European Journal of Obstetrics & Gynecology and Reproductive Biology
Adjusted leptin level (ALL) is a predictor for hyperemesis gravidarum☆
Introduction
Nausea and vomiting occur approximately in 50–80% of all pregnancies. Extreme nausea and vomiting are infrequent, but troublesome, complaints of pregnant women. This is defined as hyperemesis gravidarum (HG) and occurs in 0.5–2% of all pregnancies [1]. This syndrome is associated with weight loss, dehydratation, ketonuria, ketosis and electrolyte imbalance.
Hyperemesis gravidarum is caused by the complex interaction of endocrinologic, psychoneurotic, genetic and environmental factors. The fundamental trigger in the endocrinological pathway for the development of HG originates from the placenta. The placenta is a complex organ, producing numerous hormones such as human chorionic gonadotrophin (hCG), estrogen and thyroid hormones into the maternal bloodstream. The majority of patients with HG have higher levels of these hormones and severity of the hyperemesis may be mediated by the thyrotropic and steroidogenic activity of the hCG.
During the course of a normal pregnancy changes in thyroid hormone levels occur in the first trimester and continue throughout pregnancy. There is an inverse relationship between maternal levels of TSH and hCG. The thyroid-stimulating activity of hCG is explained by the molecular homology between hCG and TSH, and between their receptors.
Leptin is a circulating protein that regulates metabolic efficiency, energy expenditure and food intake. Leptin is a messenger of energy metabolism. Increased leptin level results in increased energy expenditure. Maternal leptin concentration begins to increase in the first trimester, reaches its peak during the second trimester and remains at that elevated level until parturition. Substantial increases in early pregnancy occur before any notable increase in body weight. Numerous studies have demonstrated that maternal leptin level in the first trimester is affected by the placental secretion [2], [3].
The first aim of the study was to compare the maternal serum leptin level according to the gestational week (adjusted leptin level (ALL): maternal leptin/gestational week) in the first trimester women with HG and with normal pregnancy. The second aim was to assess the relationship between the adjusted serum leptin level, and thyroid hormones (TSH, free T3, free T4) and hCG.
Section snippets
Study design
A prospective study was carried out at the early prenatal care unit, SSK Ankara Maternity and Women's Health Teaching Hospital. Ninety-four first trimester women in two groups were enrolled: 54 women with HG and 42 women without HG.
Hyperemesis gravidarum was defined as nausea and vomiting, positive ketonuria (++++) on urine dipstick examination and two or more hospitalisations in the present pregnancy because of electrolyte imbalance.
The study and control group were compared for age, parity,
Results
The characteristics of both groups are shown in Table 1. Gestational age and BMI were significantly lower in HG group than in the control group (p = 0.001).
Leptin levels were similar between the groups (p = 0.099). However, ALL was significantly higher in the HG group (p = 0.009). Serum TSH, free T3, free T4 levels were significantly different in HG group than in the control group (p = 0.003, 0.013, 0.012, respectively) (Table 2).
A significant positive correlation was found between ALL and BMI in HG
Discussion
Although the etiology of the HG is unknown, many placental products such as hCG, estradiol, and thyroid hormones have been considered to play a role in this syndrome. On the other hand, leptin has a role in fetal growth in both normal and complicated pregnancies [4]. According to the previous reports, placental production of leptin is an important factor for the maintenance of pregnancy [5], [6], [7]. Placental leptin secretion also interacts with hCG and estradiol secretion.
Maternal leptin
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Cited by (23)
Predictive factors of Hyperemesis Gravidarum: A systematic review
2019, European Journal of Obstetrics and Gynecology and Reproductive BiologyNeurodevelopmental delay in children exposed in utero to hyperemesis gravidarum
2015, European Journal of Obstetrics and Gynecology and Reproductive BiologyCitation Excerpt :Hormones, estrogen in particular, have been linked to development of the central nervous system in murine models [24]. While abnormal maternal serum leptin levels are a marker of HG [25,26], neonatal hyperleptinaemia has been associated with an increased level of anxiety developing in adult rats [27]. The findings described by our data, therefore, may be the result of exposure to abnormal hormone levels during fetal development.
Diagnostic markers for hyperemesis gravidarum: A systematic review and metaanalysis
2014, American Journal of Obstetrics and GynecologyCitation Excerpt :Thyroid hormones were described in 34 included articles.20,21,23,49,52,55,56,59-62,66,67,69-72,76-78,80-93 ; 65% of the studies showed decreased thyrotropin,20,23,49,52,59,60,62,69,70,72,81,82,84 and 67% of the studies showed increased FT4 in symptomatic patients compared with asymptomatic control subjects.20,23,52,55,56,59,61,66,69,70,72,77,81-83,86,87,90,91 Similar results were found for total thyroxine 4 (65%),59,62,87,88 total thyroxine 3 (50%),52,62,83,87 and free thyroxine (53%).55,72,77,81,82,86,87,90
Nausea and Vomiting of Pregnancy
2011, Gastroenterology Clinics of North AmericaCitation Excerpt :Recently, a relationship between the hormone leptin and HG has been proposed. Increased serum leptin levels during pregnancy, possibly the result of increased total fat mass and the placenta production, have been found to be significantly higher in patients with HG when compared with healthy pregnant controls.48,49 Leptin may contribute to HG by increasing hCG secretion by the paracrine action of the placenta or by decreasing appetite and promoting more severe nausea and vomiting.
Maternal Body Composition, Smoking, and Hyperemesis Gravidarum
2010, Annals of EpidemiologyCitation Excerpt :In our study, the association was even stronger, probably because we used the World Health Organization cut-off for underweight (18.5 kg/m2). Small studies from the United States and Turkey further support these findings (14, 15), although the difference between methods used does not allow direct comparisons of the results. At the same time, our results suggest that obese and probably underweight women are at increased risk of developing hyperemesis independently of other studied factors.
Hyperemesis gravidarum that requires hospitalization and the use of antiemetic drugs in relation to maternal body composition
2008, American Journal of Obstetrics and Gynecology
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Adjusted leptin level (ALL) as the fundamental factor triggering the development of hyperemesis gravidarum can also be a good predictor for this syndrome.