Supplementation with antioxidant micronutrients in pregnant women with obesity: a randomized controlled trial.

BACKGROUND/OBJECTIVE: Obesity increases maternal morbidity and adversely affects child health. Maternal inflammation may play a role in adverse outcomes. The objective of this study was to determine whether providing a higher dose of antioxidant micronutrients to pregnant women with obesity would raise concentrations of key antioxidant vitamins and impact inflammation and oxidative stress during pregnancy. SUBJECTS/METHODS: This was a double-blind, randomized controlled trial. We recruited pregnant women with a body mass index (BMI) ≥ 30 kg/m2 at their initial prenatal visit ( < 13 weeks gestation) and collected blood and urine samples at baseline, 24-28 weeks, and 32-36 weeks to measure micronutrient concentrations (vitamin C, E, B6 and folate), markers of inflammation (C-reactive protein, interleukin-6, 8, and 1ß) and oxidative stress (8-epi-PGF2α and malondialdehyde). We collected maternal and infant health data from enrollment to delivery as secondary outcomes. We enrolled 128 participants (64 in each arm), and 98 (49 in each arm) completed follow-up through delivery. INTERVENTION: Both groups received a standard prenatal vitamin containing the recommended daily allowance of micronutrients in pregnancy. In addition, the intervention group received a supplement with 90 mg vitamin C, 30 αTU vitamin E, 18 mg vitamin B6, and 800 µg folic acid, and the control group received a placebo. RESULTS: The intervention group had higher vit B6 (log transformed (ln), ß 24-28 weeks: 0.76 nmol/L (95% CI: 0.40, 1.12); ß 32-36 weeks: 0.52 nmol/L (95% CI: 0.17, 0.88)) than the control group. Vitamins C, E, erythrocyte RBC folate concentrations did not differ by randomization group. The intervention did not impact biomarkers of inflammation or oxidative stress. There were no differences in maternal or neonatal clinical outcomes by randomization group. CONCLUSIONS: Higher concentrations of antioxidant vitamins during pregnancy increased specific micronutrients and did not impact maternal inflammation and oxidative stress, which may be related to dosing or type of supplementation provided. CLINICAL TRIAL REGISTRATION: Clinical Trial Identification Number: NCT02802566; URL of the Registration Site: www. CLINICALTRIALS: gov .

Identification of the blue light intensity administered to one eye required to suppress bovine plasma melatonin and investigation into effects on milk production in grazing dairy cows.

Long-day photoperiod is known to positively affect milk production in confinement dairy systems, and it has been hypothesized that pineal melatonin (MT) secretion plays a substantial role in this process. Specialized mammalian photoreceptors that regulate MT secretion are optimally stimulated by short wavelength blue light. We investigated the blue light intensity administered to one eye required to suppress MT secretion in nonlactating dairy cows, and subsequently examined effects on milk production in grazing dairy cows. Following a 14-d light-dark 8:16 h environmental conditioning period, 5 nonlactating Holstein-Friesian cows were exposed to treatments of <1, 70, 125, 175, and 225 lx for 8 additional hours using a 5 × 5 Latin square design. Light was administered via headpieces fitted with light-emitting diodes emitting blue light (465 nm) to the right eye. All cows were then exposed to a light-dark 16:8 h cycle for one night via the indoor lighting system (>200 lx white light). Plasma samples collected at regular intervals were assayed for MT. A dose-dependent effect of light treatment on mean circulating MT concentrations (and 95% CI) was observed [9.4 (7.2, 12.3), 5.0 (3.8, 6.6), 4.4 (3.3, 5.7), 3.3 (2.5, 4.3) and 1.7 (1.3, 2.3) pg/mL for treatments of 0, 70, 125, 175, and 225 lx, respectively. Only the 225 lx treatment acutely suppressed plasma melatonin concentration to levels similar to the light-dark 16:8 h treatment [1.9 (1.4, 2.5) pg/mL]. Forty spring-calving cows were blocked on parity, calving date and Economic Breeding Index for milk production and assigned to the control treatment or blue light to a single eye (LT) treatment from calving through 32 wk of lactation. The cows assigned to LT treatment were fitted with headpieces providing 225 lx of blue light to the right eye from 1700 until 0000 h. Mean milk production (and 95% CI) during 32 wk of lactation was not affected by treatment [20.3 (19.3, 21.3) vs. 20.9 (19.8, 22.0) kg/d, control and LT, respectively]. Within multiparous cows, a treatment by week interaction was detected, whereby LT treatment increased milk production during the first 12 wk of lactation [25.8 (24.3, 27.3) vs. 28.0 (26.5, 29.5) kg/d; +8.5%], but had no effect thereafter. Treatment did not affect plasma insulin-like growth factor 1. We identified the blue light intensity to one eye required to acutely suppress MT concentrations. Transient favorable effects on milk production were observed in multiparous cows. It remains unclear how single-eye blue light treatment affects galactopoiesis in grazing dairy cows, and further research is needed to explore whether this modality of light delivery represents a useful means to aid productivity in pasture-based dairy systems.

Factors affecting breastfeeding in women with epilepsy.

OBJECTIVE: This study aimed to compare rates of breastfeeding initiation and maintenance in women with epilepsy (WWE) with those of the general population and to identify factors affecting breastfeeding patterns in WWE. METHODS: We retrospectively reviewed data for the following variables in pregnant WWE (n = 102) and healthy women without epilepsy (n = 112): demographic characteristics (age, race, ethnicity), epilepsy type (focal or generalized onset), antiseizure medication(s), psychiatric comorbidities, postpartum seizure control, breastfeeding counseling, and lactation consultation. Fisher exact test and logistic regression analyses were performed to compare the rates of breastfeeding initiation and continuation in pregnant WWE with those of healthy pregnant women and to determine factors associated with rates of breastfeeding initiation and maintenance. RESULTS: The rate of breastfeeding initiation in WWE was significantly lower than in healthy women without epilepsy (50.9% vs. 87.6%), and WWE were less likely to maintain breastfeeding at 6 weeks (38.2%) and 3 months (36%) postpartum. Nearly half (53%) of WWE received antepartum breastfeeding counseling by their neurologists, and these women had higher odds of breastfeeding initiation and continuation (odds ratio [OR] = 2.53, 95% confidence interval [CI] = 1.14-5.72, p = .02). Postpartum consultation with a board-certified lactation consultant was associated with higher odds of breastfeeding continuation at 6 weeks (OR = 5.43, 95% CI = 1.39-27.23, p = .02) and at 3 months (OR = 4.9, 95% CI = 1.34-20.87, p = .019). Women taking levetiracetam were more likely to initiate and continue breastfeeding than those taking lamotrigine (OR = 6.22, 95% CI = 2.15-20.20, p = .001). SIGNIFICANCE: The initiation rate and duration of breastfeeding were significantly lower in WWE than in healthy women without epilepsy and were significantly associated with several factors. Identification of potential barriers to breastfeeding in WWE may lead to development of intervention strategies that can improve breastfeeding rates in WWE to maximize positive health outcomes for WWE and their infants.

A multidisciplinary telemedicine model for management of coronavirus disease 2019 (COVID-19) in obstetrical patients.

Background: The COVID-19 pandemic caused by the SARS-CoV-2 has increased the demand for inpatient healthcare resources; however, approximately 80% of patients with COVID-19 have a mild clinical presentation and can be managed at home. Objective: This study aimed to describe the feasibility and clinical and process outcomes associated with a multidisciplinary telemedicine surveillance model to triage and manage obstetrical patients with known exposures and symptoms of COVID-19. Study Design: We implemented a multidisciplinary telemedicine surveillance model with obstetrical physicians and nurses to standardize ambulatory care for obstetrical patients with confirmed or suspected COVID-19 based on the symptoms or exposures at an urban academic tertiary care center with multiple hospital-affiliated and community-based practices. All pregnant or postpartum patients with COVID-19 symptoms, exposures, or hospitalization were eligible for inclusion in the program. Patients were assessed by means of regular nursing phone calls and were managed according to illness severity. Patient characteristics and clinical and process outcomes were abstracted from the electronic medical record. Results: A total of 135 patients were enrolled in the multidisciplinary telemedicine model from March 17 to April 19, 2020, of whom 130 were pregnant and 5 were recently postpartum. In this study, 116 of 135 patients (86%) were managed solely in the outpatient setting and did not require an in-person evaluation; 9 patients were ultimately admitted after ambulatory or urgent evaluations, and 10 patients were observed after hospital discharge. Although only 50% of the patients were tested secondary to limitations in ambulatory testing, 1 in 3 of those patients received positive results for SARS-CoV-2 (N=22, 16% of entire cohort). Patients were enrolled in the telemedicine model for a median of 7 days (interquartile range, 4-8) and averaged 1 phone call daily, resulting in 891 nursing calls and 20 physician calls over 1 month. Conclusion: A multidisciplinary telemedicine surveillance model for outpatient management of obstetrical patients with COVID-19 symptoms and exposures is feasible and resulted in rates of ambulatory management similar to those seen in nonpregnant patients. A centralized model for telemedicine surveillance of obstetrical patients with COVID-19 symptoms may preserve inpatient resources and prevent avoidable staff and patient exposures, particularly in centers with multiple ambulatory practice settings.

An Opportunity to Engage Obstetrics and Gynecology Patients Through Shared Visit Notes.

OBJECTIVE: To assess obstetrics and gynecology patients' interest in reading their ambulatory visit notes, identification of documentation errors, and perceptions of sensitive language through a quality improvement (QI) initiative. METHODS: Beginning April 2016, as part of a QI project all obstetrics and gynecology patients (except family planning) were invited to read their ambulatory visit notes and provide feedback using a patient reporting tool codeveloped with patients. Two physicians with safety expertise reviewed all patient-reported errors over the first 16 months. RESULTS: Among obstetrics and gynecology patients with an active portal account and an available note, 6,594 of 9,550 (69%) read at least one note. Two hundred twelve (3.2%) patients used the electronic reporting tool, submitting a total of 232 reports, in a "natural" environment with no advertisement, incentives, or clinician encouragement. In total, 94% felt they understood the notes, 95% understood the next steps in the care plan, and 92% felt the notes accurately described their visit. Of all reports, 27% of patients identified inaccuracies in the notes, including descriptions of symptoms (29%); family history (21%); medications (15%); health problems (15%); social history and physical examination, including elements that were reportedly documented but not performed (each 11%). Patients rated inaccuracies as important in 58% of reports, and, on clinician review, 75% of patient-reported mistakes had the potential to affect care. Among all reports, 7% of patients indicated bothersome words. More than half (56%) of patients included voluntary positive feedback such as appreciation for the health care provider, reassurance from notes, greater visit recall and care plan adherence, and positive effects on the patient-doctor relationship. DISCUSSION: Obstetrics and gynecology patients are interested in reading notes, which can promote engagement and safety. Few patients provided feedback, but those who did identified documentation inaccuracies in about one quarter of reports; the majority were relevant to care. Greater outreach and patient encouragement are needed to further engage patients in safety.

Effect of equine chorionic gonadotropin treatment during a progesterone-based timed artificial insemination program on reproductive performance in seasonal-calving lactating dairy cows.

The aim of this study was to investigate the effect of progesterone (P4)-based timed artificial insemination (TAI) programs on fertility in seasonal-calving, pasture-based dairy herds. A total of 1,421 lactating dairy cows on 4 spring-calving farms were stratified based on days in milk (DIM) and parity and randomly allocated to 1 of 3 treatments: (1) control: no hormonal treatment; cows inseminated at detected estrus; (2) P4-Ovsynch: cows received a 7-d P4-releasing intravaginal device (PRID Delta; CEVA Santé Animale, Libourne, France) with 100 µg of a gonadotropin-releasing hormone (GnRH) analog (Ovarelin; CEVA Santé Animale) at PRID insertion, a 25-mg injection of PGF2α (Enzaprost; CEVA Santé Animale) at PRID removal, GnRH at 56 h after device removal and TAI 16 h later; (3) P4-Ovsynch+eCG: the same as P4-Ovsynch, but cows received 500 IU of equine chorionic gonadotropin (eCG; Syncrostim; CEVA Santé Animale) at PRID removal. At 10 d before mating start date (MSD), all cows that were ≥35 DIM were examined by transrectal ultrasound to assess presence or absence of a corpus luteum; body condition score (BCS) was also recorded. Pregnancy diagnosis was performed by transrectal ultrasonography 30 to 35 d after insemination. Overall pregnancy/AI (P/AI) was not different between groups (50.9, 49.8, and 46.3% for control, P4-Ovsynch, and P4-Ovsynch+eCG, respectively) but the 21-d pregnancy rate was increased by the use of synchronization (35.0, 51.7, and 47.2%, respectively). Compared with the control group, synchronization significantly reduced the interval from MSD to conception (34.6, 23.0, and 26.5 d, respectively) and consequently reduced the average days open (98.0, 86.0, and 89.0 d). Across all treatment groups, DIM at the start of synchronization affected P/AI (42.3, 49.5, and 53.9% for <60, 60-80, and >80 DIM, respectively), but neither parity (46.5, 50.4, and 48.4% for parity 1, 2, and ≥3, respectively) nor BCS (44.0, 49.4, and 58.6% for ≤2.50, 2.75-3.25, and ≥3.50, respectively) affected the likelihood of P/AI. Two-way interactions between treatment and DIM, parity, or BCS were not detected. In conclusion, the use of TAI accelerated pregnancy establishment in cows in a pasture-based system by reducing days open, but eCG administration at PRID removal did not affect P/AI.

Obstetricians and their role in cord blood banking: promoting a public model.

Umbilical cord blood, the blood remaining in the umbilical cord at birth, can be collected at birth and be a source of stem cells for a patient in need of a bone marrow transplant. Obstetricians and other health care practitioners are recognized as a patient's primary source for medical information affecting the mother and her neonate and frequently are asked to provide education and guidance regarding options of private and public cord blood banking. As the use of cord blood continues to grow in medicine and research uncovers more potential for cord blood, cord blood banking has become an important resource. The Stem Cell Therapeutic and Research Act has provided funding to expand public banking initiatives in the United States and to create a more ethnically diverse inventory of units. Private storage is not advocated unless there is an identified need in the family such that banked cord blood would offer a benefit. A recent report outlined the challenges of increasing participation and inventory, particularly among minority groups. Obstetricians and other health care practitioners should have a primary role in efforts to increase awareness of umbilical cord blood donation and be involved in initiatives to expand current public banking activities.

Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCF.

Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγ(null) (NSG) mice. Engraftment of human HSC requires preconditioning of immunodeficient recipients, usually with irradiation. Such preconditioning increases the expression of stem cell factor (SCF), which is critical for HSC engraftment, proliferation, and survival. We hypothesized that transgenic expression of human membrane-bound stem cell factor Tg(hu-mSCF)] would increase levels of human HSC engraftment in nonirradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45(+) cell chimerism were observed after transplantation of cord blood-derived human HSCs into nonirradiated adult as well as newborn NSG mice. However, transgenic expression of human mSCF enabled heightened levels of human hematopoietic cell chimerism in the absence of irradiation. Moreover, nonirradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSCs rejected human skin grafts from a histoincompatible donor, indicating the development of a functional human immune system. These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development.

Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice.

OBJECTIVE: To create an immunodeficient mouse model that spontaneously develops hyperglycemia to serve as a diabetic host for human islets and stem cell-derived beta-cells in the absence or presence of a functional human immune system. RESEARCH DESIGN AND METHODS: We backcrossed the Ins2(Akita) mutation onto the NOD-Rag1(null) IL2rgamma(null) strain and determined 1) the spontaneous development of hyperglycemia, 2) the ability of human islets, mouse islets, and dissociated mouse islet cells to restore euglycemia, 3) the generation of a human immune system following engraftment of human hematopoietic stem cells, and 4) the ability of the humanized mice to reject human islet allografts. RESULTS: We confirmed the defects in innate and adaptive immunity and the spontaneous development of hyperglycemia conferred by the IL2rgamma(null), Rag1(null), and Ins2(Akita) genes in NOD-Rag1(null) IL2rgamma(null) Ins2(Akita) (NRG-Akita) mice. Mouse and human islets restored NRG-Akita mice to normoglycemia. Insulin-positive cells in dissociated mouse islets, required to restore euglycemia in chemically diabetic NOD-scid IL2rgamma(null) and spontaneously diabetic NRG-Akita mice, were quantified following transplantation via the intrapancreatic and subrenal routes. Engraftment of human hematopoietic stem cells in newborn NRG-Akita and NRG mice resulted in equivalent human immune system development in a normoglycemic or chronically hyperglycemic environment, with >50% of engrafted NRG-Akita mice capable of rejecting human islet allografts. CONCLUSIONS: NRG-Akita mice provide a model system for validation of the function of human islets and human adult stem cell, embryonic stem cell, or induced pluripotent stem cell-derived beta-cells in the absence or presence of an alloreactive human immune system.

Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation.

"Humanized" mouse models created by engraftment of immunodeficient mice with human hematolymphoid cells or tissues are an emerging technology with broad appeal across multiple biomedical disciplines. However, investigators wishing to utilize humanized mice with engrafted functional human immune systems are faced with a myriad of variables to consider. In this study, we analyze HSC engraftment methodologies using three immunodeficient mouse strains harboring the IL2rgamma(null) mutation; NOD-scid IL2rgamma(null), NOD-Rag1(null) IL2rgamma(null), and BALB/c-Rag1(null) IL2rgamma(null) mice. Strategies compared engraftment of human HSC derived from umbilical cord blood following intravenous injection into adult mice and intracardiac and intrahepatic injection into newborn mice. We observed that newborn recipients exhibited enhanced engraftment as compared to adult recipients. Irrespective of the protocol or age of recipient, both immunodeficient NOD strains support enhanced hematopoietic cell engraftment as compared to the BALB/c strain. Our data define key parameters for establishing humanized mouse models to study human immunity.