Symptom Severity and Quality of Life Impact in Hyperemesis Gravidarum and Nausea of Pregnancy: Evidence From a Large Cross-Sectional Study

Study Design and Settings

This study employed a cross-sectional design. Data collection was conducted between October 2025 and January 2026 across major hospitals and primary healthcare centers in the ten West Bank governorates: Nablus, Hebron, Tulkarm, Qalqilya, Jenin, Tubas, Salfit, Bethlehem, Ramallah, and Jericho. Participating hospitals included Al-Ittihad Hospital, Rafidia Surgical Hospital, St. Luke’s Hospital, Al-Hussein Governmental Hospital, Al-Meezan Specialized Hospital, Princess Alia Governmental Hospital, Ahli Hospital, Red Crescent Specialized Hospital, Martyr Dr. Thabet Thabet Government Hospital, Ibn Sina Specialized Hospital, Jenin Government Hospital, and Palestine Medical Complex. Primary healthcare centers included Al-Makhfiyyeh and Balata Camp Health Centers in Nablus, and Al-Salam Primary Healthcare Center in Hebron. These institutions serve diverse geographic and socioeconomic populations, ensuring a representative sample of pregnant women in the West Bank. This study was conducted in adherence to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist, with detailed compliance documented in Supplementary Table S1. This alignment with international reporting standards enhances transparency, reproducibility, and methodological rigor.

Study Population and Eligibility Criteria

The study population comprised Palestinian pregnant women aged 18 years or older, residing in the West Bank, who experienced symptoms of NVP or were diagnosed with HG; asymptomatic pregnant women were not eligible for inclusion. Eligible participants were those who had used pharmacological and/or non-pharmacological treatments to manage their symptoms and who provided written informed consent prior to enrollment.

Women were excluded if they had underlying medical conditions unrelated to pregnancy that could independently cause nausea and vomiting (e.g., gastrointestinal disorders, malignancies), if they were asymptomatic and did not report nausea or vomiting during pregnancy, or if they submitted incomplete questionnaires or insufficient data that precluded reliable analysis. This approach ensured that the study sample reflected the true burden of NVP and HG in pregnancy, while minimizing confounding from non-pregnancy-related causes of nausea and vomiting.

Study Size and Sampling

The sample size was calculated using the Raosoft sample size calculator (https://www.raosoft.com), assuming a 95% confidence level, a 5% margin of error, a 50% response distribution, and an estimated population of 30,845 pregnant women based on the Ministry of Health annual report. This yielded a minimum required sample size of 380 participants, which was achieved during the study period.

A non-probability convenience sampling technique was employed. Eligible participants attending antenatal services at the selected hospitals and primary healthcare centers were consecutively invited to participate until the required sample size was reached. This approach ensured feasibility and timely recruitment while capturing a diverse sample representative of pregnant women across different geographic and healthcare settings in the West Bank.

Variables, Measures, and Data Collection

In this study, the primary outcome was the prevalence of HG, defined according to the Windsor 2021 criteria.^1,3,18 Diagnosis required the presence of severe nausea and/or vomiting, inability to eat or drink normally, and a strong impact on daily living activities, with symptom onset before 16 weeks of gestation. Contributory features such as dehydration and weight loss were also considered, though not mandatory, thereby ensuring that the definition captured both functional impairment and clinical severity. The diagnosis of HG was established at the time of study enrollment by attending obstetricians using the Windsor 2021 criteria. All participants were assessed in hospital or primary care settings, and diagnoses were confirmed through direct clinical evaluation and review of medical records. This standardized approach ensured consistency across sites and minimized misclassification.

The secondary outcomes focused on the severity of NVP and its impact on maternal QoL. Symptom severity was measured using the Motherisk-modified Pregnancy-Unique Quantification of Emesis (PUQE-24) questionnaire,^{11,12,14,19,20} which quantifies the burden of NVP over the preceding 24 hours. The PUQE-24 captures three domains: the duration of nausea, the frequency of vomiting, and the number of retching episodes. Each domain is scored from 0 to 5, yielding a total score between 3 and 15. Standard cut-offs were applied to classify severity: mild (4-6), moderate (7-12), and severe (13-15). This tool has been validated internationally and was used in this study to stratify participants according to symptom burden. It is important to note that the Windsor 2021 criteria were used exclusively for the diagnosis of HG, focusing on functional impairment and inability to eat or drink normally, whereas the PUQE-24 scale was applied to measure the severity of NVP symptoms over the preceding 24 hours. This distinction ensured that diagnostic classification and symptom quantification were complementary but non-overlapping.

Maternal health-related QoL was assessed using the NVP-specific QoL (NVPQoL) questionnaire.^21-25 This instrument evaluates four domains: physical, functional, emotional, and social, over the previous week. Items are scored on a seven-point Likert scale, with higher scores reflecting worse QoL. The NVPQoL has been validated in multiple populations and provides a multidimensional measure of the impact of NVP and HG on daily functioning and psychosocial well-being.

The main explanatory variables included the type of treatment received for NVP or HG, categorized as pharmacological, non-pharmacological, or combined interventions. Specific medications (e.g., meclizine, pyridoxine, ondansetron) and remedies (e.g., ginger, lemons, herbal preparations) were recorded, along with the frequency of use. Treatment-related side effects, cultural or family influences, and the level of social support were documented. Patient satisfaction with treatment was measured using a five-point Likert scale, providing insight into perceived effectiveness and acceptability. Additional independent variables were collected to describe the study population and explore potential associations with HG, NVP severity, and QoL. For clarity, explanatory variables were grouped into four categories: (1) sociodemographic factors (age, residence, education, employment, household income satisfaction), (2) behavioral factors (smoking status, pack-year), (3) clinical and obstetric factors (gestational age, trimester, parity, multiple pregnancy, body mass index (BMI), prior HG diagnosis, dietary patterns), and (4) medical history and chronic medication use (comorbidities and medications). The final questionnaire is provided in Supplementary Table S3.

All tools used in this study were previously validated instruments. The questionnaire was translated from English into Arabic using a forward-backward translation process to ensure linguistic clarity and conceptual equivalence. Translations were reviewed by bilingual experts, and a pilot study with 20 pregnant women was conducted to assess feasibility, comprehension, and reliability. Internal consistency was evaluated using Cronbach’s alpha (>0.70), confirming the robustness of the tools in the local context. Data collection was performed through structured face-to-face interviews administered by trained research staff who were 3 final year medical students, following standardized protocols to minimize interviewer bias and ensure consistency across sites.

Statistical Analysis

All data were initially entered into Microsoft Excel and subsequently analyzed using the Statistical Package for Social Sciences (IBM SPSS), version 27. Descriptive statistics were used to summarize participant characteristics. Continuous variables were expressed as means with standard deviations (SD), while categorical variables were presented as frequencies (n) and percentages (%). Given the sample size and distribution patterns observed, parametric tests were applied under the assumption of normality.

To explore associations between the primary outcome (HG diagnosis according to Windsor et al., 2021) and secondary outcomes (PUQE severity categories, PUQE scores, and NVPQoL scores), a series of univariate analyses were conducted. Chi-square tests were used to assess associations with categorical variables, while independent-samples t-tests compared continuous variables between groups. Pearson correlation coefficients were applied to examine relationships between continuous variables. Where comparisons involved more than two groups, one-way analysis of variance (ANOVA) was performed, followed by post-hoc tests when appropriate.

To identify independent predictors of PUQE scores and NVPQoL scores, multivariable linear regression analyses were conducted. Variables were entered into the models if they demonstrated statistical significance (p < 0.05). Regression diagnostics included assessment of multicollinearity (variance inflation factor (VIF) < 5 and tolerance > 0.2), normality of residuals (Shapiro-Wilk test and Q-Q plots), homoscedasticity (Breusch-Pagan test), and linearity of relationships. Model fit was evaluated using adjusted R² values and residual plots. Results were reported as unstandardized coefficients (B), standard errors (SE), and 95% confidence intervals (CI).

For the binary outcome of HG diagnosis, logistic regression analyses were performed to identify independent predictors. Variables were selected using the same criteria as for linear regression. Diagnostics included evaluation of model fit (Hosmer-Lemeshow goodness-of-fit test), discrimination (area under the receiver operating characteristic curve, AUC), and multicollinearity (VIF). Results were reported as odds ratios (OR) with 95% CI. All statistical tests were two-sided, and a p-value < 0.05 was considered statistically significant. Cases with missing or incomplete data were excluded from analyses to maintain data integrity.

Sociodemographic, Health, Pregnancy-Related, and Lifestyle Characteristics of the Study Participants

Participants had a mean age of 27.4 ± 4.8 years and BMI of 26.9 ± 4.6 kg/m². Most were university educated (78.6%) and unemployed (77.3%). About one-fifth reported comorbidities, while strong social support was common (61.3%). The mean gestational age was 23.8 weeks, and over one-third were in their first pregnancy. Dietary patterns were largely balanced (82.8%), with only small proportions reporting unhealthy or special diets. Full details are provided in Supplementary Tables S3-S4.

Prevalence and Severity of NVP Symptoms

The mean PUQE-24 score was 5.4 ± 2.5, with nearly one-third of participants (29.4%) experiencing moderate to severe symptoms. Nausea was common, while frequent vomiting or retching episodes were rare. Detailed distributions are presented in Supplementary Table S5.

Associations Between Maternal Variables and PUQE-24 Score and Severity Classification

Univariate analysis showed that PUQE scores were highest in the first trimester (6.9 ± 2.8) compared to later stages, and were inversely correlated with gestational age (r = -0.33, p < 0.001) (Supplementary Table S6). Women with a prior history of HG reported higher scores (7.0 ± 3.5 vs. 5.0 ± 2.1, p = 0.001), and those following unhealthy or special diets also had elevated scores (p = 0.031). Regression analysis confirmed four independent factors associated with PUQE severity: prior HG history (B = 1.58, p < 0.001), current HG diagnosis (B = 1.16, p < 0.001), gestational age (B = -0.06 per week, p < 0.001), and dietary patterns (B = 0.67, p = 0.024) (Table 1).

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Table 1.

Maternal Factors Independently Associated With PUQE-24 Scores

Factor	Unstandardized coefficients		Standardized coefficients	t	p-value	Collinearity statistics
	B	SE	Beta			Tolerance	VIF
Prior diagnosis of HG in a previous pregnancy	1.58	0.39	0.24	4.04	< 0.001	0.92	1.08
Diagnosis of HG in the current pregnancy based on Windsor 2021 criteria	1.16	0.29	0.23	3.94	< 0.001	0.91	1.10
Current gestational age (weeks)	-0.06	0.01	-0.26	-4.57	< 0.001	1.00	1.00
Dietary pattern during pregnancy	0.67	0.30	0.13	2.27	0.024	0.99	1.01

Prevalence of HG

Using Windsor criteria, 43.9% of participants were diagnosed with HG. Most reported severe NVP or inability to eat and drink, with over half noting a strong impact on daily activities. Early symptom onset and dehydration were common, while complications such as weight loss (11.8%), malnutrition (7.8%), and hospitalization (5.0%) were less frequent. Full distributions are provided in Supplementary Table S7.

Associations Between Maternal Variables and HG

The diagnosis of HG was significantly associated with several maternal factors (Supplementary Table S8). Women with a prior history of HG were much more likely to be diagnosed again (27.9% vs. 7.4%, p < 0.001). PUQE-24 severity was strongly linked, with moderate/severe scores reported in 41.9% of HG cases compared to 19.7% of non-HG cases (p < 0.001). Comorbidities were also more frequent among HG cases (26.9% vs. 17.8%, p = 0.033). Multivariate logistic regression confirmed two independent predictors: prior HG history (OR = 3.47, 95% CI: 1.55-7.80, p = 0.003) and PUQE score, where each one-point increase was associated with a 30% higher likelihood of HG diagnosis (OR = 1.30, 95% CI: 1.15-1.48, p < 0.001) (Table 2).

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Table 2.

Maternal Factors Independently Associated With Likelihood of Being Diagnosed With HG in the Current Pregnancy Based on Windsor 2021 Criteria

Factor	95% CI for OR
	B	SE	Wald	p-value	OR	Lower	Upper
Presence of comorbidities	0.26	0.31	0.71	0.398	1.30	0.71	2.40
Prior diagnosis of HG in a previous pregnancy	1.25	0.41	9.09	0.003	3.47	1.55	7.80
PUQE score	0.27	0.07	16.65	< 0.001	1.30	1.15	1.48

QoL Scores and Symptom Impact

The mean NVPQoL score was 108.8 ± 33.5, indicating a substantial symptom burden (Supplementary Table S9). Fatigue and emotional distress were the most prominent domains, with high scores for tiredness, lack of energy, and feeling emotional or depressed. Functional limitations were also common, as many women reported reduced social and work activities and reliance on partners for daily tasks. Nausea-specific items showed moderate severity, while reassurance that symptoms were part of normal pregnancy scored relatively high, suggesting some psychological comfort despite the burden. Full item-level distributions are presented in Supplementary Table S9.

Associations Between QoL and Maternal Variables

Univariate analysis showed poorer QoL among university-educated women, those in the first trimester, women with prior HG, and those following unhealthy diets (Supplementary Table S10). PUQE severity was strongly correlated with QoL (r = 0.544, p < 0.001), and current HG diagnosis was associated with markedly higher scores. In regression analysis, PUQE score emerged as the strongest determinant, with each unit increase linked to a 6.18-point rise in NVPQoL (B = 6.18, p < 0.001), while current HG diagnosis contributed an additional 17.79-point increase (B = 17.79, p < 0.001). Other factors did not remain significant, underscoring symptom severity and HG as the dominant drivers of QoL deterioration (Table 3).

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Table 3.

Maternal Factors Independently Associated With NVPQoL Scores

Factor	Unstandardized coefficients		Standardized coefficients	t	p-value	Collinearity statistics
	B	SE	Beta			Tolerance	VIF
Educational level	5.93	4.07	0.08	1.46	0.146	0.97	1.03
Previous diagnosis of HG	5.86	5.05	0.06	1.16	0.247	0.86	1.16
Current gestational age (weeks)	0.11	0.18	0.03	0.61	0.544	0.91	1.10
Dietary pattern during pregnancy	-1.48	3.74	-0.02	-0.40	0.693	0.96	1.04
PUQE score	6.18	0.82	0.45	7.58	< 0.001	0.74	1.34
Diagnosis of HG based on Windsor 2021 criteria	17.79	3.79	0.26	4.69	< 0.001	0.86	1.17

Management Approaches for NVP and HG

Nearly one-quarter of women (22.3%) reported receiving no treatment for NVP or HG. Pharmacological interventions were most common, with about one-third using medications alone and another 17.6% combining them with non-medication approaches. The predominant regimen was meclizine with pyridoxine (40.5%), while ondansetron was less frequently prescribed. Non-pharmacological strategies such as herbal remedies, ginger, and lemons were also reported, though less widely. Most women used interventions once daily, and satisfaction averaged 3.5, reflecting moderate benefit. Side effects were uncommon, with drowsiness and fatigue the most frequent, while persistent nausea and constipation were reported by only a small minority (Supplementary Table S11).

Strengths and Limitations

This study has several notable strengths. Foremost is its novel application of international tools (Windsor 2021 criteria, PUQE-24, and NVPQoL) in a Palestinian population, representing the first standardized assessment of HG diagnosis and severity in the region. The multicenter design across hospitals and primary healthcare centers in ten West Bank cities ensured diverse sociodemographic and healthcare contexts. By integrating clinical, sociodemographic, behavioral, and cultural determinants, the study provides a multidimensional perspective beyond biomedical risk factors. The large sample size, calculated using robust methods, enhances reliability of estimates. Rigorous translation and pilot testing of questionnaires ensured linguistic validity, while adherence to the STROBE checklist underscores transparency and reproducibility.

Nonetheless, several limitations should be acknowledged. The use of convenience sampling may introduce selection bias, though multicenter recruitment across diverse settings helped mitigate this. The cross-sectional design limits causal inference, but remains appropriate for estimating prevalence and burden. Reliance on self-reported data may involve recall bias, yet validated instruments (PUQE-24, NVPQoL) enhance reliability. The absence of biochemical markers of dehydration or nutrition may restrict clinical characterization, though Windsor 2021 criteria emphasize functional impairment rather than laboratory confirmation. Finally, findings from the West Bank may not be fully generalizable to other regions, but they provide a novel foundation for future comparative research.