Congenital heart disease embraces a wide range of heart defects, ranging from benign lesions such as atrial septal defects to very complex conditions, such as transposition of the great vessels or univentricular heart. CHD was defined as “a gross structural abnormality of the heart or intrathoracic great vessels that is actually or potentially of functional significance” . The improvement in medical and surgical technologies leads to enhance the life expectancy patients with CHD dramatically during the last decades  . Nowadays, about 90% of children who are born with heart defects can survive into adulthood . As a result, adult patients suffering from CHD comprise a relatively new and constantly growing patient population . Similarly, females who reach the childbearing age increased. Congenital heart diseases are the most prevalent form of heart disease among pregnant women  and the leading cardiac cause of maternal morbidity and mortality in developed countries . Pregnancy is the most common non-cardiac cause of hospitalization among women suffering from CHD as it is associated with significant physiological changes that overwhelm the cardiovascular system  .
Traditionally, women suffering from CHD were recommended to avoid pregnancy . However, recent evidence has revealed that women can get pregnant with acceptable maternal and child outcomes . On the other hand, pregnancy carries many risks for women suffering from CHD as a result of the normal physiological changes associated with it in comparison with women without CHD or with other cardiac disorders . For example, cardiac output may double immediately during the postpartum period due to the increase in heart rate and stroke volume, which results from the auto-transfusion of fluid from the contracted uterus. Increased plasma volume, decreased systemic vascular resistance, aortocaval compression, circulating catecholamines from pain, and postpartum hemorrhage are important causes of cardiac and hemodynamic stress that place these women at higher risk for adverse maternal and fetal outcomes . Searching the different databases, no integrative literature review (ILR) was found that reviewed the available literature that studied pregnancy outcomes among women suffering from CHD. Accordingly, in this review, all recent and available literature that addresses these issues reviewed and integrated to get the most accurate evidence. Between the traditional perceptions of pregnancy among women suffering from CHD and the newly adapted approach regarding the risk associated with their pregnancy; there is a need to highlight the short-term and long-term outcomes that are associated with pregnancy among this population.
The results of this ILR can help in presenting synthesized evidence, in addition to adding more were information to the body of literature about pregnancy outcomes in women suffering from CHD. Moreover, having such information can help nurses and providers in providing care and education for these patients, as the identifying of outcomes of pregnancy in CHD patients will make it easier for nurses to provide an individualized care and support based on patients’ expected outcomes. This ILR will increase the awareness of nursing administrators and educators about pregnancy outcomes in women suffering from CHD.
2.1. Problem Identification
Recently, a growing number of research that addressed pregnancy outcomes among women suffering from CHD have emerged. However, the available evidence is built mostly on reviewing patients’ records in a single center with a small sample size . That makes it difficult to provide meaningful advice for women suffering from CHD who wish to get pregnant. The researcher in this ILR identified the need for integrating the results of different studies to get the best available evidence regarding pregnancy outcomes among women suffering from CHD. The purpose of this integrative literature review was to examine the literature related to pregnancy outcomes among women suffering from CHD. This ILR was conducted based on Whittemore and Knafl (2005) framework. Whittemore and Knafl (2005) modified the integrative literature review method of Cooper (1998), which consists of five stages: problem formulation; a search of literature; data evaluation; data analysis; and presentation of findings . This framework was considered for this review as it facilitates the inclusion of a large number of variables and considers both qualitative and quantitative evidence, with the intent to provide a broad perspective of the phenomenon .
2.2. Literature Search
In this review, the search was accomplished on January 2020 using different databases that include: Google Scholar, Scopus, Science Direct, Pub MED, Medline, CINAHL, EBSCO, Cochrane, ERIC uses the keywords of “congenital heart disease”, “pregnancy”, “adverse events” and “outcomes”. Initially, in a separated manner from each other, then each new search added a new keyword until including all keywords. Later, these words were searched in combination with each other. The Boolean operator “OR” and “AND” were applied separately and in combination with the keywords to expand results. However, the searching process was limited to the following inclusion criteria: 1) written in English, 2) published between 2010 and 2020 to ensure a contemporary view of pregnancy outcomes, and 3) no restriction to the research design. The experimental designs, mixed-method approach, quantitative, qualitative, and descriptive studies were considered and examined to identify outcomes. However, review papers and incomplete reports in the form of editorials, opinion pieces, and conference abstracts have excluded.
2.3. Search Results
The principal investigator searched the literature. Two thousand and seven hundred articles were retrieved and the initial evaluation of their title abstracts took place. After evaluating and removing the duplicated articles, only 650 were found related to the topic of interest. Then, related articles were printed and read in full, following a secondary evaluation, 16 articles were exactly identified to cover the inclusion criteria. As a result, those sixteen articles were included in this review (see Figure 1). The principal investigator used a research matrix to extract the necessary data (see Table 1). From each article, the following data were extracted: study purpose, design, settings, sample size, and key findings. Besides, the extracted data from the articles were used another time to check eligibility of the included articles based on the early discussed eligibility criteria. Moreover, the extracted data quality was checked by the second investigator by reading all of the 16 eligible articles and confirming the data of the research matrix. All of the 16 eligible articles are quantitative.
Figure 1. Flow diagram of the study selection strategy.
Table 1. Summary of the reviewed articles.
2.4. Data Evaluation, Rigor, and Data Quality
The quality of methods used in the included articles was assessed by using criteria for assessing the quality of quantitative studies, which was recommended by Kmet et al. (2014). The checklist comprised of 14 questions with a corresponding scoring system as follows: (Yes = 2); (Partially = 1); (No = 0); and not applicable . The manual provided comprehensive instructions for scoring each aspect. The quality of each article was then rated as being strong (>80%), good (70% - 80%), adequate (50% - 69%) or limited (<50%) .
The quality score of each article was calculated by summing the total score of items and dividing it by the highest possible total score after removing non-applicable items. The calculated summary score for each article can range between zero and two (see Table 2). This assessment was independently attained by two reviewers to determine the strengths and weaknesses of the studies and any discrepancies in opinion were resolved through discussion (Kmet et al., 2004).
2.5. Data Analysis
Following Whittemore and Knafl’s (2005) methodological approach of conducting an integrative review, analysis has four phases. 1) Data reduction: represents a process that divides the primary sources into subgroups to facilitate analysis. 2) Data display: showing data as they appeared in the research matrix (data extraction sheet), to enhance comparison. 3) Data comparison: examining data to identify patterns, relationships, and themes, by which variables can be grouped together and a conceptual map can be drawn. 4) Conclusion drawing and verification: conclusion drawing occurs when the inquirer identifies patterns and relationships at a more abstract level, and generalizes the findings to populations of interest .
The reviewed articles showed that women suffering from CHD can get pregnancy safely without any adverse events    ; however, there are still some associated risks that could affect the mother and the offspring negatively. The occurrence of such adverse events mainly depends on the severity of CHD and the residual lesions . The pregnancy outcomes were addressed by time into short-term outcomes and long-term outcomes.
3.1. Short-Term Outcomes
In the reviewed studies, pregnancy in women with CHD showed a satisfactory outcomes for both of the mothers and the fetus      . However, there are still some complications that take place which is higher in this population than women without CHD . The occurrence and severity of these complications and adverse outcomes depend mainly on the complexity of the lesions (Warrick et al., 2015). The reported short-term outcomes are divided into three major categories: maternal/obstetric, fetal, and cardiac outcomes.
3.1.1. Maternal/Obstetric Outcomes
Congenital heart diseases not only pose a cardiac impact on women, but it has obstetric impacts, too. Many adverse obstetric outcomes were reported in the literature; such as pregnancy-induced hypertension (PIH: systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg after 20 weeks of gestation), premature labor (labor before 37 weeks of gestation), DVT/PE, placenta previa, placenta abruption and postpartum hemorrhage (PPH) (blood loss in vaginal delivery ≥ 800 ml or in cesarean delivery (CS) ≥ 1, 500 ml)   . However, the placental disease was not different significantly between women with and without CHD (Schlichting et al., 2019). In some subtypes of CHD, women with CHD had significantly lower probabilities of placental disease as paralleled with the general population . Moreover, prolong hospitalization and increase utilization of the services were reported, especially with complex CHD  . A diagnosis of the ventricular septal defect (VSD) was associated with a significantly higher prevalence of maternal mortality and morbidity than the other CHD subtypes (p = 0.01)   .
Postpartum hemorrhage occurs overall at a rate of 21% in CHD . Vaginal delivery was found as a preferable mode of delivery considering the maternal risk to reduce the risk of (PPH) . Furthermore, the forceps delivery; anticoagulant medication; the complexity of CHD and Fontan circulation were identified as a predictor of PPH .
Ladouceur et al. (2017) recently assessed obstetric and fetal outcomes of 28 pregnancies among 20 women suffering from pulmonary arterial hypertension associated with congenital heart disease. Overall, 33% of pregnancies were associated with adverse cardiac events with a severe reduction in resting oxygen saturation . Obstetrical adverse events occurred in (25%) of the pregnancies, such as postpartum hemorrhage occurred in four cases, premature rupture of membranes in one case. Small for gestational age, was diagnosed in 39% of fetuses. Of the study participants, 67% of pregnancies were delivered by cesarean section, of which 10 participants were in an emergency for an obstetrical reason. Prematurity was frequent (78%), but no neonatal death occurred .
3.1.2. Fetal Outcomes
The risk of fetal and neonatal complications is higher among pregnant women with CHD as compared to healthy women   . The presence of maternal cardiovascular disease can place the fetus and neonate at greater risk . The type and severity of neonatal complications are determined by the type and severity of the maternal underlying cardiac conditions and subtype . For example, preterm birth incidence ranged from 9.7% in women with ventricular septal defects to 27.2% in women with a single ventricle . One mechanism that has been suggested as a source for these complications is insufficient uteroplacental blood flow in the setting of cardiac anomalies resulting in a slowing of fetal growth, making premature termination of pregnancy necessary or leading to spontaneous abortion . Adverse fetal and neonatal outcomes complicate 11.5% - 39% of pregnancies   . Fetal adverse events were identified as small-for-gestational-age (SGA, birth weight < 10th percentile), complications with congenital heart disease, prematurity, and intrauterine or neonatal death (within 28 days). These complications could occur in any form of CHD even if it is repaired or not . One study documented overall fetal mortality of 1% and a fetal deformity rate of 18% . Prematurity and low gestational ages were the main complications in pulmonary artery hypertension and it is increasing in severity as the resting oxygen saturation decreased . The risk for a woman with CHD to have a child who also has a congenital heart defect depends on and varies based on the type of maternal heart disease ranging from 3% to 12%. For defects with an autosomal dominant transmission pattern (such as Marfan syndrome), the risk increased by up to 50%. In such cases, genetic screening should be obtained in the 12th week of pregnancy .
3.1.3. Cardiac Outcomes
Cardiac events were reported as new onset or worsening of arrhythmia requiring treatment, heart failure which is diagnosed through the following criteria (a decline in New York Heart Association (NYHA) class, pulmonary congestion confirmed by chest radiography, the requirement for diuretic therapy), endocarditis, or thromboembolic events during pregnancy to one month after delivery . Adverse maternal cardiac events after pregnancy were more common in women who had cardiac events during pregnancy  . Moreover, Assenza and colleagues (2013) conducted a retrospective analysis to better understand the effect of pregnancy on right ventricular remodeling in women with repaired TOF, and they found that pregnancy accelerates the rate of right ventricular remodeling in pregnancy group compared with the non-pregnancy group, which means an increase in end-diastolic volume; however, the RV systolic function does not decline  .
Arrhythmia and heart failure are the most commonly occurring cardiac adverse event during pregnancy  . A pre-conception evaluation and history of SVT or the use of any cardiac medications should be assessed to predict the cardiac risks and outcomes. The presence of pre-pregnancy arrhythmias is considered a predictor of major cardiac events during pregnancy . In a prospective study to evaluate the pregnancy outcomes in women with heart disease, ten predictors were identified. Which were: five general predictors (prior cardiac events or arrhythmias, poor functional class or cyanosis, high-risk valve disease/left ventricular outflow tract obstruction, systemic ventricular dysfunction, no prior cardiac interventions); four lesion-specific predictors (mechanical valves, high-risk aortopathies, pulmonary hypertension, coronary artery disease); and the last predictor is the delivery of care (late pregnancy assessment) .
In a contradictory to the traditional thinking that pregnancy outcomes will be better in women with CHD who underwent a cardiac repair surgery; Yadav and his colleagues (2018) found no statistically significant differences in the cardiac, maternal and neonatal outcomes between the operated CHD and non-operated CHD population who pose the same baseline characteristics . Also, they recommend that every woman with CHD should do a pre-pregnancy risk assessment and consultation to obtain optimum care .
3.2. Long-Term Outcomes
Limited studies have assessed the effect of pregnancy on long-term outcomes in women suffering from CHD. To assess the cardiac outcomes in women suffering from CHD after pregnancy, Balint and colleagues (2010) conducted a prospective study recruiting a consecutive sample of pregnant women who were referred for follow up or consultation in a cardiac center. The data were collected throughout 1995-2007, antenatal, perinatal and postnatal data were collected from these pregnant women. At the first antenatal visit, comprehensive examinations and investigations to assess the cardiac conditions were performed as baseline data. Also, during pregnancy; any cardiac complications were recorded, and any obstetric or fetal complications were recorded too; to be studied as predictors with any late cardiac complications after pregnancy completion. The late cardiac complications were defined as: sudden cardiac death, pulmonary edema, cardiac arrhythmias (Tachy/Bradyarrhythmias), stroke or transient ischemic attacks . This study involved 405 pregnancies. Of them, 50 (12%) had late cardiac events; three women died after pregnancy. This incidence is higher than reported by Kampman et al. (2015) in their prospective multicenter study. The most occurred complication was cardiac arrhythmias; it occurred in thirty-five women. The most frequent arrhythmia was supraventricular tachycardia followed by atrial fibrillation. Also, fifteen women developed congestive heart failure . In this study, about 1/10 women have gotten late cardiac events. The women with poor baseline functional ability and/or cyanosis, ventricular dysfunction and left ventricular outflow tract obstruction were at the highest risk for late cardiac complications. In addition, women who developed cardiac complications during pregnancy were at higher risk of getting late cardiac complications after delivery. It is crucial to take into consideration these factors as predictors for late cardiac complications post-delivery among high-risk women during pre-pregnancy counseling and assessment .
To follow the long-term outcomes one-year post-delivery, Kampman et al. (2015) conducted a prospective multi-center cohort study. They found that the complications after one year of delivery are rare; the overall incidence rate was 6.4%. The occurrence of post-partum complications was higher in women with a mechanical prosthetic valve, in women who use cardiac medications, pre-pregnancy, especially beta-blockers and anti-coagulants, and in women with a history of arrhythmias .
Gußmann et al. (2013) conducted an analysis of a self-assessment of health, work capability, and physical activity during the longest possible follow-up period; the follow-up period reached up to eleven years. In this analysis, 107 women were followed, two-thirds of the patients reported good outcomes in the self-assessments of health, work capability and physical activity in the long-term follow-up period. The health self-assessment correlated positively with the physical activity. For the long-term outcomes, eighteen percent of the women with contraindications to pregnancy died, and all patients (with contraindications to pregnancy) who responded to the follow up questionnaire developed pulmonary hypertension. The results of this study suggest to continue in the advisement of contradictory of pregnancy considering not only the short-term outcomes, but also the long-term outcomes .
In this review, the following themes were identified: short-term outcomes that are divided into three sub-categories: maternal, cardiac, and fetal outcomes   -  and long-term outcomes    . Based on interpretation and synthesis of the reviewed articles the following results can be demonstrated; women with CHD can tolerate pregnancy with satisfactory maternal and fetal outcomes. However, they still have an increased risk of cardiac and fetal complications than the ordinary population. The overall incidence of CHD among pregnant women was 0.6% .
The calculated scores for the rigor of the research articles ranged between 0.60 and 0.73, with a mean average of 0.65. In addition, the minimum score of the included studies was 0.60 indicating adequate rigor of the included studies; therefore, no studies were excluded based on the calculated scores.
There are some limitations of the reviewed articles. Out of the 16 reviewed articles, thirteen research articles were conducted in a retrospective manner over a variable period. Of them, eleven had taken place in a single center or hospital to evaluate the cardiac and fetal outcomes for women suffering from CHD   - . While the remaining three articles were conducted prospectively, two of them were conducted in multi-center settings. Mostly, these studies have given us almost consistent results regarding the maternal and fetal outcomes among CHD patients. Reviewing the patients’ records retrospectively could be beneficial for recognizing maternal and fetal outcomes, however; it is not the most robust design to identify these outcomes. Regarding the sample size, only three research results were concluded based on a national representative sample or a population-based sample   . Additionally, the sample size was small in most of the reviewed articles, which may relate to the nature of the studied population and the availability of the cases; this is in some degree limits the generalizability of the findings.
As most of the reviewed articles are conducted in retrospective or so-called survivor cohorts, there is a need for using more robust designs to get more valid results. Moreover, for accurate estimations of serious and relatively rare complications a large-scale (multicenter and international) prospective registration remains needed.
Several limitations of the present ILR need to be discussed. The quality of the review depends on the design of the articles included. The study designs mostly based on reviewing the patients’ records retrospectively, and few prospective studies to follow the long-term outcomes; therefore, the results need to be judged with caution. Selection bias is introduced by excluding articles based on the earlier-mentioned criteria. Underreporting of complications may also be an important problem.
The last decades show a progressive advancement in the management of congenital heart disease; that results in large numbers of women with repaired CHD, who are able now to successfully become pregnant and deliver healthy offspring. Previous uncertainty about the ability of these patients to successfully become pregnant and deliver safely has been replaced by the recognition that a large number can have excellent outcomes. However, despite this, these patients do continue to have higher cardiac, obstetric, and fetal risks than the general population. This highlights the importance of preconception counseling regarding the increased risk of fetal congenital heart disease with affected mothers and referrals for genetic assessment and counseling where appropriate, moreover, providing the appropriate and accurate advice for women about the potential adverse events that they may encounter on short-term and long-term basis.
 van der Bom, T., Bouma, B.J., Meijboom, F.J., Zwinderman, A.H. and Mulder, B.J. (2012) The Prevalence of Adult Congenital Heart Disease, Results from a Systematic Review and Evidence Based Calculation. American Heart Journal, 164, 568-575.
 Stout, K.K., Daniels, C.J., Aboulhosn, J.A., Bozkurt, B., Broberg, C.S. and Colman, J.M. (2019) 2018 AHA/ACC Guideline for the Management of Adults with Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology, 73, e81-e192.
 ávila, P., Mercier, L.-A., Dore, A., Marcotte, F., Mongeon, F.-P. and Ibrahim, R. (2014) Adult Congenital Heart Disease: A Growing Epidemic. Canadian Journal of Cardiology, 30, S410-S419.
 Drenthen, W., Pieper, P.G., Roos-Hesselink, J.W., van Lottum, W.A., Voors, A.A. and Mulder, B.J. (2007) Outcome of Pregnancy in Women with Congenital Heart Disease: A Literature Review. Journal of the American College of Cardiology, 49, 2303-2311.
 Opotowsky, A.R., Siddiqi, O.K. and Webb, G.D. (2009) Trends in Hospitalizations for Adults with Congenital Heart Disease in the US. Journal of the American College of Cardiology, 54, 460-467.
 Verheugt, C.L., Uiterwaal, C.S., van der Velde, E.T., Meijboom, F.J., Pieper, P.G. and Sieswerda, G.T. (2010) The Emerging Burden of Hospital Admissions of Adults with Congenital Heart Disease. Heart, 96, 872-878.
 Ntiloudi, D., Zegkos, T., Bazmpani, M.A., Parcharidou, D., Panagiotidis, T. and Hadjimiltiades, S. (2018) Pregnancy Outcome in Women with Congenital Heart Disease: A Single-Center Experience. Hellenic Journal of Cardiology, 59, 155-159.
 Warrick, C.M., Hart, J.E., Lynch, A.M., Hawkins, J.A. and Bucklin, B.A. (2015) Prevalence and Descriptive Analysis of Congenital Heart Disease in Parturients: Obstetric, Neonatal, and Anesthetic Outcomes. Journal of Clinical Anesthesia, 27, 492-498.
 Kamiya, C.A., Iwamiya, T., Neki, R., Katsuragi, S., Kawasaki, K. and Miyoshi, T. (2012) Outcome of Pregnancy and Effects on the Right Heart in Women with Repaired Tetralogy of Fallot. Circulation Journal, 76, 957-963.
 Ramage, K., Grabowska, K., Silversides, C., Quan, H. and Metcalfe, A. (2019) Association of Adult Congenital Heart Disease with Pregnancy, Maternal, and Neonatal Outcomes. JAMA Network Open, 2, e193667.
 Karamlou, T., Diggs, B.S., McCrindle, B.W. and Welke, K.F. (2011) A Growing Problem: Maternal Death and Peripartum Complications Are Higher in Women with Grown-Up Congenital Heart Disease. The Annals of Thoracic Surgery, 92, 2193-2198.
 Pillutla, P., Nguyen, T., Markovic, D., Canobbio, M., Koos, B.J. and Aboulhosn, J.A. (2016) Cardiovascular and Neonatal Outcomes in Pregnant Women with High-Risk Congenital Heart Disease. American Journal of Cardiology, 117, 1672-1677.
 Yadav, V., Sharma, J.B., Mishra, S., Kriplani, A., Bhatla, N. and Kachhawa, G. (2018) Maternal and Fetal Outcome in Operated vs Non-Operated Cases of Congenital Heart Disease Cases in Pregnancy. Indian Heart Journal, 70, 82-86.
 Schlichting, L.E., Insaf, T.Z., Zaidi, A.N., Lui, G.K. and Van Zutphen, A.R. (2019) Maternal Comorbidities and Complications of Delivery in Pregnant Women with Congenital Heart Disease. Journal of the American College of Cardiology, 73, 2181-2191.
 Cauldwell, M., Von Klemperer, K., Uebing, A., Swan, L., Steer, P.J. and Gatzoulis, M. (2016) Why Is Post-Partum Haemorrhage More Common in Women with Congenital Heart Disease? International Journal of Cardiology, 218, 285-290.
 Ladouceur, M., Benoit, L., Radojevic, J., Basquin, A., Dauphin, C. and Hascoet, S. (2017) Pregnancy Outcomes in Patients with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease. Heart, 103, 287-292.
 Silversides, C.K., Grewal, J., Mason, J., Sermer, M., Kiess, M. and Rychel, V. (2018) Pregnancy Outcomes in Women with Heart Disease: The CARPREG II Study. Journal of the American College of Cardiology, 71, 2419-2430.
 Assenza, G.E., Cassater, D., Landzberg, M., Geva, T., Schreier, J. and Graham, D. (2013) The Effects of Pregnancy on Right Ventricular Remodeling in Women with Repaired Tetralogy of Fallot. International Journal of Cardiology, 168, 1847-1852.
 Bowater, S.E., Selman, T.J., Hudsmith, L.E., Clift, P.F., Thompson, P.J. and Thorne, S.A. (2013) Long-Term Outcome Following Pregnancy in Women with a Systemic Right Ventricle: Is the Deterioration Due to Pregnancy or a Consequence of Time? Congenital Heart Disease, 8, 302-307.
 Balint, O.H., Siu, S.C., Mason, J., Grewal, J., Wald, R. and Oechslin, E.N. (2010) Cardiac Outcomes after Pregnancy in Women with Congenital Heart Disease. Heart, 96, 1656-1661.
 Kampman, M.A., Balci, A., Groen, H., van Dijk, A.P., Roos-Hesselink, J.W. and van Melle, J.P. (2015) Cardiac Function and Cardiac Events 1-Year Postpartum in Women with Congenital Heart Disease. American Heart Journal, 169, 298-304.
 Wacker-Gussmann, A., Thriemer, M., Yigitbasi, M., Berger, F. and Nagdyman, N. (2013) Women with Congenital Heart Disease: Long-Term Outcomes after Pregnancy. Clinical Research in Cardiology, 102, 215-222.