Breastfeeding and later maternal risk of hypertension and cardiovascular disease - The role of overall and abdominal obesity.

In this study, we examined how any, full, and partial breastfeeding durations were associated with maternal risk of hypertension and cardiovascular disease (CVD), and how prepregnancy body mass index (BMI) and waist circumference 7 years postpartum influenced these associations. A total of 63,260 women with live-born singleton infants in the Danish National Birth Cohort (1996-2002) were included. Interviews during pregnancy and 6 and 18 months postpartum provided information on prepregnancy weight, height, and the duration of full and partial breastfeeding. Waist circumference was self-reported 7 years postpartum. Cox regression models were used to estimate hazard ratios of incident hypertension and CVD, registered in the National Patient Register from either 18 months or 7 years postpartum through 15 years postpartum. Any breastfeeding ≥4 months was associated with 20-30% lower risks of hypertension and CVD compared to <4 months in both normal/underweight and overweight/obese women. At follow-up starting 7 years postpartum, similar risk reductions were observed after accounting for waist circumference adjusted for BMI. Partial breastfeeding >2 months compared to ≤2 months, following up to 6 months of full breastfeeding, was associated with 10-25% lower risk of hypertension and CVD. Compared with short breastfeeding duration, additional partial breastfeeding was as important as additional full breastfeeding in reducing risk of hypertension and CVD. Altogether, longer duration of breastfeeding was associated with lower maternal risk of hypertension and CVD irrespective of prepregnancy BMI and abdominal adiposity 7 years after delivery. Both full and partial breastfeeding contributed to an improved cardiovascular health in mothers.

Effects of body size and change in body size from infancy through childhood on body mass index in adulthood.

BACKGROUND: Weight and weight gain throughout infancy are related to later obesity, but whether the strength of the associations varies during the infancy period is uncertain. AIMS: Our aims were to identify the period of infancy when change in body weight has the strongest association with adult body mass index (BMI) and also the extent to which these associations during infancy are mediated through childhood BMI. METHODS: The Copenhagen Perinatal Cohort, in which participants were followed from birth through 42 years of age, provided information on weight at 12 months and BMI at 42 years for 1633 individuals. Information on weight at birth, 2 weeks, 1, 2, 3, 4 and 6 months was retrieved from health visitors' records and information on BMI at ages 7 and 13 years from school health records. The associations of infant weight and weight gain standard deviation scores (SDS) with adult BMI-SDS were analyzed using multiple linear regression and path analysis. RESULTS: Higher-weight-SDS at all ages from birth to an age 12 months were associated with higher-BMI-SDS at 42 years (regression coefficients 0.08-0.12). Infant weight gain-SDS was associated with greater BMI-SDS at 42 years only between birth and 3 months (0.09, 95% confidence intervals (CI) 0.04, 0.15) driven by an association between 2 and 3 months (0.12, 95% CI: 0.04, 0.20). The latter was partly mediated through later BMI in the path analysis. Infant weight gain-SDS between 3 and 12 months was not associated with greater BMI-SDS at 42 years. CONCLUSIONS: Faster weight gain during only the first 3 months of infancy was associated with increased adult BMI, although not in a consistent monthly pattern. Adult BMI is more sensitive to high weight gain during early infancy than late infancy, but not specifically to the first month of life.

Household food security is associated with early childhood language development: results from a longitudinal study in rural Bangladesh.

BACKGROUND: Although household food security (HHFS) has been linked to academic performance in school children, its association with early childhood development has received less attention, particularly in low-income countries. We investigated the association of HHFS with subsequent language development of children at 18 months of age in rural Bangladesh. METHODS: We followed 1439 infants born in 2002-2003 to the mothers in Maternal and Infant Nutrition Intervention in Matlab study, a large intervention trial conducted in rural Bangladesh. A HHFS scale was created from data collected from mothers during pregnancy. At 18 months, children's language (expression and comprehension) development was assessed using a Bengali adaptation of MacArthur's Communicative Development Inventory which was based on mothers' report of their children's ability to comprehend and express words in different categories. General linear regression models were used to examine the association between HHFS and language development at 18 months of age adjusting for potential confounders. RESULTS: Household food security was associated with language comprehension (B = 0.19, 95% CI = 0.09, 0.30, P < 0.001) and expression (B = 1.01, 95% CI = 1.00, 1.02, P < 0.01) at 18 months of age. Mean language comprehension and expression at 18 months of the children in higher quartiles of HHFS were higher (P < 0.05) than those of the children in lower quartiles. CONCLUSIONS: Household food security is positively associated with subsequent language development of rural Bangladeshi children. Early language development has been reported to predict later child development. Therefore, strategies to ensure HHFS status in Bangladesh and similar settings should be considered for optimum child development.

Short-Term Practice Effects and Amyloid Deposition: Providing Information Above and Beyond Baseline Cognition.

BACKGROUND: Practice effects, which are improvements in cognitive test scores due to repeated exposure to testing materials, may provide information about Alzheimer's disease pathology, which could be useful for clinical trials enrichment. OBJECTIVES: The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to amyloid deposition on neuroimaging. PARTICIPANTS: Twenty-seven, non-demented older adults (9 cognitively intact, 18 with mild cognitive impairment) received amyloid imaging with 18F-Flutemetamol, and two cognitive testing sessions across one week to determine practice effects. RESULTS: A composite measure of 18F-Flutemetamol uptake correlated significantly with all seven cognitive tests scores on the baseline battery (r's = -0.61 - 0.59, all p's<0.05), with higher uptake indicating poorer cognition. Practice effects significantly added to the relationship (above and beyond the baseline associations) with 18F-Flutemetamol uptake on 4 of the 7 cognitive test scores (partial r's = -0.45 - 0.44, p's<0.05), with higher uptake indicating poorer practice effects. The odds ratio of being "amyloid positive" was 13.5 times higher in individuals with low practice effects compared to high practice effects. CONCLUSIONS: Short-term practice effects over one week may be predictive of progressive dementia and serve as an affordable screening tool to enrich samples for preventative clinical trials in Alzheimer's disease.

Assessing animal welfare in sow herds using data on meat inspection, medication and mortality.

This paper aims to contribute to the development of a cost-effective alternative to expensive on-farm animal-based welfare assessment systems. The objective of the study was to design an animal welfare index based on central database information (DBWI), and to validate it against an animal welfare index based on-farm animal-based measurements (AWI). Data on 63 Danish sow herds with herd-sizes of 80 to 2500 sows and an average herd size of 501 were collected from three central databases containing: Meat inspection data collected at animal level in the abattoir, mortality data at herd level from the rendering plants of DAKA, and medicine records at both herd and animal group level (sow with piglets, weaners or finishers) from the central database Vetstat. Selected measurements taken from these central databases were used to construct the DBWI. The relative welfare impacts of both individual database measurements and the databases overall were assigned in consultation with a panel consisting of 12 experts. The experts were drawn from production advisory activities, animal science and in one case an animal welfare organization. The expert panel weighted each measurement on a scale from 1 (not-important) to 5 (very important). The experts also gave opinions on the relative weightings of measurements for each of the three databases by stating a relative weight of each database in the DBWI. On the basis of this, the aggregated DBWI was normalized. The aggregation of AWI was based on weighted summary of herd prevalence's of 20 clinical and behavioural measurements originating from a 1 day data collection. AWI did not show linear dependency of DBWI. This suggests that DBWI is not suited to replace an animal welfare index using on-farm animal-based measurements.

Effect of maternal malnutrition during the reproductive cycle on growth and nutritional status of suckling rat pups.

To assess the impact of maternal malnutrition imposed at various stages of the reproductive cycle on pup growth and nutritional status, rats were fed 50% of the intake of control animals fed ad libitum either before pregnancy (R-B), before and during pregnancy (R-BP), during lactation (R-L), or throughout the experimental period (R-BPL). Regardless of the prior nutritional status of their dams, at 14 days of age pups nursed by restricted dams (R-L, R-BPL) were smaller and had less carcass fat and lower plasma albumin, plasma and liver vitamin A, and liver pyridoxine 5'-phosphate oxidase values than those nursed by dams fed ad libitum (C, R-B, R-BP). Pups nursed by chronically underfed dams (R-BPL) had lower Hb and plasma vitamin A values than those nursed by acutely malnourished (R-L) dams. The nutritional status of pups suckled by previously malnourished dams refed during lactation (R-BP) was similar to those suckled by controls except for plasma albumin and vitamin A values. We conclude that maternal nutritional status influenced pup growth and nutritional status and that permitting voluntary intake of an adequate diet during lactation was effective in preventing malnutrition in suckling young.

Malnutrition during the reproductive cycle: effects on galactopoietic hormones and lactational performance in the rat.

To examine the effects of malnutrition imposed at various stages of the reproductive cycle on galactopoietic hormones and lactational performance, rats were fed 50% of the intake of ad libitum-fed controls either before and during pregnancy (refed), during lactation only (acutely restricted), or throughout the experimental period (chronically restricted). Milk yield and litter weight at day 14 of lactation were compromised in the groups restricted during lactation. Dietary restriction during lactation had consistent negative effects on milk nutrient and energy contents. Plasma and milk corticosterone values were twice as high in the groups restricted during lactation as in the controls. Corticosterone but not prolactin values were correlated with many measures of lactational performance. These results suggest that the increase in corticosterone values may be one mechanism by which malnutrition exerts its effects on lactational performance.

Effects of varying degrees of chronic dietary restriction in rat dams on reproductive and lactational performance and body composition in dams and their pups.

To assess the effects of varying degrees of chronic dietary restriction, rats were fed ad libitum or were restricted to 75%, 50% or 40% of ad libitum intake beginning 28 days prior to breeding and continuing through day 14 of lactation. Pup birth weight did not differ among the groups, but maternal weight gain, net maternal growth, and litter number were proportional to dietary intake. During lactation, maternal weight loss was minimal in all groups and carcass protein proportions remained constant. However, maternal fat stores were mobilized in all groups, with smaller changes in the 50% group. Milk yield was reduced in restricted dams. Despite a partial compensation in milk yield by the 75% group, litter weights were proportional to maternal dietary level. In contrast, rats in the 50% group made no compensation in milk yield. Possible explanations for the discrepancy between milk yield and litter growth are explored.

Linking maternal and infant benefits of a nutritional supplement during pregnancy and lactation.

To evaluate the effect of a nutritional supplement on change in women's weight during a reproductive cycle and on the difference in birth weight between one infant and the previous one, we analyzed data on 176 complete reproductive cycles from an experiment that was conducted in rural Guatemala. Women with an initial weight <50 kg were classified as marginally nourished or malnourished. Women whose intake of the supplement was in the top 2 tertiles were distinguished from those whose intake was in the lowest tertile. Linear regression modeling was used to estimate the effect of supplementation on these outcomes and to control for confounding factors. Malnourished women gained weight during the reproductive cycle, but their second (study) infant tended to weigh less at birth than their prior-born infant. Higher intakes of supplement were associated with a less negative difference in birth weight. Marginally nourished women lost weight during the reproductive cycle and their second (study) infant tended to weigh more at birth than their prior-born infant. Higher intakes of supplement were associated with a less negative weight [corrected] trend for the women themselves. Well-nourished women and their infants did not show any of these benefits from supplementation. These findings help explain past contradictory findings on maternal depletion as well as on the benefits of nutritional supplementation for mothers and their infants.

Maternal obesity and breast-feeding success in a rural population of white women.

Maternal obesity interferes with the initiation and maintenance of lactation in animal models but it has not been investigated widely in women. We reviewed medical records from a white population to examine the relation between prepregnant overweight [body mass index (BMI; in kg/m2) 26.1-29.0] and obesity (BMI > 29.0) on initiation and duration of breast-feeding. Logistic regression revealed that of those who ever put their infants to the breast (n = 810), women who were overweight [odds ratio (OR) = 2.54, P < 0.05] or obese (OR = 3.65, P < 0.0008) had less success initiating breast-feeding than did their normal-weight counterparts (BMI < 26.1). Proportional-hazards regression revealed higher rates of discontinuation of exclusive breast-feeding in overweight (RR = 1.42, P < 0.04) and obese (RR = 1.43, P < 0.02) women and higher discontinuation of breast-feeding to any extent in overweight (RR = 1.68, P < 0.006) and obese (RR = 1.73, P = 0.001) women. Controlling for parity, socioeconomic status, maternal education, and other factors that often covary with maternal obesity and breast-feeding did not change these results. These results suggest that excessive fatness in the reproductive period may inhibit lactational performance in women.

Folacin deficiency and requirement in the squirrel monkey (Saimiri sciuresus).

Acute folacin deficiency was studied in eight young squirrel monkeys (Saimiri sciureus). Half of the animals were fed a semipurified deficient diet (no added folic acid) and half were fed a control diet (0.84 mg of added folic acid per kilogram of dry diet). Monkeys fed the deficient diet lost weight and suffered from diarrhea and dehydration leading to the death of one of the animals after 6 weeks. Folacin deficiency also was studied in six older animals fed diets containing varying levels of added folic acid. Monkeys fed diets containing 0.14 or 0.27 mg of added folic acid per kilogram of dry diet slowly developed alopecia, a scaly dermatitis, and a mild macrocytic anemia. When these animals were fed the deficient diet, they lost weight rapidly, the alopecia and dermatitis worsened, excretion of formiminoglutamic acid in the urine increased, and a severe megaloblastic anemia with profound intramedullary hemolysis developed. Deficient monkeys had low plasma and red blood cell folacin values but maintained normal plasma vitamin B12 values. Repletion of the animals fed the deficient diet with injections of folic acid reversed both the hematological and physical deterioration. The folacin requirement for maintenance of body weight in these animals was 28 micrograms of total folacin per kilogram of body weight per day. More than 75 micrograms of total folacin per kilogram of body weight/day may be needed to assure growth and normal hematological parameters and bone marrow cytology.

Conjunctival impression cytology as an indicator of vitamin A status in lactating Indonesian women.

Conjunctival impression cytology (CIC) has been used to assess the vitamin A status of children but not women. We used CIC in a randomized controlled trial of high-dose vitamin A supplementation in Indonesian women. We report its association with biochemical indicators and evaluate its usefulness for several assessment functions, using two definitions for abnormal CIC. Serum retinol concentrations of all women and milk vitamin A concentrations of unsupplemented women decreased with worsening CIC category. CIC indicated risk of low milk vitamin A and low infant serum retinol with low sensitivity and high specificity. CIC did not identify women who benefited from supplementation. The usefulness of CIC to measure response to supplementation was limited by the low prevalence of abnormal status in these women. CIC may be a useful indicator of vitamin A deficiency in women or their breast-fed infants, or to measure response to supplementation, when a more sensitive cutoff point for abnormal status is used.

Screening for nutrition interventions: the risk or the differential-benefit approach?

The risk approach has been promoted to improve screening for nutrition interventions on the premise that indicators of risk also predict greater response to interventions. This study tested whether the determinants of the risk of poor growth (eg, low length-for-age) at 36 mo of age were the same as the determinants of differential benefit from food supplementation. The sample included 460 Guatemalan children who were exposed to either a high-energy, high-protein drink (atole) or a low-energy, no-protein drink (fresco) during their first 36 mo of life [INCAP (Institute of Nutrition of Central America and Panama) supplementation trial]. Low maternal stature, poor socioeconomic status, inadequate home diet, high diarrhea rates, and low anthropometry scores at 3 or 6 mo were all determinants of the risk of poor growth. Only indicators of child's thinness at 3 or 6 mo of age (low weight-for-age, weight-for-length, or midupper arm circumference) were determinants of differential benefit from supplementation. Thus, the development of screening indicators should be based on analyses of the predictors of differential benefit, not on conventional risk-factor analysis.

Breast milk or animal-product foods improve linear growth of Peruvian toddlers consuming marginal diets.

Although breast-feeding is widely accepted as important for infant health, its benefits during the second year of life have been questioned. We analyzed data from 107 breast-fed and weaned Peruvian children living in a periurban community to determine whether breast milk contributed to improved linear growth between 12 and 15 mo of age. Breast-feeding frequency was self-reported; intakes of complementary foods and animal products were estimated from a food-frequency survey. Multivariate-linear-regression analysis was used to predict the length of the children at 15 mo of age. Determinants of length included length and weight-for-length at 12 mo of age (US National Center for Health Statistics standards), interval between 12- and 15-mo measurements, breast-feeding frequency, incidence of diarrhea, and intakes of complementary and animal-product foods. Complementary foods, animal-product foods, and breast milk all promoted toddlers' linear growth. In subjects with low intakes of animal-product foods, breast-feeding was positively associated (P < 0.05) with linear growth. There was a 0.5-cm/3 mo difference in linear growth between weaned toddlers and children who consumed the average number of feedings of breast milk. Linear growth was also positively associated with intake of animal-product foods in children with low intakes of complementary foods. The negative association between diarrhea and linear growth did not occur in subjects with high complementary-food intakes. When the family's diet is low in quality, breast milk is an especially important source of energy, protein, and accompanying micronutrients in young children. Thus, continued breast-feeding after 1 y of age, in conjunction with feeding of complementary foods, should be encouraged in toddlers living in poor circumstances.

PIP: The contribution of prolonged breast feeding to linear growth at 12-15 months of age was investigated in 107 breast-fed and weaned toddlers from a low-income neighborhood in Lima, Peru. The median duration of breast feeding in this sample was 17.1 months; by 15 months, 46 children had been weaned. The prevalence of stunting (length-for-age score -2 SD below the reference standard) was 17.8% at 12 months and 24.3% at 15 months; no child was wasted. Complementary foods, animal product foods, and breast milk all promoted toddlers' linear growth. In children with low intakes of animal product foods, breast feeding was positively associated with linear growth at 15 months (p 0.05). There was a 0.5 cm/3 months difference in linear growth between weaned toddlers and those who consumed the average number (6.3/day) of breast feeds. Linear growth was further positively associated with intake of animal product foods in children with low intakes of complementary foods. The negative association between diarrhea and linear growth did not occur in children with high intakes of complementary foods. When the household diet is of poor quality, breast feeding is an especially important source of energy, protein, and micronutrients in toddlers and should be continued beyond 12 months of age in conjunction with the provision of complementary foods. Breast milk not only added to the total diet of these young children, but also potentiated the beneficial effects of complementary foods consumed by increasing their growth promotion capacity.

Variation in energy intake during the menstrual cycle: implications for food-intake research.

The relationship between spontaneous energy consumption and menstrual cycle was evaluated in 23 subjects who participated in one of two independent studies. Ad libitum intakes of experimental diets were measured by food weighing and bomb calorimetry for 56 or 42 d. Comparisons were made between each woman's mean energy during the 10 d before and after the onset of menstruation. The significant decline (364 kJ, or 87 kcal) between these two 10-d intervals was smaller than but consistent with findings from previous studies of data from food journals. In a separate analysis with time-series techniques, two distinct periods of elevated intake were identified (during the midluteal and midfollicular phases) that were independent of illness and menstrual symptoms. This pattern of food intake is discussed with reference to normal hormonal fluctuations. These findings confirm that menstrual cycle is a potential confounding variable that should be controlled in research on human food intake.

Effects of maternal nutritional status and maternal energy supplementation on length of postpartum amenorrhea among Guatemalan women.

To investigate the extent to which better maternal nutrition leads to reduction in length of postpartum amenorrhea, multivariate-logistic and linear-regression analyses were applied to data on 339 mother-infant pairs from the longitudinal Guatemalan Four Village Study, 1969-1977. Maternal triceps skinfold thickness was negatively associated with length of amenorrhea when infant supplementation (a proxy for reduced suckling) was accounted for. However, its effect was small: amenorrhea was only 0.5 mo shorter among women at the 75th percentile than among those at the 25th, equivalent to less than even one additional child during the women's reproductive years. Maternal supplementation was not associated with length of amenorrhea when infant supplementation was controlled. This is in contrast to previous studies in which breast-feeding or infant supplementation was not controlled. These results suggest that infant, not maternal, supplementation influences length of postpartum amenorrhea, and that maternal nutritional status has minimal influence.

Nutritional supplementation: effects on child stunting because of diarrhea.

Research has shown that the positive effect of nutritional supplementation on child growth in malnourished populations is small relative to the large negative effect of diarrheal disease. To test the hypothesis that the effects of supplementation and diarrhea are synergistic in that supplementation modifies the negative effect of diarrhea on linear growth, length and diarrheal morbidity were compared at 36 mo of age for two cohorts of Colombian children: supplemented from birth and unsupplemented. Among unsupplemented children diarrhea was negatively associated with length. Among supplemented children diarrhea had no effect on length and differed from that of unsupplemented children. Thus, supplementation completely offset the negative effect of diarrheal disease on length. Targeting supplementation programs to the critical period of high diarrheal prevalence among infants and young children should increase the effectiveness of such programs in preventing growth retardation associated with diarrhea.

PIP: To test the hypothesis that supplementation modifies the negative effect of diarrhea on linear growth, body length and diarrheal morbidity were compared at 36 months of age for 2 cohorts of Columbian children: those receiving supplements from birth and those not receiving supplements. The sample was a subset from a longitudinal study that took place in Bogota, Columbia, between 1973 and 1980 and consisted of 456 families randomly assigned to 6 experimental groups. There were 148 children in the unsupplemented group. The 140 children from the supplemented group received supplements from the 6th month of pregnancy until they were 36 months old. The supplementary feeding included 30 g of protein daily, and 7.5 mg or 15 mg of ferrous sulphate daily as well as vitamin A every 6 months. Supplemented children had a mean 16 episodes of diarrhea, compared with a mean of 18 episodes of the unsupplemented cohort, and they spent a total of 73 days ill, compared with 83 days ill for unsupplemented children. Linear regression analysis showed that the slopes for unsupplemented children were significantly different from 0 (p 0.001). Each day with diarrhea was associated with a reduction of about 0.03 cm in attained length at age 36 months. In contrast, for supplemented children diarrhea had no effect on attained length at age 36 months. 2-way analysis of variance showed that the difference between supplemented and unsupplemented children in attained length in the lowest quartile of diarrhea was small, but the difference in the highest quartile was almost 5 cm. Cumulative growth patterns of children in the high quartile of diarrheal disease revealed that the difference between unsupplemented children was a median of 13 cm, thus supplementation made up nearly 40% of the deficit, compared with the reference standard (5 cm/13 cm). Targeting supplementation programs to the critical period of high diarrheal prevalence among infants and young children should help prevent growth retardation associated with diarrhea.

Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A.

A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer.

Age-specific responsiveness of weight and length to nutritional supplementation.

Evaluation of the responsiveness of weight and length to supplementary feeding shows that the two periods of greatest response coincide with weaning (ages 3-6 mo) and peak incidence and duration of diarrheal disease (ages 9-12 mo). Analyses were done for seven consecutive nonoverlapping intervals comparing children randomly assigned to receive supplemental feeding from birth to age 36 mo or to serve as control subjects. Absolute responsiveness was greatest between ages 3-6 mo; supplemented infants grew 0.61 cm more and gained 162 g more than did unsupplemented infants (p less than 0.005). Relative to rates of growth, responsiveness was greatest between ages 9 and 12 mo (the period of peak diarrheal prevalence), followed by ages 3-6 mo (the period of weaning). Responsiveness to supplementation is thus directly related to age-dependent risk patterns for malnutrition. Targeting supplementation programs to coincide with periods of high nutritional risk should maximize their effectiveness in reducing malnutrition, though caution should be exercised to avoid disruption of breast-feeding.

Adherence to iron supplementation during pregnancy in Tanzania: determinants and hematologic consequences.

Limited adherence to iron supplementation is thought to be a major reason for the low effectiveness of anemia-prevention programs. In rural Tanzania, women at 21-26 wk of gestation were randomly given either 120 mg of a conventional (Con) iron supplement or 50 mg of a gastric-delivery-system (GDS) iron supplement for 12 wk. Adherence was assessed by using a pill bottle equipped with an electronic counting device. Adherence in the GDS group was 61% compared with 42% for the Con group. In both groups, women experiencing side effects had about one-third lower adherence. Fewer side effects were observed in the GDS group. In a subgroup of women with a low initial hemoglobin concentration (< or = 120 g/L), the response to the iron supplements suggested that both of the applied doses were unnecessarily high for adequate hematologic response in a population with a marginal hemoglobin concentration. The GDS group appeared to require a dose one-fourth as high as that of the Con group for an equal effect on improving hemoglobin to normal concentrations.