Readmissions due to hyperemesis gravidarum: a nation-wide Finnish register study

Nurmi, Miina; Rautava, Päivi; Gissler, Mika; Vahlberg, Tero; Polo‐Kantola, Päivi

doi:10.1007/s00404-022-06448-w

Cited by 8 publications

(3 citation statements)

References 52 publications

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“…Second, there are factors beyond the GDF15 gene which may influence GDF15 production by the feto-placental unit. For example, female fetal sex, the presence of twins or the presence of invasive trophoblastic disease are all associated with increased HG risk 25 , 26 and, at least in the case of female fetuses, increased GDF15 levels in pregnancy 27 . In the case of the C211G HG risk variant, we found suggestive evidence for an interaction between maternal and fetal GDF15 genotypes, with fetal carriage of this variant apparently moderating the maternal effect.…”

Section: Discussionmentioning

confidence: 99%

GDF15 linked to maternal risk of nausea and vomiting during pregnancy

Fejzo,

Rocha,

Cimino

et al. 2023

Nature

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GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1–4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with β-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

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Section: Discussionmentioning

confidence: 99%

GDF15 linked to maternal risk of nausea and vomiting during pregnancy

Fejzo,

Rocha,

Cimino

et al. 2023

Nature

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“…Secondly, there are factors beyond the GDF15 gene which may influence GDF15 production by the feto-placental unit. For example, female fetal sex, the presence of twins, or the presence of invasive trophoblastic disease are all associated with increased HG risk [21,22] and, at least in the case of female fetuses, increased GDF15 levels in pregnancy [23]. In the case of the C211G HG risk variant, we found suggestive evidence for an interaction of maternal and fetal GDF15 genotype with fetal carriage of this variant apparently moderating the maternal effect.…”

Section: Discussionmentioning

confidence: 59%

Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy

Fejzo

Rocha

Cimino

et al. 2023

Preprint

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Human pregnancy is frequently accompanied by nausea and vomiting that may become severe and life-threatening, as in hyperemesis gravidarum (HG), the cause of which is unknown. Growth Differentiation Factor-15 (GDF15), a hormone known to act on the hindbrain to cause emesis, is highly expressed in the placenta and its levels in maternal blood rise rapidly in pregnancy. Variants in the maternal GDF15 gene are associated with HG. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We found that the great majority of GDF15 in maternal circulation is derived from the feto-placental unit and that higher GDF15 levels in maternal blood are associated with vomiting and are further elevated in patients with HG. Conversely, we found that lower levels of GDF15 in the non-pregnant state predispose women to HG. A rare C211G variant in GDF15 which strongly predisposes mothers to HG, particularly when the fetus is wild-type, was found to markedly impair cellular secretion of GDF15 and associate with low circulating levels of GDF15 in the non-pregnant state. Consistent with this, two common GDF15 haplotypes which predispose to HG were associated with lower circulating levels outside pregnancy. The administration of a long-acting form of GDF15 to wild-type mice markedly reduced subsequent responses to an acute dose, establishing that desensitisation is a feature of this system. GDF15 levels are known to be highly and chronically elevated in patients with beta thalassemia. In women with this disorder, reports of symptoms of nausea or vomiting in pregnancy were strikingly diminished. Our findings support a causal role for fetal derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to GDF15, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

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“…Although NVP is very common in early pregnancies, affecting as many as 85% of pregnant women (Ellilä et al, 2018; McParlin et al, 2016; Yeh et al, 2018), HG is infrequent occurring in ~0.3%–3.6% of all pregnancies (Austin et al, 2019). Nevertheless, it is the most common reason for hospitalization during the first trimester of pregnancy (Gazmararian, 2002), and readmissions are common (Fiaschi et al, 2016; Nurmi et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Hyperemesis gravidarum and eating disorders before and after pregnancy: A register‐based study

Terävä‐Utti,

Nurmi,

Laitinen

et al. 2023

Intl J Eating Disorders

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ObjectiveHyperemesis gravidarum (HG) is a severe form of excessive vomiting during pregnancy. The connection between psychiatric morbidity and HG has been debated, but only a few studies have focused on eating disorders (EDs). The objective of this study was to evaluate the association between HG and both pre‐pregnancy and new post‐pregnancy EDs.MethodsA register‐based controlled study. HG diagnoses were retrieved from healthcare registers between 2005 and 2017. Women with HG in their first pregnancy resulting in delivery were chosen as cases (n = 4265; the HG group) and women with no HG as controls (n = 302,663; the non‐HG group). The associations between EDs and HG were analyzed by binary logistic regression, adjusted with age, body mass index, smoking, socioeconomic status, and pre‐pregnancy psychiatric diagnoses.ResultsIn the HG group, 1.6% and in the non‐HG group, 0.2% had a pre‐pregnancy ED. Women with ED were more likely to have HG in their first pregnancy compared with women with no history of EDs (adjusted odds ratio [AOR] 9.4, 95% CI 6.52–13.66, p < .0001). Moreover, 0.4% of the women in the HG group and 0.1% of the women in the non‐HG group had a new ED diagnosis after pregnancy, and thus the women in the HG group were more likely to have an ED diagnosis after pregnancy (AOR I 3.5, 95% CI 1.71–7.15, p < .001, AOR II 2.7, 95% CI 1.30–5.69, p = .008).DiscussionWe found a bidirectional association between ED and HG, suggesting a shared etiology or risk factors between these disorders. This finding emphasizes the importance of collaboration across various specialties when treating these patients.Public SignificanceOur findings suggest a bidirectional association between HG and EDs before and after pregnancy. This finding provides essential information for healthcare professionals working with pregnant women. As both of these disorders are known to have far‐reaching effects on the lives of both the mother and her offspring, our results help clinicians to target special attention and interventions to the patients suffering from these disorders.

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Readmissions due to hyperemesis gravidarum: a nation-wide Finnish register study

Cited by 8 publications

References 52 publications

GDF15 linked to maternal risk of nausea and vomiting during pregnancy

GDF15 linked to maternal risk of nausea and vomiting during pregnancy

Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy

Hyperemesis gravidarum and eating disorders before and after pregnancy: A register‐based study

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