The effects of prenatal and postnatal high-dose vitamin B-12 supplementation on human milk vitamin B-12: a randomized, double-blind, placebo-controlled trial in Tanzania.

BACKGROUND: Vitamin B-12 status in human milk (HM) has critical implications for infant growth and development. Few studies have separately evaluated the effects of prenatal and postnatal maternal high-dose vitamin B-12 supplementation on HM vitamin B-12 concentration. OBJECTIVES: This randomized controlled trial aimed to assess the effects of prenatal and postnatal vitamin B-12 supplementation on HM vitamin B-12 at 6 wk and 7 mo postpartum. METHODS: Pregnant women were enrolled in Dar es Salaam, Tanzania, between 2001 and 2004. From recruitment (12-27 weeks of gestation) through 6 wk postpartum, participants were randomly assigned to daily oral multiple micronutrient supplementation or placebo. From 6 wk to 18 mo postpartum, a subset of participants was randomly assigned to a postnatal supplement or placebo. The supplement included 50 µg/d of vitamin B-12 and various other vitamins. HM vitamin B-12 concentrations were analyzed at 6 wk and 7 mo postpartum for 412 participants. RESULTS: The prevalence of HM vitamin B-12 of <310 pmol/L was 73.3% and 68.4% at 6 wk and 7 mo postpartum, respectively. Prenatal supplementation increased HM vitamin B-12 concentration (percent difference: 34.4; 95% CI: 17.0, 54.5; P < 0.001) at 6 wk; this effect was not present at 7 mo. Postnatal supplementation increased HM vitamin B-12 concentration (percent difference: 15.9; 95% CI: 1.91, 31.9; P = 0.025) at 7 mo. Effect modification between prenatal and postnatal supplementation on HM vitamin B-12 status at 7 mo was found, with the effects of prenatal and postnatal supplements more pronounced among those receiving control during the other period; the prenatal supplement had a greater effect with postnatal control, and the postnatal supplement had a greater effect with prenatal control. CONCLUSIONS: Prenatal maternal vitamin B-12 supplementation has benefits on short-term HM status, and postnatal maternal vitamin B-12 supplementation has benefits on long-term HM status. This trial was registered at clinicaltrials.gov as NCT00197548. https://clinicaltrials.gov/ct2/show/NCT00197548.

Maternal breastfeeding is associated with offspring microbiome diversity; a secondary analysis of the MicrobeMom randomized control trial.

Background: Microbial dysbiosis in infancy can influence long-term health outcomes such as childhood obesity. The aim of this study is to explore relationships among maternal well-being during pregnancy, breastfeeding, and the infant gut microbiome. Methods: This is a secondary analysis of healthy pregnant women from the MicrobeMom study, a double-blind randomized control trial of maternal probiotic supplementation (Bifidobacterium breve 702258) versus placebo antenatally and up to 3 months postpartum. Maternal well-being was assessed using the WHO-5 well-being index at 16 weeks' and 34 weeks' gestation. Breastfeeding practices were recorded at discharge from hospital and at 1 month postpartum. Infant stool samples were obtained at 1 month of age. Next generation shotgun sequencing determined infant microbial diversity. Independent sample t-tests and Mann-Whitney U tests informed adjusted regression analysis, which was adjusted for delivery mode, antibiotics during delivery, maternal age and body mass index (BMI), and probiotic vs. control study group. Results: Women (n = 118) with at least one measure of well-being were on average 33 years (SD 3.93) of age and 25.09 kg/m2 (SD 3.28) BMI. Exclusive breastfeeding was initiated by 65% (n = 74). Any breastfeeding was continued by 69% (n = 81) after 1 month. In early and late pregnancy, 87% (n = 97/111) and 94% (n = 107/114) had high well-being scores. Well-being was not associated with infant microbial diversity at 1 month. In adjusted analysis, exclusive breastfeeding at discharge from hospital was associated with infant microbial beta diversity (PC2; 0.254, 95% CI 0.006, 0.038). At 1 month postpartum, any breastfeeding was associated with infant microbial alpha diversity (Shannon index; -0.241, 95% CI -0.498, -0.060) and observed species; (-0.325, 95% CI -0.307, -0.060), and infant microbial beta diversity (PC2; 0.319, 95% CI 0.013, 0.045). Exclusive breastfeeding at 1 month postpartum was associated with infant alpha diversity (Shannon index -0.364, 95% CI -0.573, -0.194; Simpson index 0.339, 95% CI 0.027, 0.091), and infant's number of observed microbial species (-0.271, 95% CI -0.172, -0.037). Conclusion: Breastfeeding practices at 1 month postpartum were associated with lower microbial diversity and observed species in infants at 1 month postpartum, which is potentially beneficial to allow greater abundance of Bifidobacterium. Clinical trial registration: ISRCTN53023014.

Maternal Well-Being in Pregnancy and Breastfeeding Practices: Findings from the ROLO Study.

OBJECTIVE: Low mood is common during the perinatal period, which may negatively impact breastfeeding practices. Exploring predictors of successful breastfeeding is a health priority area. This study investigated if maternal well-being during pregnancy is associated with breastfeeding practices. STUDY DESIGN: This is a secondary analysis of a randomized control trial of a low glycemic index diet in pregnancy. A total of 610 secundigravida women were recruited in the National Maternity Hospital, Dublin, Ireland. Data on maternal education attainment, early pregnancy body mass index (BMI), and age were collected from hospital records. Well-being was self-reported by mothers between 10 and 28 weeks' gestation using the World Health Organization 5-Item well-being index. Scores were transformed to give percentage well-being. Mothers recorded breastfeeding practices at hospital discharge and at the study follow-up appointments. Chi-squares and independent t-tests determined initial differences in breastfeeding practices. Multiple and logistic regression analyses were used to adjust for confounders. RESULTS: Average maternal age was 32.7 years; average BMI was 26.6 kg/m2, and 56% had achieved third-level education. The average well-being score was 58.2%. In unadjusted analysis, high well-being scores were associated with exclusive breastfeeding (56.2% breastfed vs. 46%, breastfed p < 0.03). After adjusted analysis, these associations were no longer significant (odds ratio: 1.00, 95% confidence interval: 0.99-1.01). No other associations were found. CONCLUSION: Our findings indicated 25% of pregnant women in the first trimester reported low well-being scores. Associations between maternal well-being and breastfeeding patterns were explained by maternal age and education level, suggesting low mood may not be a barrier to breastfeeding initiation or duration. This trial is registered at: https://www.isrctn.com/ ISRCTN54392969. KEY POINTS: · Well-being during pregnancy is often diminished and the WHO 5-Item well-being index is a useful measure in clinical settings to assess maternal well-being.. · Breastfeeding is a high-priority research area, particularly in an Irish setting.. · Well-being was not related to breastfeeding, however age, BMI and education were the main predictors of low well-being during pregnancy..

Ability of Bifidobacterium breve 702258 to transfer from mother to infant: the MicrobeMom randomized controlled trial.

BACKGROUND: The composition of the infant microbiome can have a variety of short- and long-term implications for health. It is unclear if maternal probiotic supplementation in pregnancy can affect the infant gut microbiome. OBJECTIVE: This study aimed to investigate if maternal supplementation of a formulation of Bifidobacterium breve 702258 from early pregnancy until 3 months postpartum could transfer to the infant gut. STUDY DESIGN: This was a double-blinded, placebo-controlled, randomized controlled trial of B breve 702258 (minimum 1 × 109 colony-forming units) or placebo taken orally from 16 weeks' gestation until 3 months postpartum in healthy pregnant women. The primary outcome was presence of the supplemented strain in infant stool up to 3 months of life, detected by at least 2 of 3 methods: strain-specific polymerase chain reaction, shotgun metagenomic sequencing, or genome sequencing of cultured B breve. A total of 120 individual infants' stool samples were required for 80% power to detect a difference in strain transfer between groups. Rates of detection were compared using the Fisher exact test. RESULTS: A total of 160 pregnant women with average age of 33.6 (3.9) years and mean body mass index of 24.3 (22.5-26.5) kg/m2, of whom 43% were nulliparous (n=58), were recruited from September 2016 to July 2019. Neonatal stool samples were obtained from 135 infants (65 in intervention and 70 in control group). The presence of the supplemented strain was detected through at least 2 methods (polymerase chain reaction and culture) in 2 infants in the intervention group (n=2/65; 3.1%) and none in the control group (n=0; 0%; P=.230). CONCLUSION: Direct mother-to-infant strain transfer of B breve 702258 occurred, albeit infrequently. This study highlights the potential for maternal supplementation to introduce microbial strains into the infant microbiome.

Application of multilevel linear spline models for analysis of growth trajectories in a cohort with repeat antenatal and postnatal measures of growth: a prospective cohort study.

OBJECTIVES: To model trajectories of antenatal and postnatal growth using linear spline multilevel models. DESIGN: Prospective cohort study. SETTING: Maternity hospital in Dublin, Ireland. PARTICIPANTS: 720-759 mother-child pairs from the ROLO study (initially a randomised control trial of a low glycaemic index diet in pregnancy to prevent recurrence of macrosomia [birth weight >4 kg]). PRIMARY OUTCOMES: Trajectories of growth from 20 weeks gestation (abdominal circumference [AC], head circumference [HC] and weight) or birth (length/height) to 5 years. RESULTS: Over 50% of women had third-level education and 90% were of white ethnicity. Women were a mean (SD) age of 32 years (4.2) at recruitment. The best fitting model for AC, HC and weight included a model with 5 linear spline periods. The best fitting models for length/height included a model with 3 linear spline periods from birth to 6 months, 6 months to 2 years and 2 years to 5 years. Comparison of observed and predicted values for each model demonstrated good model fit. For all growth measures, growth rates were generally fastest in pregnancy or immediately post partum (for length/height), with rates of growth slowing after birth and becoming slower still as infancy and childhood progressed. CONCLUSION: We demonstrate the application of multilevel linear spline models for examining growth trajectories when both antenatal and postnatal measures of growth are available. The approach may be useful for cohort studies or randomised control trials with repeat prospective assessments of growth.

Associations between maternal metabolic parameters during pregnancy and fetal and child growth trajectories from 20 weeks' gestation to 5 years of age: Secondary analysis from the ROLO longitudinal birth cohort study.

OBJECTIVE: To examine the association between maternal metabolic parameters in pregnancy and growth trajectories up to 5 years of age. METHODS: Data from mother-child pairs who participated in the ROLO study, a randomized trial examining the impact of a low glycaemic index diet on the recurrence of macrosomia, were analysed. Fetal and child growth trajectories were developed from longitudinal measurements from 20 weeks gestation up to 5 years of age. We examined associations between maternal fasting glucose, insulin, HOMA-IR and leptin, taken in early pregnancy (14-16 weeks) and late pregnancy (28 weeks), and weight (kg) and abdominal circumference (cm) trajectories using linear spline multilevel models. RESULTS: We found no strong evidence of associations between any maternal metabolic parameters and fetal to childhood weight and abdominal circumference trajectories from 20 weeks gestation to 5 years. CONCLUSION: In a cohort of women with obesity with infants at risk of macrosomia, maternal metabolic markers were not strongly associated with trajectories of weight or abdominal circumference from 20 weeks gestation to 5 years of age.

Recruiting and Engaging Women of Reproductive Age with Obesity: Insights from A Mixed-Methods Study within A Trial.

Engaging women with obesity in health-related studies during preconception is challenging. Limited data exists relating to their participation. The aim of this study is to explore the experiences and opinions of women participating in a weight-related, preconception trial. This is an explanatory sequential (quan-QUAL) mixed-methods Study Within A Trial, embedded in the GetGutsy randomized controlled trial (ISRCTN11295995). Screened participants completed an online survey of eight questions (single or multiple choice and Likert scale) on recruitment, motivations and opinions on study activities. Participants with abdominal obesity (waist circumference ≥ 80 cm) were invited to a subsequent semi-structured, online focus group (n = 2, 9 participants) that was transcribed and analyzed using inductive thematic analysis, with a pragmatic epistemological approach. The survey (n = 102) showed the main research participation motivations were supporting health research (n = 38, 37.3%) and wanting health screening (n = 30, 29.4%). Most participants were recruited via email (n = 35, 34.7%) or social media (n = 15, 14.7%). In the FGs, participants valued flexibility, convenience and. research methods that aligned with their lifestyles. Participants had an expanded view of health that considered emotional well-being and balance alongside more traditional medical assessments. Clinical trialists should consider well-being, addressing the interconnectedness of health and incorporate a variety of research activities to engage women of reproductive age with obesity.

Addressing the gaps in nutritional care before and during pregnancy.

The present paper outlines current issues in the nutritional care of women during pregnancy and potential resources to address them. Globally, overnutrition, undernutrition and nutritional imbalances are widespread among women of reproductive age; increasing the risk of pregnancy complications and non-communicable diseases in both mothers and their children. Most women do not meet dietary guidelines for pregnancy. The World Health Organisation (WHO) recommends nutrition and weight counselling during pregnancy for all women. However, clinical practices focusing on nutrition vary and there is no consensus on which outcomes are most important for pregnancy nutrition interventions, with little consideration for the 'patient voice'. The International Federation of Gynaecology and Obstetrics (FIGO) nutrition checklist is a clinical practice tool that is available for healthcare professionals that will address this issue. The pregnancy nutrition core outcome set will also support advancement of antenatal nutrition by identifying the most critical nutrition-related outcomes from the perspective of healthcare professionals, researchers and women with experience of pregnancy. While poor nutrition can result in adverse outcomes across women of all weight categories, those with obesity may require specialist care to reduce their risk. Obesity is a chronic, progressive, relapsing disease that has high individual variability in its prognosis. The use of obesity staging systems, which consider mental, physical and functional health, can stratify individuals into risk categories and aid in treatment prioritisation in pregnancy. As the prevalence of obesity continues to rise, an obesity staging approach may support clinicians, especially those in limited resource settings.

Higher Inflammation Is Associated with Cardiometabolic Phenotype and Biochemical Health in Women with Obesity.

INTRODUCTION: Metabolic or inflammatory markers may predict adverse outcomes in women with obesity. We sought to describe metabolic-obesity phenotypes of women using novel staging tools and investigate relationships with inflammation. METHODS: In a cross-sectional study, we collected fasting blood samples from sixty-four females with body mass index (BMI) ≥28 kg/m2. Participants were classified as metabolically healthy or metabolically unhealthy obesity (MUO) using the cardiometabolic disease staging system (CMDS) and Edmonton obesity staging system (EOSS). Data were analyzed using independent sample t tests, Pearson's correlations, and multiple logistic regression. RESULTS: Mean (SD) age was 40.2 (9.3) years with median (IQR) BMI 31.8 (30.3-35.7) kg/m2. The prevalence of MUO was 46.9% and 81.3% using CMDS and EOSS criteria, respectively. Women with raised CMDS scores had higher C3 (1.34 [0.20] vs. 1.18 [0.15], p = 0.001) and C-reactive protein (CRP) (2.89 [1.31-7.61] vs. 1.39 [0.74-3.60], p = 0.034). C3 correlated with insulin (r = 0.52), hemoglobin A1c (r = 0.37), and C-peptide (r = 0.58), all p < 0.05. C3 above the median (>1.23 g/L) increased odds of raised CMDS score, when controlled for age, BMI, ethnicity, and smoking (OR = 6.56, 95% CI: 1.63, 26.47, p = 0.008). CONCLUSION: The prevalence of MUO was lower using CMDS than EOSS. C3 and CRP may be useful clinical biomarkers of risk or treatment targets in women with obesity.

Diet and mental health in pregnancy: Nutrients of importance based on large observational cohort data.

OBJECTIVE: To determine associations between dietary intake and well-being in pregnancy. METHODS: This retrospective cohort analysis combined three studies: the ROLO Study (a randomized controlled trial of a low-glycemic-index diet in pregnancy), the Pregnancy Exercise and nutrition Research Study with smartphone application support (PEARS), and a randomized controlled trial on probiotics. All data were collected before study interventions (16 wk). Dietary intakes during pregnancy were determined using 3-day food diaries. The five-item World Health Organization Well-Being Index was used to assess mental well-being. Initial associations were evaluated using Pearson correlations and further defined with multiple regression analysis adjusted for age, body mass index (BMI), Pobal Haase and Pratschke deprivation index, and metabolic equivalent of task minutes scores. RESULTS: A total of 1521 women were included in the analysis (mean age, 32+4 y; mean BMI, 27 kg/m2 [IQR, 17-56 kg/m2]). The mean well-being score was 59%. Regression analysis showed that fiber (B = 0.07; P = 0.02), magnesium (B = 0.08; P < 0.01), niacin (B = 0.09; P < 0.01), thiamine (B = 0.07; P = 0.01), and folate (B = 0.08; P = 0.02) were all positively and significantly associated with well-being in a pregnant population. The Benjamini-Hochberg procedure to correct for multiple testing was applied, and significance remained. CONCLUSIONS: Maternal nutrition and well-being are related during early pregnancy. Our findings suggest that fiber, magnesium, and particular B vitamins may be of importance for promoting positive mental well-being during pregnancy.

The Edmonton Obesity Staging System and pregnancy outcomes in women with overweight or obesity: A secondary analysis of a randomized controlled trial.

The Edmonton Obesity Staging System (EOSS) is a proposed clinical practice tool to determine obesity severity. In a secondary analysis of the Pregnancy Exercise and Research Study (PEARS) (a mobile-health-supported lifestyle intervention among pregnant women with body mass index [BMI] ≥25 kg/m2 ), we apply the EOSS and explore relationships with pregnancy outcomes. In early (14-16 weeks) and late (28 weeks) pregnancy, fasting lipids and glucose were measured, blood pressure was extracted from medical records and maternal well-being was assessed using the WHO-5 Well-being Index. Pearson's correlations, chi-square statistics and multiple logistic regression were used to identify relationships. One-way analysis of variance was used to compare groups. Pregnant women (n = 348) were mean (SD) age 32.44 (4.39) years and median (interquartile range) BMI 28.0 (26.57, 29.88) kg/m2 . Using metabolic criteria only, 81.9% and 98.9% had raised EOSS scores in early and late pregnancy. From early to late pregnancy, EOSS scores increased by 60.1%. Of these, 10.5% experienced a 2-point increase, moving from stage 0 to stage 2. There was a potential relationship between early EOSS and large for gestational age (χ2  = 6.42, df (2), p = .04), although significance was lost when controlled for confounders (p = .223) and multiple testing. Most women with BMI ≥25 kg/m2 had raised EOSS scores, limiting the clinical utility of the tool.

Effect of an Antenatal Lifestyle Intervention on Dietary Inflammatory Index and Its Associations with Maternal and Fetal Outcomes: A Secondary Analysis of the PEARS Trial.

We investigated the effect of an antenatal lifestyle intervention of a low-glycaemic index (GI) diet and physical activity on energy-adjusted dietary inflammatory index (E-DIITM) and explored its relationship with maternal and child health in women with overweight and obesity. This was a secondary analysis of 434 mother-child pairs from the Pregnancy Exercise and Nutrition Study (PEARS) trial in Dublin, Ireland. E-DIITM scores were calculated for early (10-16 weeks) and late (28 weeks) pregnancy. Outcomes included lipids, inflammation markers, insulin resistance, mode of delivery, infant size, pre-eclampsia, and gestational diabetes. T-tests were used to assess changes in E-DIITM. Chi-square, correlations, and multiple regression were employed to investigate relationships with outcomes. The mean (SD) age of participants was 32.45 (4.29) years with median (IQR) BMI 28.25 (26.70, 31.34) kg/m2. There was no change in E-DIITM in the controls (-0.14 (1.19) vs. -0.07 (1.09), p = 0.465) but E-DIITM reduced by 10% after the intervention (0.01 (1.07) vs -0.75 (1.05), p < 0.001). No associations were found between early pregnancy E-DIITM and maternal and child outcomes, except for increased odds of adverse cardiometabolic phenotype in women who delivered male (OR = 2.29, p = 0.010) but not female infants (OR = 0.99, p = 0.960). A low-GI antenatal intervention can reduce the inflammatory potential of diets. Sex differences should be explored further in future research.

The association of a low glycaemic index diet in pregnancy with child body composition at 5 years of age: A secondary analysis of the ROLO study.

INTRODUCTION: Childhood obesity remains a significant global health concern. Early intervention through maternal diet during pregnancy represents a possible mode of improving childhood adiposity. AIM: To examine the impact of a low glycaemic index diet during pregnancy on offspring anthropometry at 5 years of age. METHODS: This is a secondary analysis of 387 children from the ROLO pregnancy study 5 years' post-intervention. At the follow-up, BMI, circumferences and skinfold thickness were obtained. A subgroup of 103 children had a DXA scan completed. Statistical analyses included Independent sample t tests, Mann Whitney-U tests and chi-square tests to compare the intervention and control groups. Adjusted analysis using linear regression controlled for significant confounders between participants who returned at follow-up and those that did not. RESULTS: There were no significant differences in BMI (16.05 kg/m2 vs 16.16 kg/m2 , P = 0.403), general adiposity (36.60 mm vs 36.00 mm, P = 0.920), central adiposity (0.61 mm vs 0.60 mm, P = 0.540), total fat mass (4.91 kg vs 4.71 kg, P = 0.377) or total lean mass (14.29 kg vs 14.56 kg, P = 0.386) between the intervention and control groups, respectively. No associations were observed in 5-year outcomes in adjusted analyses when controlling for maternal age at delivery, maternal early pregnancy BMI, maternal education and gestational age. CONCLUSION: Our study found no evidence that a low glycaemic index diet in pregnancy impacts offspring anthropometry 5 years' post-intervention. Therefore, modulating maternal carbohydrate quality in pregnancy may not be an appropriate approach to improving weight status in childhood. Future research should investigate the impact of other dietary practices in pregnancy on child health.

Breastfeeding and maternal eating behaviours are associated with child eating behaviours: findings from the ROLO Kids Study.

BACKGROUND: Child eating behaviours can negatively contribute to the development of childhood obesity. This study investigated associations between breastfeeding habits, maternal eating behaviours and child eating behaviours, in 5-year-old children. METHODS: Secundigravida women were recruited to the ROLO dietary randomised controlled trial (Dublin, Ireland) and were followed up with their children to 5 years of age. Breastfeeding exposure and duration were obtained at postnatal and infant follow-up at 2 and 6 months and 2 and 5 years. At 5 years, maternal and child eating behaviours were measured using the Three Factor Eating Questionnaire and the Child Eating Behaviour Questionnaire, respectively. Regression determined associations between breastfeeding habits and maternal eating behaviours with child eating behaviours, controlling for RCT group, maternal education level, maternal BMI at 5 years, childcare exposure and child BMI centile at 5-year follow-up. RESULTS: There were 230 mother and child pairs analysed. One hundred and fifty-eight mothers had initiated breastfeeding. Median breastfeeding duration was 22 (IQR 33) weeks. Children who were never breastfed were more likely to express a desire to drink (B = -1.01, p = 0.022). Longer breastfeeding duration was associated with lower food responsiveness (B = -1.71, p = 0.003). Maternal uncontrolled eating was positively associated with child food responsiveness, emotional overeating and emotional undereating (B = 0.21, p < 0.001; B = 0.14, p = 0.005; B = 0.14, p = 0.005, respectively). Maternal emotional eating was associated with child emotional overeating and undereating (B = 0.27, p < 0.001, B = 0.29, p = 0.004, respectively). CONCLUSION: Not breastfeeding and short breastfeeding duration may contribute to the development of obesogenic eating behaviours in children, alongside maternal eating behaviours including uncontrolled and emotional eating. These 'food approach' eating behaviours may increase risk of overweight/obesity as they are associated with increased energy intake, hence the importance of research surrounding eating behaviours.

The impact of probiotic supplementation on metabolic health in healthy women of reproductive age: a systematic review.

Products containing probiotics are targeted at healthy or at-risk individuals as a preventative measure to minimise disease risk. Most studies assessing the efficacy of probiotics in humans include a mixture of healthy and unhealthy populations, while studies that focus solely on female populations are largely limited to pregnancy or those with health conditions. Pre-conception is a significant time-point during the life-course, and improving female health status during this period may positively influence future offspring. The objective of this review is to assess the effect of probiotics administered in oral capsule formulation, on metabolic and immune markers in healthy, non-pregnant women of reproductive age. This review followed the PRISMA guidelines. Pubmed, EMBASE, CINAHL, and Web of Science were searched for relevant studies. English language articles relating to randomised-controlled trials were included. The search returned 3250 publications after duplicates were removed. Title (2516), abstract (642), and full text (87) screening excluded 3993 studies from consideration. Five papers were identified with outcomes of interest, and analysis of these showed no conclusive evidence that probiotic capsule supplementation elicited positive effects in this healthy population. This study highlights the need for further research to investigate the role that probiotics play during the pre-conception period, on female metabolic and immune health.