Butyrylcholinesterase activity and lymphocyte subpopulations in peripheral blood of Kuwaiti women experiencing recurrent spontaneous abortion.

This study has evaluated the hypothesis that activity of the detoxifying enzyme butyrylcholinesterase (BuChE) correlates with levels of serum anti-cardiolipin antibodies (ACA) and T lymphocytes in peripheral blood of women experiencing recurrent spontaneous abortion (RSA). Peripheral venous blood from 16 non-pregnant, RSA-afflicted women and 8 healthy non-pregnant women was analyzed for frequency of T lymphocyte subpopulations by two-color flow cytometry and for serum BuChE using butyrylthiocholine iodide/spectrophotometry. RSA-afflicted women with high serum ACA, but not those with normal ACA levels, exhibited significantly increased percentages of CD4+CD25+ cells (p<0.01) and CD4+HLA-DR+ cells (p<0.05) relative to healthy women. CD4+CD25+(high) cells were significantly lower (p<0.05), while CD4+CD25+(low) cells were significantly higher (p<0.01), in women with elevated ACA compared to healthy women and to RSA women with normal ACA. Relative to healthy, non-pregnant subjects, serum BuChE activity in RSA patients was elevated, both for those with normal ACA (p<0.001) and elevated ACA levels (p<0.01). Among healthy controls, a significant positive correlation was observed between frequency of CD3+NK cells and BuChE activity (p<0.01), but not for RSA-afflicted subjects. A positive correlation between BuChE activity and frequency of CD4+CD25+ cells, as well as CD4+CD25+(high) cells, was observed in the RSA-afflicted subject group with elevated ACA (p<0.05), which may be related to induction of BuChE by toxic metabolites resulting from pathogenic T cell activity. It is concluded that, among RSA patients, high serum ACA correlates with elevated levels of activated T cells and reduced CD4+CD25+(high)/CD4+CD25+(low) cells in comparison to healthy women or those afflicted with RSA but with normal ACA. BuChE activity is observed to be elevated in RSA patients irrespective of serum ACA status.

Interleukins in preeclampsia.

BACKGROUND: Preeclampsia is a multisystemic disorder of unknown etiology. Recently, endothelial damage has been implicated in its cause. The objective of this study was to determine the role of interleukins in the etiology of preeclampsia. PATIENTS AND METHODS: Thirty-two primigravidas with preeclampsia but without any clinical evidence of infection and 32 age-matched primigravidas with uncomplicated normal pregnancies were investigated. Phlebotomy was performed at 32 weeks of gestation and blood collected for immunoassays of interleukin-2 (IL2), interleukin-2 receptor (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10), using commercially available immunoassay kits. RESULTS: Although the maternal plasma concentrations of IL-2 and IL-2R were slightly higher in normal pregnant women (76.3+/-13.7 pg/mL and 526.3+/-47.1 pg/mL, respectively) than in women with preeclampsia (57.8+/-10.8 pg/mL and 476.9+/-33.9 pg/mL, respectively), the differences were not statistically significant (P>0.05). However, maternal plasma IL-6 and IL-8 concentrations were significantly higher (P<0.05) in normal pregnancy (158.0+/-35.4 pg/mL and 5163.6+/-800 pg/mL, respectively) than in pregnancy complicated with preeclampsia (60.0+/-13.7 pg/mL and 2495.8+/-729.4 pg/mL, respectively). On the other hand, maternal plasma concentration of IL-10 was significantly higher (P<0.05) in preeclampsia (93.2+/-24.1 pg/mL) than in normal pregnancy (31.07+/-7.0 pg/mL). CONCLUSION: It is concluded that the elevated maternal plasma IL-10 concentration in preeclampsia may be a protective response to maternal immunorejection.

Emergency obstetric hysterectomy in Kuwait: a clinico pathological analysis.

The major objective of this study is to analyze the histological findings in emergency obstetric hysterectomy specimens and correlate them with the clinical diagnosis, epidemiological factors and number of tissue blocks examined. The records of all peripartum hysterectomy specimens examined between 1995 and 2001 in the Department of Pathology, Al-Sabah Hospital Kuwait were analyzed. A minimum of ten blocks from the cervix or lower uterine segment was arbitrarily regarded as adequate. Fifty-eight patients had peripartum hysterectomies (incidence of 0.07% of all deliveries) out of which 65% were aged between 30 and 40 years. The number of hysterectomy increased with parity up to five and then declined. The number of blocks examined varied from 2 to 53. Satisfactory pathology was found in 40 and absent in 18 cases. There were 33 adherent placentas. Amniotic fluid embolism (AFE) was found in seven patients. Adequate tissue blocks (>or=10) were significantly associated with positive pathological findings. P value <0.05.

Effect of IgG therapy on lymphocyte subpopulations in the peripheral blood of Kuwaiti women experiencing recurrent pregnancy loss.

Intravenously administered polyspecific IgG is being increasingly used as an immunomodulating therapy with controversial beneficial outcome. The aim of this study was to evaluate the effects of IgG infusion on peripheral T-cell subpopulations in women with recurrent pregnancy loss (RPL). Fifteen women with a history of three previous RPL between 6 and 22 weeks of gestation and positivity for the antiphospholipid antibody syndrome (APS) were randomized to one of two treatment groups: (a) an intravenous immunoglobulin therapy group (RPL-IVIg; 7 patients), 500 mg IVIg/kg/month and (b) a placebo-treated group given multivitamins (8 patients). Control groups comprised either normal pregnant women without APS (10 patients) or non-pregnant women. The T-cell markers were characterized using a monoclonal antibody panel including CD3, CD4, CD8, CD25, CD29, CD38, CD45RA, CD45RO, CD54 and HLA-DR. Analysis was performed with a two-color fluorescent-activated flow cytometer. In the first trimester, the percentage of CD4+CD25+, CD4+CD45RO+, CD8+HLA-DR+, and CD8+CD38+ populations were reduced in the multivitamin group compared to normal pregnant women (p < 0.05) while in the RPL-IVIg group only CD4+CD25+ cells were reduced (p < 0.05). By the second trimester, CD3+CD16+CD56+ was significantly higher in multivitamin- than in IVIg-treated women (p < 0.05). The percentage of CD4+HLA-DR+ was significantly higher in the two RPL groups compared to normal pregnant women (p < 0.05). IVIg therapy in women with RPL was associated with a significant reduction in CD3+CD16+CD56+ and CD4+CD25+. This may contribute to the suppression of immune-mediated processes contributing to premature abortion.

Antiphospholipid antibodies in infertile couples with two consecutive miscarriages after in-vitro fertilization and embryo transfer.

Of 682 women who had undergone in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with embryo transfer, 84 were successful on two occasions, with 16 of these resulting in miscarriage before 20 completed weeks. Antiphospholipid antibodies (APA) were estimated by enzyme-linked immunosorbent assay in these women (group 1) and compared to two control groups: 42 fertile women with three or more miscarriages (group 2) and 60 women with primary infertility undergoing IVF or ICSI (group 3). An apparently higher prevalence of seropositivity was seen in group 1 women (25%) compared to the group 3 women (6.6%) and it was similar to that seen in group 2 women (21.4%). Therefore the recommendation that women with two consecutive miscarriages after IVF or ICSI should have APA estimations performed routinely may be justified.

Differential levels of T helper cytokines in preeclampsia: pregnancy, labor and puerperium.

BACKGROUND: There are suggestions that T helper 1 cytokines may be detrimental to early pregnancy and T helper 2 cytokines protective of the pregnancy. Their role in preeclamptic pregnancy, labor and puerperium, is not clear. MATERIALS AND METHODS: Twenty-eight preeclamptic women and their matched controls were evaluated, at the Departments of Obstetrics and Gynecology, Faculty of Medicine, Kuwait University and Maternity Hospital, Kuwait. Outcome measures evaluated were serum levels of TNF alpha and interleukin-4 at 12, 24, 36 weeks of gestation, advanced labor and at 1 hour and daily postpartum until they were undetectable, using ELISA technique. RESULTS: T helper cytokines showed higher serum levels in preeclampsia than normotensive pregnancy (p < 0.01, 0.01), in established labor (p < 0.05) and at 1 hour postpartum (p < 0.01 for IL-4) and p < 0.02 for TNF alpha. There was significant increase of IL-4 between 12 to 24 weeks in normal pregnancy compared to preeclampsia (p < 0.001) but not for TNF alpha. By 24 hours postpartum, IL-4 was still detectable in eight parturients compared to one patient with detectable TNF alpha (p < 0.04). Detectable IL-4 levels after 24 hours postpartum were associated with intrauterine growth retardation (p < 0.03). CONCLUSION: IL-4 has a dichotomous role in pregnancy. Normotensive pregnancy is associated with high increase in IL-4 in the first half of the pregnancy, but in the second half of pregnancy and puerperium, high levels of IL-4 are associated with preeclampsia.

Lymphocyte subpopulation frequency and presence of anti-cardiolipin and anti-nuclear antibodies in peripheral blood of Kuwaiti women experiencing recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is often associated with elevated levels of serum antiphospholipid antibodies, which contribute to the pathology of the disorder by promoting formation of thromboses, leading to placental infarction and fetal loss. Patients with recurrent pregnancy loss also exhibit pathological alterations in composition and activity of peripheral blood lymphocytes, which may be indicative of an autoimmune processes. This investigation examines the correlation between levels of anticardiolipin antibody (AC) and specific subsets of the lymphocyte repertoire in RPL patients, with the objective of further characterising the immunological basis for RPL. Non-pregnant Kuwaiti women with a history of RPL were subdivided into two cohorts based on presence or absence of elevated plasma antibodies to cardiolipin. Whole blood from these individuals was analysed by flow cytometry for selected lymphocyte subsets and compared with a non-RPL control population. When compared with controls and low AC titre subjects, women with a high AC titre exhibited significantly elevated percentages of pathogenic CD5+ B cells; two categories of activated T cells including CD4+CD25+ and CD8+CD25; NK cells and CD3+NK cells; naive (CD4+CD45RA+) cells; and transitional (CD45RO+CD45RA+) cells. In conclusion, women with elevated levels of AC antibodies possess substantially higher levels of activated T cells and pathogenic B cells, suggesting a fundamental predisposition to immune-mediated rejection of the fetus by these patients. Further characterisation of this phenomenon may allow development of novel intervention methods for management of RPL.

A correlation of the uterine and ovarian blood flows with parity of nonpregnant women having a history of recurrent spontaneous abortions.

The aim of this prospective study was to explore the relationship between the incidence of recurrent spontaneous abortions (RSA) and values of Doppler indices characterizing the uterine and ovarian flows in nonpregnant women with a history of primary and secondary RSA using color, power and pulsed Doppler transvaginal ultrasonography. A total of 19 healthy women as a control group A and 81 women with a history of RSA as a study group B were examined on the 21st day of a regular menstrual cycle. Our study demonstrated the presence of significantly decreased uterine and ovarian blood flows in women with primary and secondary RSA if more than 3 abortions had occurred. The obtained values were less favorable in the primary RSA compared with the secondary RSA cases.

Hormone profile of Kuwaiti women with hyperemesis gravidarum.

OBJECTIVE: To evaluate the incidence of hyperemesis gravidarum among pregnant women in Kuwait and the status of HCG, TSH, Total T4 and Free T4 in the serum of patients with hyperemesis gravidarum compared with a control group of women. METHODOLOGY: During a 6-month period all patients admitted to Maternity Hospital with features of hyperemesis gravidarum (excessive vomiting and ketonuria) were enlisted into the study. In fifty of these patients and their fifty normal controls, the status of serum total (beta)hCG, TSH, total T4 and freeT4 were evaluated with AXSYM micro particle enzyme immunoassay. RESULTS: The incidence of hyperemesis in the maternity population was 45 per 1000 deliveries. Total (beta)hCG and Total T4 and FreeT4 were significantly higher in the hyperemesis patients than in the normal controls (p<0.0001, p=0.004 and p=0.01 respectively). TSH levels were significantly lower in hyperemesis patients than in their normal controls (p<0.0001). There was a strong positive correlation between the total (beta)hCG and the gestational age (r=0.8). CONCLUSION: There is a high incidence of hyperemesis gravidarum in the Kuwaiti population. Total (beta)hCG, Total T4 and Free T4 titers were significantly higher in patients with hyperemesis gravidarum, but none of the patients showed signs of hyperthyroidism.

A favorable outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome.

OBJECTIVE: To study the outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome treated with the standard treatment regimes including intravenous immunoglobulin (IV Ig). METHODS: Forty three patients with recurrent pregnancy loss associated with antiphospholipid syndrome diagnosed before pregnancy and subdivided into primary (18) and secondary (25) subgroups were closely monitored all through pregnancy with serial blood tests and ultrasonography until the pregnancy ended in miscarriage or delivery. The patients were treated with low-dose aspirin and heparin and or steroids and IV Ig given to some selected patients. The maternal and fetal outcomes were analysed. RESULTS: The mean age of the patients in the primary subgroup (24.60 +/- 4.30) years was significantly lower than the mean age of the secondary recurrent pregnancy loss group (31.50 +/- 4.50) years, (p < 0.0001). 85.00% of all the previous miscarriages were in the first trimester. There was no significant difference in the incidence of live births in the primary (77.80%) and secondary (84.00%) groups, (p > 0.05); the babies were of normal birth weight. The incidence of caesarean section in the primary and secondary groups, 22.23% and 12.00% respectively, were not significantly different (p > 0.05). Intravenous immunoglobulin added to the standard therapy resulted in 100% live births. Maternal complications were negligible. CONCLUSIONS: The fetal and maternal outcome of pregnancies in patients with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome were virtually identical and quite satisfactory. Intravenous immunoglobulin added to the standard therapy resulted in excellent fetal and maternal outcome, although its definitive role will have to wait for the outcome of randomised trials.

The aetiology and pattern of recurrent pregnancy loss.

The aims of this study were to determine the aetiological factors and the pattern of recurrent pregnancy loss in Kuwait. Ninety consecutive patients attending the special recurrent miscarriage clinic were studied prospectively. A comprehensive history of all previous miscarriages and pregnancies, past medical and gynaecological events were established. A physical examination was performed. Extensive investigations were performed. Pregnancies which occurred during the study were monitored carefully. The mean age of the patients was 30.46+/-6.04 years. The patients were subdivided into the groups of secondary (57%) and primary (43%) recurrent miscarriages. Eighty-five per cent of all previous miscarriages occurred in the first trimester. The main aetiological factors were uterine anomaly 2.2%, chromosome anomaly (parental) 2.2%, PCOS, infections and other miscellaneous factors 21.1%, positive antiphospholipid antibodies 33.3% and unexplained in 35.6%. The overall live birth rate was 82% and maternal morbidity was low. Positive antiphospholipid antibodies are the most frequently associated cause of recurrent pregnancy loss in Kuwait.