Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, and, unfortunately, variability exists among pregnant women in the therapeutic effect of anti-emetics as well as in factors that can exacerbate NVP. Identifying and managing these sources of variability will result in significant improvements in the quality of life of pregnant woman. This dissertation addressed clinical pharmacology strategies in managing NVP by focusing on three predominant areas of variability. The first challenge addressed in this dissertation was women with pre-existing gastrointestinal (GI) conditions and adherence and tolerability to prenatal multivitamin supplementation. To identify the role of iron in reducing adherence and increasing NVP and GI symptoms, two separate studies were conducted. In the first study, women randomized to a prenatal multivitamin supplementation with higher iron content experienced more adverse GI effects and increased severity of NVP symptoms. In the second study, after discontinuing iron-containing prenatal multivitamins, two-thirds of women in a prospective cohort reported improvement in their NVP symptoms which was corroborated with validated scales to quantify NVP severity. The second challenge addressed in this dissertation was the effect of heartburn and acid reflux on the severity of NVP. In a controlled, prospective study, women experiencing heartburn and acid reflux experienced greater severity of NVP compared to women with no GI symptoms. Furthermore, treatment of heartburn and acid reflux with acid-reducing pharmacotherapy with associated with a reduction in GI symptoms and NVP severity. Therefore, histamine 2 blockers or proton pump inhibitors, which do not appear to be associated with increased fetal risks, should be administered when required. The third clinical pharmacology challenge addressed in this dissertation was to determine the pharmacokinetic variability of the active ingredients of Diclectin®, first-line pharmacotherapy for the treatment of NVP. Large variability was observed in the area under the curve for both active metabolites: a 6.5-fold difference for pyridoxal-5’-phosphate and a 2.1-fold difference for doxylamine. Whether these pharmacokinetic differences contribute to suboptimal efficacy remains to be determined. In conclusion, based on the results presented in this dissertation, several improvements in clinical pharmacology strategies can be made to enhance management of NVP.

Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, and, unfortunately, variability exists among pregnant women in the therapeutic effect of anti-emetics as well as in factors that can exacerbate NVP. Identifying and managing these sources of variability will result in significant improvements in the quality of life of pregnant woman. This dissertation addressed clinical pharmacology strategies in managing NVP by focusing on three predominant areas of variability. The first challenge addressed in this dissertation was women with pre-existing gastrointestinal (GI) conditions and adherence and tolerability to prenatal multivitamin supplementation. To identify the role of iron in reducing adherence and increasing NVP and GI symptoms, two separate studies were conducted. In the first study, women randomized to a prenatal multivitamin supplementation with higher iron content experienced more adverse GI effects and increased severity of NVP symptoms. In the second study, after discontinuing iron-containing prenatal multivitamins, two-thirds of women in a prospective cohort reported improvement in their NVP symptoms which was corroborated with validated scales to quantify NVP severity. The second challenge addressed in this dissertation was the effect of heartburn and acid reflux on the severity of NVP. In a controlled, prospective study, women experiencing heartburn and acid reflux experienced greater severity of NVP compared to women with no GI symptoms. Furthermore, treatment of heartburn and acid reflux with acid-reducing pharmacotherapy with associated with a reduction in GI symptoms and NVP severity. Therefore, histamine 2 blockers or proton pump inhibitors, which do not appear to be associated with increased fetal risks, should be administered when required. The third clinical pharmacology challenge addressed in this dissertation was to determine the pharmacokinetic variability of the active ingredients of Diclectin®, first-line pharmacotherapy for the treatment of NVP. Large variability was observed in the area under the curve for both active metabolites: a 6.5-fold difference for pyridoxal-5’-phosphate and a 2.1-fold difference for doxylamine. Whether these pharmacokinetic differences contribute to suboptimal efficacy remains to be determined. In conclusion, based on the results presented in this dissertation, several improvements in clinical pharmacology strategies can be made to enhance management of NVP.

Introduction: Hyperemesis gravidarum (HG) in pregnancy can cause severe and persistent vomiting, nausea, dehydration, vitamin and mineral deficiencies. The symptoms can have varying degrees of impact on women's physical, emotional, social, and marital lives and affect their quality of life. Some women voluntarily terminate their pregnancies due to HG. Despite the severe consequences, the etiology of this disorder remains unknown. HG is thought to be caused by a mixture of hormonal variables and genetics. Various therapies have been documented with varying degrees of efficacy. Nevertheless, there is a lack of research on the actual causes of the disease and effective medications, as well as a lack of research on patients' experiences with HG, its treatments, and its consequences. Aim: This thesis aims to examine women's own experiences of HG, with the following research questions: How do women experience HG in their daily lives? What kind of support do they have in coping? What kind of approach do they receive from the health care system? What medical interventions were offered to them? and how effective were they perceived? Method: The thesis adopts a qualitative approach. Some prominent women's groups on Facebook were used to spread the information about the study, and 20 women in Sweden who had suffered from HG during pregnancy and had given birth no more than four years ago were interviewed individually online via Zoom. The data was analyzed using the thematic analysis method by creating sub-themes and themes through coding. Findings: The analysis revealed two themes: 'Trapped in my own body' and 'Longing for optimal HG care'. The first theme described the women's daily lives, which were significantly affected by HG. Due to severe vomiting and nausea, many of them were bedridden for long periods and unable to take care of their children or do household chores. They had significant problems with eating food, drinking water, odors, and oral hygiene. Many were unable to work, and most were on long-term sick leave. Women relied on their partners and families to cope with HG. The disease was compounded by mental health problems such as isolation, loneliness, sadness, and even depression. The second theme revealed that medications and their perceived effects were experienced differently. No drug could completely cure the disease in every case, and HG treatments were not considered optimal by any woman. Medical facilities often lacked knowledge about the disease and the drugs available, and there were no functioning care plans. Lack of knowledge meant that most women in the early stages of pregnancy were not taken seriously by the health system, and it took a long time for many of them to receive appropriate treatment. Conclusion: HG was perceived by women as a severe disease that caused significant physical and psychological obstacles in life and made women feel imprisoned in their bodies. Their most considerable support in coping with this illness was their partners and family. Despite these severe problems, most received inadequate care at health facilities mainly due to ignorance of the disease. This study has highlighted a great need for clear organizational structures, a working care plan, and more knowledge of HG in all health departments. Evidence-based national and local guidelines are needed to improve the availability and quality of health care. Based on the women’s experiences, the findings of this study may provide essential insights for implementing such guidelines in clinical practice.