Development of a Population-Level Dichotomous Indicator of Minimum Dietary Diversity as a Proxy for Micronutrient Adequacy in the United States Adolescents Aged 10-19 Y.

BACKGROUND: Diversity is a key component of diet quality and health, but no indicator exists for adolescents under the age of 15 y. OBJECTIVES: To establish a dichotomous indicator for population-level assessment of adolescent dietary diversity as a proxy for micronutrient adequacy. METHODS: We used the probability approach to construct the mean probability of adequacy (MPA) of 11 micronutrients from 2 d of 24-h dietary recall data from NHANES, 2007-2018. For each micronutrient, the probability of adequacy (PA) was calculated using the best linear unbiased predictor of usual intake. Adolescent dietary diversity score (ADDS) was derived with a maximum score of 10 food groups. Generalized linear mixed models were used to examine associations between ADDS and MPA. Receiver operating characteristic analysis was used to establish a cutoff for minimum dietary diversity for adolescents (MDD-A), using an energy-adjusted logistic model with ADDS predicting MPA > 0.6. RESULTS: The PA was >80% for all nutrients except vitamin C (42.1%), folate (65.7%), and calcium (23.8%). Population MPA was 79.4%, and nearly 92% of adolescents had an MPA > 0.6. ADDS was positively associated with MPA, and energy was a significant confounder. The area under the curve was >0.8 on both days with sensitivity and specificity ranging from 0.71 to 0.80. The MDD-A cutoff was calculated as 5.12 and 5.10 food groups on days 1 and 2, respectively. CONCLUSIONS: In the United States adolescents, the best cutoff for a dichotomous indicator of dietary diversity as a proxy for micronutrient adequacy is 6 food groups in a given day. Future research could validate MDD-A and its associated cutoff for use across country contexts.

Development of specific growth charts for children with Fanconi anemia.

Patients with Fanconi anemia (FA) are often perceived to have poor growth when general population growth curves are utilized. We hypothesize that FA patients have unique growth and aimed to create FA-specific growth charts. Height and weight data from ages 0 to 20 years were extracted from medical records of patients treated at the Fanconi Anemia Comprehensive Care Clinic at the University of Minnesota. Height, weight, and BMI growth curves were generated and fitted to reference percentiles using the Lambda-Mu-Sigma method. FA-specific percentiles were compared to WHO standards for ages 0-2 and CDC references for ages 2-20. In FA males, the 50th height- and weight-for-age percentiles overlap with the 3rd reference percentile. In FA females, only the 50th height-for-age percentile overlaps with the 3rd reference percentile. For weight, FA females show progressive growth failure between 6 and 24 months followed by stabilization around the 50th percentile. The FA BMI-for-age percentiles show similar patterns to the weight-for-age percentiles but have different timing of onset of adiposity rebound and broader variability in females. Growth in FA patients follows a different trajectory than available normative curves. FA-specific growth charts may be useful to better guide accurate growth expectations, evaluations, and treatment.

Comparison of Current World Health Organization Guidelines with Physiologically Based Serum Ferritin Thresholds for Iron Deficiency in Healthy Young Children and Nonpregnant Women Using Data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Current WHO serum ferritin (SF) thresholds for iron deficiency (ID) in children (<12 µg/L) and women (<15 µg/L) are derived from expert opinion based on radiometric assays in use decades ago. Using a contemporary immunoturbidimetry assay, higher thresholds (children, <20 µg/L; women, <25 µg/L) were identified from physiologically based analyses. OBJECTIVE: We examined relationships of SF measured using an immunoradiometric assay from the era of expert opinion with 2 independently measured indicators of ID, hemoglobin (Hb) and erythrocyte zinc protoporphyrin (eZnPP), using data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). The SF at which circulating Hb begins to decrease and eZnPP begins to increase provides a physiological basis for identifying the onset of iron-deficient erythropoiesis. METHODS: We analyzed NHANES III cross-sectional data from 2616 apparently healthy children, aged 12-59 mo, and 4639 apparently healthy nonpregnant women, aged 15-49 y. We used restricted cubic spline regression models to determine SF thresholds for ID. RESULTS: SF thresholds identified by Hb and eZnPP did not differ significantly in children, 21.2 µg/L (95% confidence interval: 18.5, 26.5) and 18.7 µg/L (17.9, 19.7), and, in women, were similar although significantly different, 24.8 µg/L (23.4, 26.9) and 22.5 µg/L (21.7, 23.3). CONCLUSIONS: These NHANES results suggest that physiologically based SF thresholds are higher than the thresholds from expert opinion established during the same era. SF thresholds found using physiological indicators detect the onset of iron-deficient erythropoiesis, whereas the WHO thresholds identify a later, more severe stage of ID.

Streamlining Micronutrient Biomarker Statistical Analysis in Populations: An Introduction to the SAMBA R Package.

Micronutrient deficiency is a common global health problem, and accurately assessing micronutrient biomarkers is crucial for planning and managing effective intervention programs. However, analyzing micronutrient data and applying appropriate cutoffs to define deficiencies can be challenging, particularly when considering the confounding effects of inflammation on certain micronutrient biomarkers. To address this challenge, we developed the Statistical Apparatus of Micronutrient Biomarker Analysis (SAMBA) R package, a new tool that increases ease and accessibility of population-based micronutrient biomarker analysis. The SAMBA package can analyze various micronutrient biomarkers to assess status of iron, vitamin A, zinc, and B vitamins; adjust for inflammation; account for complex survey design when appropriate; and produce reports of summary statistics and prevalence estimates of micronutrient deficiencies using recommended age-specific and sex-specific cutoffs. In this study, we aimed to provide a step-by-step procedure for how to use the SAMBA R package, including how to customize it for broader use, and made both the package and user manual publicly available on GitHub. SAMBA was validated by comparing results by analyzing 24 data sets on nonpregnant women of reproductive age from 23 countries and 30 data sets on preschool-aged children from 26 countries with those obtained by an independent analyst. SAMBA generated identical means, percentiles, and prevalence of micronutrient deficiencies to those calculated by the independent analyst. In conclusion, SAMBA simplifies and standardizes the process for deriving survey-weighted and inflammation-adjusted (when appropriate) estimates of the prevalence of micronutrient deficiencies, reducing the time from data cleaning to result generation. SAMBA is a valuable tool that facilitates the accurate and rapid analysis of population-based micronutrient biomarker data, which can inform public health research, programs, and policy across contexts.

Limits of Detection in Acute-Phase Protein Biomarkers Affect Inflammation Correction of Serum Ferritin for Quantifying Iron Status among School-Age and Preschool-Age Children and Reproductive-Age Women.

BACKGROUND: Standardized practices are needed in the analysis of inflammation biomarker values outside limits of detection (LODs) when used for inflammation correction of nutritional biomarkers. OBJECTIVE: We assessed the direction and extent to which serum C-reactive protein (CRP) and α-1-acid-glycoprotein (AGP) values outside LODs (<0.05 mg/L and >4.0 g/L, respectively) affect inflammation regression correction of serum ferritin and compared approaches to addressing such values when estimating inflammation-adjusted ferritin and iron deficiency (ID). METHODS: We examined 29 cross-sectional datasets from 7 countries with reproductive-age women (age 15-49 y) (n = 12,944), preschool-age children (age 6-59 mo) (n = 18,208), and school-age children (age 6-14 y) (n = 4625). For each dataset, we compared 6 analytic approaches for addressing CRP

A School-Based Weekly Iron and Folic Acid Supplementation Program Effectively Reduces Anemia in a Prospective Cohort of Ghanaian Adolescent Girls.

BACKGROUND: School-based iron and folic acid (IFA) supplementation is recommended for adolescent girls in countries with high burdens of anemia. OBJECTIVES: We aimed to evaluate the context-specific effectiveness of a school-based, integrated anemia control program with IFA supplementation in Ghana. METHODS: Using data from a pre-post, longitudinal program evaluation, we evaluated the effectiveness of school-based weekly IFA supplementation in reducing the burden of anemia and increasing hemoglobin concentrations (Hb; primary outcomes) in 2 regions of Ghana. Generalized linear mixed effects models with schools (clusters) as random effects were used to quantify the change in the anemia prevalence and the mean Hb associated with cumulative IFA tablet consumption over 1 school year (30-36 weeks), controlling for participant-level potential confounders. A cut point for minimum effective cumulative IFA consumption that is reflective of adequate Hb was derived following logistic regression. This cut point was verified by a restricted cubic spline model of IFA consumption and Hb. RESULTS: The analytical sample included 60 schools and 1387 girls ages 10-19 years. The prevalence of anemia declined during 1 school year of the intervention, from 25.1% to 19.6% (P = 0.001). Students consumed a mean of 16.4 IFA tablets (range, 0-36). IFA consumption was positively associated with Hb and negatively associated with anemia. Each additional IFA tablet consumed over the school year was associated with a 5% (95% CI, 1-10%) reduction in the adjusted odds of anemia at follow-up, though the relationship is nonlinear. The cut point for minimum effective consumption was 26.7 tablets over a 30-36-week school year, with tablets provided weekly. CONCLUSIONS: School-based weekly IFA supplementation is effective in improving Hb and reducing the anemia prevalence among schoolgirls in Ghana, though most participants consumed fewer than the minimum effective number of IFA tablets. Increasing intake adherence may further improve anemia outcomes in this population.

Initial engagement and persistence of health risk behaviors through adolescence: longitudinal findings from urban South Africa.

BACKGROUND: Little is known about longitudinal patterns of adolescent health risk behavior initial engagement and persistence in low- and middle-income countries. METHODS: Birth to Twenty Plus is a longitudinal birth cohort in Soweto-Johannesburg, South Africa. We used reports from Black African participants on cigarette smoking, alcohol, cannabis, illicit drug, and sexual activity initial engagement and adolescent pregnancy collected over 7 study visits between ages 11 and 18 y. We fit Kaplan-Meier curves to estimate behavior engagement or adolescent pregnancy, examined current behavior at age 18 y by age of first engagement, and performed a clustering analysis to identify patterns of initial engagement and their sociodemographic predictors. RESULTS: By age 13 y, cumulative incidence of smoking and alcohol engagement were each > 21%, while the cumulative incidence of other behaviors and adolescent pregnancy were < 5%. By age 18 y (15 y for cannabis), smoking, alcohol, and sexual activity engagement estimates were each > 65%, cannabis and illicit drug engagement were each > 16%; adolescent pregnancy was 31%. Rates of engagement were higher among males. Current risk behavior activity at age 18 y was generally unrelated to age of initial engagement. We identified three clusters reflecting low, moderate, and high-risk patterns of initial risk behavior engagement. One-third of males and 17% of females were assigned to the high-risk cluster. Sociodemographic factors were not associated with cluster membership. CONCLUSIONS: Among urban dwelling Black South Africans, risk behavior engagement across adolescence was common and clustered into distinct patterns of initial engagement which were unrelated to the sociodemographic factors assessed. Patterns of initial risk behavior engagement may inform the timing of primary and secondary public health interventions and support integrated prevention efforts that consider multiple behaviors simultaneously.

An Integrated Infant and Young Child Feeding and Small-Quantity Lipid-based Nutrient Supplementation Program Is Associated with Improved Gross Motor and Communication Scores of Children 6-18 Months in the Democratic Republic of Congo.

OBJECTIVE: To evaluate the impact of an infant, young child feeding practices-small-quantity lipid nutrient supplements (SQ-LNS) intervention on child development scores in children aged 6-18 months in the Katanga Province, Democratic Republic of Congo (DRC). STUDY DESIGN: We analyzed data of 2595 children from 2 health zones in a quasi-experimental design with preimplementation and postimplementation surveys to evaluate program impact on child development scores. Standard care was received in the comparison health zone and the intervention health zone received standard care plus enhanced infant, young child feeding practices with a monthly supply of 28 SQ-LNS sachets for up to 1 year. Program exposure and communication and motor domains of the Ages and Stages questionnaire were collected to assess changes in child development scores. A quasi-intent-to-treat and adjusted difference-in-difference analyses were used to quantify impact of the enhanced compared with the standard package. RESULTS: In adjusted models contrasting endline with baseline, there was a greater relative increase in proportion of children with normal communication (difference-in-difference, +13.7% [95%CI, 7.9-19.6; P < .001] and gross motor scores, +7.4% [95% CI: 1.3-13.5; P < .001]) in the intervention vs comparison health zones. Further, in separate analyses among children of intervention health zone at endline, each additional SQ-LNS distribution was associated with +0.09 (95% CI, 0.03-0.16) z-score unit increase in gross motor scores (P < .01). CONCLUSIONS: The integrated infant, young child feeding practice-SQ-LNS intervention was positively associated with larger relative improvements in measures of child communication and motor development in the Katanga province of DRC.

Rotavirus group A genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018.

BACKGROUND: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction. METHODS: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. RESULTS: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. CONCLUSION: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.

Prevalence and Predictors of High Blood Pressure Among Women of Reproductive Age and Children Aged 10 to 14 Years in Guatemala.

INTRODUCTION: Data on the prevalence and predictors of high blood pressure among children and non-pregnant women of reproductive age are sparse in Guatemala. Our objective was to identify the prevalence and predictors of high blood pressure among women of reproductive age and children in Guatemala. METHODS: We analyzed data on blood pressure among 560 children aged 10 to 14 years and 1,182 non-pregnant women aged 15 to 49 from a cross-sectional, nationally representative household survey, SIVESNU (Sistema de Vigilancia Epidemiológica de Salud y Nutrición). We defined high blood pressure among children by using 2004 and 2017 US pediatric guidelines. We defined high blood pressure among women by using 1999 World Health Organization (WHO) and 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. We used multivariable logistic regression to identify significant predictors of high blood pressure. A base model included key covariates (age, ethnicity, socioeconomic index, anthropometric indicators) and accounted for complex sampling. We used backward elimination to identify additional candidate predictor variables. RESULTS: High blood pressure was prevalent among 8.0% (95% confidence interval [CI], 5.4%-10.7%) and 14.0% (95% CI, 10.6%-17.5%) of children using 2004 and 2017 guidelines, respectively; and among 12.7% (95% CI, 10.7%-14.8%) and 41.1% (95% CI, 37.7%-44.4%) of women using 1999 WHO and 2017 ACC/AHA guidelines, respectively. Levels of awareness, treatment, and control of high blood pressure were low in women. Among children, significant predictors of high blood pressure were obesity, overweight, and indigenous ethnicity. Among women, significant predictors of high blood pressure included obesity, overweight, and diabetes. CONCLUSION: The prevalence of high blood pressure was high among Guatemalan women and children. Overweight and obesity were strong risk factors for high blood pressure. Increasing obesity prevention and control programs may help prevent high blood pressure, and expanding high blood pressure screening and treatment could increase awareness and control of high blood pressure in Guatemala.

An integrated infant and young child feeding and small-quantity lipid-based nutrient supplementation programme in the Democratic Republic of Congo is associated with improvements in breastfeeding and handwashing behaviours but not dietary diversity.

Integrating small-quantity lipid-based nutrient supplements (SQ-LNS) into infant and young child feeding (IYCF) programmes can increase consumption of essential nutrients among children in vulnerable populations; however, few studies have assessed the impact of integrated IYCF-SQ-LNS programmes on IYCF practices. A 2-year, enhanced IYCF intervention targeting pregnant women and infants (0-12 months) was implemented in a health zone in the Democratic Republic of Congo (DRC). The enhanced IYCF intervention included community- and facility-based counselling for mothers on handwashing, SQ-LNS, and IYCF practices, plus monthly SQ-LNS distributions for children 6-12 months; a control zone received the national IYCF programme (facility-based IYCF counselling with no SQ-LNS distributions). Cross-sectional preintervention and postintervention surveys (n = 650 and 638 in intervention and control areas at baseline; n = 654 and 653 in each area at endline, respectively) were conducted in mothers of children 6-18 months representative of both zones. Difference in differences (DiD) analyses used mixed linear regression models. There were significantly greater increases in the proportion of mothers in the intervention (vs. control) zone who reported: initiating breastfeeding within 1 hr of birth (Adj. DiD [95% CI]: +56.4% [49.3, 63.4], P < 0.001), waiting until 6 months to introduce water (+66.9% [60.6, 73.2], P < 0.001) and complementary foods (+56.4% [49.3, 63.4], P < 0.001), feeding the minimum meal frequency the previous day (+9.2% [2.7, 15.7], P = 0.005); feeding the child in a separate bowl (+9.7% [2.2, 17.2], P = 0.01); awareness of anaemia (+16.9% [10.4, 23.3], P < 0.001); owning soap (+14.9% [8.3, 21.5], P < 0.001); and washing hands after defecating and before cooking and feeding the child the previous day (+10.5% [5.8, 15.2], +12.5% [9.3, 15.6] and +15.0% [11.2, 18.8], respectively, P < 0.001 for all). The enhanced IYCF intervention in the DRC was associated with an improvement in several important IYCF practices but was not associated with a change in dietary diversity (minimum dietary diversity and minimum acceptable diet remained below 10% in both zones without significant differences between zones). The provision of fortified complementary foods, such as SQ-LNS, may be an important source of micronutrients and macronutrients for young children in areas with high rates of poverty and limited access to diverse foods. Future research should verify the potential of integrated IYCF-SQ-LNS to improve IYCF practices, and ultimately children's nutritional status.

Effect of Adjusting for Tanner Stage Age on Prevalence of Short and Tall Stature of Youths in the United States.

OBJECTIVE: To evaluate the extent to which pubertal timing alters the classification of extremes of attained stature across race-ethnicity groups of youths in the US. STUDY DESIGN: We performed analyses of height and Tanner staging data of 3206 cross-sectional national sample of youths ages 8-18 years (53% male, n = 1606), 72% of whom were non-Hispanic white, 9% Mexican American, and 19% non-Hispanic black . Specialized growth models were used to derive Tanner-stage-age-adjusted z scores (TSAHAZ). The prevalence of shortness (<-1SD) and tallness (≥+1SD) status was quantified using TSAHAZ. RESULTS: Highly variable patterns of prevalence of shortness and tallness via chronologic age height z score (CAHAZ) were observed in results stratified by race-ethnicity and sex. Tallness CAHAZ prevalence was high among non-Hispanic white and non-Hispanic black male youths relative to Mexican American (40.0%-43.3% vs 20.5%) with a similar pattern in female youths. In both sexes, this pattern was eliminated with TSAHAZ, with Mexican American youth becoming statistically not different from their non-Hispanic white and non-Hispanic black peers. CONCLUSIONS: Differences in timing of puberty between race-ethnicity groups affects estimated prevalence of shortness and tallness of attained height that remains uncaptured with CAHAZ. Adjustment for pubertal development might help isolate crucial determinants of attained stature and other aspects of body composition that may be most responsive to intervention programs in populations. The curves developed by adjusting for pubertal status may help the clinician avoid misclassification of children with early and late pubertal development.

Accounting for the influence of inflammation on retinol-binding protein in a population survey of Liberian preschool-age children.

Vitamin A deficiency (VAD) is an important contributor to child morbidity and mortality. The prevalence of VAD, measured by retinol-binding protein (RBP) or retinol, is overestimated in populations with a high prevalence of inflammation. We aimed to quantify and adjust for the effect of inflammation on VAD prevalence in a nationally representative survey of Liberian children 6 to 35 months of age. We compared five approaches to adjust RBP for inflammation and estimate VAD prevalence (defined as RBP < 0.7 µmol/L): (1) ignoring inflammation; (2) excluding individuals with inflammation (C-reactive protein (CRP) >5 mg/L or alpha1-acid glycoprotein (AGP) >1 g/)L; (3) multiplying each individual's RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP = exp(InRBP - ß1 (lnCRPobs -lnCRPref ) - ß2 (lnAGPobs -lnAGPref )). Corrected RBP was based on a regression model where reference lnCRP and lnAGP were set to the maximum of the lowest decile. The unadjusted prevalence of VAD was 24.7%. Children with elevated CRP and/or AGP had significantly lower RBP concentrations than their apparently healthy peers (geometric mean RBP 0.79 µmol/L (95% CI: 0.76, 0.82) vs. 0.95 µmol/L (95% CI: 0.92, 0.97), P < 0.001). Using approaches 2-5 resulted in a prevalence of VAD of 11.6%, 14.3%, 13.5% and 7.3%, respectively. Depending on the approach, the VAD prevalence is reduced 10-17 percentage points when inflammation is taken into account. Further quantification of the influence of inflammation on biomarkers of vitamin A status from other national surveys is needed to compare and recommend the preferred adjustment approach across populations.

Patterns of Fetal Growth Based on Ultrasound Measurement and its Relationship with Small for Gestational Age at Birth in Rural Vietnam.

BACKGROUND: Small for gestational age (SGA) is a global health problem. Identifying the timing of fetal growth faltering is critical for developing preventive interventions. We aim to describe patterns of fetal growth and to predict SGA at birth using fetal ultrasound measurements. METHODS: We studied 1412 pregnant women enrolled in a randomised-controlled trial evaluating maternal micronutrient supplementation in Thai Nguyen province, Vietnam. Ultrasound examinations included biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC), and femur length (FL). Measures were assessed using the new international fetal growth standards (INTERGROWTH-21st Project). Generalised linear mixed logit regression models were used to examine the association between ultrasound measures and SGA at birth. RESULTS: Overall fetal growth restriction began in early pregnancy and continued through delivery, but the timing of growth faltering varied by measure: it began by 20 weeks for HC, BPD and AC, earlier as compared to FL growth that started >30 weeks. SGA infants had significantly lower mean fetal growth parameters as early as 14 weeks. Ultrasound measures below the 10th percentile were associated with a two to four times higher risk of SGA at birth compared to fetuses greater than the 50th percentile, with the largest odds ratios for AC (OR 3.9, 95% confidence interval (CI) 2.7, 5.7). CONCLUSIONS: Fetal growth faltering by ultrasound begins in early gestation among rural Vietnamese populations; these patterns clearly identified those to be born SGA. Efforts to prevent fetal growth faltering must begin early in pregnancy and perhaps even before pregnancy.

The relation of peripubertal and pubertal growth to final adult height in children with classic congenital adrenal hyperplasia.

OBJECTIVES: To determine the relationships between peripubertal and pubertal timing and growth, along with glucocorticoid exposure, to the reduced final adult height seen in patients with congenital adrenal hyperplasia (CAH). STUDY DESIGN: Chart review of 104 children with classic CAH (41 males: 28 salt-wasting, 13 simple-virilizing; 63 females: 38 salt-wasting, 25 simple-virilizing) were selected from a cohort from 3 medical institutions in Minnesota. Triple logistic modeling of longitudinal data was performed to determine patterns of peripubertal and pubertal growth. RESULTS: Hydrocortisone dose was similar between subtypes and during all growth periods. Simple-virilizing boys (P < .01) and girls (P < .01) were diagnosed later than their salt-wasting counterparts. Height at take-off SDS was reduced for patients with salt-wasting (boys: P < .01; girls: P < .01), and bone age at take-off SDS was more advanced for patients with simple-virilizing (boys: P < .01; girls: P = .05). Bone age at pubertal onset SDS was advanced for all patients, but more so for boys and girls with simple-virilizing. Although all patients had reduced final adult height SDS, this was more pronounced in patients with salt-wasting. CONCLUSION: Reduced final adult height SDS in patients with salt-wasting vs simple-virilizing may be attributable in part to a later age of diagnosis and resultant less prolonged exposure to hydrocortisone. This finding suggests that duration of hydrocortisone treatment in the peripubertal period, independent of the hydrocortisone dose, may affect final adult height in patients with CAH.

Impact of hydrocortisone on adult height in congenital adrenal hyperplasia-the Minnesota cohort.

OBJECTIVE: To estimate the impact of the average daily dose of hydrocortisone (HC) on the amount of growth attained in children with congenital adrenal hyperplasia (CAH). The effect of glucocorticoid therapy on adult height (AH) in children with CAH has yet to be elucidated. STUDY DESIGN: Triple-logistic models estimating components of growth and maturation were fitted to longitudinal records of 104 patients with classic CAH from 3 pediatric medical centers in Minnesota between 1955 and 2012. A total of 3664 clinical encounters were examined. Random-effects longitudinal models with time-related covariates were used to estimate the effect of HC therapy on linear growth. RESULTS: The predicted AH z-score (-0.7) was similar between the sexes and among CAH subtypes. The mean growth period HC dose was 18.9 ± 5.6 mg/m(2)/day. In the final regression model, HC dose was negatively associated with predicted AH, with each mg/m(2)/day increase in average growth period HC dose predicting a 0.37-cm decrease in AH (P < .004). CONCLUSION: This study has quantified the fractional reduction in predicted final AH with an incremental increase in HC dose. These findings have important clinical implications in the decision making balance between HC replacement dose and adrenal androgen suppression in children with CAH.

Age at hormonal onset of puberty based on luteinizing hormone, inhibin B, and body composition in preadolescent U.S. girls.

BACKGROUND: Hormonal indicators could be useful for detecting early pubertal onset, but there is little research on how they are related to puberty in U.S. girls. We determined median age at hormonal onset of puberty based on luteinizing hormone (LH) and inhibin B (InB) and explored the extent to which body composition moderates this timing process. METHODS: We analyzed anthropometric and hormone data of 698 US peri-pubertal girls ages 6-11.99 y who had participated in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. RESULTS: Median age of hormonal onset of puberty was 10.43 y by LH and 10.08 y by InB cut-offs (1.04 mIU/ml for LH and 17.89 pg/ml for InB). Postnatal weight gain modulated onset, making it earlier by 10-11 mo among the highest (greater than +1 SD) relative to normal weight gainers. Onset occurred first in non-Hispanic black (NHB) girls, 10.08 y (95% confidence interval (CI): 10.07-10.09), followed by Mexican-American (MXAM) at 10.64 y (95% CI: 10.63-10.65), and at 10.66 y (95% CI: 10.66-10.67) for non-Hispanic white (NHW) girls using LH. With InB, onset occurred first in MXAM girls at 9.9 y, and at 10.3 y and 10.4 y for their NHB and NHW peers, respectively. CONCLUSION: Preadolescent weight gain lowers the age at hormonal onset as defined by LH concentrations. Preventing obesity in childhood may also avert the earlier initiation of the maturation process even at the hormonal level.

Physiologically based trimester-specific serum ferritin thresholds for iron deficiency in US pregnant women.

ABSTRACT: Serum ferritin (SF) concentration is the most widely used indicator for iron deficiency (ID). During pregnancy, the World Health Organization recently recommended SF thresholds for ID of <15 µg/L for the first trimester of pregnancy, based on expert opinion, and made no recommendations for the second and third trimesters. We examined the relationship of SF with 2 independent indicators of the onset of iron-deficient erythropoiesis, hemoglobin and soluble transferrin receptor 1, in cross-sectional data from US National Health and Nutrition Examination Survey for 1999 to 2010 and 2015 to 2018. We included 1288 pregnant women aged 15 to 49 years and excluded women with inflammation or potential liver disease. We used restricted cubic spline (RCS) regression analysis to determine SF thresholds for iron-deficient erythropoiesis. SF decreased during pregnancy; geometric mean SF was higher during the first and lower during the second and third trimesters. Using RCS analysis, the SF thresholds identified during pregnancy were <25.8 µg/L (18.1-28.5) during first trimester, <18.3 µg/L (16.3-22.9) during second trimester, and <19.0 µg/L (14.4- 26.1) during third trimester. These SF threshold levels track concentrations of hepcidin, the iron-regulatory hormone controlling the mobilization of iron stores. An SF concentration of <15 µg/L as the criterion for ID may underestimate the true prevalence of ID throughout pregnancy. In our study, an additional 1 of every 10 pregnant women would be recognized as iron deficient by using the physiologically based thresholds at SF of ∼25 µg/L during the first and ∼20 µg/L during the second and third trimesters.

Comparison of venous and pooled capillary hemoglobin levels for the detection of anemia among adolescent girls.

Introduction: Blood source is a known preanalytical factor affecting hemoglobin (Hb) concentrations, and there is evidence that capillary and venous blood may yield disparate Hb levels and anemia prevalence. However, data from adolescents are scarce. Objective: To compare Hb and anemia prevalence measured by venous and individual pooled capillary blood among a sample of girls aged 10-19 years from 232 schools in four regions of Ghana in 2022. Methods: Among girls who had venous blood draws, a random subsample was selected for capillary blood. Hb was measured using HemoCue® Hb-301. We used Lin's concordance correlation coefficient (CCC) to quantify the strength of the bivariate relationship between venous and capillary Hb and a paired t-test for difference in means. We used McNemar's test for discordance in anemia cases by blood source and weighted Kappa to quantify agreement by anemia severity. A multivariate generalized estimating equation was used to quantify adjusted population anemia prevalence and assess the association between blood source and predicted anemia risk. Results: We found strong concordance between Hb measures (CCC = 0.86). The difference between mean venous Hb (12.8 g/dL, ± 1.1) and capillary Hb (12.9 g/dL, ± 1.2) was not significant (p = 0.26). Crude anemia prevalence by venous and capillary blood was 20.6% and 19.5%, respectively. Adjusted population anemia prevalence was 23.5% for venous blood and 22.5% for capillary (p = 0.45). Blood source was not associated with predicted anemia risk (risk ratio: 0.99, 95% CI: 0.96, 1.02). Discordance in anemia cases by blood source was not significant (McNemar p = 0.46). Weighted Kappa demonstrated moderate agreement by severity (ĸ = 0.67). Among those with anemia by either blood source (n = 111), 59% were identified by both sources. Conclusion: In Ghanaian adolescent girls, there was no difference in mean Hb, anemia prevalence, or predicted anemia risk by blood source. However, only 59% of girls with anemia by either blood source were identified as having anemia by both sources. These findings suggest that pooled capillary blood may be useful for estimating Hb and anemia at the population level, but that caution is needed when interpreting individual-level data.

Maternal height and child growth patterns.

OBJECTIVE: To examine associations between maternal height and child growth during 4 developmental periods: intrauterine, birth to age 2 years, age 2 years to mid-childhood (MC), and MC to adulthood. STUDY DESIGN: Pooled analysis of maternal height and offspring growth using 7630 mother-child pairs from 5 birth cohorts (Brazil, Guatemala, India, the Philippines, and South Africa). We used conditional height measures that control for collinearity in height across periods. We estimated associations between maternal height and offspring growth using multivariate regression models adjusted for household income, child sex, birth order, and study site. RESULTS: Maternal height was associated with birth weight and with both height and conditional height at each age examined. The strongest associations with conditional heights were for adulthood and 2 years of age. A 1-cm increase in maternal height predicted a 0.024 (95% CI: 0.021-0.028) SD increase in offspring birth weight, a 0.037 (95% CI: 0.033-0.040) SD increase in conditional height at 2 years, a 0.025 (95% CI: 0.021-0.029 SD increase in conditional height in MC, and a 0.044 (95% CI: 0.040-0.048) SD increase in conditional height in adulthood. Short mothers (<150.1 cm) were more likely to have a child who was stunted at 2 years (prevalence ratio = 3.20 (95% CI: 2.80-3.60) and as an adult (prevalence ratio = 4.74, (95% CI: 4.13-5.44). There was no evidence of heterogeneity by site or sex. CONCLUSION: Maternal height influences offspring linear growth over the growing period. These influences likely include genetic and non-genetic factors, including nutrition-related intergenerational influences on growth that prevent the attainment of genetic height potential in low- and middle-income countries.