Sex differences in the early life correlates of natural antibody concentrations.

Innate-like B1a lymphocytes arise from long-lived progenitors produced exclusively by fetal stem cells. Any insults coinciding with this early lymphopoietic wave could have a permanent impact on the B1a population and its unique protein products, the natural antibodies (NAb). We investigated early life nutritional influences on NAb concentrations of pre-adolescent children (n=290) in rural Nepal for whom we had extensive information on exposures from pregnancy and early infancy. Infant size and growth were strongly associated with NAb concentrations at 9-13 years of age among males (e.g., for neonatal weight: ßBOYS=0.43; P<0.001), but not females (e.g., for neonatal weight: ßGIRLS=-0.16; P=0.26). In females, season of birth was associated with NAb concentrations, with marked reductions among girls born during the pre-monsoon (March-May; ßGIRLS=-0.39; P=0.01) and pre-harvest (September-November; ßGIRLS=-0.35; P=0.03) seasons. Our findings suggest that nutritional or other environmental influences on immune development may vary by sex, with potential consequences for immune function during infancy and long-term risk of immune-mediated disease.

Shear Wave Elastography May Be Superior to Greyscale Median for the Identification of Carotid Plaque Vulnerability: A Comparison with Histology.

PURPOSE: There is a need to develop methods that reliably quantify characteristics associated with vulnerable carotid plaque. Greyscale median (GSM) and shear wave elastography (SWE) are two techniques that may improve individual plaque risk stratification. SWE, which quantifies Young's Modulus (YM) to estimate tissue stiffness, has been researched in the liver, breast, thyroid and prostate, but its use in carotid plaques is novel. MATERIALS AND METHODS: The aim of this study was to quantify YM and GSM of plaques and compare to histology. 25 patients (64% male) with a mean age of 76 underwent both clinical and SWE imaging. The mean GSM was quantified over a cardiac cycle. The mean YM was quantified in multiple regions within the plaque over 5 frames. Histological features were assessed following carotid endarterectomy. RESULTS: The mean YM of unstable plaques was significantly lower than that of stable plaques (50.0 kPa vs. 79.1 kPa; p = 0.027). The presence of intra-plaque hemorrhage, thrombus and increasing numbers of foam cells was also associated with a significantly lower YM. Plaque YM did not correlate well with plaque GSM (r =  .12). The mean plaque GSM was the same in both unstable and stable plaques. Fibrous plaques had a significantly higher GSM (p = 0.036). CONCLUSION: In conclusion, SWE provides additional information on plaque stiffness which may be of clinical benefit to help identify vulnerable plaque, and warrants further study.

Beyond pregnancy--the neglected burden of mortality in young women of reproductive age in Bangladesh: a prospective cohort study.

OBJECTIVE: To describe proportionate mortality and causes of death unrelated to pregnancy. DESIGN: Prospective cohort study. SETTING: Rural northwest Bangladesh. POPULATION: A cohort of 133,617 married women of reproductive age. METHODS: Verbal autopsies were conducted for women who died whilst under surveillance in the cohort trial. Physician-assigned causes of death based on verbal autopsies were used to categorise deaths. MAIN OUTCOME MEASURES: The proportion of deaths due to non-communicable diseases, infectious diseases, injury or pregnancy. RESULTS: Of the 1107 deaths occurring among women between 2001 and 2007, 48% were attributed to non-communicable diseases, 22% to pregnancy, 17% to infections, 9% to injury and 4% to other causes. CONCLUSIONS: Although focus on pregnancy-related mortality remains important, more attention is warranted on non-communicable diseases among women of reproductive age.

The impact of potential islet precursor cells on islet autotransplantation outcomes.

Islet autotransplant patients represent excellent subjects to assess the posttransplant impact of islet precursors, as chronic pancreatitis (CP) causes an elevation of ductal cells, pancreatic precursors cells, and hormone-positive acinar cells. The relationship between these cell types and autograft outcomes should be more apparent than would be the case in the context of an allograft program with confounding immunological variables. To improve diabetic control following total pancreatectomy for CP, nonpurified islets were autotransplanted into the liver. Pancreas specimens were recovered from 23 patients and stained for antigens including: insulin, glucagon, cytokeratin 19, cytokeratin 7, and PDX-1. In line with previous reports, the prevalence of ductal cells, non-islet endocrine cells and non-islet PDX-1-expressing cells was significantly higher in CP glands compared with normal pancreata. When correlating follow-up data (i.e., fasting and stimulated C-peptide/glucose levels and HbA1c%) with pancreas immunoreactivity, high levels of ductal cells, non-islet PDX-1-positive cells, and non-islet glucagon-positive cells were associated with superior outcomes, detectable up to 2 years posttransplant. To conclude, the acinar parenchyma and ductal epithelium of the CP pancreas show an upregulation of both endocrine and pre-endocrine cell types, which appear to have a positive effect on islet graft outcomes in autotransplantation setting.

Maternal serum proteome changes between the first and third trimester of pregnancy in rural southern Nepal.

Characterization of normal changes in the serum proteome during pregnancy may enhance understanding of maternal physiology and lead to the development of new gestational biomarkers. In 23 Nepalese pregnant women who delivered at term, two-dimensional difference in-gel electrophoresis (DIGE) was used to assess changes in relative protein abundance between paired serum samples collected in the first and third trimesters. One-hundred and forty-five of over 700 protein spots in DIGE gels (pI 4.2-6.8) exhibited nominally significant (p < 0.05) differences in abundance across trimesters. Additional filtering using a Bonferroni correction reduced the number of significant (p < 0.00019) spots to 61. Mass spectrometric analysis detected 38 proteins associated with gestational age, cytoskeletal remodeling, blood pressure regulation, lipid and nutrient transport, and inflammation. One new protein, pregnancy-specific ß-glycoprotein 4 was detected. A follow-up isotope tagging for relative and absolute quantitation (iTRAQ) experiment of six mothers from the DIGE study revealed 111 proteins, of which 11 exhibited significant (p < 0.05) differences between trimesters. Four of these proteins: gelsolin, complement C1r subcomponent, α-1-acid glycoprotein, and α-1B-glycoprotein also changed in the DIGE analysis. Although not previously associated with normal pregnancy, gelsolin decreased in abundance by the third trimester (p < 0.01) in DIGE, iTRAQ and Western analyses. Changes in abundance of proteins in serum that are associated with syncytiotrophoblasts (gelsolin, pregnancy-specific ß-1 glycoprotein 1 and ß-2-glycoprotein I) probably reflect dynamics of a placental proteome shed into maternal circulation during pregnancy. Measurement of changes in the maternal serum proteome, when linked with birth outcomes, may yield biomarkers for tracking reproductive health in resource poor settings in future studies.

Supplementation with vitamin A early in life and subsequent risk of asthma.

Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma. We examined the long-term effects of vitamin A supplementation early in life on later asthma risk. In 2006-2008, we revisited participants from two cohorts in rural Nepal who were enrolled in randomised trials of vitamin A supplementation. The first cohort received vitamin A or placebo for <16 months during their pre-school years (1989-1991). The second cohort was born to mothers who received vitamin A, ß-carotene or placebo before, during and after pregnancy (1994-1997). At follow-up, we asked about asthma symptoms and performed spirometry. Out of 6,421 subjects eligible to participate, 5,430 (85%) responded to our respiratory survey. Wheezing prevalence during the previous year was 4.8% in participants aged 9-13 yrs and 6.6% in participants aged 14-23 yrs. We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction (p ≥ 0.12 for all comparisons). Vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency.

Acute computed tomography findings in patients with acute confusion of non-traumatic aetiology.

BACKGROUND: A retrospective review was undertaken of all patients referred for computed tomography (CT) scans of the head for acute onset of confusion, not consequent on head trauma, during the period June 1, 2004 to May 31, 2007. METHOD: Data were obtained by Microsoft Word search of the reports of the Radiology Department of the University Hospital of the West Indies, Kingston, Jamaica. Two hundred and twenty-one patients were reviewed: 103 men and 118 women. The mean age of the sample was 64 years; 168 patients (76%) were 50 years old or older. RESULT: Computed tomography scans were reported normal in 170 (76.9%) patients; 45 patients (20.4%) had definite acute intracranial CT findings. Findings were equivocal in three patients (1.4%) and unavailable for three (1.4%); 23.2% and 15.6% of patients above and below the age of 50 years respectively showed acute abnormalities on CT The most common acute finding on CT scan was an ischaemic infarct (68%). Other abnormalities included intracerebral haemorrhage and metastases 6.2% each, toxoplasmosis and primary brain tumour 4.2% each and subdural haematoma and meningitis 2.1% each. The diagnoses of toxoplasmosis were made based on appearances typical of toxoplasmosis on CT scans in patients whose request stated that they were HIV positive. CONCLUSION: In the sample reviewed, most patients who presented with acute confusion were above the age of 50 years. Overall, 20.4% of patients from all age groups had acute abnormalities on CT with a relative higher proportion, 23.2% versus 15.6% of those over 50 years, having acute pathology. The most common abnormality was an ischaemic infarct. This finding is similar to that in developed countries and unlike that seen in other developing countries where infectious aetiologies predominate.

Association between nutritional status and positive childhood disability screening using the ten questions plus tool in Sarlahi, Nepal.

The study was conducted to examine the association between the indicators of malnutrition and disability of children as reported by caregivers. The Ten Questions Plus questionnaire was administered to caregivers of 1,902 children aged 1-9 years, during August 2007-March 2008, in rural Nepal. Height and weight of children were also measured. The main outcome was a positive response to one or more questions. In total, 514 (27%) children had a positive response to at least one question. Moderate stunting [odds ratio (OR)=1.47, 95% confidence interval (CI) 1.02-2.12) and severe (OR=2.39, 95% CI 1.60-3.57) stunting were independently associated with reported delay in sitting, standing, or walking. Severe stunting was also associated with report of delayed learning compared to other children of similar age (OR=2.01, 95% CI 1.27-3.20). Parental report of disability was quite prevalent in this setting, with over a quarter of the sample screening positive. Chronic malnutrition may be associated with delayed motor and mental development.

Maternal supplementation with vitamin A or ß-carotene and cardiovascular risk factors among pre-adolescent children in rural Nepal.

Vitamin A plays an important role in fetal renal and cardiovascular development, yet there has been little research on its effects on cardiovascular risk factors later in childhood. To examine this question, we followed the children of women who had been participants in a cluster-randomized, double blind, placebo-controlled trial of weekly supplementation with 7000 µg retinol equivalents of preformed vitamin A or 42 mg of ß-carotene from 1994 to 1997 in rural Nepal. Women received their assigned supplements before, during and after pregnancy. Over a study period of 3 years, 17,531 infants were born to women enrolled in the trial. In 2006-2008, we revisited and assessed 13,118 children aged 9-13 years to examine the impact of maternal supplementation on early biomarkers of chronic disease. Blood pressure was measured in the entire sample of children. In a subsample of 1390 children, venous blood was collected for plasma glucose, Hb1Ac and lipids and a morning urine specimen was collected to measure the ratio of microalbumin/creatinine. Detailed anthropometry was also conducted in the subsample. The mean ± s.d. systolic and diastolic blood pressure was 97.2 ± 8.2 and 64.6 ± 8.5 mm Hg, respectively, and about 5.0% had high-blood pressure (⩾120/80 mm Hg). The prevalence of microalbuminuria (⩾30 mg/g creatinine) was also low at 4.8%. There were no differences in blood pressure or the risk of microalbuminuria between supplement groups. There were also no group differences in fasting glucose, glycated hemoglobin, triglycerides or cholesterol. Maternal supplementation with vitamin A or ß-carotene had no overall impact on cardiovascular risk factors in this population at pre-adolescent age in rural Nepal.

Degenerative disc disease of the lumbar spine on MRI.

UNLABELLED: A retrospective analysis was done of all patients referred for MRI of the lumbar spine at the University Hospital of the West Indies, Kingston, Jamaica, during the three-year period January 1, 2005 and December 31, 2007. Data were collected to determine patients 'age, gender, weight and the presence or absence of degenerative disc disease (DDD). The patients' presenting symptoms were not evaluated. There were 362 patients examined: 154 males, 204 females and four uncharacterized, aged between 8 and 87 (mean age = 50.45) years. Degenerative Disc Disease (DDD), was found in 283 (78.2%) patients: 121 males, 159 females and three unidentified, with a total of 669 degenerate discs. L 4/5 and L 5/S 1 were most frequently affected accounting for 31.2% and 30.6% of degenerate discs respectively. Patients with DDD were significantly heavier and significantly older than patients without disc disease. Gender was not predictive of DDD in general nor of involvement of any particular disc though a marginally significant tendency was found for males to more frequently have DDD at L1/2 and L5/S1. CONCLUSION: Degenerative disc disease of the lumbar spine occurred more frequently in older and heavier patients. Gender did not affect the presence or the extent of the disease; compared to females, males showed a marginally increased tendency to have DDD at L1/2 and L5/S1.

Cholelithiasis on imaging--an analysis of clinical presentations by age and gender in a Jamaican population.

OBJECTIVE: This study is a descriptive analysis of the clinical presentations in which cholelithiasis was diagnosed on imaging over a five-year period at the University Hospital of the West Indies, Jamaica and how the clinical presentation varied with age and gender. METHOD: A retrospective review was done of all cases of cholelithiasis recorded in the reports of the Radiology section during the period January 1, 2002 to December 31, 2006. Patients' age and gender were noted. Each case was assigned to one of four clinical categories based on the clinical scenario at the time of referral for imaging: Acute abdomen-Incidental: (not referable to the biliary tract); Acute abdomen-Biliary (biliary colic/acute cholecystitis); Non-acute-Incidental: (not referable to the biliary tract) and Non-acute-Biliary (suspected cholelithiasis). The data were analyzed using post-hoc cross-tabulations, ANOVA, and post-hoc Tukey-tests. RESULTS: Three hundred and forty-four females and 137 males were diagnosed with cholelithiasis with the mean age at diagnosis being 49 and 50 years respectively. Females were diagnosed with cholelithiasis at higher rates in the context of acute abdominal symptoms both referable and unrelated to the biliary tract, while males were diagnosed at higher rates as an incidental finding in a non-acute presentation. There was no significant difference between the genders in the rate of diagnosis of cholelithiasis when this was suspected clinically in the non-acute setting. CONCLUSION: More females were diagnosed with cholelithiasis. There was no gender-related difference in the mean age at which cholelithiasis was diagnosed. There were statistically significant differences between the genders in the rates at which cholelithiasis was identified in different clinical scenarios.

The effect of maternal micronutrient supplementation on early neonatal morbidity in rural Nepal: a randomised, controlled, community trial.

OBJECTIVE: Micronutrient deficiencies during pregnancy may be linked to poor newborn health and poor host defences against infection. We assessed newborn morbidity to determine the effect of four combinations of antenatal micronutrient supplements. DESIGN: Cluster-randomised, double-masked, controlled trial. SETTING: Rural community in Nepal. INTERVENTIONS: Women received daily supplements from early pregnancy through to 3 months postpartum of vitamin A alone (control) or vitamin A with folic acid, folic acid plus iron, folic acid plus iron plus zinc or a multiple micronutrient supplement containing these and 11 other nutrients. MAIN OUTCOME MEASURES: Infants were visited in their home at birth (n = 3927) and for each of 9 days thereafter to elicit a 24-h history of nine infant morbidity symptoms, measure infant respiratory rate and axial temperature, and assess the infant for chest indrawing. At 6 weeks of age, infants were visited again in their homes to elicit a 30-day and 7-day history of 10 morbidity symptoms using parental recall. RESULTS: Maternal micronutrient supplementation had no effect on 10-day morbidity or morbidity 30-day and 7-day morbidity assessed at 6 weeks of age all relative risks were close to 1. Symptoms of birth asphyxia increased by about 60% (p<0.05) in infants of women who received the multiple micronutrient supplement compared with the control. Symptoms of combinations of sepsis, preterm and birth asphyxia were associated with 8- to 14-fold increased odds of 6-month infant mortality. CONCLUSIONS: None of the combinations of antenatal micronutrient supplements tested improved symptoms of neonatal morbidity in the first 10 days of life or at 6 weeks of age. Further research is needed to elucidate the association and mechanism of increased risk of birth asphyxia following maternal multiple micronutrient supplementation. TRIAL REGISTRATION NUMBERS: NCT00115271.

The impact of a small steady stream of income for women on family health and economic well-being.

Our primary aim to evaluate the impact of a small steady stream of income on family health and well-being among rural women employed part-time in a health project in Sarlahi district, Nepal. All 870 women applying for the job of distributing nutritional supplements in their villages completed a questionnaire prior to selection for employment, 350 of whom were hired and 520 who were not. A total of 736 women completed a second questionnaire 2 years later, 341 (97.4%) of whom had been continuously employed during this period, and 395 (76.0%) who had never been employed by the project. Changes in health and well-being over 2 years were compared between women who were and were not hired. Women who were hired were younger and better educated, but were similar in other regards. After adjusting for selection differences, employed women were more likely to save cash, buy jewellery, and buy certain discretionary household goods over 2 years than those who were not hired. Expenditures on children's clothing increased more for employed women, and their children were more likely to be in private schools at follow-up, but there was no impact on health and survival of children. Women with a small steady stream of income did improve their personal economic situation by savings and increased expenditures for children and the household. Longer follow-up may reveal impacts on health access and expenditures, although these were not evident in 2 years of employment.

A randomised trial of povidone-iodine to reduce visual impairment from corneal ulcers in rural Nepal.

AIM: To assess whether povidone-iodine provided any benefit over and above a standard regimen of antibiotic therapy for the treatment of corneal ulcers. METHODS: All patients diagnosed with corneal ulcers presenting for care at a primary eye care clinic in rural Nepal were randomised to a standard protocol of antibiotic therapy versus standard therapy plus 2.5% povidone-iodine every 2 hours for 2 weeks. The main outcomes were corrected visual acuity and presence, size, and position of corneal scarring in the affected eye at 2-4 months following treatment initiation. RESULTS: 358 patients were randomised and 81% were examined at follow up. The two groups were comparable before treatment. At follow up, 3.9% in the standard therapy and 6.9% in the povidone-iodine group had corrected visual acuity worse than 20/400 (relative risk (RR) 1.77, 95% confidence interval (CI) 0.62 to 5.03). 9.4% in the standard therapy and 13.1% in the povidone-iodine group had corrected visual acuity worse than 20/60 (RR 1.39, 95% CI 0.71 to 2.77), and 17.0% and 18.8% had scars in the visual axis in each of these groups, respectively (RR 1.11, 95% CI 0.67 to 1.82). CONCLUSIONS: A small proportion of patients with corneal ulceration treated in this setting had poor visual outcomes. The addition of povidone-iodine to standard antibiotic therapy did not improve visual outcomes, although this design was unable to assess whether povidone-iodine on its own would have resulted in comparable visual outcomes to that of standard therapy.

Complex interactions with infection and diet may explain seasonal growth responses to vitamin A in preschool aged Indonesian children.

OBJECTIVE: To explore the potential contribution of respiratory infections and vitamin A intakes to the seasonal effect of vitamin A supplementation on child growth. METHODS: Data from a randomized double-blind placebo-controlled trial, in which a single high dose of vitamin A or placebo was given every 4 months to 1405 children aged 6-48 months were used for the analysis. In total, 4430 child-treatment cycles were examined, and for each cycle the children had their dietary intake, weight, and height assessed at the start and end. Linear regression models of the difference in height and weight during each treatment cycle were used and the within-child correlation was adjusted using the generalized estimating equations (GEE). Other covariables in the model included age, sex, percentage of days with acute lower respiratory infection and diarrhea, and cumulative doses of vitamin A. RESULTS: This study showed that a significant effect of vitamin A supplementation on linear growth was observed in all seasons in children with a low burden of respiratory infections, that is, < 21.5% of days with respiratory illness. In each season, the highest effect was found in children with a low burden of respiratory infections and low vitamin A intakes, that is, intakes < 400 RE/day. Children with a high burden of respiratory infections or high vitamin A intakes benefited less from vitamin A supplementation for their linear growth than children with a low burden of respiratory infections and low vitamin A intakes. Finally, there was no benefit for linear growth from vitamin A supplementation in children with both a high burden of respiratory infections and high vitamin A intakes regardless of the season. CONCLUSIONS: The effect of vitamin A supplementation on growth is dependent on season. Respiratory infections and vitamin A intakes are important factors underlying the seasonal effect of vitamin A supplementation on growth.

Vitamin A deficiency as a preventable cause of maternal mortality in undernourished societies: plausibility and next steps.

Maternal vitamin A deficiency is a public health problem in the developing world. Recent evidence from Nepal suggests that supplementing populations of rural, poor, and undernourished women with a recommended dietary amount of vitamin A--or its equivalent as beta-carotene--can lower mortality risk related to pregnancy and childbirth, presumably by reducing the severity of conditions such as sepsis, tuberculosis, and diarrheal diseases. An adequate intake of beta-carotene may also reduce some maternal health risks related to oxidative stress. These findings reveal the potential for vitamin A and other micronutrient interventions to improve maternal and infant health and survival. They also present important implementation challenges for the developing world.

Vitamin A deficiency and xerophthalmia among school-aged children in Southeastern Asia.

OBJECTIVE: To determine provisional estimates of the extent of vitamin A (VA) deficiency and xerophthalmia among school-aged children. DESIGN: Literature search of published, unpublished and website-based population survey and study reports, with country-specific imputation of prevalence rates and numbers of children affected by: (1) VA deficiency based on measured or imputed distributions of serum retinol concentration < 0.70 micromol/l (equivalent to < 20 microg/dl) and (2) xerophthalmia, by country. SETTING: Countries within the WHO South-East Asian Region. SUBJECTS: The target group for estimation was children 5-15 y of age. INTERVENTIONS: None. RESULTS: The estimated prevalence of VA deficiency is 23.4%, suggesting that there are approximately 83 million VA-deficient school-aged children in the region, of whom 10.9% (9 million, at an overall prevalence of 2.6%) have mild xerophthalmia (night blindness or Bitot's spot). Potentially blinding corneal xerophthalmia appears to be negligible at this age. CONCLUSIONS: VA deficiency, including mild xerophthalmia, appears to affect large numbers of school-aged children in South-East Asia. However, nationally representative data on the prevalence, risk factors and health consequences of VA deficiency among school-aged children are lacking within the region and globally, representing a future public health research priority.

Cigarette smoking during pregnancy in rural Nepal. Risk factors and effects of beta-carotene and vitamin A supplementation.

OBJECTIVE: We examined risk factors of smoking and the association between smoking and pregnancy-related and 6-month infant mortality in rural Nepal, where 30% women reported smoking during pregnancy. DESIGN: Cross-sectional analysis of risk factors associated with smoking status and health consequences of smoking, using prospective data collected as part of a randomized community trial to examine the effect of maternal vitamin A or beta-carotene supplementation on maternal mortality. SETTING: Rural, southeastern plains of Nepal. SUBJECTS AND METHODS: A total of 17 767 women contributed at least one pregnancy during 3.5 y of the study. Data on cigarette or bidi (rolled tobacco) smoking were collected using a 7-day recall, twice during pregnancy. Associations between smoking status and maternal diet, morbidity profile, household socioeconomic status and serum concentration of retinol, carotenoids and tocopherols were examined. Further, relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate supplement effects on pregnancy-related mortality, stratified by smoking status during pregnancy. RESULTS: Smokers were more likely to be older, illiterate and poor compared to nonsmokers. Fruit and vegetable consumption among smokers and nonsmokers did not vary. However, smokers were more likely to consume meat/fish/eggs and less likely to consume milk than nonsmokers. They were also more likely to report symptoms of vaginal bleeding, edema, severe headache and convulsions during pregnancy relative to nonsmokers. Mortality per 100,000 pregnancies appeared to be higher among smokers than nonsmokers in the placebo group (915 vs 584, RR=1.57, 95% CI: 0.80-3.08). beta-Carotene supplementation reduced pregnancy-related mortality both among smokers (RR=0.31 95% CI: 0.11-0.89) and nonsmokers (RR=0.41, 95% CI: 0.19-0.89). Similar results obtained with vitamin A supplementation were not statistically significant. Infant mortality up to 6 months was approximately 30% higher among smokers compared to nonsmokers in the placebo group both before and after adjusting for confounding factors. Neither supplement given to women reduced infant mortality. CONCLUSIONS: Cigarette smoking during pregnancy is associated with an increased risk of maternal and infant mortality in rural Nepal. beta-Carotene and to some extent vitamin A may reduce the risk of pregnancy-related mortality, but not infant mortality, among both smokers and nonsmokers.