Preconceptional Supplementation Research Articles

Prescribing patterns for higher dose folic acid in pregnant women with epilepsy treated with antiseizure medication.

This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.

The relationships between optimal infant feeding practices and child development and attained height at age 2 years and 6-7 years.

Limited evidence exists on the long-term effects of early feeding practices on child growth and development. We examined the relationships between infant feeding practices and child height and development at ages 2 and 6-7 years. We studied 885 mother-child dyads from a randomized controlled trial of preconception supplementation in Vietnam. Early initiation of breastfeeding (EIBF), exclusive breastfeeding (EBF), breastfeeding (BF) duration and minimum dietary diversity (MDD) were assessed using World Health Organization(WHO) guidelines. Child development was assessed by the Bayley Scales of Infant Development-III at 2 years and the Wechsler Intelligence Scale for Children®-IV at 6-7years. Child height-for-age z-score (HAZ) was calculated from child height and age. Multivariable regression and structural equation models were used in analyses that controlled for confounding. EIBF and EBF at 6monthsoccurred in 52% and 62% of children, respectively. Mean breastfeeding duration was 18 monthsand 83% achieved MDD at 1year. EIBF was associated with motor (β = 0.13, 95% confidence interval [CI]: 0.00, 0.28) and cognitive development at 2years(β = 0.12, 95%CI: -0.01, 0.26), which in turn were positively associated with cognitive development at 6-7years. EBF was directly associated with development at 6-7years (β = 0.21, 95% CI:0.08, 0.34) whereas motor and cognitive development at 2years explained 41%-75% of the relationship between EIBF and development at 6-7years. HAZ at 2years also mediated 70% of the association between MDD at 1year and HAZ at 6-7years. BF duration was not associated with child development and HAZ. Early infant feeding practices, especially EIBF and EBF, have important long-term implications for optimizing child linear growth and cognition as they begin school.

Preconception Micronutrient Supplementation Affects Maternal BMI and Body Composition Postpartum: A Randomized Controlled Trial in Vietnam

BackgroundAlthough there is growing evidence on the role of preconception nutrition for birth outcomes, limited evidence exists for its effects on maternal health. ObjectivesThis study evaluates the impact of preconception micronutrient supplementation on maternal BMI (kg/m2) and body composition at 6 to 7 y postpartum (PP). MethodsWe followed females who participated in a randomized controlled trial of preconception supplementation in Vietnam and delivered live offspring (n = 1599). Females received weekly supplements containing either 2800 μg folic acid (FA) only, 60 mg iron and 2800 μg FA (IFA), or multiple micronutrients (MMs) (15 micronutrients including IFA) from baseline until conception followed by daily prenatal IFA supplements until delivery. Height, weight, mid-upper arm circumference, triceps skinfold, and waist-hip circumference were measured at recruitment and at 1, 2, and 6 to 7 y PP. Body fat was assessed using bioelectric impedance at 6 to 7 y PP (n = 867). Group comparisons were made using analysis of variance or chi-square tests and general linear models for adjusted models. ResultsAt 6 to 7 y PP, we found significant differences (P < 0.05) by treatment group for mean percent fat (MM: 29.2%; IFA: 27.6%; FA: 27.8%), absolute fat mass (MM: 15.1 kg; IFA: 14.0 kg; FA: 14.3 kg), and prevalence of underweight based on BMI < 18.5 (MM: 5.8%; IFA: 10.3%; FA: 14.3%). Mean BMI and triceps skinfold thickness were higher in the MM group, but these differences were not statistically significant; the differences in absolute fat mass were also attenuated after controlling for body weight. No differences were observed for fat-free mass, prevalence of overweight (BMI >23), or other anthropometric measurements. ConclusionsPreconception MM supplementation was associated with lower prevalence of underweight and higher percent fat when compared with IFA and/or FA only. Preconception micronutrient interventions may have long-term effects on maternal health and merit further examination.This trial was registered at clinicaltrials.gov as NCT01665378.

Paternal preconceptional supplementation of n‐3 polyunsaturated fatty acids alleviates offspring nonalcoholic fatty liver disease in high‐fat diet‐induced obese mice

AbstractExposure to nutritional or environmental factors in early life determines susceptibility to nonalcoholic fatty liver disease (NAFLD). The effect of paternal preconceptional n‐3 polyunsaturated fatty acids (n‐3 PUFAs) on offspring NAFLD development remains unknown. Herein, a mouse model that weaning male mice (F0) received diet supplementation of normal n‐3 PUFA content (n‐6:n‐3 PUFA ratio = 4.3:1) or high n‐3 PUFA content (n‐6:n‐3 ratio = 1.5:1) for 12 weeks, and an n‐3 PUFA‐deficient diet as control, was used for the production of next generation. The F1 and F2 offspring were generated by mating F0 and F1 male mice with virgin female mice, respectively, and after weaning, were fed a high‐fat diet to induce NAFLD. The paternal n‐3 PUFA supplementation improved the scores of steatosis, inflammation and ballooning, and the fibrosis in the liver of two generations, with expressional upregulation of genes associated with fat oxidation (Atgl, Ppara, or Cpt1a), and downregulation of inflammatory genes (Ccl2, Tnf‐α, F4/80, CD206, or CD11c) and fibrosis genes (Tgf‐β, Timp1, or Col1a1). The lessened brown adipose tissue whitening, altered gut bacterial compositions, and altered expression of the imprinted genes (H19, Igf2, and Plagl1) might mediate the impact of paternal n‐3 PUFAs on offspring's NAFLD development, which was dose‐dependent. The data indicate that preconceptional higher paternal intake of n‐3 PUFAs might have intergenerational and transgenerational alleviating impact on obesity‐associated NAFLD development in the offspring through multiple pathways.

Evaluating Preconception Health and Behaviour Change in Australian Women Planning a Pregnancy: The OptimalMe Program, a Digital Healthy Lifestyle Intervention with Remotely Delivered Coaching.

OptimalMe is a digital healthy lifestyle intervention for women planning a pregnancy, with remotely delivered coaching. This follow-up study of Australian women, stratified by coaching delivery mode (phone vs. videoconferencing), assessed alignment to preconception care guidelines and self-reported behaviour change. Overall, 298 women enrolled with a mean (SD) age of 31.8 (4.3) years and mean BMI of 25.7 (6.1) kg/m2. Suboptimal preconception behaviours were reported at baseline, including alcohol consumption (57.2%), infrequent weighing (37.2%) and incomplete cervical cancer screening (15.8%) and prenatal supplementation (38.5). At follow-up (4.5 months) (n = 217), a statistically significant shift towards desired behaviours was reported for alcohol consumption (z = -2.6045, p = 0.00932), preconception supplementation (z = -2.7288, p = 0.00634) and frequent weight monitoring (z = -5.2911, p < 0.00001). An insignificant shift towards adherence to cervical cancer screening (z = -1.8679, p = 0.06148) was observed, with a positive trend towards adherence. Results indicate that women who are actively planning a pregnancy require support to optimise health and lifestyle in preparation for pregnancy and general health and lifestyle improvement. Women demonstrated improvement in lifestyle behaviours and self-monitoring, indicating the uptake of low-intensity, non-prescriptive information provision. Supporting the provision of knowledge-enhancing tools and general healthy lifestyle information combines with skilled health coaching as an effective method for behaviour change and self-management. OptimalMe also shows significant improvements in rates of healthcare engagement, which suggests coaching-based digital health interventions may decrease women's barriers for preconception care and improve engagement in clinical settings.

Iron, folic acid, and vitamin D supplementation during pregnancy: Did pregnant Chilean women meet the recommendations during the COVID pandemic?

Antenatal micronutrient supplementation has been defined as a priority for Low-and Middle-income Countries (LMICs). However, it is also relevant to assess its performance in middle-high income countries, such as Chile, particularly given the post-pandemic food insecurity context. To assess the use (frequency and doses) of daily recommended supplementation (iron (15-30 mg), folic acid (FA) (400-800 μg/day), and vitamin (VD) (400 IU)) in a sample of Chilean pregnant women. In 1, 507 pregnant women selected from public health care registries of the Southeast area of Santiago-Chile, we collected maternal, supplement use, sociodemographic, and nutritional information at the first (<15 weeks), second (24-28 weeks), and third trimesters (32-36 weeks) of gestation by using a researcher administer online questionnaire. The median (IQR) age of women was 29 (25-33) years. Pre-conceptional supplementation was rare (24%), but it reached >93% in the first trimester; thereafter supplement use decreased to 79% in the second and 84% in the third trimesters, particularly in women with lower income (p<0.05), lower education (p<0.05), and with excess weight (p<0.05). Use of iron supplements in the first trimester was rare (<21%) as well as the use of VD supplements across pregnancy (<31%). Most FA (70%) and iron (80%) supplement users, exceeded the recommended daily dose while ~40% of VD users took less than the recommended dose. In this sample of Chilean women, timely initiation of FA, iron, and VD supplementation was low and doses were not aligned with the recommendations. Strengthening adherence and quality of micronutrient supplementation programs delivered through public primary care could benefit particularly the most vulnerable women.

Drivers of malnutrition among late adolescent and young women in rural Pakistan: a cross-sectional assessment of the MaPPS trial

ObjectiveThis study aimed to characterise the burden of malnutrition and assess how underlying determinants at the structural and intermediary levels contributed to malnutrition among late adolescent and young women in...

Barriers and facilitators of micronutrient supplementation among non-pregnant women of reproductive age in Johannesburg, South Africa.

The prevalence of anaemia among South African women of reproductive age (WRA) remains high at 39%. Multiple micronutrient supplementation (MMS) may be an effective strategy in the prevention and management of anaemia. Our aim was to understand facilitators and barriers to preconception MMS adherence and to explore perceptions and beliefs of MMS in the prevention and treatment of anaemia among non-pregnant WRA. This qualitative study was embedded in a preconception MMS intervention trial of WRA and was conducted in two phases. Phase one assessed the barriers and facilitators of MMS adherence. Individual interviews were conducted with the community health workers (n = 7) administering MMS, and with non-pregnant WRA (n = 25) participating in the trial. Phase two included four focus groups with participating WRA (n = 26), which further explored participants' perceptions and beliefs of MMS provision and adherence, and strategies to improve adherence. The reported facilitators to supplementation were family support, interaction with the community health workers, easy access to MMS, and experienced benefits of MMS. Barriers to preconception supplementation included the lack of family support, the link of supplements to antenatal care, and the perceived lack of benefits of MMS. Participants reported negative associations of supplements with medication, individual and societal stigma around medication and challenges around the supplementation schedule. For successful preconception MMS interventions, young women, their families, and communities need to be convinced of the value of supplementation. Public health interventions utilising preconception supplementation will require specialised training for health care providers, targeted counselling materials and community household support.

Stoffwechsel und Ernährung in der Schwangerschaft

The issue of an optimal diet during pregnancy has attracted growing interest in recent years. One reason could be that the maternal diet not only has a strong influence on the course of pregnancy but also possibly has a long-term impact on child health. In principle, pregnant women are recommended to follow a balanced healthy diet, whereas the energy requirement is only moderately elevated, if at all. Women should avoid excessive weight gain during the gestational period, particularly if they are overweight or obese. In addition, preconceptional supplementation with folic acid and intake of an iodine supplement are recommended. In individual cases administration of iron, docosahexaenoic acid (DHA) and vitamin D can be meaningful. Recent studies have shown that many women wish to receive counselling, so that pregnancy care should be extended to include lifestyle and dietary counselling.

Folic Acid Supplementation on Fetal Growth at Different Gestational Ages

Introduction: Folate, Vitamin B9, is found naturally in our day to day foods. It is vital for synthesis of DNA and normal cell division in humans. Studies have revealed constantly that maternal folic acid[FA] intake prior to and in early conception decreases neural tube defects. Aim: The aim of the current study is to evaluate the relationship between FA intake by the mother during conception and fetal growth at different gestational ages and also if, periconceptional and preconceptional FA intake has a positive effect on fetal growth, hence reducing the risk of low birth weight babies or small for gestational age (SGA) babies. Materials and methods: 180 pregnant women were classified based on their period of FA intake as preconception, periconception FA intake and nil FA intake. Standard fetal biometric parameters were measured using ultrasonogram during the 1st , 2nd and 3rd trimester of their pregnancy. Results: Preconception FA intake had a positive effect on fetal growth as compared to those who abstained from FA supplementation. Intake during preconception and peri-conception i.e. immediately after confirmation of pregnancy was found to have a reduced risk of low fetal weight as against those who did not consume FA. Fetal biometry showed significant difference between preconception and periconception groups. Conclusion: In conclusion, preconceptional and periconceptional FA supplementation of 0.4-0.5 mg/day was positively affecting fetal growth and caused an optimal birth weight by decreasing the incidence of low birth weight.

Folic Acid and the Risk of Congenital Heart Defects

Source: Wang D, Jin L, Zhang J, et al. Maternal periconceptional folic acid supplementation and risk for fetal congenital heart defects [published online ahead of print September 8, 2021]. J Pediatr. doi: 10.1016/j.jpeds.2021.09.004.Investigators from Peking University and Tongzhou Maternal and Child Health Hospital, both in Beijing, China, conducted a retrospective study to assess the effectiveness of periconceptional folic acid (FA) supplementation in preventing congenital heart defects (CHD). For the study, they reviewed data contained in the Prenatal Health Care System (PHCS) and Birth Defects Surveillance System (BDSS) databases on singleton deliveries (including live births, stillbirths, and terminated pregnancies) between 2013 and 2018 in the Tongzhou District, Beijing, China. PHCS is a registry that includes data on women during pregnancy and after delivery, including maternal age and educational level, delivery date, and periconceptional FA supplementation. Information about FA supplementation was based on maternal self-report and included type of FA supplementation and when it started (prior to or after conception). In China, women are provided FA in a daily dose of 0.4 mg by the central government. However, some women take micronutrient supplements containing FA (MMFA). The BDSS includes information on birth defects, beginning at 13 weeks of gestation, including CHD.Primary study outcomes were any CHD, ventricular septal defect (VSD), and critical CHD (defined using standardized criteria). Poisson regression was used to compare the risks of these outcomes in women with FA/MMFA supplementation and in those without supplementation. Risk of CHD also was compared in women taking FA vs MMFA, and with FA/MMFA supplementation beginning prior to or after conception. Regression models also included maternal age, education, and year of delivery.Data were analyzed on 63,969 women and their offspring. Women using FA/MMFA supplementation were significantly older and more educated than those who didn’t. There were 308 cases of CHD in the offspring of study women, including 152 live births and 156 stillbirths or terminated pregnancies; the most common CHD was VSD (125 cases). The use of periconceptional FA/MMFA was associated with a reduced risk of any CHD (adjusted risk ratio [ARR], 0.60; 95% CI, 0.44, 0.83), VSD (ARR, 0.47; 95% CI, 0.30, 0.74) and critical CHD (ARR, 0.41; 95% CI, 0.26, 0.67). There were no statistical differences between FA and MMFA supplementation for risk of any CHD (ARR, 0.84; 95% CI, 0.66, 1.09), VSD (ARR, 0.94; 95% CI, 0.63, 1.41) or critical CHD (ARR, 0.64; 95% CI, 0.44, 1.00). Initiation of FA/MMFA supplementation before conception, compared to post-conception, was associated with a reduced risk of any CHD (ARR, 0.68; 95% CI, 0.48, 0.95) and critical CHD (ARR, 0.26; 95% CI, 0.10, 0.71).The authors conclude that maternal periconceptional FA supplementation was associated with a decreased risk of CHD in off-spring, particularly when initiated prior to conception.Dr Doolittle has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.FA, one of the B vitamins, is a micronutrient found in fresh fruit, vegetables, nuts, and eggs.1 FA deficiency has been associated with megaloblastic anemia and neural tube defects in infants, as well as heart disease and cancer in adults.1 Humans are unable to synthesize FA, and thus must rely on ingestion in the form of food or conversion of precursors in the gut microflora.1 FA is an important co-factor in DNA and RNA synthesis, and the formation of the heart neural crest cells are highly sensitive to FA.2 Since 1992, FA and other micronutrient deficiencies have been associated with CHD.3 However, the results of supplementation trials to prevent CHD have been equivocal.4 The results of the current investigation provide convincing evidence to support FA/MMFA supplementation to prevent CHD.The study design was robust, with a governmental registry of more than 63,000 women who were followed prospectively over 5 years. Of note, the investigators evaluated self-report of FA/MMFA supplementation. Although self-report may be imperfect, the study represents a real-world evaluation. Women who took FA/MMFA supplementation were older and better educated. As maternal age is a risk for CHD, and education usually confers better health outcomes, the investigators controlled for these variables.The results of the current study raises several provocative questions that merit future investigation. Pre-conception supplementation was associated with reduced CHD compared to peri-conception supplementation. This suggests that some independent maternal factors may influence CHD formation prior to conception. Also, despite the reduction of CHD due to supplementation, the continued prevalence of CHD suggests other factors such as genetic defects, exogenous toxin, or infection are at play.Maternal periconceptual supplementation with FA may be associated with a reduced risk of CHD, especially when initiated before conception. (See AAP Grand Rounds. 2020;44[6]:68.)5Perhaps the greater protective efficacy of preconceptual FA supplementation is related to the time it takes to achieve effective folate levels during the critical period of heart development.2

Age-Based Anthropometric Cutoffs Provide Inconsistent Estimates of Undernutrition: Findings from a Cross-Sectional Assessment of Late-Adolescent and Young Women in Rural Pakistan.

ABSTRACTAmbiguity around age ranges for adolescence and adulthood can make the application of age-based nutrition cutoffs confusing. We examined how estimates generated using the age-based anthropometric cutoffs for adolescent girls (10 to <19 y) and women of reproductive age (15–49 y) compared between late-adolescent and young women, and determined how application of both cutoffs affected late-adolescents’ estimates. Using cross-sectional data from participants aged 15–23 y in the Pakistan-based Matiari emPowerment and Preconception Supplementation (MaPPS) Trial (n = 25,447), notably large differences in estimates were observed for stunting (30.5% and 7.9% for late-adolescent and young women, respectively; P < 0.001) and thinness (9.3% and 30.8%, respectively; P < 0.001). When both cutoffs were applied to adolescents’ data, estimate differences were maintained. With each year of age, the difference for stunting increased and thinness decreased. Given the discrepancies observed both between and within groups, clarity around application of anthropometric cutoffs for youth (aged 15–24 y) is needed.This trial was registered at clinicaltrials.gov as NCT03287882.

PROTEA, A Southern African Multicenter Congenital Heart Disease Registry and Biorepository: Rationale, Design, and Initial Results.

Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or “cohort-prevalences” of CHD-subtypes with international findings.Methods: PROTEA is a prospective multicenter CHD registry and biorepository. The initial cohort was recruited from seven hospitals in the Western Cape Province of South Africa from 1 April 2017 to 31 March 2019. All patients with structural CHD were eligible for inclusion. Descriptive data for the preliminary cohort are presented. In addition, cohort-prevalences (i.e., the proportion of patients within the cohort with a specific CHD-subtype) of 26 CHD-subtypes in PROTEA's pediatric cohort were compared with the cohort-prevalences of CHD-subtypes in two global birth-prevalence studies.Results: The study enrolled 1,473 participants over 2 years, median age was 1.9 (IQR 0.4–7.1) years. Predominant subtypes included ventricular septal defect (VSD) (339, 20%), atrial septal defect (ASD) (174, 11%), patent ductus arteriosus (185, 11%), atrioventricular septal defect (AVSD) (124, 7%), and tetralogy of Fallot (121, 7%). VSDs were 1.8 (95% CI, 1.6–2.0) times and ASDs 1.4 (95% CI, 1.2–1.6) times more common in global prevalence estimates than in PROTEA's pediatric cohort. AVSDs were 2.1 (95% CI, 1.7–2.5) times more common in PROTEA and pulmonary stenosis and double outlet right ventricle were also significantly more common compared to global estimates. Median maternal age at delivery was 28 (IQR 23–34) years. Eighty-two percent (347/425) of mothers used no pre-conception supplementation and 42% (105/250) used no first trimester supplements.Conclusions: The cohort-prevalence of certain mild CHD subtypes is lower than for international estimates and the cohort-prevalence of certain severe subtypes is higher. PROTEA is not a prevalence study, and these inconsistencies are unlikely the result of true differences in prevalence. However, these findings may indicate under-diagnosis of mild to moderate CHD and differences in CHD management and outcomes. This reemphasizes the need for robust CHD epidemiological research in the region.

Child Linear Growth During and After the First 1000 Days Is Positively Associated with Intellectual Functioning and Mental Health in School-Age Children in Vietnam

BackgroundMillions of children fail to meet their developmental potential and experience mental health concerns globally. Evidence is mixed on whether growth beyond the first 1000 d of life influences intellectual functioning and mental health in school-age children. ObjectivesWe examined associations of childhood growth before and after the first 1000 d of life with child intellectual functioning and mental health at age 6–7 y. MethodsWe used data from a follow-up of a randomized controlled trial of preconception supplementation (PRECONCEPT study) in Vietnam. A total of 5011 women participated in the study and 1579 children were born during 2012–2014. At age 6–7 y, child intellectual functioning was assessed using the Wechsler Intelligence Scale for Children, and mental health concerns were measured using the Strengths and Difficulties Questionnaire. Multivariable linear models were used to examine the independent association of child size at age 2 y [height-for-age z-score (HAZ) and body-mass-index z-score (BMIZ)] and conditional measures of linear and ponderal growth between the ages of 2 and 7 y. ResultsHAZ at 2 y was positively associated with the Full-Scale Intelligence Quotient (β = 1.4; 95% CI: 0.5, 2.2 points) and its subdomains, namely Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index (β = 1.0–1.4 points). Higher HAZ at 2 y was associated with lower overall mental health concerns (β = −0.24; 95% CI: −0.47, −0.01) and peer problems (β = −0.08; 95% CI: −0.17, −0.01). Faster height gain between 2 and 7 y was associated with higher total intellectual functioning (β = 0.9; 95% CI: 0.02, 1.8) and fewer emotional issues (β = −0.09; 95% CI: −0.18, −0.01). BMIZ at 2 y was not associated with intellectual functioning but was marginally associated with higher conduct and peer problems. Conditional weight gain between 2 and 7 y was not associated with child intellectual functioning or mental health in young school-age children. ConclusionsChild linear growth both during and beyond the first 1000 d is positively associated with intellectual functioning and mental health during the early school-age years.

Dietary diversity and social determinants of nutrition among late adolescent girls in rural Pakistan.

The conditions in which adolescent girls mature shape their health, development and nutrition. Nutrient requirements increase to support growth during adolescence, but gaps between consumption and requirements exist in low‐ and middle‐income countries. We aimed to identify and quantify the relationship between dietary intake and diverse social determinants of nutrition (SDN) among a subset of adolescent girls 15–18.9 years (n = 390) enrolled within the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial. The primary outcome, dietary diversity score (DDS), was derived by applying the Minimum Dietary Diversity for Women 10‐item scale to 24‐h dietary recall data collected three times per participant. To examine the associations between the SDN‐related explanatory variables and DDS, we generated a hierarchical, causal model using mixed effects linear regression to account for the cluster‐randomized trial design. Using all data, diets lacked diversity (DDS mean ± SD: 3.35 ± 1.03 [range: 1–7; n = 1170]), and the minimum cut‐off for dietary diversity was infrequently achieved (13.5%; 95% CI: 11.6–15.6%). Consumption of starches was reported in all recalls, but micronutrient‐rich food consumption was less common. Of the SDN considered, wealth quintile had the strongest association with DDS (P < 0.0001). The diets of the sampled Pakistani adolescent girls were insufficient to meet micronutrient requirements. Poverty was the most important predictor of a diet lacking in diversity, indicating limited purchasing power or access to nutritious foods. Dietary diversification and nutrition education strategies alone are unlikely to lead to improved diets without steps to tackle this barrier, for example, through fortification of staple foods and provision of supplements.

Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial.

Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non‐pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient‐fortified lipid‐based nutrient supplement containing 250‐μg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3). Urinary I (μg/L) to creatinine (mg/dl) ratios (I/Cr) were determined at 12 weeks for Arm 1 versus Arm 2 (before supplement started) and 34 weeks for all arms. Generalized linear models were used to assess the relationship of I/Cr with arm and with newborn anthropometry. At 12 weeks gestation, adjusted mean I/Cr (μg/g) for all sites combined was significantly higher for Arm 1 versus Arm 2: (203 [95% CI: 189, 217] vs. 163 [95% CI: 152, 175], p < 0.0001). Overall adjusted prevalence of I/Cr < 150 μg/g was also lower in Arm 1 versus Arm 2: 32% (95% CI: 26%, 38%) versus 43% (95% CI: 37%, 49%) (p = 0.0052). At 34 weeks, adjusted mean I/Cr for Arm 1 (235, 95% CI: 220, 252) and Arm 2 (254, 95% CI: 238, 272) did not differ significantly but were significantly higher than Arm 3 (200, 95% CI: 184, 218) (p < 0.0001). Nominally significant positive associations were observed between I/Cr at 12 weeks and birth length and head circumference z‐scores (p = 0.028 and p = 0.005, respectively). These findings support the importance of first trimester iodine status and suggest need for preconception supplementation beyond salt iodization alone.

Preconception micronutrient supplementation positively affects child intellectual functioning at 6 y of age: A randomized controlled trial in Vietnam

ABSTRACTBackgroundAlthough there is growing evidence on the role of preconception nutrition for birth outcomes, very few studies have evaluated the long-term effects of nutrition interventions during the preconception period on offspring cognitive outcomes.ObjectiveWe evaluate the impact of preconception weekly multiple micronutrients (MMs) or iron and folic acid (IFA) supplementation compared with folic acid (FA) alone on offspring intellectual functioning at age 6–7 y.MethodsWe followed 1599 offspring born to women who participated in a double-blinded randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements containing either 2800 μg FA only, 60 mg iron and 2800 μg FA, or MMs (15 micronutrients including IFA) from baseline until conception, followed by daily prenatal IFA supplements until delivery. We used the Wechsler Intelligence Scale for Children to measure full-scale IQ (FSIQ) and 4 related domains of intellectual functioning [Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores] at 6–7 y. Group comparisons were done using ANOVA tests for all children and the subgroup born to women who consumed the supplements ≥26 wk before conception (per-protocol analyses).ResultsThe final sample with data at 6–7 y (n = 1321) was similar for baseline maternal and offspring birth characteristics and age at follow-up by treatment group. Compared with the offspring in the FA group, those in the MM group had higher FSIQ (β = 1.7; 95% CI: 0.1, 3.3), WMI (β = 1.7; 95% CI: 0.2, 3.2), and PSI (β = 2.5; 95% CI: 0.9, 4.1). Similar findings were observed in the per-protocol analyses. There were no significant differences by treatment group for VCI and PRI.ConclusionsPreconception supplementation with MMs improved certain domains of intellectual functioning at age 6–7 y compared with FA. These findings suggest the potential for preconception micronutrient interventions to have long-term benefits for offspring cognition.

Characterizing Micronutrient Status and Risk Factors among Late Adolescent and Young Women in Rural Pakistan: A Cross-Sectional Assessment of the MaPPS Trial.

Nutritional deficiencies are a leading underlying risk factor contributing to the global burden of disease. In Pakistan, late adolescence is considered a nutritionally vulnerable period, as micronutrient requirements are increased to support maturation, and dietary staples are nutrient poor. However, there has been limited evaluation of micronutrient status beyond anemia and its determinants. Using cross-sectional data from late adolescent and young women (15–23 years) at enrolment in the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial, we aimed to describe the prevalence of key micronutrient deficiencies of public health concern, and generate hierarchical models to examine associations with proxies for social determinants of health (SDoH). The prevalence of micronutrient deficiencies was high: 53.6% (95% confidence interval (CI): 53.0–54.3%) had anemia; 38.0% (95% CI: 36.4–39.6%) iron deficiency anemia; 31.8% (95% CI: 30.2–33.3%) vitamin A deficiency; and 81.1% (95% CI: 79.8–82.4%) vitamin D deficiency. At least one deficiency was experienced by 91.0% (95% CI: 90.1–92.0%). Few SDoH were maintained in the final hierarchical models, although those maintained were often related to socioeconomic status (e.g., education, occupation). To improve the micronutrient status of late adolescent and young women in Pakistan, a direct micronutrient intervention is warranted, and should be paired with broader poverty alleviation methods.

Preconceptional Resveratrol Supplementation Partially Counteracts Age-Related Reproductive Complications in C57BL/6J Female Mice.

Aging is associated with a drastic decline in fertility/fecundity and with an increased risk of pregnancy complications. Resveratrol (RES), a natural polyphenolic compound, has shown anti-oxidant and anti-inflammatory activities in both human and animal models, thus representing a potential therapeutic and prophylactic anti-aging supplement. Here, we investigated whether preconceptional resveratrol supplementation improved reproductive outcomes in mid-aged (8-month-old) and old (12-month-old) C57BL/6J female mice. Female siblings were cohoused and assigned to either RES or vehicle supplementation to drinking water for 10 consecutive weeks. Subsequently, females were mated with non-supplemented males and their pregnancy outcomes were monitored. RES improved mating success in old, but not in mid-aged females, and prevented the occurrence of delivery complications in the latter. These results indicate that preconceptional RES supplementation could partially improve age-related reproductive complications, but it was not sufficient to restore fecundity in female mice at a very advanced age.

Male preconception antioxidant supplementation may lower autism risk: a call for studies.

Current research indicates that a sizable number of autism spectrum disorder (ASD) cases arise from de novo mutations (DNMs) occurring within the paternal germline, usually in an age-dependent manner. Andrologists have reported that somatic cells and gametes share the same pathologies that generate these DNMs-specifically, DNA hypomethylation caused by oxidative nucleoside base damage. Because many ASD researchers seek to identify genetic risk factors, teams are developing methods of assessing aberrant DNA patterns, such as parental gonadal mosaicism. Several studies propose antioxidant supplementation as a strategy to lower autism risk, and/or suggest connections between childhood neurodevelopmental disorders such as autism and paternally-derived DNMs. Actual data, however, are currently not available to determine whether male preconception antioxidant supplementation effectively lowers autism risk. The purpose of this paper is to (1) explore the mechanisms causing DNMs, specifically DNA hypomethylation; (2) explain how antioxidant supplementation may lower the risk of having a child with ASD; and, (3) advocate for the implementation of large prospective studies testing (2). These studies may very well find that male preconception supplementation with antioxidants prevents neurodevelopmental disorders in offspring, in much the same way that female prenatal consumption of folate was found to decrease the risk of birth defects. If this is indeed the case, the alarming rise in autism prevalence rates of the past few decades will slow-or even cease-upon the initiation of public awareness campaigns.