RESEARCH ARTICLE
Paroxysmal Supraventricular Tachycardia in Pregnant Women and Birth Outcomes of Their Children: A Population-Based Study Ferenc Ba´nhidy,1 Nandor Acs,1 Erzsebet H. Puho,2 and Andrew E. Czeizel2* 1
Second Department of Obstetrics and Gynecology, Semmelweis University, School of Medicine, Budapest, Hungary
2
Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary
Manuscript Received: 1 February 2010; Manuscript Accepted: 12 September 2010
The aim of the study was to estimate the possible association of pregnant women with paroxysmal supraventricular tachycardia (PSVT) with the possible risk for adverse birth outcomes, particularly different congenital abnormalities (CAs) in their children. Prospectively and medically recorded PSVT was evaluated in 103 pregnant women who later had offspring with CA (case group) and 149 pregnant women who later delivered newborn infants without CA (control group) and matched to cases in the population-based data set of the Hungarian Case–Control Surveillance System of Congenital Abnormalities, 1980–1996. Of 252 pregnant women with PSVT, 115 (45.6%) had the onset of this condition before the study pregnancy, that is, their PSVT was a chronic condition, while the rest (N ¼ 137) of PSVT was considered as new onset in the study pregnancy. The comparison of occurrence of PSVT in pregnant women who had offspring with different CA groups and in control mothers showed a higher risk for cardiovascular CAs (adjusted OR with 95% CI: 2.1, 1.1–3.8) explained mainly by secundum atrial septal defect. This association was confirmed in pregnant women with PSVT in the second and/or third gestational month, that is, critical period of cardiovascular CAs. In conclusion PSVT in pregnant women associates with a higher risk of secundum atrial septal defect in their children. Ó 2015 Wiley Periodicals, Inc.
Key words: paroxysmal supraventricular tachycardia; related drug treatment; birth outcomes; congenital abnormalities; cardiovascular malformations; secundum atrial septal defect
INTRODUCTION The two major classes of cardiac arrhythmias can be classified clinically as bradyarrhythmias and tachyarrhythmias [Blanchard and Shabetai, 2004; McAnulty et al., 2008; Tedrow and Stevenson, 2008]. Tachyarrhythmias are differentiated sinus tachycardia, supraventricular arrhythmias and ventricular arrhythmias. Supraventricular tachycardias include all tachyarrhythmias that either originate from or incorporate supraventricular tissue in a reentrant circuit [Calkins, 2008]. The most common manifestation of these cardiac arrhythmias is paroxysmal supraventricular tachycardia (PSVT), a clinical syndrome characterized by a rapid, regular tachycardia with abrupt onset and termination. About two-thirds
Ó 2015 Wiley Periodicals, Inc.
How to Cite this Article:
N, Puh Banhidy F, Acs o EH, Czeizel AE. 2015. Paroxysmal supraventricular tachycardia in pregnant women and birth outcomes of their children: A population-based study. Am J Med Genet Part A 167A:1779–1786.
of patients with PSVT are caused by atrioventricular nodal reentrant tachycardia. Women are affected twice as men. The rest one-third of patients have orthodromic atrioventricular reciprocating tachycardia. PSVT is also the most common cardiac arrhythmia in pregnant women [Wiederhorn et al., 1992; Lee et al., 1995] with dizziness, palpitations, and light-headedness [McAnulty et al., 2008]. The aim of our study was to estimate the possible association between maternal PSVT and birth outcomes, particularly the risk of structural birth defects, that is, congenital abnormalities (CAs) in their children in the population-based data set of the Hungarian Case–Control Surveillance of Congenital Abnormalities (HCCSCA) [Czeizel et al., 2001]. However, the diagnosis of PSVT based on maternal information was not reliable therefore we decided to evaluate only prospectively and medically recorded PSVT in the prenatal maternity logbook.
MATERIALS AND METHODS Study Subjects Cases affected with CA were selected from the data set of the Hungarian Congenital Abnormality Registry (HCAR), 1980–1996 [Czeizel, 1997] for the HCCSCA. Notification of cases with CA is Conflicts of interest: none declared. *Correspondence to: 32, H-1026 Budapest, Hungary. Andrew E. Czeizel, T€ or€ okvesz lejto E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 27 May 2015 DOI 10.1002/ajmg.a.33759
1779
1780 mandatory for physicians from the birth until the end of first postnatal year to the HCAR. Most cases are reported by obstetricians and paediatricians. In Hungary practically all deliveries take place in inpatient obstetric clinics and the birth attendants are obstetricians. Paediatricians are working in the neonatal units of inpatient obstetric clinics, or in various inpatient and outpatient paediatric clinics. Autopsy was mandatory for all infant deaths and it was suggested in stillborn fetuses, thus the occurrence of autopsy was nearly 100% in infant deaths and about 80% of stillborn fetuses during the study period. Pathologists sent a copy of the autopsy report to the HCAR if defects were identified in stillbirths and infant deaths. Since 1984 fetal defects diagnosed in prenatal diagnostic centres with or without termination of pregnancy have also been included into the HCAR. CAs were differentiated into three groups: lethal (if defects cause stillbirths or infant deaths or pregnancies were terminated due to fetal defect in more than 50% of cases), severe (without medical intervention CAs cause handicap or death) and mild (CAs require medical intervention but life expectancy is good). Lethal and severe CAs together constitutes major CAs. (Minor anomalies or morphological variants without serious medical or cosmetic consequences are excluded from the class of CA.) In addition two main categories of cases with CAs were differentiated: isolated (only one organ is affected) and multiple (concurrence of two or more CAs in the same person affecting at least two different organ systems). The recorded total (birth þ fetal) prevalence of cases with CA diagnosed from the second trimester of pregnancy through the age of 1 year was 35.0 per 1,000 informative offspring (live-born infants, stillborn fetuses and electively terminated malformed fetuses) in the HCAR, 1980–1996, though the expected rate was 65.3 per 1,000 [Czeizel et al., 1993]. However, about 90% of major CAs was recorded in the HCAR during the 17 years of the study period [Czeizel, 1997]. The proportion of live-born infants, stillborn fetuses, and electively terminated malformed fetuses was 97.1%, 1.1%, and 1.8%, respectively. There were three exclusion criteria of cases with CAs from the HCAR for the data set of the HCCSCA: (i) cases reported after 3 months of birth or pregnancy termination (23% of cases were reported after the first 3-month time window and had mainly mild CAs), (ii) cases with three mild CAs (congenital dysplasia of hip and inguinal hernia, large hemangioma), and (iii) CA-syndromes caused by major mutant genes (e.g., achondroplasia) or chromosomal aberrations (such as Down, Patau, Edwards syndromes) with preconceptional origin. Controls were defined as newborn infants without CA and they were selected from the National Birth Registry of the Central Statistical Office for the HCCSCA. In general two controls were matched to every case according to sex, birth week in the year when cases were born, and district of parents’ residence.
Collection of Exposure Data and Confounders Three sources of data were evaluated: (1) Prospective Medically Recorded Data: Mothers were asked in an explanatory letter to send us the prenatal maternity logbook
AMERICAN JOURNAL OF MEDICAL GENETICS PART A and other medical records particularly discharge summaries concerning their diseases during the study pregnancy and their child’s CA. Prenatal care was mandatory for pregnant women in Hungary (failure to attend prenatal care clinic results in denial of maternity leave benefits which include the maternity grants and days off from work), thus nearly 100% of pregnant women visited prenatal care clinics, on average seven times in their pregnancies. The first visit occurred in the prenatal care clinic between the 6th and 12th gestational week. The task of the licensed obstetricians is to record all pregnancy complications, maternal diseases, and related drug prescriptions in the prenatal maternity logbook. (2) Retrospective Self-reported Maternal Information: A structured questionnaire with a list of medicinal products (drugs and pregnancy supplements) and diseases, plus a printed informed consent form were also mailed to the mothers immediately after the selection of cases and controls. The questionnaire requested information on pregnancy complications and maternal diseases, on medicinal products taken during pregnancy according to gestational months, and on family history of CAs. To standardize the answers, mothers were asked to read the enclosed lists of medicinal products and diseases as a memory aid before they filled in the questionnaire.The mean SD time elapsed between the birth or pregnancy termination and the return of the ‘‘information package’’ (questionnaire, logbook, discharge summary, and informed consent form) in our prepaid envelope was 3.5 1.2 and 5.2 2.9 months in the case and control groups, respectively. (3) Supplementary Data Collection: Regional nurses were asked to visit all non-respondent case mothers at home and to help mothers fill in the study questionnaire and to evaluate the available medical records. In addition they obtained data regarding smoking and drinking habit through a cross interview of mothers and their close relatives living together, and finally the so-called family consensus data were recorded. The smoking habit was evaluated on the number of cigarettes per day while three groups of drinking habit were differentiated: (i) abstinent or occasional drinkers, who consumed less than one drink per week, (ii) regular drinkers consumed from daily one drink to one drink per week, (iii) hard drinkers consumed more than one drink per day. However, the committee on ethics did not allow the home visit of non-respondent control mothers because they considered it to be disturbing to the parents of healthy children. Regional nurses therefore visited only 200 non-respondent and 600 respondent control mothers as part of two validation studies [Czeizel et al., 2003b; Czeizel and Vargha, 2004]. Regional nurses used the same method in these control mothers than in non-respondent case mothers. Overall, the necessary information was available on 96.3% of cases (84.4% from reply to the mailing, 11.9% from the nurse visit) and 83.0% of the controls (81.3% from reply, 1.7% from visit). Informed consent form was signed by 98% of mothers, names, and addresses were deleted in the rest 2%. The flowchart of cases and controls was published previously [Acs et al., 2005]. Here the 17 years’ data of the HCCSCA between 1980 and 1996 are evaluated because the data collection has been changed since
BA´NHIDY ET AL. 1997 (all mothers are visited by regional nurses), and the recent data had not been validated at the time of the analysis.
Diagnostic Criteria of PSVT Pregnant women with conduction disorders, atrial/ventricular fibrillation, premature beats, extrasystolic arrhythmia, and PSVT with other heart diseases (e.g., coronary artery disease, dilated cardiomyopathy, etc.) were excluded from the study, thus we included only pregnant women with idiopathic PSVT or PSVT without known related other diseases in our sample. At the preliminary analysis of our data showed that two categories of PSVT could be differentiated according to the source of information in the HCCSCA: (i) prospectively and medically recorded PSVT during the study pregnancy in the prenatal maternity logbook and (ii) PSVT based on only retrospective maternal information. However, the validity of PSVT diagnosis was low due to the different sensitivity of women in the latter category; in addition it was not possible to clarify whether PSVT occurred only before or during the study pregnancy. Thus we decided to evaluate only prospectively and medical recorded PSVT in the prenatal maternity logbook. Related drug treatments were also evaluated based on both medically recoded data and maternal information. Other potential confounding factors included maternal age, birth order, marital and employment status as indicators of socio-economic status [Puho et al., 2005], other maternal diseases, pregnancy supplements particularly folic acid and multivitamins as indicators of the standard of preconceptional and prenatal care. In addition, the periconceptional folic acid/multivitamin supplementation is important in the primary prevention of neural tube defects and some other CAs as well [Czeizel, 2009]. Gestational age was calculated from the first day of the last menstrual period. Three time intervals were considered: (i) The first month of gestation because it is before the organogenesis. The first 2 weeks are before conception while the third and fourth weeks comprise the pre- and implantation period of zygotes and blastocysts including omnipotent stem cells. Thus CAs cannot be induced by short-term environmental agents in the first month of gestation and it explains the ‘‘all-or-nothing effect’’ rule, that is, total loss or normal further development. (ii) The second and third months of gestation. This is the sensitive, the so-called critical period for most major CAs [Czeizel et al., 2008b; Czeizel, 2008]. (iii) The fourth through ninth months of gestation, that is, pregnancy after the organ-forming period. Beyond birth weight (g) and gestational age at delivery (weeks), the rate of low birth weight (
Paroxysmal Supraventricular Tachycardia in Pregnant Women and Birth Outcomes of Their Children: A Population-Based Study Ferenc Ba´nhidy,1 Nandor Acs,1 Erzsebet H. Puho,2 and Andrew E. Czeizel2* 1
Second Department of Obstetrics and Gynecology, Semmelweis University, School of Medicine, Budapest, Hungary
2
Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary
Manuscript Received: 1 February 2010; Manuscript Accepted: 12 September 2010
The aim of the study was to estimate the possible association of pregnant women with paroxysmal supraventricular tachycardia (PSVT) with the possible risk for adverse birth outcomes, particularly different congenital abnormalities (CAs) in their children. Prospectively and medically recorded PSVT was evaluated in 103 pregnant women who later had offspring with CA (case group) and 149 pregnant women who later delivered newborn infants without CA (control group) and matched to cases in the population-based data set of the Hungarian Case–Control Surveillance System of Congenital Abnormalities, 1980–1996. Of 252 pregnant women with PSVT, 115 (45.6%) had the onset of this condition before the study pregnancy, that is, their PSVT was a chronic condition, while the rest (N ¼ 137) of PSVT was considered as new onset in the study pregnancy. The comparison of occurrence of PSVT in pregnant women who had offspring with different CA groups and in control mothers showed a higher risk for cardiovascular CAs (adjusted OR with 95% CI: 2.1, 1.1–3.8) explained mainly by secundum atrial septal defect. This association was confirmed in pregnant women with PSVT in the second and/or third gestational month, that is, critical period of cardiovascular CAs. In conclusion PSVT in pregnant women associates with a higher risk of secundum atrial septal defect in their children. Ó 2015 Wiley Periodicals, Inc.
Key words: paroxysmal supraventricular tachycardia; related drug treatment; birth outcomes; congenital abnormalities; cardiovascular malformations; secundum atrial septal defect
INTRODUCTION The two major classes of cardiac arrhythmias can be classified clinically as bradyarrhythmias and tachyarrhythmias [Blanchard and Shabetai, 2004; McAnulty et al., 2008; Tedrow and Stevenson, 2008]. Tachyarrhythmias are differentiated sinus tachycardia, supraventricular arrhythmias and ventricular arrhythmias. Supraventricular tachycardias include all tachyarrhythmias that either originate from or incorporate supraventricular tissue in a reentrant circuit [Calkins, 2008]. The most common manifestation of these cardiac arrhythmias is paroxysmal supraventricular tachycardia (PSVT), a clinical syndrome characterized by a rapid, regular tachycardia with abrupt onset and termination. About two-thirds
Ó 2015 Wiley Periodicals, Inc.
How to Cite this Article:
N, Puh Banhidy F, Acs o EH, Czeizel AE. 2015. Paroxysmal supraventricular tachycardia in pregnant women and birth outcomes of their children: A population-based study. Am J Med Genet Part A 167A:1779–1786.
of patients with PSVT are caused by atrioventricular nodal reentrant tachycardia. Women are affected twice as men. The rest one-third of patients have orthodromic atrioventricular reciprocating tachycardia. PSVT is also the most common cardiac arrhythmia in pregnant women [Wiederhorn et al., 1992; Lee et al., 1995] with dizziness, palpitations, and light-headedness [McAnulty et al., 2008]. The aim of our study was to estimate the possible association between maternal PSVT and birth outcomes, particularly the risk of structural birth defects, that is, congenital abnormalities (CAs) in their children in the population-based data set of the Hungarian Case–Control Surveillance of Congenital Abnormalities (HCCSCA) [Czeizel et al., 2001]. However, the diagnosis of PSVT based on maternal information was not reliable therefore we decided to evaluate only prospectively and medically recorded PSVT in the prenatal maternity logbook.
MATERIALS AND METHODS Study Subjects Cases affected with CA were selected from the data set of the Hungarian Congenital Abnormality Registry (HCAR), 1980–1996 [Czeizel, 1997] for the HCCSCA. Notification of cases with CA is Conflicts of interest: none declared. *Correspondence to: 32, H-1026 Budapest, Hungary. Andrew E. Czeizel, T€ or€ okvesz lejto E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 27 May 2015 DOI 10.1002/ajmg.a.33759
1779
1780 mandatory for physicians from the birth until the end of first postnatal year to the HCAR. Most cases are reported by obstetricians and paediatricians. In Hungary practically all deliveries take place in inpatient obstetric clinics and the birth attendants are obstetricians. Paediatricians are working in the neonatal units of inpatient obstetric clinics, or in various inpatient and outpatient paediatric clinics. Autopsy was mandatory for all infant deaths and it was suggested in stillborn fetuses, thus the occurrence of autopsy was nearly 100% in infant deaths and about 80% of stillborn fetuses during the study period. Pathologists sent a copy of the autopsy report to the HCAR if defects were identified in stillbirths and infant deaths. Since 1984 fetal defects diagnosed in prenatal diagnostic centres with or without termination of pregnancy have also been included into the HCAR. CAs were differentiated into three groups: lethal (if defects cause stillbirths or infant deaths or pregnancies were terminated due to fetal defect in more than 50% of cases), severe (without medical intervention CAs cause handicap or death) and mild (CAs require medical intervention but life expectancy is good). Lethal and severe CAs together constitutes major CAs. (Minor anomalies or morphological variants without serious medical or cosmetic consequences are excluded from the class of CA.) In addition two main categories of cases with CAs were differentiated: isolated (only one organ is affected) and multiple (concurrence of two or more CAs in the same person affecting at least two different organ systems). The recorded total (birth þ fetal) prevalence of cases with CA diagnosed from the second trimester of pregnancy through the age of 1 year was 35.0 per 1,000 informative offspring (live-born infants, stillborn fetuses and electively terminated malformed fetuses) in the HCAR, 1980–1996, though the expected rate was 65.3 per 1,000 [Czeizel et al., 1993]. However, about 90% of major CAs was recorded in the HCAR during the 17 years of the study period [Czeizel, 1997]. The proportion of live-born infants, stillborn fetuses, and electively terminated malformed fetuses was 97.1%, 1.1%, and 1.8%, respectively. There were three exclusion criteria of cases with CAs from the HCAR for the data set of the HCCSCA: (i) cases reported after 3 months of birth or pregnancy termination (23% of cases were reported after the first 3-month time window and had mainly mild CAs), (ii) cases with three mild CAs (congenital dysplasia of hip and inguinal hernia, large hemangioma), and (iii) CA-syndromes caused by major mutant genes (e.g., achondroplasia) or chromosomal aberrations (such as Down, Patau, Edwards syndromes) with preconceptional origin. Controls were defined as newborn infants without CA and they were selected from the National Birth Registry of the Central Statistical Office for the HCCSCA. In general two controls were matched to every case according to sex, birth week in the year when cases were born, and district of parents’ residence.
Collection of Exposure Data and Confounders Three sources of data were evaluated: (1) Prospective Medically Recorded Data: Mothers were asked in an explanatory letter to send us the prenatal maternity logbook
AMERICAN JOURNAL OF MEDICAL GENETICS PART A and other medical records particularly discharge summaries concerning their diseases during the study pregnancy and their child’s CA. Prenatal care was mandatory for pregnant women in Hungary (failure to attend prenatal care clinic results in denial of maternity leave benefits which include the maternity grants and days off from work), thus nearly 100% of pregnant women visited prenatal care clinics, on average seven times in their pregnancies. The first visit occurred in the prenatal care clinic between the 6th and 12th gestational week. The task of the licensed obstetricians is to record all pregnancy complications, maternal diseases, and related drug prescriptions in the prenatal maternity logbook. (2) Retrospective Self-reported Maternal Information: A structured questionnaire with a list of medicinal products (drugs and pregnancy supplements) and diseases, plus a printed informed consent form were also mailed to the mothers immediately after the selection of cases and controls. The questionnaire requested information on pregnancy complications and maternal diseases, on medicinal products taken during pregnancy according to gestational months, and on family history of CAs. To standardize the answers, mothers were asked to read the enclosed lists of medicinal products and diseases as a memory aid before they filled in the questionnaire.The mean SD time elapsed between the birth or pregnancy termination and the return of the ‘‘information package’’ (questionnaire, logbook, discharge summary, and informed consent form) in our prepaid envelope was 3.5 1.2 and 5.2 2.9 months in the case and control groups, respectively. (3) Supplementary Data Collection: Regional nurses were asked to visit all non-respondent case mothers at home and to help mothers fill in the study questionnaire and to evaluate the available medical records. In addition they obtained data regarding smoking and drinking habit through a cross interview of mothers and their close relatives living together, and finally the so-called family consensus data were recorded. The smoking habit was evaluated on the number of cigarettes per day while three groups of drinking habit were differentiated: (i) abstinent or occasional drinkers, who consumed less than one drink per week, (ii) regular drinkers consumed from daily one drink to one drink per week, (iii) hard drinkers consumed more than one drink per day. However, the committee on ethics did not allow the home visit of non-respondent control mothers because they considered it to be disturbing to the parents of healthy children. Regional nurses therefore visited only 200 non-respondent and 600 respondent control mothers as part of two validation studies [Czeizel et al., 2003b; Czeizel and Vargha, 2004]. Regional nurses used the same method in these control mothers than in non-respondent case mothers. Overall, the necessary information was available on 96.3% of cases (84.4% from reply to the mailing, 11.9% from the nurse visit) and 83.0% of the controls (81.3% from reply, 1.7% from visit). Informed consent form was signed by 98% of mothers, names, and addresses were deleted in the rest 2%. The flowchart of cases and controls was published previously [Acs et al., 2005]. Here the 17 years’ data of the HCCSCA between 1980 and 1996 are evaluated because the data collection has been changed since
BA´NHIDY ET AL. 1997 (all mothers are visited by regional nurses), and the recent data had not been validated at the time of the analysis.
Diagnostic Criteria of PSVT Pregnant women with conduction disorders, atrial/ventricular fibrillation, premature beats, extrasystolic arrhythmia, and PSVT with other heart diseases (e.g., coronary artery disease, dilated cardiomyopathy, etc.) were excluded from the study, thus we included only pregnant women with idiopathic PSVT or PSVT without known related other diseases in our sample. At the preliminary analysis of our data showed that two categories of PSVT could be differentiated according to the source of information in the HCCSCA: (i) prospectively and medically recorded PSVT during the study pregnancy in the prenatal maternity logbook and (ii) PSVT based on only retrospective maternal information. However, the validity of PSVT diagnosis was low due to the different sensitivity of women in the latter category; in addition it was not possible to clarify whether PSVT occurred only before or during the study pregnancy. Thus we decided to evaluate only prospectively and medical recorded PSVT in the prenatal maternity logbook. Related drug treatments were also evaluated based on both medically recoded data and maternal information. Other potential confounding factors included maternal age, birth order, marital and employment status as indicators of socio-economic status [Puho et al., 2005], other maternal diseases, pregnancy supplements particularly folic acid and multivitamins as indicators of the standard of preconceptional and prenatal care. In addition, the periconceptional folic acid/multivitamin supplementation is important in the primary prevention of neural tube defects and some other CAs as well [Czeizel, 2009]. Gestational age was calculated from the first day of the last menstrual period. Three time intervals were considered: (i) The first month of gestation because it is before the organogenesis. The first 2 weeks are before conception while the third and fourth weeks comprise the pre- and implantation period of zygotes and blastocysts including omnipotent stem cells. Thus CAs cannot be induced by short-term environmental agents in the first month of gestation and it explains the ‘‘all-or-nothing effect’’ rule, that is, total loss or normal further development. (ii) The second and third months of gestation. This is the sensitive, the so-called critical period for most major CAs [Czeizel et al., 2008b; Czeizel, 2008]. (iii) The fourth through ninth months of gestation, that is, pregnancy after the organ-forming period. Beyond birth weight (g) and gestational age at delivery (weeks), the rate of low birth weight (
