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Introduction Syndemic theory posits that poor health outcomes co-occur and amplify each other in the context of harmful conditions that must be addressed simultaneously to improve health equity. This analysis identifies perinatal syndemic factors and examine how factors are related to STI in a sample of racially diverse young pregnant women. Methods Pregnant participants (n = 61) ages 14–21 from racially diverse backgrounds were recruited from a prenatal clinic for an ongoing longitudinal study between October 2019-February 2020. Participants completed a tablet survey assessing pregnancy intention, psychosocial factors (e.g., depression, stress, partner violence, pregnancy history) and consented to provide access to their medical records for STI and clinical urine samples screened for tobacco and cannabis use. Latent class analysis (LCA) was used to examine probabilities of co-occurring Syndemic indicators. Results Half of the women were Black (52%) and primigravida (54%). Three classes were identified in the LCA, two of them reflecting syndemics related to STI from the medical record. The largest class was half Black (51%), with a high rate of STI (65%), and was characterized by factors including depressive symptoms (93%), stress (64%), and substance use (65% cannabis, 82% tobacco). Additionally, the class with the highest rates of STI (74%) also had higher rates of partner violence (48%), morning sickness (100%), and prenatal cannabis use (63%). Conclusion Findings indicate evidence of a syndemic related to increased STI. A longitudinal evaluation of syndemics in this cohort may inform appropriately tailored intervention strategies to promote perinatal health in racially diverse young pregnant populations.

Background Nearly 14% of US women report any lifetime infertility which is associated with healthcare costs and psychosocial consequences. Tubal factor infertility (TFI) often occurs as a result of sexually transmitted diseases and subsequent pelvic inflammatory disease. We sought to evaluate for and describe potential racial disparities in TFI and in vitro fertilization (IVF) prevalence. Methods Records of women aged 19-42 years in our retrospective cohort from two US infertility clinics were reviewed. We calculated TFI prevalence, IVF initiation prevalence, and prevalence ratios (PR), with 95% confidence intervals for each estimate, overall and by race. Results Among 660 infertile women, 110 (16.7%; 95% confidence interval [CI] 13.8-19.5%) had TFI which was higher in black compared to white women (30.3% [33/109] vs. 13.9% [68/489]; PR 2.2 [95% CI 1.5-3.1]). For women with TFI, IVF was offered to similar proportions of women by race (51.5% [17/33] versus 52.9% [36/68] for black versus white women); however, fewer black than white women with TFI started IVF (6.7% [1/15] versus 31.0% [9/29]; PR 0.2 [95% CI 0-1.0]), although the difference was not statistically different. Conclusions TFI prevalence was two-fold higher among black than white women seeking care for infertility. Among women with TFI, data suggested a lower likelihood of black women starting IVF than white women. Improved sexually transmitted disease prevention and treatment might ameliorate disparities in TFI.

Despite sexual minorities' (SMs) increased risk for contracting human papillomavirus (HPV) and developing related cancers compared to their heterosexual peers, we know little about SM disparities in uptake of HPV vaccines and routine screenings. Therefore, this study examined sexuality differences in HPV preventive interventions and related screenings. From 2015 to 2016, Pennsylvania's Allegheny County Health Department commissioned a health survey of 9,026 adults in their catchment area using probability-based sampling. Multivariable models tested differences by sexual identity separately for cisgender men and women (heterosexual versus gay/lesbian, bisexual, and other) for lifetime receipt of HPV vaccine and number of HPV vaccines. Among women, we examined sexuality differences in HPV and cervical Pap tests, adjusting for age, race/ethnicity, education, marital status, and income. No differences in prevention utilization emerged when comparing heterosexual women to all SM women. However, exploratory analyses comparing heterosexual women to subgroups of SM women found lesbians had higher odds (adjusted odds ratio [AOR] = 5.27; 95% confidence interval [CI] = 1.15–24.09) of never receiving an HPV vaccine. Women who reported their sexuality as “other” had higher odds (AOR = 5.65; 95% CI = 1.03–31.02) of never receiving a cervical Pap test compared to heterosexual women. “Other” women had higher odds (AOR = 19.80; 95% CI = 1.64–239.16) of never receiving a cervical Pap test when compared to heterosexual women receiving one within the recommended screening guidelines. SM men's utilization was not significantly different from heterosexual men, though vaccination uptake for both groups was low. These findings highlight the need for additional public health surveillance to understand cancer prevention utilization among this underserved population.

Background Chlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap. Methods We identified infertility genome-wide association study (GWAS) loci using deoxyribonucleic acid from Ct-seropositive cisgender women in a tubal factor infertility study and Ct-infected cisgender women from a longitudinal pelvic inflammatory disease cohort with known fertility status. Deoxyribonucleic acid and blood messenger ribonucleic acid from 2 additional female cohorts with active Ct infection and known endometrial infection status were used to investigate the impact of infertility single-nucleotide polymorphisms (SNPs) on Ct ascension. A statistical mediation test examined whether multiple infertility SNPs jointly influenced ascension risk by modulating expression of mediator genes. Results We identified 112 candidate infertility GWAS loci, and 31 associated with Ct ascension. The SNPs altered chlamydial ascension by modulating expression of 40 mediator genes. Mediator genes identified are involved in innate immune responses including type I interferon production, T-cell function, fibrosis, female reproductive tract health, and protein synthesis and degradation. Conclusions We identified Ct-related infertility loci and their potential functional effects on Ct ascension.

Per- and polyfluoroalkyl substances (PFAS) have been found to be associated with gestational diabetes mellitus (GDM) development, a maternal health disorder in pregnancy with negative effects that can extend beyond pregnancy. Studies that report on this association are difficult to summarize due to weak associations and wide confidence intervals. One way to advance this field is to sharpen the biologic theory on a causal pathway behind this association, and to measure it directly by way of molecular biomarkers. The aim of this review is to summarize the literature that supports a novel pathway between PFAS exposure and GDM development. Epidemiological studies demonstrate a clear association of biomarkers of thyroid hormones and glucose metabolism with GDM development. We report biologic plausibility and epidemiologic evidence that PFAS dysregulation of maternal thyroid hormones and thyrotropin (TSH) may disrupt glucose homeostasis, increasing the risk of GDM. Overall, epidemiological studies demonstrate that PFAS were positively associated with TSH and negatively with triiodothyronine (T3) and thyroxine (T4). PFAS were generally positively associated with glucose and insulin levels in pregnancy. We propose dysregulation of thyroid function and glucose metabolism may be a critical and missing component in the accurate estimation of PFAS on the risk of GDM. Supplementary Information The online version contains supplementary material available at 10.1186/s12940-021-00740-z.

BackgroundChlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3 enhanced serological (Pgp3) assay.MethodsIn our case-control study of women 19–42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in two U.S. infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios (aOR) with 95% confidence intervals (CI) stratified by race. We then estimated the adjusted chlamydia population attributable fraction (aPAF) with 95% CI of TFI.ResultsAll black (n=107) and 618 of 620 non-black women had Pgp3 results. Pgp3 seropositivity was 25.9% (19.3–33.8%) for non-black cases, 15.2% (12.3–18.7%) for non-black controls, 66.0% (95% CI 51.7–77.8%) for black cases, and 71.7% (59.2–81.5%) for black controls. Among 476 non-black women without endometriosis (n=476), Pgp3 was associated with TFI (aOR 2.6 [1.5– 4.4]), adjusting for clinic, age, and income; chlamydia TFI aPAF was 19.8% (95% CI 7.7–32.2%) in these women. Pgp3 positivity was not associated with TFI among non-black women with endometriosis nor among black women (regardless of endometriosis).ConclusionsAmong non-black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in black women.

Background Caesarean section delivery is increasing worldwide and in India, yet little is known about the effect on infants. We examined the association between caesarean delivery and adverse infant outcomes in an Indian national survey, accounting for factors related to the mode of delivery. Methods Inverse probability weighted logistic regression analysis of the 2015–2016 India National Family Health Survey obtained adjusted ORs (aORs) and 95% CIs. Infant outcomes were maternal report of recent concomitant diarrhoea and acute respiratory infection (ARI) in infants age ≤6 mo and neonatal death. Results Of the 189 143 reported most recent singleton births, 15.4% were delivered by caesarean, 860 (3.2%) of all infants age ≤6 mo had concomitant diarrhoea and ARI and 3480 (1.8%) neonatal deaths were reported. In adjusted analysis, caesarean delivery was not associated with concomitant diarrhoea and ARI (aOR 0.96 [95% CI 0.71 to 1.32]) but was associated with neonatal death (aOR 1.19 [95% CI 1.02 to 1.39]). Conclusions Using nationally representative cross-sectional data for India, caesarean section delivery was found to be associated with neonatal death after accounting for factors associated with the mode of delivery. Prospective exploration of the relationship between caesarean delivery and adverse infant outcomes is warranted.

Pelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have been isolated from the genital tract of people with PID: sexually transmitted organisms such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis; bacterial vaginosis (BV)-associated species and genera such as Atopobium vaginae, Sneathia, and Megasphaera; and genera and species usually associated with the gastrointestinal or respiratory tracts such as Bacteroides, Escherichia coli, Streptococcus, or Haemophilus influenza. Although PID is often considered to be synonymous with gonorrhea or chlamydia, these pathogens are found in only one quarter to one third of people with PID, suggesting that broader screening and diagnostic and treatment strategies need to be considered to reduce the burden of PID and its associated sequelae.

In a vaginal 16S ribosomal RNA gene quantitative PCR study of 17 pelvic inflammatory disease (PID) cases and 17 controls who tested positive for Chlamydia trachomatis, women who additionally tested positive for Atopobium vaginae, Sneathia spp., BVAB-TM7, Megasphaera spp., Eggerthella-like bacterium or Mobiluncus spp. were more likely to develop PID.

Background and aims Atherosclerosis is a chronic inflammatory disease, and recent studies have shown that infection at remote sites can contribute to the progression of atherosclerosis in hyperlipidemic mouse models. In this report, we tested the hypothesis that genital Chlamydia infection could accelerate the onset and progression of atherosclerosis. Methods Apolipoprotein E (Apoe−/−) and LDL receptor knockout (Ldlr−/−) mice on a high-fat diet were infected intra-vaginally with Chlamydia muridarum. Atherosclerotic lesions on the aortic sinuses and in the descending aorta were assessed at 8-weeks post-infection. Systemic, macrophage, and vascular site inflammatory responses were assessed and quantified. Results Compared to the uninfected groups, infected Apoe−/− and Ldlr−/− mice developed significantly more atherosclerotic lesions in the aortic sinus and in the descending aorta. Increased lesions were associated with higher circulating levels of serum amyloid A-1, IL-1β, TNF-α, and increased VCAM-1 expression in the aortic sinus, suggesting an association with inflammatory responses observed during C. muridarum infection. Genital infection courses were similar in Apoe−/−, Ldlr−/−, and wild type mice. Further, Apoe−/− mice developed severe uterine pathology with increased dilatations. Apoe-deficiency also augmented cytokine/chemokine response in C. muridarum infected macrophages, suggesting that the difference in macrophage response could have contributed to the genital pathology in Apoe−/− mice. Conclusions Overall, these studies demonstrate that genital Chlamydia infection exacerbates atherosclerotic lesions in hyperlipidemic mouse and suggest a novel role for Apoe in full recovery of uterine anatomy after chlamydial infection.

Background: Spontaneous abortion (SAB) is a common early pregnancy complication globally, impacting 15% of clinically recognized pregnancies. The biological pathways leading to SAB are not clearly understood, although early SAB is often attributed to chromosomal abnormalities. Elevated blood pressure (BP) in women of reproductive age predicts cardiovascular disease later in life, but less clear is whether elevated BP during preconception and/or early pregnancy BP elevations can affect prenatal outcomes. Hypothesis: Elevated BP during preconception and the first trimester will be positively associated with SAB. Methods: We conducted a secondary analysis of data collected from 577 primiparous women (15-35 years) who participated in the Longitudinal Indian Family hEalth (LIFE) prospective pregnancy cohort study in Telangana State, India. Resting blood pressure was measured by trained technicians using a standardized study protocol at a preconception registration visit and in the first trimester. Odds ratio (OR) and 95% confidence intervals (CI) of any SAB ( Results: Preconception measurements were assessed at the first study visit, conducted at registration and within a mean±SD of 11±12 months prior to pregnancy. Higher than optimal preconception BP (120/80 mmHg) was not associated with SAB (OR adj 0.82 (95% CI 0.51, 1.32)). In contrast, first trimester elevated BP was associated with a two-fold increased likelihood of SAB, although results were of borderline significance (OR adj 2.12 (95%CI 0.87, 5.14). In addition, we observed an association between elevated first trimester BP and late SAB (OR adj 2.32 (95%CI 0.95, 5.68)); there were no associations between elevated preconception or first trimester BP and early SAB. Conclusions: We found that elevated first trimester but not preconception BP was associated with an increased risk of pregnancy loss, suggesting that dysregulated adaption to pregnancy may impact pregnancy loss more than preconception BP status, especially SABs that occur after 8 weeks gestation. Our findings support the notion that clinical and environmental factors may have a greater impact on later SABs as opposed to earlier losses. The null relationship with early pregnancy loss in our study may be due to an expected genetic mutation etiology for those losses. Studies exploring the trajectory of preconception and prenatal blood pressure changes and impact on pregnancy outcomes are warranted.

Consanguineous marriage (CM) has been linked to spontaneous abortion (SAB), although studies have largely been cross-sectional and likely underestimated early loss. We aimed to determine the relationships between CM and SAB in a prospective pregnancy cohort study in Telangana State, India. Data from 661 participants aged 15–35 years in the Longitudinal Indian Family hEalth (LIFE) study actively followed for pregnancy and pregnancy loss were analyzed. SAB was classified as early (

ObjectiveA small percentage of universities and colleges conduct mass SARS-CoV-2 testing. However, universal testing is resource-intensive, strains national testing capacity, and false negative tests can encourage unsafe behaviors.ParticipantsA large urban university campus.MethodsVirus control centered on three pillars: mitigation, containment, and communication, with testing of symptomatic and a random subset of asymptomatic students.ResultsRandom surveillance testing demonstrated a prevalence among asymptomatic students of 0.4% throughout the term. There were two surges in cases that were contained by enhanced mitigation and communication combined with targeted testing. Cumulative cases totaled 445 for the term, most resulting from unsafe undergraduate student behavior and among students living off-campus. A case rate of 232/10,000 undergraduates equaled or surpassed several peer institutions that conducted mass testing.ConclusionsAn emphasis on behavioral mitigation and communication can control virus transmission on a large urban campus combined with a limited and targeted testing strategy.

OBJECTIVE: Small studies suggest that fetal sex alters maternal inflammation. We examined the association between fetal sex, preeclampsia and circulating maternal immune markers. METHODS: This was a secondary data analysis within a nested case-control study of 216 preeclamptic women and 432 randomly selected normotensive controls from the Collaborative Perinatal Project. All women had singleton, primiparous pregnancies without chronic health conditions. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between female fetal sex and preeclampsia. Outcomes included preeclampsia, preterm preeclampsia (

ObjectiveTo ascertain the prevalence of Trichomonas vaginalis and investigate associations between trichomoniasis, endometritis and sequelae among women with pelvic inflammatory disease (PID).MethodsWe assessed the prevalence of trichomoniasis identified via wet mount and its association with histologically confirmed endometritis, infertility and recurrent PID among 647 women in the PID Evaluation and Clinical Health (PEACH) study. Participants were treated for clinically suspected PID and followed for a mean of 84 months for incident sequelae. Analyses were adjusted for age, race, Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and bacterial vaginosis. Additional adjustments were incorporated for history of infertility (models of pregnancy and infertility), history of PID (recurrent PID), and self-reported partner treatment and intercourse between baseline and 30-day follow-up (persistent endometritis).ResultsT. vaginalis was present in the vagina of 12.8% of women. The odds of having endometritis at baseline were twice as high among women with trichomoniasis as compared with those without (adjusted OR (AOR): 1.9, 95% CI 1.0 to 3.3). Persistent endometritis was highly prevalent at 30 days (52.1%) and more common among women with baseline trichomoniasis (AOR: 2.6, 95% CI 0.7 to 10.1), although non-significantly. Infertility and recurrent PID were more common among women with trichomoniasis, while rates of pregnancy and live birth were lower.ConclusionsT. vaginalis was frequently isolated from the vagina of women with PID in the PEACH cohort. Wet mount microscopy for the identification of motile trichomonads was standard practice at the time of the PEACH study, but likely resulted in an underestimation of true T. vaginalis prevalence. Our findings of modest, although non-significant, prospective associations between trichomoniasis and sequelae are novel and underscore the need for additional investigation into whether T. vaginalis may play an aetiological role in adverse reproductive and gynaecological outcomes.

BACKGROUND Ideal management of sexually transmitted infections (STI) may require risk markers for pathology or vaccine development. Previously, we identified common genetic variants associated with chlamydial pelvic inflammatory disease (PID) and reduced fecundity. As this explains only a proportion of the long-term morbidity risk, we used whole-exome sequencing to identify biological pathways that may be associated with STI-related infertility. METHODS We obtained stored DNA from 43 non-Hispanic black women with PID from the PID Evaluation and Clinical Health Study. Infertility was assessed at a mean of 84 months. Principal component analysis revealed no population stratification. Potential covariates did not significantly differ between groups. Sequencing kernel association test was used to examine associations between aggregates of variants on a single gene and infertility. The results from the sequencing kernel association test were used to choose "focus genes" (P < 0.01; n = 150) for subsequent Ingenuity Pathway Analysis to identify "gene sets" that are enriched in biologically relevant pathways. RESULTS Pathway analysis revealed that focus genes were enriched in canonical pathways including, IL-1 signaling, P2Y purinergic receptor signaling, and bone morphogenic protein signaling. CONCLUSIONS Focus genes were enriched in pathways that impact innate and adaptive immunity, protein kinase A activity, cellular growth, and DNA repair. These may alter host resistance or immunopathology after infection. Targeted sequencing of biological pathways identified in this study may provide insight into STI-related infertility.

Archived vaginal samples are frequently used in ancillary research projects, yet few studies have validated their use for nucleic acid amplification analysis after long-term storage. This study sought to examine the suitability of vaginal swab samples for Chlamydia trachomatis transcription-mediated amplification analysis after up to 20 years of biobank storage. Replication testing was conducted using a subset of vaginal swab samples originally obtained between May 1999 and June 2001 using …

ObjectivesWe sought to determine whether the relationship between a history of vaginal douching and pelvic inflammatory disease (PID) is mediated by endometrial infection with one or more novel bacterial vaginosis (BV)-associated organisms among Atopobium vaginae, the BV-associated bacterium 1 (BVAB1), neathia (Leptotrichia) amnionii and Sneathia sanguinegens.MethodsWe first conducted log-binomial regression analyses to identify risk factors for endometrial infection in 535 adolescent and adult women with clinically suspected PID in the PID Evaluation and Clinical Health (PEACH) study. We then examined whether endometrial infection by the BV-associated organisms mediated the association between a history of vaginal douching and histologically confirmed PID using inverse probability weighted marginal structural models.ResultsVaginal douching was significantly associated with endometrial infection with one or more of the targeted BV-associated organisms (relative risk (RR) 1.21, 95% CI: 1.08 to 1.35). The total effect estimate suggested that vaginal douching increased the risk of endometritis by 24% (RR 1.24, 95% CI: 1.03 to 1.49). The controlled direct effect of this association was attenuated with endometrial infection by one or more BV-associated organisms (adjusted RR (aRR) 1.00, 95% CI: 0.57 to 1.74) and endometrial infection by all four BV-associated organisms (aRR 0.95, 95% CI: 0.53 to 1.70) as intermediate variables.ConclusionsEndometrial infection with one or more of the novel BV-associated organisms partially mediated the relationship between vaginal douching and histologically confirmed endometritis in the PEACH study. Frequent vaginal douching may confer risk for endometritis through increasing the risk of endometrial infection by novel-BV-associated organisms. Other potential pathways should be explored.

Background Preterm birth (PTB) is common worldwide and causes significant neonatal morbidity. Although ascending reproductive tract infection has been implicated in approximately half of spontaneous PTB cases, the microbiologic etiology remains poorly understood and no studies have examined the role of preconception vaginal microbiota in PTB. Methods We conducted a pilot study comparing bacterial communities among 6 women who experienced a PTB Results Cases had more sequence reads from Sneathia spp., Megasphaera spp., and Atopobium vaginae than controls. Overall, the vaginal microbiota of cases was more diverse than those from controls. Women who delivered at term generally had vaginal microbiota dominated by Lactobacillus spp. Conclusion Our study suggests key differences in preconception vaginal bacterial communities between women who experience a PTB compared to women who deliver at term. Future large scale epidemiologic studies of preconception and prenatal vaginal microbiota and adverse pregnancy outcomes are warranted and may guide PTB interventions. Disclosure No significant relationships.

We sought to identify factors associated with mode of delivery in a peri-urban Indian population with a high cesarean section rate. Poisson regression with robust error variance was applied to model factors associated with cesarean compared to vaginal delivery in a prospective, preconception pregnancy cohort study in Telangana State, India. Adjusted relative risks and 95% confidence intervals from multivariable models are presented. Among 1164 singleton births between 2010 and 2015, 46% were delivered by cesarean. In multiparous women (n = 674), prior cesarean delivery (4.2, 3.2–5.6), prior twin delivery (1.4, 1.1–1.9), diagnosis of hypertension (1.4, 1.0–2.0), or preeclampsia (3.5, 2.1–5.7) in a prior pregnancy independently increased the risk of cesarean. Prepregnancy overweight/obesity (1.4, 1.0–1.9), a composite of prenatal complications (1.3, 1.0–1.7), a composite of labor complications (1.5, 1.0–2.3), nonreassuring fetal heart rate (2.3, 1.3–4.1), and breech position (2.6, 1.4–5.0) also increased the cesarean risk. Among nulliparous women (n = 233), cephalo–pelvic disproportion (1.9, 1.2–3.0), a composite of labor complications (2.9, 1.8–4.9), and breech position (3.4, 1.9–6.2) increased the risk of cesarean. The high rate of cesarean delivery in this peri-urban Indian population is attributed to history of pregnancy complications, history of prior cesarean, prepregnancy body mass index, and medical indications at delivery.

CONTEXT: Intimate partner violence and reproductive coercion are associated with unintended pregnancies and STDs. Greater condom negotiation self-efficacy among young women may mediate these associations. METHODS: A sample of 841 female adolescents (aged 16-19) and 1,387 young adult women (aged 20-24) recruited from 24 family planning clinics in western Pennsylvania in 2011-2012 reported on intimate partner violence, reproductive coercion, condom negotiation self-efficacy and sexual health outcomes at baseline and four- and 12-month follow-ups. Mixed models were used to test associations of intimate partner violence and reproductive coercion with unintended pregnancy and STD diagnosis. The Sobel test of mediation was used to measure indirect effects of condom negotiation self-efficacy. RESULTS: At baseline, 15% of adolescents and 11% of young adults reported recent intimate partner violence victimization; 7% and 6%, respectively, reported recent reproductive coercion. For both age-groups, intimate partner violence and reproductive coercion were associated with a reduced level of condom negotiation self-efficacy (coefficients, -0.27 to -0.13) and increased odds of STD diagnosis (odds ratios, 1.03-1.1). However, only reproductive coercion was associated with unintended pregnancy (odds ratios, 1.1 for each group). The only association that condom negotiation self-efficacy mediated was between reproductive coercion and unintended pregnancy among young adults (17% of total effect). CONCLUSIONS: Targeting condom negotiation self-efficacy alone in abusive relationships would likely not translate into improved sexual health outcomes in this population. Other strategies are needed to prevent unintended pregnancy and STDs.Copyright © 2016 by the Guttmacher Institute. Language: en

Objectives To determine if mid-pregnancy circulating immune biomarkers are associated with preeclampsia. Study design Nested case-control study of 410 preeclamptic women and 297 normotensive controls with primiparous singleton pregnancies enrolled in the Danish National Birth Cohort. The mean gestational age in our cohort is 16weeks (range 9–26). Main outcome measures Preeclampsia was defined by blood pressure ⩾140/90mmHg and proteinuria ⩾3g/24h. Serum immune biomarkers included interleukin (IL)-6, IL-6 receptor, IL-4, IL-4 receptor, IL-5, IL-12, IL-2, TNF-α, TNF-β, TNF-receptor, IL-1β, IL-1α, IL-8, IL-10, IFN-γ, IL-18, macrophage migration inhibitory factor, macrophage inflammatory protein, transforming growth factor-beta (TGF-β), and RANTES. Associations with preeclampsia, term preeclampsia and preterm preeclampsia were determined using two logistic regression models; (1) biomarkers were dichotomized by the limit of detection (LOD); (2) on the continuous scale, non-detectable values were imputed by LOD/2 and transformed (base 2). All models were adjusted for body mass index and smoking. Results IL1β was significantly associated with a decrease in the log odds of preeclampsia ( p =0.0065), term preeclampsia ( p =0.0230) and preterm preeclampsia ( p =0.0068). Results were similar for IL4r and preeclampsia ( p =0.0383). In the dichotomized models, detectable TNF-β was significantly associated with preeclampsia (OR adj 1.6, 95% CI 1.1–2.3) and term preeclampsia (OR 1.7, 95% CI 1.1–2.5) but not preterm preeclampsia. Detectable IL6 was significantly with term preeclampsia only (OR 1.5, 95% CI 1.1–2.2). Conclusion Mid-pregnancy circulating IL1β, IL4r, IL6, and TNFβ were associated with preeclampsia. However, results were not consistent across statistical models. As the relationship is complex, future studies should explore cytokine clusters in preeclampsia risk.

Background. Infection withChlamydia trachomatis(CT) can lead to reproductive sequelae. Information on the general population of childbearing age women in India is sparse. We reviewed the literature on CT prevalence within the general population of reproductive aged women in order to improve the efforts of public health screening programs and interventions.Objective. To conduct a literature review to determine the prevalence ofChlamydia trachomatisamong childbearing age women in India.Search Strategy. Ovid Medline and PubMed databases were searched for articles from January 1, 2003, through December 31, 2014. Search terms included “Chlamydia trachomatis”, “CT”, “prevalence”, “India”, and “sexually transmitted infections”.Selection Criteria. Studies on prevalence data for CT among women of childbearing age (15–45) living in India were included.Data Collection and Analysis. Articles that met the inclusion criteria were extracted by two readers and discrepancies solved through discussion.Results. Reported prevalence of active CT infection among lower risk groups ranged from 0.1% to 1.1% and in higher risk group from 2.7% to 28.5%.Conclusion.CT prevalence among women in India is comparable to other countries. Screening programs to prevent adverse outcomes among Indian women of childbearing age and their offspring are warranted.

Objectives As pelvic inflammatory disease (PID) aetiology is not completely understood, we examined the relationship between select novel bacteria, PID and long-term sequelae. Methods Fastidious bacterial vaginosis (BV)-associated bacteria ( Sneathia (Leptotrichia) sanguinegens , Sneathia amnionii , Atopobium vaginae and BV-associated bacteria 1 (BVAB1)), as well as Ureaplasma urealyticum and Ureaplasma parvum were identified in cervical and endometrial specimens using organism-specific PCR assays among 545 women enrolled in the PID Evaluation and Clinical Health study. Risk ratios and 95% CIs were constructed to determine associations between bacteria, histologically confirmed endometritis, recurrent PID and infertility, adjusting for age, race, gonorrhoea and chlamydia. Infertility models were additionally adjusted for baseline infertility. Results Persistent detection of BV-associated bacteria was common (range 58% for A. vaginae to 82% for BVAB1) and elevated the risk for persistent endometritis (RR adj 8.5, 95% CI 1.6 to 44.6) 30 days post-cefoxitin/doxycycline treatment, independent of gonorrhoea and chlamydia. In models adjusted for gonorrhoea and chlamydia, endometrial BV-associated bacteria were associated with recurrent PID (RR adj 4.7, 95% CI 1.7 to 12.8), and women who tested positive in the cervix and/or endometrium were more likely to develop infertility (RR adj 3.4, 95% CI 1.1 to 10.4). Associations between ureaplasmas and PID sequelae were modest. Conclusions To our knowledge, this is the first prospective study to demonstrate that S. sanguinegens , S. amnionii , BVAB1 and A. vaginae are associated with PID, failure of the Centers for Disease Control and Prevention-recommended treatment to eliminate short-term endometritis, recurrent PID and infertility. Optimal antibiotic regimens for PID may require coverage of novel BV-associated microbes.

Background Previous studies have found a relationship between cesarean section delivery and adverse outcomes in the offspring, partially attributing these findings to differential development of immunity in infants delivered by cesarean compared to vaginal delivery. The purpose of this study is to determine whether cesarean section delivery is associated with higher reports of adverse short-term infant health outcomes in a peri-urban Indian population. Methods Data from a prospective pregnancy cohort study in a peri-urban region of Telangana State, India, were analyzed to assess the association between mode of delivery, cesarean section or vaginal, and maternal report of recent infant diarrhea and/or respiratory symptoms at a 6 month follow-up visit. Inverse probability weights were applied to log-binomial regression models to account for maternal pre-pregnancy, prenatal, and labor and delivery factors. Results Of the 851 singleton infants delivered between 2010 and 2015, 46.7% were delivered by cesarean. Cesarean delivery was not associated with an increased report of infants having one or more of the outcomes (diarrhea, respiratory infection, or difficulty breathing) at 6 months (adjusted risk ratio 0.89, 95% confidence interval 0.76–1.03), nor was it associated with infants having a more severe outcome of comorbid diarrhea and respiratory infection (adjusted risk ratio 1.08, 95% confidence interval 0.58–2.04). Conclusion Unlike findings in Western populations, in this peri-urban Indian population, cesarean delivery was not associated with higher reports of short-term adverse gastrointestinal or respiratory infant outcomes after accounting for pre-delivery maternal factors. Future research in this cohort could elucidate whether mode of delivery is associated with other adverse outcomes later in childhood. Electronic supplementary material The online version of this article (10.1186/s12887-018-1324-3) contains supplementary material, which is available to authorized users.

Background Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. Objectives The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates. Study Design We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis –tubal factor infertility odds ratios and population-attributable fraction, stratified by race. Results We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73–89%) among Black and 31% (95% confidence interval, 28–35%) among non-Black participants ( P Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45–3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95–2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, –97% to 68%) among Blacks and 11% (95% confidence interval, –3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia–tubal factor infertility association and resulted in a significant association among non-Blacks. Conclusion Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates.

Objective Bacterial vaginosis (BV) is a common condition associated with serious complications including pelvic inflammatory disease (PID). However, the pathogenesis of BV is poorly understood. Toll-like receptors (TLR) are responsible for microbial recognition and elimination through inflammatory responses. TLR variants have been implicated in infectious and inflammatory diseases and may be involved in BV pathogenesis. We conducted a cross-sectional study to determine if TLR variants are associated with BV. Methods Logistic regression was used to test associations between 14 variants assayed in 6 genes (TLR1, TLR2, TLR4, TLR6, TIRAP and MyD88) and BV/intermediate flora among 192 African–American women with clinical PID from the PID Evaluation and Clinical Health (PEACH) Study. Additionally, we examined associations between variants and endometrial BV-associated anaerobes. To account for multiple comparisons a permutated p Results African–American women with PID carrying the AA genotype for TLR2 SNP rs1898830 had a threefold increased rate of BV/intermediate flora (OR 2.9, 95% CI 1.2 to 7.3). This was not significant after accounting for multiple comparisons (p=0.0201). TLR2 variants rs1898830, rs11938228 and rs3804099 were associated with increased endometrial anaerobic gram-negative rods (p=0.0107, p=0.0076 p=0.0121), anaerobic non-pigmented Gram-negative rods (p=0.0231, p=0.0083, p=0.0044), and anaerobic Gram-positive cocci (p=0.0596, p=0.0640, p=0.1459). Conclusions Among African–American women with PID, we observed trends between TLR2 variants, BV/intermediate flora, and BV-associated microbes. This provides some insight into BV pathogenesis. As not all BV-associated microbes may lead to pathology, future studies should focus on associations between TLR variants and individual BV-associated microbes.

Background We evaluated the importance of measuring early vaginal levels of eight BV-associated bacteria, at two points in pregnancy, and the risk of spontaneous preterm delivery (SPTD) among pregnant women and the subgroup of pregnant women with a history of preterm delivery (PTD).

Background Although the etiology of preeclampsia is not well understood, it has been suggested that excessive systemic inflammation may lead to oxidative stress, promoting the endothelial dysfunction characteristic of preeclampsia. Few prospective studies have examined the role of infection, an immune system stimulator, as a risk factor for preeclampsia. Methods We conducted a longitudinal study of the relationships between Chlamydia trachomatis (CT), Chlamydophila pneumoniae (CP), cytomegalovirus (CMV), herpes simplex virus (HSV) and preeclampsia among 509 preeclamptic cases and 336 normotensive controls nested within the Danish National Birth Cohort study. Antibodies were analyzed at a first prenatal visit (mean 17.0weeks) and at a late second/third trimester study visit. Prenatal infections were identified as IgG/IgM seroconversion or a fourfold rise in IgG antibody titers. Multiple regression models were adjusted for maternal age, BMI, smoking status, and time between blood draws. Results CT infection was associated with preeclampsia (OR adj 1.6, 95% CI 0.7, 3.6), severe preeclampsia (OR adj 1.8, 95% CI 0.6, 5.3), and preeclampsia resulting in preterm birth (OR adj 1.7, 95% CI 0.6–4.9) or birth of a small for gestational age infant (OR adj 2.1, 95% CI 0.6, 7.5), although CT infection was uncommon ( n =33, 4.0%) and associations were not statistically significant. CP, CMV, and HSV infection were not associated with preeclampsia. Conclusions Women with serological evidence of prenatal CT infection were more likely to develop preeclampsia, although infection was infrequent and confidence intervals were wide. Studies in populations at higher risk for STIs are needed to corroborate this association.

Pelvic inflammatory disease (PID), the infection and inflammation of the female upper genital tract, is a condition that can lead to infertility, chronic pelvic pain, and ectopic pregnancy [1]. Microbes such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and aerobes and anaerobes commonly associated with bacterial vaginosis (BV) have been implicated in the etiology of PID [2]. Race is a risk factor for PID, as well as chlamydia, gonorrhea, and BV [3–6]. Racial disparities exist in other inflammatory diseases including preterm birth, systemic lupus erythematosus, and cardiovascular disease [7–9]. The reasons for these racial differences are not completely understood. Socioeconomic, behavioral, and psychosocial factors only explain some of the racial disparities [10, 11]. Studies have found that African Americans are more likely to carry alleles that upregulate proinflammatory cytokines including interleukin 6, interleukin 1, and tumor necrosis factor (TNF) [12–14]. This may result in an imbalanced immune response, leading to excessive and harmful inflammation. As African Americans are at increased risk for inflammatory diseases, genetic variations that lead to increased inflammatory responses in the presence of infectious agents may also be more frequent in this group. The innate immune system relies on pattern recognition receptors (PRRs) for microbial recognition. Toll-like receptors (TLRs) are a family of PRRs that are essential for microbial elimination through the induction of inflammatory cytokine and chemokine genes [15]. The adaptor molecules Toll/interleukin-1 receptor domain–containing adaptor protein (TIRAP) and myeloid differentiation primary response protein 88 (MyD88) help to mediate TLR signaling. Examination of human tissues for expression of TLRs has revealed messenger RNA for TLRs 1–9 in uterine epithelium [16]. TLR2 is highly expressed in fallopian tubes and the cervix [17], whereas TLR4 is weakly expressed in fallopian tubes [17], and transcripts of TLR4 and its adaptor MD-2 are not detected in human cervical epithelial cells [18]. TLR2 forms homodimers with itself or heterodimers with TLR1 or TLR6 to bind pathogen ligands, whereas TLR4 requires the adaptor protein MD-2. TLR2 and TLR4 can recognize several bacteria associated with PID, including C. trachomatis, N. gonorrhoeae, and M. genitalium [18–20]. Although TLRs play a critical role in cytokine expression, few studies have examined racial differences in functional TLR polymorphisms. Barreiro et al suggests that variants in TLR genes may result in differential contributions to disease outcomes following infection in different populations [21]. For example, after examining the evolution of TLRs and their contribution to host defense, the authors found that Europeans had a diminished TLR2:TLR1-mediated immune response reducing inflammation. Thus, the authors concluded that those who carry certain alleles may avoid excessive inflammation, possibly inferring a selective advantage [21]. We have previously found that TLR1 variants are associated with C. trachomatis, upper genital tract infection, and reduced pregnancy rates among African American women with PID [22]. As racial disparities in reproductive and infectious diseases exist and TLR genes are involved in immunopathology, our objective was to determine the racial differences in the genotypic distribution of functional TLR variants among women with clinically suspected PID. We hypothesized that African American women would be more likely to carry TLR variants that are reported to increase inflammatory responses compared to white women. In addition, we examined the associations between race, TLR single-nucleotide polymorphisms (SNPs), and upper genital tract infection and inflammation.

Background Evidence suggests that in response to in utero insults, male versus female infants have greater disadvantages in pregnancy outcome. In addition, there is a growing body of evidence suggesting that there is a sex-specific fetal response to maternal disease during pregnancy. We considered that a sex-specific relationship may exist between preeclampsia and reduced fetal growth. Objective We investigated if the relationship between preeclampsia and fetal growth was modified by fetal sex. Methods We limited the study population to singleton pregnancies of black and white normotensive and preeeclamptic women enrolled in the Collaborative Perinatal Project (1959–1965). The patients were offspring of 516 preeclamptic and 8801 normotensive women. After adjustment for confounders, interaction terms between preeclamptic status and fetal sex were evaluated to determine if the influence of preeclampsia on fetal growth varied with fetal sex. Separate linear and logistic regression models were then fitted for males and females to report the estimate of the relationship between preeclampsia and fetal growth by fetal sex. The results were stratified by preterm status (

Introduction Circulating immune markers may be associated with preeclampsia but further investigations in early pregnancy and among preeclampsia subtypes are warranted. We examined immune markers in 208 preeclamptic women and 411 normotensive controls. Methods Our study was nested within the Collaborative Perinatal Project. A total of 242 women had first trimester serum samples and 392 had second trimester serum samples. Preeclampsia was defined as hypertension >20 weeks of gestation with proteinuria or pulmonary edema, oliguria, or convulsions. Preterm preeclampsia was defined as preeclampsia with delivery less than 37 weeks of gestation. Associations between immune markers RANTES, interleukin (IL)-6, IL4, IL5, IL12, IL10, IL8, IL1-beta, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and beta, transforming growth factor (TGF)-beta and preeclampsia were explored using a modified version of cox regression developed to address data with non-detectable levels. Models were adjusted for body mass index, gestational age of blood sampling, fetal sex, smoking, socioeconomic status and maternal age. Results In first trimester samples, IL-12 was associated with preeclampsia (p = 0.0255). IFN-gamma (p = 0.0063), IL1-beta (p = 0.0006), IL5 (p = 0.0422) and TNFr (p = 0.0460) were associated with preterm preeclampsia only. In second trimester samples, IL1-beta was associated with preeclampsia (p = 0.0180) and term preeclampsia (p = 0.0454). After correction for multiple comparisons, only IL1-beta remained associated with preterm preeclampsia in the first trimester (p = 0.0288). Discussion Elevated first trimester IL1-beta appears to be associated with preterm preeclampsia. However, few associations were observed in the second trimester. Systemic immune markers alone may not be useful for preeclampsia prediction.

Background. Infection with Chlamydia trachomatis (CT) can lead to reproductive sequelae. Information on the general population of childbearing age women in India is sparse. We reviewed the literature on CT prevalence within the general population of reproductive aged women in order to improve the efforts of public health screening programs and interventions. Objective. To conduct a literature review to determine the prevalence of Chlamydia trachomatis among childbearing age women in India. Search Strategy. Ovid Medline and PubMed databases were searched for articles from January 1, 2003, through December 31, 2014. Search terms included “Chlamydia trachomatis”, “CT”, “prevalence”, “India”, and “sexually transmitted infections”. Selection Criteria. Studies on prevalence data for CT among women of childbearing age (15–45) living in India were included. Data Collection and Analysis. Articles that met the inclusion criteria were extracted by two readers and discrepancies solved through discussion. Results. Reported prevalence of active CT infection among lower risk groups ranged from 0.1% to 1.1% and in higher risk group from 2.7% to 28.5%. Conclusion. CT prevalence among women in India is comparable to other countries. Screening programs to prevent adverse outcomes among Indian women of childbearing age and their offspring are warranted.

Chlamydia trachomatis is the most common bacterial sexually transmitted infection in the United States [1] and can lead to serious complications such as pelvic inflammatory disease (PID) and its subsequent sequelae, including ectopic pregnancy, infertility, and chronic pelvic pain [2, 3]. However, some women may develop PID and reproductive sequelae following chlamydial infection, whereas others may not [1, 4–6]. As the mechanisms underlying the pathogenesis of C. trachomatis have yet to be completely elucidated, the reasons for this variability in outcome are unknown. It is known that Chlamydia spp. can infect epithelial cells, causing secretion of proinflammatory cytokines [7–9]. Researchers have suggested that this inflammatory response may be responsible for disease progression [9], especially among those with chronic infections. Thus, it is possible that variations in host innate immune receptor genes may contribute to the variability in outcomes following chlamydial genital tract infection. The innate immune system serves as the first line of defense after exposure to pathogens and depends on pattern recognition receptors (PRRs) for microbial recognition [10–12]. A conserved family of PRRs called the Toll-like receptor (TLR) family [11] is responsible for induction of inflammatory cytokine and chemokine genes and priming of the adaptive immune system that leads to microbial elimination. Ten different TLRs (TLRs 1–10) have been identified in humans, and the overlap between them allows identification of a diverse range of pathogens through ligand binding [10–12]. Adaptor molecules, including myeloid differentiation primary response protein 88 (MyD88) and Toll/interleukin 1 receptor domain–containing adaptor protein (TIRAP), help to mediate TLR signaling [10]. However, as important as TLRs and their adaptor molecules are for a healthy immune response, variations in these genes may lead to an overexuberant or inadequate response, possibly influencing disease progression. Because TLRs are expressed in the reproductive tract [12] and can stimulate proinflammatory genes after binding to a bacterial ligand, it is possible that they may play a role in chlamydial pathogenesis. Studies have examined TLR pathways in chlamydial infections and have suggested a role for TLR2 in cytokine production [13, 14]. O’Connell et al [14] found that TLR2 was required for interleukin 8 (IL-8) expression, whereas TLR4/MD-2 had minimal effects on cytokine production in vitro. Darville et al [13], using a murine model of genital tract infection, found that mice genetically deficient for TLR2 exhibited reduced oviduct pathology and production of select proinflammatory cytokines, whereas TLR4-deficient mice had outcomes similar to wild-type mice. However, very few studies have examined TLRs in C. trachomatis pathogenesis among human subjects. Studies among Dutch white populations have been unable to show any significant associations between functional polymorphisms in the TLR4 and TLR2 genes and C. trachomatis [15–17]. Our objective was to explore the role of TLR2, TLR4, TLR6, MyD88, and TIRAP gene polymorphisms in C. trachomatis infection among women with clinically suspected PID.

Mycoplasma genitaliumis a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID). AlthoughChlamydia trachomatisandNeisseria gonorrhoeaefrequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linkingM. genitaliumto PID and its long-term reproductive sequelae. Several PCR studies have demonstrated thatM. genitaliumis associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested thatM. genitaliumwas associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID amongM. genitaliumpositive patients. Whether or notM. genitaliumupper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevatedM. genitaliumantibodies. Several lines of evidence suggest thatM. genitaliumis likely resistant to many frequently used PID treatment regimens. Correspondingly,M. genitaliumhas been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests thatM. genitaliumis associated with PID. Further study ofM. genitaliumupper genital tract infection diagnosis, treatment and long-term sequelae is warranted.