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.

Differences in Factors Associated With Preterm and Term Stillbirth: A Secondary Cohort Analysis of the DESiGN Trial.

OBJECTIVE: To identify whether maternal and pregnancy characteristics associated with stillbirth differ between preterm and term stillbirth. DESIGN: Secondary cohort analysis of the DESiGN RCT. SETTING: Thirteen UK maternity units. POPULATION: Singleton pregnant women and their babies. METHODS: Multiple logistic regression was used to assess whether the 12 factors explored were associated with stillbirth. Interaction tests assessed for a difference in these associations between the preterm and term periods. MAIN OUTCOME MEASURE: Stillbirth stratified by preterm (<37+0 weeks') and term (37+0-42+6 weeks') births. RESULTS: A total of 195 344 pregnancies were included. Six hundred and sixty-seven were stillborn (3.4 per 1000 births), of which 431 (65%) were preterm. Significant interactions were observed for maternal age, ethnicity, IMD, BMI, parity, smoking, PAPP-A, gestational hypertension, pre-eclampsia and gestational diabetes but not for chronic hypertension and pre-existing diabetes. Stronger associations with term stillbirth were observed in women with obesity compared to BMI 18.5-24.9 kg/m2 (BMI 30.0-34.9 kg/m2 term adjusted OR 2.1 [95% CI 1.4-3.0] vs. preterm aOR 1.1 [0.8-1.7]; BMI ≥ 35.0 kg/m2 term aOR 2.2 [1.4-3.4] vs. preterm aOR 1.5 [1.2-1.8]; p-interaction < 0.01), nulliparity compared to parity 1 (term aOR 1.7 [1.1-2.7] vs. preterm aOR 1.2 [0.9-1.6]; p-interaction < 0.01) and Asian ethnicity compared with White (p-interaction < 0.01). A weaker or lack of association with term, compared to preterm, stillbirth was observed for older maternal age, smoking and pre-eclampsia. CONCLUSION: Differences in association exist between mothers experiencing preterm and term stillbirth. These differences could contribute to design of timely surveillance and interventions to further mitigate the risk of stillbirth.

How are the Dietary Needs of Pregnant Incarcerated Women Being Met? A Scoping Review and Thematic Analysis.

INTRODUCTION: The number of incarcerated pregnant women is increasing globally. With many having complex health and social backgrounds, incarceration provides opportunities for health interventions, including the chance to have their nutritional needs met. Despite the additional nutritional requirements of pregnancy being well documented, how these are being met within the correctional setting is currently poorly understood. METHODS: A scoping review of the literature was conducted to identify the literature published between January 2010 and April 2023 related to the provision of nutrition for pregnant women in the international prison systems. Sixteen papers met the criteria for inclusion in the review. The relevant key findings were charted and thematically analysed. RESULTS: Two themes were identified: 'the inconsistent reality of food provision' and 'choice, autonomy and food'. There is a clear disparity in the way in which diet is prioritised and provided to pregnant incarcerated women across several countries. DISCUSSION: The findings highlight the need for a consistent approach to diet on a macro, global level to ensure the health of women and their infants in context.

Management of Impacted Fetal Head at Caesarean Birth: Scientific Impact Paper No. 73.

Over one-quarter of women in the UK have a caesarean birth (CB). More than one in 20 of these births occurs near the end of labour, when the cervix is fully dilated (second stage). In these circumstances, and when labour has been prolonged, the baby's head can become lodged deep in the maternal pelvis making it challenging to deliver the baby. During the caesarean birth, difficulty in delivery of the baby's head may result - this emergency is known as impacted fetal head (IFH). These are technically challenging births that pose significant risks to both the woman and baby. Complications for the woman include tears in the womb, serious bleeding and longer hospital stay. Babies are at increased risk of injury including damage to the head and face, lack of oxygen to the brain, nerve damage, and in rare cases, the baby may die from these complications. Maternity staff are increasingly encountering IFH at CB, and reports of associated injuries have risen dramatically in recent years. The latest UK studies suggest that IFH may complicate as many as one in 10 unplanned CBs (1.5% of all births) and that two in 100 babies affected by IFH die or are seriously injured. Moreover, there has been a sharp increase in reports of babies having brain injuries when their birth was complicated by IFH. When an IFH occurs, the maternity team can use different approaches to help deliver the baby's head at CB. These include: an assistant (another obstetrician or midwife) pushing the head up from the vagina; delivering the baby feet first; using a specially designed inflatable balloon device to elevate the baby's head and/or giving the mother a medicine to relax the womb. However, there is currently no consensus for how best to manage these births. This has resulted in a lack of confidence among maternity staff, variable practice and potentially avoidable harm in some circumstances. This paper reviews the current evidence regarding the prediction, prevention and management of IFH at CB, integrating findings from a systematic review commissioned from the National Guideline Alliance.

Antenatal detection of large-for-gestational-age fetuses following implementation of the Growth Assessment Protocol: secondary analysis of a randomised control trial.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP) affects the antenatal detection of large for gestational age (LGA) or maternal and perinatal outcomes amongst LGA babies. DESIGN: Secondary analysis of a pragmatic open randomised cluster control trial comparing the GAP with standard care. SETTING: Eleven UK maternity units. POPULATION: Pregnant women and their LGA babies born at ≥36+0  weeks of gestation. METHODS: Clusters were randomly allocated to GAP implementation or standard care. Data were collected from electronic patient records. Trial arms were compared using summary statistics, with unadjusted and adjusted (two-stage cluster summary approach) differences. MAIN OUTCOME MEASURES: Rate of detection of LGA (estimated fetal weight on ultrasound scan above the 90th centile after 34+0  weeks of gestation, defined by either population or customised growth charts), maternal and perinatal outcomes (e.g. mode of birth, postpartum haemorrhage, severe perineal tears, birthweight and gestational age, neonatal unit admission, perinatal mortality, and neonatal morbidity and mortality). RESULTS: A total of 506 LGA babies were exposed to GAP and 618 babies received standard care. There were no significant differences in the rate of LGA detection (GAP 38.0% vs standard care 48.0%; adjusted effect size -4.9%; 95% CI -20.5, 10.7; p = 0.54), nor in any of the maternal or perinatal outcomes. CONCLUSIONS: The use of GAP did not change the rate of antenatal ultrasound detection of LGA when compared with standard care.

Intrahepatic cholestasis of pregnancy - Diagnosis and management: A consensus statement of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ): Executive summary.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy liver disease, characterised by pruritus and increased total serum bile acids (TSBA), Australian incidence 0.6-0.7%. ICP is diagnosed by non-fasting TSBA ≥19 µmol/L in a pregnant woman with pruritus without rash without a known pre-existing liver disorder. Peak TSBA ≥40 and ≥100 µmol/L identify severe and very severe disease respectively, associated with spontaneous preterm birth when severe, and with stillbirth, when very severe. Benefit-vs-risk for iatrogenic preterm birth in ICP remains uncertain. Ursodeoxycholic acid remains the best pharmacotherapy preterm, improving perinatal outcome and reducing pruritus, although it has not been shown to reduce stillbirth.

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474.

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.

A comparison of technicques to disimpact the fetal head on a second stage caesearean simulator.

BACKGROUND: The rate of second stage caesarean section (CS) is rising with associated increases in maternal and neonatal morbidity, which may be related to impaction of the fetal head in the maternal pelvis. In the last 10 years, two devices have been developed to aid disimpaction and reduce these risks: the Fetal Pillow (FP) and the Tydeman Tube (TT). The aim of this study was to determine the distance of upward fetal head elevation achieved on a simulator for second stage CS using these two devices, compared to the established technique of per vaginum digital disimpaction by an assistant. METHODS: We measured elevation of the fetal head achieved with the two devices (TT and FP), compared to digital elevation, on a second stage Caesearean simulator (Desperate Debra ™ set at three levels of severity. Elevation was measured by both a single operator experienced with use of the TT and FP and also multiple assistants with no previous experience of using either device. All measurements were blinded RESULTS: The trained user achieved greater elevation of the fetal head at both moderate and high levels of severity with the TT (moderate: 30mm vs 12.5mm p<0.001; most severe: 25mm vs 10mm p<0.001) compared to digital elevation. The FP provided comparable elevation to digital at both settings (moderate: 10 vs 12.5mm p=0.149; severe 10 vs 10mm p=0.44). With untrained users, elevation was also significantly greater with the TT compared to digital elevation (20mm vs 10mm p<0.01). However digital disimpaction was significantly greater than the FP (10mm vs 0mm p<0.0001). CONCLUSION: On a simulator, with trained operators, the TT provided greater fetal head elevation than digital elevation and the FP. The FP achieved similar elevation to the digital technique, especially when the user was trained in the procedure.

Post-repair laxative management in obstetric anal sphincter injury guidelines: A narrative review.

BACKGROUND: Childbirth is a common factor which increases the risk of obstetric anal sphincter injuries (OASIS). Damage to the anal sphincters increases the risk of anal incontinence, which has a debilitating impact on the quality of life. Post-repair laxatives are prescribed in this group of women. However, there is no consensus regarding the type or frequency with which they are used, and available guidelines lack consistency and evidence to support the recommendations. AIM: The aim was to review and compare the international, national and local Australian management guidelines for recommendations regarding laxative use in women after OASIS. METHOD: An online literature search of medical and nursing databases such as PubMed, Embase, MEDLINE, CINAHL, Web of Science, Scopus and Cochrane was performed between January 2000 and October 2020. Full-text articles with MeSH headings and Text Words [TW] identified guidelines in the prevention, management and care of OASIS. The search terms included 'obstetric anal sphincter injury', 'OASIS', 'perineal tear', 'postpartum continence', 'bowel injury', 'aperient', 'laxative use' and 'bulking agents'. RESULTS: Thirteen guidelines were included. Laxatives were recommended in most guidelines; however, there was a lack of consistency regarding the type of laxative used, frequency, dose and duration of use. Guidelines were based on historical evidence, with paucity of recently acquired data identified. CONCLUSIONS: There is no consensus regarding an optimal laxative regime for women who sustain an anal sphincter injury after childbirth. Further research is required to develop evidence-based robust clinical guidelines regarding laxative use in women who sustain OASIS.

The effects of dietary and lifestyle interventions among pregnant women with overweight or obesity on early childhood outcomes: an individual participant data meta-analysis from randomised trials.

BACKGROUND: The impact of maternal obesity extends beyond birth, being independently associated with an increased risk of child obesity. Current evidence demonstrates that women provided with a dietary intervention during pregnancy improve their dietary quality and have a modest reduction in gestational weight gain. However, the effect of this on longer-term childhood obesity-related outcomes is unknown. METHODS: We conducted an individual participant data meta-analysis from RCTs in which women with a singleton, live gestation between 10+0 and 20+0 weeks and body mass index (BMI) ≥ 25 kg/m2 in early pregnancy were randomised to a diet and/or lifestyle intervention or continued standard antenatal care and in which longer-term maternal and child follow-up at 3-5 years of age had been undertaken. The primary childhood outcome was BMI z-score above the 90th percentile. Secondary childhood outcomes included skinfold thickness measurements and body circumferences, fat-free mass, dietary and physical activity patterns, blood pressure, and neurodevelopment. RESULTS: Seven primary trials where follow-up of participants occurred were identified by a systematic literature search within the International Weight Management in Pregnancy (i-WIP) Collaborative Group collaboration, with six providing individual participant data. No additional studies were identified after a systematic literature search. A total of 2529 children and 2383 women contributed data. Approximately 30% of all child participants had a BMI z-score above the 90th percentile, with no significant difference between the intervention and control groups (aRR 0.97; 95% CI 0.87, 1.08; p=0.610). There were no statistically significant differences identified for any of the secondary outcome measures. CONCLUSIONS: In overweight and obese pregnant women, we found no evidence that maternal dietary and/or lifestyle intervention during pregnancy modifies the risk of early childhood obesity. Future research may need to target the pre-conception period in women and early childhood interventions. TRIAL REGISTRATION: PROSPERO, CRD42016047165.

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.

The effect of a lifestyle intervention in obese pregnant women on gestational metabolic profiles: findings from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) randomised controlled trial.

BACKGROUND: Pregnancy is associated with widespread change in metabolism, which may be more marked in obese women. Whether lifestyle interventions in obese pregnant women improve pregnancy metabolic profiles remains unknown. Our objectives were to determine the magnitude of change in metabolic measures during obese pregnancy, to indirectly compare these to similar profiles in a general pregnant population, and to determine the impact of a lifestyle intervention on change in metabolic measures in obese pregnant women. METHODS: Data from a randomised controlled trial of 1158 obese (BMI ≥ 30 kg/m2) pregnant women recruited from six UK inner-city obstetric departments were used. Women were randomised to either the UPBEAT intervention, a tailored complex lifestyle intervention focused on improving diet and physical activity, or standard antenatal care (control group). UPBEAT has been shown to improve diet and physical activity during pregnancy and up to 6-months postnatally in obese women and to reduce offspring adiposity at 6-months; it did not affect risk of gestational diabetes (the primary outcome). Change in the concentrations of 158 metabolic measures (129 lipids, 9 glycerides and phospholipids, and 20 low-molecular weight metabolites), quantified three times during pregnancy, were compared using multilevel models. The role of chance was assessed with a false discovery rate of 5% adjusted p values. RESULTS: All very low-density lipoprotein (VLDL) particles increased by 1.5-3 standard deviation units (SD) whereas intermediate density lipoprotein and specific (large, medium and small) LDL particles increased by 1-2 SD, between 16 and 36 weeks' gestation. Triglycerides increased by 2-3 SD, with more modest changes in other metabolites. Indirect comparisons suggest that the magnitudes of change across pregnancy in these obese women were 2- to 3-fold larger than in unselected women (n = 4260 in cross-sectional and 583 in longitudinal analyses) from an independent, previously published, study. The intervention reduced the rate of increase in extremely large, very large, large and medium VLDL particles, particularly those containing triglycerides. CONCLUSION: There are marked changes in lipids and lipoproteins and more modest changes in other metabolites across pregnancy in obese women, with some evidence that this is more marked than in unselected pregnant women. The UPBEAT lifestyle intervention may contribute to a healthier metabolic profile in obese pregnant women, but our results require replication. TRIAL REGISTRATION: UPBEAT was registered with Current Controlled Trials, ISRCTN89971375 , on July 23, 2008 (prior to recruitment).

The impacted foetal head at caesarean section: incidence and techniques used in a single UK institution.

An impaction of the foetal head at caesarean section is a topical concern in modern obstetric practice. The management options for this problem are well described but the incidence or even definition of impaction, is unknown. The primary aim of this study was to ascertain the incidence of impacted foetal head at CS in labour. This prospective study used data from all women undergoing CS during a 12-month period in a single unit. Following completion of all CS, the surgeon completed a questionnaire covering: cervical dilation at time of CS; if the surgeon felt there was a difficulty in delivering the foetal head as an indicator of impaction, as well as the other techniques utilised. Of 440 EMCS in labour, 18% (n = 81) reported a difficulty delivering the head, which was most common at cervical dilation ≥8 cm (n = 124, 48%). A difficulty with the delivery of the foetal head was associated with 36% increased measured blood loss. Impact statement What is already known on this subject? Impaction of the foetal head at a caesarean section is a recognised complication of CS in late labour but there are no reliable data on the incidence of the problem. It is poorly defined and yet many techniques and devices have been described to overcome this problem, however, optimal management remains uncertain. What do the results of this study add? The primary aim of this study was to determine the incidence of the impacted foetal head during CS in labour as determined by whether the surgeon experienced difficulty with delivery of the head. We report that at least some difficulty in delivering the foetal head at CS is common, and most often encountered when cervical dilation is ≥8 cm. When additional manoeuvres were required, the 'push' technique was exclusively adopted with implications for training. A difficulty in delivering the foetal head was associated with a 36% increase in the measured maternal blood loss. What are the implications of these findings for clinical practice and/or further research? Further multi-centre investigation is required to ascertain incidence of this obstetric problem with predicting factors determined. This work will inform decisions about the optimal management.

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.

BACKGROUND: Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. RESULTS: A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

Do elevated symptoms of depression predict adherence and outcomes in the UPBEAT randomised controlled trial of a lifestyle intervention for obese pregnant women?

BACKGROUND: Lifestyle interventions for obese pregnant women have been widely researched but little is known about predictors of low adherence or poor outcomes. This study evaluated the prospective associations between elevated symptoms of antenatal depression and gestational diabetes, adherence and gestational weight gain in a large RCT of a behavioural intervention for obese pregnant women. The effect of the intervention on symptoms of depression at follow-up was also examined. METHODS: The UPBEAT RCT randomised 1555 obese pregnant women to receive a dietary and physical activity lifestyle intervention or standard care. Symptoms of antenatal depression were assessed with the Edinburgh Postnatal Depression Scale at baseline (15+ 0-18+ 6 weeks' gestation) and follow-up (27+ 0-28+ 6 weeks' gestation). Gestational diabetes was assessed with an oral glucose tolerance test at 27+ 0-28+ 6 weeks' gestation. Adherence was pre-defined as receiving at least 5 of 8 intervention sessions. Gestational weight gain was calculated as the difference between pre-pregnancy weight (estimated as measured baseline weight minus 1.25 kg) and last measured weight at 34+ 0-36+ 0 weeks' gestation. Due to substantial missing data in certain variables, multiple imputation was used to impute missing data. Women who were no longer pregnant at 27+ 0-28+ 6 weeks' gestation were excluded from the sample for these analyses. RESULTS: One thousand five-hundered twenty-six women were included in these analyses following multiple imputation; 797 (52.2%) had complete data. 13.4% had elevated symptoms of antenatal depression at baseline. There was no evidence for associations between antenatal depression status and gestational diabetes (adjusted OR 0.80, 95%CI 0.52 to 1.22, p = 0.30), adherence (adjusted OR 1.16, 95%CI 0.63 to 2.15, p = 0.63) or gestational weight gain (adjusted regression coefficient 0.52, 95%CI -0.26 to 1.29, p = 0.19). The intervention was not associated with change in depressive symptoms at follow-up (regression coefficient 0.003, 95%CI -0.49 to 0.49, p = 0.99). Similar results were obtained in complete case analyses. CONCLUSIONS: Elevated symptoms of antenatal depression did not predict gestational diabetes, adherence or gestational weight gain in this large RCT of a lifestyle intervention for obese pregnant women. The intervention also did not influence symptoms of depression at follow-up. Obese pregnant women with elevated symptoms of depression should not be excluded from lifestyle interventions. TRIAL REGISTRATION: ISRCTN89971375 . Registered 28 November 2008.

Mode of infant feeding, eating behaviour and anthropometry in infants at 6-months of age born to obese women - a secondary analysis of the UPBEAT trial.

BACKGROUND: Maternal obesity and rapid infant weight gain have been associated with increased risk of obesity in childhood. Breastfeeding is suggested to be protective against childhood obesity, but no previous study has addressed the potential benefit of breastfeeding as a preventive method of childhood obesity amongst obese women. The primary aim of this study was to assess the relationship between mode of feeding and body composition, growth and eating behaviours in 6-month-old infants of obese women who participated in UPBEAT; a multi-centre randomised controlled trial comparing a lifestyle intervention of diet and physical activity to standard care during pregnancy. METHODS: Three hundred and fifty-three mother and infant pairs attended a 6-months postpartum follow-up visit, during which they completed the Baby-Eating Behaviour Questionnaire, a parent-reported psychometric measure of appetite traits. Measures of infant body composition were also undertaken. As there was no effect of the antenatal intervention on infant feeding and appetite the study was treated as a cohort. Using regression analyses, we examined relationships between: 1) mode of feeding and body composition and growth; 2) mode of feeding and eating behaviour and 3) eating behaviour and body composition. RESULTS: Formula fed infants of obese women in comparison to those exclusively breastfed, demonstrated higher weight z-scores (mean difference 0.26; 95% confidence interval 0.01 to 0.52), higher rate of weight gain (0.04; 0.00 to 0.07) and greater catch-up growth (2.48; 1.31 to 4.71). There was also a lower enjoyment of food (p = 0.002) amongst formula fed infants, following adjustment for confounders. Independent of the mode of feeding, a measure of infant appetite was associated with sum of skinfold thicknesses (ß 0.66; 95% CI 0.12 to 1.21), calculated body fat percentage (0.83; 0.15 to 1.52), weight z-scores (0.21; 0.06 to 0.36) and catch-up growth (odds ratio 1.98; 1.21 to 3.21). CONCLUSIONS: In obese women, exclusive breastfeeding was protective against increasing weight z-scores and trajectories of weight gain in their 6-month old infants. Measures of general appetite in early infancy were associated with measures of adiposity, weight and catch up growth independent of cord blood leptin concentrations and mode of early feeding.

Metabolic profiling of gestational diabetes in obese women during pregnancy.

AIMS/HYPOTHESIS: Antenatal obesity and associated gestational diabetes (GDM) are increasing worldwide. While pre-existing insulin resistance is implicated in GDM in obese women, the responsible metabolic pathways remain poorly described. Our aim was to compare metabolic profiles in blood of obese pregnant women with and without GDM 10 weeks prior to and at the time of diagnosis by OGTT. METHODS: We investigated 646 women, of whom 198 developed GDM, in this prospective cohort study, a secondary analysis of UK Pregnancies Better Eating and Activity Trial (UPBEAT), a multicentre randomised controlled trial of a complex lifestyle intervention in obese pregnant women. Multivariate regression analyses adjusted for multiple testing, and accounting for appropriate confounders including study intervention, were performed to compare obese women with GDM with obese non-GDM women. We measured 163 analytes in serum, plasma or whole blood, including 147 from a targeted NMR metabolome, at time point 1 (mean gestational age 17 weeks 0 days) and time point 2 (mean gestational age 27 weeks 5 days, at time of OGTT) and compared them between groups. RESULTS: Multiple significant differences were observed in women who developed GDM compared with women without GDM (false discovery rate corrected p values <0.05). Most were evident prior to diagnosis. Women with GDM demonstrated raised lipids and lipoprotein constituents in VLDL subclasses, greater triacylglycerol enrichment across lipoprotein particles, higher branched-chain and aromatic amino acids and different fatty acid, ketone body, adipokine, liver and inflammatory marker profiles compared with those without GDM. CONCLUSIONS/INTERPRETATION: Among obese pregnant women, differences in metabolic profile, including exaggerated dyslipidaemia, are evident at least 10 weeks prior to a diagnosis of GDM in the late second trimester.

Prediction of uncomplicated pregnancies in obese women: a prospective multicentre study.

BACKGROUND: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. METHODS: Data form obese women (BMI ≥ 30 kg/m2) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15+0 to 18+6 weeks' gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. RESULTS: Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m2), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68-0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65-0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. CONCLUSION: Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth.

Assessment of a vaginal device for delivery of the impacted foetal head at caesarean section.

The aim of this study was to assess a new device (Tydeman Tube) designed to facilitate delivery of the impacted foetal head at caesarean section. Standard digital vaginal technique and the Tydeman Tube were each used to elevate the foetal head on a validated full dilatation caesarean simulator. Greater elevation of the foetal head was achieved with the Tydeman Tube than digital technique (mean difference +9.1 mm, p < 0.001). Although greater force was applied to achieve this elevation (mean difference +0.42 Kgf, p < 0.001), the force was spread over a greater area (6.97 cm2 versus 2.0 cm2). Therefore, mean pressures applied to the foetal head were lower (mean difference -2.3 Kg cm2, p < 0.001). The first uses of the Tydeman Tube in clinical practice were described. Clinicians found it easy to use and effective (mean score 7.7/10). The Tydeman Tube is an effective tool for delivering the impacted foetal head on a simulator and its initial use in clinical practise has proved positive.