Medicine and Health Sciences Commons^™

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins

Dartmouth Scholarship

Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels.

Methods: Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from …

Maternal Anaemia And Duration Of Zidovudine In Antiretroviral Regimens For Preventing Mother-To-Child Transmission: A Randomized Trial In Three African Countries, Benn K.D. Sartorius, Matthew F. Chersich, Mary Mwaura, Nicolas Meda, Marleen Temmerman, Marie Louise Newell, Timothy M. M. Farley, Stanley Luchters, The Kesho Bora Study Group

Obstetrics and Gynaecology, East Africa

Background: Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common.

Methods: Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12–24 months after delivery (n = 1070). Women with a CD4 count of 200-500cells/mm3 and gestational age 28–36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were …

Perinatal Outcomes Of Prenatal Probiotic And Prebiotic Administration: An Integrative Review, Leona Vandevusse, Lisa Hanson, Nasia Safdar

College of Nursing Faculty Research and Publications

The purpose of this integrative review was to identify, critique, and synthesize the maternal and neonatal evidence on the prenatal use of probiotics and prebiotics to inform perinatal health professionals. A comprehensive literature search resulted in 37 studies of prenatal probiotics and 1 on antepartal prebiotics published from 1990 through 2011 that reported maternal, fetal, and/or neonatal outcomes. The methodologic quality of the studies reviewed was high, although investigators used different probiotic combinations and inconsistently reported perinatal clinical outcomes. The extraction of perinatal outcome variables resulted in identification of 9 maternal and 5 neonatal categories. Prenatal probiotics significantly reduced the …

Wilson’S Disease In Pregnancy: Case Series And Review Of Literature, Ayesha Malik, Ali Khawaja, Lumaan Sheikh

Department of Obstetrics & Gynaecology

Background: Wilson’s disease is a rare, autosomal recessive inherited disorder characterized by impaired liver metabolism of copper leading to decreased biliary excretion and incorporation of ceruloplasmin levels mainly in the liver and brain. Untreated Wilson’s disease has been shown to cause subfertility and even in cases where pregnancy occurs, it often results in spontaneous miscarriage.

Case presentations: We present four cases of successful pregnancy outcomes in three patients diagnosed with Wilson’s disease along with the literature review. All the patients were managed with zinc sulphate without any postnatal complications.

Conclusion: Patients with Wilson’s disease receiving regular treatment who remain asymptomatic …

Community Health News, Georgia Southern University

Community Health Department News (2011-2018)

• Adults Attitudes toward Teen Pregnancy

The Association Between Hospital Obstetrical Volume And Maternal Postpartum Complications, Kathy Kyser, Xin Lu, Donna Santillan, Mark Santillan, Stephen Hunter, Alison Cahill, Peter Cram

Stephen K. Hunter

OBJECTIVE: The purpose of this study was to examine the relationship between delivery volume and maternal complications. STUDY DESIGN: We used administrative data to identify women who had been admitted for childbirth in 2006. Hospitals were stratified into deciles that were based on delivery volume. We compared composite complication rates across deciles. RESULTS: We evaluated 1,683,754 childbirths in 1045 hospitals. Decile 1 and 2 hospitals had significantly higher rates of composite complications than decile 10 (11.8% and 10.1% vs 8.5%, respectively; P < .0001). Decile 9 and 10 hospitals had modestly higher composite complications as compared with decile 6 (8.8% and …

De Novo Frameshift Mutation In Asxl3 In A Patient With Global Developmental Delay, Microcephaly, And Craniofacial Anomalies., Darrell L. Dinwiddie, Sarah E. Soden, Carol J. Saunders, Neil A. Miller, Emily G. Farrow, Laurie D. Smith, Stephen F. Kingsmore

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Currently, diagnosis of affected individuals with rare genetic disorders can be lengthy and costly, resulting in a diagnostic odyssey and in many patients a definitive molecular diagnosis is never achieved despite extensive clinical investigation. The recent advent and use of genomic medicine has resulted in a paradigm shift in the clinical molecular genetics of rare diseases and has provided insight into the causes of numerous rare genetic conditions. In particular, whole exome and genome sequencing of families has been particularly useful in discovering de novo germline mutations as the cause of both rare diseases and complex disorders.

CASE PRESENTATION: …

Patterning In Placental 11-B Hydroxysteroid Dehydrogenase Methylation According To Prenatal Socioeconomic Adversity, Allison A. Appleton, David A. Armstrong, Corina Lesseur, Joyce Lee, James F. Padbury, Barry M. Lester

Dartmouth Scholarship

Background:

Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from …

Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir

Journal Articles: Cellular & Integrative Physiology

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 …

Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado

Obstetrics & Gynaecology Publications

Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the …

Association Between Elevated Third Trimester Maternal Haemoglobin And Neonatal Gestational Age Adjusted Birth Weight, Bob Otieno Achila

Theses & Dissertations

Background: Women tend to have lower haemoglobin compared to men due to menstrual blood losses. This is often compounded by nutritional deficiencies. There is a further drop in haemoglobin during pregnancy due to red cell dilution. Pregnancy itself places a huge demand on maternal iron stores. High haemoglobin may reflect haemoconcentration due to a failure of the normal physiological expansion in plasma volume. Iron excess has also been associated with free-radical damage. In current practice, high maternal haemoglobin in pregnancy is often not given as much attention as anaemia. This study examines the association between high maternal haemoglobin in the …

Maternal Genital Tract Colonisation By Group-B Streptococcus: A Hospital Based Study, Nida Najmi, Rozina Sikandar, Nadeem F. Zuberi, Imtiaz Jehan

Department of Obstetrics & Gynaecology

Objectives: To determine the prevalence of Group B Streptococcus genital tract infection in pregnant women and to determine the risk factors for its colonisation.
Methods: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi and Sobhraj Hospital, Karachi, from May to August 2007. Pregnant women at 35-37 weeks gestation attending antenatal clinic at these hospitals constituted the study population. Based on stratified sampling, 405 patients were recruited. High vaginal swabs of these patients were taken in order to calculate the prevalence of infection at each hospital. Logistic regression was used to evaluate the risk factor association. SPSS …

Immune Dysregulation And Glucocorticoid Resistance In Minority And Low Income Pregnant Women, Elizabeth J. Corwin, Ying Guo, Kathleen Pajer, Nancy Lowe, Donna O. Mccarthy, Sarah Schmiege, Mary Weber, Thaddeus Pace, Brian Stafford

College of Nursing Faculty Research and Publications

Chronic prenatal stress contributes to poor birth outcomes for women and infants. Importantly, poor birth outcomes are most common among minority and low income women. To investigate underlying mechanisms, we tested the hypothesis that chronic stress related to minority or low income status is associated with glucocorticoid resistance as indicated by disruption in the cytokine-glucocorticoid feedback circuit. Home visits were conducted during which 3rd trimester pregnant women completed stress and depression surveys and provided blood for pro- and anti-inflammatory cytokines. Saliva was collected 5 times the preceding day for diurnal cortisol levels. For statistical analyses, women were grouped 3 ways, …

Risk Of Early & Late Obstetric Complications In Women With Ivf- Conceived Pregnancies And Polycystic Ovary Syndrome (Pcos), N. A. Bagegni, J. Blaine, Bradley J. Van Voorhis, Anuja Dokras

Bradley J Van Voorhis

There is conflicting evidence on the association between PCOS and early and late obstetric complications. It is unclear if the reported risks are independent of BMI, preexisting hypertension and diabetes. We performed a retrospective chart review to examine the risk of early and late obstetrical complications after IVF in women with PCOS (n=130) compared to controls (n=130). The miscarriage rate was 17.7% in PCOS women and 15.4% in controls. PCOS was not associated with miscarriage independent of age and BMI. The prevalence of gestational DM (GDM) was similar in both groups (12% PCOS versus 11% controls). BMI was independently associated …

Fetal Programming And Later Obesity In A Predominantly Latino Wic Population, Eric George Walsh

Loma Linda University Electronic Theses, Dissertations & Projects

Background: In utero stressors may work to program the metabolism of the developing fetus in such a way that predisposes him/her to obesity later on. Studies have shown that breastfeeding is protective against childhood obesity and suggest that after six months the weight gain in breastfed babies slows opposed to formula fed babies who continue with rapid weight gain. This slowing of weight gain has been shown to be protective against adiposity and later life weight gain.

Purpose: This study looks to further explore these findings in a low income Latino population adding mother’s feelings about the pregnancy and the …

Differential Dna Methylation In Umbilical Cord Blood Of Infants Exposed To Low Levels Of Arsenic In Utero, Devin C. Koestler, Michele Avissar-Whiting, E. Andres Houseman, Margaret R. Karagas, Carmen J. Marsit

Dartmouth Scholarship

Background: There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations, specifically by altering patterns of DNA methylation.

Objectives: In this study we aimed to identify differences in DNA methylation in cord blood samples of infants with in utero, low-level arsenic exposure.

Methods: DNA methylation of cord-blood derived DNA from 134 infants involved in a prospective birth cohort in …

Online Healthy Lifestyle Support In The Perinatal Period: What Do Women Want And Do They Use It?, Lydia A. Hearn, Margaret R. Miller, Anna Fletcher

Research outputs 2013

Unhealthy weight gain and retention during pregnancy and postpartum is detrimental to mother and child. Although various barriers limit the capacity for perinatal health care providers (PHCPs) to offer healthy lifestyle counselling, they could guide women to appropriate online resources. This paper presents a project designed to provide online information to promote healthy lifestyles in the perinatal period. Focus groups or interviews were held with 116 perinatal women and 76 PHCPs to determine what online information perinatal women and PHCPs want, in what form, and how best it should be presented. The results indicated that women wanted smartphone applications (apps) …

Defining Normal Igg Changes Throughout Pregnancy, Jena Taylor, Jona Conklin, Stephen K. Hunter, Ryan Empey, Eric M. Tyler, Ashley Christensen, Katelyn M. Talcott, Zuhair K. Ballas, Donna A. Santillan, Mark K. Santillan

Stephen K. Hunter

Immunoglobulin G (IgG) is the major serum immunoglobulin, accounting for roughly 75% of all immunoglobulin. IgG is the only class of immunoglobulin that crosses the placenta and it serves as the main immunologic barrier between the fetus and external environments. There has not been a clear consensus on what the normal values of IgG are throughout pregnancy. The aim of this study is to measure serum immunoglobulin G in each trimester of the pregnant female to determine a normal IgG profile throughout all trimesters in normal pregnancy.

Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter

Stephen K. Hunter

OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …

Promoting Abstinence From Alcohol During Pregnancy: Implications From Formative Research, Kathryn France, Robert Donovan, Nadine Henley, Carol Bower, Elizabeth Elliott, Janet Payne, Heather D'Antoine, Anne Bartu

Research outputs 2013

This research developed messages to promote abstinence from alcohol during pregnancy and identified elements that enhance message persuasiveness. An exploratory phase was conducted in 2009 that comprised four focus groups with 23 women inWestern Australia and elicited beliefs and attitudes on alcohol use during pregnancy and motivations for behavior change. Four television concepts were subsequently developed and appraised in five focus groups with 31 participants using standard advertising pretesting questions. The implications for campaigns addressing prenatal alcohol exposure and further research are noted and limitations discussed. Funding was received from Healthway and the National Health and Medical Research Council.

The Association Between A Medical History Of Depression And Gestational Diabetes In A Large Multi-Ethnic Cohort In The United States, Katherine Bowers, S. Katherine Laughon, Sungduk Kim, Sunni L. Mumford, Jennifer Brite, Michele Kiely, Cuilin Zhang

Publications and Research

Background: Both major depression and gestational diabetes mellitus (GDM) are prevalent among women of reproductive age. Our objective was to determine whether a medical history of depression is related to subsequent development of GDM.

Methods: The Consortium on Safe Labor was a US retrospective cohort study of 228 562 births between 2002 and 2008. Exclusion criteria for the present analysis included multiple gestation pregnancies (n = 5059), pre-existing diabetes (n = 12 771), deliveries(n = 395), site GDM prevalence (

Results: The final analytic population included 121 260 women contributing 128 295 pregnancies, of which 5606 were affected by GDM. …

The Association Between Hospital Obstetrical Volume And Maternal Postpartum Complications., Kathy L Kyser, Xin Lu, Donna Santillan, Mark Santillan, Stephen Hunter, Alison G Cahill, Peter Cram

Donna A. Santillan

OBJECTIVE: The purpose of this study was to examine the relationship between delivery volume and maternal complications.

STUDY DESIGN: We used administrative data to identify women who had been admitted for childbirth in 2006. Hospitals were stratified into deciles that were based on delivery volume. We compared composite complication rates across deciles.

RESULTS: We evaluated 1,683,754 childbirths in 1045 hospitals. Decile 1 and 2 hospitals had significantly higher rates of composite complications than decile 10 (11.8% and 10.1% vs 8.5%, respectively; P < .0001). Decile 9 and 10 hospitals had modestly higher composite complications as compared with decile 6 (8.8% and 8.5% vs 7.6%, respectively; P < .0001). Sixty percent of decile 1 and 2 hospitals were located within 25 miles of the nearest greater volume hospital.

CONCLUSION: Women who deliver at very low-volume hospitals have higher complication rates, as do women who deliver at …

The Effects Of Preeclampsia On Signaling To Hematopoietic Progenitor Cells, Donna Santillan, Wendy Hamilton, Ashley Christensen, Katelyn Talcott, Lindsay Gravatt, Mark Santillan, Stephen Hunter

Donna A. Santillan

Background: The role of the microenvironment is important in cell differentiation. The effect of placental disease on the growth and differentiation and hematopoietic stem cells has not been well-studied.

Methods: Enzyme linked immunoassay was used to measure erythropoietin and osteopontin in plasma from umbilical cord blood of children born to normotensive and preeclamptic women. Additionally, CD34+ cells were isolated from umbilical cord blood and grown in complete methylcellulose media. Colony types were identified and enumerated.

Results: Differences in the concentration of erythropoietin in the cord blood between the controls and the preeclamptics approached significance (P = 0.067) using a Mann-Whitney …

From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter

Donna A. Santillan

In the United States, preeclampsia (PreE) affects 5-7% of all pregnancies, yet represents 15% of all maternal-fetal morbidity and mortality. PreE causes fetal growth restriction, oligohydramnios, fetal death, and maternal seizures, stroke, cerebrovascular hemorrhage and death. It has immediate and potentially long-term effects on both the fetus and mother. To date, the molecular pathogenesis of PreE is largely unknown. Multiple pathways, including dysfunctional angiogenesis, inappropriate placentation, oxidative stress and an altered immunological milieu have been proposed as key players in the development of PreE. In addition, genetic factors in all of these pathways are essential components in the etiology of …

Preeclampsia And Micrornas, Eric J. Devor, Donna A. Santillan, Mark K. Santillan

Donna A. Santillan

Preeclampsia is a critical gestational condition that threatens the life of both mother and child. One of the most serious aspects of preeclampsia hampering both clinical management and scientific understanding is that there are, as yet, no early warning signs or risk markers. The discovery of microRNAs (miRNAs), tiny post-transcriptional regulators of gene expression, offers potentially fertile ground for developing such markers. The current state of knowledge about miRNAs in preeclampsia is presented along with information regarding miRNA detection in peripheral fluids that could lead to minimally invasive risk assessment.

Noninvasive Whole-Genome Sequencing Of A Human Fetus, J. Kitzman, M. Snyder, M. Ventura, A. Lewis, R. Qiu, L. Simmons, H. Gammill, C. Rubens, Donna Santillan, J. Murray, H. Tabor, M. Bamshad, E. Eichler, J. Shendure

Donna A. Santillan

Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 x 10(6) parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo …

Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter

Donna A. Santillan

OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …

Protective Immunization In Mice Against Group B Streptococci Using Encapsulated C5a Peptidase, Donna Santillan, M. E. Andracki, S. K. Hunter

Donna A. Santillan

OBJECTIVE: The purpose of the study was to test whether C5a peptidase encapsulated within a biodegradable polymer can act as a vaccine and elicit an immune response to prevent group B streptococci (GBS) infection in mice and provide protection to pups. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-co-glycolide). Female ICR mice were immunized with encapsulated C5a peptidase, free C5a peptidase, or empty microparticles. Booster doses were given at days 21 and 42. Antibody responses were measured by enzyme-linked immunosorbent assay. Challenge with GBS type III was performed 4 days after the final booster in the vaginal …

The Influence Of Fetal Sex On Patterns Of Change In Anti-Mullerian Hormone During Pregnancy, Ryan Empey, Donna A. Santillan, Mark Santillan, Eric M. Tyler, Stephen K. Hunter, Elaine M. Smith, Barbara J. Stegmann

Donna A. Santillan

Maternal anti-mullerian hormone declines sharply between 13-15 weeks, likely as a result of feto-placental signaling. Fetal AMH levels are known to be widely disparate after the first trimester, with high levels in male and absent levels in female. However, it is unclear as to whether differing fetal AMH levels influence the pattern of change of maternal AMH. Our objective was to examine AMH throughout gestation to determine if the maternal concentration varies according to the gender of the fetus.