Showing papers by "Paul T. Seed published in 2018"

Interpregnancy weight change and adverse pregnancy outcomes: a systematic review and meta-analysis.

Abstract: Objectives To evaluate the effect of interpregnancy body mass index (BMI) change on pregnancy outcomes, including large-for-gestational-age babies (LGA), small-for-gestational-age babies (SGA), macrosomia, gestational diabetes mellitus (GDM) and caesarean section (CS). Design Systematic review and meta-analysis of observational cohort studies. Data sources Literature searches were performed across Cochrane, MEDLINE, EMBASE, CINAHL, Global Health and MIDIRS databases. Study selection Observational cohort studies with participants parity from 0 to 1. Main outcome measures Adjusted ORs (aORs) with 95% CIs were used to evaluate the association between interpregnancy BMI change on five outcomes. Results 925 065 women with singleton births from parity 0 to 1 were included in the meta-analysis of 11 studies selected from 924 identified studies. A substantial increase in interpregnancy BMI (>3 BMI units) was associated with an increased risk of LGA (aOR 1.85, 95% CI 1.71 to 2.00, p 2 ) at first pregnancy who have a substantial increase in BMI between pregnancies had a higher risk of LGA (aOR 2.10, 95% CI 1.93 to 2.29) and GDM (aOR 3.10, 95% CI 2.74 to 3.50) when compared with a reference than women with a BMI ≥25 kg/m 2 at first pregnancy. Conclusions Gaining weight between pregnancies increases risk of developing GDM, CS and LGA, and reduces risk of SGA in the subsequent pregnancy. Losing weight between pregnancies reduces risk of GDM and LGA and increases risk of SGA. Weight stability between first and second pregnancy is advised in order to reduce risk of adverse outcomes. Trial registration number CRD42016041299.

Maternal and perinatal adverse outcomes in women with pre-eclampsia cared for at facility-level in South Africa: a prospective cohort study.

Abstract: Background Hypertensive disorders of pregnancy contribute to 14% of all maternal deaths, the majority of which occur in low- and middle-income countries. The aim of the study was to describe the maternal and perinatal clinical outcomes of women with pre-eclampsia living in middle- and low-income countries. Methods The study was a prospective observational study of women with pre-eclampsia (n = 1547, 42 twin pregnancies) at three South African tertiary facilities. Using stepwise logistic regression model area under the receiver operating characteristic curve (AUROC) values, the association between maternal baseline and admission characteristics and risk of adverse outcomes was evaluated. Main outcome measures were eclampsia, kidney injury and perinatal death. Results In 1547 women with pre-eclampsia, 16 (1%) died, 147 (9.5%) had eclampsia, four (0.3%) had a stroke and 272 (17.6%) had kidney injury. Of the 1589 births, there were 332 (21.0%) perinatal deaths; of these, 281 (84.5%) were stillbirths. Of 1308 live births, 913 (70.0%) delivered <37 completed weeks and 544 (41.7%) delivered <34 weeks' gestation. Young maternal age (AUROC = 0.76, 95% confidence interval (CI) = 0.71-0.80) and low Body Mass Index BMI (AUROC 0.65, 95% CI = 0.59-0.69) were significant predictors of eclampsia. Highest systolic blood pressure had the strongest association with kidney injury, (AUROC = 0.64, 95% CI = 0.60-0.68). Early gestation at admission was most strongly associated with perinatal death (AUROC = 0.81, 95% CI = 0.77-0.84). Conclusions The incidence of pre-eclampsia complications, perinatal death and preterm delivery in women referred to tertiary care in South Africa was much higher than reported in other low- and middle-income studies and despite access to tertiary care interventions. Teenage mothers and those with low BMI were at highest risk of eclampsia. This information could be used to inform guidelines, the research agenda and policy.

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

Abstract: 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. 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. 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 (β 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). 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.

Cord Metabolic Profiles in Obese Pregnant Women: Insights Into Offspring Growth and Body Composition

Abstract: Context: Offspring exposed in-utero to maternal obesity have an increased risk of later obesity; however, the underlying mechanisms remain unknown. Objective: To assess the effect of an antenatal lifestyle intervention in obese women on the offspring’s cord blood metabolic profile, and examine associations of cord blood metabolic profile with maternal clinical characteristics and offspring anthropometry at birth and age 6 months. Design: Randomised controlled trial and cohort study. Setting: The UK Pregnancies Better Eating and Activity randomised controlled trial (UPBEAT). Participants: 344 mother-offspring pairs. Intervention: Antenatal behavioural lifestyle (diet and physical activity) intervention. Main outcome measures: Targeted cord blood metabolic profile, including candidate hormone and metabolomic analyses. Results: The lifestyle intervention was not associated with change in the cord blood metabolic profile. Higher maternal glycaemia, specifically fasting glucose at 28 weeks’ gestation had a linear association with higher cord blood concentrations of lysophosphatidylcholines 16.1 (β=0.65; 95%CI 0.03 to 0.10) and 18.1 (0.52; 0.02 to 0.80), independent of the lifestyle intervention. A principal component of cord blood phosphatidylcholines and lysophosphatidylcholines was associated with infant z-scores of birthweight (0.04; 0.02 to 0.07) and weight at age 6 months (0.05; 0.00 to 0.10). Cord blood IGF-1 and adiponectin concentrations were positively associated with infant weight z-scores at birth and at 6 months. Conclusions: Concentrations of lysophosphatidylcholines and IGF-1 in cord blood are related to infant weight. These findings support the hypothesis that susceptibility to childhood obesity may be programmed in-utero, but further investigation is required to establish whether these associations are causally related.

Predicting delivery of a small-for-gestational-age infant and adverse perinatal outcome in women with suspected pre-eclampsia

Abstract: OBJECTIVE: To evaluate the test performance of 47 biomarkers and ultrasound parameters to predict subsequent delivery of an SGA infant and adverse perinatal outcome in women presenting with suspected preeclampsia. METHODS: In a prospective, multicentre observational study, 47 biomarkers and ultrasound parameters were measured in 397 women presenting with suspected preterm preeclampsia, with the objective of evaluating them as predictors of subsequent delivery of an SGA infant and adverse perinatal outcome. Factor analysis and stepwise logistic regression were performed in two pre-specified groups. RESULTS: In 274 women presenting at 20(+0) to 34(+6) weeks' gestation (Group 1), 96 (35%) delivered an SGA infant <3(rd) customised birthweight centile (SGA-3). For prediction of SGA-3, low maternal Placental Growth Factor (PlGF) concentrations had a sensitivity of 93% (95%CI 84% to 98%) and negative predictive value (NPV) of 90% (95%CI 76% to 97%) compared to a sensitivity of 71% (95%CI 58% to 82%) and a NPV of 79% (95%CI 68% to 87%) for ultrasound parameters (estimated fetal weight or abdominal circumference <10(th) centile). No individual biomarker evaluated had superior performance to PlGF and combinations added only small increments to test performance. Similar results were found in 123 women presenting between 35(+0) to 36(+6) weeks' gestation (Group 2). CONCLUSIONS: In women presenting with suspected preterm preeclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering an SGA infant, allowing appropriate surveillance and timely intervention.

Chronic hypertension in pregnancy: impact of ethnicity and superimposed preeclampsia on placental, endothelial, and renal biomarkers.

Abstract: Black ethnicity is associated with worse pregnancy outcomes in women with chronic hypertension. Preexisting endothelial and renal dysfunction and poor placentation may contribute, but pathophysiolo...

Evaluation of a novel device for the management of high blood pressure and shock in pregnancy in low-resource settings: study protocol for a stepped-wedge cluster-randomised controlled trial (CRADLE-3 trial)

Abstract: Obstetric haemorrhage, sepsis and pregnancy hypertension account for more than 50% of maternal deaths worldwide. Early detection and effective management of these conditions relies on vital signs. The Microlife® CRADLE Vital Sign Alert (VSA) is an easy-to-use, accurate device that measures blood pressure and pulse. It incorporates a traffic-light early warning system that alerts all levels of healthcare provider to the need for escalation of care in women with obstetric haemorrhage, sepsis or pregnancy hypertension, thereby aiding early recognition of haemodynamic instability and preventing maternal mortality and morbidity. The aim of the trial was to determine whether implementation of the CRADLE intervention (the Microlife® CRADLE VSA device and CRADLE training package) into routine maternity care in place of existing equipment will reduce a composite outcome of maternal mortality and morbidity in low- and middle-income country populations. The CRADLE-3 trial was a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care. Each cluster crossed from routine maternity care to the intervention at 2-monthly intervals over the course of 20 months (April 2016 to November 2017). All women identified as pregnant or within 6 weeks postpartum, presenting for maternity care in cluster catchment areas were eligible to participate. Primary outcome data (composite of maternal death, eclampsia and emergency hysterectomy per 10,000 deliveries) were collected at 10 clusters (Gokak, Belgaum, India; Harare, Zimbabwe; Ndola, Zambia; Lusaka, Zambia; Free Town, Sierra Leone; Mbale, Uganda; Kampala, Uganda; Cap Haitien, Haiti; South West, Malawi; Addis Ababa, Ethiopia). This trial was informed by the Medical Research Council guidance for complex interventions. A process evaluation was undertaken to evaluate implementation in each site and a cost-effectiveness evaluation will be undertaken. All aspects of this protocol have been evaluated in a feasibility study, with subsequent optimisation of the intervention. This trial will demonstrate the potential impact of the CRADLE intervention on reducing maternal mortality and morbidity in low-resource settings. It is anticipated that the relatively low cost of the intervention and ease of integration into existing health systems will be of significant interest to local, national and international health policy-makers. ISCRTN41244132. Registered on 2 February 2016. Prospective protocol modifications have been recorded and were communicated to the Ethics Committees and Trials Committees. The adapted Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist and the SPIRIT Checklist are attached as Additional file 1.

Is recreational running associated with earlier delivery and lower birth weight in women who continue to run during pregnancy? An international retrospective cohort study of running habits of 1293 female runners during pregnancy

Abstract: Background Increasingly, women of reproductive age participate in recreational running, but its impact on pregnancy outcome is unknown. We investigated whether running affects gestational age at delivery and birth weight as indicators of cervical integrity and placental function, respectively. Methods 1293 female participants were recruited from parkrun, which organises weekly runs involving 1.25 million runners across 450 parks worldwide. Those under 16 or unable to provide outcome data were excluded. Women were categorised according to whether they continued to run during pregnancy or not. Those who continued were further stratified dependent on average weekly kilometres, and which trimester they ran until. Retrospectively collected primary outcomes were gestational age at delivery and birthweight centile. Other outcomes included assisted vaginal delivery rate and prematurity at clinically important gestations. Results There was no significant difference in gestational age at delivery: 279.0 vs 279.6 days (mean difference 0.6 days, CI −1.3 to 2.4 days; P=0.55) or birthweight centile: 46.9%vs 44.9% (mean difference 2.0%, CI −1.3% to −5.3%; P=0.22) in women who stopped running and those who continued, respectively. Assisted vaginal delivery rate was increased in women who ran: 195/714 (27%) vs 128/579 (22%) (OR 1.32; CI 1.02 to 1.71; P=0.03). Conclusion Continuing to run during pregnancy does not appear to affect gestational age or birthweight centile, regardless of mean weekly distance or stage of pregnancy. Assisted vaginal delivery rates were higher in women who ran, possibly due to increased pelvic floor muscle tone. Randomised prospective analysis is necessary to further explore these findings.

Evaluation of a novel vital sign device to reduce maternal mortality and morbidity in low-resource settings: a mixed method feasibility study for the CRADLE-3 trial

Abstract: The CRADLE-3 trial is a stepped-wedge randomised controlled trial aiming to reduce maternal mortality and morbidity by implementing a novel vital sign device (CRADLE Vital Sign Alert) and training package into routine maternity care in 10 low-income sites. The MRC Guidance on complex interventions proposes that interventions and implementation strategies be shaped by early phase piloting and development work. We present the findings of a three-month mixed-methodology feasibility study for this trial, describe how this was informed by the MRC guidance and the study design was refined. The fidelity, dose, feasibility and acceptability of implementation and training materials were assessed in three representative non-trial sites (Zimbabwe, Ethiopia, India) using multiple-choice questionnaires, evaluation of clinical management (action log), healthcare provider (HCP) semi-structured interviews and focus groups 4–10 weeks after implementation. Simultaneously, the 10 sites included in the main trial (eight countries) collected primary outcome data to inform the power calculation and randomisation allocation and assess the feasibility of data collection. The package was implemented with high fidelity (85% of HCP trained, n = 204). The questionnaires indicated a good understanding of device use with 75% of participants scoring > 75% (n = 97; 90% of those distributed). Action logs were inconsistently completed but indicated that the majority of HCP responded appropriately to abnormal results. From 18 HCP interviews and two focus groups it was widely reported that the intervention improved capacity to make clinical decisions, escalate care and make appropriate referrals. Nine of the ten main trial sites achieved ethical approval for pilot data collection. Intensive care was an inconsistent marker of morbidity and stroke an infrequent outcome and therefore they were removed from the main trial composite outcome. Tools and methods of data collection were optimized and event rates used to inform randomisation. This feasibility study demonstrates that the components of the intervention were acceptable, methods of implementing were successful and the main trial design would be feasible. Qualitative work identified key moderators that informed the main trial process evaluation. Changes to the training package, implementation strategy, study design and processes were identified to refine the implementation in the main trial. ISRCTN41244132 ; Registered 24/11/2015.

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

Abstract: 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 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 125 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 One thousand five-hundered twenty-six women were included in these analyses following multiple imputation; 797 (522%) had complete data 134% had elevated symptoms of antenatal depression at baseline There was no evidence for associations between antenatal depression status and gestational diabetes (adjusted OR 080, 95%CI 052 to 122, p = 030), adherence (adjusted OR 116, 95%CI 063 to 215, p = 063) or gestational weight gain (adjusted regression coefficient 052, 95%CI -026 to 129, p = 019) The intervention was not associated with change in depressive symptoms at follow-up (regression coefficient 0003, 95%CI -049 to 049, p = 099) Similar results were obtained in complete case analyses 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 ISRCTN89971375 Registered 28 November 2008

Rationale & design of the PROMISES study: a prospective assessment and validation study of salivary progesterone as a test for preterm birth in pregnant women from rural India

Abstract: In India, 3.6 million pregnancies are affected by preterm birth annually, with many infants dying or surviving with disability. Currently, there is no simple test available for screening all women at risk of spontaneous PTB in low income setting, although high resource settings routinely use cervical length measurement and cervico-vaginal fluid fetal fibronectin for identification and care of women at risk due to clinical history. In rural India, where the public health system has limited infrastructure, trained staff and equipment, there is a greater need to develop a low-cost screening approach for providing early referral, treatment and remedial support for pregnant women at risk of preterm birth. There is interest in the use of a salivary progesterone test as a screening tool preliminary evidence from India, Egypt and UK has shown promise for this type of test. The test requires further validation in a low resource community setting. The Promises study aims to validate and test the feasibility of introducing a low-cost salivary progesterone preterm birth prediction test in two rural districts in India with high rates of prematurity. It is a prospective study of 2000 pregnant women recruited from Panna and Satna in Madhya Pradesh over approximately 24 months. Demographic and pregnancy outcome data will be collected, and pregnancies will be dated by ultrasound sonography. Saliva progesterone will be measured by ELISA in samples obtained between 24–28 weeks of gestation. The association between salivary progesterone and preterm birth will be determined and the utility of salivary progesterone to predict preterm birth < 34, as well as < 30 and < 37 weeks assessed. Additional qualitative data will be obtained in terms of acceptability and feasibility of saliva progesterone testing and knowledge of PTB. A validated cost-effective saliva test, which has potential for further adaptation to a ‘point of care’ setting will allow early identification of pregnant women at risk of preterm birth, who can be linked to an effective pathway of care and support to reduce preterm birth and associated adverse consequences. This will reduce both economic and emotional burden on the affected women and their families.

A Slow-Digesting, Low-Glycemic Load Nutritional Beverage Improves Glucose Tolerance in Obese Pregnant Women Without Gestational Diabetes

Abstract: Background: Obesity is a risk factor for gestational diabetes (gestational diabetes) Low-glycemic index diets attenuate hyperglycemia We designed a study to determine whether a slow-dige