Zarko Alfirevic

Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data

OBJECTIVE To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (≤ 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN Individual patient data metaanalysis of randomized controlled trials. RESULTS Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80), <35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and <28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight <1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.

Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review.

OBJECTIVE: To compile a systematic review of complications related to genetic amniocentesis and chorionic villus sampling (CVS) to provide benchmark data for counseling and performance assessment of individual operators. DATA SOURCES: We searched the MEDLINE database for articles published after January 1, 1995, that reported data for at least 100 women with singleton pregnancies with genetic amniocentesis after 14 weeks of pregnancy and reports of CVS carried out transabdominally between 10 and 14 weeks. METHODS OF STUDY SELECTION: For amniocentesis, 29 articles fulfilled search criteria. Sixteen studies fulfilled search criteria for CVS. TABULATION, INTEGRATION, AND RESULTS: After genetic amniocentesis, pooled pregnancy loss within 14 days was 0.6% (95% confidence interval [CI] 0.5–0.7), rising to 0.9% (95% CI 0.6–1.3) for pregnancy loss before 24 weeks and 1.9% (95% CI 1.4–2.5) for total pregnancy loss. Corresponding figures for CVS were 0.7%, 1.3%, and 2%. The data on multiple insertions showed large heterogeneity, ranging from 0.2% to 2.9% for amniocentesis (pooled risk 2.0%, 95% CI 0.9–3.6) and from 1.4% to 26.6% for CVS (pooled risk 7.8%, 95% CI 3.1–14.2). Only five amniocentesis studies provided controls, but none was matched for gestational age. Pooled relative risks for fetal loss before 28 weeks and total pregnancy loss were 1.46 (95% CI 0.86–2.49) and 1.25 (95% CI 1.02–1.53), respectively. CONCLUSION: Although the risks of pregnancy loss are relatively low, lack of adequate controls tends to underestimate the true added risk of prenatal invasive procedures.

Practice guidelines for performance of the routine mid‐trimester fetal ultrasound scan

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, teaching and research for diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practices at the time at which they were issued. Although ISUOG has made every effort to ensure that guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. They are not intended to establish a legal standard of care because interpretation of the evidence that underpins the guidelines may be influenced by individual circumstances and available resources. Approved guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

How strong is the association between maternal thrombophilia and adverse pregnancy outcome?: A systematic review

OBJECTIVE To determine whether inherited and acquired thrombophilias are associated with adverse obstetric complications. STUDY DESIGN A systematic review; studies where women with adverse obstetric complications were tested for one or more acquired and inherited thrombophilias were included. MAIN OUTCOME MEASURES Prevalence of thrombophilia in women with severe pre-eclampsia/eclampsia, severe placental abruption, intrauterine growth restriction or unexplained stillbirth. RESULTS Compared with controls, placental abruption was more often associated with homozygous and heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homocysteinaemia, activated protein C resistance or anticardiolipin IgG antibodies. Women with pre-eclampsia/eclampsia were more likely to have heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T mutation, protein C deficiency, protein S deficiency or activated protein C resistance compared with controls. Unexplained stillbirth, when compared with controls, was more often associated with heterozygous factor V Leiden mutation, protein S deficiency, activated protein C resistance, anticardiolipin IgG antibodies or lupus anticoagulant. Women with intrauterine growth restriction had a higher prevalence of heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T gene mutation, protein S deficiency or anticardiolipin IgG antibodies than controls. There was wide heterogeneity in the prevalence of thrombophilia between the studies. CONCLUSIONS Women with adverse pregnancy outcome are more likely to have a positive thrombophilia screen but studies published so far are too small to adequately assess the true size of this association. Screening for thrombophilia should not become standard practice until clear evidence emerges that thromboprophylaxis during pregnancy improves perinatal outcome. Further research into the link between the observed association, causality and heterogeneity is required.

Update on Procedure-Related Risks for Prenatal Diagnosis Techniques

Introduction: As a consequence of the introduction of effective screening methods, the number of invasive prenatal diagnostic procedures is steadily declining. The aim of this review is to summarize the risks related to these procedures. Material and Methods: Review of the literature. Results: Data from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5–1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due to very skilled operators, but these figures cannot be used for general counselling. Amniocentesis performed prior to 15 weeks had a significantly higher miscarriage rate than CVS and mid-trimester amniocentesis, and also increased the risk of talipes equinovarus. Amniocentesis should therefore not be performed before 15 + 0 weeks’ gestation. CVS on the other hand should not be performed before 10 weeks’ gestation due to a possible increase in risk of limb reduction defects. Discussion: Experienced operators have a higher success rate and a lower complication rate. The decreasing number of prenatal invasive procedures calls for quality assurance and monitoring of operators’ performance.

Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study

Objective To investigate the burden of later disease associated with moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth. Design Secondary analysis of data from the Millennium Cohort Study (MCS). Setting Longitudinal study of infants born in the United Kingdom between 2000 and 2002. Participants 18 818 infants participated in the MCS. Effects of gestational age at birth on health outcomes at 3 (n=14 273) and 5 years (n=14 056) of age were analysed. Main outcome measures Growth, hospital admissions, longstanding illness/disability, wheezing/asthma, use of prescribed drugs, and parental rating of their children’s health. Results Measures of general health, hospital admissions, and longstanding illness showed a gradient of increasing risk of poorer outcome with decreasing gestation, suggesting a “dose-response” effect of prematurity. The greatest contribution to disease burden at 3 and 5 years was in children born late/moderate preterm or early term. Population attributable fractions for having at least three hospital admissions between 9 months and 5 years were 5.7% (95% confidence interval 2.0% to 10.0%) for birth at 32-36 weeks and 7.2% (1.4% to 13.6%) for birth at 37-38 weeks, compared with 3.8% (1.3% to 6.5%) for children born very preterm (<32 weeks). Similarly, 2.7% (1.1% to 4.3%), 5.4% (2.4% to 8.6%), and 5.4% (0.7% to 10.5%) of limiting longstanding illness at 5 years were attributed to very preterm birth, moderate/late preterm birth, and early term birth. Conclusions These results suggest that health outcomes of moderate/late preterm and early term babies are worse than those of full term babies. Additional research should quantify how much of the effect is due to maternal/fetal complications rather than prematurity itself. Irrespective of the reason for preterm birth, large numbers of these babies present a greater burden on public health services than very preterm babies.

ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages safe clinical practice and high-quality teaching and research related to diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accept any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

Postnatal screening for thrombophilia in women with severe pregnancy complications.

Objective To examine the prevalence of maternal thrombophilia in women with severe preeclampsia/eclampsia, placental abruption, fetal growth restriction, and unexplained stillbirth. Methods We studied 102 women who had pregnancy complications and 44 healthy women with uncomplicated pregnancies. All women were tested 10 weeks postpartum for mutations of factor V Leiden, methylenetetrahydrofolate reductase (MTHFR) C677T, and G20210A prothrombin gene; deficiencies of protein C, protein S, and antithrombin III; and the presence of lupus anticoagulant and anticardiolipin antibodies. We aimed to recruit 100 cases and 300 controls to detect a 10% difference in thrombophilia between the groups. However, we were able to recruit only 44 controls. Results Abnormal thrombophilia screen was found in 54 women with pregnancy complications (53%) and in 17 women (39%) with normal pregnancies (odds ratio [OR] 1.8; 95% confidence interval [CI] 0.87, 3.67). Mutations encoding for factor V Leiden, G20210A prothrombin gene, and MTHFR C677T (homozygous) were identified in 18% of women with complications compared with 16% of controls (OR 1.1; 95% CI 0.44, 2.94). Activated protein C resistance, not due to factor V Leiden mutation, was the most common thrombophilic defect, found in 26% of women with pregnancy complications compared with 18% of controls Conclusion In our cohort of women with pregnancy complications, maternal thrombophilia was less common than previously thought, and multiple thrombophilias were not a major additional risk factor

Physiological changes of pregnancy and monitoring.

Advances in medical care have led to increasing numbers of complex, high-risk obstetric patients. Specialist training and a sound knowledge of normal maternal physiology are essential to optimize outcomes. One of the earliest observed changes is peripheral vasodilatation; this causes a fall in systemic vascular resistance and triggers physiological changes in the cardiovascular and renal systems, with 40-50% increases in cardiac output and glomerular filtration rates. Safety concerns over Swan Ganz catheters have driven the increasing interest in alternative techniques, such as echocardiography, thoracic bioimpedance and pulse contour analysis, although their exact roles in future obstetric high-dependency care have yet to be established. Analysis of arterial blood gases is fundamental to the management of sick patients, and correct interpretation can be aided by a systematic approach. Observation charts are almost ubiquitous in all aspects of medicine, but little evidence exists to support their use in the high-dependency setting.

Misoprostol for induction of labour: a systematic review.

Objective To determine, from the best available evidence, the effectiveness and safety of misoprostol administered vaginally or orally for third trimester cervical ripening or induction of labour.