0)	6 (5.9)	0.008
Digoxin, n (%)	0 (0)	11 (10.9)	<0.001
Diuretics, n (%)	0 (0)	6 (5.9)	0.008
Antiplatelet drugs, n (%)	3 (2.6)	14 (13.9)	0.002
Antiarrhythmic drugs, n (%)	0 (0)	3 (3.0)	0.06
Delivery method
Vaginal, n (%)	82 (70.7)	59 (58.4)	0.059
Cesarean section, n (%)	34 (29.3)	42 (41.6)
Intrapartum hemorrhage (g) (n=215)
Vaginal delivery (n=139), mean±SD	574±356	568±373	0.93
Cesarean section (n=76), mean±SD	692±365	638±362	0.53
Cardiovascular events* (n=30, 33 events)	2 (1.7)	28 (26.4)	–
Arrhythmia, no. of events (%)	1 (0.9)	8 (7.9)	0.009
Heart failure, no. of events (%)	1 (0.9)	23 (22.8)	<0.001
Neonatal
Gestational age (days), mean±SD	272±14	265±17	0.002
Birth weight (g), mean±SD	2,913±454	2,569±562	<0.001
Infant nutrition
Breast-feeding, n (%)	49 (42.2)	35 (34.7)
Bottle feeding, n (%)	10 (8.6)	11 (10.9)	0.64
Mixed feeding, n (%)	48 (41.4)	41 (40.6)
Unknown	9 (7.8)	14 (13.9)
Neonatal adverse events
Preterm delivery, n (%)	8 (6.9)	21 (20.8)	0.003
Low birth weight, n (%)	14 (12.1)	40 (39.6)	<0.001
CHD, n (%)	10 (8.6)	4 (4.0)	0.16

*Three deliveries involved both arrhythmia and heart failure. Abbreviations as in Table 1.

Compared with simple CHD, women with moderate/great complexity CHD had significantly shorter gestation and a higher incidence of preterm deliveries (P=0.002, 0.003, respectively), as well as delivering more low birth weight neonates (P<0.001). However, there was no significant difference between the 2 groups in terms of the existence of CHD in the neonates.

The gestational periods during which the CV events developed, classified by severity (simple, moderate complexity, and great complexity) are shown in the Figure. A total of 33 CV events occurred in 30 women (2 events in 2 women with simple CHD, 14 events in 13 women with moderate complexity, and 17 events in 15 women with great complexity). There were no CV events during the 1st trimester, 3 arrhythmia events occurred during the 2nd trimester (1 moderate complexity, 2 great complexity), and 5 arrhythmia events during the 3rd trimester (1 simple CHD, 2 moderate complexity, 2 great complexity). The arrhythmia events included 5 episodes of non-sustained ventricular tachycardia, 2 of paroxysmal supraventricular tachycardia, 1 paroxysmal atrial fibrillation, and 1 episode of sick sinus syndrome. There were no heart failure events before delivery in any of the women. At the time of delivery and during the postpartum period, there was 1 arrhythmia event (non-sustained ventricular tachycardia in the moderate complexity group) and 24 heart failure events (1 simple CHD, 10 moderate complexity, 13 great complexity). Heart failure events included 16 episodes of right-sided heart failure (fluid retention, pulmonary hypertension) and 5 episodes of left-sided heart failure (pulmonary congestion). Three women with moderate/great complexity CHD developed both fluid retention and pulmonary congestion.

Figure.

Cardiovascular events experienced during pregnancy in women with congenital heart disease (CHD): 33 cardiovascular events occurred in 30 women (S: 2 events in 2 women; M: 14 events in 13 women; G: 17 events in 15 women). S, simple CHD; M, moderate complexity CHD; G, great complexity CHD; W, weeks.

The results of multivariate logistic analysis are shown in Table 4. The number of deliveries was a significant predictor of CV events in Model 1 (P=0.03), Model 2 (P=0.03), and Model 3 (P=0.04). NYHA functional classification was also a significant predictor of CV events in Model 1 (P<0.001), Model 2 (P=0.004), and Model 3 (P=0.02). The severity of CHD classified according to the ACC/AHA guidelines for the management of adults with CHD was a significant predictor of CV events in Model 2 (P=0.004 for moderate complexity CHD; P<0.001 for great complexity CHD) and Model 3 (P=0.008 for moderate complexity CHD; P=0.001 for great complexity CHD) using women with simple CHD as the reference group.

Table 4. Predictors of Cardiovascular Events in Pregnant Women With CHD

	Model 1		Model 2		Model 3
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Age at last delivery	0.63 (0.41–0.99)	0.045	0.69 (0.45–1.06)	0.09	0.64 (0.38–1.09)	0.10
No. of deliveries	3.66 (1.16–11.50)	0.03	3.75 (1.18–11.95)	0.03	4.10 (1.06–15.90)	0.04
NYHA functional class	12.45 (3.85–40.20)	<0.001	7.14 (1.84–27.71)	0.004	5.02 (2.27–11.09)	0.02
Severity of CHD
Simple	–	–	1.00 (Ref.)	–	1.00 (Ref.)	–
Moderate complexity	–	–	10.24 (2.10–49.91)	0.004	9.22 (1.80–47.26)	0.008
Great complexity	–	–	5.78 (2.49–13.42)	<0.001	5.67 (2.07–15.49)	0.001
Medications before and during pregnancy
β-blockers	–	–	–	–	0.48 (0.06–3.82)	0.48
ACEI/ARB	–	–	–	–	0.51 (0.01–21.68)	0.73
Digoxin	–	–	–	–	15.22 (0.60–386.03)	0.10
Diuretics	–	–	–	–	0.09 (0.002–3.84)	0.21
Antiplatelet drugs	–	–	–	–	0.87 (0.13–5.92)	0.89
Antiarrhythmic drugs	–	–	–	–	2.30 (0.05–160.97)	0.67

Model 1: age at last delivery, number of deliveries, and NYHA functional classification for cardiovascular events. Model 2: Model 1+clinical stratification (i.e., simple vs. moderate complexity; simple vs. great complexity). Model 3: Model 2+medicines (i.e., β-blockers, Acei/ARB, digoxin, diuretics, antiplatelet drugs, and antiarrhythmic drugs). CI, confidence interval; OR, odds ratio. Other abbreviations as in Table 1.

Discussion

The pregnant women included in the present study all had CHD and an older average age at delivery compared with previous studies;^7,12 60% were primiparous, 8% had a NYHA classification of II, and 15% had complex CHD. Based on a nationwide study using the national database of health insurance claims (18.5%)²¹ and the Survey of Medical Institutions (Iryo Shisetsu Chosa) from 1999 to 2014 (17.6%),²² the rate of cesarean section among women with CHD in our study was higher than among the general population (35.0% vs. 18.5%/17.6% (national database of health insurance claims/Survey of Medical Institutions)). Among the study population, women with moderate or complex CHD experienced more CV events (arrhythmia and heart failure) during gestation than women with simple CHD. Furthermore, the onset of CV events occurred earlier in women with moderate or complex CHD compared with simple CHD. The number of deliveries (multiparity), NYHA functional classification, and severity of CHD according to the ACC/AHA guidelines were identified as predictors of CV events. However, we only collected data from women with CHD who were actually able to give birth (full-term or prematurely), and the proportion of women with complex CHD was therefore only 14.7%, and there were no women with a NYHA functional classification ≥III.

CV Events in Pregnant Women With CHD

In the present study, no women experienced CV events in the 1st trimester, but episodes of arrhythmia began to occur during the 2nd trimester in women with moderate/great complexity CHD, but not in those with simple CHD. With progression of the hemodynamic overload during pregnancy, arrhythmic events occurred first in women with great complexity CHD, followed by those with moderate complexity, and then those with simple CHD. Previous studies reported that pregnant women with CHD experienced arrhythmic events associated with increasing volume overload during pregnancy progression because of the presence of surgical scars on the atria and ventricles and structural abnormalities caused by aging, even after complete resolution of the underlying CHD.^14,23 In addition to arrhythmic events, episodes of heart failure have also been reported near the end of the 2nd trimester, which is considered a susceptible period for women with CHD because of maximal cardiac output.¹⁰ However, there were no episodes of heart failure near the end of the 2nd trimester among the women with CHD in the current study. Hemodynamic changes during the peri- and early postpartum periods are much more drastic and develop over shorter periods of time compared with changes near the end of the 2nd trimester; therefore, the women in the current study may have adapted well to the first hemodynamic changes that occurred near the end of the 2nd trimester. In patients with pending heart failure, we recommend that the women rest or stop working, which might prevent heart failure. The substantial volume overload and increased intracardiac pressure in the 3rd trimester also led to heart failure in women in the present study, especially in women with complex CHD. Previous studies reported that heart failure tended to occur during or after the occurrence of tachyarrhythmia.⁷ However, in the current study only 1 woman (with moderate complexity CHD) experienced heart failure because of continuous tachyarrhythmia. Given that 2 women with complex CHD who experienced arrhythmic events in early pregnancy also developed heart failure at delivery, we considered that the occurrence of arrhythmia during early pregnancy in women with moderate/great complexity CHD might suggest a high risk of developing heart failure in the later stages of pregnancy. Previous studies also reported that pregnant women with CHD who experienced CV events during the 3rd trimester had a significantly greater possibility of developing CV events around the time of delivery than those without CV events during the 3rd trimester.^24,25 Therefore, pregnant women with moderate/great complexity CHD require adequate peripartum management at suitable institutions,^26,27 and prepregnancy care is also essential for minimizing both maternal and neonatal risks.²⁸ We should thus support women with CHD by providing a smooth transition from pediatric to adult care, including appropriate knowledge of pregnancy, including prepregnancy counseling and contraception.^29–31

Neonatal Events

Japanese demographic statistics reported incidences of low birth weight and preterm birth of 9.6% and 5.6%, respectively, in 2016.¹⁹ The incidences of these events were much higher in the present cohort of women with CHD compared with the normal population, which suggests that women with CHD will have increased neonatal care needs for premature babies with low birth weight or various defects, and that prenatal care of women with CHD is required to minimize the occurrence of preterm delivery.^32,33

Peripartum and Puerperium Environments

Higher age at marriage and at first delivery are becoming serious problems in Japan. Moreover, the trend towards nuclear families, connected with urbanization and aging caregivers, means that pregnant women’s living situations are changing, making it increasingly difficult for women with CHD to raise their children.^5,34

Healthy women generally require 4–8 weeks for the maternal hemodynamics to recover to the normal prepregnancy state after delivery,³³ whereas women with CHD require a much longer period of 6–12 months.⁹ The present study revealed that multiparity was an independent risk factor for CV events during pregnancy and delivery. Approximately 40% of women in the present study were multiparous, indicating the need to provide women with CHD with easy access to childcare, and to psychological and social support.^35,36 This support requires a comprehensive, patient-centered, and interdisciplinary team-based approach towards the care of pregnant women with CHD, to enable the adequate provision of prepregnancy planning and diligent peri- and postpartum care for women with CHD.^37,38

Study Limitations

This multicenter study had several limitations. The data were collected retrospectively, and the follow-up protocols and outcome assessments were therefore not standardized. However, data bias was minimized by the completeness of the data and the absence of losses to follow-up. The present cohort did not include women with CHD and cyanosis or a NYHA functional classification ≥III. Furthermore, this study included women from 3 geographical areas (Fukuoka, Osaka, and Tokyo), and their lifestyle and family relationships may have differed.

Conclusions

Based on data from 4 centers with specific facilities for managing pregnant women with CHD, the severity of the underlying CHD according to the ACC/AHA guidelines for the management of adults with CHD¹⁹ and NYHA functional class were simple and useful predictors of CV events in pregnant women with CHD. The number of deliveries was also a useful predictor of CV events. This study highlights the need for careful management of women with CHD (especially those with moderate or great complexity CHD) both before and throughout the pregnancy to improve peripartum safety. Furthermore, appropriate management should be based on evaluations of CHD severity and parity in pregnant women with CHD.

Acknowledgments

We thank the staff members at the Kyushu University Hospital, Japan Community Healthcare Organization Kyushu Hospital, Department of Perinatology and Gynecology of the National Cerebral and Cardiovascular Center, and Cardiovascular Center of St. Luke’s International University Hospital for their help in collecting the data for the study. We also thank Kelly Zammit, BVSc, Susan Furness, PhD, and Jane Charbonneau, DVM, from Edanz Editing (www.edanzediting.com/ac), for editing drafts of this manuscript.

Disclosures

H.T. received lecture fees from Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Pharmaceuticals Co., Ltd., and Pfizer Inc. H.T. received grants from Japan Tobacco Inc., Nippon Boehringer Ingelheim Co., Ltd., and Mitsubishi Tanabe Pharma Co., Ltd. H.T. received scholarship donations from MSD Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Teijin Pharma Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. All other authors have no conflicts of interest.

Funding

This work was supported by a Grant-in-Aid for Scientific Research (B; #18H03083) and Grant-in-Aid for Young Scientists (Start-up; #15H06494) from the Ministry of Education, Culture, Sports, Science and Technology, and by an Intractable Disease Practical Application Business Grant (grant nos. 15ek0109123 h0001, 16ek0109123 h0002, and 17ek0109123 h0003) from the Japan Agency for Medical Research and Development.

References

• 1.   Moller JH, Taubert KA, Allen HD, Clark EB, Lauer RM. Cardiovascular health and disease in children: Current status. A Special Writing Group from the Task Force on Children and Youth, American Heart Association. Circulation 1994; 89: 923–930.
• 2.   Shiina Y, Toyoda T, Kawasoe Y, Tateno S, Shirai T, Wakisaka Y, et al. Prevalence of adult patients with congenital heart disease in Japan. Int J Cardiol 2011; 146: 13–16.
• 3.   Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the general population: Changing prevalence and age distribution. Circulation 2007; 115: 163–172.
• 4.   Ladouceur M, Iserin L, Cohen S, Legendre A, Boudjemline Y, Bonnet D. Key issues of daily life in adults with congenital heart disease. Arch Cardiovasc Dis 2013; 106: 404–412.
• 5.   Cabinet Office. Current status of declining birthrate: A 2018 White Paper, https://www8.cao.go.jp/shoushi/shoushika/whitepaper/measures/english/w-2018/index.html (accessed June 14, 2019).
• 6.   Presbitero P, Somerville J, Stone S, Aruta E, Spiegelhalter D, Rabajoli F. Pregnancy in cyanotic congenital heart disease: Outcome of mother and fetus. Circulation 1994; 89: 2673–2676.
• 7.   Khairy P, Ouyang DW, Fernandes SM, Lee-Parritz A, Economy KE, Landzberg MJ. Pregnancy outcomes in women with congenital heart disease. Circulation 2006; 113: 517–524.
• 8.   Lu C, Shih J, Chen S, Chiu H, Wang J, Chen C, et al. Comparison of 3 risk estimation methods for predicting cardiac outcomes in pregnant women with congenital heart disease. Circ J 2015; 79: 1609–1617.
• 9.   Metcalfe J, Ueland K. Maternal cardiovascular adjustments to pregnancy. Prog Cardiovasc Dis 1974; 16: 363–374.
• 10.   Bridges EJ, Womble S, Wallace M, McCartney J. Hemodynamic monitoring in high-risk obstetrics patients. I: Expected hemodynamic changes in pregnancy. Crit Care Nurse 2003; 23: 53–62.
• 11.   Siu SC, Sermer M, Harrison DA, Grigoriadis E, Liu G, Sorensen S, et al. Risk and predictors for pregnancy-related complications in women with heart disease. Circulation 1997; 96: 2789–2794.
• 12.   Ouyang DW, Khairy P, Fernandes SM, Landzberg MJ, Economy KE. Obstetric outcomes in pregnant women with congenital heart disease. Int J Cardiol 2010; 144: 195–199.
• 13.   Brickner ME. Cardiovascular management in pregnancy: Congenital heart disease. Circulation 2014; 130: 273–282.
• 14.   Niwa K. Adult congenital heart disease with pregnancy. Korean Circ J 2018; 48: 251–276.
• 15.   Pieper PG. Pre-pregnancy risk assessment and counselling of the cardiac patient. Neth Heart J 2011; 19: 477–481.
• 16.   Siu SC, Sermer M, Colman JM, Alvarez AN, Mercier LA, Morton BC, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001; 104: 515–521.
• 17.   Pijuan-Domenech A, Galian L, Goya M, Casellas M, Merced C, Ferreira-Gonzalez I, et al. Cardiac complications during pregnancy are better predicted with the modified WHO risk score. Int J Cardiol 2015; 195: 149–154.
• 18.   Balci A, Sollie-Szarynska KM, van der Bijl AG, Ruys TP, Mulder BJ, Roos-Hesselink JW, et al. Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with congenital heart disease. Heart 2014; 100: 1373–1381.
• 19.   Warnes CA, Williams RG, Bashore TM, Child JS, Connolly H, MDearani JA, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008; 52: e143–e263.
• 20.   Connolly HM. Managing congenital heart disease in the obstetric patient. Semin Perinatol 2018; 42: 39–48.
• 21.   Maeda E, Ishihara O, Tomio J, Sato A, Terada Y, Kobayashi Y, et al. Cesarean section rates and local resources for perinatal care in Japan: A nationwide ecological study using the national database of health insurance claims. J Obstet Gynaecol Res 2017; 44: 208–216.
• 22.   Yuda M. Public and social environment changes and caesarean section delivery choice in Japan. BMC Res Notes 2018; 11: 633.
• 23.   Niwa K, Tateno S, Akagi T, Himeno W, Kawasoe Y, Tatebe S, et al. Arrhythmia and reduced heart rate variability during pregnancy in women with congenital heart disease and previous reparative surgery. Int J Cardiol 2007; 122: 143–148.
• 24.   Balint OH, Siu SC, Mason J, Grewal J, Wald R, Oechslin EN, et al. Cardiac outcomes after pregnancy in women with congenital heart disease. Heart 2010; 96: 1656–1661.
• 25.   Pillutla P, Nguyen T, Markovic D, Canobbio M, Koos BJ, Aboulhosn JA. Cardiovascular and neonatal outcomes in pregnant women with high-risk congenital heart disease. Am J Cardiol 2016; 117: 1672–1677.
• 26.   Toyoda T, Tateno S, Kawasoe Y, Shirai T, Shiina Y, Matsuo K, et al. Nationwide survey of care facilities for adults with congenital heart disease in Japan. Circ J 2009; 73: 1147–1150.
• 27.   Ochiai R, Yao A, Kinugawa K, Nagai R, Shiraishi I, Niwa K. Status and future needs of regional adult congenital heart disease centers in Japan. Circ J 2011; 75: 2220–2227.
• 28.   Drenthen W, Boersma E, Balci A, Moons P, Roos-Hesselink JW, Mulder BJ, et al. Predictors of pregnancy complications in women with congenital heart disease. Eur Heart J 2010; 31: 2124–2132.
• 29.   Roos-Hesselink JW, Kerstjens-Frederikse WS, Meijboom FJ, Pieper PG. Inheritance of congenital heart disease. Neth Heart J 2005; 13: 88–91.
• 30.   Oyen N, Poulsen G, Wohlfahrt J, Boyd HA, Jensen PK, Melbye M. Recurrence of discordant congenital heart defects in families. Circ Cardiovasc Genet 2010; 3: 122–128.
• 31.   Thorne S, MacGregor A, Nelson-Piercy C. Risks of contraception and pregnancy in heart disease. Heart 2006; 92: 1520–1525.
• 32.   Gouton M, Nizard J, Patel M, Sassolas F, Jimenez M, Radojevic J, et al. Maternal and fetal outcomes of pregnancy with Fontan circulation: A multicentric observational study. Int J Cardiol 2015; 187: 84–89.
• 33.   Hayward RM, Foster E, Tseng ZH. Maternal and fetal outcomes of admission for delivery in women with congenital heart disease. JAMA Cardiol 2017; 2: 664–671.
• 34.   Muto G, Yokoyama K, Endo M. Solutions against declining birthrates confronting Japan’s aging society by supporting female workers in harmonizing work with their health and social issues: Fertility, chronic illness, and raising children. Nihon Eiseigaku Zasshi 2018; 73: 200–209 (in Japanese).
• 35.   Koerten MA, Niwa K, Szatmari A, Hajnalka B, Ruzsa Z, Nagdyman N, et al. Frequency of miscarriage/stillbirth and terminations of pregnancy among women with congenital heart disease in Germany, Hungary and Japan. Circ J 2016; 80: 1846–1851.
• 36.   McCabe N, Dunbar SB, Butler J, Higgins M, Book W, Reilly C. Antecedents of self-care in adults with congenital heart defects. Int J Cardiol 2015; 201: 610–615.
• 37.   Sillman C, Morin J, Thomet C, Barber D, Mizuno Y, Yang HL, et al. Adult congenital heart disease nurse coordination: Essential skills and role in optimizing team-based care. A position statement from the International Society for Adult Congenital Heart Disease (ISACHD). Int J Cardiol 2017; 229: 125–131.
• 38.   Shum KK, Gupta T, Canobbio MM, Durst J, Shah SB. Family planning and pregnancy management in adults with congenital heart disease. Prog Cardiovasc Dis 2018; 61: 336–346.