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Helicobacter pylori Infection and Dyspepsia in Pregnancy

McKenna, Daniel MB, MRCOG; Watson, Peter MD, FRCP; Dornan, James MD, FRCOG

ORIGINAL RESEARCH
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OBJECTIVE To investigate the relationship of Helicobacter pylori infection with dyspeptic symptoms in early and late pregnancy. Infection with H pylori and pregnancy outcome were also assessed.

METHODS H pylori seropositivity was determined in 416 antenatal patients at 10 to 14 weeks' gestation. Dyspeptic symptoms were recorded at 10 to 14 weeks' gestation and at 30 to 32 weeks' gestation by means of a well-validated questionnaire. Details of pregnancy outcome were recorded from patients' case notes.

RESULTS The incidence of H pylori infection in our population was 41.8% (164 of 404). Patients infected with H pylori were no more likely than controls to experience dyspepsia at 10 to 14 weeks' or at 30 to 32 weeks' gestation (P = .75 and .43, respectively). H pylori infection was not associated with preterm delivery, nonreassuring fetal status in labor, or birth weight less than the 10th centile (P = .17, .57, and .19, respectively).

CONCLUSION H pylori infection is not associated with an increase in dyspepsia or with maternal or neonatal morbidity.

Helicobacter pylori infection is not associated with increased dyspepsia in pregnant women.

Royal Maternity Hospital, Belfast, Northern Ireland, United Kingdom.

Address reprint requests to: Daniel McKenna, MD, MRCOG, 88A Malone Road, Belfast, BT9 5HP, United Kingdom; E-mail: dan.mckenna@virgin.net.

Received March 10, 2003. Received in revised form June 15, 2003. Accepted June 26, 2003.

Helicobacter pylori was first reported in 1979 in stomach biopsy samples taken from patients with a variety of gastrointestinal complaints.1 Its presence was confirmed in 1983.2 It is associated with a number of disease processes. It is the principal cause of peptic ulcer disease; more than 95% of patients with duodenal ulcers are infected with H pylori.3 In 1994, the World Health Organization stated that there was sufficient epidemiologic and histologic evidence to classify H pylori as a definite carcinogen because of its association with gastric cancer.4,5 It is also associated with the development of non-Hodgkin lymphoma of the stomach.6

The role of H pylori in nonulcer dyspepsia is less clear. The prevalence of H pylori infection in patients with nonulcer dyspepsia ranges from 30% to 70%.7,8 These infection rates are similar to those in the general population.9 The authors of the most comprehensive review looking at eradication of H pylori for nonulcer dyspepsia conclude that H pylori eradication therapy has a small but statistically significant effect in Helicobacter-positive non-ulcer dyspepsia.10

The role of H pylori in pregnancy has not been extensively studied. Of the studies investigating H pylori in hyperemesis gravidarum, some consider the presence of infection to be an important factor in the pathogenesis of the condition.11–13 Other studies suggest no causal relationship between H pylori infection and hyperemesis gravidarum.14,15 “Dyspepsia” is a term that encompasses a combination of symptoms. These symptoms are often related to eating and include epigastric pain, bloating, indigestion, fullness, nausea, and heartburn.16 The role of H pylori in the development of dyspepsia in late pregnancy has not been studied. Furthermore, H pylori infection and pregnancy outcome has been little studied. It has been suggested that the presence of H pylori is a risk factor in the development of intrauterine growth restriction.17

The aim of our study was to investigate the incidence of H pylori in our obstetric population and to examine its relationship with dyspeptic symptoms in early and late pregnancy. We also investigated a number of pregnancy outcomes and their relationship with the presence of H pylori infection.

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MATERIALS AND METHODS

The local ethics committee approved the study. Patients were recruited at their first antenatal visit from the antenatal clinics at the Royal Maternity Hospital, Belfast. Subjects were consecutively attending patients, and recruitment to the trial took 11 months. The inclusion criteria to the study were singleton pregnancies at 10 to 14 weeks' gestation, with gestational age confirmed by an ultrasound scan. The exclusion criteria were multiple pregnancies, uncertain gestational age, previous treatment with H pylori eradication therapy, and admission to the hospital in this pregnancy with hyperemesis gravidarum. The presence of H pylori infection was investigated by an enzyme-linked immunosorbent assay technique to determine immunoglobulin G antibodies to the bacterium.

To this end, an extra 5 mL of venous blood was drawn at the time the patient was booked. The sample was sent to our microbiology department, and a commercially available enzyme linked immunosorbent assay kit was used to determine the subject's Helicobacter status (HM CAP; Enteric Products, Westbury, NY). The sensitivity and specificity of laboratory serology is 98% and 94%, respectively, for determining H pylori status.18 The result was reported as positive, negative, or indeterminate for the presence of IgG antibodies to H pylori. Ingestion of antibiotics for other conditions may eradicate H pylori, and it may take up to 18 months for serologic tests to H pylori to become negative. The urea breath test is the best method for determining H pylori infection. However, it takes 30 minutes to perform and is expensive. We therefore chose serologic testing as our means for determining H pylori status.

Dyspeptic symptoms were recorded at the first antenatal visit (10–14 weeks' gestation) and at 30 to 32 weeks' gestation by the Glasgow Dyspepsia Severity Score (GDSS)19 (Appendix). It has been shown to be a well-validated, reproducible, and easy-to-use questionnaire in the assessment of dyspepsia. We defined dyspepsia as epigastric pain, bloating, indigestion, fullness, nausea, and heartburn.16 The dyspepsia score ranged from 0 to 20. A score of 0 indicated no dyspeptic symptoms in the preceding 4 weeks. A score of 20 indicated maximum dyspeptic symptoms in the preceding 4 weeks. Both the assessor and the subject were blind to the H pylori serology result until the second dyspepsia score was ascertained at the 30- to 32-week antenatal visit. If a patient tested positive for H pylori antibodies, a letter was sent to her family doctor informing him or her of the result. The decision to offer eradication therapy after delivery was left to the discretion of the family doctor.

The study group comprised those patients who tested positive for the presence of IgG antibodies to H pylori. The control group comprised patients who tested negative for the presence of immunoglobin antibodies to H pylori. Patients with an indeterminate result were excluded from the analysis. Primary outcome measures were the incidence of H pylori infection in our population and the relationship of infection to dyspeptic symptoms at 10 to 14 weeks' gestation and at 30 to 32 weeks' gestation. Secondary outcome measures were the development of preeclampsia, delivery before 37 weeks' gestation, mode of delivery, nonreassuring fetal status in labor, meconium liquor, and birth weight. Statistical analysis was performed by SPSS software (SPSS Inc., Chicago, IL) and Epi Info 6 (Centers for Disease Control and Prevention, Atlanta, GA). The Mann-Whitney independent-sample t test was used to compare median dyspepsia scores between the two groups. Outcome measures were compared between groups by the χ2 test with Yates correction. Odds ratios with 95% confidence limits were also calculated. Multiple regression analysis was used to adjust for the potential confounding effects of age, smoking, and deprivation on the primary outcomes.

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RESULTS

A total of 416 patients were enrolled onto the trial. H pylori serology was reported as indeterminate in 12 patients, and their data were excluded from analysis. The demographic details of those recruited to the trial are presented in Table 1. The proportion of patients who tested positive for H pylori infection in our population was 41.8% (169 of 404). These patients constituted our study group. The proportion of patients who tested negative for H pylori infection was 58.2% (235 of 404). This was our control group. Dyspeptic symptoms were reported by more than three quarters of all patients recruited to the trial at their first antenatal visit (10–14 weeks' gestation) and 30- to 32-week antenatal review (Table 2). At 10 to 14 weeks' gestation, the median GDSS was 5 in the H pylori–positive group (interquartile range [IQR], 1–7). In comparison, the median GDSS in the H pylori–negative group at 10 to 14 weeks' gestation was 5 (IQR, 1–7). There was no difference in overall dyspepsia scores between these two groups (P = .75).

Table 1

Table 1

Table 2

Table 2

At 30 to 32 weeks' gestation, the median GDSS in H pylori–positive patients was 6 (IQR, 2–9). At this gestation, the median GDSS in H pylori–negative patients was 5 (IQR, 2–9). There was no significant difference in overall dyspepsia scores at 30 to 32 weeks' gestation in H pylori–positive and H pylori–negative patients (P = .43). We considered a GDSS of 6 or more to indicate severe dyspepsia. At 10 to 14 weeks' gestation, 154 patients had dyspepsia scores of 6 or more. In this group of severely dyspeptic patients, the median score was 8 (IQR, 7–10) among H pylori–positive patients, and the median score was 8.5 (IQR, 7–10) among the H pylori–negative patients at 10 to 14 weeks' gestation. These scores were not significantly different (P = .83). At 30 to 32 weeks' gestation, 174 patients had dyspepsia scores of 6 or more. The median GDSS was 10 (IQR, 8–11) in the H pylori–positive group, compared with a GDSS of 10 (IQR, 8–12), in the H pylori–negative group. Again, these figures were not significant (P = .76). These results suggest that H pylori infection is not associated with higher dyspepsia scores at 10 to 14 and 30 to 32 weeks' gestation.

We also assessed adverse pregnancy outcome in relation to H pylori infection (Table 3). Details of pregnancy outcome were recorded from patients' charts. Infected patients were not more likely to deliver prematurely. Furthermore, their chance of labor and delivery being complicated was no higher than controls, and there was no difference in maternal and neonatal morbidity between infected and noninfected patients.

Table 3

Table 3

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DISCUSSION

Dyspepsia in pregnancy is an enigma, and its etiology in early and late pregnancy is not completely understood. Certainly the symptoms can be distressing. In early pregnancy, nausea and vomiting of pregnancy affects about two thirds of all women, although there is considerable variation among countries.20 In our population, more than three quarters of all patients were affected. Nausea and vomiting of pregnancy must be distinguished from hyperemesis gravidarum. Hyperemesis gravidarum occurs in less than 1% of all pregnancies and is characterized by intractable nausea and vomiting so severe as to cause dehydration, weight loss, electrolyte-and metabolic disturbances, and nutritional deficiency, necessitating hospital admission.21

The role of H pylori in the pathogenesis of hyperemesis gravidarum has been debated.11–15 In our study, we excluded patients who had been admitted to the hospital with a diagnosis of hyperemesis gravidarum. In our population, the incidence of nausea and vomiting of pregnancy at 10 to 14 weeks' gestation was almost identical in Helicobacter-positive and -negative patients (77.1% and 77.4%, respectively). H pylori infection is not associated with nausea and vomiting of pregnancy. One of the most plausible theories on the high incidence of nausea and vomiting of pregnancy is that it has developed in the evolutionary process. Nausea and vomiting of pregnancy helps to protect embryos from dietary toxins. The embryo is at risk from toxins and microbes from conception, with risk peaking at weeks 6 to 12, and ends at about 18 weeks' gestation. There is a striking correspondence between the period of greatest sensitivity to both toxins and pathogens and the peak occurrence of nausea and vomiting. It may be reasonable to consider nausea and vomiting of pregnancy to be physiologic.

Heartburn, the symptom of gastroesophageal reflux disease, affects 30% to 50% of all pregnant patients, and up to 80% in some populations.22,23 Again, its pathophysiology is not clear. However, a relaxed lower esophageal sphincter, in response to raised estrogen and pro-gesterone levels, seems central to its occurrence.24,25 In the nonpregnant population, H pylori appears to have a role to play in the development of nonulcer dyspepsia.10 In our study population, more than 80% of patients reported dyspeptic symptoms at 30 to 32 weeks' gestation. Again, however, H pylori–infected patients were not more likely to report dyspeptic symptoms at this gestation when compared with controls.

A retrospective power calculation suggests that the study had 90% power to detect as statistically significant (P < .05) a difference in dyspepsia rates at 10 to 14 weeks' gestation of magnitude 77% versus 90% and a difference in dyspepsia rates at 30 to 32 weeks' gestation of magnitude 85% versus 95%.

The only maternal characteristic associated with an increased risk of infection with H pylori was smoking. Infection rates of H pylori are higher amongst lower socioeconomic groups.26 Smoking rates in these groups are also higher, which probably explains the association, rather than smokers being more susceptible to H pylori infection per se. We conclude that H pylori infection is not associated with dyspepsia in pregnancy. Furthermore, its presence is not associated with abnormal pregnancy outcome.

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APPENDIX

Table

Table

27. Carstairs V, Morris R. Deprivation, mortality and resource allocation. Community Med 1989;11:364–72.
© 2003 The American College of Obstetricians and Gynecologists