Obesity may impair lactogenesis II.

Data from livestock species and experimental animal models suggest that excess body fatness may impair lactogenesis. For example, it has long been known that overfed dairy cows are at risk of fat cow syndrome, a condition characterized by lactation failure in the early postpartum period. Obese rats often lose their litters in the early postpartum period to primary lactation failure. A negative association between high body mass index (BMI) before conception and the duration of lactation has been documented in studies from diverse human populations. Findings from our laboratory establish that among women who ever attempted to breastfeed their infants, high BMI before conception was also associated with failure to initiate breastfeeding successfully. In a more recent study, we found that high prepregnant BMI was specifically associated with later onset of lactogenesis II. This was mediated by parity but not by breastfeeding behavior. Psychosocial factors related to a woman's intention to breastfeed and her planned duration of breastfeeding did not modify this association. Taken together, these findings in animals and women strongly suggest that maternal obesity in the perinatal period is a cause of delayed lactogenesis.

Evaluation of serum retinol, the modified-relative-dose-response ratio, and breast-milk vitamin A as indicators of response to postpartum maternal vitamin A supplementation.

BACKGROUND: Conflicting results have been reported regarding the relative performance of serum retinol, the modified-relative-dose-response (MRDR) ratio, and breast-milk vitamin A concentrations in detecting changes in maternal vitamin A status. OBJECTIVE: We used receiver operating characteristic analyses and standardized differences to compare the ability of these indicators to detect a response to postpartum vitamin A supplementation in lactating Bangladeshi women. DESIGN: At 2 wk postpartum, women were randomly assigned to receive either a single dose of vitamin A [200000 IU (60000 retinol equivalents); n = 74] or placebo (n = 73). Data from maternal serum and breast milk collected 3 mo postpartum and from infant serum collected 6 mo postpartum were used to examine the ability of serum retinol, the MRDR ratio, and breast-milk vitamin A to discriminate between individuals in the supplemented and unsupplemented groups. Breast milk was collected by expressing the entire contents of one breast that had not been used to feed an infant for > or =2 h (full samples) or without controlling the time since the last breast-feeding episode (casual samples). RESULTS: Casual breast-milk samples performed better than full breast-milk samples in detecting a response to maternal supplementation. The MRDR ratio performed better than serum retinol in both the women and their infants. Overall, the most responsive indicator was the measurement of breast-milk vitamin A per gram of fat in casual breast-milk samples. CONCLUSIONS: Breast-milk vitamin A and the MRDR ratio are responsive indicators of vitamin A status, especially in women with mild vitamin A deficiency.

Vitamin A supplementation selectively improves the linear growth of indonesian preschool children: results from a randomized controlled trial.

BACKGROUND: Vitamin A deficiency is associated with stunting and wasting in preschool children, but vitamin A supplementation trials have not shown a consistent effect on growth. OBJECTIVE: We examined the effect of vitamin A supplementation on height and weight increments among Indonesian preschool children. DESIGN: Data were obtained from a randomized, double-masked, placebo-controlled trial of rural Javanese children aged 6-48 mo. Children received 206000 IU vitamin A (103000 IU if aged <12 mo) or placebo every 4 mo. RESULTS: High-dose vitamin A supplementation modestly improved the linear growth of the children by 0.16 cm/4 mo. The effect was modified by age, initial vitamin A status, and breast-feeding status. Vitamin A supplementation improved height by 0.10 cm/4 mo in children aged <24 mo and by 0.22 cm/4 mo in children aged >/=24 mo. The vitamin A-supplemented children with an initial serum retinol concentration <0.35 micromol/L gained 0.39 cm/4 mo more in height and 152 g/4 mo more in weight than did the placebo group. No growth response to vitamin A was found among children with an initial serum retinol concentration >/=0.35 micromol/L. In non-breast-fed children, vitamin A supplementation improved height by 0.21 cm/4 mo regardless of age. In breast-fed children, vitamin A supplementation improved linear growth by approximately 0.21 cm/4 mo among children aged >/=24 mo, but had no significant effect on the growth of children aged <24 mo. CONCLUSION: High-dose vitamin A supplementation improves the linear growth of children with very low serum retinol and the effect is modified by age and breast-feeding.

Maternal vitamin A or beta-carotene supplementation in lactating bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency.

The effects of maternal postpartum vitamin A or beta-carotene supplementation on maternal and infant serum retinol concentrations, modified relative dose-response (MRDR) ratios and breast milk vitamin A concentrations were assessed during a community-based trial in Matlab, Bangladesh. At 1-3 wk postpartum, women were randomly assigned to receive either (1) a single dose of 200,000 international units [60,000 retinol equivalents (RE)] vitamin A followed by daily placebos (n = 74), (2) daily doses of beta-carotene [7.8 mg (1300 RE)] (n = 73) or (3) daily placebos (n = 73) until 9 mo postpartum. Compared to placebos, vitamin A supplementation resulted in lower maternal MRDR ratios (i.e., increased liver stores) and higher milk vitamin A concentrations at 3 mo, but these improvements were not sustained. The beta-carotene supplementation acted more slowly, resulting in milk vitamin A concentrations higher than the placebo group only at 9 mo. Irrespective of treatment group, over 50% of women produced milk with low vitamin A concentrations (/=0. 06. We conclude that while both interventions were beneficial, neither was sufficient to correct the underlying subclinical vitamin A deficiency in these women nor to bring their infants into adequate vitamin A status.

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.

Duration of breastfeeding associated with obesity during adolescence.

The relationship between duration of breastfeeding and obesity (body mass index > or = 85 percentile) at adolescence was investigated in a white, rural population (n = 136) in which confounding by race was absent and confounding by socioeconomic status was expected to be minimal. Relevant data were abstracted from hospital charts. When examined independently, minimal (< or = 2 months) or no breastfeeding was positively associated with adolescent obesity (p < 0.03). This association was present in the lower but not the higher socioeconomic status group. However, when sex, birthweight, and socioeconomic status were included in a multiple regression model, duration of breastfeeding was no longer significantly associated with obesity during adolescence.

Vitamin A supplementation fails to reduce incidence of acute respiratory illness and diarrhea in preschool-age Indonesian children.

Vitamin A supplementation of populations of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality, but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated. We conducted an individually randomized, placebo-controlled, double-masked trial among 1,407 Indonesian preschool-age children, to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses. Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers. High dose vitamin A supplements increased the incidence of acute respiratory illnesses (ARI) by 8%, and acute lower respiratory illnesses (ALRI) by 39%. These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status (rate ratio 1.83, 95% confidence interval 1.257-2.669). In contrast, vitamin A tended to be protective of ALRI in chronically malnourished children (rate ratio 0.71, 95% confidence interval 0.375-1.331). There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease (rate ratio 1.06, 95% confidence interval 0.920-1.225). However, we found a significant interaction between supplementation and age: vitamin A increased the incidence of diarrhea in children < 30 mo of age, but tended to reduce the incidence in older children. The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting populations of preschool-age children for vitamin A supplementation.

Clinical trial of vitamin A as adjuvant treatment for lower respiratory tract infections.

OBJECTIVE: To test the efficacy of a high dose of vitamin A as adjuvant treatment for radiographically confirmed cases of acute lower respiratory tract infection (ALRI). DESIGN: Randomized, double-masked, placebo-controlled clinical trial. SETTING: Two large urban hospitals in Guatemala City. PATIENTS: Sequential sample of 263 children aged 3 to 48 months, identified in the emergency departments and admitted to the hospital. INTERVENTIONS: Vitamin A (100,000 IU for children less than 1 year of age, and 200,000 IU for older children) or placebo in addition to standard treatment for ALRI which included antibiotics, oxygen, bronchodilators, and intravenously administered solutions. MEASUREMENTS AND MAIN RESULTS: The children were assessed every 8 hours. There were neither statistically nor clinically significant differences by treatment group in the rate of normalization in respiratory rate, oxygen saturation, temperature, or clinical score. Duration of hospitalization was not different by treatment group. Adverse outcomes (mechanical ventilation, prolonged hospitalization, readmission or transfer, and death) were equally distributed between the two groups. CONCLUSIONS: Treatment with high doses of vitamin A over and above standard care for infants and children with non-measles-related ALRI is not efficacious for the current episode. Additional trials among populations in which vitamin A deficiency is more prevalent and severe should be considered.

PIP: During October 1991 to March 1993, in Guatemala, clinical researchers conducted a randomized, double-blind, placebo-controlled clinical trial of 263 pediatric patients aged 3-48 months at the Hospital Roosevelt and the Guatemalteco Social Security Institute Hospital, both in Guatemala City. They aimed to determine the efficacy of a high dose of vitamin A (100,000 IU for children under 1 year of age and 200,000 IU for older children) as adjuvant treatment for radiographically confirmed cases of non-measles-related acute lower respiratory tract infection (ALRI). All the children received standard treatment for ALRI (antibiotics, oxygen, bronchodilators, and intravenously administered solutions). 132 children also received vitamin A and 131 received a placebo. Clinicians evaluated the childrens' condition every 8 hours. The two groups were essentially the same in duration of hospitalization; the rate of normalization in the respiratory rate, oxygen saturation, temperature, and clinical score; and adverse outcomes (mechanical ventilation, prolonged hospitalization, readmission or transfer, and death). These findings indicate that high doses of vitamin A in addition to standard treatment for non-measles-related ALRI lack efficacy for the current ALRI episode.

Serum retinol levels among preschool children in Central Java: demographic and socioeconomic determinants.

BACKGROUND: Vitamin A deficiency is a significant problem in many countries in the developing world. Reports have noted demographic and socioeconomic risk factors for vitamin A deficiency. 'Deficiency' has usually been defined by clinical signs and symptoms which represent only a small proportion of those children at increased risk for vitamin A preventable morbidity and mortality. METHODS: As part of a population-based trial of vitamin A to prevent childhood morbidity, we collected census data (n = 666), baseline socioeconomic data (n = 636) and sera (n = 666) from children aged 6-48 months in 25 adjacent villages in a rural area in Central Java, Indonesia; there was more than 95% participation. We used t tests, ANOVA, and a multiple variable linear regression model in our analyses. RESULTS: Differences in mean retinol level were detected for the following variables: village (P < 0.001), child's age (P = 0.03), size of sibship (P < 0.001), mother's occupation (P < 0.01), mother's education (P = 0.05), father's education (P = 0.03), monthly household earnings (P = 0.02), land ownership (P = 0.03), possession of ducks (P = 0.06), radio or tape player (P = 0.02), or a watch or clock (P = 0.07), and presence of a natural well (P = 0.09). Our regression model verified the predictive value of village, age, sibship, land ownership and earnings. CONCLUSIONS: We found that owning land and that the highest and lowest categories of reported household income were associated with higher serum retinol levels. We also noted clustering of serum retinol levels by village and discovered that children from larger sibships and infants had significantly lower serum retinol levels. Vitamin A supplementation of lactating mothers, particularly of high parity, and/or their infants should be considered.

PIP: Vitamin A deficiency is a significant problem in many countries in the developing world. Reports have noted demographic and socioeconomic risk factors for vitamin A deficiency. As part of a population-based trial of vitamin A to prevent childhood morbidity, census data (n = 666), baseline socioeconomic data (n = 636) and sera (n = 666) were collected from children 6-48 months old in 25 adjacent villages in a rural area in Central Java, Indonesia. Participation amounted to more than 95%. The analyses used t tests, ANOVA, and a multiple variable linear regression model. The distribution of serum retinol levels (in mcmol/l) in males shifted to the left relative to females, resulting in a higher proportion of males with a level 0.70 mcmol/l (20 mcg/dl); 216/346 males versus 173/320 females (p = 0.03). However, there was no significant difference in the means by gender. Differences in mean retinol level were detected for the following variables: village (p 0.001); child's age (p = 0.03); size of sibship (p 0.001); mother's occupation (p 0.01); mother's education (p = 0.05); father's education (p = 0.03); monthly household earnings (p = 0.02); land ownership (p = 0.03); possession of ducks (p = 0.06), radio or tape player (p = 0.02), or a watch or clock (p = 0.07); and presence of a natural well (p = 0.09). There was no significant difference in mean serum retinol level for mother's marital status; father's occupation; monthly household expenditures; house ownership; composition of floors, walls, or roofs; or possession of buffaloes, cattle, goats, kerosene light fixtures, televisions, or motorcycles. The regression model verified the predictive value of village, age, sibship, land ownership, and earnings. Owning land and the highest and lowest categories of reported household income were associated with higher serum retinol levels. Also clustering of serum retinol levels was noted by village, and children from larger sibships and infants had significantly lower serum retinol levels. Vitamin A supplementation of lactating mothers, particularly of high parity, and/or their infants should be considered.

Multiple high dose vitamin A supplementation. A report on five cases.

Vitamin A toxicity is a concern among health care providers, especially when present recommendations for vitamin A may result in multiple dosing during a short period of time. We observed no vitamin A toxicity in 5 children who received multiple high doses of vitamin A. These 8-month to 5-year-old children were part of a community trial of vitamin A during acute measles, and were being treated at a local hospital for severe acute respiratory infection, malaria, and/or diarrhoea. One 12-month-old who received 1,612,500 I.U. within a period of three weeks showed elevated serum retinol (3.42 mumol/l), but none of the five showed signs of toxicity. These cases illustrate the confusion surrounding the correct use of vitamin A for infants and children with multiple morbid conditions. A plea is made to report similar situations since clinical trials are unethical.

Conjunctival impression cytology (CIC) to detect subclinical vitamin A deficiency: comparison of CIC with biochemical assessments.

By use of sensitivity and specificity analysis, conjunctival impression cytology (CIC) was compared with fasting serum vitamin A levels and relative dose response (RDR) of Guatemalan children. One impression was taken from the temporal bulbar aspect of each eye, fasting serum vitamin A levels were then drawn, 480 RE of oil-based retinyl palmitate was given, and a 5-h postdosing vitamin A level was drawn (RDR procedure). For a 20% RDR cutoff, the sensitivity of CIC was 23% with a specificity of 80% and a positive predictive value of 9% (n = 213 children). Compared with fasting vitamin A levels alone (with 0.70 mumol/L as abnormal), the sensitivity of CIC was 26%, specificity was 81%, and positive predictive value was 22% (n = 221 children). There was no significant difference in the mean serum retinol level between those with abnormal and normal CIC. In this study population CIC does not identify the same group of children with marginal vitamin A as identified biochemically.

Conjunctival impression cytology: feasibility of a field trial to detect subclinical vitamin A deficiency.

Two hundred and thirty-six Guatemalan children aged 2-14 y were examined for subclinical vitamin A deficiency by use of conjunctival impression cytology (CIC). The feasibility of the technique and quality of a modified touch procedure were assessed. Neither lid speculum nor physical restraint in the form of a papoose board was used. The CIC technique was easily performed on children aged greater than 3 y but was more difficult among those less than or equal to 3 y. Laboratory processing of specimens is uncomplicated but interpretation may be problematic and requires clearly defined criteria of normal and abnormal cytology as well as careful standardization of readers.