Rhoda Wilson

Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension

Increased free radical activity has been implicated in the pathogenesis of pregnancy-induced hypertension. This article investigates whether changes in antioxidant systems contribute to this condition. Two extracellular (plasma thiols and ceruloplasmin) and two intracellular (red blood cell lysate thiols and red blood cell superoxide dismutase) antioxidant markers were assayed in 25 nonpregnant women, 16 pregnant women with normal blood pressure, 19 women with pregnancy-induced hypertension, and 13 women with proteinuric pregnancy-induced hypertension. In the normotensive pregnant group (in comparison with the nonpregnant group) the plasma thiol level was reduced (p less than 0.001) and the ceruloplasmin level raised (p less than 0.005), suggesting increased free radical activity. The lysate thiol level increased (p less than 0.005), which may reflect a compensatory protective response. In the hypertensive pregnant groups the lysate thiol rise was not present. These red blood cells may be more prone to oxidative stress. Whether this situation is a cause or an effect of oxidative stress in pregnancy-induced hypertension has yet to be elucidated.

Evidence of a TH 1 type response associated with recurrent miscarriage

OBJECTIVE To determine whether the T(H) 1 cytokine interferon (IFN)-gamma is associated with miscarriage whereas the T(H) 2 cytokine interleukin (IL)-10 is associated with successful pregnancy. DESIGN Controlled clinical study. SETTING Healthy volunteers in an academic setting. PATIENT(S) Group 1 comprised 10 nonpregnant women; group 2, 10 first-trimester primigravid women; group 3, 10 first-trimester primigravid women suffering spontaneous abortion; and group 4, 10 first-trimester pregnant women with a history of miscarriage. All women were pregnant at the time of sampling, but 5 miscarried later in the first trimester. INTERVENTION(S) None of the patients received any medication. MAIN OUTCOME MEASURE(S) Serum levels of IL-10 and IFN-gamma. RESULT(S) Levels of IL-10 were significantly raised in normal pregnancy. Levels of IFN-gamma were raised in the recurrent-miscarriage group as compared with normal pregnancy. When patients in group 4 were divided into those whose pregnancies went to term and those who miscarried, we found that successful pregnancy was associated with a statistically significant increase in IL-10, whereas miscarriage was associated with significantly increased levels of IFN-gamma. CONCLUSION(S) These results support the view that miscarriage is associated with a T(H) 1 type response.

The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be Important In the development of autoimmune thyroid disease. These factors were examined In (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone.

Antioxidants: their role in pregnancy and miscarriage.

The aim of this study was to examine the role of antioxidants within the normal menstrual cycle, in healthy pregnancy, and in women suffering first-trimester miscarriage. The antioxidants chosen comprised of two from peripheral blood-plasma thiol and ceruloplasmin-and two extracellular parameters-superoxide dismustase (SOD) and red cell lysate thiol. We found that antioxidant levels varied little throughout the menstrual cycle. Pregnancies that went successfully to term were associated with increased levels of ceruloplasmin and SOD early in the first trimester. These changes were thought to offer the cell protection from the damage caused by the increased oxidative stress associated with pregnancy. First-trimester miscarriage was associated with significantly reduced levels of SOD. A subgroup of patients who miscarried in their first pregnancy, but whose second pregnancies were successful, had higher levels of plasma thiol and significantly reduced levels of red cell lysate thiol in the on-going pregnancy compared to levels at the time of miscarriage. Miscarriage and pregnancy appear to be associated with increased oxidative stress. In a successful pregnancy, however, changes occurred within the peripheral blood that offered protection from oxidant attack.

Thyroid antibody titer and avidity in patients with recurrent miscarriage

OBJECTIVE To determine whether the titer and avidity of the thyroid peroxidase antibody differs between pregnant women in their first trimester who have a history of recurrent miscarriage and whose pregnancies continue to term and those whose pregnancies fail again later in the first trimester. DESIGN Controlled clinical study. SETTING Healthy volunteers in an academic research environment. PATIENT(S) Pregnant women in their first trimester who had a history of recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive for the thyroid peroxidase antibody. INTERVENTION(S) None of the patients received any medication. MAIN OUTCOME MEASURE(S) Thyroid peroxidase antibody titer and avidity (i.e., the net binding strength between antibody and antigen). RESULT(S) At the time of presentation, thyroid peroxidase antibody titer and avidity was significantly higher in those women who later miscarried compared with those whose pregnancies continued. In those whose pregnancies continued to term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S) Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who had had recurrent miscarriages, there appeared to be differences in the humoral response to the pregnancy between those whose pregnancies continued to term and those whose pregnancies failed again.

Altered interleukin 12 and nitric oxide levels in recurrrent miscarriage

The causes of recurrent miscarriage are not fully understood. Recent studies have suggested that whilst a TH 2 type immune response may be associated with a healthy pregnancy, miscarriage may be associated with a TH 1 type response. Serum levels of nitric oxide (NO) and Interleukin 12 (IL 12) were measured in; healthy non-pregnant women; healthy pregnant women; women suffering spontaneous abortion; pregnant women with a history of recurrent miscarriage; non-pregnant women with a history of recurrent miscarriage. Normal pregnancy was associated with a significant decrease in serum levels of nitrite (13.0 vs. 22.0 P < 0.0001). In women admitted with spontaneous abortion there was a significant increase in the levels of nitrite (16.0 vs. 13.0 P < 0.05), but no change in IL 12 compared to normal pregnant women. In pregnant women with a history of recurrent miscarriage levels of nitrite (16.0 vs. 13.0 P < 0.05) and IL 12 (10.0 vs. 6.0 P < 0.0006) were significantly elevated compared to normal pregnancy. When these women were sampled prior to becoming pregnant the levels of NO were found to be significantly lower than those in the non-pregnant control group (13.1 vs. 22.0 P < 0.05) although levels of IL 12 were unchanged. No correlation was found between serum nitrite and IL 12 levels. This report further supports the idea that polarisation of the immune response during pregnancy may predispose to recurrent miscarriage.

Erythrocyte glutathione balance and membrane stability during preeclampsia

This study aimed to determine whether oxidative damage to the erythrocyte occurs in preeclampsia, and relates to disease severity. The oxidative status of intact erythrocytes from preeclamptic patients and normal pregnant women was determined using spin echo 1H-NMR, which measures both the concentration and redox state of intracellular glutathione. Previous studies of preeclampsia have only measured total glutathione levels. Membrane fragility was determined from the degree of lysis caused by incubation in hypotonic saline. Erythrocytes from moderate-severe preeclamptic patients underwent more lysis than erythrocytes from control pregnant women (p < .05) or mild preeclamptic patients. It is suggested that increased lysis results from oxidative damage to the erythrocyte membrane, causing a decrease in membrane fluidity and reducing its ability to withstand osmotic changes. Intracellular glutathione was more oxidized in erythrocytes from pregnant women compared to nonpregnant controls (p < .05), and there was a less significant trend toward more oxidized glutathione with increasing severity of preeclampsia. The moderate-severe group showed a clear division in glutathione redox status: some patients had very oxidized glutathione while others had a normal redox balance. This novel finding suggests that some patients may be unusually susceptible to erythrocyte glutathione oxidation, possibly leading to general cellular damage, in particular HELLP Syndrome.

Immunological changes in normal pregnancy

During pregnancy the mother must tolerate intra-uterine allogenic fetal tissue. Failure of this tolerance may cause spontaneous abortion. The immunological changes occurring in normal pregnancy are poorly understood. The aim of this study was to investigate the immunological changes occurring in pregnancy. Thirty women in the first trimester; 10 in the second and 10 in the third trimester of pregnancy were studied and compared to age matched non-pregnant controls. In normal pregnancy there was an increase in the total white cell count with no change in the lymphocyte count. There was a fall in total T cell numbers and activated T cell numbers, with no change in helper/inducer or suppressor/cytotoxic T cell numbers. [3H]Thymidine uptake in response to three different mitogens was increased. This implies an increase in potential for the cells to respond to mitogens. There was no change in interleukin-2 receptor levels, suggesting that despite this increased potential there was no general activation of the immune system. A rise in IgM and IgG was found after mitogen stimulation of peripheral blood lymphocytes, suggesting an increase in potential antibody production. These results demonstrate that lymphocytes from pregnant women have an increased potential rather than an increased activity.

Thyroid function tests are rarely abnormal in patients with severe hyperemesis gravidarum

OBJECTIVES There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women.

Abnormal First Trimester Serum Interleukin 18 Levels are Associated with a Poor Outcome in Women with a History of Recurrent Miscarriage

Problem:  How the maternal immune system adapts to tolerate the fetus is not fully understood, but a successful pregnancy is associated with the production of Th2‐type cytokines and miscarriage is associated with the production of Th1‐type cytokines.