Angela C. Flynn

Dietary interventions in overweight and obese pregnant women: a systematic review of the content, delivery, and outcomes of randomized controlled trials.

CONTEXT Interventions targeting maternal obesity are a healthcare and public health priority. OBJECTIVE The objective of this review was to evaluate the adequacy and effectiveness of the methodological designs implemented in dietary intervention trials for obesity in pregnancy. DATA SOURCES A systematic review of the literature, consistent with PRISMA guidelines, was performed as part of the International Weight Management in Pregnancy collaboration. STUDY SELECTION Thirteen randomized controlled trials, which aimed to modify diet and physical activity in overweight and obese pregnant women, were identified. DATA SYNTHESIS There was significant variability in the content, delivery, and dietary assessment methods of the dietary interventions examined. A number of studies demonstrated improved dietary behavior in response to diet and/or lifestyle interventions. Nine studies reduced gestational weight gain. CONCLUSION This review reveals large methodological variability in dietary interventions to control gestational weight gain and improve clinical outcomes in overweight and obese pregnant women. This lack of consensus limits the ability to develop clinical guidelines and apply the evidence in clinical practice.

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.

A Nanoparticulate Ferritin-Core Mimetic Is Well Taken Up by HuTu 80 Duodenal Cells and Its Absorption in Mice Is Regulated by Body Iron

Background: Iron (Fe) deficiency anemia remains the largest nutritional deficiency disorder worldwide. How the gut acquires iron from nano Fe(III), especially at the apical surface, is incompletely understood. Objective: We developed a novel Fe supplement consisting of nanoparticulate tartrate-modified Fe(III) poly oxo-hydroxide [here termed nano Fe(III)], which mimics the Fe oxide core of ferritin and effectively treats iron deficiency anemia in rats. Methods: We determined transfer to the systemic circulation of nano Fe(III) in iron-deficient and iron-sufficient outbread Swiss mouse strain (CD1) mice with use of 59Fe-labeled material. Iron deficiency was induced before starting the Fe-supplementation period through reduction of Fe concentrations in the rodent diet. A control group of iron-sufficient mice were fed a diet with adequate Fe concentrations throughout the study. Furthermore, we conducted a hemoglobin repletion study in which iron-deficient CD1 mice were fed for 7 d a diet supplemented with ferrous sulfate (FeSO4) or nano Fe(III). Finally, we further probed the mechanism of cellular acquisition of nano Fe(III) by assessing ferritin formation, as a measure of Fe uptake and utilization, in HuTu 80 duodenal cancer cells with targeted inhibition of divalent metal transporter 1 (DMT1) and duodenal cytochrome b (DCYTB) before exposure to the supplemented iron sources. Differences in gene expression were assessed by quantitative polymerase chain reaction. Results: Absorption (means ± SEMs) of nano Fe(III) was significantly increased in iron-deficient mice (58 ± 19%) compared to iron-sufficient mice (18 ± 17%) (P = 0.0001). Supplementation of the diet with nano Fe(III) or FeSO4 significantly increased hemoglobin concentrations in iron-deficient mice (170 ± 20 g/L, P = 0.01 and 180 ± 20 g/L, P = 0.002, respectively). Hepatic hepcidin mRNA expression reflected the nonheme-iron concentrations of the liver and was also comparable for both nano Fe(III)– and FeSO4-supplemented groups, as were iron concentrations in the spleen and duodenum. Silencing of the solute carrier family 11 (proton-coupled divalent metal ion transporter), member 2 (Slc11a2) gene (DMT1) significantly inhibited ferritin formation from FeSO4 (P = 0.005) but had no effect on uptake and utilization of nano Fe(III). Inhibiting DCYTB with an antibody also had no effect on uptake and utilization of nano Fe(III) but significantly inhibited ferritin formation from ferric nitrilotriacetate chelate (Fe-NTA) (P = 0.04). Similarly, cellular ferritin formation from nano Fe(III) was unaffected by the Fe(II) chelator ferrozine, which significantly inhibited uptake and utilization from FeSO4 (P = 0.009) and Fe-NTA (P = 0.005). Conclusions: Our data strongly support direct nano Fe(III) uptake by enterocytes as an efficient mechanism of dietary iron acquisition, which may complement the known Fe(II)/DMT1 uptake pathway.

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

The Assessment of Diet Quality and Its Effects on Health Outcomes Pre-pregnancy and during Pregnancy

Overweight and obesity pre pregnancy or during pregnancy is associated with an increased risk for maternal obstetric and fetal complications. Diet is one modifiable risk factor that women may be motivated to improve. General healthy eating guidelines, micronutrient sufficiency and macronutrient quantity and quality are important nutrition considerations pre and during pregnancy. With regards to specific nutrients, health authorities have recommendations for folate and/or iodine supplementation; but not consistently for iron and omega-3 despite evidence for their association with health outcomes. There are modest additional requirements for energy and protein, but not fat or carbohydrate, in mid-late pregnancy. Diet indices and dietary pattern analysis are additional tools or methodologies used to assess diet quality. These tools have been used to determine dietary intakes and patterns and their association with pregnancy complications and birth outcomes pre or during pregnancy. Women who may unnecessarily resist foods due to fear of food contamination from listeriosis and methylmercury may limit their diet quality and a balanced approached is required. Dietary intake may also vary according to certain population characteristics. Additional support for women who are younger, less educated, overweight and obese, from socially disadvantaged areas, smokers and those who unnecessarily avoid healthy foods, is required to achieve a higher quality diet and optimal lifestyle peri conception.

The effect of a lifestyle intervention on pregnancy and postpartum dietary patterns determined by factor analysis

Optimizing maternal diet during pregnancy improves maternal and infant health. This study assessed the effect of an antenatal lifestyle intervention for women with overweight or obesity on dietary patterns during pregnancy and post partum.

The Effects of the UK Pregnancies Better Eating and Activity Trial Intervention on Dietary Patterns in Obese Pregnant Women Participating in a Pilot Randomized Controlled Trial

Objective The objective of this study is to investigate the effects of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) behavioral intervention on dietary patterns in obese pregnant women. Methods Dietary patterns were derived from Food Frequency Questionnaires using principal component analysis in 183 UPBEAT pilot study participants. Results Two unhealthy dietary patterns, processed and traditional, predominantly characterized by foods high in sugar and fat, improved [processed -0.54 (-0.92 to -0.16), P = 0.006 and traditional -0.83 (-1.20 to -0.45), P < 0.001] following the intervention, while a cultural pattern that was found to be associated with the Black African/Caribbean participants did not change [-0.10 (-0.46 to 0.26), P = 0.589]. Conclusion Unhealthy dietary patterns are evident in obese pregnant women. The UPBEAT intervention was effective in improving maternal dietary patterns; however, obese pregnant women from minority ethnic groups may be less receptive to intervention.

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.

Relationships between Maternal Obesity and Maternal and Neonatal Iron Status

Obesity in pregnancy may negatively influence maternal and infant iron status. The aim of this study was to examine the association of obesity with inflammatory and iron status in both mother and infant in two prospective studies in pregnancy: UPBEAT and SCOPE. Maternal blood samples from obese (n = 245, BMI ≥ 30 kg/m2) and normal weight (n = 245, BMI < 25 kg/m2) age matched pregnant women collected at approximately 15 weeks’ gestation, and umbilical cord blood samples collected at delivery, were analysed for a range of inflammatory and iron status biomarkers. Concentrations of C- reactive protein and Interleukin-6 in obese women compared to normal weight women were indicative of an inflammatory response. Soluble transferrin receptor (sTfR) concentration [18.37 nmol/L (SD 5.65) vs. 13.15 nmol/L (SD 2.33)] and the ratio of sTfR and serum ferritin [1.03 (SD 0.56) vs. 0.69 (SD 0.23)] were significantly higher in obese women compared to normal weight women (P < 0.001). Women from ethnic minority groups (n = 64) had higher sTfR concentration compared with white women. There was no difference in maternal hepcidin between obese and normal weight women. Iron status determined by cord ferritin was not statistically different in neonates born to obese women compared with neonates born to normal weight women when adjusted for potential confounding variables. Obesity is negatively associated with markers of maternal iron status, with ethnic minority women having poorer iron statuses than white women.

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

BackgroundMaternal 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.MethodsThree 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.ResultsFormula 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).ConclusionsIn 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.