Prediction of progression to a high risk situation in women with gestational hypertension or mild pre-eclampsia at term.

OBJECTIVE: To evaluate whether progression to a high-risk situation is predictable in women with gestational hypertension (GH) or mild pre-eclampsia (PE) at term. METHODS: Women with a singleton pregnancy, a fetus in cephalic position, between 36 and 41 weeks of gestation, complicated by GH or mild PE that were managed expectantly, were selected from the HYPITAT trial. We evaluated the predictability of progression to a high-risk situation. Logistic regression was used to determine the predictive value of clinical characteristics or laboratory findings and to generate a prediction model for progression to a high-risk situation. The predictive value of this model was assessed with receiver-operating characteristic (ROC) analysis, calibration and internal validation. RESULTS: We included 703 women, of whom 244 (34.7%) had progression to a high-risk situation. After multivariable analysis, nulliparity (OR 1.87), maternal age (OR 1.05 per year), gestational age (OR 0.88 per week), previous abortion (OR 1.26), ethnicity (OR 2.05 for non-Caucasian ethnicity), diastolic (OR 1.04 per mmHg), systolic blood pressure (OR 1.02 per mmHg) and the laboratory parameters proteinuria, haemoglobin, platelets, uric acid and alanine aminotransferase were included in the final model. The area under the ROC curve of this model was 0.71 (95% CI, 0.67-0.74). Even though the goodness of fit was moderate (P=0.40), internal validation showed the model could hold in the overall population. CONCLUSION: In the prediction of progression to a high-risk situation, in women with GH or mild PE at term, a distinction can be made between women with a low risk and women with high risk.

History of preeclampsia is not associated with an increased risk of thyroid dysfunction.

OBJECTIVE: We evaluated the thyroid function in women with a history of preeclampsia and/or HELLP syndrome at least 2 years after delivery. DESIGN: Observational retrospective study. SETTING: University Medical Center Groningen, The Netherlands. POPULATION: Women with a history of preeclampsia and/or HELLP syndrome (n = 310) or uncomplicated pregnancies (n = 363), between January 1990 and February 2003. METHODS: Measurement of serum thyroid stimulating hormone (TSH) levels and antibodies to thyroid peroxidase and the use of a questionnaire about relevant history and family history of auto-immune diseases related to thyroid disease. MAIN OUTCOME MEASURES: Prevalence of primary thyroid dysfunction and antibodies to thyroid peroxidase. RESULTS: Mean serum TSH values were not significantly different between the preeclampsia and control group (1.62 vs. 1.80 mU/l). The percentage of women who have (have had) hypothyroidism and hyperthyroidism, respectively, did not differ significantly between the preeclampsia and the control group (3.3 vs. 6.1% and 10.0 vs. 7.7%). Furthermore the prevalence of antibodies to thyroid peroxidase was not significantly different (6.1 vs. 7.7%). CONCLUSION: Preeclampsia and/or HELLP syndrome are not associated with an increased risk of thyroid dysfunction in later life.

Indirect maternal mortality increases in the Netherlands.

OBJECTIVE: To assess causes, trends, and substandard care in indirect maternal mortality in the Netherlands. DESIGN: Confidential enquiry into causes of maternal death. SETTING: Nationwide in the Netherlands. POPULATION: A total of 2,557,208 live births. METHODS: Data analysis of indirect maternal deaths in the period 1993-2005. MAIN OUTCOME MEASURES: Indirect maternal mortality. RESULTS: Of the study subjects, 97 were classified as indirect deaths, representing a maternal mortality ratio of 3.3/100,000 live births, a significant increase compared to the preceding enquiry in the period 1983-1992 (MMR 2.4, OR 1.5, 95%CI 1.0-2.1). The percentage of cases not directly reported to the Maternal Mortality Committee decreased from 15 to 5%. Cardiovascular disorders were the leading cause of indirect maternal mortality, followed by cerebrovascular disorders. Vascular dissection (n = 19) was the most frequent specified cause of death. Risk factors were advanced maternal age, non-indigenous origin (Surinam and Dutch Antilles), and medical health risks before pregnancy. Substandard care was present in 35%, mainly being misjudgment of the severity of the condition and delay in initiating therapy. CONCLUSION: The rise of mortality due to indirect causes is considered a reflection of the change in risk profile of women of childbearing age and the result of demographic alterations concerning ethnicity and maternal age. The identification of high risk groups, preferably by programs of preconception care, should lead to improved care for these women, with a multidisciplinary approach when needed.

Cytokine production by monocytes, NK cells, and lymphocytes is different in preeclamptic patients as compared with normal pregnant women.

OBJECTIVE: To measure cytokine production in ex vivo stimulated leukocyte populations of women with normal pregnancy and those with preeclampsia. METHODS: Whole blood from preeclamptic and normal pregnant women was stimulated with LPS or PMA/Ca-ionophore. The percentages of IFN gamma and IL-2, 4, and 10 producing lymphocytes and NK cells and the percentages of TNFalpha, IL-1 beta, and IL-12 producing monocytes were measured by flowcytometry. RESULTS: In women with preeclampsia, there was a significantly increased percentage IL-4 producing cytotoxic T cells. Also, a significant decreased percentage IL-2 producing T helper cells and IL-12 producing monocytes was seen as compared with normal pregnancy. CONCLUSION: Th1 cytokine production of lymphocytes and monocytes appears to be decreased in our group of preeclamptic patients compared with normal pregnant women.

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial.

BACKGROUND: 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies. METHODS/DESIGN: We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length. DISCUSSION: This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40512715.

Maternal deaths after elective cesarean section for breech presentation in the Netherlands.

BACKGROUND AND METHODS: The cesarean section rate for term singleton breech babies in the Netherlands rose from 57 to 81% after the Term Breech Trial in 2000. The Dutch Maternal Mortality Committee registered and evaluated maternal mortality due to elective cesarean section for breech. RESULTS: Four maternal deaths after elective cesarean section for breech presentation, from 2000 to 2002 inclusive, were registered, 7% of total direct maternal mortality in that period. Two women died due to massive pulmonary embolism, both were obese, and thromboprophylaxis was not adjusted to their weight. The other two women died from sepsis, one had not receive perioperative prophylactic antibiotics. The case fatality rate for elective cesarean section for breech presentation was 0.47/1,000 operations. No death after emergency cesarean section for breech presentation was registered at the committee. CONCLUSIONS: Elective cesarean section does not guarantee the improved outcome of the child, but may increase risks for the mother, compared to vaginal delivery.

Thrombophilia is not associated with an increase in placental abnormalities in women with intra-uterine fetal death.

BACKGROUND: The aim of this study was to investigate whether women with thrombophilia and intrauterine fetal death have a higher incidence of placental lesions as compared with those without thrombophilia. METHOD: In a case-control study comprising 50 women with an obstetrical history of intrauterine fetal death, placental histology comparison was made between those with thrombophilia and those without thrombophilia. RESULTS: Of the women who had an intrauterine fetal death, eight (16%) had a thrombophilia factor. There were no differences in birth weight, gestational age and parity or in placental volume and weight between the eight women with and the 42 women without thrombophilia. There was no statistically significant difference between placentas of the women with and those without thrombophilia. CONCLUSION: In a group of women who had an obstetrical history of intrauterine fetal death, those with thrombophilia do not have a difference in placental histological lesions compared with the women without a thrombophilia factor. Future thrombophilia research should be focused on placental bed specimens.

Endotoxin-induced cytokine production of monocytes of third-trimester pregnant women compared with women in the follicular phase of the menstrual cycle.

OBJECTIVE: Little is known about the function of the innate immune response during pregnancy. We therefore investigated monocyte cytokine production, as a measure of monocyte function, in pregnant women compared with nonpregnant women. STUDY DESIGN: Whole blood of women in the follicular phase (day 5-6) and of healthy pregnant women (30 weeks) was collected and stimulated with endotoxin (2 microg/mL). After incubation for 4 hours (37 degrees C, 5% carbon dioxide), red blood cells were lysed and white blood cells were permeabilized, followed by staining with anti-CD14 (fluorescein isothiocyanate labeled) and with phycoerythrin-labeled tumor necrosis factor-alpha, interleukin-1beta, or interleukin-12. The cells were analyzed by flow cytometry after fixation. Results are expressed as a percentage cytokine producing cells after endotoxin stimulation. Statistical analysis was performed with the Mann-Whitney U test (P <.05). RESULTS: Compared with the percentage endotoxin-induced cytokine producing peripheral monocytes in women in the follicular phase, this percentage in pregnancy was decreased for interleukin-12 (mean 6.63 +/- 1.34 vs 3.34 +/- 0.87, P <.05) and tumor necrosis factor-alpha (mean 50.20 +/- 5.80 vs 31.29 +/- 5.57, P >.05). No significant difference was seen in the production of interleukin-1beta (mean 58.22 +/- 11.09 vs 47.18 +/- 7.88, P >.05). CONCLUSION: The percentage of interleukin-12 and tumor necrosis factor-alpha producing monocytes is decreased in pregnant women compared with nonpregnant women, suggesting that pregnancy is a proinflammatory state.

Cytokine production in natural killer cells and lymphocytes in pregnant women compared with women in the follicular phase of the ovarian cycle.

OBJECTIVE: To test whether peripheral natural killer (NK) cells, helper T cells, and cytotoxic lymphocytes of pregnant women shift from a type 1 cytokine production toward a type 2 cytokine production as compared with these cells in women in the follicular phase. DESIGN: Prospective study. SETTING: Outpatient clinic. PATIENT(S): Healthy nullipara at 30 weeks' amenorrhea and healthy nonpregnant women in their follicular phase. INTERVENTION(S): Samples of whole blood were stimulated with phorbol myristate acetate (PMA; Sigma Chemical Co., St. Louis, MO) and Ca-ionophore in the presence of monensin (Sigma). Lymphocytes were stained with alpha-CD3, alpha-CD8, and alpha-interferon gamma (IFN-gamma) alpha-interleukin 2 (IL-2), IL-4, or IL-10. Analysis was performed by flow cytometry. Statistical evaluation was done with the Mann-Whitney U test. MAIN OUTCOME MEASURE(S): Percentage NK cells, helper lymphocytes, and cytotoxic lymphocytes that were producing IFN-gamma, IL-2, IL-4, or IL-10. RESULT(S): There is a statistically significant decrease in the percentage of NK cells, and helper and cytotoxic lymphocytes that produced IFN-gamma in pregnant women when compared with women in the follicular phase. There is also a statistically significant decrease in the percentage of helper lymphocytes producing IL-2 in pregnant women compared with nonpregnant women. CONCLUSION(S): We found a decrease in type 1 cytokine production with no change in type 2 cytokine production after in vitro stimulation of "pregnant" NK cells and lymphocytes as compared with "nonpregnant" NK cells and lymphocytes. We suggest that NK cell and lymphocyte response are shifted away from a type 1 immune response during pregnancy.