Nashita Patel

Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy

Objectives:Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum.Subjects and methods:We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire.Results:A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference −0.14 s.d., 95% confidence interval −0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (−0.49 to −0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (−35.34; −48.0 to −22.67; P<0.001) and saturated fat intake (−1.93% energy; −2.64 to −1.22; P<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet.Conclusions:This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.

Determining the consequences of maternal obesity for offspring health

What is the topic of this review? Observational studies have highlighted the association of increasing maternal body mass index with offspring adiposity and the subsequent risk of cardiometabolic disorders in adulthood. The in utero environment has become a target for intervention in order to reduce the burden of obesity, despite the mechanistic pathways of this association remaining unclear. What advances does it highlight? This short review provides a critical appraisal of the recent literature, including biological pathways and strategies to address causal relationships.

Dietary patterns in obese pregnant women; influence of a behavioral intervention of diet and physical activity in the UPBEAT randomized controlled trial

BackgroundUnderstanding dietary patterns in obese pregnant women will inform future intervention strategies to improve pregnancy outcomes and the health of the child. The aim of this study was to investigate the effect of a behavioral intervention of diet and physical activity advice on dietary patterns in obese pregnant woman participating in the UPBEAT study, and to explore associations of dietary patterns with pregnancy outcomes.MethodsIn the UPBEAT randomized controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city populations were randomly assigned to receive a diet/physical activity intervention or standard antenatal care. The dietary intervention aimed to reduce glycemic load and saturated fat intake. Diet was assessed using a food frequency questionnaire (FFQ) at baseline (15+0-18+6 weeks’ gestation), post intervention (27+0-28+6 weeks) and in late pregnancy (34+0-36+0 weeks). Dietary patterns were characterized using factor analysis of the baseline FFQ data, and changes compared in the control and intervention arms. Patterns were related to pregnancy outcomes in the combined control/intervention cohort (n = 1023).ResultsFour distinct baseline dietary patterns were defined; Fruit and vegetables, African/Caribbean, Processed, and Snacks, which were differently associated with social and demographic factors. The UPBEAT intervention significantly reduced the Processed (−0.14; 95% CI −0.19, −0.08, P <0.0001) and Snacks (−0.24; 95% CI −0.31, −0.17, P <0.0001) pattern scores. In the adjusted model, baseline scores for the African/Caribbean (quartile 4 compared with quartile 1: OR = 2.46; 95% CI 1.41, 4.30) and Processed (quartile 4 compared with quartile 1: OR = 2.05; 95% CI 1.23, 3.41) patterns in the entire cohort were associated with increased risk of gestational diabetes.ConclusionsIn a diverse cohort of obese pregnant women an intensive dietary intervention improved Processed and Snack dietary pattern scores. African/Caribbean and Processed patterns were associated with an increased risk of gestational diabetes, and provide potential targets for future interventions.Trial registrationCurrent controlled trials; ISRCTN89971375

Dietary recommendations for obese pregnant women: current questions and controversies.

With the increasing prevalence of obesity, maternal obesity is now one of the most common high‐risk obstetric conditions. Obesity and excessive gestational weight gain are important modifiable risk factors for maternal and neonatal morbidity and mortality. Maternal obesity, associated with neonatal adiposity and high birthweight, has been implicated in increased risk of childhood obesity. Considerable effort has been directed towards improving clinical outcomes by lifestyle change in pregnant obese women, but there is at present no evidence‐based intervention of adequate efficacy which can be recommended. The focus has been on preventing excessive weight gain, but studies have lacked the power to address effects on clinical outcomes; therefore preventing clinical practice translation. Adequately powered intervention studies devised to reduce neonatal adiposity by improvement of maternal glucose homeostasis, are needed to inform the optimal dietary and/or physical activity regimen.

User engagement in the delivery and design of maternity services.

User engagement is defined as a mutual exchange of information between the patient and the health professional, which has shown to improve patient experience as well as outcomes. Engaging the patient is vital for the healthcare system to remain sustainable. The National Health Service has attempted to incorporate and enhance patient engagement in the delivery of maternity services for the last decade. The financial crisis, changing socio-demographic status, increase in birth rate and public expectations-engaging the patient to take responsibility of their own health has not been achieved. Through in-depth examinations of these barriers we are able to draw conclusions as to why current policies have failed and recommend potential solutions.

Cord metabolic profiles In obese pregnant women; insights into offspring growth and body composition

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 offsprings cord blood metabolic profile and to examine associations of the cord blood metabolic profile with maternal clinical characteristics and offspring anthropometry at birth and age 6 months. Design Randomized controlled trial and cohort study. Setting The UK Pregnancies Better Eating and Activity Trial. Participants Three hundred forty-four mother-offspring pairs. Intervention Antenatal behavioral 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 glycemia, specifically fasting glucose at 28 weeks gestation, had a linear association with higher cord blood concentrations of lysophosphatidylcholines (LPCs) 16.1 (β = 0.65; 95% confidence interval: 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 LPCs was associated with infant z scores of birth weight (0.04; 0.02 to 0.07) and weight at age 6 months (0.05; 0.00 to 0.10). Cord blood insulin growth factor (IGF)-1 and adiponectin concentrations were positively associated with infant weight z score at birth and at 6 months. Conclusions Concentrations of LPCs 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.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 offsprings cord blood metabolic profile and to examine associations of the cord blood metabolic profile with maternal clinical characteristics and offspring anthropometry at birth and age 6 months. Design: Randomized controlled trial and cohort study. Setting: The UK Pregnancies Better Eating and Activity Trial. Participants: Three hundred forty-four mother-offspring pairs. Intervention: Antenatal behavioral 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 glycemia, specifically fasting glucose at 28 weeks gestation, had a linear association with higher cord blood concentrations of lysophosphatidylcholines (LPCs) 16.1 (beta = 0.65;95% confidence interval: 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 LPCs was associated with infant z scores of birth weight (0.04;0.02 to 0.07) and weight at age 6 months (0.05;0.00 to 0.10). Cord blood insulin growth factor (IGF)-1 and adiponectin concentrations were positively associated with infant weight z score at birth and at 6 months. Conclusions: Concentrations of LPCs 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.

The UPBEAT Behavioural Intervention in Obese Pregnant Women - Maternal and Infant Follow-Up 6 Months Postpartum

INTRODUCTION: Prenatal Maternal stress (PNMS) is associated with reduced type 2 11 β - hydroxysteroid deshydrogenase (11 β -HSD2) and type 1 glucose transporter (GLUT1). Cortisol exerts its action by binding to glucocorticoid receptor alpha (GR- α ) that acts as a transcription factor. The enzyme 11 β -HSD2 protects the fetus from adverse cortisol levels from the mother by converting cortisol to inactive cortisone. This study aims to determine if the placenta mediates the effects of disaster-related PNMS (i.e., 2011 Queensland Flooding, Australia) on placental endocrine function. We hypothesize that: (i) Increased PNMS will be associated with lower placental 11 β -HSD2 gene expression which will be moderated by fetal sex; and (ii) Increased PNMS will be associated with a lower placental index (fetal weight to placental weight) which will be moderated by placental 11 β -HSD2, GLUT-1 and/or GR- α gene expression. METHODS: We assessed the women’s level of objective hardship (i.e., events they experienced) and subjective distress (i.e., their psychological reaction to the flooding) shortly after the flooding. Placental villi (trophoblastic tissues) from 96 placentas were processed and samples flash frozen immediately after delivery. Gene expression was evaluated by RT-qPCR. Regression and moderation were used for statistical analyses. RESULTS: Results indicate that a higher level of subjective distress is associated with greater 11 β -HSD2 gene expression in male fetuses and lower 11 β -HSD2 gene expression in female fetuses ( ∆ R 2 =0.074). Results also indicate that high levels of objective hardship coupled with high levels of 11 β -HSD2 gene expression (R 2 =0.092), low levels of GLUT-1 gene expression (R 2 =0,126), or low levels of GR- α gene expression (R 2 =0.117) is associated with higher placental index. CONCLUSIONS: These results suggest that disaster-related PNMS influences placental gene expression in a sex dependent manner. These changes in placental gene/protein expression demonstrate the different survival strategies of the feto-placental unit in case of PNMS depending on fetal sex.INTRODUCTION: Depression during pregnancy occurs in about 20% of women, of which 13% take antidepressants. SSRIs are the most commonly prescribed antidepressants for pregnant women, although their effects on placental function have never been studied. A successful pregnancy depends on healthy placental development and function. The extravillous trophoblast cells (evTBs), which invade the uterine wall, are crucial for embryo implantation and the adaptation of maternal spiral arteries. Poor invasion/migration of evTBs can cause important pregnancy complications such as preeclampsia and possibly maternal and fetal mortality. The aim of this study was to determine whether SSRIs commonly used during pregnancy affect migratory and invasive properties of JEG3 cells, used as a model of the evTBs. METHODS: JEG3 cells were treated with increasing concentrations (0.03-10 μM) of fluoxetine, norfluoxetine or sertraline. Cell proliferation was monitored in real-time using a cell impedance-based xCELLigence system. JEG3 cell-cycle distribution was analyzed by flow cytometry. Migration was determined using a scratch test. Activities of metalloproteinases MMP-2 and MMP-9 (markers of invasion) were determined by gelatin zymography. RESULTS: Fluoxetine and sertraline significantly decreased JEG3 cell proliferation at 10 μM by 93% and 98%, respectively ([Figure 1]-fluoxetine), compared to control, whereas norfluoxetine had no effect. Fluoxetine decreased the number of cells in the G2-M at 1 and 10 μM, and the number of cells in G0-G1 at 10 μM. None of the SSRIs affected JEG3 migration ([Figure 2]-fluoxetine) or the activities of MMP-2 and MMP-9. Legend: Figure 1: Effect of fluoxetine on extravillous trophoblast-like JEG3 cell proliferation determined by real-time impedance monitoring. Statistically significantly different from DMSO-treated cells. Figure 2: Effect of fluoxetine on extravillous trophoblast-like JEG3 cell migration determined by scratch test. CONCLUSIONS: This study suggests that the SSRIs fluoxetine, norfluoxetine and sertraline do not alter extravillous trophoblast viability or migration at therapeutic levels. Our observations will be verified using primary cultures of evTBs and will include additional SSRIs.

Gestational diabetes modifies the association between PlGF in early pregnancy and preeclampsia in women with obesity

Objective To identify clinical and biomarker risk factors for preeclampsia in women with obesity and to explore interactions with gestational diabetes, a condition associated with preeclampsia. Study design In women with obesity (body mass index ≥ 30 kg/m2) from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we examined 8 clinical factors (socio-demographic characteristics, BMI, waist circumference and clinical variables) and 7 biomarkers (HDL cholesterol, hemoglobin A1c, adiponectin, interleukin-6, high sensitivity C-reactive protein, and placental growth factor (PlGF)) in the early second trimester for association with later development of preeclampsia using logistic regression. Factors were selected based on prior association with preeclampsia. Interaction with gestational diabetes was assessed. Main outcome measure Preeclampsia. Results Prevalence of preeclampsia was 7.3% (59/824). Factors independently associated with preeclampsia were higher mean arterial blood pressure (Odds Ratio (OR) 2.22; 95% Confidence Interval (CI) 1.58–3.12, per 10 mmHg) and lower PlGF (OR 1.39; 95% CI 1.03–1.87, per each lower 1 log2). The association of PlGF with preeclampsia was present amongst obese women without gestational diabetes (OR 1.91; 95% CI 1.32–2.78), but not in those with GDM (OR 1.05; 95% CI 0.67–1.63), p = 0.04 for interaction. Conclusion The relationship between PlGF and preeclampsia differed in women with obesity according to gestational diabetes status, which may suggest different mechanistic pathways to preeclampsia. Whilst replication is required in other populations, this study suggests that performance of prediction models for preeclampsia should be confirmed in pre-specified subgroups.

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

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-digesting, low-glycemic load (SD-LGL) beverage improves glucose tolerance in obese pregnant women without GDM. METHODS This was a 3-arm comparison study comparing the effects of an SD-LGL nutritional beverage (glycemic load [GL] 730), an isocaloric control beverage (GL 1124), and habitual diet on glycemia in obese pregnant women. Sixteen women (mean body mass index 37 kg/m2) were recruited at 24-28 weeks to receive either the SD-LGL or eucaloric control beverage. This was consumed with breakfast and as a midafternoon snack over 2 days with a controlled diet. Following a 2-day washout period of habitual diet, women completed 2 days on the alternative beverage with controlled diet. A 10-h fast preceded each intervention phase. Twenty-four hour glucose was measured using continuous glucose monitoring. RESULTS Consumption of the lower GL beverage was associated with improved measures of glycemia, compared with the control beverage and habitual diet at different time periods. Glucose estimates for control versus SD-LDL at 24 h (0.23 mmol/L [0.16 to 0.31], P < 0.001), daytime (0.26 mmol/L [0.18 to 0.34], P < 0.001), and nighttime (0.05 mmol/L [-0.01 to 0.11], P = 0.09). Postprandial glucose was lower after breakfast but not after dinner, compared with the control beverage (0.09 mmol/L [0.01 to 0.18], P = 0.03). CONCLUSION A slow-digesting, low-glycemic nutritional beverage may facilitate improved glucose control in obese pregnant women. To address potential benefit for clinical outcomes, a randomized controlled trial is warranted.

Placental lipid droplet composition: Effect of a lifestyle intervention (UPBEAT) in obese pregnant women

Maternal obesity is associated with adverse outcomes. Placental lipid droplets (LD) have been implicated in maternal-fetal lipid transfer but it is not known whether placental LD fat composition is modifiable. We evaluated the effects of a diet and physical activity intervention in obese pregnant women compared to routine antenatal care (UPBEAT study) on placental LD composition. LD were isolated by ultracentrifugation. Total FAs and phospholipids (phosphatidylcholines, PCs; sphingomyelins, SMs and lyso-phosphatidylcholines, Lyso-PCs) were analyzed by LC-MS/MS. Placenta MFSD2a expression was assessed by western blot. Placental LDs from obese women were comprised of predominantly saturated and monounsaturated FAs. TG and Chol composition was similar between intervention (n = 20) and control (n = 23) groups. PCs containing dihomo-ɣ-linolenic acid in LD were positively associated with gestational weight gain (P < 0.007), and lowered by the intervention. In the whole sample, PCs carrying DHA and arachidonic acid were inversely associated with placental weight. Placenta MFSD2a expression was associated with DHA cord blood metabolites and relationships were observed between LD lipids, especially DHA carrying species, and cord blood metabolites. We describe placenta LD composition for the first time and demonstrate modest, potentially beneficial effects of a lifestyle intervention on LD FAs in obese pregnant women.