Effect of maternal Helicobacter Pylori infection on gestational weight gain in an urban community of Uganda

Introduction Maternal Helicobacter pylori (H. pylori) infection has been associated with undesirable effects during pregnancy such as; hyperemesis gravidarum, anemia, intrauterine fetal growth restriction and miscarriage. Our aim was to document the effect of H. pylori infection on gestational weight gain (GWG) in a low-income urban setting in Uganda. Methods This was a prospective cohort study conducted in Kampala between May 2012 and May 2013. The participants were HIV negative, H. pylori positive and H. pylori negative primigravidae and secundigravidae. Recruitment was at gestation age of eighteen or less weeks and follow up assessments were carried out at 26 and 36 weeks gestation age. H. pylori infection was determined using H. pylori stool antigen test. Maternal weight and height were measured, and body mass index (BMI) and rates of GWG were calculated. Results The participants’ mean±standard deviation (sd) age was 20.9±2.7 years. Primigravidae were 68.8% (n = 132) and 57.3% (n = 110) of the participants were positive for H. pylori infection. Low pre-women pregnancy BMI (< 18.5 kg/m2) was recorded in 14.6% (n = 28). The mean±sd rate of GWG during second and third trimesters was 300.5±79.7 grams/week. The mean±sd weight gained by 36 weeks of gestation was 9.6±2.2 kg while gestation age at delivery was 39.4±1.0 weeks. Factors independently associated with the rates of GWG during the second and third trimesters were parity (P=0.023), H. pylori infection (P = 0.006), pre-pregnancy BMI (P = 0.037), height (P = 0.022) and household income (P = 0.003). Conclusion H. pylori infection is associated with low rates of GWG among primigravidae and secundigravidae.


Introduction
Helicobacter pylori (H. pylori) infection affects approximately one half of the world population and it is more prevalent in developing countries [1,2]. This microorganism colonizes the stomach.
Typically, it is acquired during childhood and causes asymptomatic chronic infection [3]. However, pregnancy increases the susceptibility to H. pylori infection [4] probably due to decreased cell-mediated cytotoxic immune response [5]. Although many infected individuals are asymptomatic, H. pylori is an important health problem. H. pylori infection has been recognized as a major cause of various gastroduodenal diseases, such as chronic gastritis, peptic ulcer disease, and gastric cancer [3]. In Uganda the prevalence of H. pylori infection in dyspepsia patients who underwent endoscopy was 74% and 86% in patients with cancer and benign tumors [6,7]. Recently, Baingana et al., found the prevalence of H. pylori infection of 60.5% among pregnant women attending an antenatal clinic in Kampala [8]. Pregnancy is a physiological condition in which a marked increase in body weight occurs over a short period of time. An optimum weight gain over the course of pregnancy, as recommended by the Institute of Medicine (IOM), is one that produces a healthy newborn [9].
Optimum weight gain also provides sufficient postpartum maternal fat stores to support lactation without increasing obesity risk [9].
Furthermore, there is evidence to show that maternal prepregnancy weight and the weight gained during pregnancy influence birth weight [10]. However, gestational weight gains below the IOM recommendation are common in developing countries [11]. Inadequate gestational weight gain increases the risk of preterm delivery and low birth weight infants [12,13].
Current evidence shows that total gestational weight gain and rate of weight gain decreases with increasing pre-pregnancy body mass index (BMI) [14] and this is in agreement with 2009 IOM recommendations [9].
H. pylori infection in pregnancy is associated with many adverse effects, such as extreme, persistent nausea and vomiting (hyperemesis gravidarum) [15,16], neural tube defects in newborns, pre-eclampsia, intrauterine fetal growth restriction and miscarriage, and thrombocytopenia [17][18][19][20]. Conditions such as nausea and vomiting reduce appetite. This can lead to reduced food intake and in due course, inadequate supply of nutrients to the body. Furthermore, H. pylori infection has been associated with reduced production of ghrelin and increased levels of gastric leptin [21,22]. Ghrelin increases appetite, facilitates fat storage, and may influence energy homeostasis [23][24][25]. Increased expressions of gastric leptin make the affected individuals to experience decreased appetites and subsequently weight loss [26]. An association between H. pylori and weight loss has been suggested [25,26].
However, there is limited data on association between H. pylori and gestation weight gain especially in developing countries where inadequate GWG is already common. The objective of this study was to establish the association between H. pylori infection and maternal weight gain during pregnancy.

Methods
The study protocol was reviewed and approved by the Research and

Study design, site and population
This was a prospective cohort study conducted between May 2012 and May 2013. Pregnant women were followed from early second trimester to late third trimester. The study was conducted at the antenatal clinic of Kawempe Health Centre IV. The Health Centre is supported by the Ministry of Health, Uganda and the services in the antenatal clinic are free to the public. This clinic serves a denselypopulated, low-income area in Kawempe Division, one of the five divisions forming Kampala District in Uganda. The division is located in the Northern part of Kampala District. The study targeted HIV negative primigravidae and secundigravidae.

Sample size
We used the online openEpi software, based on Kelsey Lesley formula (1996) to calculate the sample size. In the formula we used a confidence level of 95%, power of 80%, ratio of H. pylori positive to H. pylori negative of one. Furthermore, in the formula we used 18 and 35 as the percentages of unexposed and exposed participants with outcome of interest according to Elsick [21]. The exposed group comprised of those who tested positive for H. Page number not for citation purposes 3 pylori infection while the unexposed group comprised those who tested negative for H. pylori infection.

Recruitment and follow up
A consecutive sampling procedure was used to select participants who met the selection criteria until the sample size was achieved.
The participants were chosen as they got registered at the antenatal women were excluded from this study based on the following criteria; not able to recall their pre-pregnancy weight, not able to schedule their return visits, not able to speak and/or hear, mentally ill, history of drug or alcohol abuse Based on the set exclusion criteria, a total of 56 women were excluded from this study.
Fourteen of them could not adhere to the scheduled return visits, two had sickle cell disease, four had alcohol related problems, twenty-eight could not recall their pre-pregnancy weight, six had active peptic ulcers and two were carrying twins.

Data collection and determination of nutritional status
During the participant's interview, demographic data including social, behavioral and medical history were collected in researcheradministered structured questionnaires. Nutritional status of each participant was assessed using anthropometric parameters. and measurement parameters were summarized into frequencies and mean ± standard deviation (sd). The outcome variable was rates of GWG while the independent variables were H. pylori infection, pre-pregnancy weight, pre-pregnancy BMI, parity and maternal height. Continuous data were checked for normality.
Tests for the significance of association were made using the Pearson chi-square (χ2) test for categorical variables and independent sample t test for continuous variables. Factors associated with GWG were determined with linear regression.
Factors associated with rates of GWG with P values < 0.2 during bivariate analysis were considered for multivariate analysis using linear regression to determine factors independently associated with rates of GWG. At multivariate analysis, statistical significance was determined if p < 0.05. Table 1

Discussion
The pattern of maternal weight gain during pregnancy is an important determinant of fetal growth [9]. Although several studies have reported how differences in the timing of maternal weight gain Page number not for citation purposes 5 may be related to fetal growth outcomes [28,29], none addresses the effect of maternal H. pylori infection on GWG especially in a developing country. In this paper, we investigated the relationship between maternal H. pylori infection and rates of GWG during the second and third trimesters of pregnancy because these trimesters greatly influence birth outcome [9]. Although effects of H. pylori infection on fetal growth and birth outcome are known [17][18][19][20], our study is among the first to evaluate the relationship between H. pylori infection and rates of GWG during the second and third trimesters among primigravidae and secundigravidae. We found that the presence of H. pylori infection significantly affects the rate of GWG in this population.
In this current study we found the mean±sd rate of GWG of H. pylori positive pregnant women (288.2±81.8 grams/week) to be significantly lower than that of H. pylori negative pregnant women (317.0±74.1 grams/week), P = 0.013. We did not come across any published information relating H. pylori infection to GWG but studies involving non-pregnant have associated H. pylori infection with reduced appetite and weight loss [25,26]. Our study found no differences in pre-pregnancy weight and pre-pregnancy BMI between H. pylori positive and H. pylori negative participants. This can be explained by the fact that the participants were more of a homogenous and apparently healthy population. This same study also found out that the mean rate of weight gain in primi-gravidae was higher than in secudi-gravidae. This finding is in agreement with recent findings of other studies [30][31][32][33] which found that primigravidae are more likely to gain a greater amount of gestational weight and experience excessive GWG than their multigravidae counterparts. This present study further found a positive correlation between rates of GWG during the second and third trimesters and birth weight (P < 0.001). Our finding agrees with several other studies [34][35][36].
Helicobacter pylori infection was found to be independently associated with low rates of gestation weight gain (P = 0.006).
Studies have associated H. pylori infection with weight loss [25] and weight gain after eradication [21]. One of the mechanisms through H. pylori infection may lead to low GWG is by reducing the production of ghrelin and increasing the production of gastric leptin [21,22]. Ghrelin increases appetite and facilitates fat storage [23] whereas leptin reduces appetite and leads to weight loss [25].
Maternal pre-pregnancy BMI was also found to be independently associated with the rate of GWG (P = 0.037). This is in agreement with other studies that have showed that low pre-pregnancy BMI increases rates of maternal weight gain [37]. Total gestational weight gain and rate of weight gain decreases with increasing prepregnancy body mass index [9,14]. Parity was another factor independently associated with rate of GWG (P = 0.023) in this study as seen in Table 4. This finding is in agreement with the findings of other studies which found that primigravidae are more likely to gain a greater amount of gestational weight and experience excessive GWG than their multigravidae counterparts [30][31][32][33]. Furthermore, household monthly income was also found to be associated with GWG during the 2 nd and 3 rd trimesters. In sub Saharan Africa, increased income is associated with lifestyle factors including increased food intake especially calories and reduced physical activity [38]. These factors have been associated with increased total GWG [39,40]. Although Pickett and colleagues [41] found no interaction between maternal height and net pregnancy weight gain, our present findings show that there is a significant relationship between maternal height and rates of GWG during the second and third trimesters. This is in agreement with the findings of several authors [42,43]. The strength of our study lies in the fact it was a prospective cohort and we were able to control for some of the known risk factors for GWG such as chronic and genetic diseases. We also included a homogenous population and we are able to attribute the rates of GWG to H. pylori infection. However, this current study had some limitations. We did not collect data of all the risk factors for low GWG, for example, level of physical activity during pregnancy, number of antenatal visits, previous poor pregnancy outcome for secundigravidae, neither did we consider other infections, such as malaria and helminth infestations, which are endemic in the study area and have been associated with low rates of GWG [44,45].

Conclusion
Helicobacter pylori infection has a negative effect on GWG during second and third trimesters. Other factors which independently affect GWG are parity, household monthly income, maternal height and pre-pregnancy BMI. We recommend that women of child  Maternal H. pylori infection has no effect on prepregnancy weight and height.

Competing interests
The authors declare no competing interests.

Acknowledgments
We are thankful to the pregnant women who participated in this study. The authors would like to thank the administration and staff of Kawempe Health Centre antenatal clinic. This study was supported by the International Atomic Energy Agency (IAEA). The content is solely our responsibility as authors and does not necessarily represent the official views of the IAEA. Table 1: Socio-demographics characteristics of participants