Urinary ferritin as a non-invasive means of assessing iron status in young children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin is the preferred biomarker for measuring iron status as it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A Non-invasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVE: 1) To determine the correlation between urinary and serum ferritin in young children; 2) To determine if correcting urinary ferritin for creatinine and specific gravity improves the correlation; and 3) To determine a urine ferritin cut point to predict ID. METHODS: Validation study using paired serum and urine collected from 3-year-old children (n=142) participating in a longitudinal birth cohort study; the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive value of urinary ferritin in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin r=0.53 (0.40-0.64) and performed well in predicting those with ID (area under the curve 0.85, 95% CI 0.75-0.94). Urine ferritin < 2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) due to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin showed good diagnostic performance for ID. The non-invasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Effective interventions in preventing gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Lifestyle choices, metformin, and dietary supplements may prevent GDM, but the effect of intervention characteristics has not been identified. This review evaluated intervention characteristics to inform the implementation of GDM prevention interventions. METHODS: Ovid, MEDLINE/PubMed, and EMBASE databases were searched. The Template for Intervention Description and Replication (TIDieR) framework was used to examine intervention characteristics (who, what, when, where, and how). Subgroup analysis was performed by intervention characteristics. RESULTS: 116 studies involving 40,940 participants are included. Group-based physical activity interventions (RR 0.66; 95% CI 0.46, 0.95) reduce the incidence of GDM compared with individual or mixed (individual and group) delivery format (subgroup p-value = 0.04). Physical activity interventions delivered at healthcare facilities reduce the risk of GDM (RR 0.59; 95% CI 0.49, 0.72) compared with home-based interventions (subgroup p-value = 0.03). No other intervention characteristics impact the effectiveness of all other interventions. CONCLUSIONS: Dietary, physical activity, diet plus physical activity, metformin, and myoinositol interventions reduce the incidence of GDM compared with control interventions. Group and healthcare facility-based physical activity interventions show better effectiveness in preventing GDM than individual and community-based interventions. Other intervention characteristics (e.g. utilization of e-health) don't impact the effectiveness of lifestyle interventions, and thus, interventions may require consideration of the local context.

The effect of any given intervention to prevent gestational diabetes (high blood sugar levels that arise during pregnancy) may depend on the way it is delivered (how, when, what, etc). This study reviewed published literature to investigate if the effects of interventions (diet, exercise, metformin, probiotics, myoinositol) to prevent gestational diabetes differ according to the way it is being delivered (e.g., online vs in-person, by health professionals or others, etc.). Exercise delivered to group settings, or those delivered at a healthcare facility worked better to prevent gestational diabetes. Although we did not observe any differences with other delivery characteristics (e.g., online vs in-person), it does not mean they are always equally effective, it is important to consider individual situations when prescribing or developing interventions.

Plasma Sphingomyelins and Carnitine Esters of Infants Consuming Whole Goat or Cow Milk-Based Infant Formulas or Human Milk.

BACKGROUND: Infant formulas are typically manufactured using skimmed milk, whey proteins, and vegetable oils, which excludes milk fat globule membranes (MFGM). MFGM contains polar lipids, including sphingomyelin (SM). OBJECTIVE: The objective of this study was comparison of infant plasma SM and acylcarnitine species between infants who are breastfed or receiving infant formulas with different fat sources. METHODS: In this explorative study, we focused on SM and acylcarnitine species concentrations measured in plasma samples from the TIGGA study (ACTRN12608000047392), where infants were randomly assigned to receive either a cow milk-based infant formula (CIF) with vegetable oils only or a goat milk-based infant formula (GIF) with a goat milk fat (including MFGM) and vegetable oil mixture to the age ≥4 mo. Breastfed infants were followed as a reference group. Using tandem mass spectrometry, SM species in the study formulas and SM and acylcarnitine species in plasma samples collected at the age of 4 mo were analyzed. RESULTS: Total SM concentrations (∼42 µmol/L) and patterns of SM species were similar in both formulas. The total plasma SM concentrations were not different between the formula groups but were 15 % (CIF) and 21% (GIF) lower in the formula groups than in the breastfed group. Between the formula groups, differences in SM species were statistically significant but small. Total carnitine and major (acyl) carnitine species were not different between the groups. CONCLUSIONS: The higher total SM concentration in breastfed than in formula-fed infants might be related to a higher SM content in human milk, differences in cholesterol metabolism, dietary fatty acid intake, or other factors not yet identified. SM and acylcarnitine species composition in plasma is not closely related to the formula fatty acid composition. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12608000047392.

Too Much Too Little: Clarifying the Relationship Between Maternal Iodine Intake and Neurodevelopmental Outcomes.

BACKGROUND: In 2009, the Australian government mandated the fortification of bread salt with iodine. In 2010, pregnant and lactating women were also advised to take an iodine-containing supplement. Our assessment of this policy in an iodine-sufficient population showed that children whose mothers were in the highest and lowest quartiles of iodine intake performed more poorly on early childhood tests of cognition and language than those in the second quartile. However, we did not quantify the iodine intake associated with optimal neurodevelopment. OBJECTIVES: The aim was to establish the iodine intake range in pregnancy associated with optimal child neurodevelopment. METHODS: A prospective cohort study of pregnant women and their young children (n = 699). Iodine intake was assessed by a validated food frequency questionnaire at 16 and 28 wk of gestation. Child neurodevelopment at 18 mo of age was measured using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). The relationship between average iodine intake during pregnancy and child neurodevelopment was assessed using linear regression with fractional polynomials and adjustment for confounders. RESULTS: Mean (SD) iodine intake was similar at study entry and 28 wk, 308 (120) µg/d, with 82% of women taking iodine supplements at study entry. The relationship between iodine intake during pregnancy and Bayley-III cognitive and language scores was curvilinear (P = 0.001 and P = 0.004, respectively), with the lowest Bayley-III scores observed at lower and higher iodine intakes. The inflection point that drove the association between lower iodine intake in pregnancy and poorer child neurodevelopment scores was around 185 µg/d; for the higher pregnancy iodine intakes, language and cognitive scores were negatively affected from ∼350 µg/d to 370 µg/d, respectively. Higher iodine intakes were being driven by supplement use. CONCLUSIONS: Targeted, not blanket, iodine supplementation may be needed for pregnant women with low-iodine intake from food.

Participant characteristics in the prevention of gestational diabetes as evidence for precision medicine: a systematic review and meta-analysis.

BACKGROUND: Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention. METHODS: We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022. RESULTS: From 10347 studies, 116 studies (n = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses. CONCLUSIONS: GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.

An individual's characteristics, such as medical, biochemical, social, and behavioural may affect their response to interventions aimed at preventing gestational diabetes, which occurs during pregnancy. Here, we evaluated the published literature on interventions such as diet, lifestyle, drug treatment and nutritional supplement and looked at which individual participant characteristics were associated with response to these interventions. Certain participant characteristics were associated with greater prevention of gestational diabetes through particular treatments. Some interventions were more effective when started prior to conception. Future studies should consider individual characteristics when assessing the effects of preventative measures.

Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial - study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Observational studies suggest both low and high iodine intakes in pregnancy are associated with poorer neurodevelopmental outcomes in children. This raises concern that current universal iodine supplement recommendations for pregnant women in populations considered to be iodine sufficient may negatively impact child neurodevelopment. We aim to determine the effect of reducing iodine intake from supplements for women who have adequate iodine intake from food on the cognitive development of children at 24 months of age. METHODS AND ANALYSIS: A multicentre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. Using a hybrid decentralised clinical trial model, 754 women (377 per group) less than 13 weeks' gestation with an iodine intake of ≥165 µg/day from food will be randomised to receive either a low iodine (20 µg/day) multivitamin and mineral supplement or an identical supplement containing 200) µg/day (amount commonly used in prenatal supplements in Australia), from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age assessed with the Cognitive Scale of the Bayley Scales of Infant Development, fourth edition. Secondary outcomes include infant language and motor development; behavioural and emotional development; maternal and infant clinical outcomes and health service utilisation of children. Cognitive scores will be compared between groups using linear regression, with adjustment for location of enrolment and the treatment effect described as a mean difference with 95% CI. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/17/WCHN/187). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04586348.

Iodine-only supplements for breastfeeding women: a call to action in New Zealand.

Nil.

Maternal metabolic factors and the association with gestational diabetes: A systematic review and meta-analysis.

Gestational diabetes (GDM) is associated with several adverse outcomes for the mother and child. Higher levels of individual lipids are associated with risk of GDM and metabolic syndrome (MetS), a clustering of risk factors also increases risk for GDM. Metabolic factors can be modified by diet and lifestyle. This review comprehensively evaluates the association between MetS and its components, measured in early pregnancy, and risk for GDM. Databases (Cumulative Index to Nursing and Allied Health Literature, PubMed, Embase, and Cochrane Library) were searched from inception to 5 May 2021. Eligible studies included ≥1 metabolic factor (waist circumference, blood pressure, fasting plasma glucose (FPG), triglycerides, and high-density lipoprotein cholesterol), measured at <16 weeks' gestation. At least two authors independently screened potentially eligible studies. Heterogeneity was quantified using I2 . Data were pooled by random-effects models and expressed as odds ratio and 95% confidence intervals (CIs). Of 7213 articles identified, 40 unique articles were included in meta-analysis. In analyses adjusting for maternal age and body mass index, GDM was increased with increasing FPG (odds ratios [OR] 1.92; 95% CI 1.39-2.64, k = 7 studies) or having MetS (OR 2.52; 1.65, 3.84, k = 3). Women with overweight (OR 2.17; 95% CI 1.89, 2.50, k = 12) or obesity (OR 4.34; 95% CI 2.79-6.74, k = 9) also were at increased risk for GDM. Early pregnancy assessment of glucose or the MetS, offers a potential opportunity to detect and treat individual risk factors as an approach towards GDM prevention; weight loss for pregnant women with overweight or obesity is not recommended. Systematic review registration: PROSPERO CRD42020199225.

Prevalence of thyroid dysfunction in postpartum women with suboptimal iodine and selenium and adequate iron status.

OBJECTIVE: Postpartum women experience thyroid dysfunction at twice the prevalence of the general population. Adequate biosynthesis of thyroid hormones depends on three trace elements: iodine, selenium and iron. This study aimed to investigate thyroid dysfunction within a cohort of women at six months postpartum in relation to iodine, selenium and iron status. DESIGN: This cross-sectional study was part of an observational longitudinal cohort Mother and Infant Nutrition Investigation; data obtained at six months postpartum are reported. SUBJECTS: Mother-infant pairs (n = 87) were recruited at three months postpartum and followed up at six months postpartum (n = 78). MEASUREMENTS: Thyroid hormones (free triiodothyronine, free thyroxine, thyroid-stimulating hormone) and thyroid peroxidase antibodies were measured. Urinary iodine concentration, breast milk iodine concentration, serum thyroglobulin, plasma selenium, serum ferritin and serum soluble transferrin receptors were determined. Nonparametric data were expressed as median (25th, 75th percentile). RESULTS: Thyroid dysfunction was found in 18% of women, and 4% of women had iron deficiency. Median urinary iodine concentration was 85 (43, 134) µg/L, median breast milk iodine concentration was 59 (39, 109) µg/L, and median serum thyroglobulin at 11.4 (8.6, 18.6) µg/L, indicating iodine deficiency. Median plasma selenium concentration was 105.8 (95.6, 115.3) µg/L. Women with marginally lower plasma selenium concentration were 1.12% times more likely to have abnormal TSH concentrations (p = .001). CONCLUSIONS: There was a high prevalence of thyroid dysfunction. Plasma selenium concentration was the only significant predictor of the likelihood that women had thyroid dysfunction within this cohort, who were iodine deficient and mostly had adequate iron status. Strategies are required to improve both iodine and selenium status to better support maternal thyroid function.

Use of Iodine Supplements by Breastfeeding Mothers Is Associated with Better Maternal and Infant Iodine Status.

Adequate iodine status during conception, pregnancy and lactation is essential for supporting infant neurodevelopment. Iodine status in adults and children was improved after two New Zealand government initiatives, but the status of breastfeeding women is unknown. This study aimed to investigate the iodine intake and status of lactating mother-infant pairs at 3 months postpartum and to assess maternal iodine knowledge and practice. Iodine intake was estimated by a weighed 4-day diet diary (4DDD). Maternal urinary iodine concentrations (UIC) in spot urine, breast milk iodine concentrations (BMIC) and infant UIC were measured. Questions about iodine-specific knowledge and practice were asked. In 87 breastfeeding mother-infant pairs, maternal iodine intake was 151 (99, 285) µg/day, and 58% had an intake below the estimated average requirement (EAR) of 190 µg/day. Maternal median UIC (MUIC) was 82 (46, 157) µg/L indicating iodine deficiency (i.e., < 100 µg/L). Women who used iodine-containing supplements had a significantly higher MUIC (111 vs 68 µg/L, P = 0.023) and BMIC (84 vs 62 µg/L, P < 0.001) than non-users. Infants fed by women using iodine-containing supplements had a higher MUIC (150 vs 86 µg/L, P = 0.036) than those of non-users. A total of 66% (57/87) of women had no or low iodine knowledge. The iodine knowledge score was a statistically significant predictor of consuming iodine-containing supplements [(beta = 1.321, P = 0.008)]. Despite a decade of initiatives to increase iodine intakes in New Zealand, iodine knowledge was low; iodine intake and status of these lactating women were suboptimal, but women who used iodine-containing supplement were more likely to achieve adequate status.Study Registration Number (Australia and New Zealand Clinical Trials Registry): ACTRN12615001028594.

Mother and Infant Nutrition Investigation in New Zealand (MINI Project): Protocol for an Observational Longitudinal Cohort Study.

BACKGROUND: Thyroid dysfunction is associated with cognitive impairment, mood disturbance, and postnatal depression. Sufficient thyroid hormone synthesis requires adequate intake of iodine, selenium, and iron. Iodine deficiency was historically a problem for New Zealand, and initiatives were introduced to overcome the problem: (1) mandatory fortification of all bread (except organic) with iodized salt (2009) and (2) provision of subsidized iodine supplements for pregnant and breastfeeding women (2010). Subsequent to these initiatives, most adults and children have adequate iodine status; however, status among breastfeeding women and their infants remains unclear. This paper outlines the methodology of the Mother and Infant Nutrition Investigation (MINI) study: an observational longitudinal cohort study of breastfeeding women and their infants. OBJECTIVE: This study will determine (1) women's iodine intake and status among supplement users and nonusers; (2) women's intake and status of iodine, selenium, and iron relating to thyroid function; (3) associations between women's selenium status, thyroid function, and postnatal depression; (4) infants' iodine and selenium status relating to first year neurodevelopment. METHODS: Breastfeeding women aged over 16 years with a healthy term singleton infant were recruited from Manawatu, New Zealand. Participants attended study visits 3, 6, and 12 months postpartum. Maternal questionnaires investigated supplement use before and after birth, iodine knowledge, and demographic information. Dietary assessment and urine, blood, and breast milk samples were taken to measure iodine, selenium, and iron intake/status. The Edinburgh Postnatal Depression Scale was used repeatedly to screen for postnatal depression. Thyroid hormones (free triiodothyronine, free thyroxine, thyroid stimulating hormone, thyroglobulin, antithyroglobulin antibodies, and antithyroid peroxidase) were measured in blood samples, and thyroid gland volume was measured by ultrasound at 6 months postpartum. Infant iodine and selenium concentrations were determined in urine. The Ages and Stages Questionnaire was used to assess infant development at 4, 8, and 12 months. RESULTS: Data collection was completed. Biological samples analysis, excluding nail clippings, is complete. Data analysis and presentation of the results will be available after 2020. CONCLUSIONS: This study will provide data on the current iodine status of breastfeeding women. It will also provide a greater understanding of the three essential minerals required for optimal thyroid function among breastfeeding women. The prospective longitudinal design allows opportunities to examine women's mental health and infant neurodevelopment throughout the first year, a crucial time for both mothers and their infants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615001028594; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369324. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18560.

Does maternal smoking in pregnancy explain the differences in the body composition trajectory between breastfed and formula-fed infants?

Growth patterns are known to differ between breastfed and formula-fed infants, but little is known about the relative impact of maternal smoking in pregnancy v. feeding mode on growth trajectory in infancy. We conducted a secondary analysis of a trial, the Tolerance of Infant Goat Milk Formula and Growth Assessment trial involving 290 healthy infants, to examine whether smoking in pregnancy modified the association between feeding mode and body composition of infants. Fat mass (FM) and fat-free mass (FFM) were estimated at 1, 2, 3, 4, 6 and 12 months of age using bioimpedance spectroscopy. Formula-fed infants (n 190) had a higher mean FFM at 4 months (mean difference (MD) 160 g, 95 % CI 50·4, 269·5 g, P < 0·05)) and 6 months (MD 179 g, 95 % CI 41·5, 316·9 g, P < 0·05) compared with the breastfed infants (n 100). Sub-group analysis of breastfed v. formula-fed infants by maternal smoking status in pregnancy showed that there were no differences in the FM and FFM between the breastfed and formula-fed infants whose mothers did not smoke in pregnancy. Formula-fed infants whose mothers smoked in pregnancy were smaller at birth and had a lower FM% and higher FFM% at 1 month compared with infants of non-smoking mothers regardless of feeding mode, but the differences were not significant at other time points. Adequately powered prospective studies with an appropriate design are warranted to better understand the relative impact of maternal smoking, feeding practice and the growth trajectory of infants.

Association Between Maternal Iodine Intake in Pregnancy and Childhood Neurodevelopment at Age 18 Months.

There are limited and inconsistent data suggesting that mild iodine deficiency in pregnancy might be associated with poorer developmental outcomes in children. Between 2011 and 2015, we conducted a prospective cohort study in Australia examining the relationship between maternal iodine intake in pregnancy and childhood neurodevelopment, assessed using Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), in 699 children at 18 months. Maternal iodine intake and urinary iodine concentration (UIC) were assessed at study entry (<20 weeks' gestation) and at 28 weeks' gestation. Maternal iodine intake in the lowest (<220 µg/day) or highest (≥391 µg/day) quartile was associated with lower cognitive, language, and motor scores (mean differences ranged from 2.4 (95% confidence interval (CI): 0.01, 4.8) to 7.0 (95% CI: 2.8, 11.1) points lower) and higher odds (odds ratios ranged from 2.7 (95% CI: 1.3, 5.6) to 2.8 (95% CI: 1.3, 5.7)) of cognitive developmental delay (Bayley-III score <1 SD) compared with mothers with an iodine intake in the middle quartiles. There was no association between UIC in pregnancy and Bayley-III outcomes regardless of whether UIC and the outcomes were analyzed as continuous or categorical variables. Both low and high iodine intakes in pregnancy were associated with poorer childhood neurodevelopment in this iodine-sufficient population.

Comparison of breast milk fatty acid composition from mothers of premature infants of three countries using novel dried milk spot technology.

Long chain polyunsaturated fatty acid (LCPUFA) intake during infancy has been associated with many health benefits, and the LCPUFA intake of breastfed infants is largely dependent on the composition of breast milk. The conventional method for breast milk fatty acid profiling is complicated by the need for cold-chain transportation and storage, and the newly developed dried milk spot (DMS) technology overcomes these difficulties. This study aimed to determine the accuracy, sensitivity and applicability of the DMS method developed based on the PUFAcoat™ technology. Two hundred breast milk samples were analyzed using the conventional method and compared with the DMS method. In order to evaluate the usefulness of DMS for large scale international studies, we analyzed another 786 breast milk samples collected from mothers of preterm infants who participated in a large clinical trial conducted in Australia, New Zealand and Singapore. Fatty acids were measured using capillary gas chromatography and results were reported as weight percentage of total fatty acids. Strong correlations and tight variation were observed in total saturated, monounsaturated, n-6 and n-3 PUFAs between the conventional and DMS methods. The DMS method proved to be sensitive in differentiating the breast milk fatty acid profiles of women consuming different habitual diets as evidenced by the differences between the breast milk fatty acid composition between Australian and Singaporean population. This study demonstrates that the DMS and the conventional method provide interchangeable results, and the DMS method is a particularly useful tool for large-scale studies.

Comparison of Human Milk Fatty Acid Composition of Women From Cambodia and Australia.

BACKGROUND: Human milk is a rich source of omega-3 long-chain polyunsaturated fatty acids, which are postulated to be important for brain development. There is a lack of data on the human milk fatty acid composition of Cambodian women compared with data from Western women. Research Aim: The aim of this study was to determine the human milk fatty acid composition of women living in Cambodia and compare it with that of women living in Australia. METHOD: Human milk samples from Cambodian ( n = 67) and Australian ( n = 200) mothers were collected at 3 to 4 months postpartum. Fatty acid composition was analyzed using capillary gas chromatography followed by Folch extraction with chloroform/methanol (2:1 v/v), and fat content was measured gravimetrically. RESULT: Compared with Australian participants, human milk from Cambodian participants contained a significantly lower level of total fat (2.90 vs. 3.45 g/dL, p = .028), lower percentages of linoleic acid (9.30% vs. 10.66%, p < .0001) and α-linolenic acid (0.42% vs. 0.95%, p < .0001), but higher percentages of arachidonic acid (0.68% vs. 0.38%, p < .0001) and docosahexaenoic acid (0.40% vs. 0.23%, p < .0001). CONCLUSION: Differences in human milk fatty acid composition between Cambodian and Australian participants may be explained by differences in the dietary patterns between the two populations.

Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial.

INTRODUCTION: Preterm birth accounts for more than 85% of all perinatal complications and deaths. Seventy-five per cent of early preterm births (EPTBs) occur spontaneously and without identifiable risk factors. The need for a broadly applicable, effective strategy for primary prevention is paramount. Secondary outcomes from the docosahexaenoic acid (DHA) to Optimise Mother Infant Outcome trial showed that maternal supplementation until delivery with omega-3 (ω-3) long chain polyunsaturated fatty acid (LCPUFA), predominantly as DHA, resulted in a 50% reduction in the incidence of EPTB and an increase in the incidence of post-term induction or post-term prelabour caesarean section due to extended gestation. We aim to determine the effectiveness of supplementing the maternal diet with ω-3 LCPUFA until 34 weeks' gestation on the incidence of EPTB. METHODS AND ANALYSIS: This is a multicentre, parallel group, randomised, blinded and controlled trial. Women less than 20 weeks' gestation with a singleton or multiple pregnancy and able to give informed consent are eligible to participate. Women will be randomised to receive high DHA fish oil capsules or control capsules without DHA. Capsules will be taken from enrolment until 34 weeks' gestation. The primary outcome is the incidence of EPTB, defined as delivery before 34 completed weeks' gestation. Key secondary outcomes include length of gestation, incidence of post-term induction or prelabour caesarean section and spontaneous EPTB. The target sample size is 5540 women (2770 per group), which will provide 85% power to detect an absolute reduction in the incidence of preterm birth of 1.16% (from 2.45% to 1.29%) between the DHA and control group (two sided α=0.05). The primary analysis will be based on the intention-to-treat principle. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trial Registry Number: 2613001142729; Pre-results.

Iodine status of postpartum women and their infants in Australia after the introduction of mandatory iodine fortification.

Mandatory I fortification in bread was introduced in Australia in 2009 in response to the re-emergence of biochemical I deficiency based on median urinary I concentration (UIC)<100 µg/l. Data on the I status of lactating mothers and their infants in Australia are scarce. The primary aim of this study was to assess the I status, determined by UIC and breast milk I concentration (BMIC), of breast-feeding mothers in South Australia and UIC of their infants. The secondary aim was to assess the relationship between the I status of mothers and their infants. The median UIC of the mothers (n 686) was 125 (interquartile range (IQR) 76-200) µg/l and median BMIC (n 538) was 127 (IQR 84-184) µg/l. In all, 38 and 36 % of the mothers had a UIC and BMIC below 100 µg/l, respectively. The median UIC of infants (n 628) was 198 (IQR 121-296) µg/l, and 17 % had UIC<100 µg/l. Infant UIC was positively associated with maternal UIC (ß 0·26; 95 % CI 0·14, 0·37, P<0·001) and BMIC (ß 0·85; 95 % CI 0·66, 1·04, P<0·001) at 3 months postpartum after adjustment for gestational age, parity, maternal secondary and further education, BMI category and infant feeding mode. The adjusted OR for infant UIC<100 µg/l was 6·49 (95 % CI 3·80, 11·08, P<0·001) in mothers with BMIC<100 µg/l compared with those with BMIC≥100 µg/l. The I status of mothers and breast-fed infants in South Australia, following mandatory I fortification, is indicative of I sufficiency. BMIC<100 µg/l increased the risk of biochemical I deficiency in breast-fed infants.

Differentiation of Bifidobacterium longum subspecies longum and infantis by quantitative PCR using functional gene targets.

BACKGROUND: Members of the genus Bifidobacterium are abundant in the feces of babies during the exclusively-milk-diet period of life. Bifidobacterium longum is reported to be a common member of the infant fecal microbiota. However, B. longum is composed of three subspecies, two of which are represented in the bowel microbiota (B. longum subsp. longum; B. longum subsp. infantis). B. longum subspecies are not differentiated in many studies, so that their prevalence and relative abundances are not accurately known. This may largely be due to difficulty in assigning subspecies identity using DNA sequences of 16S rRNA or tuf genes that are commonly used in bacterial taxonomy. METHODS: We developed a qPCR method targeting the sialidase gene (subsp. infantis) and sugar kinase gene (subsp. longum) to differentiate the subspecies using specific primers and probes. Specificity of the primers/probes was tested by in silico, pangenomic search, and using DNA from standard cultures of bifidobacterial species. The utility of the method was further examined using DNA from feces that had been collected from infants inhabiting various geographical regions. RESULTS: A pangenomic search of the NCBI genomic database showed that the PCR primers/probes targeted only the respective genes of the two subspecies. The primers/probes showed total specificity when tested against DNA extracted from the gold standard strains (type cultures) of bifidobacterial species detected in infant feces. Use of the qPCR method with DNA extracted from the feces of infants of different ages, delivery method and nutrition, showed that subsp. infantis was detectable (0-32.4% prevalence) in the feces of Australian (n = 90), South-East Asian (n = 24), and Chinese babies (n = 91), but in all cases at low abundance (<0.01-4.6%) compared to subsp. longum (0.1-33.7% abundance; 21.4-100% prevalence). DISCUSSION: Our qPCR method differentiates B. longum subspecies longum and infantis using characteristic functional genes. It can be used as an identification aid for isolates of bifidobacteria, as well as in determining prevalence and abundance of the subspecies in feces. The method should thus be useful in ecological studies of the infant gut microbiota during early life where an understanding of the ecology of bifidobacterial species may be important in developing interventions to promote infant health.

Growth patterns during the first 12 months of life: post-hoc analysis for South Australian Aboriginal and Caucasian infants in a randomised controlled trial of formula feeding.

BACKGROUND AND OBJECTIVES: To compare growth characteristics of Aboriginal and Caucasian formula-fed in-fants in the first 12 months of life. METHODS AND STUDY DESIGN: We conducted post-hoc data analysis of infants who were part of a previous randomised controlled trial comparing infants randomly assigned to cow or goat milk-based infant formulae. Weight, height, and body composition were assessed at serial time points between study entry (~1-2 weeks of age) and 12 months. There was no growth difference between the randomised groups so the two groups were combined and the data were used to conduct a non-randomised comparison of the growth between Aboriginal (n=11) and Caucasian formula-fed (n=169) infants. RESULTS: Aboriginal formula-fed infants had significantly higher mean z-scores for weight (0.65 difference, [95% CI 0.11, 1.18], p=0.018) and weight-for-length (0.82 difference [95% CI 0.20, 1.44], p=0.010) at 2 months, and all time points onward compared with Caucasian formula-fed infants. Mean length z-scores and the overall growth trajectory across time did not differ between Aboriginal and Caucasian formula-fed infants. Concordant with the weight and weight-for-length z-scores, Aboriginal infants had increased fat mass at 2 months (292 g difference [95% CI 56, 528], p=0.015), and all time points onward compared to Caucasian infants. There was no difference in fat free mass. CONCLUSIONS: Though there was only a small number of Aboriginal infants for comparison, our data indicate Aboriginal formu-la-fed infants were heavier and had a larger increase in fat mass over time compared with Caucasian formula-fed infants. Further studies using a larger cohort are needed to substantiate these findings.

Knowledge and practices regarding iodine supplementation: A national survey of healthcare providers.

BACKGROUND: Little is known of healthcare providers' awareness and implementation of the National Health and Medical Research Council's recommendation regarding iodine supplementation during pre-conception, pregnancy and lactation. AIM: To assess knowledge and practices of Australian healthcare providers in relation to the National Health and Medical Research Council's iodine supplement recommendation. METHODS: Obstetricians, gynaecologists, general practitioners, dietitians and midwives were recruited through their relevant professional bodies to participate in an online survey. FINDINGS: The survey was completed by 396 healthcare providers Australia-wide. While 71% of healthcare providers' were aware of the National Health and Medical Research Council's recommendation for iodine supplementation, fewer were aware of the recommended dose (38%) or duration (44%). Seventy-three percent of healthcare providers recommended iodine supplements in pregnancy, 56% when planning pregnancy and 52% during lactation. The main reasons for not recommending iodine supplements included belief there was no need for iodine supplements due to mandatory iodine fortification of food (28%) and unawareness of the recommendation (25%). Awareness of the recommendation was positively associated with recommending iodine supplements while length of practice, time spent per consultation, age or area of practice were not associated with recommending iodine supplements. DISCUSSION AND CONCLUSIONS: There is a need to improve healthcare providers' knowledge of and adherence to the National Health and Medical Research Council's iodine supplement recommendation. Strategies within antenatal and postnatal services, as well as public health initiatives, are required to improve the knowledge and practices of healthcare providers.