Fordjour, Lawrence
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Publication Open Access Benefits of pre-, pro- and Syn-biotics for lung angiogenesis in malnutritional rats exposed to intermittent hypoxia.(2014-10-11) Ahmad, Asma; Cai, Charles L; Kumar, Dharmendra; Cai, Fayme; D'Souza, Antoni; Fordjour, Lawrence; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V; Beharry, Kay DExtremely low birth weight and reduced caloric intake have significant adverse effects on lung development and are risk factors for bronchopulmonary dysplasia. Vascular endothelial growth factor (VEGF) is highly involved in lung microvascular development, and may be affected by nutritional status. To test the hypothesis that suboptimal nutrition decreases VEGF signaling in formula-fed neonatal rats, and to determine whether supplementation with probiotics, prebiotics, or synbiotics ameliorate the effects, rat pups at birth (P0) were placed in room air (RA) or intermittent hypoxia (12%) during hyperoxia (50% O2) from birth to P3. The pups were either maternally-fed; or formula-fed with or without supplementation. Formula-fed pups were separated from their mothers at birth and hand-gavaged every 3 hours. Lung VEGF signaling was determined on P3. In RA, all formula-fed groups were significantly growth suppressed with decreased lung weights. Hyperoxia had a less remarkable effect on body weight; and mean lung weight was lower only in the unsupplemented formula-fed group. Lung VEGF was decreased in all formula-fed RA and hyperoxia groups, except the probiotics group. In RA, sVEGFR-1 levels were elevated in all formula-fed groups except the synbiotics group. However in hyperoxia, sVEGFR-1 levels were higher in the unsupplemented formula group. All genes involved in angiogenesis were downregulated in the formula-fed groups compared to maternally-fed. Formula feeding results in significant malnutrition associated with decreased lung size and lung VEGF levels in neonatal rat pups. Probiotic supplementation prevented the adverse effects of combined hyperoxia and suboptimal nutrition on lung VEGF suggesting preservation of angiogenesis.Publication Open Access Associations between nutrients in one-carbon metabolism and fetal DNA methylation in pregnancies with or without gestational diabetes mellitus(Springer Science and Business Media LLC, 2023-08-26) Kadam, Isma’il; Dalloul, Mudar; Hausser, Jeanette; Huntley, Monique; Hoepner, Lori; Fordjour, Lawrence; Hittelman, Joan; Saxena, Anjana; Liu, Jia; Futterman, Itamar D.; Minkoff, Howard; Jiang, XinyinBackground: Gestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B12, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM. Results: In this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25-33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = - 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = - 0.13, p = 0.049 and r = - 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants (r = - 0.28, p = 0.015). Conclusions: In conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.Publication Open Access Genetic Disorders of Calcium and Phosphorus Metabolism(MDPI AG, 2022-03-17) Miller, Assia; Mathew, Serina; Patel, Sneha; Fordjour, Lawrence; Chin, Vivian L.In this review, we describe genetic mutations affecting metabolic pathways of calcium and phosphorus homeostasis. Calcium and phosphorus homeostasis has tight hormonal regulation by three major hormones: vitamin D, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). We describe the physiology and pathophysiology of disorders, their biochemical profile, clinical characteristics, diagnostics, and treatments.Publication Open Access Genetics of Thyroid Disorders(MDPI AG, 2022-04-13) Gavryutina, Irina; Fordjour, Lawrence; Chin, Vivian L.Thyroid diseases in children and adolescents include acquired or congenital conditions, including genetic disorders either isolated or part of a syndrome. Briefly, we will review the physiology and pathophysiology of the thyroid gland and its disorders. The aim of this chapter is to describe genetic abnormalities of the thyroid gland.Publication Open Access The introduction of nursing led bubble-CPAP in a neonatal unit in Ghana: A 32-month observational report(Elsevier BV, 2023-10) Fordjour, Lawrence; Washburn, Lisa; Darko, Elizabeth; Koffie, Vivian; Rabiu, Fauziya; Brako, Nana Okai; Sereboe, Nana; Seidel, Corey; King, Bryan; Bodkin, Darren; Owen, MedgeNeonatal deaths account for nearly 50 % of under-five deaths in Ghana with prematurity as the leading factor. Bubble continuous positive airway pressure (bCPAP) is important in treating respiratory distress (RD) associated with prematurity but its use in Africa is challenging. There is limited equipment to care for vulnerable newborns and insufficiently trained healthcare staff. This 32-month observational study describes the characteristics and outcomes of bCPAP treated newborns as a nursing led intervention at a regional referral hospital in Ghana. In May 2014, bCPAP was introduced to newborn intensive care unit (NICU) nursing staff. Three bCPAP machines and supplies were donated by Medical Technology Transfer and Services (MTTS). A training program provided learning opportunities for US-based and Ghanaian staff. Locally collected data included: NICU census, staffing, admitting diagnosis, birth weight, gestational age, Apgar scores, antenatal corticosteroid administration, days on bCPAP, and survival. From May 2014 to December 2016, 189 newborns received bCPAP. The mean ± SD (range) gestational age was 30.0 ± 4.2 (24–42) weeks, birth weight was 1.5 ± 0.7 (0.5–4.25) kg, and bCPAP duration was 3.2 ± 3.3 (0–14) days. In 155 (82.0 %), the admission diagnosis was prematurity with RD. Survival in this group was higher compared to other diagnostic categories and improved as birthweight increased (p < 0.05). Overall, 57.8 % of bCPAP treated newborns survived, but survival decreased during the last 12 months for newborns < 1.5 kg. This study supports the long-term sustainability of a nursing-led bCPAP program in Africa, but positive outcomes may be compromised by staffing, equipment, and resource limitations.Publication Open Access Maternal Lutein Intake during Pregnancies with or without Gestational Diabetes Mellitus and Cognitive Development of Children at 2 Years of Age: A Prospective Observational Study(MDPI AG, 2024-01-22) Kadam, Isma’il; Nebie, Chauntelle; Dalloul, Mudar; Hittelman, Joan; Fordjour, Lawrence; Hoepner, Lori; Futterman, Itamar D.; Minkoff, Howard; Jiang, XinyinLutein and its isomer zeaxanthin serve as antioxidants and preserve cognitive function during aging. However, whether lutein/zeaxanthin (L + Z) exposure early in life improves cognitive development of children is rarely explored. It is also unknown whether gestational diabetes mellitus (GDM), characterized by heightened oxidative stress, affects lutein metabolism. This prospective longitudinal cohort study examined the differences in L + Z intake and metabolism, as well as the association between maternal L + Z intake and children's cognitive development in GDM versus non-GDM pregnancies. Seventy-six pregnant women (n = 40 with GDM) were recruited between 25 and 33 weeks of gestation and dietary intakes were recorded. At delivery, cord blood was collected, and 2 years later, the Bayley III developmental test was conducted on a subset of children (n = 38). The results suggest that GDM reduced cord blood lutein levels at birth; L + Z intake during pregnancy was associated with better cognitive (β = 0.003, p = 0.001) and language (β = 0.002, p = 0.038) scoring of children at 2 years regardless of GDM status. In conclusion, maternal L + Z intake was positively associated with children's developmental scores, regardless of GDM. More studies are needed to confirm such associations.Publication Open Access Cytokines and Toll-like receptor signaling pathways in the terminal ileum of hypoxic/hyperoxic neonatal rats: benefits of probiotics supplementation.(2012-04-10) D'Souza, Antoni; Cai, Charles L; Kumar, Dharmendra; Cai, Fayme; Fordjour, Lawrence; Ahmad, Asma; Valencia, Gloria; Aranda, Jacob V; Beharry, Kay DOxidative stress and inflammation are associated with the development of inflammatory bowel diseases such as necrotizing enterocolitis. We tested the hypothesis that probiotics, prebiotics or synbiotics (a combination of pre- and probiotics) is effective for prevention of inflammatory responses to formula-feeding in the terminal ileum of neonatal rats.Publication Open Access Gestational diabetes status and dietary intake modify maternal and cord blood allostatic load markers.Jack-Roberts, Chauntelle; Maples, Patricia; Kalkan, Betul; Edwards, Kaydine; Gilboa, Ella; Djuraev, Ikhtiyor; Zou, Shuli; Hoepner, Lori; Fordjour, Lawrence; Lee, Wen-Ching; Kral, John; Dalloul, Mudar; Jiang, XinyinIntroduction: Allostatic load (AL) defines cardiometabolic, inflammatory, and neuroendocrine changes in the body in response to internal and external stressors. It is largely unknown whether gestational diabetes mellitus (GDM) alters maternal and fetal AL, which in turn affects GDM outcomes. Whether dietary intakes and quality can modify AL and thus influence GDM progression is also unknown. Research design and methods: In this study, we recruited 35 GDM and 30 non-GDM women in gestational week 25-33. Fasting blood samples were collected at enrollment, and cord venous blood samples were collected at delivery for the measurement of a series of AL biomarkers to calculate the composite AL index. Three-day dietary recalls were conducted at enrollment. Results: Results suggest that GDM women had 60% higher composite AL index scores (p value=0.01). Maternal AL index was associated with shorter duration of gestation (β=-0.33, p value=0.047) and higher fetal AL index (β=0.47, p value=0.006) after adjusting for GDM status. Dietary intake of monounsaturated fatty acids was negatively associated with maternal AL index (β=-0.20, p value=0.006). GDM women had lower total caloric intake and dietary glycemic load, yet their linolenic acid, vitamin C and E intakes were also decreased (all p value<0.05). These dietary differences were not related to birth outcomes measured. Conclusions: In this study, GDM status and dietary intakes modify AL in this population. AL may serve as an indicator of GDM control. Future research on dietary interventions that can improve maternal AL markers during GDM is warranted.Publication Open Access Growth factors in the fetus and pre-adolescent offspring of hyperglycemic rats(SAGE Publications, 2021-04-29) Fordjour, Lawrence; Cai, Charles; Bronshtein, Vadim; Bronshtein, Mayan; Aranda, Jacob V; Beharry, Kay DBackground: Maternal hyperglycemia influences childhood metabolic syndrome, including obesity and hyperglycemia. We tested the hypothesis that the maternal hyperglycemia influences growth factors in the fetal and pre-adolescent offspring. Methods: Hyperglycemia was induced in pregnant rats on embryonic day (E)16 using streptozocin followed by implantation with insulin or placebo pellets at embryonic day 18 (E18). Fetuses at E20 and pre-adolescent pups at postnatal day 14 (P14) were studied: (1) normal untreated controls (CTL) at E20; (2) hyperglycemic placebo-treated (HPT) at E20; (3) hyperglycemic insulin-treated (HIT) at E20; (4) CTL at P14; and (5) HIT at P14. Fetal and pre-adolescent growth factors were determined. Results: Biomarkers of hypoxia were elevated in the HPT group at E20. This group did not survive to term. Maternal insulin improved fetal survival despite lower fetal body weight at E20, however, at normal birth (postnatal day 0 (P0)) and at P14, body weights and blood glucose were higher than CTL. These high levels correlated with aberrant growth factors. Maternal hyperglycemia influenced glucose-6-phosphate dehydrogenase, glucagon, insulin, interleukin-10, and leptin genes. Conclusions: The impact of maternal hyperglycemia on pre-adolescent glucose and body weight was not a consequence of maternal overnutrition. This suggests an independent link which may affect offspring metabolic health in later life.Publication Open Access A Case of Transient Neonatal Diabetes Mellitus Successfully Managed with Basal Rate only Insulin Pump(2023-01) Henry, Michael M; Arora, Sumeet; Umpaichitra, Vatcharapan; Kochummen, Elna; Ch’ng, Tong Wooi; Hagerty, Dawn; Ibrahim, Zachary; Perez-Colon, Sheila; Chin, Vivian L; Fordjour, LawrenceIntroduction: Neonatal diabetes mellitus is a rare condition that presents in the first few weeks to months of life. The neonate presents with low birth weight, dehydration, and hyperglycemia with or without ketoacidosis. Management using insulin drip, subcutaneous insulin injection and continuous subcutaneous insulin infusion (CSII) each present their own challenges. There is risk of hypoglycemia even with tiny doses of insulin. Case: We present a case of transient neonatal diabetes mellitus (TNDM) due to paternal uniparental disomy at the 6q24 region, initially diagnosed late at DOL 29 due to the intermittent nature of hyperglycemia. The patient was born with low birth weight, macroglossia, umbilical hernia, and required repair of bilateral inguinal hernia. The other challenges involve management of insulin administration due to the limited amount of subcutaneous tissue in neonates as well as the minute doses of insulin required. Our patient was successfully managed with the most advanced insulin pump at the time with diluted insulin, using a basal rate-only regimen at total daily dose of 0.01-0.2u/kg/day, which is much lower than reported in the current literature. Additionally, this report shows that by titrating to pre-feed glucose, no episodes of hypoglycemia were noted. She had much less blood sugar variability and remained euglycemic. A 90-degree steel catheter was used successfully. Conclusion: TNDM due to paternal uniparental disomy at the 6q24 region can successfully be treated using basal rate-only CSII regimen, titrated to pre-feed glucoses, and 90-degree steel catheter.