Diane Farrar

Measuring placental transfusion for term births: weighing babies with cord intact

Please cite this paper as: Farrar D, Airey R, Law G, Tuffnell D, Cattle B, Duley L. Measuring placental transfusion for term births: weighing babies with cord intact. BJOG 2011;118:70–75.

The importance of postpartum glucose tolerance testing after pregnancies complicated by gestational diabetes

Diabet. Med. 27, 650–654 (2010)

Association between hyperglycaemia and adverse perinatal outcomes in south Asian and white British women: analysis of data from the Born in Bradford cohort

Summary Background Diagnosis of gestational diabetes predicts risk of infants who are large for gestational age (LGA) and with high adiposity, which in turn aims to predict a future risk of obesity in the offspring. South Asian women have higher risk of gestational diabetes, lower risk of LGA, and on average give birth to infants with greater adiposity than do white European women. Whether the same diagnostic criteria for gestational diabetes should apply to both groups of women is unclear. We aimed to assess the association between maternal glucose and adverse perinatal outcomes to ascertain whether thresholds used to diagnose gestational diabetes should differ between south Asian and white British women. We also aimed to assess whether ethnic origin affected prevalence of gestational diabetes irrespective of criteria used. Methods We used data (including results of a 26–28 week gestation oral glucose tolerance test) of women from the Born in Bradford study, a prospective study that recruited women attending the antenatal clinic at the Bradford Royal Infirmary, UK, between 2007 and 2011 and who intended to give birth to their infant in that hospital. We studied the association between fasting and 2 h post-load glucose and three primary outcomes (LGA [defined as birthweight >90th percentile for gestational age], high infant adiposity [sum of skinfolds >90th percentile for gestational age], and caesarean section). We calculated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for a 1 SD increase in fasting and post-load glucose. We established fasting and post-load glucose thresholds that equated to an OR of 1·75 for LGA and high infant adiposity in each group of women to identify ethnic-specific criteria for diagnosis of gestational diabetes. Findings Of 13 773 pregnancies, 3420 were excluded from analyses. Of 10 353 eligible pregnancies, 4088 women were white British, 5408 were south Asian, and 857 were of other ethnic origin. The adjusted ORs of LGA per 1 SD fasting glucose were 1·22 (95% CI 1·08–1·38) in white British women and 1·43 (1·23–1·67) in south Asian women (pinteraction with ethnicity = 0·39). Results for high infant adiposity were 1·35 (1·23–1·49) and 1·35 (1·18–1·54; pinteraction with ethnicity=0·98), and for caesarean section they were 1·06 (0·97–1·16) and 1·11 (1·02–1·20; pinteraction with ethnicity=0·47). Associations between post-load glucose and the three primary outcomes were weaker than for fasting glucose. A fasting glucose concentration of 5·4 mmol/L or a 2 h post-load level of 7·5 mmol/L identified white British women with 75% or higher relative risk of LGA or high infant adiposity; in south Asian women, the cutoffs were 5·2 mmol/L or 7·2 mml/L; in the whole cohort, the cutoffs were 5·3 mmol/L or 7·5 mml/L. The prevalence of gestational diabetes in our cohort ranged from 1·2% to 8·7% in white British women and 4% to 24% in south Asian women using six different criteria. Compared with the application of our whole-cohort criteria, use of our ethnic-specific criteria increased the prevalence of gestational diabetes in south Asian women from 17·4% (95% CI 16·4–18·4) to 24·2% (23·1–25·3). Interpretation Our data support the use of lower fasting and post-load glucose thresholds to diagnose gestational diabetes in south Asian than white British women. They also suggest that diagnostic criteria for gestational diabetes recommended by UK NICE might underestimate the prevalence of gestational diabetes compared with our criteria or those recommended by the International Association of Diabetes and Pregnancy Study Groups and WHO, especially in south Asian women. Funding The National Institute for Health Research.

Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis

Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. Design Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials. Data sources Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts. Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome. Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools. Results 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses. Conclusions This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes. Systematic review registration PROSPERO CRD42013004608

Lipidomic analysis reveals prostanoid profiles in human term pregnant myometrium

Prostanoids modulate the activity of human pregnant myometrium and their functional role can be appreciated through characterisation of prostanoid receptors and tissue concentration of prostanoids. We have applied a lipidomic approach to elucidate the profile of prostanoids in human non-labouring and labouring myometrium. We have identified a total of nineteen prostanoids including prostacyclin, thromboxanes, prostaglandins and dihydro-prostaglandins. Prostacyclin was the predominant prostanoid in both non-labouring and labouring myometria, with PGD(2) and PGF(2alpha) being the second most abundant. Although the total amount of prostanoids was increased in the labouring tissue, PGE(2) and 13,14-dihydro-15-keto-PGE(2) were the only prostanoids to increase significantly at early and late labour (p< or =0.001). Our data suggest that PGF(2alpha) plays an important role in parturition, whilst the increase in PGE(2) could occur to facilitate cervical dilation and relaxation of the lower myometrium during labour. Although the elevation in TXA(2) was less marked than expected, in terms of translation to function even a relatively small increase in the level of this potent spasmogen may have significant effects.

Small-for-gestational age and large-for-gestational age thresholds to predict infants at risk of adverse delivery and neonatal outcomes: are current charts adequate? An observational study from the Born in Bradford cohort

Objectives Construct an ethnic-specific chart and compare the prediction of adverse outcomes using this chart with the clinically recommended UK-WHO and customised birth weight charts using cut-offs for small-for-gestational age (SGA: birth weight <10th centile) and large-for-gestational age (LGA: birth weight >90th centile). Design Prospective cohort study. Setting Born in Bradford (BiB) study, UK. Participants 3980 White British and 4448 Pakistani infants with complete data for gestational age, birth weight, ethnicity, maternal height, weight and parity. Main outcome measures Prevalence of SGA and LGA, using the three charts and indicators of diagnostic utility (sensitivity, specificity and area under the receiver operating characteristic (AUROC)) of these chart-specific cut-offs to predict delivery and neonatal outcomes and a composite outcome. Results In White British and Pakistani infants, the prevalence of SGA and LGA differed depending on the chart used. Increased risk of SGA was observed when using the UK-WHO and customised charts as opposed to the ethnic-specific chart, while the opposite was apparent when classifying LGA infants. However, the predictive utility of all three charts to identify adverse clinical outcomes was poor, with only the prediction of shoulder dystocia achieving an AUROC>0.62 on all three charts. Conclusions Despite being recommended in national clinical guidelines, the UK-WHO and customised birth weight charts perform poorly at identifying infants at risk of adverse neonatal outcomes. Being small or large may increase the risk of an adverse outcome; however, size alone is not sensitive or specific enough with current detection to be useful. However, a significant amount of missing data for some of the outcomes may have limited the power needed to determine true associations.

A comparison of South Asian specific and established BMI thresholds for determining obesity prevalence in pregnancy and predicting pregnancy complications: findings from the Born in Bradford cohort

Objective:To describe how maternal obesity prevalence varies by established international and South Asian specific body mass index (BMI) cut-offs in women of Pakistani origin and investigate whether different BMI thresholds can help to identify women at risk of adverse pregnancy and birth outcomes.Design:Prospective bi-ethnic birth cohort study (the Born in Bradford (BiB) cohort).Setting:Bradford, a deprived city in the North of the UK.Participants:A total of 8478 South Asian and White British pregnant women participated in the BiB cohort study.Main outcome measures:Maternal obesity prevalence; prevalence of known obesity-related adverse pregnancy outcomes: mode of birth, hypertensive disorders of pregnancy (HDP), gestational diabetes, macrosomia and pre-term births.Results:Application of South Asian BMI cut-offs increased prevalence of obesity in Pakistani women from 18.8 (95% confidence interval (CI) 17.6–19.9) to 30.9% (95% CI 29.5–32.2). With the exception of pre-term births, there was a positive linear relationship between BMI and prevalence of adverse pregnancy and birth outcomes, across almost the whole BMI distribution. Risk of gestational diabetes and HDP increased more sharply in Pakistani women after a BMI threshold of at least 30 kg m−2, but there was no evidence of a sharp increase in any risk factors at the new, lower thresholds suggested for use in South Asian women. BMI was a good single predictor of outcomes (area under the receiver operating curve: 0.596–0.685 for different outcomes); prediction was more discriminatory and accurate with BMI as a continuous variable than as a binary variable for any possible cut-off point.Conclusion:Applying the new South Asian threshold to pregnant women would markedly increase those who were referred for monitoring and lifestyle advice. However, our results suggest that lowering the BMI threshold in South Asian women would not improve the predictive ability for identifying those who were at risk of adverse pregnancy outcomes.

Assessment of cognitive function across pregnancy using CANTAB: A longitudinal study

Significant changes in endogenous plasma hormone levels are required to sustain pregnancy which provides a unique opportunity to study their effect on cognitive function. Four carefully selected tests from the Cambridge Neuropsychological Automated Test Battery (CANTAB) were administered to assess the cognitive function of a group of 23 women during each trimester of pregnancy and at three months following birth. Test scores were compared with a control group of 24 non-pregnant women. The Edinburgh Postnatal Depression Scale was administered to assess anxiety and risk of depression. The National Adult Reading Test (NART) was used as a measure of verbal intelligence. Plasma hormone levels were measured at each time-point. The pregnant group scored significantly lower than the control group on the Spatial Recognition Memory (SRM) test at the second trimester and postpartum assessments (p⩽0.004). A significant pregnant group-time interaction (p=0.005) for SRM performance was demonstrated. Compared to their first trimester assessment, the pregnant group scored on average 11.7% less on each subsequent SRM test. The pregnant group reported more symptoms of anxiety and depression compared to the control group (EPDS-4 point increase in mean score at each assessment, p=0.002). There were no plasma hormone levels and test score associations identified. These data suggest SRM performance is adversely affected by pregnancy. Other aspects of executive function seem to be unaffected. Although the pregnant group reported more symptoms of anxiety and depression compared to the control group, analysis indicates that this confounder is not responsible for the SRM differences.

Treatments for gestational diabetes: a systematic review and meta-analysis

Objective To investigate the effectiveness of different treatments for gestational diabetes mellitus (GDM). Design Systematic review, meta-analysis and network meta-analysis. Methods Data sources were searched up to July 2016 and included MEDLINE and Embase. Randomised trials comparing treatments for GDM (packages of care (dietary and lifestyle interventions with pharmacological treatments as required), insulin, metformin, glibenclamide (glyburide)) were selected by two authors and double checked for accuracy. Outcomes included large for gestational age, shoulder dystocia, neonatal hypoglycaemia, caesarean section and pre-eclampsia. We pooled data using random-effects meta-analyses and used Bayesian network meta-analysis to compare pharmacological treatments (ie, including treatments not directly compared within a trial). Results Forty-two trials were included, the reporting of which was generally poor with unclear or high risk of bias. Packages of care varied in their composition and reduced the risk of most adverse perinatal outcomes compared with routine care (eg, large for gestational age: relative risk0.58 (95% CI 0.49 to 0.68; I2=0%; trials 8; participants 3462). Network meta-analyses suggest that metformin had the highest probability of being the most effective treatment in reducing the risk of most outcomes compared with insulin or glibenclamide. Conclusions Evidence shows that packages of care are effective in reducing the risk of most adverse perinatal outcomes. However, trials often include few women, are poorly reported with unclear or high risk of bias and report few outcomes. The contribution of each treatment within the packages of care remains unclear. Large well-designed and well-conducted trials are urgently needed. Trial registration number PROSPERO CRD42013004608.

Hyperglycemia in pregnancy: prevalence, impact, and management challenges

Gestational diabetes mellitus (GDM) is one of the most common medical conditions in pregnancy, and the prevalence is growing with increasing rates of women of advanced age becoming pregnant and the increasing prevalence of maternal obesity and inactivity. GDM is associated with an increased risk of maternal and infant short- and long-term ill-health. There is a positive linear association between increasing maternal glucose at oral glucose tolerance testing and risk of important perinatal outcomes, including cesarean section, large for gestational age, and infant adiposity. A “step-up” approach, where diet and lifestyle information is provided followed by pharmacological interventions as required to control and reduce hyperglycemia, is effective at reducing the risk of macrosomia, but treatment of GDM will increase demand on health services. There is limited evidence to suggest which identification strategy is best or what thresholds should be used to diagnose GDM or what the effects of different diagnostic strategies have on short- or long-term maternal and offspring outcomes. Trials of interventions in pregnancy aimed at preventing GDM have not demonstrated a benefit; therefore, trials are needed to evaluate interventions aimed at optimizing the health of all women of childbearing age, outside of pregnancy. A consistent, evidence-based, sustained approach to supporting women to live healthily, including the achievement of a normal body mass index before and after pregnancy, is urgently needed.