Peruka Neumaier-Wagner

Longitudinal determination of serum placental protein 13 during development of preeclampsia

Objective: To determine maternal serum placental protein 13 (PP13) in normal pregnancy and preeclampsia. Methods: A prospective, longitudinal study with 41 normal pregnant women, 18 cases with preterm delivery or cervix insufficiency and 4 with developing late-onset preeclampsia. Six hundred and sixty-six maternal blood samples were obtained every 2–4 weeks starting at 5–8 weeks gestation (10–12 samples/patient) and tested for serum PP13 by ELISA. Results: In normal pregnant women delivering at term, median maternal serum PP13 levels were growing from 166 to 202 pg/ml and 382 pg/ml in the first, second and third trimester, respectively. Preeclamptic women had significantly reduced PP13 levels in the first trimester (multiples of median of 0.14 at 7–8 weeks; p = 0.005 compared to normal). PP13 in the third trimester was significantly higher compared to normal at 35–36 weeks with PP13 multiples of median of 1.79. Conclusion: This preliminary study indicates that low levels of PP13 in early pregnancy identify at-risk pregnancies, whereas high levels precede the syndrome in late pregnancy and suggest syncytiotrophoblast necrosis.

BMI : new aspects of a classical risk factor for hypertensive disorders in pregnancy

HDP (hypertensive diseases in pregnancy) are one of the leading causes of maternal and fetal mortality and morbidity. BMI (body mass index) is an established risk factor for pre-eclampsia, but its role in HELLP syndrome is unknown. We therefore investigated BMI as a risk factor in the development of HELLP syndrome. At the beginning of pregnancy, BMI was measured in 1067 women with a history of HDP and 1063 controls. Diagnoses of HDP were classified according to ISSHP (International Society for the Study of Hypertension in Pregnancy) and BMI according to WHO (World Health Organization) criteria. After verification of exclusion criteria and matching for confounders, 687 women with hypertensive diseases in pregnancy and 601 controls remained for statistical evaluation by chi(2) test and multiple logistic regressions. As a continuous variable, the increase in BMI was associated with an increase in the development of gestational hypertension {OR (odds ratio), 1.1 [95% CI (confidence interval) 1.062-1.197]} and pre-eclampsia [OR, 1.1 (95% CI, 1.055-1.144)]}, but not for HELLP syndrome. According to WHO definitions, overweight women (BMI > or =25 and <30 kg/m(2)) had a 2-fold (95% CI, 1.365-2.983) risk and obese women (BMI > or =30 kg/m(2)) had a 3.2-fold (95% CI, 1.7-5.909) risk of developing pre-eclampsia when compared with women of normal weight (BMI > or =15.5 and <25 kg/m(2)). Being overweight or having obesity had no effect on the risk of HELLP syndrome. As an increased BMI is correlated with the risk of developing pre-eclampsia but not HELLP syndrome, both diseases have a different risk profile. This finding supports that underlying physiological mechanisms in pre-eclampsia vary from those in HELLP syndrome.

Emotional stress and the risk to develop hypertensive diseases in pregnancy.

Objective: Cardiovascular diseases are strongly influenced by stress and do share several risk factors with hypertensive diseases in pregnancy (HDP). The aim of the study is to investigate the correlation between emotional stress during pregnancy and the risk for HDP. Methods: A self-administered questionnaire comprising obstetrical and psychosocial questions was completed by 725 patients and 880 controls matched for age, parity, nationality, and educational level. Results: Emotional stress during pregnancy was associated with a 1.6-fold increased risk for HDP. Conclusion: Psychosocial interventions to reduce emotional stress during pregnancy may help to decrease the risk to develop HDP.

The relationship between cervical dilatation, interleukin-6 and interleukin-8 during term labor

Background. To determine interleukin‐6 and interleukin‐8 levels in amniotic fluid, retroplacental blood and maternal serum and relate these values with cervical dilatation in term labor.

Maternal serum interleukin-1β, -6 and -8 levels and potential determinants in pregnancy and peripartum

Abstract Aims: To measure maternal serum interleukins (IL) in pregnancy, delivery and early puerperium, and to identify their potential determinants. Methods: Prospective longitudinal measures of serum IL-1β, IL-6 and IL-8 in 38 healthy pregnant women at antenatal visits, through labor and delivery, with clinical correlates (infection, vaginal hemorrhage and anemia) recorded by questionnaire. Results: Pregnancy IL levels remained consistently low. IL-1β increased shortly before delivery, then returned to pregnant levels, except where blood loss exceeded 500 ml. IL-6 and IL-8 rose at labor onset and exceeded pregnancy levels through postpartum day three. Postpartum IL-6 was higher after non-elective cesarean section than after spontaneous delivery (P < 0.0001), and where blood loss exceeded 500 ml. IL-6 and IL-8 were higher with systemic infection during delivery (P < 0.0001) and on postpartum day one (P < 0.05); IL-8 was higher in anemia (delivery: P < 0.005; postpartum day 1: P < 0.05). Differences due to delivery mode and systemic infection remained significant after correction for other conditions. Conclusions: Labor-dependent inflammation increases all IL levels at delivery. Further studies with larger sample sizes are required to establish reference values differentiating physiology from pathology as an aid to peripartum management.

Breast-feeding in women with hypertensive disorders in pregnancy.

Abstract Aims: Breast feeding is particularly important and difficult in children born prematurely, especially after hypertensive diseases in pregnancies (HDP). Therefore, we aimed to investigate breast feeding in women who developed HDP. Methods: Data on breast-feeding was collected within a nationwide research project on psychosocial factors in HDP. A self-administered questionnaire was given to 2600 women with a suspected history of HDP and 1233 controls. After matching and confirming diagnosis according to ISSHP criteria, 877 women with HDP and 623 controls were included into the study. Results: Control women initiated (48.9/39.2%; P<0.001) and continued (42.2/37.2%; P<0.005) breast-feeding significantly more often than women with HDP. This holds particularly for women who developed HELLP syndrome (48.9/34.7%; P<0.0001, 42.2/33.5%; P<0.0001). A delivery before the 32nd gestational week (19.5/81.8%; P<0.0001) and a birth weight of less than 1500 g (18.8/75%; P<0.0001) were associated with the decision not to breast-feed. Conclusions: Women affected by HDP breast fed significantly less often than control women. This effect is at least partly caused by the increased rate of prematurity. Encouraging and supporting these women in breast-feeding is important to improve neonatal physical and mental development.

Neither maternal nor fetal mutation (E474Q) in the α-subunit of the trifunctional protein is frequent in pregnancies complicated by HELLP syndrome

Abstract Objective: An association between maternal HELLP syndrome and fetal long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been proposed. LCHAD catalyzes the third step in the β-oxidation of fatty acids in mitochondria. Whereas about 75% of LCHAD-deficient patients carry a G-to-C mutation at nucleotide position 1528 (Glu474Gln, E474Q) on both chromosomes, compound heterozygosity for E474Q on one chromosome and a second different LCHAD mutation on the other can be observed in up to 25% of LCHAD-deficiency cases; only very few patients carry two mutations different from E474Q. Genetic analysis of the mother alone is insufficient in case of compound heterozygosity. Since information on the fetal carrier status of the E474Q mutation in maternal HELLP syndrome is rare, we investigated the frequency of the E474Q mutation in families where the mother had HELLP syndrome. Methods: The occurrence of the E474Q mutation was analyzed by PCR and RFLP in 103 mothers with HELLP syndrome, in 82 children of affected pregnancies and in 21 fathers in families where fetal DNA was not available. In addition, 103 control women with only uncomplicated pregnancies were investigated. Results: The mutation E474Q was not detected in the study population. Conclusion: Neither maternal nor fetal heterozygosity for the E474Q mutation is a relevant factor of HELLP syndrome.

Concerted Upregulation of CLP36 and Smooth Muscle Actin Protein Expression in Human Endometrium during Decidualization

The human endometrium prepares for implantation of the blastocyst by reorganization of its whole cellular network. Endometrial stroma cells change their phenotype starting around the 23rd day of the menstrual cycle. These predecidual stroma cells first appear next to spiral arteries, and after implantation these cells further differentiate into decidual stroma cells. The phenotypical changes in these cells during decidualization are characterized by distinct changes in the actin filaments and filament-related proteins such as α-actinin. The carboxy-terminal LIM domain protein with a molecular weight of 36 kDa (CLP36) is a cytoskeletal component that has been shown to associate with contractile actin filaments and to bind to α-actinin supporting a role for CLP36 in cytoskeletal reorganization and signal transduction by binding to signaling proteins. The expression patterns of CLP36, α-actinin and actin were studied in endometrial stroma cells from different stages of the menstrual cycle and in decidual stroma cells from the 6th week of gestation until the end of pregnancy. During the menstrual cycle, CLP36 is only expressed in the luminal and glandular epithelium but not in endometrial stroma cells. During decidualization and throughout pregnancy, a parallel upregulation of CLP36 and smooth muscle actin, an early marker of decidualization in the baboon, was observed in endometrial decidual cells. Since both proteins maintain a high expression level throughout pregnancy, a role of both proteins is suggested in the stabilization of the cytoskeleton of these cells that come into close contact with invading trophoblast cells.

Childhood sexual abuse (CSA) experiences: an underestimated factor in perinatal care

Background. Childhood sexual abuse can have several negative consequences on pregnancy, birth, and the early neonatal period. However, most obstetricians are not aware if their patients have a history of childhood sexual abuse. We therefore investigated childhood sexual abuse experiences in 226 women three to eight months after delivery of a healthy child. Methods. 415 women were approached to answer a self‐administered questionnaire including obstetrical questions and questions focusing on abuse experiences. 320 women agreed to participate, 226 (69.1% of the women fulfilling inclusion criteria) of which returned a completed questionnaire. Sexual abuse was explored using a modified version of a questionnaire developed by Wyatt. The complete questionnaire was designed in cooperation with the German “Frauennotruf”, a society providing care for victims of sexual abuse. Results. The prevalence of childhood sexual abuse was a minimum of 11.5% and a maximum of 14.6% if women who were not sure about such experiences during their childhood were included. Another 1.3% of the women had experienced sexual abuse as an adult. Lifetime sexual abuse prevalence was 12.8% and 15.9%, respectively. Of the women with an experience of childhood sexual abuse, 42.3% mentioned an ongoing abuse situation for at least six months. Conclusions. As approximately every 9th woman presenting for obstetrical care has experienced childhood sexual abuse, and as those experiences may have a negative impact on fetal and maternal well‐being, adequate counseling models should be offered to victims of sexual abuse.

Recurrence risks of hypertensive diseases in pregnancy after HELLP syndrome

Abstract Aim: To determine the recurrence risk for hypertensive diseases in pregnancy after HELLP (Hemolysis Elevated Liver enzymes and Low Platelets) syndrome in a first pregnancy. Methods: The study was designed as a cohort study investigating 148 Caucasian primiparae with a diagnosis of HELLP syndrome in a first pregnancy and at least one subsequent pregnancy conducted beyond the 24th gestational week. Diagnoses were verified by reviewing medical records and classified according to ISSHP (International Society for the Study of Hypertension in Pregnancy) criteria. The recurrence risk of HELLP syndrome or other hypertensive disorders in the subsequent pregnancy was calculated with regard to disease severity in the index pregnancy. Results: Among 148 pregnancies subsequent to HELLP syndrome, 56.1% of the women were normotensive. The recurrence rate was 12.8% for HELLP syndrome, 16.2% for pre-eclampsia, and 14.2% for gestational hypertension only. Women with HELLP syndrome ≤32 gestational weeks tended to show a greater risk of complicated subsequent pregnancies compared to women presenting with HELLP after 32 gestational weeks. Conclusions: Women with a diagnosis of HELLP syndrome are at a strongly increased risk of recurrent HELLP syndrome, pre-eclampsia or gestational hypertension, however, currently no clinical or laboratory parameters allow the prediction of recurrence risk in any individual case.