Norman Goco

Antioxidant Therapy to Prevent Preeclampsia A Randomized Controlled Trial

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and &agr;=.05. The &agr; level for the final analysis, adjusted for interim looks, was 0.0458. RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61–1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, preterm delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79–12.62). CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among patients with chronic hypertension and/or prior preeclampsia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00097110 LEVEL OF EVIDENCE: I

Tobacco use and secondhand smoke exposure during pregnancy: An investigative survey of women in 9 developing nations:

OBJECTIVES We examined pregnant womens use of cigarettes and other tobacco products and the exposure of pregnant women and their young children to secondhand smoke (SHS) in 9 nations in Latin America, Asia, and Africa. METHODS Face-to-face surveys were administered to 7961 pregnant women (more than 700 per site) between October 2004 and September 2005. RESULTS At all Latin American sites, pregnant women commonly reported that they had ever tried cigarette smoking (range: 78.3% [Uruguay] to 35.0% [Guatemala]). The highest levels of current smoking were found in Uruguay (18.3%), Argentina (10.3%), and Brazil (6.1%). Experimentation with smokeless tobacco occurred in the Democratic Republic of the Congo and India; one third of all respondents in Orissa, India, were current smokeless tobacco users. SHS exposure was common: between 91.6% (Pakistan) and 17.1% (Democratic Republic of the Congo) of pregnant women reported that smoking was permitted in their home. CONCLUSIONS Pregnant womens tobacco use and SHS exposure are current or emerging problems in several low- and middle-income nations, jeopardizing ongoing efforts to improve maternal and child health.

Antioxidant Supplementation and Premature Rupture of the Membranes: A Planned Secondary Analysis

OBJECTIVE The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM). STUDY DESIGN A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo. RESULTS Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group. CONCLUSION Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM.

Meat consumption is associated with less stunting among toddlers in four diverse low-income settings

Background Early growth faltering is common but is difficult to reverse after the first 2 years of life. Objective To describe feeding practices and growth in infants and young children in diverse low-income settings prior to undertaking a complementary feeding trial. Methods This cross-sectional study was conducted through the Global Network for Womens and Childrens Health Research in Guatemala, Democratic Republic of Congo, Zambia, and Pakistan. Feeding questionnaires were administered to convenience samples of mothers of 5- to 9-month old infants and 12- to 24-month-old toddlers. After standardized training, anthropometric measurements were obtained from the toddlers. Following the 2006 World Health Organization Growth Standards, stunting was defined as length-for-age < −2SD, and wasting as weight-for-length < −2SD. Logistic regression was applied to evaluate relationships between stunting and wasting and consumption of meat (including chicken and liver and not including fish). Results Data were obtained from 1,500 infants with a mean (± SD) age of 6.9 ± 1.4 months and 1,658 toddlers with a mean age of 17.2 ± 3.5 months. The majority of the subjects in both age groups were breastfed. Less than 25% of the infants received meat regularly, whereas 62% of toddlers consumed these foods regularly, although the rates varied widely among sites. Stunting rate ranged from 44% to 66% among sites; wasting prevalence was less than 10% at all sites. After controlling for covariates, consumption of meat was associated with a reduced likelihood of stunting (OR = 0.64; 95% CI, 0.46 to 0.90). Conclusions The strikingly high stunting rates in these toddlers and the protective effect of meat consumption against stunting emphasize the need for interventions to improve complementary feeding practices, beginning in infancy.

Neither a Zinc Supplement nor Phytate-Reduced Maize nor Their Combination Enhance Growth of 6- to 12-Month-Old Guatemalan Infants

After age 6 mo, the combination of breast-feeding and unfortified plant-based complementary feeding provides inadequate zinc (Zn). Additionally, high phytate intakes compromise the bioavailability of zinc. Our principal objective in this randomized controlled, doubly masked trial was to determine the effect of substituting low-phytate maize, a daily 5-mg zinc supplement, or both, in infants between ages 6-12 mo on impaired linear growth velocity, a common feature of zinc deficiency. In the Western Highlands of Guatemala, 412 infants were randomized to receive low-phytate or control maize. Within each maize group, infants were further randomized to receive a zinc supplement or placebo. Length, weight, and head circumference were measured at 6, 9, and 12 mo of age. There were no significant differences between the 2 maize groups or between the Zn supplement and placebo groups and no treatment interaction was observed for length-for-age (LAZ), weight-for-length (WLZ) or head circumference Z-scores. Overall mean (+/- SD) Z-scores at 6 mo for combined treatment groups were: LAZ, -2.1 +/- 1.1; WLZ, 0.7 +/- 1.0; and head circumference Z-score, -0.7.0 +/- 1.0. At 12 mo, these had declined further to: LAZ, -2.5 +/- 1.1; WLZ, -0.0 +/- 0.9; and head circumference Z-score, -0.9 +/- 1.1; 83.3% were stunted and 2% were wasted. Low linear growth in older Guatemalan infants was not improved with either low-phytate maize or a daily 5-mg zinc supplement. Low contribution of maize to the complementary food of the infants negated any potential advantage of feeding low-phytate maize.

High Dosage Folic Acid Supplementation, Oral Cleft Recurrence and Fetal Growth

Objectives: To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth. Patients and Methods: The study included 2,508 women who were at-risk for oral cleft recurrence and randomized into two folic acid supplementation groups: 0.4 and 4 mg per day before pregnancy and throughout the first trimester. The infant outcome data were based on 234 live births. In addition to oral cleft recurrence, several secondary outcomes were compared between the two folic acid groups. Cleft recurrence rates were also compared to historic recurrence rates. Results: The oral cleft recurrence rates were 2.9% and 2.5% in the 0.4 and 4 mg groups, respectively. The recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups). The rate of cleft lip with palate recurrence was 2.9% in the 0.4 mg group and 0.8% in the 4 mg group. There were no elevated fetal growth complications in the 4 mg group compared to the 0.4 mg group. Conclusions: The study is the first double-blinded randomized clinical trial (RCT) to study the effect of high dosage folic acid supplementation on isolated oral cleft recurrence. The recurrence rates were similar between the two folic acid groups. However, the results are suggestive of a decrease in oral cleft recurrence compared to the historic recurrence rate. A RCT is still needed to identify the effect of folic acid on oral cleft recurrence given these suggestive results and the supportive results from previous interventional and observational studies, and the study offers suggestions for such future studies. The results also suggest that high dosage folic acid does not compromise fetal growth.

Description of the methodology used in an ongoing pediatric care interventional study of children born with cleft lip and palate in South America (NCT00097149)

BackgroundThe contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally.Methods/DesignWe are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include childs neurological and physical development and family social and economic conditions.DiscussionLarge-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight.

Complementary feeding: a Global Network cluster randomized controlled trial

BackgroundInadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated.Methods/DesignA cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Womens and Childrens Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial.DiscussionFindings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children.Trial registrationNCT01084109

Oral cleft prevention program (OCPP)

BackgroundOral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.Methods/designThis study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group.The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.DiscussionThe costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women.ClinicalTrials.gov IdentifierNCT00397917

Infant Stunting Is Associated With Short Maternal Stature

ABSTRACT The objectives were to determine the range of maternal height associated with growth velocity of older infants and the magnitude of this association in an indigent population. Maternal height and infant length-for-age z scores (LAZ) were positively correlated at both 6 (n = 412, r = 0.324) and 12 (n = 388, r = 0.335) months (P < 0.0001) and for maternal heights from 131 to 164 cm. Maternal height is independently associated with infant LAZ and stunting (LAZ <−2) at both 6 and 12 months (P < 0.001) and with linear growth velocity from 6 to 12 months (P = 0.0023).