Thrombotic Markers in Pregnant Patients with and without SARS-CoV-2 Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities and increased risk for venous and arterial thrombi. This study aimed to evaluate D-dimer levels and lupus anticoagulant (LAC) positivity in pregnant individuals with and without Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: This was a prospective cohort study of pregnant individuals delivering at a single academic institution from April 2020 to March 2022. Individuals with a positive SARS-CoV-2 result during pregnancy were compared with a convenience sample of those without a positive SARS-CoV-2 result. For individuals with SARS-CoV-2 infection, severity was assessed based on the National Institutes of Health classification system. The primary outcome was D-dimer level measured during delivery admission. The secondary outcomes were LAC positivity and thromboembolic events. Outcomes were compared between individuals with and without a positive SARS-CoV-2 result, and further by disease severity. RESULTS: Of 98 participants, 77 (78.6%) were SARS-CoV-2 positive during pregnancy. Among individuals with SARS-CoV-2 infection, severity was asymptomatic in 20 (26.0%), mild in 13 (16.9%), moderate in 4 (5.2%), severe in 38 (49.4%), and critical in 2 (2.6%). The D-dimer concentration at delivery did not significantly differ between those with a SARS-CoV-2 positive result compared with those without (mean 2.03 µg/mL [95% confidence interval {CI} 1.72-2.40] vs. 2.37 µg/mL [95% CI 1.65-3.40]; p = 0.43). Three individuals (4%) with SARS-CoV-2 infection and none (0%) without infection were LAC positive (p = 0.59). There were no clinically apparent thromboses in either group. D-dimer concentrations and LAC positive results did not differ by COVID-19 severity. CONCLUSION: Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection; however, high rates of LAC positivity were detected. KEY POINTS: · Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection.. · Higher than expected rates of LAC positivity were detected.. · There were no clinically apparent thromboses..

Impact of Prenatal Cannabis Use Disorder on Perinatal Outcomes.

OBJECTIVES: With legislative changes to cannabis legalization and increasing prevalence of use, cannabis is the most commonly used federally illicit drug in pregnancy. Our study aims to assess the perinatal outcomes associated with prenatal cannabis use disorder. METHODS: We conducted a retrospective cohort study using California linked hospital discharge-vital statistics data and included singleton, nonanomalous births occurring between 23 and 42 weeks of gestational age. χ 2 Test and multivariable logistic regression were used for statistical analyses. RESULTS: A total of 2,380,446 patients were included, and 9144 (0.38%) were identified as using cannabis during pregnancy. There was a significantly increased risk for adverse birthing person outcomes, including gestational hypertension (adjusted odds ratio [AOR], 1.19; 95% confidence interval [CI], 1.06-1.34; P = 0.004), preeclampsia (AOR, 1.16; 95% CI, 1.0-1.28; P = 0.006), preterm delivery (AOR, 1.45; 95% CI, 1.35-1.55; P < 0.001), and severe maternal morbidity (AOR, 1.22; 95% CI, 1.02-1.47; P = 0.033). Prenatal cannabis use disorder was also associated with an increased risk of neonatal outcomes including respiratory distress syndrome (AOR, 1.16; 95% CI, 1.07-1.27; P < 0.001), small for gestational age (AOR, 1.47; 95% CI, 1.38-1.56; P < 0.001), neonatal intensive care unit admission (AOR, 1.24; 95% CI, 1.16-1.33; P < 0.001), and infant death (AOR, 1.86; 95% CI, 1.44-2.41; P < 0.001). There was no statistically significant difference in stillbirth (AOR, 0.96; 95% CI, 0.69-1.34; P = 0.80) and hypoglycemia (AOR, 1.22; 95% CI, 1.00-1.49; P = 0.045). CONCLUSIONS: Our study suggests that prenatal cannabis use disorder is associated with increased maternal and neonatal morbidity and mortality. As cannabis use disorder in pregnancy is becoming more prevalent, our findings can help guide preconception and prenatal counseling.

Opioid Use in Pregnancy: A Review.

Importance: The use and misuse of opioids in pregnancy have been increasing and are a major public health issue. Opioid use in pregnancy and during lactation has been associated with increased maternal and neonatal morbidity and mortality. Objective: This review aims to summarize the existing literature and current recommendations for opioid use while pregnant or lactating. Evidence Acquisition: A PubMed, Cochrane Library, and Google Scholar literature search using the following terms was performed to gather relevant data: "opioids," "opioid maintenance therapy," "opioid use disorder," "suboxone," "buprenorphine," "methadone," "medication for opioid use disorder," "fetal outcomes," "perinatal outcomes," "pregnancy," "lactation," and "neonatal abstinence syndrome." Results: Available studies on opioid use in pregnancy and during lactation were reviewed and support association with increased odds of maternal death, placental insufficiency, cardiac arrest, preterm birth, neonatal intensive care unit admission, low birth weight, and small for gestational age infants. Studies were also reviewed on pharmacotherapy options in pregnancy and promising prenatal care models. Conclusion and Relevance: There is a critical need for research on the effects of opioid use and related pharmacotherapy options in pregnancy. Once the adverse perinatal effects of opioid exposure are identified and well-characterized, patient education, intervention, and antenatal surveillance can be developed to predict and mitigate its impact on maternal and fetal health.

The role of oral iron in the treatment of adults with iron deficiency.

Iron deficiency is the most common nutrient deficiency in the world, affecting over 20% of premenopausal women worldwide. Oral iron supplementation is often the first-line treatment for the acute and chronic management of iron deficiency due to its ease and accessibility. However, there is no consensus on the optimal formulation or dosing strategy, or which patients should be preferentially treated with intravenous iron. Management of iron deficiency is complicated by the hepcidin-ferroportin iron regulatory pathway, which has evolved to prevent iron overload and thereby creates an inherent limit on gastrointestinal iron uptake and efficacy of oral iron. Unabsorbed iron propagates many of the side effects that complicate oral iron use including dyspepsia and constipation, all of which can thus be exacerbated by excessive oral iron doses. Daily low dose and every other day dosing protocols have attempted to bypass this physiologic bottleneck to allow for effective absorption and limit side effects; however, this approach has still resulted in low fractional iron absorption. In the following manuscript, we review the pathophysiology of iron absorption and current evidence for various preparations of oral iron. Lastly, we highlight opportunities for further study to advance the care of individuals affected by iron deficiency.

Association between short interpregnancy interval and placenta accreta spectrum.

BACKGROUND: The incidence of placenta accreta spectrum is increasing in parallel with the growing number of cesarean deliveries performed. A shorter interpregnancy interval following cesarean delivery may prevent adequate scar healing, which could impact the risk of placenta accreta spectrum. OBJECTIVE: We aimed to investigate the association between short interpregnancy intervals and placenta accreta spectrum. STUDY DESIGN: We conducted a retrospective cohort study of patients at risk for placenta accreta spectrum at a tertiary academic center between 2002 and 2020. Our cohort was defined as pregnant individuals at risk for placenta accreta spectrum meeting the following criteria: placenta previa with previous cesarean delivery and/or uterine surgery, anterior low-lying placenta with previous cesarean delivery and/or uterine surgery, ≥3 previous cesarean deliveries, or any previous cesarean delivery with sonographic findings suspicious for placenta accreta spectrum. The primary outcome was surgically or histopathologically confirmed placenta accreta spectrum. Short interpregnancy interval was defined as <18 completed months from previous delivery and last menstrual period of the index pregnancy. Univariable analyses were performed with chi-square and Student's t-test, as appropriate, and Kruskal-Wallis for nonparametric variables. The unadjusted and adjusted odds ratios were calculated using multivariate logistic regression models. Covariates were selected if P<.2 in univariable analyses or defined a priori as clinically meaningful. The final models were derived using reverse stepwise selection of variables. We used Stata Statistical Software, version 15 (StataCorp, College Station, TX) to perform descriptive statistics. RESULTS: Of 262 patients at risk of placenta accreta spectrum with complete records, 112 (42.7%) had placenta accreta spectrum. Pregnant individuals with short interpregnancy intervals of <18 months were no more likely than those with optimal interpregnancy intervals to have previa (58% [46/80] vs 46% [84/182]; P=.09) or placenta accreta spectrum (49% [39/80] vs 40% [73/182]; P=.19). Short interpregnancy interval of <18 months was not associated with placenta accreta spectrum (unadjusted odds ratio, 1.06; 95% confidence interval, 0.62-1.80). This association did not change when adjusting for previa and number of previous cesarean deliveries (adjusted odds ratio, 1.04; 95% confidence interval, 0.51-2.15). In a secondary analysis, an interpregnancy interval of <12 months was also not associated with placenta accreta spectrum (unadjusted odds ratio, 0.79; 95% confidence interval, 0.04-1.56; adjusted odds ratio, 0.52; 95% confidence interval, 0.21-1.27). CONCLUSION: In patients at risk for placenta accreta spectrum, short interpregnancy intervals of <18 months or <12 months were not associated with placenta accreta spectrum, even when controlling for number of previous cesarean deliveries and previa. Short interpregnancy interval is not likely to be an important modifiable independent risk factor for placenta accreta spectrum.

The incidence, complications, and treatment of iron deficiency in pregnancy.

Iron deficiency and/or iron deficiency anemia (IDA) complicate nearly 50% of pregnancies globally, negatively impacting both maternal and fetal outcomes. Iron deficiency can cause a range of symptoms that range from aggravating to debilitating including fatigue, poor quality of life, pagophagia, and restless leg syndrome. Iron deficiency and IDA are also associated with maternal complications including preterm labor, increased rates of cesarean delivery, postpartum hemorrhage, and maternal death. Fetal complications include increased rates of low birth weight and small for gestational age newborns. Prenatal maternal anemia has also been associated with autism spectrum disorders in the neonate, although causation is not established. Deficiency in the newborn is associated with compromised memory, processing, and bonding, with some of these deficits persisting into adulthood. Despite the prevalence and consequences associated with iron deficiency in pregnancy, data show that it is routinely undertreated. Due to the physiologic changes of pregnancy, all pregnant individuals should receive oral iron supplementation. However, the bioavailability of oral iron is poor and it is often ineffective at preventing and treating iron deficiency. Likewise, it frequently causes gastrointestinal symptoms that can worsen the quality of life in pregnancy. Intravenous iron formulations administered in a single or multiple dose series are now available. There is increasing data suggesting that newer intravenous formulations are safe and effective in the second and third trimesters and should be strongly considered in pregnant individuals without optimal response to oral iron repletion.

Confirmatory Middle Cerebral Artery Doppler Testing in Alloimmunized Patients with Suspected Fetal Anemia.

OBJECTIVE: This article aimed to evaluate pregnancy outcomes when a plan to perform fetal blood sampling (FBS) or delivery was based solely on the first abnormal middle cerebral artery peak velocity (MCA-PV) measurement compared with making a plan after a confirmatory test on a subsequent day. STUDY DESIGN: We performed a descriptive study of pregnancy outcomes including all patients in a single healthcare system with maternal red cell alloimmunization undergoing ultrasound between 2005 and 2017 who had at least one MCA-PV>1.5 multiples of the median (MoM). We excluded patients with any sign of hydrops prior to the index visit or abnormal MCA-PV at>35 weeks. The first exam with a MCA-PV>1.5 MoM was deemed the index visit. RESULTS: Fifty patients were identified. Twenty-one patients underwent intervention (FBS or delivery) based on the first abnormal MCA-PV. Of those, 9 had moderate or severe anemia (positive predictive value [PPV]: 43%), while 12 had mild or no anemia. The other 29 patients underwent a confirmatory MCA test between 2 and 8 days later. Of these, 13 patients had an abnormal confirmatory test and 11 of these underwent FBS and 7 had moderate or severe anemia (PPV: 54%). Sixteen patients undergoing confirmatory MCA Doppler had a normal test on repeat and did not undergo FBS. Of those, none developed moderate or severe anemia. CONCLUSION: A substantial number of patients (55%) had normal MCA-PV testing on repeat, allowing avoidance of invasive testing. Deferring FBS until the abnormal MCA-PV was confirmed was not associated with undetected moderate or severe anemia. KEY POINTS: · False-positive results from MCA-PV Doppler prediction of fetal anemia are common.. · Repeat noninvasive testing is normal in many patients with suspected fetal anemia.. · Invasive fetal testing can often be safely avoided by performing a confirmatory Doppler exam ination..

Adjunct Therapy at Time of Examination-Indicated Cervical Cerclage in Singleton Pregnancies: A Systematic Review and Meta-analysis.

OBJECTIVE: Physical examination-indicated cerclage for cervical insufficiency prolongs gestation, but evidence on the addition of adjuncts to further prolong latency is limited. The aim of this systematic review and meta-analysis was to compare gestational latency between those who did and did not receive adjunct antibiotic or tocolytic therapy at the time of examination-indicated cerclage. STUDY DESIGN: Electronic databases (1966-2020) were searched for randomized controlled trials (RCTs) and cohort studies comparing adjunct antibiotic or tocolytic use versus nonuse at time of examination-indicated cerclage, defined as placement for cervical dilation ≥1 cm, in a current singleton pregnancy. Studies including individuals with intra-amniotic infection, cerclage in place, nonviable gestation, or ruptured membranes were excluded. The primary outcome was latency from cerclage placement to delivery. Secondary outcomes included preterm birth, preterm premature rupture of membranes, birth weight, and neonatal survival. Risk of bias was assessed using standardized tools. Heterogeneity was assessed using χ 2 and I 2 tests. Results were pooled and analyzed using a random-effects model. This study is registered with The International Prospective Register of Systematic Reviews (PROSPERO) with registration no.: CRD42021216370. RESULTS: Of 923 unique records, 163 were reviewed in full. Three met inclusion criteria: one RCT and two retrospective cohorts. The included RCT (n = 50) and one cohort (n = 142) compared outcomes with and without adjunct use of antibiotic and tocolytic, while the second cohort (n = 150) compared outcomes with and without adjunct tocolytic, with a subpopulation also receiving antibiotics. The RCT was nested within one of the cohorts, and therefore only one of these two studies was utilized for any given outcome to eliminate counting individuals twice. Risk of bias was "critical" for one cohort study, "moderate" for the other cohort study, and "some concerns" for the RCT. Gestational latency could not be pooled and meta-analyzed. Adjunct tocolytic-antibiotic therapy was not associated with a decrease in risk of preterm delivery <28 weeks (relative risk [RR] = 0.90, 95% confidence interval [CI]: 0.65-1.26; χ 2 = 0.0, I 2 = 0.0%) or neonatal survival to discharge (RR = 1.11, 95% CI: 0.91-1.35; χ 2 = 0.05, I 2 = 0.0%). CONCLUSION: There is not enough evidence to robustly evaluate the use of adjunct tocolytics or antibiotics at time of examination-indicated cerclage to prolong latency. KEY POINTS: · Limited data on adjunct antibiotic tocolytics at cerclage.. · Widely variable practices at time of cerclage identified.. · Role of adjunct therapies at time of examination-indicated cerclage remains unclear..

Transfusion Preparedness in the Labor and Delivery Unit: An Initiative to Improve Safety and Cost.

OBJECTIVE: To evaluate patient safety, resource utilization, and transfusion-related cost after a policy change from universal type and screen to selective type and screen on admission to labor and delivery. METHODS: Between October 2017 and September 2019, we performed a single-center implementation study focusing on risk-based type and screen instead of universal type and screen. Implementation of our policy was October 2018 and compared 1 year preimplementation with 1 year postimplementation. Patients were risk-stratified in alignment with California Maternal Quality Care Collaborative recommendations. Under the new policy, the blood bank holds a blood sample for processing (hold clot) on patients at low- and medium-risk of hemorrhage. Type and screen and crossmatch are obtained on high-risk patients or with a prior positive antibody screen. We collected patient outcomes, safety and cost data, and compliance and resource utilization metrics. Cost included direct costs of transfusion-related testing in the labor and delivery unit during the study period, from a health system perspective. RESULTS: In 1 year postimplementation, there were no differences in emergency-release transfusion events (4 vs 3, P>.99). There were fewer emergency-release red blood cell (RBC) units transfused (9 vs 24, P=.002) and O-negative RBC units transfused (8 vs 18, P=.016) postimplementation compared with preimplementation. Hysterectomies (0.05% vs 0.1%, P=.44) and intensive care unit admissions (0.45% vs 0.51%, P=.43) were not different postimplementation compared with preimplementation. Postimplementation, mean monthly type and screen-related costs (ABO typing, antibody screen, and antibody workup costs) were lower, $9,753 compared with $20,676 in the preimplementation year, P<.001. CONCLUSION: Implementation of selective type and screen policy in the labor and delivery unit was associated with projected annual savings of $181,000 in an institution with 4,000 deliveries per year, without evidence of increased maternal morbidity.

16th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome.

Obstetric antiphospholipid syndrome (APS) remains a clinical challenge for practitioners, with several controversial points that have not been answered so far. This Obstetric APS Task Force met on the 16th International Congress on Antiphospholipid Antibodies in Manchester, England, to discuss about treatment, diagnostic and clinical aspects of the disease. This report will address evidence-based medicine related to obstetric APS, including limitations on our current management, the relationship between antibodies against domain 1 of ß2GPI and obstetric morbidity, hydroxychloroquine use in patients with obstetric APS and factors associated with thrombosis after obstetric APS. Finally, future directions for better understanding this complex condition are also reported by the Task Force coordinators.

Outpatient Cervical Ripening: A Cost-Minimization and Threshold Analysis.

OBJECTIVE: To evaluate cost of outpatient (OP) versus inpatient (IP) ripening with transcervical balloons, and determine circumstances in which each strategy would be cost saving. STUDY DESIGN: We created a decision model comparing OP and IP balloon ripening in term (≥37 weeks) singleton pregnancies with unfavorable cervix. We performed a cost-minimization analysis and threshold analyses comparing two OP ripening strategies (broad and limited use) to IP ripening from a health system perspective. Base case estimates of probability, utilization, and cost were derived from the literature. The primary outcome was incremental cost of OP versus IP ripening from a hospital perspective. One- and two-way sensitivity analyses explored uncertainty in the model. RESULTS: Both OP ripening strategies were cost saving compared with IP ripening: incremental cost -$228.40/patient with broad use and -$73.48/patient with limited use. OP ripening was no longer cost saving if hours saved on labor and delivery (L&D) were <3.5, insertion visit cost >$714, or facility cost/hour on L&D <$61. Two-way sensitivity analyses showed that OP ripening was cost saving under the most plausible clinical circumstances. CONCLUSION: In patients with unfavorable cervix, OP transcervical balloon ripening was cost saving under a wide range of circumstances, particularly if OP ripening can shorten time spent on L&D by 3.5 hours.

Assessment of maternal referral systems used for a rural Zambian hospital: the development of setting specific protocols for the identification of complications.

BACKGROUND: In resource-limited countries, it is estimated that up to 75% of maternal deaths are preventable. Maternal referral systems are an effective measure to help prevent these deaths. OBJECTIVE: The objective of this study was to delineate criteria that health care workers use to identify obstetrical emergencies and make referrals, in order to evaluate the effectiveness of the established referral system and to implement improvements to this system. METHODS: Using a qualitative study design, the individuals with the highest level of formal obstetrics training at 10 health posts that refer to a rural Zambian hospital were surveyed using semi-structured interviews regarding their referral protocols. Data were analyzed through open-coding. At the conclusion of the interview, standardized referral protocols for obstetric emergencies derived from published guidelines and local practices were distributed. RESULTS: Identified complications resulting in referral most commonly included post-partum hemorrhage (70%), prolonged labor (70%), malpresentation (50%), antepartum hemorrhage (40%), and retained placenta (40%). While numerous reasons for referral were identified, there was little consensus on the referral protocol used for each complication. Obstacles to successful referral most commonly included cellular network disruptions (70%), distance (50%), and lack of transportation (30%).The referral protocols distributed to health posts covered only 11 of the 23 complications cited as the most common reason for referral. CONCLUSION: The referral criteria and protocols were updated to include all of the reported complications. We propose this document for others working in resource-limited settings attempting to establish or evaluate a maternal referral systems.

Asynchronous evolutionary origins of Aß and BACE1.

Neurodegenerative plaques characteristic of Alzheimer's disease (AD) are composed of amyloid beta (Aß) peptide, which is proteolyzed from amyloid precursor protein (APP) by ß-secretase (beta-site APP cleaving enzyme [BACE1]) and γ-secretase. Although γ-secretase has essential functions across metazoans, no essential roles have been identified for BACE1 or Aß. Because their only known function results in a disease phenotype, we sought to understand these components from an evolutionary perspective. We show that APP-like proteins are found throughout most animal taxa, but sequences homologous to Aß are not found outside gnathostomes and the ß cut site is only conserved within sarcopterygians. BACE1 enzymes, however, extend through basal chordates and as far as cnidaria. We then sought to determine whether BACE1 from a species that never evolved Aß could proteolyze APP substrates that include Aß. We demonstrate that BACE1 from a basal chordate is a functional ortholog that can liberate Aß from full-length human APP, indicating BACE1 activity evolved at least 360 My before Aß.