Cindy M. Anderson

Placental Insufficiency Leads to Developmental Hypertension and Mesenteric Artery Dysfunction in Two Generations of Sprague-Dawley Rat Offspring

Abstract It is generally accepted that preeclampsia results from reduction in perfusion to the uteroplacental unit leading to maternal hypertension and fetal growth restriction. Placental insufficiency creates an environment of fetal undernutriton, predisposing the fetus to the development of adult disease. In this study, we characterized the development and perpetuation of hypertension in two generations of male and female offspring subjected to an environment of fetal undernutrition via reduced uteroplacental perfusion pressure. Further, we examined vascular responses of resistance arteries in these animals to determine the influence of placental insufficiency on the development and perpetuation of hypertension. Experimental dams underwent a surgical procedure to reduce uteroplacental perfusion pressure, with resulting offspring comprising the first generation (F1). One male and one female from each of the F1 experimental litters served as breeders of the second generation (F2). Weekly systolic blood pressure measurements were obtained from 4 to 24 wk in control, F1, and F2 offspring. Vascular responsiveness to the vasoconstrictors phenylephrine and potassium chloride and the vasorelaxants acetylcholine and sodium nitroprusside was determined in the three offspring groups at 6, 9, and 12 wk of age. Our findings indicate that placental insufficiency during a critical developmental window in late gestation leads to hypertension in juvenile Sprague-Dawley rat offspring and is perpetuated in a second generation of offspring in a gender-specific manner. Further, exposure to placental insufficiency during late gestation leads to developmental alterations characterized by vascular hyperresponsiveness, perpetuated to a second generation of offspring in the absence of persistent environmental stimuli, contributing to hypertension.

The EPIIC hypothesis: Intrapartum effects on the neonatal epigenome and consequent health outcomes

There are many published studies about the epigenetic effects of the prenatal and infant periods on health outcomes. However, there is very little knowledge regarding the effects of the intrapartum period (labor and birth) on health and epigenetic remodeling. Although the intrapartum period is relatively short compared to the complete perinatal period, there is emerging evidence that this time frame may be a critical formative phase for the human genome. Given the debates from the National Institutes of Health and World Health Organization regarding routine childbirth procedures, it is essential to establish the state of the science concerning normal intrapartum epigenetic physiology. EPIIC (Epigenetic Impact of Childbirth) is an international, interdisciplinary research collaboration with expertise in the fields of genetics, physiology, developmental biology, epidemiology, medicine, midwifery, and nursing. We hypothesize that events during the intrapartum period - specifically the use of synthetic oxytocin, antibiotics, and cesarean section - affect the epigenetic remodeling processes and subsequent health of the mother and offspring. The rationale for this hypothesis is based on recent evidence and current best practice.

Preeclampsia: Exposing Future Cardiovascular Risk in Mothers and Their Children

There is an increased risk for future cardiovascular disease in women who have had preeclampsia. In infants born to mothers with preeclampsia, there is growing evidence of increased risk for both cardiovascular disease and preeclampsia. Epidemiologic and experimental data provide a strong link between intrauterine exposure to preeclampsia and subsequent risk for the development of cardiovascular disease in women.

Reduced uteroplacental perfusion alters uterine arcuate artery function in the pregnant Sprague-Dawley rat

Abstract Evidence continues to implicate reduced placental perfusion as the cause of preeclampsia, initiating a sequence of events leading to altered vascular function and hypertension. The present study was designed to determine the influence of reduced uteroplacental perfusion pressure (RUPP) on the responsiveness of uterine arcuate resistance arteries. A condition of RUPP was surgically induced in pregnant Sprague-Dawley rats on Gestational Day 14. On Gestational Day 20, uterine arcuate arteries were mounted on a small-vessel wire myograph and challenged with incremental concentrations of vasoconstrictors and vasorelaxants for measurement of isometric tension. Compared to the sham-operated controls, uterine arteries from the RUPP group demonstrated an increased maximal tension in response to phenylephrine (P < 0.01); potassium chloride at 30 mM (P < 0.05), 60 mM (P < 0.01), and 120 mM (P < 0.01); and angiotensin II (P < 0.05). In arteries from the RUPP and sham-operated control groups, endothelium-dependent relaxation in response to acetylcholine (P < 0.05) and calcium ionophore (A23187; P < 0.05) was significantly reduced in the RUPP group compared to the sham-operated controls. Fetal growth indices, including litter size, fetal weight, and placental weight, were significantly reduced in the RUPP group compared to sham-operated controls, which is consistent with significant growth restriction. Data suggest that RUPP promotes hyperresponsiveness and impaired endothelium-dependent relaxation in uterine arcuate arteries, leading to intrauterine fetal growth restriction.

Maternal Vitamin D Supplementation to Meet the Needs of the Breastfed Infant A Systematic Review

Maternal vitamin D insufficiency during lactation, related to lack of sun exposure and minimal intake of vitamin D from the diet, contributes to low breast milk vitamin D content and, therefore, infant vitamin D deficiency. The objective of this review was to examine the literature regarding evidence for achieving maternal vitamin D status that promotes sufficient vitamin D transfer from mother to infant exclusively from breast milk. PubMed and CINAHL databases were searched using the terms lactation or breastfeeding or milk, human and vitamin D. The resulting articles were further limited to those written in English, published within the last 10 years, and involving clinical or randomized controlled trials of humans. The search yielded 13 studies, 3 of which provide evidence for maternal intake of vitamin D and the correlation with exclusively breastfed infants’ serum 25-hydroxyvitamin D level. A strong positive correlation exists between maternal vitamin D intake during exclusive breastfeeding and infant serum 25-hydroxyvitamin D levels. There is support to conclude that when maternal vitamin D intake is sufficient, vitamin D transfer via breast milk is adequate to meet infant needs. In the reviewed studies, doses up to 10 times the current recommended daily intake of vitamin D were needed to produce sufficient transfer from mother to breastfed infant. Further research is needed to refine the dose and gestational timing of maternal vitamin D supplementation. Due to the high rates of vitamin D deficiency during lactation and the correlations between vitamin D deficiency and multiple diseases, providers should consider monitoring lactating mothers’ vitamin D status.

Mesenteric vascular responsiveness in a rat model of pregnancy-induced hypertension.

Reduced perfusion to the placenta in early pregnancy is believed to be the initiating factor in the development of preeclampsia, triggering local ischemia and systemic vascular hyperresponsiveness. This sequence of events creates a predisposition to the development of altered vascular function and hypertension. This study was designed to determine the influence of placental insufficiency on the responsiveness of mesenteric resistance arteries in an animal model of preeclampsia. Placental insufficiency was induced by reduction in uteroplacental perfusion pressure (RUPP) in experimental Sprague-Dawley rat dams. The uterine branches of the ovarian arteries and the abdominal aortae of pregnant rats were surgically constricted on gestational Day 14. Dams in the control group underwent a sham procedure. Rats were euthanized on gestational Day 20, followed by removal of the small intestine and adjacent mesentery. First-order mesenteric resistance arteries were mounted on a small vessel wire myograph and challenged with incremental concentrations of vasoconstrictors and vasorelaxants. Mesenteric arteries in dams with placental insufficiency demonstrated an increased maximal tension to phenylephrine (7.15 ± 0.15 vs. 5.4 ± 0.27 mN/mm, P < 0.001); potassium chloride at 60 mM (3.43 ± 0.11 vs. 2.77 ± 0.14 mN/mm, P < 0.01) and 120 mM (3.92 ± 0.18 vs. 2.97 ± 0.16 mN/mm, P < 0.01); and angiotensin II (2.59 ± 0.42 vs. 1.51 ± 0.22 mN/mm, P < 0.05). Maximal relaxation to endothelium-dependent relaxants acetylcholine and calcium lonophore (A23187) was not significantly reduced. Data suggest that placental insufficiency leads to hyperresponsiveness to vasoconstrictor stimuli in mesenteric arteries.

DNA methylation as a biomarker for preeclampsia.

Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

Time Management Strategies for Research Productivity

Researchers function in a complex environment and carry multiple role responsibilities. This environment is prone to various distractions that can derail productivity and decrease efficiency. Effective time management allows researchers to maintain focus on their work, contributing to research productivity. Thus, improving time management skills is essential to developing and sustaining a successful program of research. This article presents time management strategies addressing behaviors surrounding time assessment, planning, and monitoring. Herein, the Western Journal of Nursing Research editorial board recommends strategies to enhance time management, including setting realistic goals, prioritizing, and optimizing planning. Involving a team, problem-solving barriers, and early management of potential distractions can facilitate maintaining focus on a research program. Continually evaluating the effectiveness of time management strategies allows researchers to identify areas of improvement and recognize progress.

Breast Feeding on Campus: Personal Experiences, Beliefs, and Attitudes of the University Community

Breast feeding a new baby is a special challenge for college students and university employees. Although success is usually associated with availability of support from the community, little is known about the social context for breast feeding on campus. Personal breast feeding experiences, beliefs about outcomes of breast-feeding and bottle feeding, attitudes toward breast feeding and bottle feeding, and regard for appropriateness of various settings for breast feeding in the campus community were investigated. One hundred seven students, faculty, staff, and administrators at a North Central state university participated in the study. Almost all reported at least one personal breast-feeding experience. Benefits of breast feeding over bottle feeding were acknowledged; however, the university community regarded both feeding methods favorably and saw practical advantages to bottle feeding. Personal spaces, such as infant home or family car, were regarded as more appropriate for breast feeding than public settings. Implications for promotion, support, and protection of breast feeding on campus are discussed.

Educating Future Nursing Scientists: Recommendations for Integrating Omics Content in PhD Programs

Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Sciences Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals.