Cholecystokinin secretion in pregnancy.

The gallbladder volume is increased in pregnancy, and its contraction during a meal is impaired. This is of importance for the increased risk of gallstones in pregnancy, since it may cause retention of cholesterol crystals in the gallbladder lumen. Cholecystokinin (CCK) is responsible for the food-induced gallbladder contraction. We have consequently measured the plasma concentrations of CCK in the fasting and the stimulated state in pregnant women and in age-matched non-pregnant controls. In a subset of pregnant women and controls the gallbladder volume was measured with ultrasound. The results show that whereas basal CCK concentrations were normal, the response to an oral preparation that contracts the gallbladder was increased in pregnancy. Moreover, the secretion of CCK correlated well with gallbladder emptying. We conclude that the behaviour of the gallbladder in pregnancy is not due to impaired secretion of CCK.

Nausea and vomiting in pregnancy: a review.

Throughout pregnancy, women with nausea and vomiting in early pregnancy showed a different metabolic pattern compared to asymptomatic pregnancies. Women suffering from nausea and vomiting seem to have a low "functional reserve" of their liver capacity and could tentatively be described as hypersensitive to estrogens or their metabolites, e.g., catecholestrogens. These steroids have "emetic" properties, which might be explained by their direct stimulation of area postrema. It is known that estrogens increase the brain's excitability. Another possible mechanism could be by interacting with liver metabolism, resulting in the production of irregular metabolites, which in turn possess "emetic" qualities.

PIP: The definition, history, incidence, diagnosis, possible etiology and treatment of nausea and vomiting in early pregnancy, also called emesis gravidarum, are reviewed. The condition may involve nausea, retching and/or occasional vomiting in early pregnancy: severe vomiting is termed hyperemesis gravidarum. The condition was described as early as 2000 B.C. It occurs in 50-70% of pregnancies in Western societies, but is said to be rare in some primitive societies. A lower incidence of nausea and vomiting has been associated with spontaneous abortion before 20 weeks gestation. Among selected hormones measured in pregnant women, those with nausea and vomiting in early pregnancy had significantly lower cortisol and progesterone, but higher hCG, while those with vomiting in late pregnancy had significantly lower testosterone and hCG and higher dehydroepiandrosterone than unaffected women. Other factors proposed as causative agents include tissue polypeptide antigen, high LDLs and VLDLs, and low HDLs, gall bladder disease, and ovulation from the right ovary. Women who develop nausea while taking oral contraceptives also have a tendency to do so in pregnancy. Possibly the steroid load on the liver may explain the condition. In the absence of a theory to explain nausea in pregnancy, no specific treatment is known. Experimental use of S-adenosyl-L-methionine, a methyl donor active in estrogen conjugation, reverses some estrogen-induced liver changes, such as cholestasis, pruritus, and bile acid abnormalities in pregnancy.

Serum lipids and lipoproteins in pregnancies associated with emesis gravidarum.

Nausea and/or vomiting in pregnancy (emesis gravidarum) is a very common event. The specific etiology of this disorder is still unknown. In this study we examined serum lipid and lipoprotein concentrations in 98 healthy pregnant women in early and late pregnancy. Sixty of these women complained of emesis gravidarum. Compared to non-pregnant controls the pregnancy values of serum cholesterol, triglycerides and phospholipids were elevated in all subjects due to an increase in all lipoprotein classes. In addition, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were enriched in triglycerides relative to other components. Differences in serum lipids and lipoproteins between the emetic and non-emetic subjects were found. The lipid contents of LDL and HDL were significantly higher and lower, respectively, in the emetic women in early pregnancy. During late pregnancy the total lipid content in all fractions was higher in previously emetic subjects. Thus, a metabolic difference between the groups persisted throughout pregnancy. It is suggested that an altered influence of estrogen on the liver might be responsible for these dissimilarities.

Steroid hormones in emetic and non-emetic pregnancy.

Nausea and/or vomiting in early pregnancy is common enough to be generally accepted as normal or 'physiological'. The specific etiology of these complaints is still obscure. One possibility is that endocrine factors may play some part. In this study, 102 healthy pregnant women, of whom 62 complained of nausea, were followed throughout pregnancy and the circulating levels of cortisol, testosterone, dehydroepiandrosterone sulphate (DHEA-S), progesterone, oestradiol and total and free oestriol were measured. In early pregnancy, serum levels of cortisol and progesterone were significantly lower in emetic subjects. In the last trimester, significantly higher DHEA-S concentrations and lower testosterone values were found in women who had suffered from nausea and vomiting in early pregnancy compared to asymptomatic subjects. Overt differences were found between emetic and non-emetic pregnancy and it is concluded that endocrine factors are of etiological importance in emesis gravidarum.

Serum bile acids, gamma-glutamyltransferase and routine liver function tests in emetic and nonemetic pregnancies.

The etiology of nausea and vomiting in pregnancy is still unknown. One possibility is that ovarian and placental hormones may play some part. The liver is the major site of metabolic inactivation of steroid hormones. In this study, 102 healthy pregnant women, of whom 62 complained of nausea, were followed throughout pregnancy. Liver function tests were performed to ascertain whether emesis gravidarum is related to impaired hepatic function. In this series, all values were within the normal ranges. Serum levels of total bilirubin and gamma-glutamyl-transferase were significantly decreased and those of total serum bile acids significantly increased in emetic women compared to nonemetic subjects. Furthermore, the metabolic load on the liver seems to follow a biphasic course as there is an apparent minimum in liver function variables in the second trimester. It is concluded that a slow adaptation to the increased hormonal load on the liver might be responsible for the condition of emesis gravidarum.

Non-steroid hormones and tissue polypeptide antigen (TPA) in emetic and non-emetic pregnancy.

In order to investigate further the endocrine and metabolic features of the common condition emesis gravidarum, serum concentrations of some non-steroid hormones and tissue polypeptide antigen (TPA) were determined in 102 healthy pregnant women. 62 complained of nausea and vomiting in early pregnancy. Significantly higher and lower levels of human chorionic gonadotropin were noted in early and late pregnancy, respectively, in women with emesis gravidarum. A significant rise in serum prolactin and TPA was found throughout pregnancy in all subjects, no differences between emetic and non-emetic pregnancies being registered. Serum concentrations of growth hormone (hGH) showed a significant decline as pregnancy advanced. Emetic women demonstrated higher hGH levels in late pregnancy than did asymptomatic subjects. Free T4 concentrations remained stable when comparing early with late pregnancy, no dissimilarities being found between women with and without nausea and vomiting in pregnancy. These data do not support the hypothesis of major metabolic disturbances as an etiologic factor for nausea and vomiting in pregnancy. However, as overt differences between emetic and non-emetic pregnancy were found, hormonal factors may be involved in the pathogenesis of this condition.

Does position and size of corpus luteum have any effect on nausea of pregnancy?

It is a puzzling fact that emesis might occur in one pregnancy, whereas other pregnancies in the same woman could be either free or again associated with nausea. Pregnancy-associated hormones are believed to cause nausea, possibly through effects mediated via the liver. In 43 women who applied for a legal abortion in early pregnancy the occurrence of nausea was recorded and the position and size of the corpus luteums were measured by means of ultrasound. It was found that emesis was associated with corpus luteum located predominantly on the right side, while the non-emetic pregnancy often had a left-sided corpus luteum. It is suggested that the venous drainage, which differs between the right and the left side, may be responsible for the fact that the same woman can either suffer from or be free from nausea during pregnancy. Ovarian vein insufficiency, being more common in multigravidity, may also explain why nausea is more common in multigravidae.

Gallbladder disease related to use of oral contraceptives and nausea in pregnancy.

In our series of women with confirmed gallbladder disease, intolerance of oral contraceptives was remarkably high. Among women who did not tolerate oral contraceptives there was a remarkably high percentage of emesis gravidarum. The frequency of cholecystectomy declined substantially between 1971 and 1981. This decrement was especially pronounced in women younger than 40, which could be attributed to the reduced "hormonal load" from both fewer pregnancies and reduced intake of contraceptive steroids.

Some new aspects on emesis gravidarum. Relations to clinical data, serum electrolytes, total protein and creatinine.

Although nausea and vomiting in early pregnancy is extremely common, very little information on the cause and course of this disorder is available in the literature. A prospective laboratory and clinical study of 102 consecutive healthy pregnant women was undertaken to evaluate nausea and vomiting in relation to clinical data, serum electrolytes, creatinine, total protein and hemoglobin. Multigravidae suffered from emesis gravidarum at a higher rate than did primigravidae. The frequency of emesis was especially high in women with short intergestational intervals. During pregnancy there was a decline in systolic blood pressure only in non-emetic women. The diastolic blood pressure in late pregnancy was significantly higher in emetic women than in non-emetic subjects. All laboratory values were within normal ranges. However, major changes occurred during pregnancy but some alterations were noted only in the emetic pregnancy. A different response to the hormonal situation is suggested to explain the dissimilarities between the emetic and non-emetic pregnancy.

Nausea and vomiting in pregnancy--a contribution to its epidemiology.

Nausea in pregnancy is very common but it is astonishing that so little data are available concerning the cause and course of this disorder. A questionnaire was mailed to all women who had given birth to at least 3 children, the last delivered in 1980 or 1981 in our department. 244 (75%) responded, mean age 33 years, range 23-45. A total of 948 pregnancies resulted in 855 children, 56 spontaneous and 25 legal abortions, 8 twins and 4 ectopics. 70% of all pregnancies were associated with nausea and 52% of the patients always experienced nausea during their pregnancies, while 17% never and 31% only occasionally felt sick. For 91% of the cases, the onset of nausea was during the first 3 months. There was no difference concerning intensity, 'peak nausea' or onset, whereas duration decreased with subsequent pregnancies. 7 of 8 women with twin pregnancies complained of nausea, contrasting to 50% with spontaneous and 80% with legal abortions. Age, smoking or 'pregnancy complications' did not correlate with nausea. There were, however, correlations (p less than 0.05) between nausea and gallbladder disease, gastritis and allergy. All patients with gallbladder disease had nausea and so had 90% of those with allergy and gastritis. There was also a strong correlation (p less than 0.001) between nausea in pregnancy and 'intolerance' of oral contraceptives, as 98% of these women experienced nausea. The data obtained do not support a correlation between HCG and emesis gravidarum, but rather suggest an association with steroidal hormones and liver function.