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result(s) for
"Enquobahrie, Daniel A"
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Early pregnancy vitamin D status and risk of preeclampsia
by
McElrath, Thomas F.
,
Carey, Vincent
,
Enquobahrie, Daniel A.
in
Adolescent
,
Adult
,
Alfacalcidol
2016
Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia.
We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32-38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia.
Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61-1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD <30 ng/ml) (adjusted odds ratio, 0.28; 95% CI, 0.10-0.96). Differential expression of 348 vitamin D-associated genes (158 upregulated) was found in peripheral blood of women who developed preeclampsia (FDR <0.05 in the Vitamin D Antenatal Asthma Reduction Trial [VDAART]; P < 0.05 in a replication cohort). Functional enrichment and network analyses of this vitamin D-associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses, including some nodes with a high degree of connectivity.
Vitamin D supplementation initiated in weeks 10-18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia.
ClinicalTrials.gov NCT00920621.
Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.
Journal Article
Isoniazid preventive therapy during infancy does not adversely affect growth among HIV-exposed uninfected children: Secondary analysis of data from a randomized controlled trial
by
Mecha, Jerphason
,
Iribarren, Sarah J.
,
Enquobahrie, Daniel A.
in
Analysis
,
Antitubercular Agents - administration & dosage
,
Antitubercular Agents - therapeutic use
2024
Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure.
The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms.
Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (β = 0.04 [95% CI:-0.14, 0.22]), HAZ (β = 0.14 [95% CI:-0.06, 0.34]), and WHZ [β = -0.07 [95% CI:-0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (β to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm.
IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.
Journal Article
Trends and spatio temporal distribution of HIV related programmatic indicators in North West Ethiopia from July 2018 up to June 2024
by
Tegegne, Awoke Seyoum
,
Enquobahrie, Daniel A.
,
Yenesew, Muluken Azage
in
692/308
,
692/499
,
692/699
2025
Ethiopia is one of the HIV high burden countries in Africa. This was compounded by the Conflict and health system breakdown in the northern Ethiopia over the past several years. This study was aimed to assess the trends and spatio-temporal distribution of HIV between
July2018-June 2024
. The District Health Information software2 (DHIS2) data was obtained from Health facilities with a total catchment area of 170,000 km2. Spatial interpolation and ordinal kriging were conducted to identify hotspot zones in the current study. The data analysis was conducted using SPSS software version 27. Between July, 2018 and June, 2024, a total of 8,592, 243 individuals were tested for HIV in Amhara region (North-west Ethiopia) and among these, 54,746 (0.64%) were HIV positive or HIV test positivity rate. The number of individuals who received HIV testing was ranged from 6,170 in East Gojjam health department to 567 in Debre Tabor town health office. The number of individuals who received HIV test decreased from 1,764,397 in July 2018 to 1,057,879 in June, 2024. The spatial distribution of HIV-related programmatic indicators in the current study indicate that, the hot spot areas for HIV test positivity rate were Kombolcha, Bahir Dar, Dessie, Debre Markos, Debre Birhan, and Woldia town health offices. Similarly, the hot spot areas for PLHIV newly initiated ART were Kombolcha, Dessie and Debre Markos Towns and the hot spot areas for PLHIV currently on ART were also Debre Markos, Kombolcha and Dessie towns. Experience sharing among zonal health departments and town health offices should be conducted to get important lessons from those who had best practice related to HIV tests and ART initiation. More attention in testing HIV should be given for hotspot areas to get more clients living with HIV. Special attention should be given in HIV tests on segregated or marginalized population to get more number of HIV test positivity rate instead of focusing on the test volume.
Journal Article
Retrospective cohort study of the association between maternal employment precarity and infant low birth weight in women in the USA
2020
ObjectivesTo investigate the association between maternal employment precarity and infant low birth weight (LBW), and to assess if this association differs by race/ethnicity.MethodsData were collected from 2871 women enrolled in the National Longitudinal Survey of Youth 1979 and the National Longitudinal Survey of Youth 1979 Children and Young Adult Cohort. Employment precarity was evaluated using a summary variable that combined several employment attributes: availability of employer-sponsored insurance, income, long shifts, non-daytime shifts, availability of employer sponsored training or educational benefits and membership in a union or collective bargaining unit. Employment precarity scores (a sum of the number of negative employment attributes) were categorised into low (0–2), medium (3) and high (4-6). LBW was defined as weight less than 2500 g at birth. Modified Poisson models were fit to calculate risk ratios and 95% CIs and adjusted for maternal age, race/ethnicity, educational attainment, nativity, prepregnancy body mass index, alcohol consumption, smoking during pregnancy and infant year of birth. We assessed effect modification by maternal race/ethnicity using a composite exposure-race variable.ResultsWomen with high employment precarity had higher risk of a LBW delivery compared with women with low employment precarity (RR: 1.48, 95% CI: 1.11 to 1.98). Compared to non-Hispanic/non-black women with low employment precarity, non-Hispanic black women (RR: 2.68; 95% CI: 1.72 to 4.15), Hispanic women (RR: 2.53; 95% CI: 1.54 to 4.16) and non-Hispanic/non-black women (RR: 1.46; 95% CI: 0.98 to 2.16) with high employment precarity had higher risk of LBW.ConclusionsWe observed higher risk of LBW in pregnancies of women with high employment precarity; this association was stronger among black and Hispanic mothers compared to non-Hispanic/non-black women. Findings of this study can be used to inform antenatal care and identify workplace policies to better support women who work during pregnancy.
Journal Article
Gestational Diabetes Mellitus in Relation to Maternal Dietary Heme Iron and Nonheme Iron Intake
by
Gelaye, Bizu
,
Qiu, Chunfang
,
Enquobahrie, Daniel A
in
administration & dosage
,
Adult
,
adverse effects
2011
OBJECTIVE: Higher heme iron intake is associated with increased type 2 diabetes risk. However, no previous study has evaluated gestational diabetes mellitus (GDM) risk in relation to heme iron intake during pregnancy. We investigated associations of maternal preconceptional and early pregnancy heme and nonheme iron intake with subsequent GDM risk. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 3,158 pregnant women. A food frequency questionnaire was used to assess maternal diet. Multivariable generalized linear regression models were used to derive estimates of relative risks (RRs) and 95% CIs. RESULTS: Approximately 5.0% of the cohort developed GDM (n = 158). Heme iron intake was positively and significantly associated with GDM risk (Ptrend = 0.04). After adjusting for confounders, women reporting the highest heme iron intake levels (≥1.52 vs. <0.48 mg per day) experienced a 3.31-fold-increased GDM risk (95% CI 1.02-10.72). In fully adjusted models, we noted that a 1-mg per day increase in heme iron was associated with a 51% increased GDM risk (RR 1.51 [95% CI 0.99-2.36]). Nonheme iron was inversely, though not statistically significantly, associated with GDM risk, and the corresponding RRs were 1.00, 0.83, 0.62, and 0.61 across quartiles of nonheme iron intake (Ptrend = 0.08). CONCLUSIONS: High levels of dietary heme iron intake during the preconceptional and early pregnancy period may be associated with increased GDM risk. Associations of GDM risk with dietary nonheme iron intake are less clear. Confirmation of these findings by future studies is warranted.
Journal Article
Implementation research logic model in the design and execution of eHealth innovations for maternal and newborn healthcare in Ethiopia
by
Enquobahrie, Daniel A.
,
Alemneh, Esubalew
,
Woldie, Mirkuzie
in
Analysis
,
Childbirth
,
Childbirth & labor
2025
Background
The use of eHealth innovations is becoming increasingly important in improving health outcomes, especially for maternal and newborn health. However, planning and executing these innovations can be challenging due to their complex nature. To provide guidance and clarity on implementation approaches, researchers need to use implementation research (IR) tools. We conducted IR to recognize the challenges in implementing eHealth innovations in the context of maternal and newborn healthcare using the implementation research logic model (IRLM). Therefore, this paper aims to describe the practical application of IRLM to design, execute and evaluate eHealth innovations that improve maternal and newborn care in public facilities in Ethiopia.
Methods
We employed rapid review, formative assessment and process evaluation of an eHealth innovation in selected healthcare facilities serving maternal and newborn care. The eHealth innovation we developed and deployed was named ‘ADHERE’ (
A
ntenatal Care, Chil
D
birt
H
Car
E
and Postnatal Ca
RE
), representing the continuum of maternal care. The rapid review was conducted as an initial step using the Consolidated Framework for Implementation Research (CFIR). We employed a mix of data collection methods: interview/discussion, eHealth system or document review and direct observation. Furthermore, we executed various stakeholder engagement activities: two co-creation workshops and on-site iterative discussions. We applied the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) to capture ongoing implementation learnings.
Results
We developed IRLM of the eHealth innovation implementation for three contexts: urban, peri-urban and remote public healthcare facilities. The model depicted the mechanism of interaction between implementation determinants and implementation strategies to produce the intended implementation outcomes. The IRLM helped to identify more than 35 implementation barriers or facilitators for eHealth interventions and to develop over 17 mitigation strategies for the study contexts. The initial IRLM was refined through ongoing implementation learnings and the mitigation strategies that were executed.
Conclusions
The IRLM is a comprehensive and effective guiding tool for the development, implementation and evaluation of innovations in various low- and middle-income contexts. Researchers and implementing partners should adapt and use it.
Journal Article
Placental Genome and Maternal-Placental Genetic Interactions: A Genome-Wide and Candidate Gene Association Study of Placental Abruption
by
Enquobahrie, Daniel A.
,
Gelaye, Bizu
,
Sanchez, Sixto E.
in
Abdomen
,
Abruptio Placentae - genetics
,
Abruptio Placentae - pathology
2014
While available evidence supports the role of genetics in the pathogenesis of placental abruption (PA), PA-related placental genome variations and maternal-placental genetic interactions have not been investigated. Maternal blood and placental samples collected from participants in the Peruvian Abruptio Placentae Epidemiology study were genotyped using Illumina's Cardio-Metabochip platform. We examined 118,782 genome-wide SNPs and 333 SNPs in 32 candidate genes from mitochondrial biogenesis and oxidative phosphorylation pathways in placental DNA from 280 PA cases and 244 controls. We assessed maternal-placental interactions in the candidate gene SNPS and two imprinted regions (IGF2/H19 and C19MC). Univariate and penalized logistic regression models were fit to estimate odds ratios. We examined the combined effect of multiple SNPs on PA risk using weighted genetic risk scores (WGRS) with repeated ten-fold cross-validations. A multinomial model was used to investigate maternal-placental genetic interactions. In placental genome-wide and candidate gene analyses, no SNP was significant after false discovery rate correction. The top genome-wide association study (GWAS) hits were rs544201, rs1484464 (CTNNA2), rs4149570 (TNFRSF1A) and rs13055470 (ZNRF3) (p-values: 1.11e-05 to 3.54e-05). The top 200 SNPs of the GWAS overrepresented genes involved in cell cycle, growth and proliferation. The top candidate gene hits were rs16949118 (COX10) and rs7609948 (THRB) (p-values: 6.00e-03 and 8.19e-03). Participants in the highest quartile of WGRS based on cross-validations using SNPs selected from the GWAS and candidate gene analyses had a 8.40-fold (95% CI: 5.8-12.56) and a 4.46-fold (95% CI: 2.94-6.72) higher odds of PA compared to participants in the lowest quartile. We found maternal-placental genetic interactions on PA risk for two SNPs in PPARG (chr3:12313450 and chr3:12412978) and maternal imprinting effects for multiple SNPs in the C19MC and IGF2/H19 regions. Variations in the placental genome and interactions between maternal-placental genetic variations may contribute to PA risk. Larger studies may help advance our understanding of PA pathogenesis.
Journal Article
Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia
by
van Uitert, Miranda
,
Enquobahrie, Daniel A.
,
Laivuori, Hannele
in
Bioinformatics
,
Biology
,
Biomarkers
2015
Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.
Journal Article
Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study
by
Sumner, Susan J.
,
Gelaye, Bizu
,
Enquobahrie, Daniel A.
in
Abruptio Placentae - blood
,
Abruptio Placentae - etiology
,
Abruptio Placentae - metabolism
2016
Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy.
Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC).
Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003).
Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts.
Journal Article
Risk of glucose intolerance and gestational diabetes mellitus in relation to maternal habitual snoring during early pregnancy
by
Gelaye, Bizu
,
Enquobahrie, Daniel A.
,
Qiu, Chunfang
in
Adult
,
Apnea
,
Biology and Life Sciences
2017
Obstructive sleep apnea (OSA) or habitual snoring is known to be associated with impaired glucose tolerance and type 2 diabetes among both men and non-pregnant women. We examined the association of habitual snoring during early pregnancy with risk of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM).
A cohort of 1,579 women was interviewed during early pregnancy. We collected information about snoring frequency during early pregnancy. Results from screening and diagnostic tests for IGT and GDM were abstracted from medical records. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI) of IGT and GDM associated with snoring in early pregnancy.
Overall, women who snored \"most or all of the time\" had a 2.1-fold increased odds of IGT (OR 2.10; 95% CI 1.31-3.35) and a 2.5-fold increased odds of GDM (OR 2.50; 95% CI 1.34-4.67) as compared with women who never snored. Compared with lean women (pre-pregnancy body mass index (BMI) <25 kg/m2) who did not snore, lean snorers had a 2-fold increased odds of GDM (OR = 1.99, 95% CI: 1.07-3.68). The odds of GDM risk was particularly elevated among overweight women (BMI ≥ 25 kg/m2) who snored (OR = 5.01; 95% CI 2.71-9.26). However, there was no evidence of an interaction between overweight and snoring with GDM risk (p-value = 0.144).
These findings, if confirmed, may have important implications for tailoring prenatal care for overweight pregnant women, and /or those with a history of habitual snoring in early pregnancy.
Journal Article