Nonpregnant Control Subjects Research Articles

Insulin receptor binding to erythrocytes in the first half of pregnancy is increased in healthy pregnant women as compared with non-pregnant or gestational diabetic women

Insulin binding to erythrocytes was measured longitudinally by a competitive radioreceptor assay in 21 healthy pregnant (HP) and 20 well-controlled gestational diabetic women (GD) in 4-week intervals throughout pregnancy and at day 4 post-partum. Maximum insulin binding (maxbdg) at weeks 8–14 was increased ( P < 0.001) in HP (median: 6.0%) but not in GD (median: 2.7%) as compared with non-pregnant control subjects (C) (median: 3.6%; previously reported: Clin. Chim. Acta 1992;207:57–71) due to an increased number of high-affinity insulin receptors. Throughout gestation the binding decreased continuously, to reach at term the levels found in C. In GD maxbdg remained close to the level of C throughout pregnancy. Binding differences between HP and GD were independent of the body mass index. Maxbdg did not differ between diet- and insulin-treated patients. It was higher in women whose offspring had low umbilical cord insulin levels (< 10 μunits/ml). The findings suggest that (a) higher insulin binding in HP could contribute to the improved glucose tolerance in early pregnancy and (b) the lack of increase in insulin binding during early pregnancy in gestational diabetes might be one factor leading to the manifestation of the disease in late pregnancy. However, it must be kept in mind that insulin receptors on erythrocytes do not necessarily resemble those on the major target tissues of insulin.

Behavior of Diluted Activated Partial Thromboplastin Time in Pregnant Women with a Lupus Anticoagulant

The present study was developed to verify whether a reduction in phospholipid concentration could increase the activated partial thromboplastin time (APTT) sensitivity to detect lupus anticoagulant (LA) during pregnancy. The authors studied 38 pregnant women (10 normal subjects and 28 patients with associated clinical complications) and 40 nonpregnant control subjects. Tests to detect LA, including APTT, platelet neutralization procedure (standard APTT), the kaolin clotting time, the diluted Russell viper venom test neutralized by lysed platelets, and factor assays, were performed. Positive results were found in 5 of 28 pregnant women with associated clinical complications. The APTT, using three different phospholipid concentrations (standard and more diluted cephalin), was performed on plasma samples and on its 1:1 mixture with normal plasma. The behavior of standard and diluted APTT was similar in negative LA pregnant women and nonpregnant control subjects. The mean values showed nonsignificant differences. Four of five pregnant women with positive LA findings had a prolonged APTT, which was not corrected by the addition of normal plasma using standard conditions. When diluted phospholipids were used, only one of them had a prolonged APTT that was corrected by the addition of normal plasma. Therefore, the highest sensitivity (80%) and specificity (100%) of the APTT to detect LA in pregnant women were obtained using the standard conditions.

Neutrophil Platelet-Activating Factor in Normal and Hypertensive Pregnancy and in Pregnancy-Induced Hypertension

1. Platelet-activating factor is a phospholipid with potent vasodilator and platelet-activating properties. To test the hypothesis that a generalized change in cellular platelet-activating factor metabolism may be involved in the systemic vasodilatation of normal pregnancy or pregnancy-induced hypertension, we studied platelet-activating factor and eicosanoid synthesis in isolated leucocytes obtained from pregnant women before and after delivery compared with age-matched non-pregnant control subjects. Parallel observations were carried out in age- and gestation-matched women with uncomplicated hypertension in pregnancy and in women with pregnancy-induced hypertension and a further set of normotensive pregnant control subjects. 2. Leucocyte counts were higher in all pregnant groups compared with non-pregnant control subjects. Neutrophil production of platelet-activating factor and metabolites of prostacyclin, prostaglandin E2 and thromboxane in response to calcium ionophore stimulation were all lower in pregnant women compared with non-pregnant control subjects, but returned to similar levels 6 weeks post partum. There was no significant difference between essential hypertensive and normotensive groups. When women with pregnancy-induced hypertension were a priori sub-divided into those with or without proteinuria, subjects with proteinuria showed significantly lower levels of neutrophil platelet-activating factor synthesis. 3. Plasma levels of the platelet-activating factor metabolite (lyso-platelet-activating factor) were also lower in pregnancy, suggesting alterations in the activity of enzymes controlling synthesis or degradation of this phospholipid in pregnancy. In pregnancy-induced hypertension the levels of plasma lyso-platelet-activating factor were higher than in normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal and fetal outcome after breast cancer in pregnancy

We compared 118 women with breast cancer (119 pregnancies) with 269 nonpregnant control subjects matched on important prognostic factors. The distribution of breast cancer stages among the 118 pregnant women was compared with that among 5115 cases of breast cancer in women of reproductive age. Fetal outcome was compared with that of a control group matched for maternal age. Women having breast cancer in pregnancy were 2.5 times more likely to have metastatic disease (95% confidence interval 1.1 to 5.3) and had a significantly lower chance of having stage I disease ( p = 0.015). Survival of pregnant women did not differ from that of the controls. Birth weights of babies born to women with breast cancer were significantly lower than those of control babies after gestational age was adjusted for (3010 ± 787 vs 3451 ± 515 gm, p = 0.016). The two stillbirths in 85 pregnancies that continued to term (2.4%) was not statistically different from the 1.1% rate for Ontario. We analyzed all 223 births occurring in women who had any form of cancer in the same hospital during the same 30 years. There were 10 stillbirths among these 223 cases (4.4%), significantly more than expected in Ontario ( p

Cutaneous Blood Flow in Gestational Hypertension and Normal Pregnancy

A laser Doppler flowmeter was used to assess skin blood flow changes in three groups of young subjects: women with gestational hypertension, healthy pregnant women, and healthy non-pregnant women. Responses to four vasoactive stimuli were studied: isometric and cognitive activities, cutaneous post ischemic reactive hyperemia, and local heating. The first two stimuli are vasoconstrictive and were performed on the fingertip, whereas the latter two are vasodilative and were performed on the forearm. The most prominent differences were observed in the isometric test, where the expected decrease, which was indeed registered in non-pregnant women, was almost absent in the healthy pregnant group. The gestational hypertension group had a greater decrease in blood flow than normal pregnancy, but lesser than non-pregnant control subjects. We conclude that although normal pregnancy modifies the response of the skin microvasculature to some vasoactive stimuli, gestational hypertension pushes that response back toward the non-pregnancy state.

Maternal and fetal outcome after breast cancer in pregnancy

We compared 118 women with breast cancer (119 pregnancies) with 269 nonpregnant control subjects matched on important prognostic factors. The distribution of breast cancer stages among the 118 pregnant women was compared with that among 5115 cases of breast cancer in women of reproductive age. Fetal outcome was compared with that of a control group matched for maternal age. Women having breast cancer in pregnancy were 2.5 times more likely to have metastatic disease (95% confidence interval 1.1 to 5.3) and had a significantly lower chance of having stage I disease (p = 0.015). Survival of pregnant women did not differ from that of the controls. Birth weights of babies born to women with breast cancer were significantly lower than those of control babies after gestational age was adjusted for (3010 +/- 787 vs 3451 +/- 515 gm, p = 0.016). The two stillbirths in 85 pregnancies that continued to term (2.4%) was not statistically different from the 1.1% rate for Ontario. We analyzed all 223 births occurring in women who had any form of cancer in the same hospital during the same 30 years. There were 10 stillbirths among these 223 cases (4.4%), significantly more than expected in Ontario (p less than 0.0005; relative risk of 4.23 with 95% confidence interval 2.0 to 7.8). Our data suggest that pregnant women are at a higher risk of presenting with advanced disease because pregnancy impedes early cancer detection.

Subclinical pregnancy loss in clomiphene citrate-treated women

To ascertain the subclinical pregnancy loss rate in clomiphene citrate (CC)-treated infertile women compared with women of normal fertility. Following a prospective format, serum samples were taken during the luteal phase of 92 menstrual cycles associated with CC treatment and 47 cycles in normal women. Human chorionic gonadotropin (hCG) assay sensitivity was 0.25 IU/L. Human chorionic gonadotropin assay was validated against 95 nonpregnant cycles. Criterion for pregnancy was a single serum sample ≥ 0.5 IU/L. All subjects were under clinical management at the University of Virginia Health Sciences Center. Patients undergoing CC induction of ovulation with satisfactory ovulatory response were candidates for the study group (n = 34). Control subjects of proven normal fertility were recruited (n = 22). Nonpregnant control subjects were sexually abstinent or had been surgically sterilized (n = 89). A serum sample was taken during the late luteal phase of all subjects. Thirteen percent of CC-treated cycles and 4.3% of normal control cycles were subclinical losses ( P = 0.09). Fifty percent of CC-induced pregnancies were subclinical losses compared with 16.6% of normal control pregnancies ( P = 0.05). Of CC patients who had at least one subclinical loss 47.6% later conceived a term pregnancy compared with 15.3% who did not have a subclinical loss ( P = 0.06). Subclinical pregnancy loss is more common in CC-treated women than normal women and may be a predictor of subsequent normal conception.

Size and shape of the pituitary gland during pregnancy and post partum: measurement with MR imaging.

Cranial magnetic resonance (MR) imaging was performed in 38 pregnant and postpartum women and 30 nonpregnant age-matched control subjects to establish standards for pituitary gland size and shape during this period. Gland height and infundibulum width were measured on midline T1-weighted sagittal images. Gland convexity or concavity was graded qualitatively. Throughout pregnancy, gland height increased linearly by approximately 0.08 mm/wk. No gland exceeded 10 mm in height during pregnancy. Increases in gland convexity also correlated with progression of pregnancy. The largest glands were seen in the immediate postpartum period; during this period, five of 12 glands measured 10.0-11.8 mm. Beyond the first week post partum, glands rapidly returned to normal size, apparently regardless of the status of breast-feeding. The mean diameter of the infundibulum was 2.2 mm (range, 0.8-4.0 mm). The pituitary gland enlarges throughout pregnancy but should probably not exceed 10 mm during most of this period. Size of up to 12 mm may be acceptable immediately post partum.

Changes in immunologic parameters in normal pregnancy and spontaneous abortion

To study the immunologic characteristics of miscarriage, 40 nonpregnant control subjects, 40 primigravid women in the first trimester of pregnancy, and 18 patients admitted with a spontaneous abortion were investigated. The total white blood cell count was raised significantly in normal pregnancy and spontaneous abortion (p \\lt 0.0005). The lymphocyte count was unchanged. The total T-cell number fell significantly in normal pregnancy and abortion (p \\lt 0.01 ). No change was seen in the cytotoxic suppressor or helper/inducer T-cell numbers. The number of activated T cells fell significantly in both groups of patients (p \\lt 0.0005). The response to mitogens was greatly increased in both normal patients and those with miscarriage. A marked rise in interleukin-2 receptor levels was noted in patients with spontaneous abortion (p \\lt 0.005). The changes in white blood cell count, total T-cell number, activated T-cell number, and mitogen activity were thought to be a direct result of pregnancy. The rise in interleukin-2 receptor levels was seen only in the miscarriage group. Although it is not known if these changes are cause or effect, it would appear that immunologic abnormalities are associated with spontaneous abortion.

Influence of Sample Type on the Interpretation of the Oral Glucose Tolerance Test for Gestational Diabetes Mellitus

The World Health Organization (1985) criteria allow evaluation of the oral glucose tolerance test using venous or capillary whole blood or plasma glucose measurements. However, the empirical factors used for interconversion may not reflect observed differences, especially during pregnancy, causing inconsistent classification. To investigate how choice of sample would influence the interpretation of results, venous and capillary blood was taken during oral glucose tolerance tests in 36 pregnant women at risk of gestational diabetes and in 21 non-pregnant control subjects. Glucose was measured on whole blood and plasma by a glucose oxidase method. No cases of gestational diabetes were identified. Eight subjects had gestational Impaired Glucose Tolerance using either venous plasma or venous whole blood results, but only five were similarly classified with capillary whole blood and only four using capillary plasma. Plasma-whole blood differences (venous 0.6 +/- 0.2 (+/- SD) mmol l-1, capillary 0.7 +/- 0.3 mmol l-1) and capillary-venous differences (plasma 0.5 +/- 0.4, whole blood 0.4 +/- 0.5 mmol l-1) at 2 h were lower (all p less than 0.05) than in the WHO criteria (1.1 mmol l-1). When compared with venous plasma, capillary measurements may give a lower incidence and venous whole blood measurements a higher incidence of Impaired Glucose Tolerance in pregnancy.

Interrelationship between atrial natriuretic factor concentrations and acute volume expansion in pregnant and nonpregnant women

The secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention. To determine whether acute intravascular volume expansion affects atrial natriuretic factor concentrations during pregnancy, circulating atrial natriuretic factor levels were measured in pregnant women at term (before elective cesarean section) and nonpregnant control subjects before and during intravenous infusion of lactated Ringer's solution (approximately 30 ml/kg). Venous plasma concentrations of alpha-human atrial natriuretic factor were determined by a specific radioimmunoassay. A significant increase in alpha-human atrial natriuretic factor levels in nonpregnant subjects was seen. Pregnant women did not show a significant response to a similar stimulus. Finally, basal alpha-human atrial natriuretic factor levels in pregnant and nonpregnant women were not different. Volume expansion (long-term or short-term) in normal human pregnancy may not be sensed by atrial volume sensors, possibly because it is accommodated by an enlarged maternal vascular compartment.

Veränderungen von T-Zell-Subpopulationen während der normalen Schwangerschaft und bei Patientinnen mit Spontanaborten

From the immunological point of view, pregnancy is a privileged allograft, with complex mechanisms of adaptation within the maternal immune system preventing rejection. The importance of lymphocytes and their specific subsets for this mechanism is a controversial issue. This study was designed to examine changes within T-cell subsets during uneventful pregnancy and to evaluate their significance by comparison with findings in patients undergoing spontaneous pregnancy loss. When compared to non-pregnant control subjects, normal pregnant women showed significantly decreased numbers for peripheral T-lymphocytes, for helper/inducer-T-cells and for the helper/suppressor-T-cell ratio (T4/T8). In contrast, patients undergoing spontaneous abortion showed a significantly elevated T4/T8-ratio, if compared to normal pregnant women. The clinical relevance of these findings is uncertain. Nevertheless, in individual cases of spontaneous miscarriage, the analysis of T-cell subsets might indicate a possible immunological aetiology.

Characterization of theophylline binding to serum proteins in pregnant and nonpregnant women

Sera from 10 subjects in the third trimester of pregnancy and from 10 nonpregnant women were studied to elucidate the mechanism underlying decreased theophylline protein binding during pregnancy. Consistent with the physiologic hypoalbuminemia of pregnancy, serum albumin concentrations averaged only 3.2 +/- 0.3 gm/dl (+/- SD) in pregnant subjects, compared with 4.4 +/- 0.3 gm/dl in control subjects (p less than 1 x 10(-6], and this was the main cause of decreased theophylline binding. Saturation binding studies indicated a single class of theophylline binding sites. Theophylline binding capacity (N) was greater in pregnant (N = 4.3 +/- 1.0) than in nonpregnant (N = 3.3 +/- 0.4) subjects, but binding affinity (ka) averaged only 227 +/- 69 (mol/L)-1 in pregnant subjects, compared with 303 +/- 44 (mol/L)-1 in control subjects (F2,17 = 4.26; p = 0.032). At a theophylline plasma concentration of 10 micrograms/ml, the combined effects of hypoalbuminemia and lowered ka would reduce theophylline binding to 31% +/- 3% in pregnant women, compared to 39% +/- 3% in nonpregnant control subjects (p less than 1 x 10(-5]. Nonesterified fatty acid concentrations were similar in both subject groups and did not contribute to the pregnancy-associated decrease in theophylline binding.

Reduced Urinary Excretion of Calcium in Pregnancy-Induced Hypertension: Relationship to Renal Prostaglandin Excretion

Urinary excretion of calcium, sodium, creatinine, proteins and renal prostaglandins (PGE2, 6kPGF1α) and serum levels of calcium, sodium, creatinine and albumin were determined in 10 normotensive pregnant women throughout pregnancy and in 30 normotensive pregnant women (NTP) and 30 women with pregnancy-induced hypertension or preeclampsia (HTP) and intact kidney function in the third trimester in comparison with 13 nonpregnant control subjects (C).Urinary excretion of calcium was found to be significantly reduced in the HTP group and was correlated with PGE2 excretion (p < 0.01). A weak correlation was detectable in the NTP group, which, however, as in the HTP and C groups, showed a close correlation between urinary calcium and sodium values (p < 0.05). In the NTP group, there was a significant increase in calcium excretion, which might reasonably be regarded as related to increased renal PG activity.

Serum iron, zinc, folacin and vitamin B-12 in pregnant and non-pregnant adolescents

Iron status, blood folacin, vitamin B-12 and zinc were compared for 32 pregnant adolescents and 19 agematched non-pregnant controls. Blood samples were collected during the second and third trimesters (approximately 22 and 34 weeks gestation) and 6 to 8 weeks post-partum from the pregnant subjects and once from the controls. Second trimester pregnant subjects had significantly lower erythrocyte counts (p<0.001), hemoglobin (p<0.001), hematocrit (p<0.001) and serum B-12 levels (p<0.05) compared to the values noted in nonpregnant control subjects. Serum and red blood cell folacin values were significantly higher in pregnant subjects during the second trimester than values in control subjects (p<0.05 and p<0.001, respectively). Erythrocyte count, hemoglobin, hematocrit and serum B-12 were all significantly increased at post-partum as compared to the third trimester period (p<0.05 for all measures). Serum iron and transferrin saturation all decreased significantly between the second and third trimesters (p<0.05), then increased significantly from third trimester to post-partum (p<0.05). Total iron binding capacity (TIBC) showed no significant change between the second and third trimesters, but decreased significantly between third trimester and post-partum (p<0.05). The data indicate this sample of pregnant adolescents is not at significant risk for deficiencies of iron, zinc, folacin or B-12.

Enhanced thrombin generation in normal and hypertensive pregnancy

We investigated the plasma levels of thrombin-antithrombin III complexes in women with uncomplicated pregnancy, patients with preeclampsia, gestational hypertension, and nonpregnant control subjects. In addition, we measured the coagulation inhibitors antithrombin III, protein C, and protein S. In normal pregnancy we observed a progressive increase in plasma thrombin-antithrombin III levels, and a decrease in protein S levels. In preeclampsia we observed increased thrombin-antithrombin III levels, reduced antithrombin III and protein C levels, and no further reduction of protein S compared with normal pregnancy. These new methods provide solid evidence for a prethrombotic state in normal pregnancy, especially in preeclampsia.

Oral glucose tolerance test in healthy pregnant Nigerian women.

Oral glucose tolerance tests (OGTTs) with 75 g glucose were performed in 20 healthy pregnant Nigerian women in each trimester of pregnancy and the puerperium; 34 nonpregnant control subjects matched for age and parity were also studied. The blood glucose levels from fasting to 60 min were lower in pregnant subjects, but the 90- and 120-min values were higher. The highest blood glucose values were observed in the first trimester with an apparent improvement in glucose tolerance in the second and third trimesters. This observation is strikingly different from the established pattern of OGTT in pregnant Caucasian women. With pooled data from OGTT results in the three trimesters for the 20 pregnant women (60 OGTTs), a statistically derived criterion (based on mean + 2SD approximated to the nearest 5) for the interpretation of OGTT in pregnant Nigerian women was devised. This criterion defines the upper limits of normal for venous whole-blood glucose in pregnant Nigerian women during an OGTT with a 75-g glucose load as follows: fasting, 90; 30 min, 135; 60 min, 150; 90 min, 145; and 120 min, 125 mg/dl. These values are lower than those recommended for pregnant women by the National Diabetes Data Group (O'Sullivan and Mahan criteria) and the World Health Organization. The results from this study underscore the need for caution regarding uncritical application of data from one racial or ethnic group to others.

Host defense during pregnancy: Neutrophil chemotaxis and adherence

Pregnancy is associated with impairment in several immunologic functions that effect the outcome of certain infectious and autoimmune diseases. Previous studies have indicated that pregnant women have decreased neutrophil motility, but results are discordant. We performed a longitudinal study of polymorphonuclear leukocyte chemotaxis using a micropore filter assay and polymorphonuclear leukocyte adherence using a nylon wool column assay in 58 women during pregnancy, delivery, and the postpartum period. Polymorphonuclear leukocyte chemotaxis was decreased significantly in pregnant women during the second (-20%) and third (-17%) trimesters and 1 to 3 months post partum (-18%), but not during the first trimester (-6%) compared with nonpregnant control subjects. The impairment in polymorphonuclear leukocyte chemotaxis appeared to be a cell-associated rather than a humoral defect. Polymorphonuclear leukocyte adherence was decreased significantly in pregnant women during the third trimester (-16%). These data may help explain the increased incidence of infection and amelioration of certain immunologically mediated illnesses during pregnancy.

Alterations in platelet concentration and aggregation in normal pregnancy and preeclampsia

Platelets were evaluated in normal pregnant women and in pregnant subjects with mild and severe preeclampsia, nonpregnant control subjects, and pregnant subjects with chronic hypertension. The parameters studied included platelet count, presence of circulating platelet aggregates, and in vitro platelet aggregability by means of a variety of agonists of platelet aggregation. When subjects with a normal pregnancy were compared to nonpregnant controls, they demonstrated a significantly lower platelet count and an increase in circulating platelet aggregates and in vitro hypoaggregability. Significant differences among the groups of pregnant subjects could not be found. These studies suggest the occurrence of platelet activation in pregnancy. This activation causes in vivo platelet aggregation followed by exhaustion of platelets.

Two-dimensional and M-mode echocardiographic findings in hypertensive pregnant women

Two-dimensional and M-mode echocardiograms were obtained during the thirty-second week of gestation from 69 women classified as follows: group I, 22 normotensive primigravid women; group II, 16 primigravid women with pregnancy-induced hypertension; group III, 21 pregnant women with essential hypertension; and group IV, 10 normotensive nonpregnant control subjects. Systolic, diastolic, and mean arterial pressures were higher in groups II and III than in groups I and IV (p < 0.001). Echocardiographic dimensions were significantly increased in group III compared with the other groups (p < 0.01). No significant differences were observed among the other groups in the echocardiographic parameters or in the indices of ventricular performance studied. In echocardiographic studies, chronic hypertensive pregnant women are distinguished from patients with pregnancy-induced hypertension because the former have ventricular hypertrophy resulting from the pressure overload exerted for a long period of time. Our patients with essential hypertension experienced no changes in left ventricular performance because of the early stage of their hypertensive disease.