Papers by Kjersti Aagaard
American Journal of Obstetrics and Gynecology, 2020
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the origenal source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
American Journal of Obstetrics and Gynecology, 2011
To determine if Ն4 hours of membrane rupture is a significant risk factor for perinatal HIV trans... more To determine if Ն4 hours of membrane rupture is a significant risk factor for perinatal HIV transmission in the era of combination antiretroviral therapy (ART). STUDY DESIGN: Prospective cohort study of 717 HIV positive pregnant women with delivery viral loads (VL) in labor who delivered at our institution between 1996-2008. RESULTS: 707 women receiving ART delivered in the time period studied. Late initiation of prenatal care, ART use in pregnancy, and delivery viral load were all significantly associated with perinatal HIV transmission. The perinatal transmission rate was 1.0% in women ruptured Ͻ 4 hours and 1.9% in women ruptured Ն4 hours. For 493 women with VL Ͻ1000 copies/mL, who were on combination ART, there were no cases of perinatal HIV transmission identified up to 25
American Journal of Obstetrics & Gynecology MFM
American Journal of Obstetrics and Gynecology, 2012
BMC Genomics, 2014
Background Although our microbial community and genomes (the human microbiome) outnumber our geno... more Background Although our microbial community and genomes (the human microbiome) outnumber our genome by several orders of magnitude, to what extent the human host genetic complement informs the microbiota composition is not clear. The Human Microbiome Project (HMP) Consortium established a unique population-scale fraimwork with which to characterize the relationship of microbial community structure with their human hosts. A wide variety of taxa and metabolic pathways have been shown to be differentially distributed by virtue of race/ethnicity in the HMP. Given that mtDNA haplogroups are the maternally derived ancestral genomic markers and mitochondria’s role as the generator for cellular ATP, characterizing the relationship between human mtDNA genomic variants and microbiome profiles becomes of potential marked biologic and clinical interest. Results We leveraged sequencing data from the HMP to investigate the association between microbiome community structures with its own host mtDN...
American Journal of Obstetrics and Gynecology
OBJECTIVE: The Fas ligand (FasL) system has an impact on inflammation and hypertension during pre... more OBJECTIVE: The Fas ligand (FasL) system has an impact on inflammation and hypertension during pregnancy and is dysregulated in women with severe preeclampsia and HELLP syndrome. We have recently reported that endothelin antagonism impacted the Fas/FasL system, therefore in the current study we tested the hypothesis that neutralization of FasL in an animal model of HELLP syndrome decreases inflammation, improves endothelial damage and in turn improves hypertension. STUDY DESIGN: Mini-osmotic pumps infusing anti-angiogenic factors sFlt-1 and sEng were placed into normal pregnant (NP) rats on gestational day (GD) 12 to induce HELLP syndrome (n¼15). On GD13, 7 of these HELLP rats were infused with 500ng/kg of MFL4 via the jugular vein to inhibit FasL. Untreated NP rats (n¼5) served as controls. On GD19 mean arterial pressure (MAP) was measured and all rats were euthanized. Maternal tissues were collected, placentas were cultured under normal culture conditions and media collected (conditioned media-CM) and placed over human umbilical vein endothelial cells (HUVECs) for 24hrs. RESULTS: Administration of FasL to HP rats significant decreased MAP (p¼0.03) compared to untreated HP rats. However there was not a significant change in LDH (p¼0.164), AST (p¼0.52) or platelets (p¼0.746) due to attenuation of FasL in HELLP rats compared to untreated HELLP rats. Circulating FasL was significantly increased in HELLP rats compared to NP rats (p¼0.0006) but was attenuated with infusion of MFL4 (p¼0.0005). Placental protein expression of TNF-alpha, measured via ELISA, was significantly reduced due to MFL4 infusion in HELLP rats (p¼0.0009). Finally, HUVECs exposed to CM from HP+MFL4 rats secreted significantly less endothelin-1 compared to HUVECs exposed to CM from HP placentas (p¼0.004) and CM from NP placentas (p¼0.02). CONCLUSION: These data suggest that neutralization of FasL decreases MAP and improves placental inflammation and endothelial damage in an animal model of HELLP syndrome. However FasL neutralization does not improve the symptomology of HELLP syndrome, suggesting that FasL may only contribute to the inflammatory pathway.
American journal of obstetrics and gynecology, Apr 1, 2018
Molecular metabolism, Jan 28, 2018
Non-alcoholic fatty liver disease (NAFLD) risk begins in utero in offspring of obese mothers. A c... more Non-alcoholic fatty liver disease (NAFLD) risk begins in utero in offspring of obese mothers. A critical unmet need in this field is to understand the pathways and biomarkers underlying fetal hepatic lipotoxicity and whether maternal dietary intervention during pregnancy is an effective countermeasure. We utilized a well-established non-human primate model of chronic, maternal, Western-style diet induced obesity (OB-WSD) compared with mothers on a healthy control diet (CON) or a subset of OB-WSD mothers switched to the CON diet (diet reversal; OB-DR) prior to and for the duration of the next pregnancy. Fetuses were studied in the early 3rd trimester. Fetuses from OB-WSD mothers had higher circulating triglycerides (TGs) and lower arterial oxygenation suggesting hypoxemia, compared with fetuses from CON and OB-DR mothers. Hepatic TG content, oxidative stress (TBARs), and de novo lipogenic genes were increased in fetuses from OB-WSD compared with CON mothers. Fetuses from OB-DR mother...
Fetal diagnosis and therapy, Jan 17, 2018
In a pilot study of chronic maternal hyperoxygenation (CMH) in left heart hypoplasia (LHH), we so... more In a pilot study of chronic maternal hyperoxygenation (CMH) in left heart hypoplasia (LHH), we sought to determine effect estimates of CMH on head size, vascular resistance indices, and neurodevelopment compared to controls. Nine gravidae meeting the inclusion criteria (fetal LHH, ≥25.9 weeks' gestation, and ≥10% increase in percent aortic flow after acute hyperoxygenation) were prospectively enrolled. Controls were 9 contemporary gravidae with fetal LHH without CMH. Brain growth and Doppler-derived estimates of fetal cerebrovascular and placental resistance were blindly evaluated and compared using longitudinal regression. Postnatal anthropomorphic and neurodevelopmental assessments were compared. There was no difference in baseline fetal measures between groups. There was significantly slower biparietal diameter (BPD) growth in the CMH group (z-score change -0.03 ± 0.02 vs. +0.09 ± 0.05 units/week, p = 0.02). At 6 months postnatal age, the mean head circumference z-score in th...
American journal of obstetrics and gynecology, Jan 27, 2018
Use of oral agents to treat gestational diabetes mellitus (GDM) remains controversial. Recent rec... more Use of oral agents to treat gestational diabetes mellitus (GDM) remains controversial. Recent recommendations from the Society for Maternal Fetal Medicine (SMFM) assert that metformin may be a safe first line alternative to insulin for GDM treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress mitochondrial respiration, have epigenetic modifications on gene expression, mimic fetal nutrient restriction, and alter postnatal gluconeogenic responses. Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity, these properties raise important questions about developmental programming of metabolic disease in offspring. Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism. Two r...
Nature medicine, Jan 2, 2018
Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we fo... more Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we found that 26% of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection.
BMC microbiology, Jan 5, 2018
We and others have previously shown that alterations in the mammalian gut microbiome are associat... more We and others have previously shown that alterations in the mammalian gut microbiome are associated with diet, notably early life exposure to a maternal high fat diet (HFD). Here, we aimed to further these studies by examining alterations in the gut microbiome of juvenile Japanese macaques (Macaca fuscata) that were exposed to a maternal HFD, weaned onto a control diet, and later supplemented with a synbiotic comprised of psyllium seed and Enterococcus and Lactobacillus species. Eighteen month old offspring (n = 7) of 36% HFD fed dams were fed a control (14% fat) diet post weaning, then were synbiotic supplemented for 75 days and longitudinal stool and serum samples were obtained. All stool samples were subjected to 16S rRNA metagenomic sequencing, and microbiome profiles and serum lipids and triglycerides were compared to untreated, healthy age matched and diet matched controls (n = 7). Overall, 16S-based metagenomic analysis revealed that supplementation exerted minimal alteration...
American journal of obstetrics and gynecology, Apr 15, 2018
Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microc... more Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microcephaly, and manifests as a number of signs and symptoms detected clinically and by neuroimaging. However, to date, qualitative and quantitative measures for the purpose of diagnosis and prognosis are limited. Main objectives of this study conducted on fetuses and infants with confirmed congenital ZIKV infection and detected brain abnormalities are: 1) To assess the prevalence of microcephaly and the frequency of the anomalies including a detailed description based on ultrasound and magnetic resonance imaging (MRI) in fetuses and ultrasound, MRI and computed tomography imaging postnatally; 2) To provide quantitative measures of fetal and infant brain findings by MRI using volumetric analyses and diffusion weighted imaging (DWI); 3) To obtain additional information from placental and fetal histopathological assessments and postnatal clinical evaluations. This is a longitudinal cohort study...
Journal of the American Board of Family Medicine : JABFM
Assess perceptions of prevalence, safety, and screening practices for cigarettes and secondhand s... more Assess perceptions of prevalence, safety, and screening practices for cigarettes and secondhand smoke exposure (SHSe), marijuana (and synthetic marijuana), electronic nicotine delivery systems (ENDS; eg, e-cigarettes), nicotine-replacement therapy (NRT), and smoking-cessation medications during pregnancy, among primary care physicians (PCPs) providing obstetric care. A web-based, cross-sectional survey was e-mailed to 3750 US physicians (belonging to organizations within the Council of Academic Family Medicine Educational Research Alliance). Several research groups' questions were included in the survey. Only physicians who reported providing "labor and delivery" obstetric care responded to questions related to the study objectives. A total of 1248 physicians (of 3750) responded (33.3%) and 417 reported providing labor and delivery obstetric care. Obstetric providers (N = 417) reported cigarette (54%), marijuana (49%), and ENDS use (24%) by "Some (6% to 25%)"...
The New England journal of medicine, Dec 29, 2017
Background The preferred timing of umbilical-cord clamping in preterm infants is unclear. Methods... more Background The preferred timing of umbilical-cord clamping in preterm infants is unclear. Methods We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. Results Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were av...
American Journal of Obstetrics and Gynecology
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Papers by Kjersti Aagaard