Adiposity and cardiovascular outcomes in three-year-old children of participants in UPBEAT, an RCT of a complex intervention in pregnant women with obesity.

BACKGROUND: Maternal obesity is associated with offspring cardiometabolic risk. UPBEAT was a randomised controlled trial of an antenatal diet and physical activity intervention in 1555 women with obesity. The intervention was associated with lower gestational weight gain, healthier diet and metabolic profile in pregnancy, and reduced infant adiposity at six months. OBJECTIVE: We have investigated whether the UPBEAT intervention influenced childhood cardiometabolic outcomes or was associated with sustained improvements in maternal lifestyle 3-years after delivery. METHODS: In UPBEAT mother-child dyads at the 3-year follow-up, we assessed childhood blood pressure, resting pulse rate, and adiposity (body mass index, skinfold thicknesses, body fat, waist and arm circumferences) and maternal diet, physical activity, and anthropometry. RESULTS: 514 three-year-old children attended the appointment (49% intervention, 51% standard care). There was no difference in the main outcome of interest, subscapular skinfold thickness, between the trial arms (-0.30 mm, 95% confidence interval: -0.92, 0.31). However, the intervention was associated with a lower resting pulse rate (-5 bpm [-8.41, -1.07]). There was also a non-significant lower odds of overweight/obesity (OR 0.73; 0.50, 1.08). Maternal dietary improvements observed in the UPBEAT trial, including glycaemic load and saturated fat were maintained 3-years postpartum. CONCLUSION: This study has demonstrated that an antenatal dietary and physical activity intervention in women with obesity is associated with lower offspring pulse rate and sustained improvement in maternal diet. Whilst larger than previous cohorts, there remains potential for bias from attrition and these findings require validation in future cohorts.

Persistent inaccuracies in completion of medical certificates of stillbirth: A cross-sectional study.

BACKGROUND: The UK Medical Certificate of Stillbirth (MCS) records information relevant to the cause of stillbirth of infants ≥24 weeks' gestation. A cross-sectional audit demonstrated widespread inaccuracies in MCS completion in 2009 in North West England. A repeat study was conducted to assess whether practice had improved following introduction of a regional care pathway. METHODS: 266 MCS issued in 14 North West England obstetric units during 2015 were studied retrospectively. Cause of death was assigned following review of information available at the time of MCS completion. This was compared to that documented on the MCS, and to data from 2009. RESULTS: Twenty-three certificates were excluded (20 inadequate data, 3 late miscarriages). 118/243 (49%) MCS contained major errors. Agreement between the MCS and adjudicated cause of stillbirth was fair (Kappa 0.31; 95% CI 0.24, 0.38) and unchanged from 2009 (0.29). In 2015, excluding 34 terminations of pregnancy, the proportion of MCSs documenting "unexplained" stillbirths (113/211; 54%) was reduced compared to 2009 (158/213; 74%); causality could be assigned after case note review in 78% cases. Recognition of fetal growth restriction (FGR) as a cause of stillbirth improved (2015: 30/211; 14% vs 2009: 1/213; 0.5%), although 71% cases were missed. 47% MCSs following termination of pregnancy documented an iatrogenic primary cause of death. CONCLUSIONS: Completion of MCSs remains inaccurate, particularly in recognition of FGR as a cause of stillbirth. Detailed case note review before issuing the MCS could dramatically improve the usefulness of included information; evaluation of practitioner education programmes/internal feedback systems are recommended.

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. FUNDING: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

Evaluation of the quality of guidelines for the management of reduced fetal movements in UK maternity units.

BACKGROUND: The development of evidence-based guidelines is a key step in ensuring that maternity care is of a universally high standard. To influence patient care national and international guidelines need to be interpreted and implemented locally. In 2011, the Royal College of Obstetricians and Gynaecologists published guidelines for the management of reduced fetal movements (RFM), which can be an important symptom of fetal compromise. Following dissemination it was anticipated that this guidance would be implemented in UK maternity units. This study aimed to assess the quality of local guidelines for the management of RFM in comparison to published national standards. METHODS: Cross-sectional survey of maternity unit guidelines for RFM. The guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Tool and scored by two independent investigators. Two national guidelines were used as standards to evaluate unit guidelines. RESULTS: Responses were received from 98 units (42%); 12 units had no guideline. National guidelines scored highly using the AGREE II tool but there was wide variation in the quality of individual maternity unit guidelines, which were frequently of low quality. No guidelines incorporated all the recommendations from the national guideline. Maternity unit guidelines performed well for clarity and presentation but had low scores for stakeholder involvement, rigour of development and applicability. CONCLUSIONS: In contrast to national evidence based guidance the quality of maternity unit guidelines for RFM is variable and frequently of low quality. To increase quality, guidelines need to include up to date evidence and audit standards which could be taken directly from national evidence-based guidance. Barriers to local implementation and resource implications need to be taken into consideration. Training may also improve the implementation of the guideline. Research is needed to inform strategies to realize the benefits of clinical guidance in practice.

The feasibility phase of a community antenatal lifestyle programme [The Lifestyle Course (TLC)] for women with a body mass index (BMI)≥ 30 kg/m(2.).

INTRODUCTION: maternal obesity [body mass index (BMI)≥30kg/m(2)] is a cause for concern because of increasing rates and risk of associated complications. However, little is known about how to improve the health of women with a BMI≥30kg/m(2). OBJECTIVE AND METHODS: a 10-week antenatal lifestyle programme (The Lifestyle Course - TLC), underpinned by behaviour change theory, was developed in a programme of research which included a prospective, multicentred, feasibility phase (n=227). Participants had a BMI≥30kg/m(2) at the start of their pregnancy, planned to deliver in two areas of Greater Manchester and were aged 18 or over. The objectives were to (1) assess the feasibility of the intervention and (2) to pilot the trial processes and outcome measures. FINDINGS: (1) Trial intervention: only 22% of women in the feasibility phase had received gestational weight advice prior to the study. One or more TLC sessions were attended by 79% of women and 97% said they would recommend TLC to a friend due to the content suitability, perceived personal gains and extra care received. Changes to the TLC were suggested and implemented in the pilot phase. (2) Trial processes: recruitment rates (36%), retention rates (100%) and questionnaire completion rates up to one year (33%) were found. Daily general 'lifestyle' diaries and pedometers were not acceptable data collection tools (response rates of 32% and 16% respectively). However, specific food diaries were acceptable (response rates of 80-81%). The major challenge was the collection of maternal weight data at the follow-up points. CONCLUSIONS AND IMPLICATIONS: the antenatal intervention (TLC) designed for this programme of work appears to suit the needs of women with a BMI≥30kg/m(2). The need for an antenatal intervention is clear from this study and also highlights reflections on effective communication with pregnant women with a BMI≥30kg/m(2). Lessons learnt for designing a future trial include effective ways to communicate with pregnant women with a BMI≥30kg/m(2). TRIAL REGISTRATION: ISRCTN29860479.

A randomised controlled trial comparing standard or intensive management of reduced fetal movements after 36 weeks gestation--a feasibility study.

BACKGROUND: Women presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10th centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit. METHODS: Women with RFM ≥36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires. RESULTS: 137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study. CONCLUSION: An RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid. TRIAL REGISTRATION: ISRCTN07944306.

Do medical certificates of stillbirth provide accurate and useful information regarding the cause of death?

Stillbirth affects one in 200 pregnancies in the UK. Understanding the causes of stillbirth is essential to reducing perinatal mortality. Stillbirth certificates represent a potential source of data on perinatal mortality. We aimed to assess whether the information on stillbirth certificates used in the UK is accurate. A retrospective cross-sectional audit of stillbirth certificates issued in a geographical region of the UK in 2009 was undertaken. Data were recorded from the stillbirth certificate and health records. The cause of death was classified using the ReCoDe system. Two hundred and thirteen stillbirth certificates were issued for stillbirths (feticides for fetal anomaly were excluded). Agreement for the primary factor associated with the stillbirth was fair (Kappa = 0.286). This contrasts with the gestation of stillbirth, which was almost complete agreement (Kappa = 0.883). The majority of stillbirths (58.7%) were classified on the certificate as 'unknown cause'. A proportion of 9.4% of stillbirths were classified as congenital anomaly and 8.0% as placental abruption. Only 0.5% of stillbirth certificates cited fetal growth restriction as a relevant condition contributing to death. A total of 49.6% of 'unexplained' stillbirths were associated with fetal growth restriction on review. Errors were present in 77.9% of certificates, including missing co-morbidities (55.9%) and the wrong cause of death (40.4%). The cause(s) of death is (are) not recorded accurately on the UK medical certificate of stillbirth, and the majority of certificates contain one or more errors. Training is required to improve understanding of the causes of stillbirth and completion of medical certificates. Data recorded directly from medical certificate of stillbirths are not sufficiently reliable for descriptive studies of causation and epidemiology.

Regulation of fibroblast growth factor-2 activity by human ovarian cancer tumor endothelium.

Fibroblast growth factor-2 (FGF-2) is a potent angiogenic cytokine that is dependent on heparan sulfate for its biological activity. We have investigated the relationship among heparan sulfate, FGF-2, and the signal-transducing receptors in human, advanced-stage, serous ovarian adenocarcinoma. Using a unique molecular probe, FR1c-Ap, which consisted of a soluble FGF receptor 1 isoform IIIc covalently linked to an alkaline phosphatase moiety, the distribution of heparan sulfate that had the ability to support the formation of a heparan sulfate/FGF-2/FGFR1 isoform IIIc alkaline phosphatase heparan sulfate construct complex was determined. This may be taken as a surrogate marker for the distribution of biologically active heparan sulfate and was distributed predominantly in endothelial cells and stroma but was absent from adenocarcinoma cells. In situ hybridization revealed the expression of FGFR1 mRNA in the endothelium and reverse transcription-PCR confirmed the presence of FGFR1 isoform IIIc but not isoform IIIb. The presence of FGF-2 around tumor endothelium was detected through immunohistochemistry. Double-staining techniques showed that heparan sulfate was found predominantly at the basal aspect of the endothelium and suggested that syndecan-3 might function as one of the proteoglycans involved in FGF-2 signaling in the endothelium. The data suggest that the entire extracellular signaling apparatus, consisting of FGF-2, biologically active heparan sulfate, and FGFRs capable of responding to FGF-2, is present in ovarian cancer endothelium, thereby highlighting the cytokine and its cognate receptor as potential targets for the antiangiogenic treatment of this disease.