INTRODUCTION

Hyperemesis gravidarum (HG) is a condition that occurs in pregnancy, characterized by incoercible nausea and vomiting ^1). It is an important condition, hospitalizing approximately 59,000 pregnant women each year, according to U.S. records ². This number of admissions is due to the multiple maternal-fetal complications that HG can cause, such asfetal growth restriction, maternal dehydration, Wernicke's encephalopathy and even death ^3). Its incidence worldwide is 0.5%-2%, and even up to 10.8% described in a study from China ^4). Therefore, HG is an important pathology due to the complications it can cause.

Among the main associated factors are pregnancy, maternal age, gestational age, multiple pregnancy, among others ^5). It has been shown that women in their first gestation with multiple pregnancies are more prone to have HG ^6). Likewise, young pregnant women have a higher risk of HG than older patients ^7). Multiple studies find that an increase in gestational age is less related to the development of HG ³ - HG is more frequent in the first trimester. Regarding psychological factors, several studies consider that the emotional factor is associated with HG, with greater presence of anxiety disorders and depression ^8). For clinical factors, hydatidiform mole and hyperthyroidism are related to HG due to the hormonal increase generated by these pathologies, causing nausea and incoercible vomiting ^9-11).

The Instituto Nacional Materno Perinatal (INMP) is a public institution specialized in maternal-perinatal care. The gynecological-obstetrics area is divided into four services -A, B, C and D-, which house pregnant women with different pathologies. Service 'B' is in charge of metabolic pathologies, as well as hemorrhagic pathologies. HG is a pathology admitted only in this service, with low prevalence. There are not many national studies on this pathology. By investigating the problem in a national reference institution will help to update the knowledge about this disease.

Therefore, the aim of this study was to identify the risk factors associated with hyperemesis gravidarum in women attended at the Instituto Nacional Materno Perinatal in Lima, 2022.

MATERIALS AND METHODS

This is an analytical observational case-control study. The study population included all pregnant women attended at the 'B' service of obstetrics and gynecology of the Instituto Nacional Materno Perinatal of Lima, Peru, during the period January-December 2022. The sample consisted of 126 medical records of pregnant women. Using the case-control formula based on a previous study, a sample size of 126 (63 cases and 63 controls) was estimated, assuming an exposure ratio of 48.9%, an OR of 2.9, 95% confidence and 80% power, with a 1:1 ratio between cases and controls. A convenience sampling was chosen due to the low prevalence of hyperemesis gravidarum, selecting pregnant women diagnosed with the condition as cases and pregnant women without the diagnosis as controls, excluding those with second and third trimester pathologies or incomplete medical records.

This retrospective study used a data collection form designed and validated by experts that included eleven items focused on identifying associated factors. The variables analyzed included:

• Dependent variable: diagnosis of hyperemesis gravidarum.

• Independent variables: extreme maternal age, higher education level, maternal obesity, maternal hCG concentrations in the first trimester, parity, multiple pregnancy, female fetus, history of mental illness, hyperthyroidism and hydatidiform mole.

The information collected was stored in Excel 2020 and statistically analyzed with SPSS 25. We chose to use ultrasound-derived gestational age, as it has been shown to improve the efficiency of the test ^12).

We chose to limit our study to women at 13 weeks' gestation, as HG generally occurs at this stage of gestation and the hCG level peaks at the end of the first trimester ^(13).

The study used univariate analysis to present frequencies and percentages, and bivariate analysis to show frequencies, percentages, and p values. In the multivariate analysis, multiple logistic regression was used to evaluate the odds ratio (OR) ^14), p values, and 95% confidence intervals. Analyses were performed using SPSS version 25, at a significance level of 0.05.

Regarding ethical considerations, the study was submitted for evaluation and review by the prestigious CIEI-UPSJB, under registration code N°1302-2023-CIEI-UPSJB, and also by the Ethics Committee of the INMP, with file number N°23- 21915-1. It is important to mention that this project consisted of a retrospective study based on clinical histories, avoiding the use of invasive methods and without establishing direct contact with the participants. Rigorous measures were implemented to ensure the confidentiality of the participants' data, storing all the information under alphanumeric codes to which only thesis students and their supervisors have access. No face captures were taken and no visual evidence was kept that could lead to the identification of participants. In addition, no names or sensitive information of those involved has been publicly disclosed.

RESULTS

This study analyzed the characteristics of 126 pregnant women attended at the Instituto Nacional Materno Perinatal in Lima, Peru, during the year 2022. In general, the evaluated pregnant women were characterized by obesity (77/126; 61.1%), high first trimester maternal hCG concentrations (86/126; 68.3%) and multiparity (98/126; 77.8%). History of hyperthyroidism and hydatidiform mole was reported in 6.3% (8/126) and 7.9% (10/126) of the patients evaluated, respectively (Table 1).

Table 1 Descriptive and bivariate analysis of factors associated with hyperemesis gravidarum. 

hCG: human chorionic gonadotropin.

* Statistical significance set at p-value less than 0.05.

Among the patients reporting hyperemesis gravidarum, 19% (12/63) were found to have extreme reproductive age, 25.4% (16/63) had a higher level of education, 96.8% (61/63) had high maternal hCG concentrations during the first trimester, and 95.2% (60/63) had female fetuses. Therefore, in the bivariate analysis, the chi-square tests indicated statistical significance for higher education level (p<0.001), maternal obesity (p=0.03), high hCG concentrations in the first trimester (p=0.04), nulliparity (p=0.02) and female fetus (p=0.01). The rest of the variables evaluated did not have statistical significance (Table 1).

In Table 2, in the multivariate analysis adjusted for possible confounding variables, the adjusted ORs were found, concluding that higher education level was a protective factor for hyperemesis gravidarum with an OR of 0.85, being statistically non-significant. Among the factors that increased the risk for hyperemesis gravidarum were maternal obesity (OR: 2.78), high hCG concentrations during the first trimester (OR: 3.19), nulliparity (OR: 3.76) and female fetus (OR: 3.13), all statistically significant.

Table 2 Multivariate analysis of factors associated with hyperemesis gravidarum. 

OR: odds ratio; hCG: human chorionic gonadotropin

* Statistical significance set at p-value less than 0.05

DISCUSSION

In the present study, 126 pregnant women attended at the Instituto Nacional Materno Perinatal of Lima, Peru, during 2022 were analyzed. Pregnant women with hyperemesis gravidarum presented a high prevalence of obesity, high hCG concentrations in the first trimester and nulliparity. In the bivariate analysis, statistical significance was found for higher education level, maternal obesity, high hCG concentrations in the first trimester, nulliparity and female fetus. Multivariate analysis showed that maternal obesity, high first trimester hCG levels, nulliparity and female fetus increased the risk of hyperemesis gravidarum.

In the study, higher education level was identified as a protective factor, with not statistically significance. This agrees with the study by Demewez Adane K ² conducted in Ethiopia, which found that low education was more common in women with hyperemesis gravidarum, finding statistically significant (p = 0.02). Similarly, Seid AM ¹⁵ found that having a low educational level was a statistically significant risk factor (OR: 5.7). These results could be due to the fact that the study population in Ethiopia was attended in a general hospital and the number of pregnant women was larger, in addition to possible differences in the populations studied or variables not considered in the adjustment.

Another finding of our study was maternal obesity (OR: 2.78) as a statistically significant risk factor. Obese women were almost three times more likely to experience hyperemesis gravidarum compared to those without obesity. This result differs from that found by Yeon Kim H(16), where obese women are 4% more likely to develop hyperemesis gravidarum. The result is not statistically significant, indicating that obesity may not be a relevant risk factor in the population studied. However, Thakur M(17) found that low weight was significantly associated with HG. This variability of results may be due to the type of population, geographic location, and different lifestyles in each.

Our study also identified that being nulliparous (OR: 3.76) was a statistically significant risk factor. This suggests that women who have not had children are almost four times more likely to develop hyperemesis gravidarum compared to those who had children. Similar result was found by Yeon Kim H ^16), in which being nulliparous was a statistically significant risk factor with 18% higher odds of developing hyperemesis gravidarum (OR: 1.18). Both studies agree that nulliparity is a risk factor for HG, but our study shows a stronger association, possibly due to differences in sample size or demographic characteristics. Likewise, Thakur M ¹⁷ found that being nulliparous was significantly associated with HG. It is important to consider that variations in ORs could reflect differences in study methodology or heterogeneity of the populations studied, underscoring the need for further research to confirm these findings.

On the other hand, having a female fetus (OR: 3.13) was also a statistically significant risk factor. This implies that women expecting a female baby are more than three times more likely to develop hyperemesis gravidarum compared to those expecting a male baby. Similar result was found by Yeon Kim H ¹⁶ and Miina Nurmi ^18), in which women expecting a female baby are respectively 34% and 26% more likely to develop hyperemesis gravidarum (OR: 1.34), with statistical significance. Although all studies agree that fetal sex is a risk factor for HG, our study indicated a higher risk, which could reflect variations in diagnostic criteria or in the characteristics of the populations studied.

This study provides a contribution to the existing knowledge on hyperemesis gravidarum (HG) by identifying specific risk factors associated with its development in pregnant women attended at the Instituto Nacional Materno Perinatal in Lima, Peru. Through multivariate analysis it was determined that maternal obesity high hCG concentrations in the first trimester, nulliparity and gestation of a female fetus significantly increased the risk of HG. These findings not only confirm previous results from other studies but also provide specific local data that can be used to improve prevention strategies and clinical management of HG in the Peruvian population.

The study performed has several limitations, including the use of a convenience sampling design which may not be representative of the general population and could bias the results. In addition, being a retrospective case-control study there are inherent limitations such as the possible lack of information in the medical records and the difficulty in establishing causality between the factors studied and hyperemesis gravidarum. To mitigate these limitations, the authors collected the medical records that had complete data.

Regarding the strengths of the study, we highlight the robust analytical methodology employed, which included a well-structured case-control design and the use of advanced statistical analyses such as logistic regression to adjust for possible confounding variables. In addition, the study used the SPSS 25 software for data analysis, ensuring rigorous statistical treatment. Data collection was carried out using a data sheet designed and validated by experts which guarantees the accuracy and relevance of the information collected for the objectives of the study. These methodological characteristics strengthen the reliability of the findings and support their potential applicability in other clinical and research contexts.

CONCLUSION

The present study identified that maternal obesity, high hCG concentrations in the first trimester, nulliparity and gestation of a female fetus were significant risk factors for the development of hyperemesis gravidarum in women attended at the Instituto Nacional Materno Perinatal in Lima, Peru. In addition, it was observed that a higher level of education could act as a protective factor, although it did not reach statistical significance. These findings provide valuable information for the prevention and management of hyperemesis gravidarum in the Peruvian population, suggesting the need for educational programs and more rigorous monitoring of pregnant women with these risk factors.