Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

Earlier studies have reported the effectiveness of aspirin in preventing preeclampsia in women considered to be at moderate to high risk of developing this disorder. This current study was a meta-analysis of cohort studies examining risk factors for preeclampsia with the goal of estimating early in pregnancy (r16wk gestation) a woman’s risk of developing preeclampsia based on the presence of absence of various risk factors. Three practical estimates were generated: the absolute risk of developing preeclampsia in the presence or absence of a given risk factor; the relative risk in the presence or absence of a given risk factor, and the population attributable fraction (PAF) for preeclampsia in relation to each risk factor. On the basis of their analysis, the authors aimed to provide a list of risk factors that could be used to identify those women at high risk for developing preeclampsia. The PubMed and Embase databases were used to identify articles studying the association between preeclampsia and one or more risk factors in a previous pregnancy or in the current pregnancy. They specifically evaluated practical risk factors that were patient specific, easily remembered by the patient or found in previous medical records, and could be determined in the first trimester by the physician. Risk factors studied included: previous history of preeclampsia, placental abruption, intrauterine growth restriction (IUGR), or stillbirth; nulliparity; advanced maternal age; chronic hypertension; preexisting diabetes; high body mass index (BMI); kidney disease; lupus; antiphospholipid (aPL) antibody syndrome; multiple gestation, and assisted reproduction. The pooled preeclampsia event rate in the exposed and unexposed groups was calculated for each risk factor and pooled relative risk was calculated. Subsequently the PAF for each risk factor was calculated using the pooled relative risks. A total of 25,356,688 pregnancies from 92 studies were included in the meta-analysis. The mean pooled event rate for preeclampsia among all risk factors was 2.7% (SD=0.93%) for unexposed groups, while the mean pooled event rate for all exposed groups was 7.3% (SD= 4.6%). The highest pooled rate of preeclampsia was observed in women with aPL antibody syndrome [17.3%, 95% confidence Interval (CI), 6.8%-31.4%] while a previous history of preeclampsia had the highest pooled relative risk (8.4; 95% CI, 7.1-9.9). Chronic hypertension was the risk factor with the second highest pooled rate (16.0%; 95% CI, 12.6%-19.7%) and pooled relative risk (5.1%; 95% CI, 4.0%-6.5%) for preeclampsia. Preexisting diabetes, BMI >30, and pregnancy achieved by assisted reproduction were other risk factors with notably high pooled rates and relative risks. The presence of all but one of the risk factors evaluated (IUGR) was determined to significantly increase the risk of developing preeclampsia. Although aPL antibody syndrome was associated with the highest rate of preeclampsia it is a relatively uncommon disorder and therefore had one of the lowest PAFs for preeclampsia (0.18%; 95% CI, 0.08%-0.33%), whereas nulliparity, prepregnancy BMI >25, and prior preeclampsia were found to have the highest PAFs (32.3%; 95% CI, 27.4%-37.0%; 23.8%; 95% CI, 22.0%-25.6%; and 22.8%; 95% CI, 19.6%-26.3%, respectively). On the basis of their meta-analysis, the investigators identified multiple risk factors that could be used to identify early in pregnancy women who are at “high risk” of developing preeclampsia. They suggest this information could be used to develop a clinical prediction model that would be useful in determining those women who would benefit from aspirin prophylaxis during their pregnancies.

/pdf/clinical-risk-factors-for-preeclampsia-determined-in-early-seyf5wieqa.pdf

Clinical Risk Factors for Preeclampsia Determined in Early Pregnancy: Systematic Review and Meta-Analysis of Large Cohort Studies

Postpartum haemorrhage (PPH) is an important cause of maternal mortality. We conducted a systematic review of the prevalence of PPH with the objective of evaluating its magnitude both globally and in different regions and settings: global figures, as well as regional, country and provincial variations, are likely to exist but are currently unknown. We used prespecified criteria to select databases, recorded the database characteristics and assessed their methodological quality. After establishing PPH (>or=500 mL blood loss) and severe PPH (SSPH) (>or=1000 mL blood loss) as main outcomes, we found 120 datasets (involving a total of 3,815,034 women) that reported PPH and 70 datasets (505,379 women) that reported SPPH in the primary analysis. The prevalence of PPH and SPPH is approximately 6% and 1.86% of all deliveries, respectively, with a wide variation across regions of the world. The figures we obtained give a rough estimate of the prevalence of PPH and suggest the existence of some variations. For a reliable picture of PPH worldwide - its magnitude, distribution and consequences - a global survey tackling this condition is necessary.

Epidemiology of postpartum haemorrhage: a systematic review

New discoveries reveal how crucial interactions which determine our destiny occur before birth, when our genes interact with their environment as the embryo and fetus develop. These processes - in the matrix of the womb - are evolutionary echoes of mechanisms which allowed our hunter-gatherer ancestors to survive. These exciting insights into predictive adaptive responses suggest new ways of protecting the health of the fetus, infant and adult. If inappropriate they can trigger obesity, diabetes and heart disease, formerly thought to result solely from adult lifestyle. The new concepts in this book are crucial to understanding the daunting public health burden in societies undergoing rapid transition from poverty to affluence. They add an important new dimension to evolutionary theory. Synthesising developmental biology, evolutionary history, medical science, public health and social policy, this is a ground-breaking and fascinating account by two of the world's leading pioneers in this important emerging field.

https://bilder.buecher.de/zusatz/21/21302/21302478_vorw_1.pdf

The Fetal Matrix: Evolution, Development and Disease

In mammals, survival both before and after birth depends on a number of key physiological processes such as the provision of 02, a supply of oxidative substrates and a means of removing the waste products of metabolism. In adults these processes are carried out by a number of different tissues, whereas in the fetus they are carried out primarily by the placenta. The successful transition from intrato extra-uterine life, therefore, depends on the ability of specific tissues and organ systems to take over the functions of the placenta at birth. Consequently, organs such as the lungs, liver, kidneys and gut undergo maturational changes during late gestation in preparation for extra-uterine life. Most of these changes are glucocorticoid dependent and can be induced prematurely by exogenous glucocorticoid administration (Silver, 1990; Liggins, 1994; Fowden, 1995). As a consequence, synthetic glucocorticoids are now routinely administered to women in threatened preterm labour to improve neonatal viability (NIH Consensus Development Conference, 1995). In all species studied so far, there is an increase in the circulating glucocorticoid concentration in the fetus towards term (Fig. 1). The magnitude and timing of this cortisol surge vary between species, as does the precise mechanism by which it occurs (Fig. 1; Fowden & Silver, 1995; Wood & Cudd, 1997). In most species, the prepartum cortisol surge is due to increased adrenal cortisol output, but in certain animals, such as the rat and horse, its effect is enhanced by a fall in the level of plasma corticosteroidbinding globulin (Challis et al. 1993; Wood & Cudd, 1997). In normal conditions, therefore, fetal tissues are exposed to increasing levels of bioactive glucocorticoid for periods of up to 10-15 d before delivery.

/pdf/glucocorticoids-and-the-preparation-for-life-after-birth-are-13uxxa95mv.pdf

Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance?

We report the clinical features, biochemical details, and treatment of the first detected cases of an inborn error of aromatic L-amino acid decarboxylase. Male monozygotic twins presented with extreme hypotonia and oculogyric crises. Concentrations of biogenic amines and their metabolites were reduced considerably both centrally and peripherally. Pterin and phenylalanine metabolism were normal. Activity of aromatic L-amino acid decarboxylase was virtually absent in a liver biopsy sample and greatly reduced in plasma. Concentrations of L-dopa, 3-methoxytyrosine, and 5-hydroxytryptophan were elevated in CSF, plasma, and urine. CSF S-adenosylmethionine concentrations were reduced. Pyridoxine treatment had no clinical effect but led to a fall in CSF L-dopa and 3-methoxytyrosine and a rise in S-adenosylmethionine. Treatment with either bromocriptine or tranylcypromine stopped the abnormal eye movements; tranylcypromine treatment also improved muscle tone and led to a rise in plasma norepinephrine and whole blood serotonin. Combined treatment with pyridoxine, bromocriptine, and tranylcypromine produced sustained improvement in tone and voluntary movements. The twins' parents were asymptomatic but had reduced plasma aromatic L-amino acid decarboxylase activity, consistent with heterozygosity. We monitored a subsequent pregnancy through biochemical analyses of a fetal liver biopsy sample and of amniotic fluid. We predicted an unaffected fetus, which was confirmed clinically and biochemically after birth.

Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis.

Use of oral misoprostol in the prevention of postpartum haemorrhage

Prenatal diagnosis of triploidy during the second trimester of pregnancy.

Carbohydrate-deficient glycoprotein syndrome: normal glycosylation in the fetus.

Rectally administered misoprostol for the treatment of postpartum hemorrhage unresponsive to oxytocin and ergometrine: a descriptive study - A comparison between two dose regimens of misoprostol and of their effect on blood pressure

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