Publications by authors named "Kjersti M Aagaard"

97 Publications

Complex species and strain ecology of the vaginal microbiome from pregnancy to postpartum and association with preterm birth.

Med (N Y) 2021 Sep 1;2(9):1027-1049. Epub 2021 Jul 1.

Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX, United States.

Background: was described as a keystone bacterial taxon in the human vagina over 100 years ago. Using metagenomics, we and others have characterized lactobacilli and other vaginal taxa across health and disease states, including pregnancy. While shifts in community membership have been resolved at the genus/species level, strain dynamics remain poorly characterized.

Methods: We performed a metagenomic analysis of the complex ecology of the vaginal econiche during and after pregnancy in a large U.S. based longitudinal cohort of women who were initially sampled in the third trimester of pregnancy, then validated key findings in a second cohort of women initially sampled in the second trimester of pregnancy.

Findings: First, we resolved microbial species and strains, interrogated their co-occurrence patterns, and probed the relationship between keystone species and preterm birth outcomes. Second, to determine the role of human heredity in shaping vaginal microbial ecology in relation to preterm birth, we performed a mtDNA-bacterial species association analysis. Finally, we explored the clinical utility of metagenomics in detection and co-occurrence patterns for the pathobiont Group B (causative bacterium of invasive neonatal sepsis).

Conclusions: Our highly refined resolutions of the vaginal ecology during and post-pregnancy provide insights into not only structural and functional community dynamics, but highlight the capacity of metagenomics to reveal finer aspects of the vaginal microbial ecologic framework.

Funding: NIH-NINR R01NR014792, NIH-NICHD R01HD091731, NIH National Children's Study Formative Research, Burroughs Wellcome Fund Preterm Birth Initiative, March of Dimes Preterm Birth Research Initiative, NIH-NIGMS (K12GM084897, T32GM007330, T32GM088129).
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http://dx.doi.org/10.1016/j.medj.2021.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491999PMC
September 2021

Antenatal corticosteroids in COVID-19 perspective.

World J Exp Med 2021 Sep 20;11(4):37-43. Epub 2021 Sep 20.

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Texas Children's Hospital, Baylor College Medicine, Houston, TX 77030, United States.

The aim of this manuscript is to discuss the practice of antenatal corticosteroids administration for fetal maturation in severe acute respiratory syndrome coronavirus 2 positive pregnant women. Recent high-quality evidence supports the use of dexamethasone in the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Randomized disease outcome data have identified an association between disease stage and treatment outcome. In contrast to patients with more severe forms who benefit from dexamethasone, patients with mild disease do not appear to improve and may even be harmed by this treatment. Therefore, indiscriminate usage of fluorinated corticosteroids for fetal maturation, regardless of disease trajectory, is unadvisable. Obstetrical care needs to be adjusted during the COVID-19 pandemic with careful attention paid to candidate selection and risk stratification.
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http://dx.doi.org/10.5493/wjem.v11.i4.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462011PMC
September 2021

Society for Maternal-Fetal Medicine Special Statement: Beyond the scalpel: in utero fetal gene therapy and curative medicine.

Am J Obstet Gynecol 2021 Dec 17;225(6):B9-B18. Epub 2021 Sep 17.

Society for Maternal-Fetal Medicine, 409 12 St. SW, Washington, DC 20024, USA.

With the recent advances in gene editing with systems such as CRISPR-Cas9, precise genome editing in utero is on the horizon. Sickle cell disease is an excellent candidate for in utero fetal gene therapy, because the disease is monogenic, causes irreversible harm, and has life-limiting morbidity. Gene therapy has recently been proven to be effective in an adolescent patient. Several hurdles still impede the progress for fetal gene therapy in humans, including an incomplete understanding of the fetal immune system, unclear maternal immune responses to in utero gene therapy, risks of off-target effects from gene editing, gestational age constraints, and ethical questions surrounding fetal genetic intervention. However, none of these barriers appears insurmountable, and the journey to in utero gene therapy for sickle cell disease and other conditions should be well underway.
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http://dx.doi.org/10.1016/j.ajog.2021.09.001DOI Listing
December 2021

Society for Maternal-Fetal Medicine Special Statement: COVID-19 research in pregnancy: progress and potential.

Am J Obstet Gynecol 2021 12 3;225(6):B19-B31. Epub 2021 Sep 3.

Society for Maternal-Fetal Medicine, 409 12 St. SW, Washington, DC 20024, USA.

The COVID-19 global pandemic has broad implications for obstetrical care and perinatal outcomes. As we approach the 2-year mark into an unprecedented international pandemic, this review presents the progress and opportunities for research related to COVID-19 and pregnancy. Research is the basis for evidence-based clinical guidelines, and we aim to provide the structure and guidance for framing COVID-19-related obstetrical research. This structure will pertain not only to this pandemic but future ones as well.
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http://dx.doi.org/10.1016/j.ajog.2021.08.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413099PMC
December 2021

YouTube as a Source of Patient Information Regarding Placenta Accreta Spectrum.

Am J Perinatol 2021 Jul 29. Epub 2021 Jul 29.

Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

Objective:  As the awareness of the accompanying morbidity of placenta accreta spectrum (PAS) has increased over recent decades. We sought to analyze the precision and reliability of the currently available content regarding PAS on YouTube.

Study Design:  A YouTube search was performed on June 17, 2019 by using the search terms "placenta accreta," "PAS," and "invasive placentation." Search results were sorted by relevance, and up to 200 videos per search term were systematically evaluated by four independent reviewers. A quality assessment checklist relating to aspects of PAS was developed with a Likert's scale from 0 to 12 points to quantify video content. Videos were classified as poor educational quality (grade 0 to ≤4), moderate quality (grade >4-8), and high quality (grade >8-12).

Results:  Of the 318 videos identified, 99 videos met inclusion criteria. The majority of videos (61.6%) were produced by a professional source, that is, appearing to be from a hospital, university, or educational service. Of the remaining videos, 16.2% were classified as personal, that is, posted from personal YouTube accounts and depicting a personal or family member experience, and 22.2% were classified as other. The majority of the "other" category consisted of news segments and short clips from talk shows. Overall, 60.6% of videos were of poor educational quality, 32.3% were of moderate quality, and 7.1% were deemed high quality. All seven of the high-quality videos were produced by a professional source and intended for an audience of medical professionals. There were neither high-quality videos intended for the general public nor the likely affected and relevant patient population.

Conclusion:  This study suggests that the currently available videos on YouTube regarding PAS are poor educational sources for patients seeking information, and demonstrates a need for high-quality content videos produced by medical professionals specifically focused on meeting the needs of patient population.

Key Points: · Awareness of the accompanying morbidity of placenta accreta spectrum has increased over recent decades.. · YouTube videos are poor educational sources for patients seeking information regarding PAS.. · YouTube videos and all social media warrant improvements regarding patient's information..
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http://dx.doi.org/10.1055/s-0041-1732453DOI Listing
July 2021

Prenatal Diethylstilbestrol Exposure and Cancer Risk in Males.

Cancer Epidemiol Biomarkers Prev 2021 Oct 16;30(10):1826-1833. Epub 2021 Jul 16.

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Background: The influence of prenatal diethylstilbestrol (DES) exposure on cancer incidence among middle-aged men has not been well-characterized. We investigated whether exposure to DES before birth impacts overall cancer risk, and risk of site-specific cancers.

Methods: Men (mean age in 2016 = 62.0 years) who were or were not prenatally DES exposed were identified between 1953 and 1994 and followed for cancer primarily via questionnaire approximately every 5 years between 1994 and 2016. The overall and site-specific cancer rates of the two groups were compared using Poisson regression and proportional hazards modeling with adjustment for age.

Results: DES exposure was not associated with either overall cancer [hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.77-1.15] or total prostate cancer rates (HR, 0.95; 95% CI, 0.68-1.33), but was inversely associated with urinary tract cancer incidence (HR, 0.48; 95% CI, 0.23-1.00).

Conclusions: There was no increase in either overall or prostate cancer rates among men prenatally DES exposed relative to those unexposed. An unexpected risk reduction was observed for urinary system cancers among the exposed relative to those unexposed. These findings suggest that prenatal DES exposure is unlikely to be an important contributor to cancer development in middle-aged men.

Impact: The results of this study could lend reassurance to middle-aged men who were prenatally DES exposed that their exposure does not adversely influence their overall cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492497PMC
October 2021

Western-style diet consumption impairs maternal insulin sensitivity and glucose metabolism during pregnancy in a Japanese macaque model.

Sci Rep 2021 06 21;11(1):12977. Epub 2021 Jun 21.

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.

The prevalence of maternal obesity is increasing in the United States. Offspring born to women with obesity or poor glycemic control have greater odds of becoming obese and developing metabolic disease later in life. Our group has utilized a macaque model to study the metabolic effects of consumption of a calorically-dense, Western-style diet (WSD; 36.3% fat) during pregnancy. Here, our objective was to characterize the effects of WSD and obesity, alone and together, on maternal glucose tolerance and insulin levels in dams during each pregnancy. Recognizing the collinearity of maternal measures, we adjusted for confounding factors including maternal age and parity. Based on intravenous glucose tolerance tests, dams consuming a WSD showed lower glucose area under the curve during first study pregnancies despite increased body fat percentage and increased insulin area under the curve. However, with (1) prolonged WSD feeding, (2) multiple diet switches, and/or (3) increasing age and parity, WSD was associated with increasingly higher insulin levels during glucose tolerance testing, indicative of insulin resistance. Our results suggest that prolonged or recurrent calorically-dense WSD and/or increased parity, rather than obesity per se, drive excess insulin resistance and metabolic dysfunction. These observations in a highly relevant species are likely of clinical and public health importance given the comparative ease of maternal dietary modifications relative to the low likelihood of successfully reversing obesity in the course of any given pregnancy.
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http://dx.doi.org/10.1038/s41598-021-92464-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217225PMC
June 2021

Dysregulation in Sphingolipid Signaling Pathways is Associated With Symptoms and Functional Connectivity of Pain Processing Brain Regions in Provoked Vestibulodynia.

J Pain 2021 May 23. Epub 2021 May 23.

G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California; Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California, Los Angeles, California.

Provoked vestibulodynia (PVD) is a chronic pain disorder characterized by local hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Despite decades of study, the lack of identified biomarkers has slowed the development of effective therapies. The primary aim of this study was to use metabolomics to identify novel biochemical mechanisms in vagina and blood underlying brain biomarkers and symptoms in PVD, thereby closing this knowledge gap. Using a cross-sectional case-control observational study design, untargeted and unbiased metabolomic profiling of vaginal fluid and plasma was performed in women with PVD compared to healthy controls. In women with PVD, we also obtained assessments of vulvar pain, vestibular and vaginal muscle tenderness, and 24-hour symptom intensity alongside resting-state brain functional connectivity of brain regions involved in pain processing and modulation. Compared to healthy controls, women with PVD demonstrated differences primarily in vaginal (but not plasma) concentrations of metabolites of the sphingolipid signaling pathways, suggesting localized effects in vagina and vulvar vestibule rather than systemic effects. Our findings reveal that dysregulation of sphingolipid metabolism in PVD is associated with increased vulvar pain and muscle tenderness, sexual dysfunction, and decreased functional connectivity strength in pain processing/modulatory brain regions. This data collectively suggests that alterations in sphingolipid signaling pathways are likely an important molecular biomarker in PVD that could lead to new targets for therapeutic intervention. PERSPECTIVE: This manuscript presents the results of a robust, unbiased molecular assessment of plasma and vaginal fluid samples in women with provoked vestibulodynia compared to healthy controls. The findings suggest that alterations in sphingolipid signaling pathways are associated with symptoms and brain biomarkers and may be an important molecular marker that could provide new targets for therapeutic intervention.
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http://dx.doi.org/10.1016/j.jpain.2021.04.017DOI Listing
May 2021

SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain.

Am J Perinatol 2021 May 3. Epub 2021 May 3.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.

Objective:  Obesity in pregnancy bears unique maternal and fetal risks. Obesity has also been associated with chronic inflammation, including elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher serum lipopolysaccharide (LPS) levels have been implicated in driving this inflammation, a phenomenon called metabolic endotoxemia (ME). GLP-2, a proglucagon-derived peptide, is believed to be integral in maintaining the integrity of the intestine in the face of LPS-mediated endotoxemia. We hypothesized that obesity and/or excess weight gain in pregnancy would be associated with an increase in maternal and neonatal markers of ME, as well as GLP-2.

Study Design:  Paired maternal and neonatal (cord blood) serum samples ( = 159) were obtained from our pregnancy biobank repository. Serum levels of LPS, endotoxin core antibody-immunoglobulin M (EndoCAb-IgM), and GLP-2 were measured by ELISA. IL-6 and TNF-α were measured using a Milliplex assay. Results were stratified by maternal body mass index (BMI), maternal diabetes, and gestational weight gain (GWG).

Results:  Maternal IL-6 is significantly decreased in the obese, diabetic cohort compared with the nonobese, nondiabetic cohorts (95.28 vs. 99.48 pg/mL,  = 0.047), whereas GLP-2 is significantly increased (1.92 vs. 2.89 ng/mL,  = 0.026). Neonatal TNF-α is significantly decreased in the obese cohort compared with the nonobese cohort (12.43 vs. 13.93 pg/mL,  = 0.044). Maternal GLP-2 is significantly increased in women with excess GWG compared with those with normal GWG (2.27 vs. 1.48 ng/mL,  = 0.014). We further found that neonatal IL-6 and TNF-α are negatively correlated with maternal BMI (-0.186,  = 0.036 and -0.179,  = 0.044, respectively) and that maternal and neonatal IL-6 showed a positive correlation (0.348,  < 0.001).

Conclusion:  Although we observed altered levels of markers of inflammation (IL-6 and TNF-α) with maternal obesity and diabetes, no changes in LPS or endoCAb-IgM were observed. We hypothesize that the increased GLP-2 levels in maternal serum in association with excess GWG may protect against ME in pregnancy.

Key Points: · Maternal serum levels of GLP-2, a proglucagon-derived peptide, are increased in obese, diabetic gravidae.. · Maternal serum GLP-2 levels are also increased in association with excess gestational weight gain compared with normal gestational weight gain.. · GLP-2 may be increased in association with obesity and weight gain to protect against metabolic endotoxemia in pregnancy..
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http://dx.doi.org/10.1055/s-0041-1728828DOI Listing
May 2021

SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission.

Genome Res 2021 04 18;31(4):635-644. Epub 2021 Feb 18.

Department of Computer Science, Rice University, Houston, Texas 77005, USA.

The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 lineages that have spread throughout the world. In this study, we investigated 129 RNA-seq data sets and 6928 consensus genomes to contrast the intra-host and inter-host diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights intra-host single nucleotide variant (iSNV) and SNP similarity, albeit with differences in C > U changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of insertions and deletions contribute to the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.
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http://dx.doi.org/10.1101/gr.268961.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015855PMC
April 2021

The timing of aspirin administration in pregnancy is important to prevent preeclampsia.

Am J Obstet Gynecol MFM 2021 05 18;3(3):100314. Epub 2021 Jan 18.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX; Department of Molecular and Human Genetics, Department of Molecular and Cell Biology, Baylor College of Medicine, 1 Baylor Plaza, Jesse H. Jones Hall, Room 314C, Houston, TX 77030. Electronic address:

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http://dx.doi.org/10.1016/j.ajogmf.2021.100314DOI Listing
May 2021

Low-dose aspirin for preeclampsia prevention: efficacy by ethnicity and race.

Am J Obstet Gynecol MFM 2020 11 21;2(4):100184. Epub 2020 Jul 21.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX. Electronic address:

Background: Low-dose aspirin is recommended for the prevention of preeclampsia among women at a high risk of developing the disease. Aspirin undergoes polymorphic metabolism, and it is well known that common genetic polymorphisms are related to aspirin intolerance. We hypothesized that the efficacy of aspirin prophylaxis may differ by ethnicity and race.

Objective: This study aimed to compare the rates of preeclampsia among low- and high-risk women who received aspirin compared with placebo, stratifying results by ethnicity and race as a first-pass approximation of genomic polymorphisms.

Study Design: This is a secondary analysis of 2 randomized controlled trials previously performed by the Maternal-Fetal Medicine Units Network: the Low-Risk Aspirin trial and the High-Risk Aspirin trial. For the Low-Risk Aspirin trial, normotensive, nulliparous women were enrolled between 13 and 26 weeks' gestation and randomized to 60 mg aspirin daily or placebo. For the High-Risk Aspirin trial, women with pregestational insulin-treated diabetes mellitus, chronic hypertension, multiple gestations, or a history of preeclampsia in a previous pregnancy were enrolled between 13 and 26 weeks' gestation and randomized to 60 mg aspirin daily or placebo. The primary outcome of our secondary analysis was preeclampsia. Secondary outcomes included gestational age at delivery, preterm delivery, placental abruption, small for gestational age, stillbirth, and neonatal death. Outcomes were stratified by ethnicity and race (Hispanic, non-Hispanic white, non-Hispanic black, or other).

Results: In the Low-Risk Aspirin trial of 3135 women, the risk of preeclampsia was significantly reduced among non-Hispanic white women who received aspirin compared with non-Hispanic white women who received placebo (relative risk, 0.19; 95% confidence interval, 0.06-0.63; P=.007). The risk of preeclampsia was not different when comparing the aspirin and placebo groups among the Hispanic, non-Hispanic black, or other ethnicity and race groups. The efficacy among non-Hispanic white women persisted after consideration of compliance and gestational age at randomization (relative risk, 0.07; 95% confidence interval, 0.009-0.51; P=.009). As noted in the original trial, there was an increased risk of placental abruption in the aspirin group overall compared with placebo (P=.025). The risk of stillbirth was significantly increased among non-Hispanic black women who received aspirin compared with non-Hispanic black women who received placebo (P=.048). In the High-Risk Aspirin trial of 2539 women, 269 were Hispanic (10.6%), 832 were non-Hispanic white (32.8%), 1426 were non-Hispanic black (56.2%), and 12 were categorized as other (0.5%). Stratification by ethnicity and race did not reveal a decreased incidence of preeclampsia for any of the subgroups (P>.05). Moreover, there was no significant difference in other measured outcomes including preterm delivery at <37 weeks' gestation, placental abruption, small for gestational age, stillbirth, or neonatal death.

Conclusion: The incidence of preeclampsia was significantly reduced among low-risk non-Hispanic white women who received aspirin compared with placebo (P=.007), but not overall or among Hispanic or non-Hispanic black women. The analysis of high-risk women did not indicate a difference in the efficacy of aspirin by ethnicity and race.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100184DOI Listing
November 2020

Maternal diet alters human milk oligosaccharide composition with implications for the milk metagenome.

Sci Rep 2020 12 16;10(1):22092. Epub 2020 Dec 16.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, One Baylor Plaza, Jones 314, Houston, TX, 77030, USA.

Human milk is the optimal nutrition source for infants, and oligosaccharides represent the third most abundant component in milk after lactose and fat. Human milk oligosaccharides (HMO) are favorable macromolecules which are, interestingly, indigestible by the infant but serve as substrates for bacteria. Hypothesizing that the maternal diet itself might influence HMO composition, we sought to directly determine the effect maternal diet on HMO and the milk bacteria. Employing a human cross-over study design, we demonstrate that distinct maternal dietary carbohydrate and energy sources preferentially alter milk concentrations of HMO, including fucosylated species. We find significant associations between the concentration of HMO-bound fucose and the abundance of fucosidase (a bacterial gene that digests fucose moieties) harbored by milk bacteria. These studies reveal a successive mechanism by which the maternal diet during lactation alters milk HMO composition, which in turn shapes the functional milk microbiome prior to infant ingestion.
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http://dx.doi.org/10.1038/s41598-020-79022-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745035PMC
December 2020

Interactions between Environmental Exposures and the Microbiome: Implications for Fetal Programming.

Curr Opin Endocr Metab Res 2020 Aug 3;13:39-48. Epub 2020 Oct 3.

Baylor College of Medicine, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Departments of Molecular & Human Genetics, Molecular & Cell Biology, and Molecular Physiology & Biophysics, 1 Baylor Plaza, Houston, TX 77030.

Decades of population-based health outcomes data highlight the importance of understanding how environmental exposures in pregnancy affect maternal and neonatal outcomes. Animal model research and epidemiological studies have revealed that such exposures are able to alter fetal programming through stable changes in the epigenome, including altered DNA methylation patterns and histone modifications in the developing fetus and infant. It is similarly known that while microbes can biotransform environmental chemicals via conjugation and de-conjugation, specific exposures can also alter the community profile and function of the human microbiome. In this review, we consider how alterations to the maternal and or fetal/infant microbiome through environmental exposures could directly and indirectly alter fetal programming. We highlight two specific environmental exposures, cadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs), and outline their effects on the developing fetus and the perinatal (maternal and fetal/infant) microbiome. We further consider how chemical exposures in the setting of natural disasters may be of particular importance to environmental health.
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http://dx.doi.org/10.1016/j.coemr.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716732PMC
August 2020

Perinatal COVID-19 outcomes: evaluating the strength of current evidence.

J Matern Fetal Neonatal Med 2020 Nov 29:1-7. Epub 2020 Nov 29.

Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.

Viral respiratory diseases, like those caused by novel strains of influenza and Coronaviridae, have historically disproportionately affected pregnant women and conferred increased risk of adverse perinatal outcomes. Initial reports published from Wuhan, China identified only limited symptoms in pregnant women and no cases of mortality, but more recent reports from other regions of the world have reported contrasting information. The purpose of the study was to evaluate initially published cases of SARS-CoV-2 infection in pregnant women in China and compare them to subsequently published studies from the remainder of the world. This review curates 199 maternal published cases of SARS-CoV-2 infection and COVID-19 initially reported in the literature from China and contrasts them to more recent literature reporting clinical findings and outcomes of 729 selected cases from the rest of the world, including the United States. Overall, initial case reports and series from China reported no cases of maternal mortality, which contrasts with subsequent reports from other regions of the world demonstrating significant morbidity and mortality can and does occur in pregnant women infected with SARS-CoV-2. While initial reports suggest limited risks of infection in pregnancy with SARS-CoV-2, subsequent findings have demonstrated pregnant women are at risk for severe morbidity and mortality. Case studies and series that are imperative in the early stages of a pandemic to provide data on a novel pathogen cannot be used to provide generalizable information predicting group risks.
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http://dx.doi.org/10.1080/14767058.2020.1849101DOI Listing
November 2020

Prenatal diethylstilbestrol exposure and risk of diabetes, gallbladder disease, and pancreatic disorders and malignancies.

J Dev Orig Health Dis 2021 08 28;12(4):619-626. Epub 2020 Oct 28.

Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6-51 and HR = 7.0, 95% CI 1.5-33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88-1.5) or diabetes (HR = 1.1, 95% CI 0.9-1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84-20) or general population (SIR: 1.9, 95% CI 1.0-3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.
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http://dx.doi.org/10.1017/S2040174420000872DOI Listing
August 2021

Identifying the Transcriptional Response of Cancer and Inflammation-Related Genes in Lung Cells in Relation to Ambient Air Chemical Mixtures in Houston, Texas.

Environ Sci Technol 2020 11 16;54(21):13807-13816. Epub 2020 Oct 16.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

Atmospheric pollution represents a complex mixture of air chemicals that continually interact and transform, making it difficult to accurately evaluate associated toxicity responses representative of real-world exposure. This study leveraged data from a previously published article and reevaluated lung cell transcriptional response induced by outdoor atmospheric pollution mixtures using field-based exposure conditions in the industrialized Houston Ship Channel. The tested hypothesis was that individual and co-occurring chemicals in the atmosphere relate to altered expression of critical genes involved in inflammation and cancer-related processes in lung cells. Human lung cells were exposed at an air-liquid interface to ambient air mixtures for 4 h, with experiments replicated across 5 days. Real-time monitoring of primary and secondary gas-phase pollutants, as well as other atmospheric conditions, was simultaneously conducted. Transcriptional analysis of exposed cells identified critical genes showing differential expression associated with both individual and chemical mixtures. The individual pollutant identified with the largest amount of associated transcriptional response was benzene. Tumor necrosis factor () and interferon regulatory factor 1 () were identified as key upstream transcription factor regulators of the cellular response to benzene. This study is among the first to measure lung cell transcriptional responses in relation to real-world, gas-phase air mixtures.
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http://dx.doi.org/10.1021/acs.est.0c02250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757424PMC
November 2020

Pregnancy and Lactation in a 67-Year-Old Elderly Gravida following Donor Oocyte Fertilization.

Case Rep Obstet Gynecol 2020 12;2020:9801565. Epub 2020 Sep 12.

Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX, USA.

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum course was uncomplicated, and she was able to successfully breastfeed for six months and resume prepregnancy activity. For comparison, we analyzed deliveries among gravidae > 45 years of age from our institutional obstetrical database (2011-2018). This case represents the eldest gravidae identified in the literature and illustrates the potential for a relatively uncomplicated perinatal course with successful lactation. This case may enable other providers to counsel elderly patients on anticipated outcomes inclusive of ability to breastfeed.
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http://dx.doi.org/10.1155/2020/9801565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509548PMC
September 2020

Neonatal mortality rates and association with antenatal corticosteroids at Kamuzu Central Hospital.

Early Hum Dev 2020 12 19;151:105158. Epub 2020 Aug 19.

Department of Pediatrics at Baylor College of Medicine, United States of America; Section of Neonatology at Texas Children's Hospital, United States of America.

Objective: Malawi has one of the highest child mortality rates in the world, and neonates account for nearly half of all under-five mortality. No previous study has reported neonatal outcomes in Malawi over 12 months. We aimed to evaluate outcomes in the neonatal intensive care unit (NICU) at Kamuzu Central Hospital (KCH) and to determine if there was an association between increased survival and antenatal corticosteroid (ACS) exposure.

Study Design: We introduced a prospective, observational electronic database to collect 122 de-identified variables related to neonatal outcomes for all neonates admitted to the KCH NICU over 12 months. Patients with congenital anomalies were excluded. We compared neonatal mortality rates in neonates who were exposed to ACS compared to those who were not. Statistical methodology included the Wilcoxon rank sum test, Fisher's exact test, and logistic regression.

Results: Of 2051 neonates admitted to the KCH NICU, the overall neonatal mortality rate was 23.1% and remained similar across 12 months. Mortality was inversely related to birth weight, and outborn neonates referred to KCH had the highest mortality rate (29%). After controlling for confounding covariates, inborn infants exposed to ACS had significantly lower odds of death compared to those without exposure to ACS (adjusted odds ratio = 0.46, 95% confidence interval: 0.24-0.88, p = 0.020).

Conclusion: Lower birth weight, outborn, and no ACS exposure were associated with increased mortality. ACS was associated with a 54% reduction in odds of mortality in inborn neonates highlighting the need for further evaluations of ACS use in resource-limited settings.
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http://dx.doi.org/10.1016/j.earlhumdev.2020.105158DOI Listing
December 2020

Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission.

bioRxiv 2020 Jul 2. Epub 2020 Jul 2.

Department of Computer Science, Rice University, Houston, TX, USA.

The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.
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http://dx.doi.org/10.1101/2020.07.02.184481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337385PMC
July 2020

In vitro fertilization as an independent risk factor for placenta accreta spectrum.

Am J Obstet Gynecol 2020 10 30;223(4):568.e1-568.e5. Epub 2020 Apr 30.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX. Electronic address:

Background: Placenta accreta spectrum is well known for its association with catastrophic maternal outcomes. However, its pathophysiology is not well defined. There have been emerging data that in vitro fertilization may be a risk factor for placenta accreta spectrum.

Objective: We investigated the hypothesis that in vitro fertilization is an independent risk factor for placenta accreta spectrum.

Study Design: A retrospective analysis of all deliveries in a prospective, population-based cohort (2012-2019) was performed in a tertiary academic center. Primary outcome variable was placenta accreta spectrum. Univariate analysis was performed on potential risk factors for predicting placenta accreta spectrum, and a multivariate model was designed to best fit the prediction of placenta accreta spectrum adjusted for risk factors such as cesarean delivery, placenta previa, age, and parity. History of previous cesarean delivery was known as a risk factor for both placenta previa and placenta accreta spectrum; hence, the interaction between "placenta previa" and "previous cesarean delivery" was included in the final model. Odds ratios were calculated as exponential of beta coefficients from the multivariate regression analysis.

Results: A total of 37,461 deliveries were included in this analysis, 5464 (15%) of which had a history of cesarean delivery, 281 (0.7%) had placenta previa in their index pregnancy, and 571 (1.5%) had in vitro fertilization pregnancy. The frequency of placenta accreta spectrum was 230 (0.6%). Independent risk factors for placenta accreta spectrum were in vitro fertilization pregnancy (adjusted odds ratio, 8.7; 95% confidence interval, 3.8-20.3), history of previous cesarean delivery (adjusted odds ratio, 21.1; 95% confidence interval, 11.4-39.2), and presence of placenta previa (adjusted odds ratio, 94.6; 95% confidence interval, 29.3-305.1). After adjustment for number of previous cesarean deliveries, the correlation persisted for in vitro fertilization (adjusted odds ratio, 6.7; 95% confidence interval, 2.9-15.6).

Conclusion: Our data suggested that in vitro fertilization is an independent risk factor for placenta accreta spectrum, although its relative clinical importance compared with that of the presence of placenta previa and history of cesarean delivery is small. The pathophysiology behind this relationship remains to be investigated.
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http://dx.doi.org/10.1016/j.ajog.2020.04.026DOI Listing
October 2020

Maternal Metabolic Biomarkers are Associated with Obesity and Excess Gestational Weight Gain.

Am J Perinatol 2021 08 31;38(S 01):e173-e181. Epub 2020 Mar 31.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.

Objective: The purpose of this study was to evaluate the independent contribution of maternal obesity and gestational weight gain (GWG) in excess of the Institute of Medicine's guidelines on levels of maternal serum inflammatory and metabolic measures.

Study Design: Banked maternal serum samples from 120 subjects with documented prepregnancy or first trimester body mass index (BMI) were utilized for analyte analyses. Validated, BMI-specific formulas were utilized to categorize GWG as either insufficient, at goal or excess based on the Institute of Medicine guidelines with gestational age adjustments. Serum was analyzed for known inflammatory or metabolic pathway intermediates using the Luminex xMap system with the MILLIPLEX Human Metabolic Hormone Magnetic Bead Panel. Measured analytes included interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α and metabolic markers amylin, c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, pancreatic polypeptide, and peptide YY. Kruskal-Wallis ANOVA and Pearson's correlation coefficients were calculated for each marker.

Results: C-peptide, insulin, and leptin all varied significantly with both obesity and GWG while glucagon-like peptide-1 varied by BMI but not GWG. These analytes covaried with other metabolic analytes, but not with inflammatory analytes.

Conclusion: Maternal metabolic biomarkers at delivery vary significantly with both obesity and GWG. Taken together, these findings suggest that GWG (with and without comorbid obesity) is an important mediator of measurable metabolites in pregnancy but is not necessarily accompanied by inflammatory measures in serum. These findings are consistent with GWG being an independent risk factor for metabolic disturbances during pregnancy.
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http://dx.doi.org/10.1055/s-0040-1708855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630982PMC
August 2021

Population-Based Estimation of the Preterm Birth Rate in Lilongwe, Malawi: Making Every Birth Count.

AJP Rep 2020 Jan 9;10(1):e78-e86. Epub 2020 Mar 9.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.

 The objective of this study was to perform a population-based estimation of the preterm birth (PTB) rate in regions surrounding Lilongwe, Malawi.  We partnered with obstetrician specialists, community health workers, local midwives, and clinicians in a 50 km region surrounding Lilongwe, Malawi, to perform a population-based estimation of the PTB rate during the study period from December 1, 2012 to May 19, 2015.  Of the 14,792 births captured, 19.3% of births were preterm, including preterm early neonatal deaths. Additional PTB risk factors were similarly prevalent including domestic violence, HIV, malaria, anemia, and malnutrition.  When performing a population-based estimation of the rate of PTB, including women without antenatal care and women delivering at home, the 19.3% rate of PTB is among the highest recorded globally. This is accompanied by a high rate of risk factors and comorbid conditions.
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http://dx.doi.org/10.1055/s-0040-1708491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062552PMC
January 2020

Turning the "Phage" on Malnutrition and Stunting.

Cell Host Microbe 2020 02;27(2):159-161

Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cell Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. Electronic address:

Bacteriophages shape bacterial ecosystems, including community membership and their metabolic function. In this issue of Cell Host & Microbe, Mirzaei et al. (2020) identify harbored bacteriophages among a Proteobacteria-dominant community unique to toddlers with stunted growth from Bangladesh, and that confer the capacity to similarly tailor microbiota profiles in vitro.
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http://dx.doi.org/10.1016/j.chom.2020.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387105PMC
February 2020

The impact of tobacco chemicals and nicotine on placental development.

Prenat Diagn 2020 08 11;40(9):1193-1200. Epub 2020 Feb 11.

Baylor College of Medicine, Department of Obstetrics and Gynecology, Houston, TX.

Despite decades of messages warning about the dangers of tobacco use in pregnancy, 10% to 15% of pregnant women continue to smoke. Furthermore, an increased popularity of electronic nicotine delivery systems (ENDS) over the past decade in women of childbearing age raises parallel concerns regarding the effects of vaporized nicotine use in pregnancy. While research using animal models which mimic tobacco smoke and nicotine exposure in pregnancy have largely replicated findings in humans, few studies focus directly on the effects of these exposures on the placenta. Because the placenta is a fetal derived tissue, and nicotine and other components of tobacco smoke are either processed by or transported directly through the placenta, such studies help us understand the risks of these exposures on the developing fetus. In this review, we summarize research on the placenta and placental-derived cells examining either tobacco smoke or nicotine exposure, including both histologic and subcellular (ie, epigenetic and molecular) modifications. Collectively, these studies reveal that tobacco and nicotine exposure are accompanied by some common and several unique molecular and epigenomic placental modifications. Consideration of the nature and sequelae of these molecular mediators of risk may help to better inform the public and more effectively curtail modifiable behavior.
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http://dx.doi.org/10.1002/pd.5660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396310PMC
August 2020

Mode of delivery and pondering potential sources of the neonatal microbiome.

EBioMedicine 2020 Jan 31;51:102554. Epub 2019 Dec 31.

Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, 1 Baylor Plaza, Houston, TX 77401, United States; Center for Microbiome and Metagenomics Research, 1 Baylor Plaza, Houston, TX 77401, United States; Molecular & Human Genetics, 1 Baylor Plaza, Houston, TX 77401, United States; Molecular & Cell Biology at Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77401, United States. Electronic address:

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http://dx.doi.org/10.1016/j.ebiom.2019.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940648PMC
January 2020

Population-Based Estimation of Dental Caries and Periodontal Disease Rates of Gravid and Recently Postpartum Women in Lilongwe, Malawi.

AJP Rep 2019 Jul 20;9(3):e268-e274. Epub 2019 Aug 20.

Department of Obstetrics and Gynecology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas.

 The objective of this study was to determine the rate of dental caries and periodontal disease among gravid and recently postpartum women at five delivery centers within and surrounding Lilongwe, Malawi.  We partnered with obstetric specialists, community health workers, and dentists to perform dental history interviews and dental examinations during the study period from December 2012 to May 2014. Dental examinations were performed according to World Health Organization standards to assess periodontal and oral health status.  Among the 387 gravid and recently postpartum women, the rate of dental caries was 69.3% and the rate of composite dental disease (caries and periodontal disease) was 76.7%. The majority (69.5%) of women examined had a decayed-missing-filled (DMF) index greater than or equal to one; the average DMF Index was 2.48. The majority of women had never seen a dentist (62.8%). However, most did perform oral hygiene, two or more times per day (90.2%); most women reported brushing with toothpaste (88.1%).  When assessing this population for dental caries and periodontal disease, the rate of dental disease was high. Therefore, this may be an ideal setting to test for impactful interventions aimed at reducing caries and periodontal disease.
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http://dx.doi.org/10.1055/s-0039-1695003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702028PMC
July 2019

The Development of the Human Microbiome: Why Moms Matter.

Gastroenterol Clin North Am 2019 09 2;48(3):357-375. Epub 2019 Jul 2.

Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine 1 Baylor Plaza, Houston, TX 77030, USA. Electronic address:

The human body is cohabitated with trillions of commensal bacteria that are essential for our health. However, certain bacteria can also cause diseases in the human host. Before the microbiome can be attributed to disease risk and pathogenesis, normal acquisition and development of the microbiome must be understood. Here, we explore the evidence surrounding in utero microbial exposures and the significant of this exposure in the proper development of the fetal and neonatal microbiome. We further explore the development of the fetal and neonatal microbiome and its relationship to preterm birth, feeding practices, and mode of delivery, and maternal diet.
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http://dx.doi.org/10.1016/j.gtc.2019.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261593PMC
September 2019

The Neonatal Microbiome and Metagenomics: What Do We Know and What Is the Future?

Neoreviews 2019 05;20(5):e258-e271

Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine.

The human microbiota includes the trillions of microorganisms living in the human body whereas the human microbiome includes the genes and gene products of this microbiota. Bacteria were historically largely considered to be pathogens that inevitably led to human disease. However, because of advances in both cultivation-based methods and the advent of metagenomics, bacteria are now recognized to be largely beneficial commensal organisms and thus, key to normal and healthy human development. This relatively new area of medical research has elucidated insights into diseases such as inflammatory bowel disease and obesity, as well as metabolic and atopic disorders. However, much remains unknown about the complexity of microbe-microbe and microbe-host interactions. Future efforts aimed at answering key questions pertaining to the early establishment of the microbiome, alongside what defines its dysbiosis, will likely lead to long-term health and mitigation of disease. Here, we review the relevant literature pertaining to modulations in the perinatal and neonatal microbiome, the impact of environmental and maternal factors in shaping the neonatal microbiome, and future questions and directions in the exciting emerging arena of metagenomic medicine.
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http://dx.doi.org/10.1542/neo.20-5-e258DOI Listing
May 2019

Association between elevated placental polycyclic aromatic hydrocarbons (PAHs) and PAH-DNA adducts from Superfund sites in Harris County, and increased risk of preterm birth (PTB).

Biochem Biophys Res Commun 2019 08 14;516(2):344-349. Epub 2019 Jun 14.

Section of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA. Electronic address:

The preterm birth (PTB) rate in Harris County, Texas, exceeds the U.S. rate (11.4% vs.9.6%), and there are 15 active Superfund sites in Harris County. Polycyclic aromatic hydrocarbons (PAHs) are contaminants of concern (COC) at Superfund sites across the nation. In this investigation, we tested the hypothesis that higher levels of exposure to PAHs and PAH-DNA adducts in placenta of women living near Superfund sites contribute to the increased rate of PTBs. Levels of benzo[a]pyene (BP), benzo[b]fluorene (BbF) and dibenz[a,h]anthracene (DBA), were higher in placentae from preterm deliveries compared with term deliveries in women living near Superfund sites, whereas this was not the case for women living in non-Superfund site areas. Among the PAHs, DBA levels were significantly higher than BP or BbF, and DBA levels were inversely correlated with gestational age at delivery and birth weight. Bulky PAH-DNA adducts are more prevalent in placental tissue from individuals residing near Superfund sites. Expression of Ah receptor (AHR) and NF-E2-related factor 2 (NRF2) was decreased in preterm deliveries in subjects residing near Superfund sites. Unbiased metabolomics revealed alterations in pathways involved in pentose phosphate, inositol phosphate and starch and sucrose metabolism in preterm subjects in Superfund site areas. In summary, this is the first report showing an association between PAH levels, DNA adducts, and modulation of endogenous metabolic pathways with PTBs in subjects residing near Superfund sites, and further studies could lead to novel strategies in the understanding of the mechanisms by which PAHs contribute to PTBs in women.
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http://dx.doi.org/10.1016/j.bbrc.2019.06.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637943PMC
August 2019
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