First name
Michal
Middle name
A
Last name
Elovitz

Title

Associations of public water system trihalomethane exposure during pregnancy with spontaneous preterm birth and the cervicovaginal microbial-immune state.

Year of Publication

2021

Number of Pages

111288

Date Published

2021 May 06

ISSN Number

1096-0953

Abstract

<p><strong>BACKGROUND: </strong>Water total trihalomethanes (TTHMs) are disinfectant byproducts found in municipal water supplies. TTHM exposure has been linked to cancer and may be associated with adverse reproductive outcomes. A non-optimal cervicovaginal microbiota and low cervicovaginal beta-defensin-2 levels are associated with increased risk of spontaneous preterm birth. Whether TTHM exposure increases the risk of spontaneous preterm birth or alters the cervicovaginal microbial or immune state is unknown.</p>

<p><strong>OBJECTIVE: </strong>Investigate associations of water TTHM levels with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and beta-defensin-2 levels in a completed, diverse, urban pregnancy cohort. We hypothesized that higher TTHM levels would be associated with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and lower beta-defensin-2 levels.</p>

<p><strong>DESIGN: </strong>/Methods: This was a secondary analysis of participants (n=474) in the Motherhood &amp; Microbiome (M&amp;M) study (n=2000), who lived in Philadelphia and had cervicovaginal samples analyzed for cervicovaginal microbiota composition and beta-defensin-2 levels. The microbiota was classified into community state types (CSTs). CST IV (non-optimal microbiota) is characterized by a paucity of Lactobacillus species and wide array of anaerobes. Municipal water TTHM levels were obtained from 16 sites monthly across the city of Philadelphia to establish mean residential water supply levels for each participant for the first four months of pregnancy (prior to vaginal swab collection at 16-20 weeks' gestation). Associations of water TTHM levels with spontaneous preterm birth and a non-optimal cervicovaginal microbiota birth were analyzed using multivariable logistic regression. Multivariable linear regression was used to model associations of water TTHM levels with log-transformed cervicovaginal beta-defensin-2 levels. Since water TTHM levels vary by season and Beta-defensin-2 levels have been shown to differ by race, stratified models by warm (April-September) and cold (October-March) seasons as well as by self-identified race were utilized.</p>

<p><strong>RESULTS: </strong>Participants' water supply TTHM levels (mean μg/L [SD]) were higher in the warm (53.5 [9.4]) than cold (33.4 [7.5]) season (p&lt;0.0001). TTHM levels were non-significantly higher among Black participants than non-Black participants (44.8[13.5] vs. 41.8[11.8], p=0.07). No associations were detected between TTHM with spontaneous preterm birth (per SD increment of TTHM, aOR 0.94, 95%CI: 0.66, 1.34) or with CST IV (aOR 0.94, 95%CI: 0.86, 1.16). Counter to our hypothesis, we observed positive associations of water TTHM with log-transformed cervicovaginal beta-defensin-2 levels in unadjusted models (β 0.20 [95%CI: 0.02, 0.39)] per SD increment of TTHM), but the association was null after adjustment for season. However, in models adjusted for covariates including season and stratified by race, TTHM was significantly associated with lower beta-defensin-2 levels among non-Black participants (β -0.75 [95%CI: -1.43, -0.08]) but not among Black participants (β 0.17 [95%CI: -0.15, 0.49]), interaction p=0.013).</p>

<p><strong>CONCLUSION: </strong>We did not detect associations of water TTHM levels with spontaneous preterm birth or the structure of the cervicovaginal microbiota. However, the finding of a significant interaction between TTHM and race on beta-defensin-2 levels suggest that environmental exposures may contribute to differences in reproductive tract innate immune function by race. Future studies to delineate environmental contributions to the cervicovaginal microbial-immune state, a potentially important biologic underpinning for preterm birth, are warranted.</p>

DOI

10.1016/j.envres.2021.111288

Alternate Title

Environ Res

PMID

33965388

Title

Effect of a Nonoptimal Cervicovaginal Microbiota and Psychosocial Stress on Recurrent Spontaneous Preterm Birth.

Year of Publication

2020

Date Published

2020 Oct 08

ISSN Number

1098-8785

Abstract

<p><strong>OBJECTIVE: </strong> While select cervicovaginal microbiota and psychosocial factors have been associated with spontaneous preterm birth, their effect on the risk of recurrence remains unclear. It is also unknown whether psychosocial factors amplify underlying biologic risk. This study sought to determine the effect of nonoptimal cervicovaginal microbiota and perceived stress on the risk of recurrent spontaneous preterm birth.</p>

<p><strong>STUDY DESIGN: </strong> This was a secondary analysis of a prospective pregnancy cohort, . The Cohen's Perceived Stress Scale (PSS-14) was administered and cervical swabs were obtained between 16 and 20 weeks of gestation. PSS-14 scores ≥30 reflected high perceived stress. We analyzed cervicovaginal microbiota using 16S rRNA sequencing and classified microbial communities into community state types (CSTs). CST IV is a nonoptimal cervicovaginal microbial community characterized by anaerobes and a lack of . The final cohort included a predominantly non-Hispanic Black population of women with prior spontaneous preterm birth who had recurrent spontaneous preterm birth or term birth and had stress measurements ( = 181). A subanalysis was performed in the subset of these women with cervicovaginal microbiota data ( = 74). Multivariable logistic regression modeled adjusted associations between CST IV and recurrent spontaneous preterm birth, high stress and recurrent spontaneous preterm birth, as well as high stress and CST IV.</p>

<p><strong>RESULTS: </strong> Among the 181 women with prior spontaneous preterm birth, 45 (24.9%) had high perceived stress. We did not detect a significant association between high stress and recurrent spontaneous preterm birth (adjusted odds ratio [aOR] 1.67, 95% confidence interval [CI]: 0.73-3.85). Among the 74 women with prior spontaneous preterm birth and cervicovaginal microbiota analyzed, 29 (39.2%) had CST IV; this proportion differed significantly among women with recurrent spontaneous preterm birth (51.4%) compared with women with term birth (28.2%) ( = 0.04). In models adjusted for race and marital status, the association between CST IV and recurrent spontaneous preterm birth persisted (aOR 3.58, 95% CI: 1.25-10.24). There was no significant interaction between stress and CST IV on the odds of spontaneous preterm birth ( = 0.328). When both stress and CST IV were introduced into the model, their associations with recurrent spontaneous preterm birth were slightly stronger than when they were in the model alone. The aOR for stress with recurrent spontaneous preterm birth was 2.02 (95% CI: 0.61-6.71) and for CST IV the aOR was 3.83 (95% CI: 1.30-11.33). Compared to women with neither of the two exposures, women with both high stress and CST IV had the highest odds of recurrent spontaneous preterm birth (aOR = 6.01, 95% CI: 1.002-36.03).</p>

<p><strong>CONCLUSION: </strong> Among a predominantly non-Hispanic Black cohort of women with a prior spontaneous preterm birth, a nonoptimal cervicovaginal microbiota is associated with increased odds of recurrent spontaneous preterm birth. Adjustment for perceived stress may amplify associations between CST IV and recurrent spontaneous preterm birth. Identification of modifiable social or behavioral factors may unveil novel nonpharmacologic interventions to decrease recurrent spontaneous preterm birth among women with underlying biologic risk.</p>

<p><strong>KEY POINTS: </strong>· CST IV, a nonoptimal microbiota, is associated with increased odds of recurrent spontaneous preterm birth.. · Adjustment for perceived stress amplified associations between CST IV and recurrent spontaneous preterm birth.. · Identification of modifiable psychosocial factors may unveil novel nonpharmacologic interventions to decrease recurrent preterm birth..</p>

DOI

10.1055/s-0040-1717098

Alternate Title

Am J Perinatol

PMID

33032329

Title

Neighborhood Violent Crime and Perceived Stress in Pregnancy.

Year of Publication

2020

Date Published

2020 Aug 03

ISSN Number

1660-4601

Abstract

<p>Stress has been shown to adversely affect pregnancy outcomes. Neighborhood crime rates may serve as one publicly available social determinant of health for pregnancy studies that use registry or electronic health record datasets in which individual-level stress data are not available. We sought to determine whether neighborhood violent crime incidents were associated with measured perceived stress in a largely minority, urban pregnancy cohort. We performed a secondary analysis of the 1309 Philadelphia residents participating in the cohort ( = 2000) with both neighborhood violent crime and Cohen's Perceived Stress Scale (PSS-14) data. Generalized linear mixed models accounting for confounding variables and geographic clustering demonstrated that, regardless of race, women with the highest quartile of neighborhood violent crime had significantly elevated odds of high stress compared to women with lower crime. We also found that Black women were more likely to have both the highest quartile of neighborhood violent crime and high stress than non-Black women. Overall, this study demonstrates that neighborhood violent crime is associated with perceived stress in pregnancy. Given disparate exposure to crime and prenatal stress by race, future work is warranted to determine whether urban neighborhood violence and/or stress reduction strategies would improve birth outcome racial disparities.</p>

DOI

10.3390/ijerph17155585

Alternate Title

Int J Environ Res Public Health

PMID

32756321

Title

SARS-CoV-2 seroprevalence among parturient women in Philadelphia.

Year of Publication

2020

Date Published

2020 Jul 29

ISSN Number

2470-9468

Abstract

<p>Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important for determining SARS-CoV-2 exposures within both individuals and populations. We validated a SARS-CoV-2 spike receptor binding domain serological test using 834 pre-pandemic samples and 31 samples from COVID-19 recovered donors. We then completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate exposure to SARS-CoV-2 within the community.</p>

DOI

10.1126/sciimmunol.abd5709

Alternate Title

Sci Immunol

PMID

32727884

Title

SARS-CoV-2 Seroprevalence Among Parturient Women.

Year of Publication

2020

Date Published

2020 Jul 10

Abstract

<p>Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ~1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.</p>

DOI

10.1101/2020.07.08.20149179

Alternate Title

medRxiv

PMID

32676623

Title

The stepwise assembly of the neonatal virome is modulated by breastfeeding.

Year of Publication

2020

Number of Pages

470-474

Date Published

2020 May

ISSN Number

1476-4687

Abstract

<p>The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which-in some cases-leads to gastrointestinal disorders. Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool samples shows few or no particles, but by one month of life particle numbers increase to 10 per gram, and these numbers seem to persist throughout life. We investigated the origin of these viral populations using shotgun metagenomic sequencing of virus-enriched preparations and whole microbial communities, followed by targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut and by one month prophages induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies who were exclusively fed on&nbsp;formula milk compared with those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections. Bacteriophage populations also differed depending on whether or not the infant was breastfed. We show that the colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells; this second phase is modulated by breastfeeding.</p>

DOI

10.1038/s41586-020-2192-1

Alternate Title

Nature

PMID

32461640

Title

Bacterial colonization reprograms the neonatal gut metabolome.

Year of Publication

2020

Date Published

2020 Apr 13

ISSN Number

2058-5276

Abstract

<p>Initial microbial colonization and later succession in the gut of human infants are linked to health and disease later in life. The timing of the appearance of the first gut microbiome, and the consequences for the early life metabolome, are just starting to be defined. Here, we evaluated the gut microbiome, proteome and metabolome in 88 African-American newborns using faecal samples collected in the first few days of life. Gut bacteria became detectable using molecular methods by 16 h after birth. Detailed analysis of the three most common species, Escherichia coli, Enterococcus faecalis and Bacteroides vulgatus, did not suggest a genomic signature for neonatal gut colonization. The appearance of bacteria was associated with reduced abundance of approximately 50 human proteins, decreased levels of free amino acids and an increase in products of bacterial fermentation, including acetate and succinate. Using flux balance modelling and in vitro experiments, we provide evidence that fermentation of amino acids provides a mechanism for the initial growth of E. coli, the most common early colonizer, under anaerobic conditions. These results provide a deep characterization of the first microbes in the human gut and show how the biochemical environment is altered by their appearance.</p>

DOI

10.1038/s41564-020-0694-0

Alternate Title

Nat Microbiol

PMID

32284564

Title

The promise and pitfalls of precision medicine to resolve black-white racial disparities in preterm birth.

Year of Publication

2019

Date Published

2019 Aug 05

ISSN Number

1530-0447

Abstract

<p>Differences in preterm birth rates between black and white women are the largest contributor to racial disparities in infant mortality. In today's age of precision medicine, analysis of the genome, epigenome, metabolome, and microbiome has generated interest in determining whether these biomarkers can help explain racial disparities. We propose that there are pitfalls as well as opportunities when using precision medicine analyses to interrogate disparities in health. To conclude that racial disparities in complex conditions are genetic in origin ignores robust evidence that social and environmental factors that track with race are major contributors to disparities. Biomarkers measured in omic assays that may be more environmentally responsive than genomics, such as the epigenome or metabolome, may be on the causal pathway of race and preterm birth, but omic observational studies suffer from the same limitations as traditional cohort studies. Confounding can lead to false conclusions about the causal relationship between omics and preterm birth. Methodological strategies (including stratification and causal mediation analyses) may help to ensure that associations between biomarkers and exposures, as well as between biomarkers and outcomes, are valid signals. These epidemiologic strategies present opportunities to assess whether precision medicine biomarkers can uncover biology underlying perinatal health disparities.</p>

DOI

10.1038/s41390-019-0528-z

Alternate Title

Pediatr. Res.

PMID

31382269

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