Comparison of pregnancy outcomes in women with repaired versus unrepaired atrial septal defect

Authors


Dr SC Yap, Department of Cardiology, Room Ba 308, Erasmus Medical Centre, Thoraxcentre, ‘s-Gravendijkwal 230, 3015 CE, Rotterdam, the Netherlands. Email s.c.yap@erasmusmc.nl

Abstract

Objective  To compare the risks of complications during pregnancy in women with repaired and unrepaired atrial septal defects (ASDs) without associated complex cardiac lesions.

Design  A retrospective multicentre study.

Setting  Tertiary centres in the Netherlands and Belgium.

Population  Women with ASD without associated complex cardiac lesions.

Methods  Women were identified using two congenital heart disease registries. One hundred women were identified who had 243 pregnancies, including 49 miscarriages and six terminations of pregnancy. Detailed information on each completed pregnancy (n = 188; unrepaired ASD, n = 133; repaired ASD, n = 55) was obtained using medical records and telephone interviews. In addition, data from the Generation R database (a prospective cohort study; n = 9667) were used to determine the background risk (control group).

Main outcome measures  Adjusted odds ratios (AORs) for cardiac, obstetric and neonatal events controlled for multiple pregnancies per woman using general estimating equation analysis.

Results  Women with an unrepaired ASD had a higher risk of neonatal events (AOR = 2.99, 95% confidence interval [CI] 1.14–7.89, P = 0.027) than women with a repaired ASD. The risk of cardiac and obstetric complications was comparable between women with unrepaired and repaired ASDs. Compared with the general population, women with an unrepaired ASD had higher risks of pre-eclampsia (AOR = 3.54, 95% CI 1.26–9.98, P = 0.017), small-for-gestational-age births (AOR = 1.95, 95% CI 1.15–3.30, P = 0.013) and fetal mortality (AOR = 5.55, 95% CI 1.77–17.4, P = 0.003). By contrast, no differences were observed when comparing women with a repaired ASD versus controls.

Conclusions  Women with an unrepaired ASD are at increased risk of neonatal events in comparison with women with a repaired ASD. Compared with the general population, women with an unrepaired ASD are at increased risk of pre-eclampsia, small-for-gestational-age births and fetal mortality.

Introduction

Atrial septal defect (ASD) is one of the most common lesions occurring in pregnant women with congenital heart disease.1,2 Most women with a simple isolated ASD are free of overt symptoms and may even be unaware of their heart defect. It is generally accepted that pregnancy and delivery in the context of a maternal ASD are well tolerated. The rare concomitant occurrence of pulmonary arterial hypertension or ventricular dysfunction is an important reason to discourage pregnancy.1,3,4 Current guidelines recommend cardiological surveillance for all pregnant women with an ASD because they are at risk (albeit a small risk) of paradoxical embolism, arrhythmia and heart failure.5 These recommendations are based on relatively small series or reports that do not differentiate between patients with different shunt lesion and surgical status, thus limiting the availability of ASD-specific pregnancy data.1,2,6–9

The aim of the present study was to compare pregnancy risks in women with unrepaired and repaired simple secundum or sinus venosus ASDs without associated complex cardiac defects such as anomalous pulmonary venous return or an atrioventricular septal defect, ventricular dysfunction or pulmonary hypertension.

Patients and methods

Study population

For the present study, 229 women with an ASD (age 18–45 years) were identified in 2006 using the nationwide Congenital Corvitia (CONCOR; http://www.concor.net) registry in the Netherlands and the adult congenital heart disease database of a Belgian tertiary medical centre (these registries do not include pregnancy data).10 We excluded women with ostium primum defect as they should be regarded as a subset of women with atrioventricular septal defect. We previously addressed the specific pregnancy risk in women with balanced atrioventricular septal defect.11 All women contacted for the present study were treated in one of the six participating tertiary medical centres. The institutional review board or ethics committee at each participating centre approved the protocol. A total of 188 women (participation rate 82.1%) provided written informed consent and were enrolled in the study.

Study protocol

Data were collected using medical records; additionally, answers to a detailed questionnaire were obtained by telephone interview. Recorded baseline data included prior surgical procedures; co-morbidity and medical history using the European Paediatric Cardiac Coding; age at inclusion; medication; fertility (infertility: more than 2 years of pregnancy attempts and documented by gynaecologist); miscarriages (spontaneous fetal loss before 20 weeks of gestation); and terminations of pregnancies.

Detailed information concerning each completed pregnancy (>20 weeks of gestation) was recorded for women with unrepaired and repaired ASDs: parity status; mode of delivery; use of cigarettes, alcohol and drugs; use of medication; New York Heart Association (NYHA) functional class; and physical examination. Documented cardiac, obstetric and neonatal events were classified according to predefined criteria.11

Cardiac complications

Symptomatic documented arrhythmia or symptomatic heart failure requiring treatment (according to the attending cardiologist); postpartum persistent (>1 year postpartum) NYHA functional class deterioration; angina; stroke; transient ischaemic attack; syncope; and/or endocarditis.

Obstetric complications/interventions

Pregnancy-induced hypertension (new onset hypertension after 20 weeks of gestation: blood pressure >140 mmHg systolic or >90 mmHg diastolic without significant proteinuria); pre-eclampsia (pregnancy-induced hypertension criteria and >0.3 g proteinuria in 24-hour urine sample); eclampsia (pre-eclampsia with grand mal seizures); haemolysis elevated liver enzymes low platelets (HELLP) syndrome; infections requiring antibiotic treatment; thrombo-embolic complications; gestational diabetes; assisted vaginal (forceps or vacuum) delivery or caesarean section; premature rupture of membranes (membrane rupture before the onset of uterine contractions); prolongation of second stage of delivery (nullipara more than 2 hours; multipara more than 1 hour); premature labour (spontaneous onset of labour before 37 weeks gestation); and postpartum haemorrhage (vaginal delivery > 500 ml, caesarean section > 1000 ml, documented by gynaecologist and requiring transfusion).

Neonatal complications

Premature birth (delivery < 37 weeks of gestation); small-for-gestational-age birthweight (<tenth percentile); fetal demise (intrauterine death ≥ 20 weeks of gestation); perinatal death (within the first month after birth); and/or recurrence of congenital heart defect.

To compare the pregnancy outcomes of women with an ASD with those of the general population, we used data from the Generation R study. This is a population-based prospective cohort study, which is conducted in Rotterdam, the Netherlands.12 In total, 9778 mothers with a delivery date from April 2002 until January 2006 were enrolled in Generation R. Of this group, 9667 women had a completed pregnancy (29 underwent an induced abortion; 45 were lost to follow up; 37 had a miscarriage). Available data from the Generation R database on pregnancy outcome were (using above-mentioned definitions): hypertension-related disorders, pregnancy-induced hypertension, pre-eclampsia, eclampsia, pregnancy duration, premature delivery, small for gestational age, and fetal and perinatal mortality. The incidence of other pregnancy complications in the general population was derived from the literature.13

Statistical analysis

Descriptive statistics for nominal data were expressed in absolute numbers and percentages. Mean values and standard deviations (SD) are presented for normally distributed continuous variables. For nonnormally distributed continuous variables, median and ranges were computed.

First, we tested whether there was a difference in the risk of pregnancy complications among women with an unrepaired ASD, those with a repaired ASD and controls. To correct for multiple pregnancies per woman, we used general estimating equation (GEE) analysis. The strength of association was represented by adjusted odds ratios (AORs) and their accompanying 95% confidence intervals (CIs). Second, we determined which baseline variables were associated with pregnancy outcome. In this analysis, pregnancy outcome was defined using a composite outcome of cardiac events (i.e. heart failure, stroke, transient ischaemic attack, arrhythmias and endocarditis), obstetric events (i.e. pregnancy-induced hypertension, pre-eclampsia, eclampsia, HELLP syndrome, premature labour and postpartum haemorrhage) or neonatal events (i.e. premature delivery, small-for-gestational-age births and fetal and perinatal mortality). To prevent variables being included in the final model by chance, we tested only variables that may potentially be associated with pregnancy outcome. Therefore, history of arrhythmia, history of thrombo-embolic complications, history of previous completed pregnancy, smoking (before and during pregnancy), presence of right ventricular dilatation, maternal age > 30 years and corrective status, which is the main goal of interest in this study, were accepted as potential explanatory factors associated with pregnancy outcome. These potential explanatory factors were evaluated in univariable analysis and factors with P < 0.10 were entered into a multivariable analysis.

Results

For the present study, 188 women (82.1%) with a simple ASD provided informed consent. Of these women, 88 were not pregnant at inclusion in the study, of whom 65 (73.9%) would like to bear children in the future. The self-reported reasons for being childless were: age (too young; 43.2%), no wish to have children (15.9%), social or economic situation (e.g. career or education; 13.6%), infertility (8.0%), no partner (6.8%), currently trying to become pregnant (4.5%), a genetic disorder (e.g. Down, Noonan or Holt-Oram syndrome; 4.5%) and other (3.4%).

Table 1 shows the characteristics at inclusion of 100 women with an ASD and a history of pregnancy. A total of 243 pregnancies were recorded, including 188 completed pregnancies, 49 miscarriages (20.2%) and six terminations of pregnancy (2.5%). The incidences of miscarriages were comparable between women with unrepaired and repaired ASDs.

Table 1.   Characteristics at inclusion of 100 women with ASD and a history of pregnancy
Characteristics  
  1. ASD, atrial septal defect.

  2. Data are expressed as n (%), unless otherwise stated.

Number of women100
Age at menarche (years), mean ± SD 13.2 ± 1.4
Age at inclusion (years), mean ± SD 37.5 ± 6.2
Type of ASD
Ostium secundum95 (95.0%)
Sinus venosus5 (5.0%)
Repair74 (74.0%)
Age at repair (years), mean ± SD 25.9 ± 14.4
Pregnancies
History of miscarriage29 (29.0%)
Number of miscarriages (% of total number of pregnancies)49 (20.2%)
History of termination of pregnancy4 (4.0%)
Number of terminations of pregnancy (% of total number of pregnancies)6 (2.5%)
History of completed pregnancy98 (98.0%)
Number of completed pregnancies (% of total number of pregnancies)188 (77.4%)

Baseline characteristics for all 188 completed pregnancies (98 women; two women had miscarriages only) are outlined in Table 2. No baseline differences were found between women with unrepaired and repaired ASDs. Table 3 describes cardiac, obstetric and neonatal complications per completed pregnancy. Table 4 presents the AORs (corrected for multiple pregnancies per woman) of adverse pregnancy outcomes for women with an unrepaired ASD, those with a repaired ASD and controls, respectively.

Table 2.   Baseline characteristics, hospitalisations and mode of delivery for all completed pregnancies in women with unrepaired and repaired ASDs
 Unrepaired ASD (= 133)Repaired ASD (= 55)AOR (95% CI)P-value
  1. AOR, adjusted odds ratio; ASD, atrial septal defect; CI, confidence interval.

  2. Data are expressed as n (%), unless otherwise stated. AORs were adjusted for multiple pregnancies per woman.

  3. *AOR not estimate because of the absence of events in one group.

  4. **Percentage of vaginal planned deliveries.

Number of women        67     31  
Maternal age at pregnancy (years), mean ± SD        28.7 ± 4.4     28.4 ± 4.41.00 (0.99–1.01)0.42
Medical history
Arrhythmia before pregnancy19 (14.3%)10 (18.2%)1.31 (0.38–4.48)0.67
Thrombo-embolic complication before pregnancy9 (6.8%)0**
Smoking before pregnancy27 (20.3%)17 (30.9%)0.80 (0.42–1.53)0.50
Smoking during pregnancy16 (12.0%)6 (10.9%)1.08 (0.70–1.69)0.72
Parity status
Nulliparous67 (50.4%)31 (46.4%)0.99 (0.97–1.01)0.19
Presence of right ventricular dilatation during pregnancy13 (9.8%)3 (5.5%)1.14 (0.91–1.42)0.25
Mode of delivery
Planned caesarean delivery10 (7.5%)4 (7.3%)0.99 (0.88–1.11)0.89
Vaginal planned123 (92.5%)51 (92.7%)1.01 (0.90–1.14)0.89
 Artificial rupture of membranes**51 (41.5%)22 (43.1%)0.99 (0.98–1.01)0.41
 Episiotomy**54 (43.9%)18 (35.3%)1.01 (0.98–1.03)0.53
 Forceps**7 (5.7%)1 (2.0%)1.03 (0.98–1.08)0.31
 Vacuum extraction**9 (7.3%)9 (17.6%)0.98 (0.94–1.02)0.23
 Emergency caesarean delivery**9 (7.3%)5 (9.8%)0.99 (0.93–1.07)0.86
Table 3.   Maternal and neonatal outcomes for 188 completed pregnancies in 98 women with an ASD and controls from Generation R
 Unrepaired ASD (= 133)Repaired ASD (= 55)Generation R data (= 9667)Expected occurrence based on literature
  1. ASD, atrial septal defect; CHD, congenital heart disease; NYHA ↓, New York Heart Association functional class deterioration.

  2. The incidence of complications in the general population is based on data from Generation R12 or derived from the literature.13 Data are expressed as n (%), unless otherwise stated. The values in brackets are represented in percentage

Cardiac complications
Arrhythmias6 (4.5)2 (3.6)<0.5%
Postpartum persistent NYHA ↓4 (3.0)2 (3.6)<0.5%
Syncope4 (3.0)1 (1.8)
Transient ischaemic attack1 (0.8)0<0.01%
Obstetric complications
Hypertension-related disorders14 (10.5)6 (10.9)5.7%
Pre-eclampsia9 (6.8)2 (3.6)2.0%
Pregnancy-induced hypertension5 (3.8)4 (7.3)3.7%
Postpartum haemorrhage11 (8.3)9 (16.4)2.4%
Infection13 (9.8)3 (5.5)
Premature rupture of membranes8 (6.0)3 (5.5)3.5%
Premature labour9 (6.8)2 (3.6)10.0–12.0%
Gestational diabetes2 (1.5)1 (1.8)1.0–2.0%
Thrombo-embolic event01 (1.8)0.1%
Placental abruption1 (0.8)0<0.5%
Neonatal outcome
Offspring (n)136569744
Number of twins3 (2.3)1 (1.8)1.2%
Pregnancy duration (weeks), mean ± SD   39.0 ± 2.7  39.1 ± 2.639.8 ± 1.9
Premature delivery11 (8.3)3 (5.4)6.3%
Infant weight (g), mean ± SD 3169 ± 7203312 ± 646  3409 ± 565
Small for gestational age29 (21.3)6 (10.7)12.0%
Fetal mortality3 (2.3)00.4%
Perinatal mortality1 (0.7)1 (1.8)0.4%
Recurrence of CHD2 (1.5)3 (5.5)
Table 4.   AORs for adverse pregnancy outcomes by presence of unrepaired or repaired ASD for completed pregnancies
 Unrepaired versus repaired ASDUnrepaired ASD versus controlsRepaired ASD versus controls
AOR (95% CI)P-valueAOR (95% CI)P-valueAOR (95% CI)P-value
  1. AOR, Adjusted odds ratio; ASD, atrial septal defect; CHD, congenital heart disease; CI, confidence interval; NYHA ↓, New York Heart Association functional class deterioration.

  2. AORs were adjusted for multiple pregnancies per woman.

  3. *AOR not estimated because of the absence of events in one group.

Cardiac complications
Arrhythmias1.15 (0.74–1.80)0.52
Postpartum persistent NYHA ↓0.84 (0.56–1.25)0.39
Syncope1.06 (0.94–1.19)0.35
Transient ischaemic attack**
Obstetric complications
Hypertension-related disorders0.97 (0.78–1.20)0.761.93 (0.87–4.29)0.112.01 (0.61–6.62)0.25
Pre-eclampsia0.98 (0.63–1.52)0.933.54 (1.26–9.98)0.0171.84 (0.43–7.83)0.41
Pregnancy-induced hypertension0.96 (0.76–1.21)0.711.01 (0.31–3.31)0.992.02 (0.41–9.90)0.39
Postpartum haemorrhage0.93 (0.82–1.06)0.29
Infection1.01 (0.93–1.11)0.76
Premature rupture of membranes0.97 (0.81–1.16)0.73
Premature labour1.07 (0.97–1.19)0.19
Gestational diabetes0.86 (0.57–1.28)0.45
Thrombo-embolic event**
Placental abruption**
Neonatal outcome
Number of twins0.95 (0.77–1.17)0.631.88 (0.61–5.84)0.271.51 (0.20–11.2)0.69
Pregnancy duration (weeks)1.00 (0.99–1.01)0.920.88 (0.83–0.94)<0.0010.89 (0.81–0.97)0.011
Premature delivery1.07 (0.92–1.26)0.381.35 (0.64–2.86)0.430.57 (0.14–2.33)0.43
Infant weight (g)1.00 (1.00–1.00)0.451.00 (1.00–1.00)0.0011.00 (1.00–1.00)0.13
Small for gestational age1.07 (0.98–1.16)0.121.95 (1.15–3.30)0.0130.73 (0.30–1.76)0.48
Fetal mortality**5.55 (1.77–17.4)0.003**
Perinatal mortality0.95 (0.85–1.06)0.352.05 (0.29–14.6)0.475.01 (0.69–36.6)0.11
Recurrence of CHD0.95 (0.88–1.02)0.18

Cardiac complications

The incidence of cardiac complications was comparable between women with unrepaired and repaired ASDs (Table 4). The most frequent cardiac complication was the occurrence of clinically significant arrhythmia during eight pregnancies (4.3%) in six women, including nonsustained ventricular tachyarrhythmias (two pregnancies) and supraventricular tachyarrhythmias (six pregnancies, including two episodes of atrial fibrillation). One woman with a repaired ASD experienced supraventricular tachyarrhythmias (>200/minute) complicated by syncope during the third trimester of two consecutive pregnancies. Several episodes of nonsustained ventricular tachyarrhythmias (frequency 174–197/minute, documented using a 24-hour electrocardiogram) were observed during two consecutive pregnancies in the same woman with an unrepaired ASD. Management consisted of bed rest, without initiation of treatment with anti-arrhythmic drugs. The other women with an unrepaired ASD with documented supraventricular tachyarrhythmias experienced palpitations. No electrical cardioversion was performed.

Persistence (>1 year postpartum) of pregnancy-related NYHA class deterioration was observed after six pregnancies (3.2%). Two of these women needed diuretics.

One woman with an unrepaired ASD experienced temporary right-sided hemiparesis in the early stages postpartum. She had no history of thrombo-embolic events or arrhythmias. The diagnosis of transient ischaemic attack was made after exclusion of cerebral infarction or bleeding using a computed tomography scan. No episodes of heart failure, endocarditis or stroke were documented.

Obstetric complications

No differences were observed between women with unrepaired and repaired ASDs with regard to obstetric complications (Table 4). No episodes of eclampsia or HELLP syndrome were documented. Compared with the general population (Generation R), women with an unrepaired ASD had a higher risk of pre-eclampsia (AOR = 3.54, 95% CI .26–9.98).

There was no difference in mode of delivery between women with unrepaired and repaired ASDs (Table 2). In total, 28 caesarean deliveries (14.8%) were performed (14 planned and 14 emergency caesarean sections). None was performed for maternal cardiac reasons. Indications for planned caesarean sections were: history of caesarean section (14.3%), fetal distress (14.3%), breech presentation (14.3%), twin pregnancy (14.3%), cephalopelvic disproportion (14.3%) and unknown reasons (28.6%). Emergency caesarean sections were performed for prolonged first or second stage of labour (42.9%), fetal distress (42.9%), umbilical cord prolapse (7.1%) and cephalopelvic disproportion (7.1%).

Neonatal complications

In comparison with the general population (Generation R), women with an unrepaired ASD had a higher risk of fetal mortality (AOR 5.55, 95% CI 1.77–17.4) and offspring who were more often small for gestational age (AOR 1.95, 95% CI 1.15–3.30) (Table 4). By contrast, the outcome for offspring of women with a repaired ASD was comparable with that in the general population.

Recurrence of congenital heart disease was reported in five children (2.6%). Women with a repaired ASD had two children with a haemodynamically unimportant ventricular septal defect and a child with an interrupted aortic arch. Women with an unrepaired ASD had a child with a secundum ASD and a child with a haemodynamically unimportant ventricular septal defect. There were three intrauterine deaths, all in women with an unrepaired ASD. The cause of fetal death was twin-to-twin transfusion syndrome, nephroblastomatosis and unknown cause. Furthermore, two children died within the first month after birth. One premature child (24 weeks gestation) of a woman with a repaired ASD died on the day of delivery and the other child died 1 week postpartum as a consequence of severe neurological damage secondary to chorioamnionitis.

Factors associated with pregnancy outcome

After adjustment for multiple pregnancies per woman, univariable analysis showed that a history of arrhythmias (AOR 5.37, 95% CI 1.04–27.8, P = 0.045) and maternal age > 30 years (AOR 5.89, 95% CI 1.44–24.1, P = 0.014) were associated with a higher risk of the combined endpoint of cardiac complications (Table 5). Multivariable analysis demonstrated that only a maternal age > 30 years was independently associated with a higher risk of cardiac events (AOR 5.20, 95% CI 1.92–18.6, P = 0.011).

Table 5.   Factors associated with the combined endpoints of cardiac, obstetric and neonatal events
 Univariable analysisMultivariable analysis
AOR (95% CI)P-valueAOR (95% CI)P-value
  1. AOR, adjusted odds ratio; ASD, atrial septal defect; CI, confidence interval.

  2. AORs were adjusted for multiple pregnancies per woman. Potential explanatory factors that were tested in the univariable logistic regression analysis were (1) history of arrhythmia, (2) history of thrombo-embolic complications, (3) history of previous completed pregnancy, (4) smoking before pregnancy, (5) smoking during pregnancy, (6) presence of right ventricular dilatation, (7) maternal age > 30 years and (8) unrepaired ASD. Only factors with a P-value < 0.10 in the univariable analysis were tested in the multivariable analysis.

Cardiac complications
History of arrhythmias5.37 (1.04–27.84)0.0453.97 (0.74–21.28)0.107
Maternal age > 30 years5.89 (1.44–24.08)0.0145.20 (1.92–18.64)0.011
Obstetric complications
Maternal age > 30 years2.34 (1.10–4.95)0.027
Neonatal complications
Unrepaired ASD2.99 (1.14–7.89)0.027

For the combined endpoint of obstetric events, univariable analysis indicated that only maternal age > 30 years was associated with a higher risk (AOR 2.34, 95% CI 1.10–4.95, P = 0.027). As no other potential explanatory factor was associated with a P-value < 0.10, multivariable analysis was not performed for obstetric events.

With regard to neonatal events, univariable analysis indicated that only an unrepaired ASD was associated with a higher risk (AOR 2.99, 95% CI 1.14–7.89, P = 0.027). As no other potential explanatory factor was associated with a P-value < 0.10, multivariable analysis was not performed for neonatal events.

Discussion

The population of adults with congenital heart disease is increasing as a result of diagnostic and therapeutic advances in cardiology and cardiac surgery. As a consequence, more women with congenital heart disease are contemplating pregnancy. These women should be offered appropriate pre-pregnancy counselling regarding the risk of pregnancy and the incidence of recurrence of congenital heart disease in their offspring. In this multicentre study, we report the outcome of pregnancy in women with a ‘simple’ ASD, with particular emphasis on the differences between women who have unrepaired and repaired lesions.

Right ventricular volume overload as a result of an ASD is aggravated during pregnancy. During pregnancy, clinically important haemodynamic alterations are needed to sustain intrauterine life and maintain maternal homeostasis. There is an increase in plasma volume (40–50%) mediated by neurohormonal alterations leading to increased levels of aldosterone and hence sodium and water retention.14,15 In women with an ASD, this ‘pregnancy-related volume load’ may trigger ventricular failure. Distention of atrial tissue may further increase the risk of arrhythmias (mainly atrial fibrillation or flutter).16,17

In the present study, the outcome of pregnancy was associated with corrective status. The presence of an unrepaired ASD was associated with an adverse neonatal outcome. The higher incidence of neonatal events can partly be explained by the reduced capacity to increase cardiac output in the presence of a left-to-right shunt. Because of the limited autoregulatory capacity, the uteroplacental circulation is directly dependent on cardiac output. Decreased cardiac output has been associated with intrauterine growth restriction and a higher incidence of premature delivery.18,19 Furthermore, reduced placental perfusion may result in pre-eclampsia.20 In the present study, women with an unrepaired ASD had a higher risk of fetal mortality, pre-eclampsia and children born small for gestational age compared with the general population. Actis Dato et al. demonstrated that women with an unrepaired ASD had an increased incidence of miscarriages, preterm deliveries and cardiac symptoms compared with women with a repaired ASD.8 Other studies have shown that earlier closure of an ASD seems beneficial, as older age at surgical repair is a risk factor for premature late death, which becomes progressively more powerful with increasing age at operation.17,21,22 The above-mentioned data provide an additional argument in favour of closing clinically significant ASDs (i.e. shunt fraction > 1.5 or presence of right heart dilatation) before pregnancy, if circumstances allow.23 However, many women with an ASD are unaware of their heart defect before pregnancy. This explains the relatively late age at repair in women with a repaired ASD (25.9 ± 14.4 years) in our study, which was also demonstrated in the study of Zuber et al.1

Arrhythmias were the most frequently reported cardiac complication (4.3%) in our study; in particular, older women and women with a previous history of arrhythmias appeared to be at increased risk. This high risk of arrhythmias was not found in our recent systematic literature review of pregnancies in women with an ASD, where the risk of arrhythmias was 0.8% of completed pregnancies.13 Whether these complications are attributable to pregnancy or are part of the patient’s natural history, or a combination of the two, remain difficult to determine.

Pregnancy is a thrombogenic state as a consequence of changes in the coagulation cascade and stasis resulting from compression of the vena cava. Paradoxical embolus of a deep venous thrombosis is one of the major concerns if septal defects are still present during pregnancy.24–26 This was demonstrated in our study by the postpartum occurrence of a transient ischaemic attack in a woman with an unrepaired ASD. Obviously, preconception closure of the ASD eliminates the hazard of paradoxical embolisation during pregnancy.

Finally, our data identified older maternal age as a risk factor for obstetric complications, which is consistent with studies in the general population.27 Interestingly, older age was also independently associated with an increased risk of cardiac complications. These findings may indicate that there should be closer follow up of older women with an ASD contemplating pregnancy.

Study limitations

Several potential limitations must be noted. First, the retrospective design necessitated a review of patients’ medical records and consequently missing values are inevitable. Nevertheless, all mentioned complications had to be documented by medically qualified personnel in the records according to the pre-set definitions before data entry. The size and shunt fraction of the unrepaired ASD were not systematically available; however, we used right ventricular dilatation as a marker of severe left-to-right shunting. Second, this study was performed in women who had survived pregnancy and were alive at the time of this study. This may underestimate the risk of complications during pregnancy; however, the prognosis of most patients with an ASD is relatively good and the risk of mortality during pregnancy is deemed low.22 Third, confounding by indication may represent an important bias in this observational study. The allocation of surgical repair was not randomised and the indication for surgery may be related to the risk of future health outcomes; the resulting imbalance in the underlying risk profile between the groups with repaired and unrepaired ASDs can generate biased results. However, one would expect that women with a repaired ASD would have a higher background risk with more pregnancy complications compared with women with an unrepaired ASD. In the present study, women with an unrepaired ASD were more at risk of pregnancy complications. Finally, together with the low number of events (for cardiac events, in particular, over-fitting may be a problem) and the possible effects of multi-testing, for example inflation of type I error (e.g. false positive results), any conclusions based on the present study must be drawn with caution. The conclusions drawn should be regarded as hypothesis-generating and need to be validated in prospective studies.

Conclusion

This multicentre study of women with an ASD shows that the outcome of pregnancy is in general favourable, despite the increased risk of arrhythmias and pre-eclampsia. The low recurrence rate of congenital heart disease does not preclude pregnancy, although the risk of complex congenital heart disease is present. The incidences of cardiac and obstetric complications were comparable between women with unrepaired and repaired ASDs. However, women with an unrepaired ASD had an increased risk of neonatal events; in particular, the risk of having offspring who are small for gestational age was increased. Whether this justifies aggressive corrective repair before pregnancy requires a prospective study with detailed information on the severity of the shunt before pregnancy. The data support current preconception management to close haemodynamically significant ASD lesions.

Disclosure of interest

Nothing to declare.

Contribution to authorship

S-CY, WD, JWR-H, JMM, EAPS and PGP were responsible for the conception and design of the study. S-CY, VWVJ and WD were responsible for the acquisition of data. S-CY, APJvD, HWV, PM, WD and VWVJ analysed the data. All authors were responsible for interpretation of the data. S-CY drafted the article. All co-authors were responsible for critical revision of the manuscript. Finally, all authors approved the final version of the manuscript.

Details of ethics approval

The study received ethical approval in all participating tertiary centres.

Funding

This study was supported by funding from Netherlands Heart Foundation (2002 B125 to PGP); Interuniversity Cardiology Institute, the Netherlands.

Acknowledgements

The authors would like to thank Els Huyghe and Els Costermans for data collection in Belgium. Furthermore, we would like to thank Professor Eric Boersma for his statistical analysis.

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