Alternative regimens of magnesium sulfate for treatment of preeclampsia and eclampsia: a systematic review of non-randomized studies.

INTRODUCTION: The optimal dosing regimen of magnesium sulfate for treating preeclampsia and eclampsia is unclear. Evidence from the Cochrane review of randomized controlled trials (RCTs) was inconclusive due to lack of relevant data. MATERIAL AND METHODS: To complement the evidence from the Cochrane review, we assessed available data from non-randomized studies on the comparative efficacy and safety of alternative magnesium sulfate regimens for the management of preeclampsia and eclampsia. Sources included Medline, EMBASE, Popline, CINAHL, Global Health Library, African Index Medicus, Biological abstract, BIOSIS and reference lists of eligible studies. We selected non-randomized study designs including quasi-RCTs, cohort, case-control and cross-sectional studies that compared magnesium sulfate regimens in women with preeclampsia or eclampsia. RESULTS: Of 6178 citations identified, 248 were reviewed in full text and five studies of low to very low quality were included. Compared with standard regimens, lower-dose regimens appeared equally as good in terms of preventing seizures [odds ratio (OR) 1.02, 95% confidence interval (CI) 0.46-2.28, 899 women, four studies], maternal morbidity (OR 0.47, 95%CI 0.32-0.71, 796 women, three studies), and fetal and/or neonatal mortality (OR 0.87, 95%CI 0.38-2.00, 800 women, four studies). Comparison of loading dose only with maintenance dose regimens showed no differences in seizure rates (OR 0.99, 95%CI 0.22-4.50, 146 women, two studies), maternal morbidity (OR 0.53, 95%CI 0.15-1.93, 146 women, two studies), maternal mortality (OR 0.63, 95%CI 0.05-7.50, 146 women, two studies), and fetal and/or neonatal mortality (OR 0.49, 95%CI 0.23-1.03, 146 women, two studies). CONCLUSION: Lower-dose and loading dose-only regimens could be as safe and efficacious as standard regimens; however, this evidence comes from low to very low quality studies and further high quality studies are needed.

Non-anaemic iron deficiency - a disease looking for recognition of diagnosis: a systematic review.

OBJECTIVE: To capture all data meeting a rigid definition of non-anaemic iron deficiency (NAID) and determine whether it is associated with poor outcomes compared with normal iron status and whether iron supplementation improves outcomes in NAID. DESIGN: Systematic review. DATA SOURCES: EMBASE, Medline, Web of Science, clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP) and Central from database inception to April 2014. ELIGIBILITY CRITERIA: Ferritin <16 µg/L (<12 µg/L if age <5 yr) in the absence of anaemia in observational studies or randomised trials. Where populations were deemed to be sufficiently similar, meta-analysis was undertaken. RESULTS: There were 21 studies included. NAID in pregnancy associated with reduction in birthweight (P = 0.028). Iron supplementation in NAID was associated with improvement in objective scores (P = 0.005) and self-rating (P = 0.03) of fatigue. Meta-analysis was limited and, where possible, was not statistically significant including the comparison of NAID with cardiovascular function in adults (VO2max P = 0.21, RERmax P = 0.68), educational attainment in children (P = 0.14), infant mental (P = 0.29) and psychomotor (P = 0.07) development, and iron supplementation in NAID with educational attainment in language (P = 0.31). CONCLUSIONS: There is emerging evidence that NAID is a disease in its own right, deserving of further research in the development of strategies for detection and treatment.

Interventions for treating constipation in pregnancy.

BACKGROUND: Constipation is a common symptom experienced during pregnancy. It has a range of consequences from reduced quality of life and perception of physical health to haemorrhoids. An understanding of the effectiveness and safety of treatments for constipation in pregnancy is important for the clinician managing pregnant women. OBJECTIVES: To assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2015), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (30 April 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We considered all published, unpublished and ongoing randomised controlled trials (RCTs), cluster-RCTs and quasi-RCTs, evaluating interventions (pharmacological and non-pharmacological) for constipation in pregnancy. Cross-over studies were not eligible for inclusion in this review. Trials published in abstract form only (without full text publication) were not eligible for inclusion.We compared one intervention (pharmacological or non-pharmacological) against another intervention, placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Four studies were included, but only two studies with a total of 180 women contributed data to this review. It was not clear whether they were RCTs or quasi-RCTs because the sequence generation was unclear. We classified the overall risk of bias of three studies as moderate and one study as high risk of bias. No meta-analyses were carried out due to insufficient data.There were no cluster-RCTs identified for inclusion. Comparisons were available for stimulant laxatives versus bulk-forming laxatives, and fibre supplementation versus no intervention. There were no data available for any other comparisons.During the review process we found that studies reported changes in symptoms in different ways. To capture all data available, we added a new primary outcome (improvement in constipation) - this new outcome was not prespecified in our published protocol. Stimulant laxatives versus bulk-forming laxativesNo data were identified for any of this review's prespecified primary outcomes: pain on defecation, frequency of stools and consistency of stools.Compared to bulk-forming laxatives, pregnant women who received stimulant laxatives had significantly more improvement in constipation (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.21 to 2.09; 140 women, one study, moderate quality of evidence), but also significantly more abdominal discomfort (RR 2.33, 95% CI 1.15 to 4.73; 140 women, one study, low quality of evidence), and borderline difference in diarrhoea (RR 4.50, 95% CI 1.01 to 20.09; 140 women, one study, moderate quality of evidence). In addition, there was no significant difference in women's satisfaction (RR 1.06, 95% CI 0.77 to 1.46; 140 women, one study, moderate quality of evidence).No usable data were identified for any of this review's secondary outcomes: quality of life; dehydration; electrolyte imbalance; acute allergic reaction; or asthma. Fibre supplementation versus no interventionPregnant women who received fibre supplementation had significantly higher frequency of stools compared to no intervention (mean difference (MD) 2.24 times per week, 95% CI 0.96 to 3.52; 40 women, one study, moderate quality of evidence). Fibre supplementation was associated with improved stool consistency as defined by trialists (hard stool decreased by 11% to 14%, normal stool increased by 5% to 10%, and loose stool increased by 0% to 6%).No usable data were reported for either the primary outcomes of pain on defecation and improvement in constipation or any of this review's secondary outcomes as listed above. Quality Five outcomes were assessed with the GRADE software: improvement in constipation, frequency of stools, abdominal discomfort, diarrhoea and women's satisfaction. These were assessed to be of moderate quality except for abdominal discomfort which was assessed to be of low quality. The results should therefore be interpreted with caution. There were no data available for evaluation of pain on defecation or consistency of stools. AUTHORS' CONCLUSIONS: There is insufficient evidence to comprehensively assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy, due to limited data (few studies with small sample size and no meta-analyses). Compared with bulk-forming laxatives, stimulant laxatives appear to be more effective in improvement of constipation (moderate quality evidence), but are accompanied by an increase in diarrhoea (moderate quality evidence) and abdominal discomfort (low quality evidence) and no difference in women's satisfaction (moderate quality evidence). Additionally, fibre supplementation may increase frequency of stools compared with no intervention (moderate quality evidence), although these results were of moderate risk of bias.There were no data for a comparison of other types of interventions, such as osmotic laxatives, stool softeners, lubricant laxatives and enemas and suppositories.More RCTs evaluating interventions for treating constipation in pregnancy are needed. These should cover different settings and evaluate the effectiveness of various interventions (including fibre, osmotic, and stimulant laxatives) on improvement in constipation, pain on defecation, frequency of stools and consistency of stools.

Routine ultrasound in late pregnancy (after 24 weeks' gestation).

BACKGROUND: Diagnostic ultrasound is used selectively in late pregnancy where there are specific clinical indications. However, the value of routine late pregnancy ultrasound screening in unselected populations is controversial. The rationale for such screening would be the detection of clinical conditions which place the fetus or mother at high risk, which would not necessarily have been detected by other means such as clinical examination, and for which subsequent management would improve perinatal outcome. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine late pregnancy ultrasound, defined as greater than 24 weeks' gestation, in women with either unselected or low-risk pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All acceptably controlled trials of routine ultrasound in late pregnancy (defined as after 24 weeks). DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Thirteen trials recruiting 34,980 women were included in the systematic review. Risk of bias was low for allocation concealment and selective reporting, unclear for random sequence generation and incomplete outcome data and high for blinding of both outcome assessment and participants and personnel. There was no difference in antenatal, obstetric and neonatal outcome or morbidity in screened versus control groups. Routine late pregnancy ultrasound was not associated with improvements in overall perinatal mortality. There is little information on long-term substantive outcomes such as neurodevelopment. There is a lack of data on maternal psychological effects.Overall, the evidence for the primary outcomes of perinatal mortality, preterm birth less than 37 weeks, induction of labour and caesarean section were assessed to be of moderate or high quality with GRADE software. There was no association between ultrasound in late pregnancy and perinatal mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.67 to 1.54; participants = 30,675; studies = eight; I² = 29%), preterm birth less than 37 weeks (RR 0.96, 95% CI 0.85 to 1.08; participants = 17,151; studies = two; I² = 0%), induction of labour (RR 0.93, 95% CI 0.81 to 1.07; participants = 22,663; studies = six; I² = 78%), or caesarean section (RR 1.03, 95% CI 0.92 to 1.15; participants = 27,461; studies = six; I² = 54%). Three additional primary outcomes chosen for the 'Summary of findings' table were preterm birth less than 34 weeks, maternal psychological effects and neurodevelopment at age two. Because none of the included studies reported these outcomes, they were not assessed for quality with GRADE software. AUTHORS' CONCLUSIONS: Based on existing evidence, routine late pregnancy ultrasound in low-risk or unselected populations does not confer benefit on mother or baby. There was no difference in the primary outcomes of perinatal mortality, preterm birth less than 37 weeks, caesarean section rates, and induction of labour rates if ultrasound in late pregnancy was performed routinely versus not performed routinely. Meanwhile, data were lacking for the other primary outcomes: preterm birth less than 34 weeks, maternal psychological effects, and neurodevelopment at age two, reflecting a paucity of research covering these outcomes. These outcomes may warrant future research.