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Journal of the International AIDS... Oct 2023Predictors of neurodevelopment among children who are HIV-exposed uninfected (CHEU) are poorly understood.
INTRODUCTION
Predictors of neurodevelopment among children who are HIV-exposed uninfected (CHEU) are poorly understood.
METHODS
Mothers with and without HIV and their children were enrolled during 6-week postnatal care visits across seven sites in Kenya between March 2021 and June 2022. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool, including social, language, fine motor and gross motor domains. We used multivariate linear mixed effects models to identify associations between 1-year neurodevelopment scores, HIV and antiretroviral therapy (ART) exposures, and household factors, adjusted for potential confounders and clustered by the site.
RESULTS
At 1-year evaluation, CHEU (n = 709) and children who are HIV-unexposed uninfected (CHUU) (n = 715) had comparable median age (52 weeks) and sex distribution (49% vs. 52% female). Mothers living with HIV were older (31 vs. 27 years), had lower education (50% vs. 26% primary) and were more likely to be report moderate-to-severe food insecurity (26% vs. 9%) (p < 0.01 for all). Compared to CHUU, CHEU had higher language scores (adjusted coeff: 0.23, 95% CI: 0.06, 0.39) and comparable social, fine and gross motor scores. Among all children, preterm birth was associated with lower gross motor scores (adjusted coeff: -1.38, 95% CI: -2.05, -0.71), food insecurity was associated with lower social scores (adjusted coeff: -0.37, 95% CI: -0.73, -0.01) and maternal report of intimate partner violence (IPV) was associated with lower fine motor (adjusted coeff: -0.76, 95% CI: -1.40, -0.13) and gross motor scores (adjusted coeff: -1.07, 95% CI: -1.81, -0.33). Among CHEU, in utero efavirenz (EFV) exposure during pregnancy was associated with lower gross motor scores compared to dolutegravir (DTG) exposure (adjusted coeff: -0.51, 95% CI: -1.01, -0.03). Lower fine and gross motor scores were also associated with having a single or widowed mother (adjusted coeff: -0.45, 95% CI: -0.87, -0.03) or a deceased or absent father (adjusted coeff: -0.81, 95% CI: -1.58, -0.05), respectively.
CONCLUSIONS
Biologic and social factors were associated with child neurodevelopment. Despite socio-demographic differences between CHEU and CHUU, 1-year neurodevelopment was similar. Addressing IPV and food insecurity may provide benefits regardless of maternal HIV status. DTG use was associated with higher neurodevelopmental scores in CHEU, compared to EFV regimens, potentially contributing to a lack of neurodevelopmental difference between CHEU and CHUU.
Topics: Pregnancy; Infant; Humans; Child; Infant, Newborn; Female; Male; Pregnancy Complications, Infectious; HIV Infections; Kenya; Child Development; Premature Birth; Mothers
PubMed: 37909174
DOI: 10.1002/jia2.26149 -
Biochimica Et Biophysica Acta.... Oct 2023A unique immunological condition, pregnancy ensures fetus from maternal rejection, allows adequate fetal development, and protects against microorganisms. Infections...
A unique immunological condition, pregnancy ensures fetus from maternal rejection, allows adequate fetal development, and protects against microorganisms. Infections during pregnancy may lead to devastating consequences for pregnant women and fetuses, resulting in the mother's death, miscarriage, premature childbirth, or neonate with congenital infection and severe diseases and defects. Epigenetic (heritable changes in gene expression) mechanisms like DNA methylation, chromatin modification, and gene expression modulation during gestation are linked with the number of defects in the fetus and adolescents. The feto-maternal crosstalk for fetal survival during the entire gestational stages are tightly regulated by various cellular pathways, including epigenetic mechanisms that respond to both internal as well outer environmental factors, which can influence the fetal development across the gestational stages. Due to the intense physiological, endocrinological, and immunological changes, pregnant women are more susceptible to bacterial, viral, parasitic, and fungal infections than the general population. Microbial infections with viruses (LCMV, SARS-CoV, MERS-CoV, and SARS-CoV-2) and bacteria (Clostridium perfringens, Coxiella burnetii, Listeria monocytogenes, Salmonella enteritidis) further increase the risk to maternal and fetal life and developmental outcome. If the infections remain untreated, the possibility of maternal and fetal death exists. This article focused on the severity and susceptibility to infections caused by Salmonella, Listeria, LCMV, and SARS-CoV-2 during pregnancy and their impact on maternal health and the fetus. How epigenetic regulation during pregnancy plays a vital role in deciding the fetus's developmental outcome under various conditions, including infection and other stress. A better understanding of the host-pathogen interaction, the characterization of the maternal immune system, and the epigenetic regulations during pregnancy may help protect the mother and fetus from infection-mediated outcomes.
Topics: Infant, Newborn; Adolescent; Pregnancy; Female; Humans; Pregnancy Complications, Infectious; COVID-19; SARS-CoV-2; Epigenesis, Genetic; Fetal Development
PubMed: 37269984
DOI: 10.1016/j.bbadis.2023.166768 -
Critical Care (London, England) Sep 2023We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection.
BACKGROUND
We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection.
METHODS
We conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models.
RESULTS
Covid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76-2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79-5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95-1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09-2.04). Severe antepartum (RR 13.60, 95% CI 10.72-17.26) and peripartum infections (RR 20.93, 95% CI 17.11-25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42-4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron.
CONCLUSIONS
Covid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.
Topics: Female; Pregnancy; Humans; COVID-19; SARS-CoV-2; Canada; Disseminated Intravascular Coagulation; Pregnancy Complications, Infectious
PubMed: 37670329
DOI: 10.1186/s13054-023-04584-6 -
Frontiers in Public Health 2024This study aimed to determine the prevalence and factors associated with maternal and neonatal sepsis in sub-Saharan Africa. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to determine the prevalence and factors associated with maternal and neonatal sepsis in sub-Saharan Africa.
METHODS
This systematic review and meta-analysis used the PRISMA guideline on sepsis data in sub-Saharan Africa. The bibliographic search was carried out on the following databases: Medline/PubMed, Cochrane Library, African Index Medicus, and Google Scholar. Additionally, the reference lists of the included studies were screened for potentially relevant studies. The last search was conducted on 15 October 2022. The Joanna Briggs Institute quality assessment checklist was applied for critical appraisal. Estimates of the prevalence of maternal and neonatal sepsis were pooled using a random-effects meta-analysis model. Heterogeneity between studies was estimated using the Q statistic and the I2 statistic. The funnel plot and Egger's regression test were used to assess the publication bias.
RESULTS
A total of 39 studies were included in our review: 32 studies on neonatal sepsis and 7 studies on maternal sepsis. The overall pooled prevalence of maternal and neonatal sepsis in Sub-Saharan Africa was 19.21% (95% CI, 11.46-26.97) and 36.02% (CI: 26.68-45.36), respectively. The meta-analyses revealed that Apgar score < 7 (OR: 2.4, 95% CI: 1.6-3.5), meconium in the amniotic fluid (OR: 2.9, 95% CI: 1.8-4.5), prolonged rupture of membranes >12 h (OR: 2.8, 95% CI: 1.9-4.1), male sex (OR: 1.2, 95% CI: 1.1-1.4), intrapartum fever (OR: 2.4, 95% CI: 1.5-3.7), and history of urinary tract infection in the mother (OR: 2.7, 95% CI: 1.4-5.2) are factors associated with neonatal sepsis. Rural residence (OR: 2.3, 95% CI: 1.01-10.9), parity (OR: 0.5, 95% CI: 0.3-0.7), prolonged labor (OR: 3.4, 95% CI: 1.6-6.9), and multiple digital vaginal examinations (OR: 4.4, 95% CI: 1.3-14.3) were significantly associated with maternal sepsis.
CONCLUSION
The prevalence of maternal and neonatal sepsis was high in sub-Saharan Africa. Multiple factors associated with neonatal and maternal sepsis were identified. These factors could help in the prevention and development of strategies to combat maternal and neonatal sepsis. Given the high risk of bias and high heterogeneity, further high-quality research is needed in the sub-Saharan African context, including a meta-analysis of individual data. PROSPERO (ID: CRD42022382050).
Topics: Pregnancy; Humans; Female; Infant, Newborn; Male; Neonatal Sepsis; Prevalence; Africa South of the Sahara; Mothers; Pregnancy Complications, Infectious
PubMed: 38327574
DOI: 10.3389/fpubh.2024.1272193 -
MMWR. Morbidity and Mortality Weekly... Nov 2023Congenital syphilis cases in the United States increased 755% during 2012-2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal...
INTRODUCTION
Congenital syphilis cases in the United States increased 755% during 2012-2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal and infant morbidity; these outcomes can be prevented through appropriate screening and treatment.
METHODS
A cascading framework was used to identify and classify missed opportunities to prevent congenital syphilis among cases reported to CDC in 2022 through the National Notifiable Diseases Surveillance System. Data on testing and treatment during pregnancy and clinical manifestations present in the newborn were used to identify missed opportunities to prevent congenital syphilis.
RESULTS
In 2022, a total of 3,761 cases of congenital syphilis in the United States were reported to CDC, including 231 (6%) stillbirths and 51 (1%) infant deaths. Lack of timely testing and adequate treatment during pregnancy contributed to 88% of cases of congenital syphilis. Testing and treatment gaps were present in the majority of cases across all races, ethnicities, and U.S. Census Bureau regions.
CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE
Addressing missed opportunities for prevention, primarily timely testing and appropriate treatment of syphilis during pregnancy, is important for reversing congenital syphilis trends in the United States. Implementing tailored strategies addressing missed opportunities at the local and national levels could substantially reduce congenital syphilis.
Topics: Infant; Infant, Newborn; Pregnancy; Female; Humans; United States; Syphilis, Congenital; Syphilis; Pregnancy Complications, Infectious; Population Surveillance; Stillbirth; Vital Signs
PubMed: 37971936
DOI: 10.15585/mmwr.mm7246e1 -
Obstetrics and Gynecology Mar 2024To evaluate the prevalence, timing, clinical risk factors, and adverse outcomes associated with postpartum readmissions for maternal sepsis.
OBJECTIVE
To evaluate the prevalence, timing, clinical risk factors, and adverse outcomes associated with postpartum readmissions for maternal sepsis.
METHODS
We conducted a retrospective cohort study of delivery hospitalizations and 60-day postpartum readmissions for females aged 15-54 years with and without sepsis using the 2016-2020 Nationwide Readmissions Database. Temporal trends in sepsis diagnoses during delivery hospitalizations and 60-day postpartum readmissions were analyzed with the National Cancer Institute's Joinpoint Regression Program to estimate the average annual percent change with 95% CIs. Logistic regression models were fit to determine whether delivery hospitalization characteristics were associated with postpartum sepsis readmissions, and unadjusted and adjusted odds ratios with 95% CIs were reported. Adverse outcomes associated with sepsis during delivery hospitalization and readmission were described, including death, severe morbidity, a critical care composite, and renal failure.
RESULTS
Overall, 15,268,190 delivery hospitalizations and 256,216 associated 60-day readmissions were included after population weighting, of which 16,399 (1.1/1,000 delivery hospitalizations) had an associated diagnosis of sepsis at delivery, and 20,130 (1.3/1,000 delivery hospitalizations) had an associated diagnosis of sepsis with postpartum readmission. A sepsis diagnosis was present in 7.9% of all postpartum readmissions. Characteristics associated with postpartum sepsis readmission included younger age at delivery, Medicaid insurance, lowest median ZIP code income quartile, and chronic medical conditions such as obesity, pregestational diabetes, and chronic hypertension. Postpartum sepsis readmissions were associated with infection during the delivery hospitalization, including intra-amniotic infection or endometritis, wound infection, and delivery sepsis. Sepsis diagnoses were associated with 24.4% of maternal deaths at delivery and 38.4% postpartum, 2.2% cases of nontransfusion severe morbidity excluding sepsis at delivery and 13.6% postpartum, 15.6% of critical care composite diagnoses at delivery and 30.1% postpartum, and 11.1% of acute renal failure diagnoses at delivery and 36.4% postpartum.
CONCLUSION
Sepsis accounts for a significant proportion of postpartum readmissions and is a major contributor to adverse outcomes during delivery hospitalizations and postpartum readmissions.
Topics: Pregnancy; Female; United States; Humans; Puerperal Infection; Patient Readmission; Retrospective Studies; Risk Factors; Hospitalization; Postpartum Period; Sepsis
PubMed: 37944152
DOI: 10.1097/AOG.0000000000005437 -
Journal of Women's Health (2002) Jun 2024Sexually transmitted infections (STIs) continue to increase in the United States with more than 2.5 million cases of gonorrhea, chlamydia, and syphilis reported to the... (Review)
Review
Sexually transmitted infections (STIs) continue to increase in the United States with more than 2.5 million cases of gonorrhea, chlamydia, and syphilis reported to the Centers for Disease Control and Prevention in 2022. Untreated STIs in women can lead to adverse outcomes, including pelvic inflammatory disease, infertility, chronic pelvic pain, and pregnancy complications such as ectopic pregnancy, early pregnancy loss, stillbirth, and neonatal transmission. STI-related guidelines can be complex and are frequently updated, making it challenging to stay informed on current guidance. This article provides high-yield updates to support clinicians managing STIs by highlighting changes in screening, diagnosis, and treatment. One important topic includes new guidance on syphilis screening, including a clarified description of high community rates of syphilis based on Healthy People 2030 goals, defined as a case rate of primary or secondary syphilis > 4.6 per 100,000. Reproductive aged persons living in counties above this threshold should be offered syphilis screening. Additionally, American College of Obstetricians & Gynecologists now recommends syphilis screening three times during pregnancy regardless of risk-at the first prenatal visit, during the third trimester, and at delivery. In addition, new guidance to support consideration for extragenital screening for gonorrhea and chlamydia in women at sites such as the anus and pharynx is discussed. Other topics include the most recent chlamydia, gonorrhea, trichomoniasis, and pelvic inflammatory disease treatment recommendations; screening and treatment guidance for ; genital herpes screening indications and current diagnostic challenges; and the diagnosis and management of mpox in women and during pregnancy.
Topics: Humans; Female; Sexually Transmitted Diseases; Pregnancy; United States; Syphilis; Pregnancy Complications, Infectious; Mass Screening; Chlamydia Infections; Gonorrhea; Practice Guidelines as Topic; Adult
PubMed: 38770770
DOI: 10.1089/jwh.2024.0367 -
Frontiers in Immunology 2023Fetal inflammatory response mediated by the influx of immune cells and activation of pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is the...
BACKGROUND
Fetal inflammatory response mediated by the influx of immune cells and activation of pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is the major determinant of infection-associated preterm birth (PTB, live births < 37 weeks of gestation).
OBJECTIVE
To reduce the incidence of PTB by minimizing inflammation, extracellular vesicles (EVs) were electroporetically engineered to contain anti-inflammatory cytokine interleukin (IL)-10 (eIL-10), and their efficacy was tested in an ascending model of infection (vaginal administration of E. ) induced PTB in mouse models.
STUDY DESIGN
EVs (size: 30-170 nm) derived from HEK293T cells were electroporated with recombinant IL-10 at 500 volts and 125 Ω, and 6 pulses to generate eIL-10. eIL-10 structural characters (electron microscopy, nanoparticle tracking analysis, ExoView [size and cargo content] and functional properties (co-treatment of macrophage cells with LPS and eIL-10) were assessed. To test efficacy, CD1 mice were vaginally inoculated with E. (10CFU) and subsequently treated with either PBS, eIL-10 (500ng) or Gentamicin (10mg/kg) or a combination of eIL-10+gentamicin. Fetal inflammatory response in maternal and fetal tissues after the infection or treatment were conducted by suspension Cytometer Time of Flight (CyTOF) using a transgenic mouse model that express red fluorescent TdTomato (mT+) in fetal cells.
RESULTS
Engineered EVs were structurally and functionally stable and showed reduced proinflammatory cytokine production from LPS challenged macrophage cells . Maternal administration of eIL-10 (10 µg/kg body weight) crossed feto-maternal barriers to delay E. -induced PTB to deliver live pups at term. Delay in PTB was associated with reduced feto-maternal uterine inflammation (immune cell infiltration and histologic chorioamnionitis, NF-κB activation, and proinflammatory cytokine production).
CONCLUSIONS
eIL-10 administration was safe, stable, specific, delayed PTB by over 72 hrs and delivered live pups. The delivery of drugs using EVs overcomes the limitations of in-utero fetal interventions. Protecting IL-10 in EVs eliminates the need for the amniotic administration of recombinant IL-10 for its efficacy.
Topics: Animals; Female; Humans; Mice; Pregnancy; Cytokines; Disease Models, Animal; Escherichia coli; Extracellular Vesicles; Fetus; HEK293 Cells; Interleukin-10; Lipopolysaccharides; NF-kappa B; Premature Birth; Recombinant Proteins; Inflammation; Pregnancy Complications, Infectious
PubMed: 37600782
DOI: 10.3389/fimmu.2023.1196453 -
Zeitschrift Fur Geburtshilfe Und... Feb 2024During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced...
During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced coronavirus disease 19 (COVID-19) has an impact on maternal health and pregnancy outcomes; peripartum and perinatal morbidity and mortality are increased. Pregnancy is considered a risk factor for severe COVID-19 course. Additional risk factors during pregnancy are diabetes mellitus, gestational diabetes mellitus (GDM), and obesity. Systemic inflammation can lead to severe metabolic dysregulation with ketoacidosis. The endocrine pancreas is a target organ for SARS-CoV-2 and the fetal risk depends on inflammation of the placenta. Up to now there is no evidence that SARS-CoV-2 infection during pregnancy leads to permanent diabetes in mothers or their offspring via triggering autoimmunity or beta cell destruction. The frequently observed increased prevalence of GDM compared to the years before the pandemic is most likely due to changed lifestyle during lockdown. Furthermore, severe COVID-19 may be associated with the development of GDM due to worsening of glucose tolerance. Vaccination with a mRNA vaccine is safe and highly effective to prevent infection and to reduce hospitalization. Registries support offering evidence-based recommendations on vaccination for pregnant women. Even with the current omicron virus variant, there are increased risks for symptomatic and unvaccinated pregnant women.
Topics: Pregnancy; Female; Humans; COVID-19; SARS-CoV-2; Communicable Disease Control; Pregnancy Outcome; Diabetes, Gestational; Pregnancy Complications, Infectious; Inflammation
PubMed: 37918833
DOI: 10.1055/a-2180-7715 -
Nature Cell Biology Jul 2023During pregnancy the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show...
During pregnancy the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show increased incidences of adverse pregnancy outcomes in patients with COVID-19; however, the mechanism remains unclear. Here we analysed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced substantial changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.
Topics: Pregnancy; Female; Humans; COVID-19; Transcriptome; SARS-CoV-2; Epigenomics; Pregnancy Complications, Infectious; Single-Cell Analysis
PubMed: 37400500
DOI: 10.1038/s41556-023-01169-x