Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes.

BACKGROUND: Diabetes results in a rise in blood glucose above normal physiological levels; if untreated this may cause damage to many systems including the cardiovascular and renal systems. Pregnancy increases resistance to insulin action; for those women who have pre-gestational diabetes, this results in an increasing insulin requirement. There are several methods of administering insulin. Conventionally, insulin has been administered subcutaneously, formally referred to as intensive conventional treatment, but now more usually referred to as multiple daily injections (MDI). An alternative method of insulin administration is the continuous subcutaneous insulin infusion pump (CSII). OBJECTIVES: To compare CSII with MDI of insulin for pregnant women with pre-existing and gestational diabetes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing CSII with MDI for pregnant women with diabetes. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies and two review authors extracted data. Disagreements were resolved through discussion with the third author. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included five single-centre trials (undertaken in Italy) with 153 women and 154 pregnancies in this review.There were no clear differences in the primary outcomes reported between CSII and MDI in the included trials: caesarean section (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.66 to 1.77; three trials, 71 women, evidence graded very low), large-for-gestational age (RR 4.15, 95% CI 0.49 to 34.95; three trials, 73 infants; evidence graded very low), and perinatal mortality (RR 2.33, 95% CI 0.38 to 14.32; four trials, 83 infants, evidence graded very low). Other primary outcomes were not reported in these trials (hypertensive disorders of pregnancy, development of type 2 diabetes, composite outcome of serious neonatal outcomes, and neurosensory disability).There was no clear evidence of differences in the maternal secondary outcomes: maternal weight gain during pregnancy, 24 hour mean blood glucose in each trimester, mean maternal HbA1c in each trimester, maternal hypoglycaemia, and maternal hyperglycaemia. The included studies did not report several GRADE outcomes: perineal trauma, return to pre-pregnancy weight, postnatal depression, induction of labour. Many maternal secondary outcomes were also not reported.In two trials, including a total of 61 infants, CSII was associated with an increase in mean birthweight compared with MDI (mean difference (MD) 220.56 g, 95% CI -2.09 g to 443.20 g; P = 0.05). However, the large CI including anything from a small reduction to an increase in mean birthweight and the lack of a difference in macrosomia rate (RR 3.20, CI 0.14 to 72.62; two trials, 61 infants) suggests uncertainty. Large-for-gestational age (see above), andsmall-for-gestational age also suggests uncertainty of effect. No significant differences were found in: gestation at delivery, preterm birth < 37 weeks' gestation, preterm birth < 32 weeks' gestation, neonatal hypoglycaemia (evidence graded very low), respiratory distress syndrome, neonatal hyperbilirubinaemia, and fetal anomaly. There were no data reported on many important infant outcomes, including the GRADE outcomes adiposity and diabetes. There was no follow-up of infants in childhood or adulthood, so longer-term outcomes were not reported.The only outcome reported for use of health service resources wasmaternal days hospitalised, which did not show a difference between groups in the small number of women included (MD 9.40, CI -6.04 to 24.84; one trial, 10 women).The methods used by the trials were poorly reported, for example although blinding of participants and clinicians regarding intervention allocation is impossible, it is possible to blind assessors and this along with other aspects of trial methods was not reported, which means that the trials are at an unclear or high risk of bias. We do not know if the women who participated were representative, and therefore if the results can be generalised. Most GRADE outcomes were not reported. For the GRADE outcomes that were reported, our assessment was that the evidence is very low quality (caesarean section, large-for-gestational age, perinatal mortality, andneonatal hypoglycaemia). This was due to design limitations in the included trials, small sample sizes in the trials contributing data, wide CIs crossing both the line of no effect and the line of appreciable benefit and/or harm, and often few events. We are therefore uncertain whether CSII or MDI improves outcomes for pregnant women with diabetes and their infants, and the results of further studies may differ substantially from those presented in this review. AUTHORS' CONCLUSIONS: There is no evidence to support the use of one particular form of insulin administration over another for pregnant women with diabetes. There are only a small number of trials appropriate for meta-analysis, a small number of women included and questionable generalisability of the trial population.Pump technology has progressed since these trials were undertaken. Well-designed randomised trials are required to evaluate comparisons such as patch pumps against MDI and more conventional CSII against MDI. These trials should be adequately powered to assess the effect of interventions, and report the core set of outcomes used in Cochrane reviews of diabetes in pregnancy. Trials to assess the effects of pumps on birthweight and macrosomia rates are needed. It would be beneficial for future trials to undertake longer-term follow-up of participants and their infants, assess women's preferences, and conduct an economic evaluation.

Severe maternal sepsis in the UK, 2011-2012: a national case-control study.

BACKGROUND: In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK. METHODS AND FINDINGS: A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2-5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82-2.51), were primiparous (aOR = 1.60; 95% CI 1.17-2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01-1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11-17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32-4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24-6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65-13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1-7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54-21.45) and infection with group A streptococcus (aOR = 4.84; 2.17-10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h-and for 24 (75%) women, <9 h-between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%). CONCLUSIONS: For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency. Please see later in the article for the Editors' Summary.

Interventions for women in subsequent pregnancies following obstetric anal sphincter injury to reduce the risk of recurrent injury and associated harms.

BACKGROUND: Perineal damage occurs frequently during childbirth, with severe damage involving injury to the anal sphincter reported in up to 18% of vaginal births. Women who have sustained anal sphincter damage are more likely to suffer perineal pain, dyspareunia (painful sexual intercourse), defaecatory dysfunction, and urinary and faecal incontinence compared to those without damage. Interventions in a subsequent pregnancy may be beneficial in reducing the risk of further severe trauma and may reduce the risk of associated morbidities. OBJECTIVES: To examine the effects of Interventions for women in subsequent pregnancies following obstetric anal sphincter injury for improving health. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014). SELECTION CRITERIA: Randomised controlled trials, cluster-randomised trials and multi-arm trials assessing the effects of any intervention in subsequent pregnancies following obstetric anal sphincter injury to improve health. Quasi-randomised controlled trials and cross-over trials were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: No trials were included. In future updates of this review, at least two review authors will extract data and assess the risk of bias of included studies. MAIN RESULTS: No eligible completed trials were identified. One ongoing trial was identified. AUTHORS' CONCLUSIONS: No relevant trials were included. The effectiveness of interventions for women in subsequent pregnancies following obstetric anal sphincter injury for improving health is therefore unknown. Randomised trials to assess the relative effects of interventions are required before clear practice recommendations can be made.

Treatments for gestational diabetes.

BACKGROUND: Gestational diabetes (GDM) affects 3% to 6% of all pregnancies. Women are often intensively managed with increased obstetric monitoring, dietary regulation, and insulin. However, there has been no sound evidence base to support intensive treatment. The key issue for clinicians and consumers is whether treatment of GDM improves perinatal outcome. OBJECTIVES: To compare the effect of alternative treatment policies for GDM on both maternal and infant outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2009) and bibliographies of relevant papers. SELECTION CRITERIA: Randomised controlled trials comparing alternative management strategies for women with GDM and impaired glucose tolerance in pregnancy. DATA COLLECTION AND ANALYSIS: Two authors and a member of the Cochrane Pregnancy and Childbirth Group's editorial team extracted and checked data independently. Disagreements were resolved through discussion with the third author. MAIN RESULTS: Eight randomised controlled trials (1418 women) were included.Caesarean section rate was not significantly different when comparing any specific treatment with routine antenatal care (ANC) including data from five trials with 1255 participants (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.80 to 1.12). However, when comparing oral hypoglycaemics with insulin as treatment for GDM, there was a significant reduction (RR 0.46, 95% CI 0.27 to 0.77, two trials, 90 participants). There was a reduction in the risk of pre-eclampsia with intensive treatment (including dietary advice and insulin) compared to routine ANC (RR 0.65, 95% CI 0.48 to 0.88, one trial, 1000 participants). More women had their labours induced when given specific treatment compared to routine ANC (RR 1.33, 95% CI 1.13 to 1.57, two trials, 1068 participants). The composite outcome of perinatal morbidity (death, shoulder dystocia, bone fracture and nerve palsy) was significantly reduced for those receiving intensive treatment for mild GDM compared to routine ANC (RR 0.32, 95% CI 0.14 to 0.73, one trial, 1030 infants).There was a reduction in the proportion of infants weighing more than 4000 grams (RR 0.46, 95% CI 0.34 to 0.63, one trial, 1030 infants) and the proportion of infants weighing greater than the 90th birth centile (RR 0.55, 95% CI 0.30 to 0.99, three trials, 223 infants) of mothers receiving specific treatment for GDM compared to routine ANC. However, there was no statistically significant difference in this proportion between infants of mothers receiving oral drugs compared to insulin as treatment for GDM. AUTHORS' CONCLUSIONS: Specific treatment including dietary advice and insulin for mild GDM reduces the risk of maternal and perinatal morbidity. However, it is associated with higher risk of labour induction. More research is needed to assess the impact of different types of intensive treatment, including oral drugs and insulin, on individual short- and long-term infant outcomes.

Associations of circulating calcium and 25-hydroxyvitamin D with glucose metabolism in pregnancy: a cross-sectional study in European and South Asian women.

BACKGROUND: Vitamin D deficiency is thought to impair insulin action and glucose metabolism; however, previous studies have not examined ethnic differences or the influence of calcium and parathyroid hormone. We investigated this in a cohort of predominantly white European and south Asian women during pregnancy. METHODS: In this cross-sectional study from an urban population in northern England (53.8°N), 1467 women were recruited when undergoing glucose tolerance testing (75 g oral glucose tolerance test) at 26 weeks' gestation. RESULTS: Gestational diabetes mellitus (GDM) was diagnosed in 137 women (9.3%). Median 25-hydroxyvitamin D concentration for the study population was 9.3 ng/mL (interquartile range 5.2, 16.9) and was higher in European [15.2 ng/mL (10.7, 23.5)] than in south Asian women [5.9 ng/mL (3.9, 9.4), P < .001]. After appropriate adjustment for confounders, 25-hydroxyvitamin D showed a weak inverse association with fasting plasma glucose (FPG; mean difference 1.0% per 1 SD; the ratio of geometric means (RGM) 0.99, 95% confidence interval (CI) 0.98, 1.00), and PTH was weakly associated with FPG (RGM 1.01, 95% CI 1.00, 1.02), but neither was associated with fasting insulin, postchallenge glucose, or GDM. Serum calcium (albumin adjusted) was strongly associated with fasting insulin (RGM 1.06; 95% CI 1.03, 1.08), postchallenge glucose (RGM 1.03, 95% CI 1.01, 1.04), and GDM (odds ratio 1.33, 95% CI 1.06, 1.66) but not with FPG. Associations were similar in European and south Asian women. CONCLUSIONS: These findings do not indicate any important association between vitamin D status and glucose tolerance in pregnancy. Relationships between circulating calcium and glucose metabolism warrant further investigation.

Outcomes of pregnancies in women with pre-existing type 1 or type 2 diabetes, in an ethnically mixed population.

OBJECTIVE: To compare the outcomes of pregnancies in women with pre-existing, type 1 and type 2, diabetes and to examine the influence of ethnicity on these outcomes. DESIGN: Prospective cohort study. SETTING: Large district hospital in Yorkshire with an ethnically mixed population. SAMPLE: Case series of all 202 pregnancies in women with pre-existing diabetes, ending in miscarriage, termination of pregnancy or delivery between January 1994 and December 2002. METHODS: Univariate and multivariate logistic regression analysis comparing outcomes in type of diabetes and in ethnic group. MAIN OUTCOME MEASURES: Fetal loss, perinatal and infant mortality and congenital anomaly. RESULTS: All 14 stillbirths and infant deaths and 13 of the 15 congenital malformations were to Asian women. Analysis within this ethnic group showed a very high rate of adverse birth outcome for type 1 diabetic women and for type 2 diabetic women on insulin before the pregnancy. Total pregnancy loss among type 1 diabetic women was 156 per 1000 and among type 2 diabetic women on insulin was 167 per 1000. Congenital abnormality rates were 156 per 1000 for type 1 diabetic women and 261 per 1000 for type 2 diabetic women on insulin. Asian type 2 diabetic women not on insulin prior to pregnancy had significantly better outcomes: Total pregnancy loss was 123 per 1000 and congenital abnormality rate was 32 per 1000. After adjustment for confounders, including type of diabetes, Asian women had significantly worse outcomes (combined perinatal loss and malformation) than Caucasian women [odds ratio (OR) 4.96, 95% confidence interval (CI) 1.16-21.1]. CONCLUSION: Ethnicity has a significant impact on the outcome of diabetic pregnancies, with worse outcomes for babies born to Asian mothers compared with Caucasian mothers. The use of insulin pre-pregnancy rather than type of diabetes appears to predict adverse outcome.

Amniotic fluid embolism.

PURPOSE OF REVIEW: To review the recent literature on amniotic fluid embolism and how it may influence the clinical management and further study of the condition. Morbidity and mortality from amniotic fluid embolism in the international context will be described, given the recent Confidential Enquiries into Maternal Deaths in the United Kingdom and other studies. With this rare condition we need to look for clues as to how to facilitate diagnosis and improve outcomes. RECENT FINDINGS: Amniotic fluid embolism continues to be a leading cause of maternal death. There has been a decrease in mortality from amniotic fluid embolism in the UK from 5.1 to 3.7 per million maternities, but it is still the fifth greatest cause of direct maternal death. In France, 13% of deaths are caused by amniotic fluid embolism, the third highest cause. In Singapore, a study of postmortems found that over 30% of direct maternal deaths were caused by amniotic fluid embolism, the most common cause. Case-specific mortality may not be as high as previously thought. The early data from the UK Register of cases show only 16% mortality, although there is significant maternal and neonatal morbidity. Early diagnosis may be the best way to improve outcomes. Case reports suggest that plasma exchange techniques may be helpful after initial resuscitation. SUMMARY: With a rare condition additions to the literature are sparse. Early consideration of the diagnosis after prompt resuscitation is needed. Further data are needed to advance beyond this.