Abstracts

INTRODUCTION

The importance of perceptions about health and health-related quality of life (HRQoL), as well as of the impact of both disease and treatment, has been widely acknowledged in clinical and epidemiological studies⁽⁹9. Guyatt GH, Feeney DH, Patrick DL. Measuring health-related quality of life. Ann Intern Med. 1993;118(8):622-9.⁾. The generic description of differences in health-related quality of life for a single disease and their comparison with differences for other diseases may demonstrate its importance for an individual in a given community. HRQoL parameters are therefore necessary to provide guidelines for more adequate health policy decisions⁽⁶6. Ciconelli RM, Ferraz MB, Santos W, Meinão I, Quaresma MR. Tradução para a língua portuguesa e validação do questionário genérico de avaliação de qualidade de vida SF-36 (Brasil SF-36). Rev Bras Reumat. 1999;39:143-50.⁾.

Although other generic instruments are available - such as the SIP (Sickness Impact Profile), NHP (Nottingham Health Profile), QWB (Quality of Well Being Scale), PGWB (Psychological General Well-Being Index) - the SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey) is still the most used, particularly in gastroenterology, to quantify differences between patients with gastrointestinal diseases and controls⁽²¹21. Yacavone RF, Locke GR, Provenzale DT, Eisen GM. Quality of life measurement in gastroenterology: What is available? Am J Gastroenterol. 2001;96(2):285-97.⁾. The SF-36 has been studied in many populations with specific diseases and is considered an appropriate tool to describe health and HRQoL during pregnancy.

According to The Montreal Consensus, Gastroesophageal Reflux Disease (GERD) is a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The characteristic symptoms of GERD, recognized by the Consensus are heartburn and regurgitation⁽¹⁸18. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900-20.⁾.

It has been previously reported that GERD is common during pregnancy, and the prevalence reaches around 30%-80% of pregnant women⁽¹³13. Malfertheiner SF, Malfertheiner MV, Kropf S, Costa SD, Malfertheiner P. A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy. BMC Gastroenterol. 2012;12:2-7.^{, 16}16. Ramu B, Mohan P, Rajasekaran MS, Jayanthi V. Prevalence and risk factors for gastroesophageal reflux in pregnancy. Indian J Gastroenterol 2011;30(3):144-7.⁾. Heartburn and regurgitation are the most prevalent symptoms of GERD, that often occur in pregnancy, becoming worse as pregnancy advances, and decreasing following the delivery⁽³3. Baron TH, Richter JE. Gastroesophageal reflux disease in pregnancy. Gastroenterol Clin North Am. 1992;21(4):777-91.^{, 13}13. Malfertheiner SF, Malfertheiner MV, Kropf S, Costa SD, Malfertheiner P. A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy. BMC Gastroenterol. 2012;12:2-7.^{, 16}16. Ramu B, Mohan P, Rajasekaran MS, Jayanthi V. Prevalence and risk factors for gastroesophageal reflux in pregnancy. Indian J Gastroenterol 2011;30(3):144-7.⁾. However, their impact on health-related quality of life has not yet been sufficiently studied.

The pathogenesis of GERD in pregnancy is multifactorial. Some combined factors play an important role in the etiology of GERD in pregnancy: decreased lower esophageal sphincter pressure and alteration in gastrointestinal transit due to hormone changes, and increased intragastric and intra-abdominal pressure secondary to the enlarged gravid uterus⁽¹1. Arantes MR, Fraga FC. Doenças do aparelho digestivo. In: Rezende J. Obstetrícia. 8ª ed. Rio de Janeiro: Guanabara Koogan; 1998. p. 440-6l.^{, 13}13. Malfertheiner SF, Malfertheiner MV, Kropf S, Costa SD, Malfertheiner P. A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy. BMC Gastroenterol. 2012;12:2-7.⁾.

The objective of this study was evaluate the HRQoL during pregnancy in the presence of symptoms of GERD, such as heartburn and regurgitation. The hypothesis was that pregnant women with symptoms have a worse quality of life than those without symptoms.

METHODS

Sample size calculation for this case-control study was based on mean SF-36 scores according to data published by Revicki et al.⁽¹⁷17. Revicki DA, Wood M, Maton P, Sorensen S. The impact of gastroesophageal reflux disease on health-related quality of life. Am J Med. 1998;104(3):252-8.⁾.

Scores to quantify patients’ general HRQoL were obtained by means of the Portuguese version of the SF-36 (Medical Outcomes Study 36- Item Short-Form Health Survey) generic questionnaire, validated by Ciconelli et al.⁽⁶6. Ciconelli RM, Ferraz MB, Santos W, Meinão I, Quaresma MR. Tradução para a língua portuguesa e validação do questionário genérico de avaliação de qualidade de vida SF-36 (Brasil SF-36). Rev Bras Reumat. 1999;39:143-50.⁾. The questionnaire is composed of 36 questions that assess 8 health concepts: physical functioning, role function as limited by physical problems, pain, general health, vitality, social functioning, role function as limited by emotional problems, and mental health. Scores range from zero to 100; zero corresponds to the lowest general health status, and 100, to the highest⁽²⁰20. Ware JE, Sherbourne CD. The MOS 36 item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473-83.⁾.

All pregnant women at 28 or more weeks of gestation consecutively seen at a low-risk prenatal outpatient service of Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, were invited to participate in the study. They answered a questionnaire about symptoms and symptom intensity, age, ethnicity, obstetric history, medication, and anthropometric measurements.

In this cross-sectional study eighty-two third-trimester pregnant women were studied: 62 had heartburn and/or regurgitation (symptomatic group), and 20 were asymptomatic. Patients with diabetes, hypertension or other chronic diseases, as well as those that were taking any medication for heartburn and/or regurgitation, were excluded from the study.

The following statistical tests were used for data analysis: Student t test for two independent samples, and ANOVA for more than two samples, followed by Dunnett test for quantitative variables; nonparametric Wilcoxon-Mann-Whitney test for quantitative variables that did not meet requirements for the t test; Fisher exact test for categorical variables that did not meet requirements for the chi-square test; kappa coefficient and corresponding confidence interval to assess agreement between symptoms of the same patient on different occasions. Significance was established at P<0.05.

RESULTS

Mean age (± standard deviation) was 26 ± 6.42 years. Mean pregestational weight and height were, respectively, 60.0 ± 9.5 kg and 1.6 ± 0.1 m. Mean pregestational body mass index (BMI) was 23.2 ± 3.4 kg/m². Mean weight gain was 12.2 ± 2.6 kg, and mean gestational age was 33.8 ± 3.7 weeks. Sixty-two (76%) women reported heartburn, and 58 (71%) regurgitation. The level of education for the group under study was: 17 (21%) - less than primary school; 14 (17%) - primary school; 13 (16%) less than secondary school; 29 (35%) - secondary school; and 1 (1%) - at least some college education. Mean time to fill out the self-administered questionnaire was 11.5±3.7 minutes. When these variables were analyzed by symptom, there was not statistically difference in age (P=0.890), pregestational BMI (P=0.391), current BMI (P=0.167), weight gain (P=0.161), and level of education (P=0.405) in women with and without heartburn. When analyzed by regurgitation, it was also not found any statistically difference (P≥0.05 for all).

Thirty-five (43%) pregnant women reported a family history of heartburn and/or regurgitation; 25 (31%) had pregestational heartburn, and 57 (70%) reported not having these symptoms when not pregnant. Among multiparous women, 54 (65%) had already had heartburn in previous pregnancies, and there was agreement between heartburn in third trimester and in previous pregnancies (kappa= 0.33; P=0.005; 95% CI, 0.05-0.56). No significant correlation was found between pregestational heartburn and heartburn in present pregnancy (kappa = 0.09; P=0.121; 95% CI, -0,31 to -0,11). Mean weight of pregnant women with heartburn (73.7 ± 11.0 kg) was significantly greater than that of asymptomatic patients (67.8 ± 10.4 kg) (P=0.037), but no significant difference in weight gain was found between the two groups (pregnant women with heartburn = 12.7 ± 5.0 kg; asymptomatic pregnant

women =10.8 ± 5.2 kg; P=0.161).

No pregnant women reported alcohol drinking during pregnancy, but six (7%) smoked, and 22 (27%) were ex-smokers. Forty-five (55%) patients took medication; the drug most frequently used was ferrous sulphate. These and other general characteristics of all pregnant women are shown in Table 1.

Scores of HRQoL concepts were lower for pregnant women with heartburn and/or regurgitation than for controls. Two health concepts were significantly affected for women with heartburn: physical problems (P=0.009) and social functioning (P=0.020), shown in Table 2. For women with regurgitation, two aspects were significantly affected: physical problems (P=0.004); and emotional problems (P=0.002), stated in Table 3.

More than 51% of the symptomatic pregnant women had three or more heartburn episodes per week. The scores of HRQoL between pregnant women with heartburn twice or more times a week and less than twice a week are shown in Table 4.

DISCUSSION

Pregnant women were recruited for the study at a low-risk prenatal outpatient service in an attempt to reduce biases, such as the inclusion of pregnant women with diabetes, hypertension, or any other disease either associated with pregnancy or not.

According to the Brazilian Health Ministry, low maternal schooling (fewer than 5 schooling years) and maternal age in the extremes of the reproductive age group are the risk factors associated with negative obstetric outcomes. Most of the pregnant women in this study were older than 17 and younger than 35 years, and were multiparous. Most of them (80%) had finished at least elementary school, and the time that they took to fill out the self-administered SF-36 questionnaire suggested that they could understand it easily.

Our results suggest that both heartburn and regurgitation are highly prevalent and frequent in the third trimester of pregnancy. Other authors have reported high prevalence rates for heartburn in pregnancy⁽²2. Bainbridge ET, Temple JG, Nicholas SP, Newton JR, Boriah V. Symptomatic gastroesophageal reflux in pregnancy. A comparative study of white Europeans and Asians in Birmingham. Br J Clin Prac. 1983;37(2):53-7.^{, 11}11. Knudsen A, Lebech M, Hansen M. Upper gastrointestinal symptoms in the third trimester of the normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 1995;60(1):29-33.^{, 14}14. Marrero JM, Goggin PM, Caestecker JS, Pearce JM, Maxwell JD. Determinants of pregnancy heartburn. Br J Obstet Gynaecol. 1992;99(9):731-4.

15. Meyer LC, Peacock JL, Bland JM, Anderson HR. Symptoms and health problems in pregnancy: their association with social factors, smoking, alcohol, caffeine and attitude to pregnancy. Paediatr Perinat Epidemiol. 1994;8(2):145-55.^-1616. Ramu B, Mohan P, Rajasekaran MS, Jayanthi V. Prevalence and risk factors for gastroesophageal reflux in pregnancy. Indian J Gastroenterol 2011;30(3):144-7.⁾, but prevalence rates of regurgitation have been less investigated. The high prevalence rate for regurgitation found in our sample was similar to the rate for heartburn (one pregnant woman with regurgitation for each 1.6 with heartburn), differently from rates found in the general population, which is one person with regurgitation for each three individuals with heartburn⁽⁴4. Barros SGS, Lopes AB, Grüber AC. Doença do Refluxo Gastroesofágico: diagnóstico e Conduta Clínica. In: Nader F. Gastroenterologia IV. Pelotas: Ed. Universitária, UFPEL; 2001. p. 33-46.⁾. In a cohort study, it was found that 35.3% of pregnant women during third trimester of pregnancy suffered at least once a week from heartburn and 40.7% from regurgitation⁽¹³13. Malfertheiner SF, Malfertheiner MV, Kropf S, Costa SD, Malfertheiner P. A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy. BMC Gastroenterol. 2012;12:2-7.⁾. The same study also showed a GERD prevalence of 51.2% in third trimester of pregnancy. Regurgitation is more prevalent in this period of life, and it seems to affect quality of life more significantly than heartburn.

When our data were analyzed according to the frequency of symptoms of heartburn (two or more times a week), no significant differences in HRQoL were observed. At a later stage, data on patients with symptoms one or more times a week were compared to data on patients with less frequent symptoms; this comparison revealed signs of a negative impact in the quality of life of women in the first group. However, the most significant negative impact of symptoms (heartburn and/or regurgitation) in HRQoL was observed when data on pregnant women with heartburn and/or regurgitation at any frequency were compared to data on those that were asymptomatic. This finding suggests that criteria to diagnose GERD in pregnant women should be different from those used for the general population. It also suggests that even sporadic complaints should be taken into consideration during pregnancy, because one monthly episode of heartburn, depending on its intensity and duration, may be enough to reduce the quality of life of a pregnant woman.

Heartburn in pregnancy does not seem to be associated with the patient’s history, differently from what is observed in the general population. However, most pregnant women that had these symptoms in previous pregnancies also reported them for the present pregnancy. These facts are in agreement with studies that suggest that the increase in the levels of progesterone and/or estrogen during pregnancy is the main cause of the decreased pressure of the lower esophageal sphincter⁽⁵5. Broussard CN, Richter JE. Treating gastroesophageal reflux during pregnancy and lactation: what are the safest therapy options? Drug Saf. 1998;19(4):325-37.^{, 7}7. Fisher RS, Roberts GS, Grabowski CJ, Cohen S. Inhibition of lower esophageal sphincter circular muscle by female sex hormones. Am J Physiol 1978; 234(3):243-7.^{, 8}8. Fisher RS, Roberts GS, Grabowski CJ. Altered lower esophageal sphincter function during early pregnancy. Gastroenterol. 1978;74(6):1233-7.^{, 10}10. Hey VM, Cowely DJ, Ostick DG, Skinner L, Ganguli PC, Cowely DJ. Proceedings: gastroesophageal reflux in late pregnancy. Gut. 1975;16(5):403-4.

11. Knudsen A, Lebech M, Hansen M. Upper gastrointestinal symptoms in the third trimester of the normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 1995;60(1):29-33.^-1212. Lind JF, Smith AM, McIver DK, Coopland AT, Crispin JS. Heartburn in pregnancy - a manometry study. Can Med Assoc J. 1968;98(12):571-4.^{, 14}14. Marrero JM, Goggin PM, Caestecker JS, Pearce JM, Maxwell JD. Determinants of pregnancy heartburn. Br J Obstet Gynaecol. 1992;99(9):731-4.^{, 19}19. Van Thiel DM, Gaveler JS, Joshi SN, Sara RK, Stremple J. Heartburn of pregnancy. Gastroenterology. 1977;72 (4 Pt 1):666-8.⁾. These studies suggest that the symptoms studied here are not associated with mechanical factors, such as weight gain, and are not triggered by increased intraabdominal and intragastric pressure.

CONCLUSIONS

Our study revealed a high prevalence of heartburn and regurgitation among women in the third trimester of pregnancy. Patients with heartburn and/or regurgitation obtained lower scores in several HRQoL concepts than asymptomatic pregnant women. No association was found with pregestational heartburn, but there was agreement between reports of symptoms in present and previous pregnancies.

Ethical standards

The study was approved by the Ethics Committee of the Hospital de Clínicas de Porto Alegre - UFRGS and PUCRS. All patients who agreed to participate were informed about the research objectives and included after signing the Informed Consent. This was done in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The authors declare that they have complete control of all primary data and agree to allow the journal to review the data if requested.

Authors’ contributions

Dall’Alba V: protocol/project development, data collection and management, data analysis, manuscript writing/editing. Callegari-Jacques SM: data analysis, and interpretation of data. Krahe C: project development, and manuscript writing/editing. Bruch JP: data collection, and data analysis. Alves BC: data collection, and data analysis. Barros SGS: protocol/project development, management, data analysis, manuscript writing/editing.

REFERENCES

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