A home calendar and recall method of last menstrual period for estimating gestational age in rural Bangladesh: a validation study

Background: The best method of gestational age assessment is by ultrasound in the first trimester; however, this method is impractical in large field trials in rural areas. Our objective was to assess the validity of gestational age estimated from prospectively collected date of last menstrual period (LMP) using crown-rump length (CRL) measured in early pregnancy by ultrasound. Methods: As part of a large, cluster-randomized, controlled trial in rural Bangladesh, we collected dates of LMP by recall and as marked on a calendar every 5 weeks in women likely to become pregnant. Among those with a urinetest confirmed pregnancy, a subset with gestational age of <15 weeks (n = 353) were enrolled for ultrasound follow-up to measure CRL. We compared interview-assessed LMP with CRL gestational age estimates and classification of preterm, term, and post-term births. Results: LMP-based gestational age was higher than CRL by a mean (SD) of 2.8 (10.7) days; differences varied by maternal education and preterm birth (P < 0.05). Lin\u2019s concordance correlation coefficient was good at ultrasound [0.63 (95 % CI 0.56, 0.69)] and at birth [0.77 (95 % CI 0.73, 0.81)]. Validity of classifying preterm birth was high but post-term was lower, with specificity of 96 and 89 % and sensitivity of 86 and 67 %, respectively. Results were similar by parity. Conclusions: Prospectively collected LMP provided a valid estimate of gestational age and preterm birth in a rural, low-income setting and may be a suitable alternative to ultrasound in programmatic settings and large field trials. Trial registration: ClinicalTrials.gov NCT0086047

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries.

Inadequate micronutrient intakes are relatively common in low- and middle-income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost-effectiveness of MMS compared with IFA. Recent meta-analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual-participant data meta-analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost-effective method to reduce the risk of adverse birth outcomes

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection

Background: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. Methods: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. Discussion: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses

Vitamin D metabolites across the menstrual cycle: a systematic review

Abstract Background Accurate estimation of vitamin D status is important for health research and can impact prevention and treatment of deficiency in women of reproductive age. We aimed to assess if blood concentrations of 25-hydroxyvitamin D [25(OH)D] or 1,25-dihydroxyvitamin D [1,25(OH)2D] change across the menstrual cycle. Methods We conducted a systematic search in PubMed, Web of Science, CAB and BIOSIS of literature published until December 2018 which reported concentrations of vitamin D metabolites at two or more identified points among women with regular menstrual cycles. Results Ten longitudinal studies met the inclusion criteria; nine studies measured 1,25(OH)2D and five studies measured 25(OH)D. Study size ranged from 5 to 47 subjects, with an age range of 18–47 years. One study found a decrease in concentration of 25(OH)D in the periovulatory and luteal phase. Four studies found no changes in concentrations of 25(OH)D. Two studies found a rise in 1,25(OH)2D within the follicular phase, including a 128% increase from day 1 to 15 and a 56% increase from day 0 to 12. Two studies found rises in 1,25(OH)2D concentrations from the follicular to luteal phase of 13 and 26%. Five studies did not find any changes in concentrations of 1,25(OH)2D. Conclusions No conclusion can be drawn on the pattern of 1,25(OH)2D concentrations across the normal menstrual cycle due to inconsistencies in study findings. Evidence is currently insufficient to assess 25(OH)D concentrations across the cycle. Future studies should aim to measure 1,25(OH)2D and 25(OH)D longitudinally, to understand relationships with other hormones and the potential impact on estimates of vitamin D deficiency

Micronutrient deficiencies in pregnancy worldwide: health effects and prevention.

Micronutrients, vitamins and minerals accessible from the diet, are essential for biologic activity. Micronutrient status varies widely throughout pregnancy and across populations. Women in low-income countries often enter pregnancy malnourished, and the demands of gestation can exacerbate micronutrient deficiencies with health consequences for the fetus. Examples of efficacious single micronutrient interventions include folic acid to prevent neural tube defects, iodine to prevent cretinism, zinc to reduce risk of preterm birth, and iron to reduce the risk of low birth weight. Folic acid and vitamin D might also increase birth weight. While extensive mechanistic and association research links multiple antenatal micronutrients with plausible materno-fetal health advantages, hypothesized benefits have often been absent, minimal or unexpected in trials. These findings suggest a role for population context in determining health responses and filling extensive gaps in knowledge. Multiple micronutrient supplements reduce the risks of being born with low birth weight, small for gestational age or stillborn in undernourished settings, and justify micronutrient interventions with antenatal care. Measurable health effects of gestational micronutrient exposure might persist into childhood but few data exists on potential long-term benefits. In this Review, we discuss micronutrient intake recommendations, risks and consequences of deficiencies, and the effects of interventions with a particular emphasis on offspring

Protocol for meta-research on the evidence informing micronutrient dietary reference intakes for pregnant and lactating women

© 2020 He S et al. Nutrient reference values are important parameters that guide nutrition and public health work globally. Micronutrient requirements during the peri-conception period are generally increased, which is essential in ensuring maternal, fetal, and neonatal health. Nevertheless, the current dietary reference intakes (DRIs) may be limited in terms of the methods used and the populations included, particularly the DRIs for pregnancy and lactation. In this proposed review, we will examine the methods (rigor of design, utilization of molecular methods, and presence of modern methods) and the population (inclusion of women, and in particular, pregnant and lactating people) in the studies used to inform the current DRIs. We will apply meta-science methods to this review, which involves formally reviewing the current evidence, and identifying opportunities to improve how we fund, perform, evaluate, and incorporate nutrition science into public health programs for better outcomes

Nutritious Supplemental Foods for Pregnant Women from Food Insecure Settings: Types, Nutritional Composition, and Relationships to Health Outcomes

There is growing evidence that the provision of nutritious supplemental foods to undernourished pregnant women can improve maternal and infant outcomes. However, comparing and synthesizing the evidence base is complicated by differences in interventions and products and the use of ambiguous terminology. We aimed to define 2 common types of nutritious supplemental foods used in pregnancy, balanced energy-protein (BEP) supplements and lipid-based nutrient supplements (LNS), and to review the evidence supporting each via a narrative review of systematic reviews and meta-analyses (SRMAs). Information about the nutritional composition of the food supplements and their effects on maternal and infant outcomes was abstracted. Five SRMAs ( = 20 trials) evaluated the effect of BEP compared with no BEP/control (comparison group commonly received iron and folic acid [IFA]). BEP foods/products ranged in calories (118-1017 kcals), protein (3-50 g), fat (6-57 g), and micronutrient content. Overall, maternal BEP improved birth weight and reduced the risk of stillbirth and small for gestational age when compared with no BEP/control in pregnancy. Three SRMAs ( = 5 trials) evaluated the effect of LNS compared with IFA or multiple micronutrients (MMNs). The LNS interventions comprised small- and large-quantity LNS that ranged in calories (118-746 kcals), protein (3-21 g), fat (10-53 g), and micronutrient content. LNS compared with IFA increased pregnancy duration, birth weight, and birth length and reduced the risk of small for gestational age and infant stunting; however, no beneficial effect of LNS was identified when compared with MMN. Despite heterogeneity in the nutritional composition of BEP supplements, the evidence suggests that in nutritionally at-risk populations, these products may improve birth outcomes in pregnant women. The evidence is limited but promising when LNS is compared with IFA in improving maternal and infant outcomes. Overall, BEP, compared with MMN or LNS, are key areas that have not been studied and deserve attention