Iron deficiency anemia in pregnancy.

PURPOSE OF REVIEW: Anemia in pregnancy is associated with increased maternal and neonatal morbidity. There is increasing awareness amongst obstetricians about the need to screen for iron deficiency anemia (IDA), as well as growing literature on diagnosis and treatment. This review aims to summarize causes, consequences, treatment, and evaluation of IDA in pregnancy. RECENT FINDINGS: National guidelines provide varying guidance on diagnosis and treatment of IDA in pregnancy. Serum ferritin is a helpful adjunct for the diagnosis of IDA. Oral iron remains an option for treatment; absorption is improved with every other day dosing and is effective for patients able to tolerate. Emerging studies on modern generations of intravenous (IV) iron demonstrate shorter infusion times and improved safety profiles. Notably, recent UK guidelines provide consideration for universal IV iron supplementation for treatment of anemia beyond 34 weeks of pregnancy. SUMMARY: Iron, in dietary, oral, and IV forms, has been found effective in resolving anemia in pregnancy. Pregnant people with IDA in the third trimester are more likely to benefit from IV iron. Future studies designed and powered to assess maternal and perinatal morbidity indicators and blood transfusion rates can strengthen recommendations.

Comparison of rapid immunoassays for rupture of fetal membranes.

BACKGROUND: Rupture of membranes (ROM) before the onset of uterine contractions, particularly in pregnancies less than 37 weeks gestational age, is a common diagnostic problem in obstetrical practice. Timely detection of ROM is vital to support gestational age-specific interventions to optimize perinatal outcomes and minimize the risk of serious complications such as preterm delivery, fetal distress and maternal/fetal infections. Rapid bedside immunoassay tests designed to detect amniotic fluid proteins in cervicovaginal fluids have emerged as valuable clinical tools to provide timely ROM diagnosis. METHODS: In this prospective observational study, two commercially-available immunoassay tests (ROM Plus®, AmniSure®) were evaluated concurrently in 111 pregnant women who presented with the chief complaint of ROM. Immunoassay results were compared to clinical parameters for determining ROM via comprehensive, retrospective clinical chart review. Diagnostic performance characteristics were calculated including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. RESULTS: Overall, diagnostic performance characteristics were robust and similar between ROM Plus® and AmniSure®, respectively: sensitivity (96.4 and 89.3%), specificity (98.8 and 100%), PPV (96.4 and 100%), NPV (98.8% and 96.5) and accuracy (98.2 and 97.3%). For term patients (≥37 weeks gestation), the sensitivities were 93.8 and 81.3% and specificities were 97.1 and 100% for ROM Plus® and AmniSure®, respectively. For preterm patients (<37 weeks gestation), both immunoassay tests provided exact concordance with clinical confirmation of ROM resulting in 100% diagnostic accuracy. CONCLUSIONS: Both rapid immunoassay tests provided similarly excellent diagnostic accuracy for the rapid detection of ROM with only two discrepant results for ROM Plus® and three discrepant results for AmniSure® compared to clinical confirmation. The findings from this study recommend these tests for pregnant women presenting with suspected ROM to guide correct clinical management decisions to improve obstetrical and neonatal outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02208011 (1 August 2014).

Zika Virus: Common Questions and Answers.

Since local mosquito-borne transmission of Zika virus was first reported in Brazil in early 2015, the virus has spread rapidly, with active transmission reported in at least 61 countries and territories worldwide, including the United States. Zika virus infection during pregnancy is a cause of microcephaly and other severe brain anomalies. The virus is transmitted primarily through the bite of an infected Aedes mosquito, but other routes of transmission include sexual, mother-to-fetus during pregnancy, mother-to-infant at delivery, laboratory exposure, and, possibly, transfusion of blood products. Most persons with Zika virus infection are asymptomatic or have only mild symptoms; hospitalizations and deaths are rare. When symptoms are present, maculopapular rash, fever, arthralgia, and conjunctivitis are most common. Zika virus testing is recommended for persons with possible exposure (those who have traveled to or live in an area with active transmission, or persons who had sex without a condom with a person with possible exposure) if they have symptoms consistent with Zika virus disease. Testing is also recommended for pregnant women with possible exposure, regardless of whether symptoms are present. Treatment is supportive, and no vaccine is currently available. The primary methods of prevention include avoiding bites of infected Aedes mosquitoes and reducing the risk of sexual transmission. Pregnant women should not travel to areas with active Zika virus transmission, and men and women who are planning to conceive in the near future should consider avoiding nonessential travel to these areas. Condoms can reduce the risk of sexual transmission.

Preventing Transmission of Zika Virus in Labor and Delivery Settings Through Implementation of Standard Precautions - United States, 2016.

Zika virus transmission was detected in the Region of the Americas (Americas) in Brazil in May 2015, and as of March 21, 2016, local mosquito-borne transmission of Zika virus had been reported in 32 countries and territories in the Americas, including Puerto Rico and the U.S. Virgin Islands.* Most persons infected with Zika virus have a mild illness or are asymptomatic. However, increasing evidence supports a link between Zika virus infection during pregnancy and adverse pregnancy and birth outcomes (1), and a possible association between recent Zika virus infection and Guillain-Barré syndrome has been reported (2). Although Zika virus is primarily transmitted through the bite of Aedes species of mosquitoes, sexual transmission also has been documented (3). Zika virus RNA has been detected in a number of body fluids, including blood, urine, saliva, and amniotic fluid (3-5), and whereas transmission associated with occupational exposure to these body fluids is theoretically possible, it has not been documented. Although there are no reports of transmission of Zika virus from infected patients to health care personnel or other patients, minimizing exposures to body fluids is important to reduce the possibility of such transmission. CDC recommends Standard Precautions in all health care settings to protect both health care personnel and patients from infection with Zika virus as well as from blood-borne pathogens (e.g., human immunodeficiency virus [HIV] and hepatitis C virus [HCV]) (6). Because of the potential for exposure to large volumes of body fluids during the labor and delivery process and the sometimes unpredictable and fast-paced nature of obstetrical care, the use of Standard Precautions in these settings is essential to prevent possible transmission of Zika virus from patients to health care personnel.

Zika Virus Infection Among U.S. Pregnant Travelers - August 2015-February 2016.

After reports of microcephaly and other adverse pregnancy outcomes in infants of mothers infected with Zika virus during pregnancy, CDC issued a travel alert on January 15, 2016, advising pregnant women to consider postponing travel to areas with active transmission of Zika virus. On January 19, CDC released interim guidelines for U.S. health care providers caring for pregnant women with travel to an affected area, and an update was released on February 5. As of February 17, CDC had received reports of nine pregnant travelers with laboratory-confirmed Zika virus disease; 10 additional reports of Zika virus disease among pregnant women are currently under investigation. No Zika virus-related hospitalizations or deaths among pregnant women were reported. Pregnancy outcomes among the nine confirmed cases included two early pregnancy losses, two elective terminations, and three live births (two apparently healthy infants and one infant with severe microcephaly); two pregnancies (approximately 18 weeks' and 34 weeks' gestation) are continuing without known complications. Confirmed cases of Zika virus infection were reported among women who had traveled to one or more of the following nine areas with ongoing local transmission of Zika virus: American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico, and Samoa. This report summarizes findings from the nine women with confirmed Zika virus infection during pregnancy, including case reports for four women with various clinical outcomes. U.S. health care providers caring for pregnant women with possible Zika virus exposure during pregnancy should follow CDC guidelines for patient evaluation and management. Zika virus disease is a nationally notifiable condition. CDC has developed a voluntary registry to collect information about U.S. pregnant women with confirmed Zika virus infection and their infants. Information about the registry is in preparation and will be available on the CDC website.

Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure - United States, July 2016.

CDC has updated its interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure, to include the emerging data indicating that Zika virus RNA can be detected for prolonged periods in some pregnant women. To increase the proportion of pregnant women with Zika virus infection who receive a definitive diagnosis, CDC recommends expanding real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. Possible exposures to Zika virus include travel to or residence in an area with active Zika virus transmission, or sex* with a partner who has traveled to or resides in an area with active Zika virus transmission without using condoms or other barrier methods to prevent infection.(†) Testing recommendations for pregnant women with possible Zika virus exposure who report clinical illness consistent with Zika virus disease(§) (symptomatic pregnant women) are the same, regardless of their level of exposure (i.e., women with ongoing risk for possible exposure, including residence in or frequent travel to an area with active Zika virus transmission, as well as women living in areas without Zika virus transmission who travel to an area with active Zika virus transmission, or have unprotected sex with a partner who traveled to or resides in an area with active Zika virus transmission). Symptomatic pregnant women who are evaluated <2 weeks after symptom onset should receive serum and urine Zika virus rRT-PCR testing. Symptomatic pregnant women who are evaluated 2-12 weeks after symptom onset should first receive a Zika virus immunoglobulin (IgM) antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR testing should be performed. Testing recommendations for pregnant women with possible Zika virus exposure who do not report clinical illness consistent with Zika virus disease (asymptomatic pregnant women) differ based on the circumstances of possible exposure. For asymptomatic pregnant women who live in areas without active Zika virus transmission and who are evaluated <2 weeks after last possible exposure, rRT-PCR testing should be performed. If the rRT-PCR result is negative, a Zika virus IgM antibody test should be performed 2-12 weeks after the exposure. Asymptomatic pregnant women who do not live in an area with active Zika virus transmission, who are first evaluated 2-12 weeks after their last possible exposure should first receive a Zika virus IgM antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR should be performed. Asymptomatic pregnant women with ongoing risk for exposure to Zika virus should receive Zika virus IgM antibody testing as part of routine obstetric care during the first and second trimesters; immediate rRT-PCR testing should be performed when IgM antibody test results are positive or equivocal. This guidance also provides updated recommendations for the clinical management of pregnant women with confirmed or possible Zika virus infection. These recommendations will be updated when additional data become available.

Learning Lessons from the COVID-19 Pandemic-A Qualitative Assessment of the Experiences of Pregnant Latinas Infected with COVID-19 and Their Perspectives on Vaccination.

OBJECTIVES: To examine the experiences of pregnant Hispanic/Latine people with COVID-19, as well as their perspectives on COVID-19 vaccination in pregnancy. METHODS: We interviewed birthing parents who received care from a teaching hospital in California and tested positive for COVID-19 during pregnancy or delivery. We analyzed transcripts using the constant comparative method for analyzing data to using a phenomological epidemiological approach. We used root cause analysis to identify consistent themes across interviews and assess relationships between social determinants of health and COVID-19 infectivity. RESULTS: We interviewed 14 women from November 2021 to June 2022. Participants reported COVID-19 adversely impacted their clinical care and well-being during pregnancy or postpartum. Impacts among Spanish-speaking participants included unexpected financial hardships, challenges navigating in-patient experiences, and difficulty securing reliable childcare. While most participants were at least partially vaccinated, participants also described doubts and concerns about the vaccine. CONCLUSIONS: Our findings suggest that Spanish-speaking Hispanic/Latine patients could benefit from receiving more information about COVID-19 in pregnancy from their healthcare providers. Leveraging familial and social networks, providing reliable information in people's preferred language, and increasing communication through trusted partners may also help combat vaccine hesitancy.

Racial and Ethnic Disparities in Anemia and Severe Maternal Morbidity.

OBJECTIVE: To evaluate antepartum anemia prevalence by race and ethnicity, to assess whether such differences contribute to severe maternal morbidity (SMM), and to estimate the contribution of antepartum anemia to SMM and nontransfusion SMM by race and ethnicity. METHODS: We conducted a population-based cohort study using linked vital record and birth hospitalization data for singleton births at or after 20 weeks of gestation in California from 2011 through 2020. Pregnant patients with hereditary anemias, out-of-hospital births, unlinked records, and missing variables of interest were excluded. Antepartum anemia prevalence and trends were estimated by race and ethnicity. Centers for Disease Control and Prevention criteria were used for SMM and nontransfusion SMM indicators. Multivariable logistic regression modeling was used to estimate risk ratios (RRs) for SMM and nontransfusion SMM by race and ethnicity after sequential adjustment for social determinants, parity, obstetric comorbidities, delivery, and antepartum anemia. Population attributable risk percentages were calculated to assess the contribution of antepartum anemia to SMM and nontransfusion SMM by race and ethnicity. RESULTS: In total, 3,863,594 births in California were included. In 2020, Black pregnant patients had the highest incidence of antepartum anemia (21.5%), followed by Pacific Islander (18.2%), American Indian-Alaska Native (14.1%), multiracial (14.0%), Hispanic (12.6%), Asian (10.6%), and White pregnant patients (9.6%). From 2011 to 2020, the prevalence of anemia increased more than100% among Black patients, and there was a persistent gap in prevalence among Black compared with White patients. Compared with White patients, the adjusted risk for SMM was high among most racial and ethnic groups; adjustment for anemia after sequential modeling for known confounders decreased SMM risk most for Black pregnant patients (approximated RR 1.47, 95% CI 1.42-1.53 to approximated RR 1.27, 95% CI 1.22-1.37). Compared with White patients, the full adjusted nontransfusion SMM risk remained high for most groups except Hispanic and multiracial patients. Within each racial and ethnic group, the population attributable risk percentage for antepartum anemia and SMM was highest for multiracial patients (21.4%, 95% CI 17.5-25.0%), followed by Black (20.9%, 95% CI 18.1-23.4%) and Hispanic (20.9%, 95% CI 19.9-22.1%) patients. The nontransfusion SMM population attributable risk percentages for Asian, Black, and White pregnant patients were less than 8%. CONCLUSION: Antepartum anemia, most prevalent among Black pregnant patients, contributed to disparities in SMM by race and ethnicity. Nearly one in five to six SMM cases among Black, Hispanic, American Indian-Alaska Native, Pacific Islander, and multiracial pregnant patients is attributable in part to antepartum anemia.

The obstetrical research landscape: a cross-sectional analysis of clinical trials from 2007-2020.

Background: Obstetrical complications affect more than a third of women globally, but are underrepresented in clinical research. Little is known about the comprehensive obstetrical clinical trial landscape, how it compares with other fields, or factors associated with the successful completion of obstetrical trials. Objective: This study aimed to characterize obstetrical clinical trials registered on ClinicalTrials.gov with the primary objective of identifying features associated with early discontinuation and results reporting. Study Design: This is a cross-sectional study with descriptive, logistic regression and Cox regression analyses of clinical trials registered on ClinicalTrials.gov. Our primary exposure variables were trial focus (obstetrical or nonobstetrical) and trial funding (industry, United States government, or academic). We conducted additional exploratory analyses of other trial features including design, enrollment, and therapeutic focus. We examined the associations of exposure variables and other trial features with 2 primary outcomes: early discontinuation and results reporting. Results: We downloaded data for all studies (N=332,417) registered on ClinicalTrials.gov from October 1, 2007, to March 9, 2020, from the Aggregate Analysis of ClinicalTrials.gov database. We excluded studies with a noninterventional design (n=63,697) and those registered before October 1, 2007 (n=45,209). A total of 4276 obstetrical trials (1.9%) (ie, interventional studies) and 219,235 nonobstetric trials (98.1%) were compared. Among all trials, 2.8% of academic-funded trials, 1.9% of United States government-funded trials, and 0.4% of industry-funded trials focused on obstetrics. The quantity of obstetrical trials increased over time (10.8% annual growth rate). Compared with nonobstetrical trials, obstetrical trials had a greater risk of early discontinuation (adjusted hazard ratio, 1.40; 95% confidence interval, 1.21-1.62; P<.0001) and similar odds of results reporting (adjusted odds ratio, 0.89; 95% confidence interval, 0.72-1.10; P=.19). Among obstetrical trials funders after controlling for confounding variables, United States government-funded trials were at the lowest risk of early discontinuation (United States government, adjusted hazard ratio, 0.23; 95% confidence interval, 0.07-0.69; P=.009; industry reference; academic, adjusted hazard ratio, 1.04; 95% confidence interval, 0.62-1.74; P=.88). Academic-funded trials had the lowest odds of results reporting after controlling for confounding variables (academic institutions, adjusted odds ratio, 0.39; 95% confidence interval, 0.22-0.68; P=.0009; industry reference; United States government, adjusted odds ratio, 1.06; 95% confidence interval, 0.53-2.09; P=.87). Conclusion: Obstetrical trials represent only 1.9% of all clinical trials in ClinicalTrials.gov and have comparatively poor completion. All stakeholders should commit to increasing the number of obstetrical trials and improving their completion and dissemination to ensure clinical research reflects the obstetrical burden of disease and advances maternal health.

Bone marrow connexin-43 expression is critical for hematopoietic regeneration after chemotherapy.

Contact between bone marrow (BM) hematopoietic stem cells (HSC) and osteoblast/stromal (OS) cells has been shown to be crucial in the regulation of hematopoiesis. However, very little is known about the regulatory mechanisms of direct cell-to-cell communication in the hematopoietic microenvironment. Gap junction channels (connexons) are formed by polypeptides (connexins) arranged in hexamers and represent the best described intercellular communication system. Connexin-43 (Cx43) is expressed by BM OS cells and has been associated with the cadherin/beta -catenin signaling pathway, recently reported as relevant in the OS/HSC interaction at the stem cell niche. Here, we employed an inducible gene-targeted murine approach to study the role of Cx43 in HSC proliferation and differentiation in vivo. Mx-Cre/Cx43+/+ and Mx-Cre/Cx43flox/flox littermates have been analyzed after gene deletion induced in vivo by the interferon-inducer poly (I)-poly (C), generating control (Cx43+) and Cx43-deficient (Cx43-/-) mice. After one week, Cx43+ and Cx43-/- mice were treated with 5-fluorouracil (5-FU). Cx43 expression in Cx43-/- BM was markedly reduced (> 90%) as analyzed on day +14 post-5-FU treatment. Cx43 deficiency did not induce a significant change in peripheral blood counts before 5-FU treatment, but the hematopoiesis recovery after 5-FU treatment was severely impaired as demonstrated by absence of recovery of peripheral blood counts, including profound neutropenia, anemia with reticulocytopenia, thrombocytopenia and a 5- to 8-fold decrease of cellularity and hematopoietic progenitor content (granulomacrophagic colony-forming-units (CFU-GM-), erythroid burst forming units (BFU-E) and mixed colony forming units (CFU-mix-) in BM and spleen on day +14 post-5-FU treatment. However, the femoral content of Lin-/c-kit+/Sca1+ cells in Cx43-/- BM was maintained when compared to Cx43+ BM. Short-term competitive repopulation ability of Cx43-/- BM cells was diminished as compared to Cx43+ mice, specifically for myeloid and B lymphoid cells, but showed spared long-term competitive repopulation ability with roughly normal hematopoietic differentiation. These data suggest that hematopoietic regeneration after cycle-specific chemotherapy is blocked in Cx43-deficient mice at the long-term HSC repopulating level. Cx43 expression within the BM appears to be crucial in the development of an efficient response to hematopoietic stress.