Breastfeeding behaviours in women with obesity; associations with weight retention and the serum metabolome: a secondary analysis of UPBEAT.

BACKGROUND/OBJECTIVES: Maternal obesity is associated with a decreased intention and initiation of breastfeeding as well as a shortened duration of breastfeeding. This analysis was undertaken to identify breastfeeding behaviours, and relationships with maternal anthropometry and the serum metabolome at 6-months postpartum in an ethnically diverse cohort of women with obesity. SUBJECTS/METHODS: A cohort analysis of 715 women from the UK Pregnancies Better Eating and Activity Trial (UPBEAT); a multi-centre randomised controlled trial of an antenatal lifestyle intervention in women with obesity. Maternal data were collected in early pregnancy and included body mass index (BMI), socio-demographic characteristics and anthropometry. At 6-months postpartum, breastfeeding behaviours, anthropometry and 158 maternal metabolic measures from blood samples were recorded. Kaplan-Meier curves of breastfeeding duration were constructed and were stratified by obesity class (I: BMI 30.0-34.9 kg/m2, II: 35.0-39.9 kg/m2, III: ≥40.0 kg/m2). Relationships between breastfeeding behaviours, socio-demographic characteristics, the metabolome, and anthropometry were determined using regression analyses. RESULTS: Eighty-two percent (591/715) of the cohort-initiated breastfeeding and at the 6-month follow-up 40% (283/715) were breastfeeding exclusively or partially. Duration of exclusive breastfeeding decreased with increasing BMI: Compared to BMI class I (mean 90.4 ± 64 days) the difference in mean for classes II and III were -15.8 days (95% confidence interval: -28.5, -3.1, p < 0.05) and -16.7 (95% CI: -32.0 to -1.35, p < 0.05), respectively. Compared to no breastfeeding, any breastfeeding at 6-months postpartum was associated with improvements in metabolites towards a healthier profile, reduced weight retention by -1.81 kg (95% CI -0.75, -2.88, p < 0.05 ) and reduced anthropometric measures, including mid-upper arm and hip circumferences. The breastfeeding related changes in anthropometry were not evident in women of Black ethnicity. CONCLUSIONS: Greater emphasis on enabling breastfeeding for women with obesity could improve duration, women's weight management and metabolic health. The lack of breastfeeding related anthropometric effects in Black women requires further investigation. CLINICAL TRIAL REGISTRY: ISRCTN reference 89971375.

Women's preconception health in England: a report card based on cross-sectional analysis of national maternity services data from 2018/2019.

OBJECTIVE: To present the first national-level report card on the state of women's preconception health in England. DESIGN: Cross-sectional population-based study. SETTING: Maternity services, England. POPULATION: All pregnant women in England with a first antenatal (booking) appointment recorded in the national Maternity Services Dataset (MSDS) from April 2018 to March 2019 (n = 652 880). METHODS: We analysed the prevalence of 32 preconception indicator measures in the overall population and across socio-demographic subgroups. Ten of these indicators were prioritised for ongoing surveillance based on modifiability, prevalence, data quality and ranking by multidisciplinary UK experts. RESULTS: The three most prevalent indicators were the proportion of the 22.9% of women who smoked 1 year before pregnancy who did not quit smoking before pregnancy (85.0%), those who had not taken folic acid supplementation before pregnancy (72.7%) and previous pregnancy loss (38.9%). Inequalities were observed by age, ethnicity and area-based deprivation level. The ten indicators prioritised were not taking folic acid supplementation before pregnancy, obesity, complex social factors, living in the most deprived areas, smoking around the time of conception, overweight, pre-existing mental health condition, pre-existing physical health condition, previous pregnancy loss and previous obstetric complication. CONCLUSIONS: Our findings suggest important opportunities to improve the state of preconception health and reduce socio-demographic inequalities for women in England. In addition to MSDS data, other national data sources that record further and possibly better quality indicators could be explored and linked to build a comprehensive surveillance infrastructure.

Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT.

BACKGROUND/OBJECTIVES: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. SUBJECTS/METHODS: Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. RESULTS: Compared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS -0.03 cm (-0.05 to -0.008); PW -0.03 cm (-0.05 to -0.01); RWT -0.02 cm (-0.04 to -0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. CONCLUSIONS: Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375.

Midwifery continuity of care versus standard maternity care for women at increased risk of preterm birth: A hybrid implementation-effectiveness, randomised controlled pilot trial in the UK.

BACKGROUND: Midwifery continuity of care is the only health system intervention shown to reduce preterm birth (PTB) and improve perinatal survival, but no trial evidence exists for women with identified risk factors for PTB. We aimed to assess feasibility, fidelity, and clinical outcomes of a model of midwifery continuity of care linked with a specialist obstetric clinic for women considered at increased risk for PTB. METHODS AND FINDINGS: We conducted a hybrid implementation-effectiveness, randomised, controlled, unblinded, parallel-group pilot trial at an inner-city maternity service in London (UK), in which pregnant women identified at increased risk of PTB were randomly assigned (1:1) to either midwifery continuity of antenatal, intrapartum, and postnatal care (Pilot study Of midwifery Practice in Preterm birth Including women's Experiences [POPPIE] group) or standard care group (maternity care by different midwives working in designated clinical areas). Pregnant women attending for antenatal care at less than 24 weeks' gestation were eligible if they fulfilled one or more of the following criteria: previous cervical surgery, cerclage, premature rupture of membranes, PTB, or late miscarriage; previous short cervix or short cervix this pregnancy; or uterine abnormality and/or current smoker of tobacco. Feasibility outcomes included eligibility, recruitment and attrition rates, and fidelity of the model. The primary outcome was a composite of appropriate and timely interventions for the prevention and/or management of preterm labour and birth. We analysed by intention to treat. Between 9 May 2017 and 30 September 2018, 334 women were recruited; 169 women were allocated to the POPPIE group and 165 to the standard group. Mean maternal age was 31 years; 32% of the women were from Black, Asian, and ethnic minority groups; 70% were in employment; and 46% had a university degree. Nearly 70% of women lived in areas of social deprivation. More than a quarter of women had at least one pre-existing medical condition and multiple risk factors for PTB. More than 75% of antenatal and postnatal visits were provided by a named/partner midwife, and a midwife from the POPPIE team was present at 80% of births. The incidence of the primary composite outcome showed no statistically significant difference between groups (POPPIE group 83.3% versus standard group 84.7%; risk ratio 0.98 [95% confidence interval (CI) 0.90 to 1.08]; p = 0.742). Infants in the POPPIE group were significantly more likely to have skin-to-skin contact after birth, to have it for a longer time, and to breastfeed immediately after birth and at hospital discharge. There were no differences in other secondary outcomes. The number of serious adverse events was similar in both groups and unrelated to the intervention (POPPIE group 6 versus standard group 5). Limitations of this study included the limited power and the nonmasking of group allocation; however, study assignment was masked to the statistician and researchers who analysed the data. CONCLUSIONS: In this study, we found that it is feasible to set up and achieve fidelity of a model of midwifery continuity of care linked with specialist obstetric care for women at increased risk of PTB in an inner-city maternity service in London (UK), but there is no impact on most outcomes for this population group. Larger appropriately powered trials are needed, including in other settings, to evaluate the impact of relational continuity and hypothesised mechanisms of effect based on increased trust and engagement, improved care coordination, and earlier referral on disadvantaged communities, including women with complex social factors and social vulnerability. TRIAL REGISTRATION: We prospectively registered the pilot trial on the UK Clinical Research Network Portfolio Database (ID number: 31951, 24 April 2017). We registered the trial on the International Standard Randomised Controlled Trial Number (ISRCTN) (Number: 37733900, 21 August 2017) and before trial recruitment was completed (30 September 2018) when informed that prospective registration for a pilot trial was also required in a primary clinical trial registry recognised by WHO and the International Committee of Medical Journal Editors (ICMJE). The protocol as registered and published has remained unchanged, and the analysis conforms to the original plan.

Longitudinal phenotyping of maternal antenatal depression in obese pregnant women supports multiple-hit hypothesis for fetal brain development, a secondary analysis of the UPBEAT study.

Background: Maternal antenatal depression is associated with offspring psychological disorders, but obesity is also widely implicated in maternal depression and neurodevelopment. In pregnant women with obesity we explored interrelationships between antenatal depressive symptom trajectories and multiple exposures implicated in fetal neurodevelopment which could explain these associations, as a prelude to exploring associations with infant mental health. Methods: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) recruited multi-ethnic pregnant women with obesity (BMI >= 30kg/m2) between March 2009 and June 2014 from 8 UK sites and 1369 were included to model longitudinal antenatal depressive symptoms from Edinburgh Postnatal Depression Scale (EPDS) scores using Latent Class Growth Analysis. Classes were compared on maternal baseline demography, biomarkers of metabolism, inflammation and placental function, infection, diet and by pregnancy and birth outcomes. Odds ratios, mean differences and 95% Confidence Intervals were calculated using robust auxiliary modelling techniques. Findings: The chosen model produced four classes: "Not Depressed" (n=575 [42%], "reference"), "Mild" (n=523 [37·5%]), "Moderate" (n=219 [16%]) and "Severe" (n=62 [4·5%]) symptom trajectories. Socio-economic deprivation and ethnic diversity were greater in Severe and Moderate classes. Dietary glycaemic load and saturated fat intake were higher in Severe and Moderate classes (at 17 and 27 weeks). Higher Interleukin-6, glycoprotein acetyls (17 weeks), glucose (34 weeks) and lower placental growth factor (PlGF, 17 and 27 weeks) was found in the Severe class. PlGF was lower in the Moderate class (27 weeks). Infection was least likely in the Not Depressed class across gestation. Risks of preterm birth were associated with Severe depressive symptoms (aOR 3·05[1·11 to 8·36]). Interpretation: Comprehensive phenotyping exposes important fetal exposures implicated in adverse neurodevelopment, differing by depression class. This study expands substantially on causal models of suboptimal fetal neurodevelopment and offers potential new targets for intervention in obese pregnant women. Funding: JNS was funded by a PhD studentship from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. UPBEAT was supported by the European Union's 7th Framework Programme (FP7/2007-2013), project EarlyNutrition; grant agreement no. 289346 and the National Institute for Health Research (NIHR) (UK) Programme Grants for Applied Research Programme (RP-0407-10452), Medical Research Council UK Project Grant (MR/L002477/1). Support was also provided by the Chief Scientist Office Scotland, Guy's and St Thomas' Charity and Tommy's Charity (Registered charity no. 1060508). LP and SLW are funded by Tommy's Charity.

A multi-centered trial investigating gestational treatment with ursodeoxycholic acid compared to metformin to reduce effects of diabetes mellitus (GUARD): a randomized controlled trial protocol.

BACKGROUND: Each year in the UK, approximately 35,000 women develop gestational diabetes mellitus (GDM). The condition increases the risk of obstetric and neonatal complications for mother and child, including preeclampsia, preterm birth, and large for gestational age babies. Biochemical consequences include maternal hyperglycemia, neonatal hypoglycemia, and dyslipidemia. Metformin is the most commonly used firstline pharmacological treatment. However, there are concerns about its widespread use during pregnancy, due to its limited efficacy and potential safety concerns. Therefore, there is a need for additional therapies that improve both maternal-fetal glucose and lipid metabolism. Ursodeoxycholic acid (UDCA) is not currently used for treatment for GDM. However, it can improve glucose control in type 2 diabetes, and it improves fetal lipid profiles in gestational cholestasis. Consequentially, it is hypothesized that treatment with UDCA for women with GDM may improve both maternal metabolism and neonatal outcomes. The primary outcome of this trial is to assess the efficacy of UDCA compared with metformin to improve glucose levels in women with GDM. METHODS: The trial is a two-armed, open-label, multi-center, randomized controlled trial. Women are eligible if they have been diagnosed with GDM by an oral glucose tolerance test between 24 + 0 and 30 + 6 weeks' gestation, and if they require pharmacological intervention. In total, 158 pregnant women will be recruited across seven NHS Trusts in England and Wales. Women who consent will be recruited and randomized to either metformin or UDCA, which will be taken daily until the birth of their baby. Maternal and neonatal blood samples will be taken to evaluate the impact of the treatments on maternal glucose control, and maternal and neonatal lipid metabolism. Maternal and fetal outcomes will be evaluated, and acceptability of UDCA compared with metformin will be assessed. DISCUSSION: This trial has the potential to identify a potential new treatment for women with GDM. If successful, a future large multi-center trial will be designed to investigate where decisions can be personalized to identify which women will respond more effectively to UDCA than alternatives to improve maternal and baby outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04407650.

Impact of maternal obesity on neonatal heart rate and cardiac size.

BACKGROUND: Maternal obesity may increase offspring risk of cardiovascular disease. We assessed the impact of maternal obesity on cardiac structure and function in newborns as a marker of fetal cardiac growth. METHODS: Neonates born to mothers of healthy weight (body mass index (BMI) 20-25 kg/m2, n=56) and to mothers who were obese (BMI ≥30 kg/m2, n=31) underwent 25-minute continuous ECG recording and non-sedated, free-breathing cardiac MRI within 72 hours of birth. RESULTS: Mean (SD) heart rate during sleep was higher in infants born to mothers who were versus were not obese (123 (12.6) vs 114 (9.8) beats/min, p=0.002). Heart rate variability during sleep was lower in infants born to mothers who were versus were not obese (SD of normal-to-normal R-R interval 34.6 (16.8) vs 43.9 (16.5) ms, p=0.05). Similar heart rate changes were seen during wakefulness. Left ventricular end-diastolic volume (2.35 (0.14) vs 2.54 (0.29) mL/kg, p=0.03) and stroke volume (1.50 (0.09) vs 1.60 (0.14), p=0.04) were decreased in infants born to mothers who were versus were not obese. There were no differences in left ventricular end-systolic volume, ejection fraction, output or myocardial mass between the groups. CONCLUSION: Maternal obesity was associated with increased heart rate, decreased heart rate variability and decreased left ventricular volumes in newborns. If persistent, these changes may provide a causal mechanism for the increased cardiovascular risk in adult offspring of mothers with obesity. In turn, modifying antenatal and perinatal maternal health may have the potential to optimise long-term cardiovascular health in offspring.

"It's like a bus, going downhill, without a driver": A qualitative study of how postpartum haemorrhage is experienced by women, their birth partners, and healthcare professionals.

PROBLEM: Postpartum haemorrhage [PPH] remains a major cause of maternal morbidity and mortality. Whilst low-resource settings bear the greatest burden of deaths, women live with associated morbidities in all healthcare settings. Limited data exists regarding the experience for women, their partners, or healthcare professionals [HCPs], affected by PPH. AIM: To qualitatively investigate the experience of PPH, for women (n=9), birth partners (n=4), and HCPs (n=9) in an inner-city tertiary referral centre. To provide multi-faceted insight into PPH and improve understanding and future care practices. METHODS: Participants were interviewed about their experiences within two weeks of a PPH. Data were analysed using thematic analysis. FINDINGS: Four distinct, but related, themes were identified: 'Knowledge specific to PPH'; 'Effective and appropriate responses to PPH'; 'Communication of risk factors'; and 'Quantifying blood loss'; which collected around a central organising concept of 'Explaining the indescribable'. DISCUSSION: PPH was viewed as a 'crisis-style emergency', generating respectful fear in HCPs, whilst women and partners had little-to-no prior knowledge. Specific PPH knowledge dictated HCPs' response and risk communication. PPH risks were typically linked to quantification of blood loss, assessment of which varied with acknowledged questionable accuracy. Women's and partners' confidence in HCPs' ability to deal with PPH was unquestionable. Non-verbal communication was highlighted, with HCP body language betraying professional confidence. CONCLUSION: Information about blood loss during childbirth must be imparted in a sensitive, timely manner. Whilst training for HCPs results in effective PPH management, consideration should be given to their non-verbal cues and the impact of dealing with this stressful, 'everyday emergency'.

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.

Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): study protocol for a randomised controlled feasibility trial.

BACKGROUND: Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD during pregnancy. Serial prophylactic exchange blood transfusion (SPEBT) has been shown to be effective in treating SCD outside pregnancy, but evidence is lacking regarding its use during pregnancy. The aim of this study is to assess the feasibility and acceptability of conducting a future phase 3 randomised controlled trial (RCT) to establish the clinical and cost effectiveness of SPEBT in pregnant women with SCD. METHODS: The study is an individually randomised, two-arm, feasibility trial with embedded qualitative and health economic studies. Fifty women, 18 years of age and older, with SCD and a singleton pregnancy at ≤ 18 weeks' gestation will be recruited from six hospitals in England. Randomisation will be conducted using a secure online database and minimised by centre, SCD genotype and maternal age. Women allocated to the intervention arm will receive SPEBT commencing at ≤ 18 weeks' gestation, performed using automated erythrocytapheresis every 6-10 weeks until the end of pregnancy, aiming to maintain HbS% or combined HbS/HbC% below 30%. Women in the standard care arm will only receive transfusion when clinically indicated. The primary outcome will be the recruitment rate. Additional endpoints include reasons for refusal to participate, attrition rate, protocol adherence, and maternal and neonatal outcomes. Women will be monitored throughout pregnancy to assess maternal, sickle, and foetal complications. Detailed information about adverse events (including hospital admission) and birth outcomes will be extracted from medical records and via interview at 6 weeks postpartum. An embedded qualitative study will consist of interviews with (a) 15-25 trial participants to assess experiences and acceptability, (b) 5-15 women who decline to participate to identify barriers to recruitment and (c) 15-20 clinical staff to explore fidelity and acceptability. A health economic study will inform a future cost effectiveness and cost-utility analysis. DISCUSSION: This feasibility study aims to rigorously evaluate SPEBT as a treatment for SCD in pregnancy and its impact on maternal and infant outcomes. TRIAL REGISTRATION: NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19).