Thyrotropic action of human chorionic gonadotropin

Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent with the finding that the beta-CTP truncated hCG with higher thyrotropic potency is substantially deglycosylated and desialylated in the beta-subunit relative to intact hCG because all four O-linked glycosylation sites occur within the missing C-terminal extension. The desialylated hCG variant also interacts directly with recombinant hTSH receptors transfected into human thyroid cancer cells. There is thyroid-stimulating activity in sera of normal pregnant women, and this correlates with serum hCG levels. The thyroid gland of normal pregnant women may be stimulated by hCG to secrete slightly excessive quantities of T4 and induce a slight suppression of TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid hormone during early pregnancy in response to the thyrotropic activity of hCG that overrides the normal operation of the hypothalamic-pituitary-thyroid feedback system. Biochemical hyperthyroidism associated with hyperemesis gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum, thyrotropic in serum correlated with hCG immunoreactivity, and the severity of vomiting as indicated by clinical and biochemical parameters correlated with the degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is necessary to know whether hCG activates the same domain of the TSH receptor as does TSH. The identification of the molecular structure of the hCG isoform with the highest thyrotropic potency will resolve the enigma of gestational thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and hCG-producing tumors.     

Calcium and vitamin D status of pregnant teenagers in Maiduguri, Nigeria

This study investigates parameters related to calcium and bone metabolism by determining the concentrations of total calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, and phosphorous in young pregnant women. The patient population was 30 pregnant Nigerian teenage women grouped by trimester (10 per group), 10 women immediately following delivery, and 21 healthy age-matched controls. On the basis of serum prealbumin levels, the general nutrition of the pregnant women was found to be significantly below that of the more privileged and better-educated nonpregnant controls. The mean total calcium concentration in sera of the third-trimester women was 8.83 mg/dL, which was significantly below that of the controls (9.77 mg/dL) and the first-trimester group (9.30 mg/dL). Despite the 10% to 15% decline in the serum level of total calcium during pregnancy, the parathyroid hormone level decreased markedly from 0.60 to 0.61 ng/mL in the first and second trimesters to 0.41 ng/mL in the third trimester. Serum vitamin D and 1,25-dihydroxyvitamin D levels in the second and third trimesters were within the normal range. These data indicate that toward the end of gestation, pregnant teenagers in northern Nigeria appear to become calcium deficient and do not exhibit the expected increase in serum parathyroid hormone levels normally seen in pregnant women.     

Circulating iodide concentrations during and after pregnancy

Early, indirect studies suggested that an important aspect of thyroid economy during pregnancy was a decline in plasma or serum inorganic iodide (PII) concentrations, but there is little information concerning circulating iodide concentrations as assessed by direct measurement. The present study was undertaken to determine the relationship between gestation and serum iodide concentrations as assessed by direct measurement of PII. PII concentrations, urinary iodide levels, and other parameters of thyroid economy were measured during the first, second, and third trimesters and after delivery in 16 women. Mean serum T4 concentrations were significantly higher in all 3 trimesters than those after delivery. Serum free T4 index concentrations were significantly higher in the first trimester than during later periods of gestation or after delivery, but serum TSH concentrations were not depressed in the first trimester. Serum thyroglobulin concentrations were similar during pregnancy and after delivery. There was wide variability in PII and urinary iodide concentrations during and after pregnancy, but there was no trend for PII concentrations to be depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions, does not have an important influence on circulating concentrations of iodide.     

Changes in the binding capacity of thyroxine-binding globulin (TBC), of total thyroxine (T4), of the free thyroxine index (FT4-I) and of thyrotropin (TSH) during normal pregnancy and in hydatidiform mole

TBC-index and total serum thyroxine were measured in 100 healthy nonpregnant and in 163 pregnant women during the 8. and 41. weeks of gestation. The free thyroxine index was calculated. The TBC-index was found to be elevated in pregnant women and rose continously with duration of pregnancy. The amount of total serum thyroxine was greater in pregnant women (p less than 0,01) without difference between early and late pregnancy. The free thyroxine index decreased continously during pregnancy (p less than 0,01). Serum TSH level were elevated during the first two trimesters of pregnancy. At the third trimester the TSH level were found within the normal range. In patients with hydatidiform mole TSH, total thyroxine, FT4-index, ETR-index as well as TSH levels were increased.     

Leptin in human pregnancy: the relationship with gestational hormones

OBJECTIVES: The aims of the study were (1) to examine the relationship between leptin and placental hormones by measuring serial changes in serum levels of leptin during and after pregnancy and (2) to study the effects of several gestational hormones on leptin release from fully differentiated 3T3-L1 adipocyte cell cultures. STUDY DESIGN: Serum levels of leptin were measured throughout pregnancy and at 3 months post partum in 29 healthy women and were also measured in 18 healthy women at delivery by cesarean section and on postpartum day 3. In addition, 3T3-L1 mouse adipocytes were incubated for 24 hours in media containing various reproductive hormones and leptin production was measured. RESULTS: Serum leptin levels increased significantly (8.4 +/- 0.9 vs 13.5 +/- 1.5 ng/mL; P <.001) between the first 2 trimesters of pregnancy but not between the second and third trimesters. These changes in leptin did not correlate significantly with changes in body mass index. Leptin levels dropped significantly during the immediate postpartum period, from 34.1 +/- 4.9 at cesarean delivery to 7.3 +/- 1.4 ng/mL on postpartum day 3 (P <.001). Fasting insulin level did not correlate significantly with leptin level during pregnancy but did so during the postpartum period (r = 0.60; P <.05). Leptin secretion from 3T3-L1 adipocytes was increased significantly when cells were cultured with human chorionic gonadotropin (150%, P <.01) and also when they were cultured with estrogen (120%, P <.03). CONCLUSION: The data suggest that leptin production by adipose tissue is stimulated by several hormones of pregnancy, which may contribute to the increased leptin levels observed during gestation.     

Crucial role of serum human chorionic gonadotropin for the aggravation of thyrotoxicosis in early pregnancy in Graves' disease

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and is closely associated with postpartum recurrence of stimulative thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), was responsible for this early aggravation, the respective TSA due to TSAb or hCG was evaluated by a highly sensitive cAMP accumulation assay using FRTL-5 cells. TSA was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG concentration, and was abolished completely by the pretreatment of serum sample with the solid-phase hCG antibody coupled with Sepharose 4B. The model serum samples of Graves' disease with pregnancy were made by the mixture of normal pregnant and Graves' sera, and their TSA were reduced by the pretreatment with the solid-phase hCG antibody, just corresponding with the reduction in hCG-induced TSA. TSA of early pregnant sera in 20 patients with Graves' disease decreased significantly but were still positive even after the pretreatment with the hCG antibody. Serial changes in TSAb and hCG-induced TSA were measured in 5 of these 20 pregnant patients. hCG-induced TSA increased associated with the increase in free thyroxine, while TSAb did not show striking change in early pregnancy. These data indicate that (1) respective TSA due to TSAb or hCG can be measured distinctively by using the solid-phase hCG antibody and (2) hCG plays a crucial role in the aggravation of Graves' thyrotoxicosis in early pregnancy.     

Pregnancy and multiple sclerosis. A prospective study

OBJECTIVE: To conduct a prospective assessment of pregnancy on women with multiple sclerosis (MS), focusing on pregnancy outcome and relapses during gestation and up to 6 months after delivery. DESIGN: Expected numbers of relapses were based on data for (1) "self-controls": the mothers ("cases") themselves prior to becoming pregnant and (2) "matched controls": female patients with MS "matched" to the mothers for year of birth, age of MS onset, MS type, MS course, and initial MS symptom(s). SETTING: Cases and controls were identified from an ambulatory care MS clinic that serves the province of British Columbia, Canada. PATIENTS OR OTHER PARTICIPANTS: Women with a diagnosis of MS who attended the MS clinic during 1982 through 1986 and subsequently became pregnant during 1982 through 1989 inclusive were included in this study as cases. Matched controls were women with MS who attended the MS clinic during the same period but did not become pregnant. RESULTS: No significant increase in relapse rate was found for cases during the first two trimesters of gestation. The number of relapses was significantly less than expected during the third trimester compared with matched controls (chi 2 = 6.80, df = 1, P < .02), but not compared with self-controls (chi 2 = 3.39, df = 1, P > .05). The observed number of relapses for the 6 months after delivery did not differ significantly from expected (self-controls: chi 2 = 2.84, df = 2, P > .05; matched controls: chi 2 = 1.76, df = 2, P > .05). CONCLUSION: These data suggest that neither pregnancy nor the 6-month period after delivery is a risk factor for relapse in MS. They are consistent with previous observations that, in the long term, pregnancy does not influence subsequent MS disability.     

Brief communication: effects of diagnostic irradiation during pregnancy on head circumference at birth

A historical cohort study was carried out to evaluate the effects in utero medical ionizing radiation on head circumference at birth. The nature of medical practice in Rochester, Minnesota, and the Mayo Clinic medical records linkage system enabled us to provide accurate estimates of medical radiation absorbed dose in 9,793 pregnancies of 2,980 women pregnant in Rochester between 1917 through 1973. Data were controlled for sex of the fetus, duration of pregnancy and congenital head abnormalities. It was found that medical ionizing radiation in the second and third trimesters of more than 300 mrad were related to significantly decreased head circumference. There was no significant effect of radiation exposure in the first trimester or periconceptional period. Medical ionizing radiation in the second and third trimesters of more than 300 mrad is related to a significant yet minimal, decreasing head circumference at birth. Maximum effects were seen during the midgestational and second trimester periods.     

Nitric oxide synthase activities in human myometrium and villous trophoblast throughout pregnancy

OBJECTIVE: To study the changes in nitric oxide synthase activities in human myometrium and trophoblast throughout pregnancy and around delivery. METHODS: Samples of villous trophoblast were collected from women undergoing elective cesarean delivery at term (n = 12) or voluntary termination of pregnancy in the first (n = 27) or second (n = 11) trimesters of pregnancy. Myometrial samples were obtained from nonpregnant women undergoing hysterectomy (n = 5) and pregnant women both before (n = 7) and after (n = 7) the onset of spontaneous labor at term. Nitric oxide synthase activity was quantified for homogenized samples using the L-citrulline assay in the presence and absence of calcium. RESULTS: The highest levels of nitric oxide synthase activity were found in first-trimester villi (range 2-29 nmol L-citrulline/minute/g protein), with a significant fall in activity in the third trimester (range 2-10 nmol L-citrulline/minute/g protein; P < .001 for both calcium-dependent and calcium-independent activity). Myometrial activities were relatively low compared with those in the trophoblast (0-2 nmol L-citrulline/minute/g protein), with no significant differences in calcium-dependent activities between subgroups. Myometrial calcium-independent activities were lower in pregnant than in nonpregnant women (P = .007), with those in labor having levels higher than those not in labor (P = .048). CONCLUSION: Levels of nitric oxide synthase activity are relatively high in villous trophoblast, particularly during the first trimester. Although the contribution to total nitric oxide production in the uterus by myometrial nitric oxide synthase appears to be relatively small, nitric oxide produced by the trophoblast may play a role in maintaining uterine quiescence by a paracrine effect. Further work is needed to test this hypothesis and explore other possible roles for trophoblast-derived nitric oxide in early pregnancy.     

Identification of lymphocyte subsets in pregnancy gingivitis

The percentage of gingival tissue and peripheral T, T Subsets and B lymphocytes were assessed in ten pregnant women during the first, second and third trimesters. Clinically the gingival index (GI) was found to be higher during pregnancy than in the control group. The percentage of the T3, T4 and B cells appeared to decrease in peripheral blood and gingival tissues during pregnancy as compared to control group.     

Quinine pharmacokinetics in young children with severe malaria

In this study, we determined selenium concentrations in serum samples of healthy women (146 pregnant and 74 nonpregnant) living in the Mediterranean area of the coast of Granada (southeast Spain). The subjects were distributed in two groups: group A (pregnant women), divided into three categories according to the trimester of pregnancy, and group B (nonpregnant women). No significant differences were observed in the selenium levels either among pregnant women according to the trimester of pregnancy or in the group of nonpregnant women. No other significant differences were determined as regards the age of pregnant women (P > 0.05). Serum selenium levels are slightly lower during pregnancy. Considering that serum selenium levels affect the body selenium status, the concentrations determined establish the non-existence of selenium problems in the daily dietary intake with respect to maternal and fetal necessities during pregnancy.     

Diagnosing gestational hypertension and preeclampsia with the 24-hour mean of blood pressure

The use of ambulatory blood pressure monitoring has provided a method of blood pressure assessment that may compensate for some of the limitations of isolated measurements. Here we aim to examine prospectively the effectiveness of the commonly used 24-hour mean as a potential screening test for the identification of gestational hypertension and preeclampsia. We analyzed 503 blood pressure series from 71 healthy pregnant women and 256 series from 42 women who developed gestational hypertension or preeclampsia. Forty-eight-hour blood pressure monitoring was done once every 4 weeks after the first obstetric consultation. Sensitivity and specificity of the 24-hour mean of blood pressure were computed for each trimester of pregnancy by comparing distributions of values obtained for healthy and complicated pregnancies, without assuming an a priori threshold for diagnosing gestational hypertension on the basis of mean blood pressure. Sensitivity ranges from 31.8% for diastolic blood pressure in the second trimester to 84.1% for systolic blood pressure in the third trimester. However, specificity is as low as 6.9% for diastolic blood pressure in the first trimester. The positive predictive value does not reach 55% for any variable in any trimester. The higher relative risk was consistently obtained for systolic blood pressure (4.9 in the third trimester). Despite the highly statistically significant differences in blood pressure found between healthy and complicated pregnancies in all trimesters, the daily mean of blood pressure does not provide a proper and stable individualized test for diagnosing hypertensive complications in pregnancy. Other indexes obtained from the blood pressure series have been shown, however, to identify early in pregnancy those women who subsequently will develop gestational hypertension or preeclampsia, rendering ambulatory blood pressure monitoring a useful, but still costly, technique in pregnancy.     

Protein solution structure calculations in solution: solvated molecular dynamics refinement of calbindin D9k

Data were collected on the drinking behavior of 415 pregnant adolescents from 1990 to 1994. The relationships between knowledge and attitudes about drinking and drinking behavior were examined. Knowledge about drinking was not related to average daily volume of alcohol before or during pregnancy. Those with specific knowledge about fetal alcohol effects drank less before pregnancy, and in the first trimester, and were also less likely to drink to intoxication. Among drinkers, general knowledge about drinking was significantly related to a decrease in drinking between pre-pregnancy and first trimester, as well as between first and third trimesters. Those with more intolerant attitudes about drinking drank less before and during pregnancy. They had fewer episodes of binge drinking, intoxication, negative consequences, and problem drinking during pregnancy. They were more likely to decrease drinking from the first to third trimesters. These relationships are relevant to developing effective education programs for the high-risk group of pregnant teenagers who drink.     

Near infrared spectroscopy detects cerebral ischemia during hypotension in piglets

OBJECTIVE: To determine if platelet angiotensin II binding density during the second or third trimester of pregnancy can be used as a marker for early detection of women who will develop preeclampsia. METHODS: We collected blood samples from 412 nulliparous pregnant women during their second or third trimesters. They were classified in four groups after delivery: normotensive (n=297), transient hypertensive (n=54), preeclamptic (n=39), and chronic hypertensive (n=22). We also studied 35 nonpregnant women and 122 women in the peripartum period. The binding capacity of platelet angiotensin II receptors was analyzed in each patient. RESULTS: In normotensive pregnancies, there was a significant decrease in mean (+/-standard error of the mean [SEM]) platelet binding in the second trimester (1.6+/-0.2 fmol/10(9) cells) compared with nonpregnant women (3.3+/-0.7 fmol/10[9] cells). No statistical differences were observed in the mean (+/-SEM) number of platelet angiotensin II binding sites between the groups studied in the third trimester (normal: 1.7+/-0.1 fmol/10(9) cells; transient hypertensive: 2.3+/-0.4 fmol/10(9) cells; preeclamptic: 1.6+/-0.4 fmol/10(9) cells, and chronic hypertensive: 1.6+/-0.6 fmol/10(9) cells), nor were any significant differences found in second-trimester values. At cutoff levels providing identical sensitivities, angiotensin II binding showed significantly lower positive predictive values than mean arterial pressure (P < .05). With this study's sample size, we could have demonstrated an improvement in positive predictive values of 20% with a statistical power (1-beta) of 90%. CONCLUSION: The measurement of platelet angiotensin II receptor density cannot be recommended for the early detection of preeclampsia.     

Antibiotic susceptibility of Neisseria gonorrhoeae in Trinidad and Tobago

The authors studied the state of humoral immunity in thirty six female individuals with normal pregnancy, 52 ones presenting with mild anemia, 33 with moderately severe, and 14 with severe anemia, as well as in twelve healthy non-pregnant women. The studies were made by trimesters in the time course of pregnancy. Those pregnant with no anemia demonstrated lowering of B-lymphocytes, rise in circulating immune complexes (CIC) as compared to the non-pregnant individuals; no difference in the immunoglobulins content was noted. In anemia of the pregnant women the immunity B-system gets suppressed with progression of anemia, CIG tend to be on the increase, IgM and IgG get augmented during the second and third trimesters of pregnancy. The above changes suggest some inadequacy of humoral immunity in anemia of pregnancy.     

Potent thyrotropic activity of human chorionic gonadotropin variants in terms of 125I incorporation and de novo synthesized thyroid hormone release in human thyroid follicles

Using a highly sensitive bioassay for TSH, in which human thyroid follicles incorporate 125I and release de novo synthesized thyroid hormone into the culture medium, the thyrotropic activities of various hCG preparations were studied. Under the culture conditions employed, bovine TSH (bTSH) was approximately 6- to 9-fold more active than human TSH (hTSH). Highly purified hCG prepared from urine of normal pregnant women (CR 127) had only a trivial thyrotropic activity equipotent to 0.00022 microU bTSH/U hCG or 0.0013 microU hTSH/U hCG (19.7 microU hTSH/mg hCG). Hybrid hCG (AB1ER) also elicited low thyrotropic activity (14.0 microU hTSH/mg), whereas crude hCG had moderate thyrotropic activity (0.041 hTSH microU/U hCG or 127 microU/mg protein). Deglycosylated hCG, a very weak LH/hCG receptor agonist, was the most potent agonist in thyroid follicles (588 microU hTSH/mg protein). hCGs purified from urine of patients with trophoblastic tumors had greater TSH-like activity (37-84 microU hTSH/mg protein) than purified hCG. Asialo-hCG purified from a patient with choriocarcinoma had very potent TSH-like activity (468 microU hTSH/mg). Submaximal doses of bTSH and hCG variants produced additive stimulation of thyroid function. Furthermore, the thyrotropic effect of hCG was inhibited by anti-TSH receptor antibody obtained from patients with myxedema. These in vitro findings suggest that although hCG is reported to exert potent cAMP-stimulating activity on rat thyroid-like cells (FRTL-5) and Chinese hamster ovary cells transfected with hTSH receptor complementary DNA (0.092-0.72 microU hTSH/U hCG), the thyrotropic activity induced by authentic hCG in human thyroid follicles is too weak to cause hyperthyroidism in normal pregnancy. However, hCG produced by some trophoblastic tumors, particularly asialo-hCG, has potent thyrotropic activity sufficient to cause clinically overt hyperthyroidism when produced excessively.     

Changes in levels of cell adhesion molecules, acute phase proteins, lipids and hemostasis in relation to levels of endogenous estrogens during pregnancy and after ovariectomy

The protective effect of oestrogens is probably caused also by the active inhibition of the inflammatory reaction of the acute phase and release of inflammatory cytokines type IL-1 beta or TNF-alpha by this hormone. We formulated this hypothesis because we recorded a drop of the protein of the acute stage, orosomucoid, in relation to the rising oestrogen level during pregnancy (r = -0.511, p < 0.0001). It ensues also from the finding of a lower level of cytoadhesive molecules of sE-selectins in a group of 66 pregnant women (sE-sel.: 32.95 +/- 12.5 ng/ml) with a higher level of 17-beta estradiol (17-beta E2: 9.34 +/- 7.8 nmol/l), as compared with the sE-selectin level in a group of 14 women after ovariectomy (sE-sel.: 43.97 +/- 8.174 ng/ml, p < 0.016) who lacked oestrogen (17-beta E2 0.14 +/- 0.13 nmol/l) and in a group of pregnant women (n 19) in the first trimester with level of 17-beta E2: 1.89 +/- 0.711 nmol/l where the sE-selectin concentrations at the onset pregnancy was higher (sE-sel.: 35.59 +/- 9.5 ng/ml) than in a group of pregnant women (n 38) during the second and third trimester (sE-sel.: 30.58 +/- 13.3 ng/ml, p < 0.05) with 17-beta E2 concentration 11.96 +/- 7.18 ng/ml. The finding of lower sE-selectin levels which is a sign that the endothelium is not exposed to the action of inflammatory cytokines IL-1 or TNF may thus be associated with the active "control" of thrombophilia in pregnancy. When during pregnancy in conjunction with oestrogen levels changes in the lipid concentration were investigated a compensating mechanism could be observed. Hypercholesterolaemia and hypertriglyceridaemia in pregnant women was associated with a rise of oestrogen levels as well as of "cardioprotective" HDL-cholesterol (the HDL level was during the first trimester 1.31 +/- 0.26 nmol/l, in the second and third trimester 1.69 +/- 0.48 nmol/l, p < 0.0167).     

Expression of the mnb (dyrk) protein in adult and embryonic mouse tissues

Remission of Graves' disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associated with type 2 rather than type 1 cytokine production, a decrease in thyroid-stimulating antibody (TSAb) activity alone is unlikely to account for the remission during pregnancy. We hypothesized that a change in the antibody characteristics may occur as pregnancy advances. Fifteen women were studied in the first, second, and third trimesters of pregnancy and 4 months postpartum. TSH receptor antibodies were determined using human thyroid cell cultures, and lymphocyte subsets were measured by flow cytometry. Median TSAb (determined by cAMP release) decreased from 280% (96-3200) to 130% (range, 35-350; P < 0.05) during pregnancy, but no significant change was noted with the TSH binding inhibitory antibody (TBII; determined by RRA). Thyroid stimulation-blocking antibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased from 16 +/- 9% to 43 +/- 16% (mean +/- SD; P < 0.005). The increase in TSBAb was observed even among those patients who were in clinical remission before pregnancy. Overall, a negative correlation was observed between TSBAb activities and free T4 levels during pregnancy (r = -0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were observed in the seven patients who relapsed during the postpartum period. In comparison, the healthy pregnant women (n = 14) were all negative for TSAb, TBII, and TSBAb throughout pregnancy. The absolute number of T lymphocytes, T helper cells, and natural killer cells, but not B cells, decreased significantly during pregnancy in both healthy women and GD patients. GD patients had significantly more CD5+ B cells at all stages of pregnancy compared to controls. In conclusion, a change in specificity from stimulatory to blocking antibodies was observed in GD patients during pregnancy and may contribute to the remission of GD during pregnancy.     

Energy intake and net weight gain in pregnant women according to body mass index (BMI) status

OBJECTIVE: To investigate whether body mass index (BMI) is related to energy intake during pregnancy, and whether BMI, energy intake and other factors are related to net weight gain. DESIGN: Longitudinal, duration of pregnancy. SUBJECTS: 156 healthy pregnant women residing in Quedlinburg county, Germany. METHODS: Weighed 7 d food records and standardized anthropometric measures in the first, second and third trimester. The analysis of variance (ANOVA) statistical technique was used to analyze differences in energy intake, net weight gain and birthweight across BMI groups, and the Cochran-Mantel Haenszel test was used to analyze food group intake by BMI group. RESULTS: Women at the highest level of BMI were significantly less often in the high energy intake category than women at the medium or low level of BMI (15% vs 36% and 48%). Net weight gain during pregnancy was independently influenced by BMI status and energy intake. Women at the highest level of BMI gained significantly less weight (4.2 kg) from first to third trimester than women at the medium or low levels of BMI (weight gains of 6.2 kg and 5.9 kg, respectively). Women with a low daily energy intake gained 4.6 kg during pregnancy, while women with medium and high energy intakes gained 6.0 kg and 6.1 kg, respectively. Examination of net weight gain simultaneously across BMI and parity groups revealed a much lower net weight gain among multigravid women at the highest BMI level (3.3 kg). Primigravid high BMI women, in contrast, gained 6.9 kg, whereas multigravid and primigravid women at medium and low BMI levels gained average of 4.8 kg and 6.5 kg, respectively. The mean birth weight in the three BMI groups did not differ and was not influenced by age, marital status, education, parity or smoking. CONCLUSION: Because other studies have shown that weight gain during pregnancy increases the risk of subsequent overweight, multigravid high BMI women may prevent an increased weight retention after pregnancy due to lower weight gain in the current gestation. A lower caloric diet may help to accomplish a lower weight gain during pregnancy in overweight women without increased risk of low birth weight infants. These findings indicate further investigation of the associations between BMI, parity and caloric intake during pregnancy are needed to increase understanding of factors affecting subsequent weight gain.     

Longitudinal study of carbohydrate metabolism in healthy obese pregnant women

OBJECTIVE: To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy. RESEARCH DESIGN AND METHODS: Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500-600 pmol/l) clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester (36.8 +/- 0.9) of pregnancy and again 15.6 +/- 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6-2H2]glucose) and oxidation (with indirect calorimetry) were measured. RESULTS: There were no significant changes with respect to the action of insulin on rates of glucose disappearance (GRd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (-28%, P < 0.05, compared with the second trimester and -40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (-39% compared with -79% at the second trimester and -77% postpartum, P < 0.01). CONCLUSIONS: Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterations were reversed after delivery and appeared to be adaptive mechanisms to cope with the increased demand for glucose of the growing fetus.