1) The study examined the impact of maternal vitamin D status on fetal skeletal development through 3D ultrasound measurements in 424 pregnant women.
2) It found that suboptimal maternal vitamin D status was associated with increased femur cross-sectional area and splaying in utero, resembling signs of rickets.
3) This suggests that ensuring optimal maternal vitamin D levels during pregnancy may be important for proper fetal skeletal development.
Vitamin D Deficiency In Pre Birth Studiesalisonegypt
1) Lower maternal vitamin D status was associated with greater femoral metaphyseal cross-sectional area and higher femoral splaying index in fetuses at 19 weeks and 34 weeks gestation, suggesting maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks.
2) Over 30% of mothers had vitamin D levels considered insufficient or deficient. Lower maternal vitamin D levels were related to increased femoral splaying and larger femoral cross-sectional area in fetuses.
3) The findings suggest that improving maternal vitamin D status early in pregnancy through supplementation may help support optimal fetal bone development.
Vita D Defic Insuffic Pregnancy Johnson Am J Perinatol 2010alisonegypt
This study found that vitamin D deficiency and insufficiency are common among pregnant women in the United States, especially for African American and Hispanic women. The study measured vitamin D levels in 154 African American, 194 Hispanic, and 146 Caucasian pregnant women early in their pregnancies. It found that 97% of African American women, 81% of Hispanic women, and 67% of Caucasian women had insufficient or deficient vitamin D levels. African American women were the most likely to have deficiency, while Caucasian women were the most likely to have sufficient levels. Race was identified as the most important risk factor for deficiency or insufficiency.
Vita D Supple Breatfed Infants Pediatrics 2010alisonegypt
This document summarizes a study examining the use of supplemental vitamin D among infants who were breastfed for prolonged periods. The study found that among infants who were predominantly breastfed for at least 6 months, the rate of receiving supplemental vitamin D was only 15.9%. Parental decisions about vitamin D supplementation were significantly associated with whether the parent agreed their pediatrician recommended it and whether they believed breast milk contains all needed nutrition. Educational efforts are needed to increase compliance with guidelines recommending all breastfed infants receive vitamin D supplementation.
Vita D Defic Mothers Newborns Merewood Pediatrics 2010alisonegypt
This study found high rates of vitamin D deficiency in mothers and newborns in Boston, Massachusetts. 58% of infants and 36% of mothers had vitamin D levels below 20 ng/mL. Risk factors for infant deficiency included a deficient mother, winter birth, black race, and a maternal BMI over 35. Prenatal vitamin use was protective against deficiency for both mothers and infants, however 30% of mothers still had low vitamin D levels despite taking prenatal vitamins.
a presentation by Abdulkareeem Toyyib Oladimeji at the department of physiology, faculty of basic medical sciences, univeristy of ilorin teaching hospital, Ilorin, Kwara state, Nigeria.
Rosalina Villalon Landeros is a PhD candidate at the University of Wisconsin-Madison studying under Professor R Magness. Her research examines the role of estradiol-17β and its metabolites in vascular endothelial function using an ovine model of unilateral pregnancy. She hypothesizes that uterine artery endothelial cells isolated from the gravid horn will exhibit pregnancy-specific responses to estradiol, while cells from the non-gravid horn will not. Preliminary results support increased proliferation and nitric oxide production in response to estradiol metabolites in cells from the gravid horn.
The document discusses the developmental origins of health and disease theory proposed by Barker, which links poor fetal and early life nutrition to increased risk of chronic diseases like heart disease and diabetes later in life. Barker observed correlations between low birth weights in the 1920s and higher heart disease rates decades later. His theory proposes that the fetus adapts to inadequate nutrition by diverting resources from organs like the heart to the brain, with health consequences appearing later. Subsequent studies found links between small fetal size and later health issues. The theory suggests these effects may be passed on to later generations through epigenetic changes and fetal programming of gene expression.
Dr. Narendra Malhotra gave the POGS oration on fetal origins of adult diseases. He has had an illustrious career as an obstetrician and gynecologist in India, holding many leadership positions and publishing extensively. His research has shown that adverse conditions in the womb and early life can program the fetus's development and permanently increase risks for diseases like diabetes, hypertension, and heart disease later in adulthood. Maternal nutrition, infections, and other environmental factors during pregnancy can influence the fetus through hormonal and epigenetic changes leading to effects on organs like the pancreas, kidneys and blood vessels that manifest as disease in later life.
Vitamin D Deficiency In Pre Birth Studiesalisonegypt
1) Lower maternal vitamin D status was associated with greater femoral metaphyseal cross-sectional area and higher femoral splaying index in fetuses at 19 weeks and 34 weeks gestation, suggesting maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks.
2) Over 30% of mothers had vitamin D levels considered insufficient or deficient. Lower maternal vitamin D levels were related to increased femoral splaying and larger femoral cross-sectional area in fetuses.
3) The findings suggest that improving maternal vitamin D status early in pregnancy through supplementation may help support optimal fetal bone development.
Vita D Defic Insuffic Pregnancy Johnson Am J Perinatol 2010alisonegypt
This study found that vitamin D deficiency and insufficiency are common among pregnant women in the United States, especially for African American and Hispanic women. The study measured vitamin D levels in 154 African American, 194 Hispanic, and 146 Caucasian pregnant women early in their pregnancies. It found that 97% of African American women, 81% of Hispanic women, and 67% of Caucasian women had insufficient or deficient vitamin D levels. African American women were the most likely to have deficiency, while Caucasian women were the most likely to have sufficient levels. Race was identified as the most important risk factor for deficiency or insufficiency.
Vita D Supple Breatfed Infants Pediatrics 2010alisonegypt
This document summarizes a study examining the use of supplemental vitamin D among infants who were breastfed for prolonged periods. The study found that among infants who were predominantly breastfed for at least 6 months, the rate of receiving supplemental vitamin D was only 15.9%. Parental decisions about vitamin D supplementation were significantly associated with whether the parent agreed their pediatrician recommended it and whether they believed breast milk contains all needed nutrition. Educational efforts are needed to increase compliance with guidelines recommending all breastfed infants receive vitamin D supplementation.
Vita D Defic Mothers Newborns Merewood Pediatrics 2010alisonegypt
This study found high rates of vitamin D deficiency in mothers and newborns in Boston, Massachusetts. 58% of infants and 36% of mothers had vitamin D levels below 20 ng/mL. Risk factors for infant deficiency included a deficient mother, winter birth, black race, and a maternal BMI over 35. Prenatal vitamin use was protective against deficiency for both mothers and infants, however 30% of mothers still had low vitamin D levels despite taking prenatal vitamins.
a presentation by Abdulkareeem Toyyib Oladimeji at the department of physiology, faculty of basic medical sciences, univeristy of ilorin teaching hospital, Ilorin, Kwara state, Nigeria.
Rosalina Villalon Landeros is a PhD candidate at the University of Wisconsin-Madison studying under Professor R Magness. Her research examines the role of estradiol-17β and its metabolites in vascular endothelial function using an ovine model of unilateral pregnancy. She hypothesizes that uterine artery endothelial cells isolated from the gravid horn will exhibit pregnancy-specific responses to estradiol, while cells from the non-gravid horn will not. Preliminary results support increased proliferation and nitric oxide production in response to estradiol metabolites in cells from the gravid horn.
The document discusses the developmental origins of health and disease theory proposed by Barker, which links poor fetal and early life nutrition to increased risk of chronic diseases like heart disease and diabetes later in life. Barker observed correlations between low birth weights in the 1920s and higher heart disease rates decades later. His theory proposes that the fetus adapts to inadequate nutrition by diverting resources from organs like the heart to the brain, with health consequences appearing later. Subsequent studies found links between small fetal size and later health issues. The theory suggests these effects may be passed on to later generations through epigenetic changes and fetal programming of gene expression.
Dr. Narendra Malhotra gave the POGS oration on fetal origins of adult diseases. He has had an illustrious career as an obstetrician and gynecologist in India, holding many leadership positions and publishing extensively. His research has shown that adverse conditions in the womb and early life can program the fetus's development and permanently increase risks for diseases like diabetes, hypertension, and heart disease later in adulthood. Maternal nutrition, infections, and other environmental factors during pregnancy can influence the fetus through hormonal and epigenetic changes leading to effects on organs like the pancreas, kidneys and blood vessels that manifest as disease in later life.
This document discusses the relationship between the plasminogen activator inhibitor type-1 (PAI-1) gene polymorphism and recurrent spontaneous abortion. PAI-1 inhibits fibrinolysis, which can increase the risk of thrombosis during pregnancy. Several meta-analyses found an association between the 4G/5G PAI-1 polymorphism and increased risk of recurrent miscarriage in Caucasian, African, and Asian populations, but not in Latino populations. Therapeutic options like anticoagulation therapy or metformin may help reduce the risk of recurrent abortion in women with certain PAI-1 polymorphisms and thrombophilia. More large, prospective studies are still needed to validate these findings.
Lecture held at the 4th Evidence-Based Neonatology conference, Nov 12 2017, in Hyderabad, India.
The lecture gives a short overview of the "fetal programming" theory, also referred to as the Developmental Origin of Health and Disease (DOHaD).
Luis Alberto Velasquez Cumplido
Grado académico: Doctor en Ciencias Biológicas, Mención Ciencias Fisiológicas
Institución: Pontificia Universidad Católica (PUC)
Fecha: 28 de Noviembre de 1997
LINEAS DE INVESTIGACIÓN
Mi foco de investigación se ha centrado en el uso de herramientas de biología molecular, celular y nanociencia para abordar problemas biomédicos básicos y aplicados. Mis proyectos básicos se centran en caracterizar las relaciones huésped hospero a nivel celular y molecular. Mis proyectos aplicados se centran en el uso de la nanopartículas para la liberación de compuestos con actividad biológica.
En los últimos 10 años he publicado 33 manuscritos en revistas con comité editorial, he participado en la presentación de 5 patentes y he presentado numerosos resúmenes en congresos nacionales e internacionales. Soy revisor de numerosas revistas nacionales e internacionales y mi laboratorio ha recibido numerosas distinciones a la excelencia científica.
Respecto a mis proyectos, soy director de Biomedicina del proyecto basal en Nanociencia y Nanotecnología CEDENNA. Me adjudique un proyecto a centros científicos de excelencia en la Wellcome trust, Inglaterra. Tengo un FONDECYT regular y un PBCT y soy subdirector de un proyecto INNOVA.
En mis proyectos colaboro con Robert Lange, del MIT, USA, con Andrew Sharkey de la Universidad de Cambridge y el Dr. Myron Cristodoulides de la Universidad de Southampton. En mi laboratorio he dirigido 14 tesis de pregrado, 4 de postgrado y un post-doctorado.
Recovery from developmental nonylphenol exposure is possible i. maleAlexander Decker
This study examined whether the effects of developmental exposure to the endocrine disrupting chemical nonylphenol (NP) could be reversed in subsequent unexposed generations of rats. Female rats were exposed to NP during pregnancy and lactation, and their offspring (F1 generation) showed increased body weight and hyperadrenalism at adulthood. The F1 females were bred to produce the F2 generation without further NP exposure. The F2 offspring did not show increased body weight or hyperadrenalism, indicating the developmental effects of NP exposure were reversed. This suggests that the "default state" can be recovered after a generation that experiences the health impacts and costs of developmental NP exposure.
Global Health Crises Caused By The Collision Of Biological And Cultural Evolu...Global Risk Forum GRFDavos
This document discusses global health crises caused by the collision of biological and cultural evolution. It notes that the human biological genome is becoming stressed by rapid changes in cultural evolution and modern diets. Currently, limited healthcare resources focus on "crisis medicine" to treat chronic diseases like diabetes and heart disease that result from poor nutrition. However, the document proposes that preventing harmful prenatal exposures during the pregnancies of the 3 billion babies expected by 2100 could reduce risks of diseases later in life, based on the Barker Hypothesis that prenatal environments can influence later health. It advocates shifting resources from crisis to preventive medicine by educating parents on healthy diets during pregnancy and development.
The study aimed to identify genetic factors associated with pre-eclampsia by genotyping over 650 women affected by pre-eclampsia and their families at 28 SNPs in 7 candidate genes. Using transmission disequilibrium testing to distinguish maternal and fetal effects, they found that none of the genetic variants tested conferred a statistically significant risk of pre-eclampsia based on their criteria. The results emphasize the need for large, well-designed studies to reliably identify genetic risks and avoid false positives.
Hatching status before embryo transfer is not correlatd with implantation rat...Joe Lee
This study aimed to determine if the reproductive outcomes differ between fully hatched (FH) blastocysts versus not fully hatched (NFH) blastocysts that have undergone chromosomal screening. The study analyzed 808 IVF cycles involving the transfer of a single euploid blastocyst. Results showed no significant differences in implantation rates, biochemical pregnancy rates, live birth rates or early pregnancy loss rates between FH and NFH blastocysts, whether in fresh or frozen embryo transfer cycles. The findings suggest that FH embryos are not more fragile or less likely to implant compared to NFH embryos.
This article challenges the hypothesis that the modern genetic predisposition to obesity has arisen through random genetic drift following predation release. The authors present evidence to support the hypothesis that famines and seasonal food shortages in the post-agricultural era have exerted natural selection favoring fat storage, mediated through fertility selection. The authors conclude that genetic and bioinformatic methods will soon provide a definitive resolution to the long-standing debate over the "thrifty gene" theory of obesity.
The Potential Impact of Preimplantation Genetic Diagnosis on Discrimination o...blaine_5
The argument that selection against specific genetic traits will lead to increased discrimination is both compelling and troubling. Indeed, it is reasonable to conclude that if a large number of people use PGD to select against traits they consider to be disabilities then the probability of increased discrimination and marginalization would be greatly increased. However, as this Note argues, most participants in the PGD disability debate overlook important limitations of both trait selection and large-scale PGD adoption that will likely mitigate the negative potentially negative impact of PGD technology.
This document discusses how prenatal nutrition can impact the risk of adult obesity through long-term effects on epigenetic mechanisms regulating gene expression. Nutrition during early development can influence DNA methylation patterns and histone modifications, which are epigenetic regulators of gene expression. This epigenetic programming during prenatal development and infancy may underlie the developmental origins of adult diseases like obesity and cardiovascular disease.
This document summarizes key topics from an education course on developmental biology. It discusses several topics:
1. The relevance of teratology to understanding tumors and embryonic development, covering important discoveries from the 18th-21st centuries.
2. The effects of the microbiome on embryonic and postembryonic development, how the microbiome is structured by diet, and how diet can treat pathogenic bacteria.
3. Genomic approaches to understanding normal and abnormal brain development using holoprosencephaly as an example, covering causes, presentation, and challenges in diagnosis and treatment.
4. The role of maternal nutrition as a key modulator of embryonic and fetal development.
This study investigated genetic variants in the C-reactive protein (CRP) and interleukin-6 (IL-6) genes and their association with obstructive sleep apnea (OSA) in European American and Southeast European children. The study found that genetic variants in the CRP and IL-6 genes were associated with increased risk of OSA in European American children but not in Southeast European children, suggesting different genetic or environmental influences between the populations. Specifically, variants in the CRP 1444C/T and 1919A/T genes showed significant association with OSA in European American children.
This document summarizes research on the relationship between psychosocial stress from racism and adverse birth outcomes among racial groups. Key findings include:
1) Racism exposure, particularly from vicarious childhood experiences, predicts lower birth weight in African Americans and partially explains their lower birth weight compared to whites.
2) African American women show signs of neuroendocrine dysregulation like high ACTH and low cortisol levels, which racism is associated with. Higher cortisol levels late in pregnancy mediate the link between childhood racism and lower birth weight.
3) Experiences of and distress from racism vary between racial groups, with African Americans and Latinas reporting the most exposure but Asian/Pacific Islanders and whites the most distress.
Clinical genetics is one of the most rapidly advancing fields in medicine. Spectacular progress has been achieved in this century with unravelling of the entire draft sequence of the human genome. A major contribution of these advances has been in diagnosis, management and prenatal diagnosis of genetic disorders as treatment in most cases is difficult or impossible and where available beyond the means of most families. Genetic technology is advancing rapidly, bringing new, safer and more sensitive ways to diagnose genetic conditions pre- and postnatally. These advances will bring about profound changes in the way we deliver obstetric services to women and their families. Diagnosing a genetic disorder not only allows for disease-specific management options but also has implications for the affected individual's entire family. Hence, a working understanding of the underlying concepts of genetic disease is important for all practicing clinicians. Although it is impossible to know all aspects of clinical and molecular genetics, basic knowledge of certain topics is a must for all practicing obstetrician/gynecologists.
This study examined the role of genetic and autoimmune factors in premature ovarian failure (POF) in 78 women. The women were divided into 3 groups based on the number of CGG repeats in the FMR1 gene: less than 28 repeats, 28-36 repeats, and more than 36 repeats. The study found that women with 28-36 repeats were most strongly associated with the presence of anti-ovarian antibodies, suggesting an autoimmune cause of POF. Women with autoimmune-driven POF had significantly higher anti-Mullerian hormone levels than those without an autoimmune cause. The presence of anti-ovarian antibodies above 10 IU/mL was associated with a normal CGG repeat number and better preservation
This document summarizes a study that examined the effect of a community-based group physical activity (CBGPA) program on the risk of preeclampsia during pregnancy. The study found that among 88 women who participated in the standardized CBGPA program, the rate of preeclampsia was significantly lower (2.2%) than the overall rate at the hospital (7.8%). Pregnancies in the CBGPA group also had lower rates of preterm birth and low birthweight compared to the overall rates. The study concludes that CBGPA may help reduce the risk of complications like preeclampsia during pregnancy.
Vitamin D supplementation during pregnancy: Is it really necessary?
1) There is ongoing debate around the optimal vitamin D levels during pregnancy and definitions of vitamin D deficiency. 2) Studies have shown associations between vitamin D deficiency and adverse pregnancy outcomes like gestational diabetes and preeclampsia. 3) The placenta plays a role in vitamin D metabolism and higher placental activity of the CYP24A1 enzyme is associated with vitamin D deficiency in pregnancies with gestational diabetes. 4) While routine vitamin D screening in all pregnancies is not currently recommended, high-risk women may benefit from screening and supplementation to treat deficiency.
Effects of raising vit D levels on birth complications
"Differences by race/ethnicity were not statistically significant when 25(OH)D concentration was included as a covariate in multivariable regression analysis."
This document discusses vitamin D in pregnancy. It covers the physiology of vitamin D, risks of deficiency like preeclampsia, low birthweight, and neonatal hypocalcemia. It recommends screening high-risk women like those with limited sun exposure or high BMI and supplementing deficient women with 1000-2000IU of vitamin D daily during pregnancy. Vitamin D supplementation is considered safe and may provide benefits, though more research is still needed on optimal dosing.
Raccomandazioni della iof (international osteoporosis foundation) sull’impieg...Merqurio
This position paper from the International Osteoporosis Foundation makes recommendations for vitamin D intake in older adults. Based on randomized controlled trials, daily vitamin D intake of 20-25 μg (800-1000 IU) is estimated to achieve a target serum 25OHD level of 75 nmol/L (30 ng/ml), which is associated with reduced risk of falls and fractures. Higher daily intakes may be needed for those with risk factors like obesity, limited sun exposure, or malabsorption. Doses above 20 μg/day have not been thoroughly evaluated, so higher intakes cannot be generally recommended at this time.
This document discusses the relationship between the plasminogen activator inhibitor type-1 (PAI-1) gene polymorphism and recurrent spontaneous abortion. PAI-1 inhibits fibrinolysis, which can increase the risk of thrombosis during pregnancy. Several meta-analyses found an association between the 4G/5G PAI-1 polymorphism and increased risk of recurrent miscarriage in Caucasian, African, and Asian populations, but not in Latino populations. Therapeutic options like anticoagulation therapy or metformin may help reduce the risk of recurrent abortion in women with certain PAI-1 polymorphisms and thrombophilia. More large, prospective studies are still needed to validate these findings.
Lecture held at the 4th Evidence-Based Neonatology conference, Nov 12 2017, in Hyderabad, India.
The lecture gives a short overview of the "fetal programming" theory, also referred to as the Developmental Origin of Health and Disease (DOHaD).
Luis Alberto Velasquez Cumplido
Grado académico: Doctor en Ciencias Biológicas, Mención Ciencias Fisiológicas
Institución: Pontificia Universidad Católica (PUC)
Fecha: 28 de Noviembre de 1997
LINEAS DE INVESTIGACIÓN
Mi foco de investigación se ha centrado en el uso de herramientas de biología molecular, celular y nanociencia para abordar problemas biomédicos básicos y aplicados. Mis proyectos básicos se centran en caracterizar las relaciones huésped hospero a nivel celular y molecular. Mis proyectos aplicados se centran en el uso de la nanopartículas para la liberación de compuestos con actividad biológica.
En los últimos 10 años he publicado 33 manuscritos en revistas con comité editorial, he participado en la presentación de 5 patentes y he presentado numerosos resúmenes en congresos nacionales e internacionales. Soy revisor de numerosas revistas nacionales e internacionales y mi laboratorio ha recibido numerosas distinciones a la excelencia científica.
Respecto a mis proyectos, soy director de Biomedicina del proyecto basal en Nanociencia y Nanotecnología CEDENNA. Me adjudique un proyecto a centros científicos de excelencia en la Wellcome trust, Inglaterra. Tengo un FONDECYT regular y un PBCT y soy subdirector de un proyecto INNOVA.
En mis proyectos colaboro con Robert Lange, del MIT, USA, con Andrew Sharkey de la Universidad de Cambridge y el Dr. Myron Cristodoulides de la Universidad de Southampton. En mi laboratorio he dirigido 14 tesis de pregrado, 4 de postgrado y un post-doctorado.
Recovery from developmental nonylphenol exposure is possible i. maleAlexander Decker
This study examined whether the effects of developmental exposure to the endocrine disrupting chemical nonylphenol (NP) could be reversed in subsequent unexposed generations of rats. Female rats were exposed to NP during pregnancy and lactation, and their offspring (F1 generation) showed increased body weight and hyperadrenalism at adulthood. The F1 females were bred to produce the F2 generation without further NP exposure. The F2 offspring did not show increased body weight or hyperadrenalism, indicating the developmental effects of NP exposure were reversed. This suggests that the "default state" can be recovered after a generation that experiences the health impacts and costs of developmental NP exposure.
Global Health Crises Caused By The Collision Of Biological And Cultural Evolu...Global Risk Forum GRFDavos
This document discusses global health crises caused by the collision of biological and cultural evolution. It notes that the human biological genome is becoming stressed by rapid changes in cultural evolution and modern diets. Currently, limited healthcare resources focus on "crisis medicine" to treat chronic diseases like diabetes and heart disease that result from poor nutrition. However, the document proposes that preventing harmful prenatal exposures during the pregnancies of the 3 billion babies expected by 2100 could reduce risks of diseases later in life, based on the Barker Hypothesis that prenatal environments can influence later health. It advocates shifting resources from crisis to preventive medicine by educating parents on healthy diets during pregnancy and development.
The study aimed to identify genetic factors associated with pre-eclampsia by genotyping over 650 women affected by pre-eclampsia and their families at 28 SNPs in 7 candidate genes. Using transmission disequilibrium testing to distinguish maternal and fetal effects, they found that none of the genetic variants tested conferred a statistically significant risk of pre-eclampsia based on their criteria. The results emphasize the need for large, well-designed studies to reliably identify genetic risks and avoid false positives.
Hatching status before embryo transfer is not correlatd with implantation rat...Joe Lee
This study aimed to determine if the reproductive outcomes differ between fully hatched (FH) blastocysts versus not fully hatched (NFH) blastocysts that have undergone chromosomal screening. The study analyzed 808 IVF cycles involving the transfer of a single euploid blastocyst. Results showed no significant differences in implantation rates, biochemical pregnancy rates, live birth rates or early pregnancy loss rates between FH and NFH blastocysts, whether in fresh or frozen embryo transfer cycles. The findings suggest that FH embryos are not more fragile or less likely to implant compared to NFH embryos.
This article challenges the hypothesis that the modern genetic predisposition to obesity has arisen through random genetic drift following predation release. The authors present evidence to support the hypothesis that famines and seasonal food shortages in the post-agricultural era have exerted natural selection favoring fat storage, mediated through fertility selection. The authors conclude that genetic and bioinformatic methods will soon provide a definitive resolution to the long-standing debate over the "thrifty gene" theory of obesity.
The Potential Impact of Preimplantation Genetic Diagnosis on Discrimination o...blaine_5
The argument that selection against specific genetic traits will lead to increased discrimination is both compelling and troubling. Indeed, it is reasonable to conclude that if a large number of people use PGD to select against traits they consider to be disabilities then the probability of increased discrimination and marginalization would be greatly increased. However, as this Note argues, most participants in the PGD disability debate overlook important limitations of both trait selection and large-scale PGD adoption that will likely mitigate the negative potentially negative impact of PGD technology.
This document discusses how prenatal nutrition can impact the risk of adult obesity through long-term effects on epigenetic mechanisms regulating gene expression. Nutrition during early development can influence DNA methylation patterns and histone modifications, which are epigenetic regulators of gene expression. This epigenetic programming during prenatal development and infancy may underlie the developmental origins of adult diseases like obesity and cardiovascular disease.
This document summarizes key topics from an education course on developmental biology. It discusses several topics:
1. The relevance of teratology to understanding tumors and embryonic development, covering important discoveries from the 18th-21st centuries.
2. The effects of the microbiome on embryonic and postembryonic development, how the microbiome is structured by diet, and how diet can treat pathogenic bacteria.
3. Genomic approaches to understanding normal and abnormal brain development using holoprosencephaly as an example, covering causes, presentation, and challenges in diagnosis and treatment.
4. The role of maternal nutrition as a key modulator of embryonic and fetal development.
This study investigated genetic variants in the C-reactive protein (CRP) and interleukin-6 (IL-6) genes and their association with obstructive sleep apnea (OSA) in European American and Southeast European children. The study found that genetic variants in the CRP and IL-6 genes were associated with increased risk of OSA in European American children but not in Southeast European children, suggesting different genetic or environmental influences between the populations. Specifically, variants in the CRP 1444C/T and 1919A/T genes showed significant association with OSA in European American children.
This document summarizes research on the relationship between psychosocial stress from racism and adverse birth outcomes among racial groups. Key findings include:
1) Racism exposure, particularly from vicarious childhood experiences, predicts lower birth weight in African Americans and partially explains their lower birth weight compared to whites.
2) African American women show signs of neuroendocrine dysregulation like high ACTH and low cortisol levels, which racism is associated with. Higher cortisol levels late in pregnancy mediate the link between childhood racism and lower birth weight.
3) Experiences of and distress from racism vary between racial groups, with African Americans and Latinas reporting the most exposure but Asian/Pacific Islanders and whites the most distress.
Clinical genetics is one of the most rapidly advancing fields in medicine. Spectacular progress has been achieved in this century with unravelling of the entire draft sequence of the human genome. A major contribution of these advances has been in diagnosis, management and prenatal diagnosis of genetic disorders as treatment in most cases is difficult or impossible and where available beyond the means of most families. Genetic technology is advancing rapidly, bringing new, safer and more sensitive ways to diagnose genetic conditions pre- and postnatally. These advances will bring about profound changes in the way we deliver obstetric services to women and their families. Diagnosing a genetic disorder not only allows for disease-specific management options but also has implications for the affected individual's entire family. Hence, a working understanding of the underlying concepts of genetic disease is important for all practicing clinicians. Although it is impossible to know all aspects of clinical and molecular genetics, basic knowledge of certain topics is a must for all practicing obstetrician/gynecologists.
This study examined the role of genetic and autoimmune factors in premature ovarian failure (POF) in 78 women. The women were divided into 3 groups based on the number of CGG repeats in the FMR1 gene: less than 28 repeats, 28-36 repeats, and more than 36 repeats. The study found that women with 28-36 repeats were most strongly associated with the presence of anti-ovarian antibodies, suggesting an autoimmune cause of POF. Women with autoimmune-driven POF had significantly higher anti-Mullerian hormone levels than those without an autoimmune cause. The presence of anti-ovarian antibodies above 10 IU/mL was associated with a normal CGG repeat number and better preservation
This document summarizes a study that examined the effect of a community-based group physical activity (CBGPA) program on the risk of preeclampsia during pregnancy. The study found that among 88 women who participated in the standardized CBGPA program, the rate of preeclampsia was significantly lower (2.2%) than the overall rate at the hospital (7.8%). Pregnancies in the CBGPA group also had lower rates of preterm birth and low birthweight compared to the overall rates. The study concludes that CBGPA may help reduce the risk of complications like preeclampsia during pregnancy.
Vitamin D supplementation during pregnancy: Is it really necessary?
1) There is ongoing debate around the optimal vitamin D levels during pregnancy and definitions of vitamin D deficiency. 2) Studies have shown associations between vitamin D deficiency and adverse pregnancy outcomes like gestational diabetes and preeclampsia. 3) The placenta plays a role in vitamin D metabolism and higher placental activity of the CYP24A1 enzyme is associated with vitamin D deficiency in pregnancies with gestational diabetes. 4) While routine vitamin D screening in all pregnancies is not currently recommended, high-risk women may benefit from screening and supplementation to treat deficiency.
Effects of raising vit D levels on birth complications
"Differences by race/ethnicity were not statistically significant when 25(OH)D concentration was included as a covariate in multivariable regression analysis."
This document discusses vitamin D in pregnancy. It covers the physiology of vitamin D, risks of deficiency like preeclampsia, low birthweight, and neonatal hypocalcemia. It recommends screening high-risk women like those with limited sun exposure or high BMI and supplementing deficient women with 1000-2000IU of vitamin D daily during pregnancy. Vitamin D supplementation is considered safe and may provide benefits, though more research is still needed on optimal dosing.
Raccomandazioni della iof (international osteoporosis foundation) sull’impieg...Merqurio
This position paper from the International Osteoporosis Foundation makes recommendations for vitamin D intake in older adults. Based on randomized controlled trials, daily vitamin D intake of 20-25 μg (800-1000 IU) is estimated to achieve a target serum 25OHD level of 75 nmol/L (30 ng/ml), which is associated with reduced risk of falls and fractures. Higher daily intakes may be needed for those with risk factors like obesity, limited sun exposure, or malabsorption. Doses above 20 μg/day have not been thoroughly evaluated, so higher intakes cannot be generally recommended at this time.
The document discusses vitamin D, its production, metabolism, and biological functions. It notes that vitamin D acts more like a hormone than a vitamin, as it is synthesized in one part of the body, transported through the bloodstream, and exerts effects in distant tissues by binding to receptors. The document also summarizes several studies that found associations between low vitamin D levels and increased risks of various diseases such as colorectal cancer, metabolic syndrome, and type 2 diabetes.
—Chronic patients of spinal cord injury has been detected severe reduction of bone density. Patients with SCI show mostly osteopenia or osteoporosis of the hip and spine. Vitamin D deficiency may contribute to development of osteoporosis in SCI. So a study was conducted on 100 chronic SCI patients to find out status of correlation of Vitamine D and bone mineral density (BMD). Blood samples were collected and investigated routine biochemistry with serum 25(OH)D. DXA scan of hip and spine was also done. This study observed that 55% patients had suboptimal vitamin D. Positive correlation was found between vitamin D & bone mineral density. It is concluded from this study that monitoring of Serum 25(OH)D levels and annual surveillance of bone mineral density is crucial among persons with chronic SCI to reduce progression of osteoporosis and minimize the risk for further fractures. Keywords: 25(OH)D: 25 Hydroxy Vitamin D, DXA: Dual Energy X-Ray Absorptiometry, BMD: Bone Mineral Density.
This document presents a thesis protocol investigating vitamin D levels between fertile and infertile women. It will be a prospective comparative study conducted at Bokaro General Hospital, Jharkhand, India. The study aims to assess and compare serum 25-hydroxyvitamin D levels in 60 infertile women and 60 fertile women between ages 21-40 years. Exclusion criteria include women with medical illnesses or using medications affecting vitamin D. Blood samples will be collected and 25-hydroxyvitamin D levels measured using ELISA to classify vitamin D status. Results will be statistically analyzed to compare vitamin D deficiency between the two groups and assess any associations with factors. The study aims to help evaluate prevalence of vitamin D deficiency in infertile women and potential benefits of
This document discusses vitamin D metabolism and requirements during pregnancy and lactation. It covers:
1) Vitamin D metabolism, including sources, conversion to active forms in the liver and kidneys, and role of vitamin D binding protein.
2) Increased vitamin D levels and requirements during pregnancy to support fetal development. Supplementation guidelines recommend 1500-2000 IU/day to maintain optimal levels.
3) Associations between vitamin D deficiency and gestational diabetes and preeclampsia, though the evidence is mixed and relationships may be indirect. Maintaining sufficient vitamin D status may help reduce risks of complications.
Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease CKD population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children CKiD and the Cardiovascular Comorbidity in Children with CKD 4 C should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes. Dr. Prafull Dawale | Neha Jain "Vitamin D in Chronic Kidney Disease" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd26778.pdfPaper URL: https://www.ijtsrd.com/medicine/other/26778/vitamin-d-in-chronic-kidney-disease/dr-prafull-dawale
Vita d defic mothers newborns merewood pediatrics 2010Alison Stevens
This study found high rates of vitamin D deficiency in newborns and their mothers in Boston, Massachusetts. The median vitamin D level was below the sufficient level in 58% of infants and 36% of mothers. Risk factors for infant deficiency included having a deficient mother, winter birth, black race, and a maternal BMI over 35. Prenatal vitamin use was protective against deficiency for both infants and mothers, however over 30% of mothers still had insufficient levels despite prenatal vitamin use. The results suggest prenatal vitamins may not provide enough vitamin D to ensure sufficiency.
Vitamin D is essential for pregnancy and low levels can lead to complications. It is synthesized from sun exposure and obtained through diet and supplements. During pregnancy, vitamin D levels increase substantially to support fetal growth and development. Deficiency has been associated with preeclampsia, gestational diabetes, preterm birth, and low birthweight. Supplementation is recommended for at-risk groups to help prevent complications.
ROLE OF VIT D IN FEMALE REPRODUCTION. PROF ABOUBAKR ELNASHARAboubakr Elnashar
This document discusses the role of vitamin D in female reproduction. It begins by covering the production and metabolism of vitamin D, noting the two major forms and how they are converted in the liver and kidneys to their active form. It then discusses optimal vitamin D levels and biological activity, including genomic and non-genomic actions. The main section covers the role of vitamin D in female reproduction, such as its effects on sex hormones, ovarian reserve markers, endometriosis, PCOS, uterine fibroids, and IVF outcomes. It concludes that vitamin D is involved in regulating the female reproductive system and modulating gonadal function through its receptor, but more research is needed to fully understand its role in infertility treatment.
CISPLATIN AND VITAMIN D.............pptxAlyaaKaram1
This document discusses recent research on the impact of vitamin D on various cancers. It summarizes findings on how vitamin D status impacts breast, ovarian, brain, blood, and other cancers. Several key findings are highlighted, including that vitamin D supplementation may increase survival for some cancer patients, particularly African Americans. Vitamin D is shown to have anti-cancer effects through various pathways and may help overcome resistance to cancer therapies like immunotherapy and chemotherapy.
This document discusses the use of vitamin D in preventing and treating non-bone diseases. It begins with an introduction and covers topics like immunomodulation related to allergy, fetal development, and the prevention and modification of diseases like asthma, COPD, allergic rhinitis, atopic dermatitis, and food allergy. It also briefly mentions autoimmunity and other diseases. The document provides information on vitamin D synthesis and metabolism and cites several studies on vitamin D levels in different populations and its effects. It concludes with a discussion of vitamin D's immunomodulatory effects in relation to allergy.
Calcitriol hormone and its up and down regulationArubSultan
Description: these slides explain the calcitriol hormone production and regulation. The effects of calcitriol on body and the related disorders. and also explain the up and down regulation of calcitriol hormone.
This document discusses whether it is time for mandatory vitamin B-12 fortification in flour in the United States. It notes that while folic acid fortification has been successful in reducing neural tube defects and shifting folate status, vitamin B-12 deficiency is still highly prevalent, especially in elderly populations. However, unlike with folic acid, no trials have demonstrated the efficacy of vitamin B-12 supplementation or fortification in preventing neural tube defects. Additionally, severe vitamin B-12 deficiency is usually due to malabsorption rather than intake, so fortification levels may not help these individuals. The document outlines key research questions around the nutritional impacts, epidemiology, neurocognition, cancer risks, causes and assessment of deficiency that need
This clinical trial compared the efficacy of calcifediol (calcidiol) and cholecalciferol (vitamin D3) in improving vitamin D status in postmenopausal women with vitamin D deficiency. 298 postmenopausal women with baseline 25-hydroxyvitamin D levels <20 ng/ml were randomized to receive either calcifediol 0.266 mg capsules monthly for 12 months, calcifediol for 4 months then placebo for 8 months, or cholecalciferol 25,000 IU monthly for 12 months. After 4 months of treatment, 35.0% of those receiving calcifediol reached 25-hydroxyvitamin D levels >30 ng/ml, compared to
Vitamina D ed Asma - Prof. Boner Attilio Università di VeronaRoberto Conte
1) Several studies show high rates of vitamin D deficiency and insufficiency among children with asthma. Low vitamin D levels are associated with worse asthma control, including increased exacerbations and hospitalizations.
2) Observational studies link higher maternal vitamin D intake during pregnancy to lower rates of wheezing and asthma in offspring. However, the evidence for a causal relationship is still insufficient.
3) Maintaining adequate vitamin D levels, especially during pregnancy and childhood, may help reduce asthma risk and severity by supporting lung development and function. Further research is still needed.
losses of both vitamin D binding protein and 25(OH)D in the urine
The urinary losses of vitamin D binding protein may be secondary to proteinuria.
Deficiency in 25(OH)D may lead to hypocalcemia, hyperparathyroidism, and diminished bone mineral density/content.
Vitamin D deficiency has also been associated with multiple systemic effects including elevated blood pressure ,metabolic syndrome, cardiovascular disease ,anemia and impaired immune system regulation .
Asthma, allergy and respiratory infections: the vitamin D hypothesisAriyanto Harsono
The document discusses the relationship between vitamin D and respiratory conditions like asthma. It suggests that vitamin D deficiency has been associated with increased risk of respiratory infections and asthma exacerbations. This may be because vitamin D plays important roles in immune function and lung development. The document reviews studies showing links between low vitamin D levels and higher risks of respiratory infections, asthma symptoms, and impaired lung function. However, the relationships are complex and not fully understood, as some studies have also linked high vitamin D supplementation to increased asthma risk. More research is still needed to clarify the roles and optimal levels of vitamin D.
Vita D Perrine Cg Ea At Adherence To Vit D Recommendations Among Us Infants P...alisonegypt
This study examined adherence to vitamin D recommendations among US infants using data from the Infant Feeding Practices Study II from 2005-2007. The researchers estimated the percentage of infants meeting the 2003 and 2008 vitamin D recommendations from the American Academy of Pediatrics at various ages from 1 to 10.5 months. They found that use of oral vitamin D supplements was low, ranging from 1% to 13% regardless of whether infants were breastfed, formula-fed, or mixed-fed. Most infants did not consume adequate amounts of vitamin D according to the 2008 recommendation, suggesting pediatricians should encourage vitamin D supplementation for breastfed and partially breastfed infants.
Vinchon M Sdh In Infants Can It Occur Spontaneously Childs Nerv Sys 2010[1]alisonegypt
This study examines cases of subdural hematoma (SDH) in infants that were considered to have occurred spontaneously rather than from nonaccidental trauma. The study identified 16 cases of spontaneous SDH in infants (SSDHI) from a prospective database that met criteria for lack of trauma history or suspicious findings. Most SSDHI cases involved males and had predisposing factors like macrocephaly, arachnoidomegaly, or obstetric complications. The study aims to better characterize SSDHI and identify risk factors to differentiate it from cases of traumatic SDH caused by nonaccidental injury.
This document discusses trial tactics and techniques based on the advice of experienced litigators. It recommends gaining experience through taking on as many trials as possible in one's early career, even if they are minor cases. While advocacy skills can be learned, experience trying many cases, preferably dozens per year, is the best teacher. Different advocates have different styles as well, so one should not slavishly copy others but develop their own approach. Overall, industry, hard work, and experience are more important than innate talent for most advocates to achieve success.
1) Recent reports in England have outlined issues with forensic science evidence and its presentation in courts, including concerns about biases towards prosecution experts.
2) There is a large funding gap between the prosecution and publicly funded defense, undermining the principle of a fair trial.
3) English courts have been reluctant to assess the reliability and validity of novel scientific techniques, allowing potentially unreliable evidence that has contributed to past miscarriages of justice.
The Next Innocence Project Law Reivew On Sbsalisonegypt
The article discusses shaken baby syndrome (SBS) convictions and new scientific research casting doubt on the forensic significance of the diagnostic triad used to convict hundreds of caregivers. It presents the case of Audrey Edmunds, who was convicted of murder and sentenced to 18 years in prison based solely on expert testimony that an infant suffered from SBS, despite no evidence the caregiver shook the baby. New research has undermined the triad as proof of shaking and removed shaking from the syndrome. However, the criminal justice system has been slow to incorporate this, and triad-based convictions continue regularly. The author argues this constitutes a criminal justice crisis requiring resolution.
This document summarizes the changing role of expert witnesses in court. It discusses how expert witnesses are traditionally expected to say whatever can reasonably support the client's position, rather than provide objective assistance. Courts have taken a more aggressive role in screening out "junk" testimony. One reform is the "gatekeeper" role of judges to exclude dubious expertise, based on criteria like testing and peer review. However, studies show judges rarely discuss these criteria and more often exclude evidence based on relevance or witness qualifications. There is a clash between the legal system's need for settled conclusions and experts' view that some issues have no settled answer. Through screening and cross-examination, the legal process does not always succeed at exposing problematic expert testimony that could lead
Strengthening Forensic Science A Way Station On The Way To Justicealisonegypt
1) The document discusses the need to strengthen forensic science through ongoing validation research to determine which practices are scientifically valid and the limits of their validity.
2) It proposes a series of "validation investigations" be conducted by a respected body like the National Academy of Sciences to determine if certain forensic techniques and theories have already been scientifically validated or not.
3) The validation investigations would examine all prior studies to determine if a technique has been validated, has not been validated, or has been found invalid. This would provide clarity on forensic practices and could reveal issues requiring re-examination of past convictions.
The document discusses the scientific and legal history of shaken baby syndrome. It describes the medical theory behind shaken baby syndrome - that violently shaking an infant can cause subdural hematomas and retinal hemorrhages leading to death. It notes the debate between experts who support the theory and those who are critical of it. The author argues that this is a genuine battle between qualified experts on both sides, and that expert testimony from both sides should be admitted in court under the Daubert and Kumho standards for expert testimony."
This document discusses shaken baby syndrome (SBS) cases and challenges the prevailing assumptions around SBS. It summarizes that shaking alone cannot cause the injuries typically associated with SBS, and that many other causes could result in retinal hemorrhages and subdural hematomas. It provides tips for challenging SBS claims using Daubert motions and expert witnesses in biomechanics, radiology, neurology and pathology that can argue alternative causes. Contact information is given for several medical experts who may be willing to review cases or testify that the injuries were not necessarily caused by shaking.
This case involves a negligence claim brought by L.C. and L.S. against the Ministry of Children and Families regarding their investigation into injuries sustained by L.C.'s infant son, D.C. D.C. was found to have a serious skull fracture and was initially removed from L.C.'s care. The Ministry conducted an investigation but L.C. maintained her innocence. The key issues are whether the Ministry owed a duty of care to L.C. and L.S., whether the Ministry breached the standard of care in its investigation, and whether any breach caused damages.
This document summarizes the growing issue of vitamin D deficiency (DD) in infants and children. It discusses how DD rates have risen significantly in recent decades across diverse populations. Multiple factors are contributing to the problem, including decreased food fortification of vitamin D, more sun avoidance behaviors, increased obesity rates, and longer breastfeeding durations without adequate supplementation. The document outlines how DD can manifest radiographically as softening of the skull and indistinct facial bones in young infants, as well as subtle metaphyseal changes in the long bones that could be mistaken for abuse-related fractures without consideration of the underlying DD.
The Canadian Paediatric Surveillance Program is a national surveillance system that identifies cases of rare diseases in children through the participation of over 2300 pediatricians. A recent study using this program identified over 100 cases of vitamin D deficiency rickets in Canadian children. National surveillance systems are important for collecting epidemiological data on uncommon conditions to answer research questions and guide public health policy. The Canadian Paediatric Surveillance Program provides valuable data and stimulates collaborative research that can improve children's health.
Nutritional rickets, once thought to be conquered, has reemerged as a public health issue in the United States. Recent case reports have highlighted dark-skinned breastfed infants, especially those in northern latitudes without vitamin D supplementation, as being most vulnerable. This article reviews a seminal 1917 study by Alfred Hess on using cod liver oil to prevent rickets in a black community in New York. The study found that cod liver oil effectively prevented and treated rickets in African American infants. Hess's success led to the development of the first rickets clinic and was an important step in overcoming the early 20th century rickets epidemic through vitamin D supplementation.
This document summarizes a court case from the Supreme Court of British Columbia regarding two parents, Muhammad and Muzzammil Rahman, appealing a lower court's decision granting continuing custody of their four children to the Director of Child, Family and Community Service. The case involves the death of the parents' two-year-old niece while in their care. While the mother was initially charged and acquitted of manslaughter, the Director has had custody of the Rahmans' four children since 2005. The Rahmans are appealing to have custody of their four children returned to them.
Multiple Fractures From Metabolic Bone Diseasealisonegypt
This document discusses multiple potential causes of fractures in infants that can be mistakenly attributed to child abuse, including metabolic bone diseases, prematurity, and nutritional deficiencies. It notes that fractures from metabolic causes often involve no pain, no soft tissue damage, and no dislocations, unlike traumatic fractures. It emphasizes the need for differential diagnosis to rule out conditions like rickets, scurvy, osteopenia of prematurity, and immobilization-related bone loss before accusing parents of abuse. Failure to consider other causes can lead to misdiagnosis of abuse when fractures actually have metabolic origins.
Mscr 2 Newer Clinical Signs Of Early Ricketsalisonegypt
This document summarizes a 1924 medical article on newer clinical signs of early rickets. It discusses:
1) Craniotabes, or softening of the cranial bones, was found in 60% of infants examined in the first 4 months, most commonly on the occiput and parietals. Associated findings included palpable parietal bosses and flattened areas on the back or sides of the head.
2) Common abnormal chest shapes in the first 4 months were square, triangular, and oval, rather than the normal circular shape. Specific characteristics of each shape are described.
3) Costomalacia, or softening of the cartilage portion of ribs near the sternum, was a
1. COMMENTARY JBMR
Vitamin D Insufficiency and Skeletal Development
In Utero
Martin Hewison and John S Adams
UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
Mahon and colleagues,(9) the authors have defined sufficiency as
O ver the last 10 years, our perception of what constitutes
normal vitamin D status has undergone a substantial
revision. Prior to this, suboptimal vitamin D was defined at a very
being 25-OHD concentrations greater than 70 nM based on
National Diet and Nutrition Survey data from the United
basic level by the presence or absence of associated bone Kingdom. Vitamin D deficiency was defined as being less than
disease (i.e., rickets in children and osteomalacia in adults). As a 25 nM 25-OHD, and interestingly, the authors then subdivided
consequence, vitamin D deficiency was determined by serum intervening serum concentrations of 25-OHD into two groups:
concentrations of 25-hydroxyvitamin D (25-OHD) of less than 25 ‘‘borderline’’ (50 to 70 nM) and ‘‘insufficient’’ (25 to 50 nM),
nM (10 ng/mL), and anything higher was ‘‘normal.’’ However, this providing an additional perspective on the physiologic impact of
has changed with the observation that several parameters of maternal vitamin D status.
calcium homeostasis continue to correlate with serum levels of High-resolution 3D ultrasound (3DUS) analysis of the pregnant
25-OHD up to concentrations as high as approximately 80 nM (32 women showed that suboptimal vitamin D status is associated
ng/mL).(1,2) The implication is that optimal vitamin D status is with increased femur metaphyseal cross-sectional area and
achieved only at 25-OHD concentrations above this; anything femur splaying index at 19 and 34 weeks of gestation. These
less is suboptimal or ‘‘insufficient.’’ Based on these revised changes contrasted with the measurement of femur length,
parameters, it has been concluded that vitamin D insufficiency is which showed no variability across the different categories of
a global phenomenon, with an estimated 1 billion people vitamin D status. The authors have shown previously that
worldwide having suboptimal levels of 25-OHD.(3) Some groups children born to mothers with vitamin D deficiency (<25 nM 25-
appear to be at greater risk of vitamin D insufficiency than others, OHD) or insufficiency (<50 nM 25-OHD) during pregnancy
notably pregnant women.(4–8) In a study carried out in exhibit deficits in bone mineral content at 9 years of age.(11)
Pittsburgh, PA, Bodnar and colleagues showed that 74% to However, the 3DUS study presented here is the first of its kind to
95% of pregnant black women and 46% to 62% of pregnant describe changes in skeletal morphology in utero that are related
white women were vitamin D insufficient.(5) Notably, during early to maternal vitamin D status. The splaying and associated
pregnancy, almost 45% of the African-American mothers had 25- metaphyseal widening documented in this study are analogous
OHD levels that were less than 37.5 nM.(5) A key question arising to the radiographic characteristic of the femoral and tibial
from these epidemiologic data concerns the physiologic impact bowing that occurs with rickets. In the case of the latter, changes
of vitamin D insufficiency during pregnancy. In the current issue in metaphyseal morphology occur as a consequence of
of the Journal, Mahon and colleagues have addressed this gravitational compression of ‘‘soft’’ undermineralized bone. By
through a prospective longitudinal study of pregnant women in contrast, the in utero observations described in the current study
which they have characterized the impact of maternal vitamin D occur despite a low-gravity environment. The underlying basis
status on in utero measures of fetal skeletal development.(9) for this remains unclear and will be the focus of future studies.
The precise definition of what constitutes vitamin D The data presented by Mahon and colleagues remain
insufficiency versus vitamin D deficiency is still subject to some observational, and causality cannot be assumed automatically.
debate. In some instances, vitamin D deficiency is defined as a Nevertheless, they are provocative on several levels given
serum concentration of 25-OHD of less than 50 nM, whereas current interest in the clinical impact of vitamin D insufficiency.
vitamin D sufficiency refers to a 25-OHD level of greater than 75 Significantly, the authors demonstrated differences in skeletal
nM.(10) As a result, serum concentrations of 25-OHD of between development associated with vitamin D status as early as week
these values correspond to the aforementioned vitamin D 19 of gestation. This is coincident with the well-documented
insufficiency. In the study of 424 pregnant women described by rise in maternal levels of the active form of vitamin D,
Address correspondence to: Martin Hewison, PhD, Department of Orthopaedic Surgery, Room 410D, OHRC, Geffen School of Medicine, UCLA, Los Angeles,
CA 90095, USA. E-mail: mhewison@mednet.ucla.edu
Journal of Bone and Mineral Research, Vol. 25, No. 1, January 2010, pp 11–13
DOI: 10.1002/jbmr.2
ß 2010 American Society for Bone and Mineral Research
11
2. 1,25-dihydroxyvitamin D [1,25-(OH)2D], that occurs early in and joint disease in adult life. Previous studies have supported a
gestation, thereby facilitating enhanced intestinal uptake of link between dietary and environmental factors during preg-
calcium in the mother as compensation for the increased fetal nancy, childhood growth, and risk of osteoporotic fracture in
demand for calcium as pregnancy progresses.(12) Enhanced adult life.(19) Thus in future studies it will be interesting to
conversion of 25-OHD to 1,25-(OH)2D in the setting of pregnancy determine the extent to which the alterations in 3DUS
is thought to be due primarily to activity of the enzyme 25- parameters measured in the current article continue into adult
hydroxyvitamin D-1a-hydroxylase (1a-hydroxylase) in maternal life. In this respect, it is noteworthy that analysis of the
kidneys. Renal activity of this enzyme is defined principally by the chondrocyte-specific Cyp27b1-knockout and Cyp27b1-overex-
stimulatory effects of parathyroid hormone (PTH) in response to pressing mice did not reveal any persistence of fetal bone
decreased serum calcium levels. The authors of the current study phenotype beyond the immediate neonatal period,(18) suggest-
measured only circulating levels of maternal 25-OHD and not ing that other factors, such as endocrine maintenance of calcium
1,25-(OH)2D. Nevertheless, it seems unlikely that the variations in and phosphate balance (the two mineral components of the
vitamin D status they describe will have a major impact on hydroxyapatite bone matrix), are more important in defining
maternal synthesis of 1,25-(OH)2D, questioning the involvement postnatal bone development.
of such a mechanism in mediating fetal responses to vitamin D. By demonstrating a clear phenotypic consequence of
Synthesis of 1,25-(OH)2D also occurs in the decidual and impaired maternal vitamin D status, Mahon and colleagues
trophoblastic cells of the placenta.(13,14) This may contribute to have added to the growing body of evidence supporting
circulating levels of the hormone in pregnant women but may improved strategies for vitamin D supplementation during
equally be more important for localized actions of vitamin D such pregnancy. In common with other association studies that have
as immune responses to infection.(15) Notably, in contrast to the linked vitamin D status with physiologic or disease parameters,
kidneys, activity of 1a-hydroxylase in placental cells is not prospective clinical trials are required to define a more causal
subject to regulation by PTH. Instead, placental synthesis of 1,25- role for vitamin D. For pregnant women in particular, this is
(OH)2D is more akin to that described for cells such as complicated by the need for studies to fully define the dosage
macrophages, where the capacity for extrarenal 1a-hydroxylase and timing of supplementation regimes that will safely ensure
activity depends primarily on the availability of substrate for the optimal serum levels of 25-OHD. In the current study,
enzyme, namely, 25-OHD. In this setting, the variations in vitamin metaphyseal cross-sectional area and splaying data showed
D status described in the current article by Mahon and the greatest difference when comparing vitamin D–deficient
colleagues may lead to concomitant changes in placental (<25 nM 25-OHD) versus vitamin D–sufficient (>75 nM 25-OHD)
synthesis of 1,25-(OH)2D, but it is unclear whether this will have mothers. It will be interesting in the future to explore more
any significant effect on fetal development and/or function. closely the potential differences between vitamin D–sufficient
Clearly, this is likely to be a focal point for future research, but mothers and more common status groups such as vitamin D
another possibility is that effects of maternal 25-OHD are insufficiency. In this respect, the authors’ use of a ‘‘borderline’’
mediated via extrarenal synthesis of 1,25-(OH)2D within the fetal sufficiency/insufficiency grouping remains contentious given the
skeleton itself. It has been recognized for many years that 25- broad acceptance of vitamin D insufficiency as a general term for
OHD can cross the placenta(16) and that chondrocytes are an suboptimal vitamin D status.(3,10) Irrespective of the categoriza-
extrarenal source of 1a-hydroxylase activity.(17) The significance tion of vitamin D status, perhaps the most noteworthy
of this with respect to skeletal development in the fetus has been observation is that the authors were able to link vitamin D
underlined by recent characterization of mouse models in which status with relatively early changes in skeletal phenotype.
the gene for 1a-hydroxylase (Cyp27b1) was either knocked out or Although this was based on a single measurement of serum 25-
overexpressed in chondrocytes.(18) In this study, loss of OHD levels in the pregnant women, the overarching conclusion
chondrocyte 1a-hydroxylase activity was sufficient to increase is that any strategies to tackle maternal vitamin D insufficiency
the width of the hypertrophic zone of the mouse growth plate at need to be initiated at an early stage of pregnancy. Given
day 15.5 of a conventional 21-day gestation. By contrast, the evidence linking vitamin insufficiency with adverse events
chondrocyte-specific Cyp27b1 transgenic mice had reduced in pregnancy, such as preeclampsia,(20) it is possible that
width of the hypertrophic zone in embryonic growth plates. The such strategies will have benefits above and beyond the
authors hypothesize that local conversion of 25-OHD to 1,25- developmental changes documented in the current issue of the
(OH)2D acts to regulate osteoclast invasion via changes in Journal.
vascular endothelial growth factor signaling. Loss or gain of
function within this mechanism thus would lead to dysregulation
of the cartilaginous matrix at the chondroosseous junction and Disclosures
concomitant alterations in bone size. While it is difficult to draw
immediate parallels between this study and the work of Mahon The authors have no conflicts of interest to declare.
and colleagues, it is nevertheless tempting to speculate that
extrarenal metabolism of 25-OHD plays a key role in mediating
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VITAMIN D INSUFFICIENCY IN UTERO Journal of Bone and Mineral Research 13