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OBJECTIVE The angiotensinogen gene M235T polymorphism is related to an increased risk of hypertension. Hypertension and pregnancy-induced hypertension have been suggested to share common etiologic factors. We examined whether this mutation also increases the risk of preeclampsia/eclampsia. METHODS Pubmed/Medline, Web of Science and EMBASE were searched and a hand search of bibliographies was conducted. In all, 17 studies (including 1446 cases and 3829 controls) published in English between 1993 and October 2006 on the association of angiotensinogen gene M235T polymorphism with preeclampsia/eclampsia were selected. RESULTS The overall odds ratio (OR) under a random effects model revealed that individuals homozygous for the T allele were 1.62 times more likely to develop preeclampsia/eclampsia [95% confidence interval (CI), 1.12 to 2.33; P = 0.01) compared to individuals homozygous for the M allele. The relation in Caucasians (OR = 1.99; 95% CI, 1.18-3.36; P = 0.01) was similar to that in East Asian populations (OR = 1.74; 95% CI, 0.92-3.28; P = 0.09), although the latter was not statistically significant due to lower numbers of studies. Under additive, recessive and dominant genetic models positive associations were also found. A meta-regression analysis showed that ethnic background was a significant source of between-study heterogeneity (P = 0.04) but design of the study, study size and Hardy-Weinberg equilibrium deviation were not. There was a low probability of publication bias. CONCLUSION Our meta-analysis expands the findings on hypertension by showing that the presence of the T allele of the angiotensinogen gene is associated with an increased risk to develop preeclampsia/eclampsia.

Contains fulltext : 70119.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To investigate the effect of prednisolone on HELLP syndrome by assessing several markers of the inflammatory response and hepatic damage associated with HELLP syndrome. DESIGN: Prospective study. SETTING: Single-center, tertiary obstetric care facility at the University Medical Centre Utrecht, The Netherlands. POPULATION: Study subjects included normal controls, patients with non-HELLP preeclampsia, and patients with preeclampsia and HELLP syndrome. METHODS: HELLP syndrome was defined by hemolysis (serum lactate dehydrogenase [LDH] >600 IU/L and/or haptoglobin 70 U/L and/or serum alanine aminotransferase [ALT] >70 U/L), and a low platelet count (

Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein ( P =0.04). Preeclampsia was associated with higher IL-1β ( P P TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers.

Preterm birth is the most common cause of neonatal morbidity and mortality. Around one third of preterm deliveries starts with preterm prelabor rupture of membranes (PPROM). The aim of this trial was to study the effect of prolonged tocolysis with nifedipine versus placebo in women with PPROM on perinatal outcome and prolongation of pregnancy.The Apostel IV was a nationwide multicenter randomized placebo controlled trial. We included women with PPROM without contractions between 24(+0) and 33(+6) weeks of gestation. Participants were randomly allocated to daily 80mg nifedipine or placebo, until the start of labor, with a maximum of 18 days. The primary outcome measure was a composite of poor neonatal outcome, including perinatal death, bronchopulmonary dysplasia, periventricular leukomalaciagrade 1, intraventricular hemorrhagegrade 2, necrotizing enterocolitisstage 1 and culture proven sepsis. Secondary outcomes were gestational age at delivery and prolongation of pregnancy. Analysis was by intention to treat. To detect a reduction of poor neonatal outcome from 30% to 10%, 120 women needed to be randomized.NTR 3363.Between October 2012 and December 2014 we randomized 25 women to nifedipine and 25 women to placebo. Due to slow recruitment the study was stopped prematurely. The median gestational age at randomization was 29.9 weeks (IQR 27.7-31.3) in the nifedipine group and 27.0 weeks (IQR 24.7-29.9) in the placebo group. Other baseline characteristics were comparable. The adverse perinatal outcome occurred in 9 neonates (33.3%) in the nifedipine group and 9 neonates (32.1%) in the placebo group (RR 1.04, 95% CI 0.49-2.2). Two perinatal deaths occurred, both in the nifedipine group. Bronchopulmonary dysplasia was seen less frequently in the nifedipine group (0% versus 17.9%; p=0.03). Prolongation of pregnancy did not differ between the nifedipine and placebo group (median 11 versus 8 days, HR 1.02; 95% CI 0.58-1.79).This randomized trial did not show a beneficial effect of prolonged tocolysis on neonatal outcomes or prolongation of pregnancy in women with PPROM without contractions. However, since results are based on a small sample size, a difference in effectiveness cannot be excluded.

Introduction Placental pathology is an important contributor in preterm birth, both spontaneous and indicated. The aim of this study was to describe and compare placental histological features of spontaneous preterm birth versus indicated preterm birth. Methods A case control study was performed at the University Medical Center Utrecht. Women with spontaneous or indicated preterm birth (17–37 weeks of gestation) delivered in 2009 were included. Women with a pregnancy complicated by congenital and/or chromosomal abnormalities were excluded. Placentas were systematically examined by an expert pathologist blinded for pregnancy outcome, except for gestational age. Placental histological abnormalities were classified into infectious inflammatory lesions and maternal vascular malperfusion lesions and compared between spontaneous and indicated preterm birth. Analysis was stratified for immature (17–23 +6 weeks), extremely (24–27 +6 weeks), very (28–31 +6 weeks) and moderate/late (32–36 +6 weeks) preterm birth. Results We included 233 women, 121 women with spontaneous preterm birth and 112 women with indicated preterm birth. Among women with spontaneous extremely preterm birth, higher rates of severe chorioamnionitis were found (56.0% vs. 0%). Furthermore, a shift from infectious-inflammatory lesions to maternal vascular malperfusion lesions was seen after 28 weeks; in women with spontaneous very and moderate/late preterm birth, maternal vascular malperfusion lesions were the main finding (46.8% and 47.7% respectively). In women with indicated preterm birth, maternal vascular malperfusion lesions were most often contributing through all gestational age categories. Conclusion Maternal vascular malperfusion lesions are most frequent in both spontaneous and indicated very and moderate/late preterm birth. In spontaneous extreme preterm birth chorioamnionitis is the main finding.

Item does not contain fulltext BACKGROUND: In the past decades evidence has accumulated that women with reproductive and pregnancy-related disorders are at increased risk of developing cardiovascular disease (CVD) in the future. Up to now there is no standardised follow-up of these women becausee guidelines on cardiovascular risk management for this group are lacking. However, early identification of high-risk populations followed by prevention and treatment of CVD risk factors has the potential to reduce CVD incidence. Therefore, the Dutch Society of Obstetrics and Gynaecology initiated a multidisciplinary working group to develop a guideline for cardiovascular risk management after reproductive and pregnancy-related disorders. METHODS: The guideline addresses the cardiovascular risk consequences of gestational hypertension, preeclampsia, preterm delivery, small-for-gestational-age infant, recurrent miscarriage, polycystic ovary syndrome and premature ovarian insufficiency. The best available evidence on these topics was captured by systematic review. Recommendations for clinical practice were formulated based on the evidence and consensus of expert opinion. The Dutch societies of gynaecologists, cardiologists, vascular internists, radiologists and general practitioners reviewed the guideline to ensure support for implementation in clinical practice. RESULTS: For all reproductive and pregnancy-related disorders a moderate increased relative risk was found for overall CVD, except for preeclampsia (relative risk 2.15, 95% confidence interval 1.76-2.61). CONCLUSION: Based on the current available evidence, follow-up is only recommended for women with a history of preeclampsia. For all reproductive and pregnancy-related disorders optimisation of modifiable cardiovascular risk factors is recommended to reduce the risk of future CVD.

OBJECTIVE: To perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy. DESIGN: External validation of all published prognostic models in large scale, prospective, multicentre cohort study. SETTING: 31 independent midwifery practices and six hospitals in the Netherlands. PARTICIPANTS: Women recruited in their first trimester (

Objective: To determine if presence of the Roach muscle, a small muscle bundle lying just beside the umbilical artery, contributes to umbilical cord coiling. Methods: 251 umbilical cords were examined. The umbilical coiling index (UCI) was calculated as the number of coils divided by the cord length in cm. Cords were classified as hypocoiled (UCIbp10), normocoiled (UCI p10–p90) or hypercoiled (UCINp90). On microscopic examination of a cross section of the cord, absence or presence of a Roach muscle was determined. The t-test for independent samples and logistic regression were used for statistical analysis. Results: A Roach muscle was observed in 101 cords. The mean UCI was higher in cords with the muscle bundle (0.23 coils/cm) than in cords without a muscle (0.18coils/cm). Difference inmean: 0.05coils/cm (95%C.I.0.01–0.09).ORfor hypercoilinginpresenceofthemusclewas 2.98 (95%C.I.1.57–5.64).ORforhypocoilinginthepresenceofthemusclewas1.49(95%C.I.0.79–2.81). Conclusions: Our results suggest that presence of a Roach muscle bundle contributes to umbilical cord coiling. Given the divergence in umbilical cord coiling within subgroups with or without this muscle, other factors must play a more dominant role.

Preeclampsia is characterized by generalized endothelial dysfunction as a result of an inappropriate maternal immune response against the fetus. It has been postulated that the adaptive immune system plays a key role in the etiology of preeclampsia by generating a pro-inflammatory Th1 type immune reaction. In this review, recent studies on Th1 and Th2 type cytokine mapping in preeclampsia are reviewed, as well as on the sources of pro-inflammatory cytokines and the role of regulatory cytokines and chemokines. In addition, we discuss the possible role of Toll-like receptors of the innate immune system in the pathophysiology of preeclampsia.ObstetriciansGynecologists, Family Physicians.After completion of this article, the reader should be able to summarize the newer concepts related to the pathogenesis of preeclampsia and explain the role of the maternal immune system and the role of pro-inflammatory and regulatory cytokines and chemokines in the pathophysiology of the disease.

Proactive Support of Labor enhances professional labor and delivery skills by providing the expertise for preventing prolonged labor which is the root-cause of women's dissatisfaction with the experience of childbirth. Step-by-step, evidence-based guidance on good practice during labor is given, including fetal and maternal monitoring, pain relief, and the prevention and timely correction of everyday labor disorders. It leaves no aspect of childbirth practice untouched. Included are guidance on adequate pre-labor education, psychological support, and well-defined birth-planning - including strict diagnoses and timely corrective measures in abnormal labor, and constant audit of all procedures. The birth-plan promotes team spirit between obstetricians, midwives and nurses, good communication, and sound organization. Proactive Support of Labor strikes a new balance between natural birth and intervention and invariably enhances women's satisfaction with the childbirth experience. The book will be essential reading for obstetricians, midwives, labor room nurses, and maternal-fetal medicine specialists and trainees. For more information, reviews and forums visit the publication's website at www.proactivesupportoflabor.com.

Introduction Uterine Natural Killer (uNK) cells are key regulators of the placental bed during early placental development and account for 40% of decidual cells. uNK cells have been suggested to play a role in pregnancy complications including maternal placental syndromes, such as preeclampsia. Furthermore uNK cells are involved in angiogenesis, immunomodulation, trophoblast invasion and spiral artery remodeling. These temporal processes are essential for normal placentation and may suggest a time dependent role for uNK cells. Objective To determine uNK cell phenotypic changes during early human placental development. Methods uNK cells were isolated from first (7–8 wks, n = 6) and second trimester decidual tissue (13–14 wks, n = 6) by enzymatic digestion and flow sorting, based on uNK cell specific surface marker expression (CD56 high CD16-CD3-). Total RNA was isolated and subjected to genome-wide gene expression profiling. Expression patterns were validated by quantitative rt-PCR. Results Using purified uNK cells we identified 140 transcripts that are differentially expressed between the first and second trimester of pregnancy. Many of these transcripts cluster into promising novel and established NK cell functional characteristics. Conclusion The uNK cell phenotype changes over the course of early pregnancy. We propose that these phenotypic changes of NK cells may be dictated by the “uterine niche” to promote the orderly and precisely timed process of placentation.

Background: Results from a number of long-term follow-up studies have suggested that hypertensive disorders in pregnancy are associated with increased risk of cardiovascular disease later in life. More recently, this putative relationship has been substantiated with findings of elevated cardiovascular risk factors, such as lipid profiles and glucose, in women with a history of hypertensive pregnancy disorders. Homocysteine is a sensitive indicator of increased risk but data on homocysteine levels in women with a history of hypertensive pregnancy disorders are inconsistent. Design: This cohort study included 279 women with a history of hypertensive pregnancy disorders at term and 85 women with a history of uncomplicated pregnancies who participated in the Hypitat Risk Assessment Study (HyRAS). Methods: Blood samples for total homocysteine determination were taken 2.5 years postpartum. Homocysteine levels were determined in plasma using an immunoassay. Results: Women with a history of hypertensive pregnancy disorders had significant higher median homocysteine levels (10.66mol/L) 2.5 years postpartum compared with women with a history uncomplicated pregnancies (9.82mol/L; p=0.002). Women with a history of hypertensive pregnancy disorders had a higher risk of having a homocysteine level in the highest quartile (odds ratio 3.4, 95% confidence interval 1.5-7.6). Conclusion: At 2.5 years postpartum, women with a history hypertensive pregnancy disorders had higher homocysteine levels than women who had uncomplicated pregnancies. Although higher homocysteine levels might be a potential link between a history of hypertensive pregnancy disorders and increased cardiovascular disease risk later in life, the clinical implications remain an area for future research.

Objective: To analyse preventive interventions of women with cardiovascular risk factors postpartum. Methods: 3.5 years postpartum, women with history of hypertension in pregnancy were invited for a questionnaire, 1 year after a cardiovascular risk assessment. Results: Two hundred and fifty-seven women completed the questionnaire. At risk factor analyses, 35% had hypertension, 37% abnormal lipid-or glucose levels, 63% BMI >= 25 and 19% smoked. One year later, 36% of women with hypertension used anti-hypertensives, 0% of women with abnormal laboratory findings used anticholesterol and 1% anti-diabetes medication, 31% of the obese women achieved BMI reduction (>= 5%), 42% of the women who smoked, quit. Conclusion: A minority improved their risk profile.

BACKGROUND: Women with a complication of pregnancy are at increased risk of cardiovascular morbidity and mortality later in life. Yet, information on risk of recurrent events in women with a previous cardiovascular event is lacking. We aimed to assess the relationship between early preterm delivery, (recurrent) miscarriage and the risk for recurrent cardiovascular events in women with manifest vascular disease. METHODS: We included 1014 women with a mean age of 60 years from the SMART study, a prospective ongoing cohort study among subjects with clinically manifest vascular disease. The included women had a history of ≥1 pregnancy and were followed for the occurrence of subsequent vascular events. The relationship between the pregnancy complications ((miscarriage (gestational age

To determine the long-term risk of developing type II diabetes (T2D) and cardiovascular disease (CVD) for women with a history of gestational diabetes mellitus.Systematic review and meta-analysis.Two search strategies were used in PubMed and Embase to determine the long-term risks of developing T2D and CVD after a pregnancy complicated by gestational diabetes mellitus. After critical appraisal of the papers found, 11 papers were included, involving a total of 328,423 patients. Absolute and relative risks (RRs) were calculated.Eight studies (n=276,829) reported on the long-term risk of T2D and 4 (n=141,048) on the long-term risk of CVD. Follow-up ranged from 3.5 to 11.5 years for T2D and from 1.2 to 74.0 years for CVD. Women with gestational diabetes had a risk of T2D varying between 9.5% and 37.0% and a risk of CVD of between 0.28% and 15.5%. Women with gestational diabetes were at increased risk of T2D (weighted RR: 13.2; 95% CI: 8.5-20.7) and CVD (weighted RR: 2.0; 95% CI: 1.1-3.7) compared to women without gestational diabetes.Women with prior gestational diabetes mellitus have a significantly increased risk of developing T2D and CVD. It is very important that gestational diabetes is recognised as a cardiovascular risk factor in daily practice. It would be desirable to screen this group of women for the presence of hyperglycaemia and other cardiovascular risk factors. Further research is required to be able to specify the long-term risk of T2D and CVD and to demonstrate whether such screening is cost-effective.

Objectives: To evaluate the effect of prolonged administration of high-dose prednisolone on early onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome during expectant management. Study design: A randomized, double-blind trial was performed in 31 pregnant women with HELLP syndrome with an onset before 30 weeks gestation. Patients received either 50 mg prednisolone or placebo intravenously twice a day. Primary outcome measures were the entry-to-delivery interval and the number of recurrent HELLP exacerbations in the antepartum period. Results: Serious maternal morbidity was considerable, in particular in the placebo group where even on maternal occurred as a consequence of liver rupture. The mean entry-delivery interval did not differ between the prednisolone group (6.9 days) and the placebo group (8.0 days). However, patients in the prednisolone group had a significant lower risk of a recurrent HELLP exacerbation after the initial crisis had subsided, as compared to patients in the placebo group (HR 0.3, with 95% CI 0.3-0.9). Platelet count recovered faster in the prednisolone group as compared to the placebo group (mean 1.7 days versus 6.2 days, P < 0.01). Conclusions: HELLP syndrome remote from term causes high risk for serious maternal morbidity and mortality. When expectant management is pursued in selected patients with a HELLP syndrome remote from term, prolonged administration of prednisolone reduces the risk of recurrent HELLP syndrome exacerbations.

Objective The aim of this study was to report outcome of subsequent pregnancy after early-onset preeclampsia in first pregnancy, and to evaluate potential risk factors for recurrence of preeclampsia and preterm delivery. Study design Reproductive follow-up data were obtained for women with a history of early-onset preeclampsia, resulting in delivery before 34 weeks of gestation at the University Medical Center Utrecht, The Netherlands, between July 1993 and September 2002. The relative contributions of demographic data, outcome variables of first pregnancy, and common thrombophilias to the recurrence risk of preeclampsia and preterm delivery in subsequent pregnancy, were estimated by Cox proportional hazard models. Results Subsequent pregnancy outcome data were available for 120 women. Overall, preeclampsia reoccurred in the second pregnancy in 30 women (25%). However, 6 women delivered before 34 weeks of gestation (5%), 20 women between 34 and 37 weeks of gestation (17%), and 94 women after 37 weeks of gestation (78%). Forty-one women (34%) had an uneventful pregnancy. Recurrence rates for preeclampsia or preterm delivery were not related to severity of first pregnancy complications, including delivery before 28 weeks of gestation, occurrence of hemolysis, elevated liver enzymes, and low platelet count syndrome, small-for-gestational age infants, and to hereditary or acquired thrombophilias. Chronic hypertension was related to a higher recurrence risk of preeclampsia in the second pregnancy (hazard ratio 2.1, 95% CI 1.0-4.4), and smoking was related to a higher recurrence risk of preterm birth (hazard ratio 2.4, 95% CI 1.1-5.6). Conclusion Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia is generally favorable.

Background Preeclampsia is characterized by an increase in peripheral vasoconstriction. Studies of central hemodynamics are limited. Noninvasive evaluation of aortic stiffness and pressure waveform is possible by applanation tonometry. We determined pulse wave velocity (PWV), augmentation index (AI), subendocardial viability ratio (SEVR), and the central to brachial pressure amplification in normotensive, hypertensive, and preeclamptic pregnancies. Methods In 51 normotensive, 38 hypertensive, and 33 preeclamptic pregnancies we measured carotid-femoral PWV. The AI, SEVR, and central pressures were determined by analysis of the aortic pressure waveform derived from the radial artery. Measurements were performed in lateral position after 10 min of rest. Linear regression models and ANOVA multiple comparisons were used for statistical analyses. Results There were no differences in age or other baseline characteristics. The mean PWV for the normotensive, hypertensive, and preeclamptic groups was 5.1 m/sec (SD 0.6), 6.2 m/sec (SD 1.0), and 7.0 m/sec (SD 1.3), respectively. The AI was 6.7% (SD 14.0), 17.7% (SD 15.9), and 31.1% (SD 12.4), respectively. The SEVR was 1.38 (SD 0.2), 1.50 (0.2), and 1.48 (0.3), respectively. Central to brachial pressure amplification was 1.6 (SD 0.2), 1.4 (SD 0.2), and 1.3 (SD 0.2), respectively. After adjustment for blood pressure, no significant differences remained between the groups. Conclusions In hypertensive and preeclamptic pregnancies, aortic stiffness and augmentation are significantly higher as compared to normotensive pregnancy. Amplification of central pulse pressure is significantly lower in hypertensive and preeclamptic pregnancies, resulting in relatively higher central pressure. Nevertheless, the supply and demand ratio of the heart is not impaired in hypertensive and preeclamptic pregnancies.

Introduction: Pregnancy has recently been described as a generalized intravascular inflammatory response to the conceptus. Total fibrinogen concentrations increase during pregnancy. The percentage high molecular weight fibrinogen (HMW-Fg) of the concentration total fibrinogen is known to increase during acute-phase conditions like inflammation. Therefore, we investigated whether the percentage high molecular weight fibrinogen increases during normal pregnancy. Materials and Methods: Eighteen healthy nulliparous women with uncomplicated pregnancies with normal course and outcome participated in this study. Five blood samples were drawn from every woman in the gestational age periods 9 to 16, 17 to 24, 25 to 33 and 34 to 42 weeks and at 12 to 20 weeks after delivery. Total fibrinogen concentrations were determined according to Clauss and the percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. One-way analysis of variance (ANOVA) was used to evaluate differences between gestational age periods and correlation coefficients were calculated by Pearson's method. Results: Total fibrinogen concentrations increased with advancing gestational age and decreased after delivery. The percentage high molecular weight fibrinogen of the total fibrinogen remained unaltered during and after pregnancy. Conclusions: During normal pregnancy, there is an increase of total fibrinogen concentrations with advancing gestational age, without a rise in percentage high molecular weight fibrinogen. After delivery, the total fibrinogen returns to baseline concentrations.

Background Baseline distributions of pregnancy disorders' biomarkers PlGF and PAPP-A levels are primarily based on Western European populations of Caucasian ethnicity. Differences in PAPP-A and PlGF concentrations by ethnicity have been observed, with increased levels in Afro-Caribbean, East Asian, and South Asian women. Baseline concentrations of sub-Saharan African women have not been evaluated. Objectives To investigate PlGF and PAPP-A in a sub-Saharan African population and assess the performance of existing reference values of PAPP-A and PlGF. Methods A nested cross-sectional study was conducted in two public hospitals in Accra, Ghana. Out of the original 1010 women enrolled in the cohort, 398 participants were eligible for inclusion with a normotensive singleton gestation and serum samples taken between 56 and 97days of pregnancy. PAPP-A and PlGF concentrations were measured with an automated immunoassay. Multiple of the median (MoM) values corrected for gestation and maternal weight for PAPP-A and PlGF were calculated using reference values of a Dutch perinatal screening laboratory based on over 10.000 samples, and PlGF manufacturer reference values, respectively. Results The PAPP-A median MoM was 2.34 (interquartile range (IQR) 1.24–3.97). Median PlGF MoM was 1.25 (IQR 0.95–1.80). Correlation between PAPP-A and PlGF MoM values was 0.21. Median MoM values for PAPP-A and PlGF tended to be slightly different for various Ghanaian ethnic subgroups. Conclusions PAPP-A and PlGF MoM values appear to be substantially higher in a sub-Saharan African population compared to the Caucasian or Afro-Caribbean MoM values previously reported. The difference suggests the need for a specific correction factor for this population to avoid underestimation of risk for fetal aneuploidies or placental disorders when using PAPP-A and PlGF MoM for screening purposes.

Objective Although a large variety of automated blood pressure devices are available, only some have been validated for use in clinical practice. The British Hypertension Society (BHS) recommends separate validation of automated devices in special subgroups, e.g. the elderly and pregnant women. The aim of this study was to compare the Finometer (FM) and the earlier validated SpaceLabs 90207 (SL) with standard auscultatory blood pressure measurements in normal, pre-eclamptic and hypertensive pregnancy, following the guidelines of the BHS and the Association for the Advancement of Medical Instrumentation (AAMI). Methods The total study group consisted of 123 pregnant women, of whom were 54 normotensive, 31 pre-eclamptic and 38 hypertensive. Automated readings with the FM and SL were compared with auscultatory blood pressure measurements. Bland-Altman plots, BHS grades, mean pressure differences and 95% limits of agreement were used for analysis. Results Bland-Altman plots showed a wide scatter of the pressure differences between auscultatory and automated measurements. FM achieved BHS grades C/D, C/B, D/D and D/D in the total, normotensive, pre-eclamptic and hypertensive group, respectively. The AAMI criteria were only met for diastolic blood pressure in the normotensive group. For SL almost identical BHS grades and 95% limits of agreement as compared to our earlier study were found. Conclusions The accuracy and precision of the Finometer are not sufficient for determination of absolute blood pressure levels in individual pregnant women. Our present findings on the SpaceLabs 90207 reconfirm our earlier results.

Introduction: The major coagulation protein fibrinogen (Fg) is a heterogeneous protein with three main fractions: high molecular weight fibrinogen (HMW-Fg), low molecular weight fibrinogen (LMW-Fg) and low molecular weight′ fibrinogen. The clottability of high molecular weight fibrinogen is highest as compared to the other fractions. Pre-eclampsia is associated with a state of hypercoagulability, and with an increase of fibrinogen concentration. The aim of the present study was to examine if the increased total fibrinogen plasma concentration in patients with pre-eclampsia is associated with a change in distribution of the main fibrinogen fractions. Material and Methods: Plasma was collected from 14 patients with pre-eclampsia and from 14 healthy pregnant matched controls. Total fibrinogen concentrations were determined according to Clauss. The percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. The study groups were compared by the Mann–Whitney U-test. Results: The median (range) total fibrinogen concentration in the pre-eclampsia group was 5.04 (3.25–6.51) g/l and in the control group 4.19 (3.61–5.38) g/l (p

Background Maternity care is an integrated care process, which consists of different services, involves different professionals and covers different time windows. To measure performance of maternity care based on clients' experiences, we developed and validated a questionnaire. Methods and Findings We used the 8-domain WHO Responsiveness model, and previous materials to develop a self-report questionnaire. A dual study design was used for development and validation. Content validity of the ReproQ-version-0 was determined through structured interviews with 11 pregnant women (>= 28 weeks), 10 women who recently had given birth (

BackgroundThe physiologic transformation of uterine spiral arteries in the human placental bed is essential for a healthy pregnancy. Failure of this transformation due to deficient trophoblast invasion is widely believed to underlie pregnancy complications such as preeclampsia, foetal growth restriction, miscarriage and preterm labour. Understanding of invasive behaviour and remodelling properties of trophoblasts in the uterine wall is essential in elucidating the aetiology of these pregnancy complications. However, there is a lack of satisfactory specimens of the placental bed to enhance our knowledge on the mechanisms that control trophoblast invasion. Several techniques can be used to obtain biopsies from the placental bed and sample handling can be executed differently depending on the research question.MethodsThis systematic review provides an overview of all studies investigating the placental bed and sampling techniques used. Papers that described surgical techniques, specimen handling, complications and/or success rate of the placental bed biopsy procedures were included. Placental bed biopsies are an essential and feasible technique to study abnormalities in the placental bed associated with pregnancy complications.ResultsDepending on the technique used the likelihood of sampling a spiral artery and trophoblast from the placental bed is 51%–78% per case, without significant complications.ConclusionsCaution is needed when interpreting data if the placental bed is subjected to labour. We propose a uniform sampling technique and conservation protocol for the study of the placental bed and provide tools for selection of the appropriate technique for future placental bed collections.

STUDY QUESTION: Is type 1 diabetes a determinant of advanced ovarian ageing, resulting in an early age at natural menopause? SUMMARY ANSWER: No clear evidence was provided that type 1 diabetes is a determinant of accelerated ovarian ageing resulting in an early menopause. WHAT IS KNOWN ALREADY: The association between type 1 diabetes and early menopause has been examined previously with inconsistent results. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was performed in 140 post-menopausal women with, and 5426 postmenopausal women without, diabetes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Both women with and without diabetes had experienced natural menopause. Study participants filled out a standardized questionnaire including report of their age at last menstrual period. Differences in menopausal age were analysed using linear regression analyses, with adjustment for possible confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age at natural menopause was 49.8 +/- 4.7 years in women with type 1 diabetes and 49.8 +/- 4.1 in women without diabetes. Linear regression analyses showed that type 1 diabetes was not associated with an earlier menopause compared with the reference group without diabetes, after adjustment for age, smoking history and parity (difference in age at menopause between women with type 1 diabetes and reference group 0.34 years, 95% confidence interval -0.34, 1.01). LIMITATIONS, REASON FOR CAUTION: Age at menopause was self-reported and assessed retrospectively. We had no information regarding microvascular complications therefore a possible association between vascular health and menopausal age could not be investigated. WIDER IMPLICATIONS OF THE FINDINGS: It has been hypothesized that the possible mechanism behind an accelerated ovarian ageing process in type 1 diabetes is prolonged poor glycaemic control and subsequent effects on vascular health. The improved glycaemic control during the last decades may have prevented vascular damage from occurring to an extent that would affect organ function. Nevertheless, the present findings are reassuring for reproductive health prospects in women with type 1 diabetes.

How does insulin action change during pregnancy in women with polycystic ovary syndrome (PCOS) who develop gestational diabetes (GDM) compared with women with PCOS who do not?Women with PCOS who develop GDM already show disturbed insulin action early in pregnancy.Pregnant women with PCOS are at increased risk of developing GDM compared with women without PCOS.This study represents a post hoc analysis of a subgroup of pregnant women with PCOS participating in a multicentre prospective cohort study. A total of 72 women were included.Women with PCOS and a wish to conceive were included before conception and followed during pregnancy. Insulin, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), sex hormone-binding globulin (SHBG) and testosterone were analysed at three different time points in women who developed GDM and women who did not.Seventy-two pregnant women with PCOS were included of which 22 (31%) women developed GDM. Both insulin levels and HOMA-IR were significantly higher at each sampling point in women with PCOS who developed GDM. SHBG levels were significantly lower before conception and in the second trimester compared with women who did not develop GDM. Testosterone concentrations were significantly lower before conception in women who developed GDM. After adjusting for BMI, waist circumference and waist/hip ratio, the differences in insulin, HOMA-IR, SHBG and testosterone levels remained largely the same.Selection bias cannot be excluded since only women from one centre with a complete blood sampling set were included in this study.The knowledge that women with PCOS who develop GDM already have a disturbed insulin action early in pregnancy is likely to be useful in considering the pathophysiology processes underlying this disorder in this specific group of women.This study was funded by the Child Health research programme of the University Medical Centre Utrecht. M.A.d.W., A.J.G., S.M.V.-V., A.F. and M.P.H.K. have no conflicts of interest to disclose. M.J.C.E. has received grant support from the following companies (in alphabetic order): Illumina and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Ferring, Ova-Science, PregLem SA, Roche and Watson Laboratories. The authors declare complete independence from funders.Clinicaltrials.gov, number NCT00821379.

We report a case of a 20-week pregnant woman, who underwent embolisation of a cervical fibroid to end a life-threatening massive bleeding. This is the first reported case in the literature of a super-selective uterine fibroid embolisation (UFE) in a pregnant woman, even though pregnancy is considered an absolute contraindication for UFE. This rare case demonstrates that UFE can be safely performed during pregnancy providing an excellent short- and long-term clinical outcome for both mother and child.

To provide reference values for the umbilical coiling index in uncomplicated pregnancy. Umbilical cords were collected from livebom singleton infants born after uncomplicated pregnancies. The umbilical coiling index (UCI) was calculated as the number of coils divided by the cord length in centimeters. The mean value (SD) for the UCI was calculated, and possible correlations of the UCI with maternal age, parity, gestational age at delivery, mode of delivery, sex and birth weight of the infant were examined. A total of 122 umbilical cords were included. The frequency distribution of the UCI was skewed to the right. The mean (SD) UCI was 0.17 (0.009) coils/cm. There were no significant correlations of the UCI with maternal age, parity, gestational age at delivery, mode of delivery, sex or birth weight of the infant. This is the first study to determine the UCI in a group exclusively consisting of uncomplicated pregnancies. The mean value that we found for the UCI may serve as the standard reference, allowing proper interpretation of umbilical coiling in complicated pregnancy

To determine whether the diurnal blood pressure profiles in pregnant women with pre-eclampsia and/or intrauterine growth restriction (IUGR) differ from those in normal pregnant controls, and, if so, to establish whether such a difference is accompanied by altered diurnal rhythms of fetal heart rate (FHR) and its variation.Twenty-two women in the third trimester of pregnancy with pre-eclampsia, IUGR, or both, entered the study. Eleven healthy pregnant women served as controls. Maternal systolic and diastolic blood pressures and heart rate (MHR) were determined automatically at 30-min intervals during a period of 26 h starting at 09.00. During the study period, nine 1-h recordings of FHR were made at predetermined timepoints. FHR was analyzed numerically.Systolic and diastolic blood pressures and MHR showed diurnal patterns, with the highest values during the day and a trough during the night in all women. Daytime and night-time blood pressures were higher in pre-eclamptic women (p0.001), and the day-night difference was smaller than in controls (p0.001). Diurnal patterns of FHR and its variation did not differ qualitatively between the three study groups. However, FHR was affected by the maternal blood pressure profile, and all FHR parameters and their diurnal ranges were quantitatively different in IUGR fetuses (p0.05).In pre-eclamptic women, there was blunting of the diurnal blood pressure profile. This altered maternal hemodynamics was associated with a similar reduction in FHR amplitude during the 26-h period but not with FHR variation. Although diurnal rhythms of FHR and its variation persisted qualitatively in the IUGR fetuses, they seemed to have been reset quantitatively, leading to a flattened diurnal pattern.

Question Preeclampsia is associated with long-term chronic hypertension and accelerated development of atherosclerosis, which may lead to premature arterial calcifications and arterial stiffness. However, the degree and distribution of these subclinical signs of atherosclerosis in women with a history of preeclampsia has not been previously addressed. In this study, we prospectively evaluate arterial calcifications by low-dose computed tomography (CT) and arterial stiffness by pulse wave velocity (PWV) in asymptomatic women with a history of preeclampsia. Methods Women with a history of preeclampsia ( N = 153) who participated in a prospective multicenter evaluation of cardiovascular health at age 45–55 years were screened for subclinical arterial disease using low-dose CT and pulse wave velocity (PWV) analysis. Coronary artery calcium score (CACS), thoracic aortic calcium score (TACS) excluding the aortic arch, and valvular calcium score (VCS) were assessed on a non-contrast cardiac CT scan and carotid siphon calcium score (CSCS) on a non-contrast carotid siphon scan. PWV was assessed as a measure of arterial stiffness (TensioMed Arteriograph). Correlations between vascular calcifications and the relationship between vascular calcifications and CVD risk factors were assessed. Results Study participants had a mean age at inclusion of 49.0 years (SD 3.9 years). Of these, 54.6% had hypertension and 35.3% fulfilled criteria for metabolic syndrome. Vascular calcifications were seen in 110 women (71.9%) on low-dose CT: 49 (32.0%) had CACS >0; 22 (14.9%) had TACS >0; 5 (3.3%) had VCS >0 and 95 (69.9%) had CSCS >0. CACS was strongly correlated with TACS ( R = 0.98, p 0 and hypertension (OR 2.50, 95%CI 1.22–5.13). The presence of calcifications (CACS >0) was not related to other cardiovascular risk factors including obesity, smoking, hyperlipidemia and increased PWV. Conclusions Coronary and vascular calcifications in general are common in women with a history of preeclampsia at age 45–55 years. Only CACS >0 appears to be associated with chronic hypertension, but not with increased arterial stiffness or other cardiovascular risk factors.

Item does not contain fulltext OBJECTIVE: To evaluate long-term effects of maintenance tocolysis with nifedipine on neurodevelopmental outcome of the infant. DESIGN, SETTING AND POPULATION: Follow up of infants of women who participated in a multicentre randomised controlled trial on maintenance tocolysis with nifedipine versus placebo. METHODS: Two years after the APOSTEL II trial on maintenance tocolysis with nifedipine versus placebo, we asked participants to complete the Ages and Stages Questionnaire. MAIN OUTCOME MEASURES: Infant development was measured in five domains. Developmental delay was defined as a score of

Objective To compare the performance of the lecithin/sphingomyelin ratio and the lamellar body count in the prediction of neonatal respiratory distress syndrome. Design Meta-analysis. Sample Six studies reporting on the performance of both the lecithin/sphingomyelin ratio and the lamellar body count published between January 1966 and August 1999. Methods We performed a computerised MEDLINE search to identify articles published on the subject. For the six selected studies, prevalence of respiratory distress syndrome and sensitivity and specificity of the tests in the prediction of respiratory distress syndrome were calculated, and overall performance was assessed by constructing summary receiver–operating characteristic curves. Results The constructed summary receiver–operating characteristic curves showed the lamellar body count to perform slightly better than the lecithin/sphingomyelin ratio in the prediction of respiratory distress syndrome (P= 0.13). Conclusions Since the lamellar body count can be performed quickly and since it is less expensive than the lecithin/sphingomyelin ratio, we recommend the former as the test of first choice in the assessment of fetal lung maturity.

One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states that the placenta secretes one or more cytotoxic factors resulting in maternal endothelial dysfunction. Among the candidate factors are the products of increased oxidative stress. Although there is circumstantial evidence of such an increase, direct evidence is still lacking. Electron paramagnetic spin trap resonance (EPR), the most direct method to detect free radicals in tissues, was used to measure superoxide levels in placentae from normal pregnancies (n=13) and pregnancies complicated by PE (n=10). The superoxide level was significantly increased in the placental tissue of pre-eclamptic women. Moreover, upon inhibition of Cu-Zn superoxide dismutase (SOD) activity the relative increase of the superoxide levels was significantly smaller in the placentae from the PE patients, implying decreased basal Cu-Zn SOD activity. These findings lend direct support to the hypothesis that oxidative stress in placental tissue is increased in PE.