Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia.

Protein misfolding disorders are a group of diseases characterized by supra-physiologic accumulation and aggregation of pathogenic proteoforms resulting from improper protein folding and/or insufficiency in clearance mechanisms. Although these processes have been historically linked to neurodegenerative disorders, such as Alzheimer's disease, evidence linking protein misfolding to other pathologies continues to emerge. Indeed, the deposition of toxic protein aggregates in the form of oligomers or large amyloid fibrils has been linked to type 2 diabetes, various types of cancer, and, in more recent years, to preeclampsia, a life-threatening pregnancy-specific disorder. While extensive physiological mechanisms are in place to maintain proteostasis, processes, such as aging, genetic factors, or environmental stress in the form of hypoxia, nutrient deprivation or xenobiotic exposures can induce failure in these systems. As such, pregnancy, a natural physical state that already places the maternal body under significant physiological stress, creates an environment with a lower threshold for aberrant aggregation. In this review, we set out to discuss current evidence of protein misfolding in pregnancy and potential mechanisms supporting a key role for this process in preeclampsia pathogenesis. Improving our understanding of this emerging pathophysiological process in preeclampsia can lead to vital discoveries that can be harnessed to create better diagnoses and treatment modalities for the disorder.

Work-Life Balance and Academic Productivity Among College of Medicine Faculty During the Evolution of the COVID-19 Pandemic: The New Normal.

Background: Work and home stress, productivity, and self-care of academic medicine faculty in Spring 2021 was contrasted to faculty's experience in the Spring of 2020, both of which were relatively compared with the prepandemic period. Methods: A 93-question survey was sent to academic medicine faculty at an urban public university medical center in March 2020 and again in March 2021. Demographic, family, and academic characteristics, work distribution and productivity before and during the pandemic, perceived stress related to work and home activities, and self-care data compared with the prepandemic period were collected. Differences were assessed using chi-square or Fisher exact tests. Student t-test was used for the difference in mean values, while logistic regression was used to determine predictors of work stress. Results: Two hundred thirty-one faculty completed the survey in Spring 2020 and 118 faculty responded in Spring 2021. The proportion of faculty reporting increased work and home stress decreased in Spring 2021 compared with Spring 2020. A higher proportion of women compared with men reported increased work stress in both surveys. In Spring 2021, work stress decreased significantly for men but not for women. Home stress decreased significantly for women in Spring 2021 but remained stable for the men faculty. Research productivity increased for both genders in Spring 2021, but a greater percentage of women reported disturbed sleep and diet. There were no differences in home stress levels between genders when caring for young children. Conclusions: Men faculty are more likely to adapt to the "new normal" by lowering work stressors and increasing productivity, whereas women's continued high work stress and increased productivity may occur at the expense of decreased self-care. The challenges associated with having young children continue to affect the productivity and well-being of all faculty.

Is Faster Better? Relationships of Cesarean Acuity with Risk of Low Apgar Scores and Fetal Acidemia.

OBJECTIVE: Timely response to obstetrical emergencies is highly desired. The recommendation for decision-to-incision (DTI) time in cesarean delivery (CD) of not more than 30 minutes was issued to prevent neonatal hypoxic-ischemic morbidities. We analyzed the efficiency with which an institutional-specific CD acuity classification system (emergent case: target DTI ≤ 15 minutes; urgent case: target DTI ≤ 30 minutes) reflected in the actual DTI time, Apgar scores, and newborn acid-base status. STUDY DESIGN: Data on all 610 cesarean sections (CSs) performed over a 14-month period at a tertiary medical center were retrospectively extracted. Cases grouped by target DTI time categories were compared for proportions in low Agar scores and fetal acidosis. Multivariable regression was used to identify clinical variables associated with the need for neonatal resuscitation. RESULTS: During the study period, 60 (10%) of CSs were emergent, 296 (49%) urgent, and 254 (41%) elective. The target DTI ≤ 15 minutes was achieved in 68% of emergent CSs with 93% having a DTI ≤ 30 minutes. Among urgent surgeries, the target DTI ≤ 30 minutes was reached in 48% of cases with 83% having DTI ≤ 45 minutes. Compared with both urgent and scheduled procedures the incidence of newborn acidosis and Apgar scores ≤4 and ≤7 was the highest among emergent CSs. The proportion of moderate and severe acidosis for deliveries with DTI ≤ 15 minutes was significantly higher compared with procedures with DTI 16 to 30 and >30 minutes. The need for neonatal resuscitation, including intubation, was independently associated with fetal acidosis, low gestational age, surgery acuity level, general anesthesia, but not with the actual DTI time. CONCLUSION: Adherence to tight DTI time targets is pragmatically difficult. The need for neonatal resuscitation varies with the acuity of the procedure but not with the actual DTI interval, implying that within certain time limits, the indication for surgery plays a greater role in the status of the newborn than the speed of the CS. KEY POINTS: · Adherence to prespecified DTI times for cesarean is pragmatically difficult.. · Emergent CS had the highest proportion of newborns with acidosis and low Apgar scores despite shorter DTI.. · The need for neonatal resuscitation associated with fetal acidemia, prematurity and general anesthesia..

Surgical Instrument Designers and Inventors-Where are the Women?

Historically, surgical instruments were designed by men for male surgeons. Although instrumentation has changed with the changing paradigms of surgery, it has failed to adapt to the changing surgical workforce. Almost 30% of surgeons are female and nearly 90% of surveyed female surgeons report poor instrument design and associated musculoskeletal injuries from use. Understanding the current state of handheld surgical instrument design, published literature was reviewed, surgical instrument collections were contacted, and the U.S. Patent and Trademark databases were queried to identify public patents and pre-granted applications of female inventors of handheld surgical instruments. Twenty-five female inventors were identified from published literature and 1551 unique females hold patents. This number pales when the denominator of male inventors is considered. Hence, to address the female surgeon's lack of instrumentation and design, there is a critical need for participatory ergonomics whereby both the female surgeon and engineer collaborate on design.

PAPP-A as a screening tool for assessment of gestational age before medication abortion in an intended-use population.

Introduction: Prior studies indicate that PAPP-A could serve as a marker of gestational age (GA) with the potential to determine eligibility for medication abortion. The authors validated the relationship between PAPP-A and GA in an actual-use population. Materials & methods: The authors collected blood samples, medical histories and ultrasound-determined GA from patients presenting for abortion services. They measured PAPP-A using two immunoassays and assessed diagnostic accuracy for predicting GA ≥71 days. Results: The Ansh Labs and R&D Systems immunoassays produced an area under the ROC curve of 0.982 (95% CI: 0.958-0.994) and 0.986 (95% CI: 0.963-0.996), respectively, for predicting GA ≥71 days. Conclusion: This validation study in an intended-use population confirmed that PAPP-A has a strong ability to distinguish pregnancies above and below 71 days' gestation. Clinical trial registration: NCT04232189 (ClinicalTrials.gov).

In the USA, abortion with pills is an option for people with pregnancies of less than 71 days. Usually, people use ultrasound to find out how far along a pregnancy is. Ultrasound can be pricey and hard to find. Some studies show that a protein in blood, called PAPP-A, may be another option. The authors took blood from and did ultrasounds for people who wanted an abortion. They measured how much PAPP-A was in the blood using two different methods. The level of PAPP-A in the blood did a good job of distinguishing pregnancies that were higher and lower than 71 days.

Transcriptomics-Based Subphenotyping of the Human Placenta Enabled by Weighted Correlation Network Analysis in Early-Onset Preeclampsia With and Without Fetal Growth Restriction.

BACKGROUND: Placental disorders contribute to pregnancy complications, including preeclampsia and fetal growth restriction (FGR), but debate regarding their specific pathobiology persists. Our objective was to apply transcriptomics with weighted gene correlation network analysis to further clarify the placental dysfunction in these conditions. METHODS: We performed RNA sequencing with weighted gene correlation network analysis using human placental samples (n=30), separated into villous tissue and decidua basalis, and clinically grouped as follows: (1) early-onset preeclampsia (EOPE)+FGR (n=7); (2) normotensive, nonanomalous preterm FGR (n=5); (2) EOPE without FGR (n=8); (4) spontaneous idiopathic preterm birth (n=5) matched for gestational age; and (5) uncomplicated term births (n=5). Our data was compared with RNA sequencing data sets from public databases (GSE114691, GSE148241, and PRJEB30656; n=130 samples). RESULTS: We identified 14 correlated gene modules in our specimens, of which most were significantly correlated with birthweight and maternal blood pressure. Of the 3 network modules consistently predictive of EOPE±FGR across data sets, we prioritized a coexpression gene group enriched for hypoxia-response and metabolic pathways for further investigation. Cluster analysis based on transcripts from this module and the glycolysis/gluconeogenesis metabolic pathway consistently distinguished a subset of EOPE±FGR samples with an expression signature suggesting modified tissue bioenergetics. We demonstrated that the expression ratios of LDHA/LDHB and PDK1/GOT1 could be used as surrogate indices for the larger panels of genes in identifying this subgroup. CONCLUSIONS: We provide novel evidence for a molecular subphenotype consistent with a glycolytic metabolic shift that occurs more frequently but not universally in placental specimens of EOPE±FGR.

Prevalence of and Risk Factors for Iron Deficiency in Twin and Singleton Newborns.

Iron deficiency (ID) in utero and in infancy can cause irreversible neurocognitive damage. Iron status is not routinely tested at birth, so the burden of neonatal ID in the United States is unknown. Infants born from twin or higher-order pregnancies may be at elevated risk of inadequate nutrient endowment at birth. The present study sought to compare the burden of neonatal ID in cord blood serum samples from twin (n = 54) and singleton pregnancies (n = 24). Iron status (serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) biomarker concentrations were measured by immunoassay. The prevalence of ID (SF < 76 ng/mL) among twins was 21% (23/108) and among singletons 20% (5/24). Gestational age at birth, maternal race and infant sex predicted SF levels. Maternal anemia (hemoglobin < 11 g/dL) was observed in 40% of mothers but was not associated with neonatal iron biomarkers. More research is needed to identify risk factors and regulatory mechanisms for inadequate fetal iron accrual to identify higher risk pregnancies and neonates for screening and intervention.

Evaluation of a Maternal Plasma RNA Panel Predicting Spontaneous Preterm Birth and Its Expansion to the Prediction of Preeclampsia.

Preterm birth is the principal contributor to neonatal death and morbidity worldwide. We previously described a plasma cell-free RNA panel that between 16 and 20 weeks of pregnancy had potential to predict spontaneous preterm birth (sPTB) ≤ 32 weeks caused by preterm labor (PTL) or preterm premature rupture of membranes (PPROM). The present study had three objectives: (1) estimate the RNA panel prognostic accuracy for PTL/PPROM ≤ 32 weeks in a larger series; (2) improve accuracy by adding clinical characteristics to the predictive model; and (3) examine the association of the RNA panel with preeclampsia. We studied 289 women from Memphis TN prospectively sampled 16.0-20.7 weeks and found: (1) PSME2 and Hsa-Let 7g were differentially expressed in cases of PTL/PPROM ≤ 32 weeks and together provided fair predictive accuracy with AUC of 0.76; (2) combining the two RNAs with clinical characteristics improved good predictive accuracy for PTL/PPROM ≤ 32 weeks (AUC 0.83); (3) NAMPT and APOA1 were differentially expressed in women with 'early-onset preeclampsia' (EOP) and together provided good predictive accuracy with AUC of 0.89; and (4) combining the two RNAs with clinical characteristics provided excellent predictive accuracy (AUC 0.96). Our findings suggest an underlying common pathophysiological relationship between PTL/PPROM ≤ 32 weeks and EOP and open inroads for the prognostication of high-risk pregnancies.

Gender-differences of proceduralists in perception of hand-held surgical instrument fit - A cross-sectional survey.

OBJECTIVE: Determining perception of hand size as it relates to instrument use and ability to perform a procedure in a diverse population of proceduralists across surgical and medical specialties. METHODS: Cross-sectional survey was distributed via electronic format to a convenience sample of surgeons/physicians. Secondary analysis included identified instrument use and choice of/perception of ability to learn and perform procedures. RESULTS: 488 respondents, 84.4% (female), 75.8% (glove size ≤6.5), and 82.2% (surgical specialties). 67.8% reported trouble using surgical instruments, primarily endoscopes, laparoscopic instruments, and needle drivers. Latent class analysis identified two groups of female respondents with similar hand sizes but differ in the perception of their hand's abilities. CONCLUSIONS AND RELEVANCE: Instruments beyond laparoscopic instruments do not fit all hands. Even among female with physicians with similar hand size, there is a sub-set who struggle using surgical tools. Beyond gender and hand size, the operator's perception of their hand and their ability is critical in determining the viability of instrument mastery.

A Novel Role for Plasminogen Activator Inhibitor Type-2 as a Hypochlorite-Resistant Serine Protease Inhibitor and Holdase Chaperone.

Plasminogen activator inhibitor type-2 (PAI-2), a member of the serpin family, is dramatically upregulated during pregnancy and in response to inflammation. Although PAI-2 exists in glycosylated and non-glycosylated forms in vivo, the majority of in vitro studies of PAI-2 have exclusively involved the intracellular non-glycosylated form. This study shows that exposure to inflammation-associated hypochlorite induces the oligomerisation of PAI-2 via a mechanism involving dityrosine formation. Compared to plasminogen activator inhibitor type-1 (PAI-1), both forms of PAI-2 are more resistant to hypochlorite-induced inactivation of its protease inhibitory activity. Holdase-type extracellular chaperone activity plays a putative non-canonical role for PAI-2. Our data demonstrate that glycosylated PAI-2 more efficiently inhibits the aggregation of Alzheimer's disease and preeclampsia-associated amyloid beta peptide (Aß), compared to non-glycosylated PAI-2 in vitro. However, hypochlorite-induced modification of non-glycosylated PAI-2 dramatically enhances its holdase activity by promoting the formation of very high-molecular-mass chaperone-active PAI-2 oligomers. Both PAI-2 forms protect against Aß-induced cytotoxicity in the SH-SY5Y neuroblastoma cell line in vitro. In the villous placenta, PAI-2 is localised primarily to syncytiotrophoblast with wide interpersonal variation in women with preeclampsia and in gestational-age-matched controls. Although intracellular PAI-2 and Aß staining localised to different placental cell types, some PAI-2 co-localised with Aß in the extracellular plaque-like aggregated deposits abundant in preeclamptic placenta. Thus, PAI-2 potentially contributes to controlling aberrant fibrinolysis and the accumulation of misfolded proteins in states characterised by oxidative and proteostasis stress, such as in Alzheimer's disease and preeclampsia.

Endocan, a Soluble Marker of Endothelial Cell Activation Is a Molecular Marker of Disease Severity in Women with Preeclampsia.

Endocan is a proteoglycan secreted by activated endothelium that regulates angiogenesis via interaction with hepatocyte growth factor (HGF). We hypothesized that women diagnosed with preeclampsia (PE) and/or fetal growth restriction (FGR) have elevated circulating endocan concentrations in direct relationship with severity of clinical manifestations. Serum concentration of endocan and HGF were analyzed in 224 women grouped as healthy pregnant controls (P-CRL, n = 77), PE with severe features (sPE, n = 83), chronic hypertension (crHTN: n = 36), idiopathic FGR (n = 18), and healthy non-pregnant controls (NP-CRL, n = 7). Endocan and HGF measured by immunoassay were analyzed along with markers of inflammation, angiogenesis, and protein misfolding (urine congophilia). Endocan expression in the placenta and/or myometrium was studied by immunohistochemistry and real-time PCR. Compared to gestational age-matched P-CRL, women with early-onset sPE had higher circulating endocan concentrations. Among women with PE and/or FGR, endocan concentration correlated with soluble endoglin and urine congophilia but not with HGF or markers of inflammation or angiogenesis. In the placenta, endocan was expressed in villous and extravillous trophoblasts and endothelium. Intense endocan immunostaining was observed in plaque-like aggregations of sPE placentas complicated with FGR. In addition, thickened blood vessels in the myometrium of sPE patients stained positive for endocan. Women with early-onset sPE have elevated serum endocan likely reflecting chronic endothelial activation. Enhanced expression and/or deposition of endocan at the sites of placental injury and in remodeled maternal blood vessels supports a role for endocan in either vascular rescue or as a contributor to FGR and perhaps long-term cardiovascular morbidity.

Conformation-dependent anti-Aß monoclonal antibody signatures of disease status and severity in urine of women with preeclampsia.

Prior research has shown that urine of women with preeclampsia (PE) contains amyloid-like aggregates that are congophilic (exhibit affinity for the amyloidophilic dye Congo red) and immunoreactive with A11, a polyclonal serum against prefibrillar ß-amyloid oligomers, thereby supporting pathogenic similarity between PE and protein conformational disorders such as Alzheimer's and prion disease. The objective of this study was to interrogate PE urine using monoclonal antibodies with previously characterized A11-like epitopes. Over 100 conformation-dependent monoclonals were screened and three (mA11-09, mA11-89, and mA11-205) selected for further confirmation in 196 urine samples grouped as follows: severe features PE (sPE, n = 114), PE without severe features (mPE, n = 30), chronic hypertension (crHTN, n = 14) and normotensive pregnant control (P-CRL, n = 38). We showed that the selected conformation-specific monoclonals distinguished among patients with varying severities of PE from P-CRL and patients with crHTN. By use of latent class analysis (LCA) we identified three classes of subjects: Class 1 (n = 94) comprised patients whose urine was both congophilic and reactive with the monoclonals. These women were more likely diagnosed with early-onset sPE and had severe hypertension and proteinuria; Class 2 patients (n = 55) were negative for congophilia and against the antibodies. These were predominantly P-CRL and crHTN patients. Lastly, Class 3 patients (n = 48) were positive for urine congophilia, albeit at lower intensity, but negative for monoclonal immunoreactivities. These women were diagnosed primarily as mPE or late-onset sPE. Collectively, our study validates conformation-dependent Aß imunoreactivity of PE urine which in conjunction to urine congophilia may represent an additional indicator of disease severity.

Accuracy of anemia screening by point-of-care hemoglobin testing in patients seeking abortion.

OBJECTIVE: Accurate and timely diagnosis of anemia in pregnancy is necessary for safe management of abortion care. Screening for anemia in abortion care is often accomplished using commercially-available point-of-care tests from capillary blood, but the validity of this test has not been investigated in the context of abortion care. We sought to determine the accuracy of a capillary hemoglobin (Hb) among pregnant patients seeking induced abortion. STUDY DESIGN: We conducted a retrospective study of patients seeking abortion care at the University of Illinois at Chicago. We identified 108 subjects with paired capillary Hb and venous complete blood count (CBC) hemoglobin measurements within 7 days of each other and within 14 days before abortion. Agreement analysis was performed using Passing-Bablok regression and Bland-Altman plots. RESULTS: More patients were deemed anemic by capillary than by venous Hb measurement (32% vs 19%, p = 0.030). Capillary Hb correlated with venous Hb (r = 0.85, p < 0.001). The average bias for capillary Hb was -1.1 ± 1.0 g/dL. Step-wise, multivariable linear regression identified venous Hb as the only determinant of capillary Hb, and failed to identify any other predictors of bias. The agreement analysis between capillary and venous Hb by Passing-Bablok regression demonstrated systematic and proportional differences. CONCLUSION: Results from capillary Hb may be biased toward diagnosing anemia and should be interpreted with caution. IMPLICATIONS: Misdiagnosing anemia in abortion care can have several consequences and may prevent timely medical abortion or cause delayed procedural abortion. Clinical correlation, and possibly confirmation by venous complete blood count measurement, should be considered before clinical decision-making based solely upon the capillary point-of-care assay.

Work-Life Balance and Productivity Among Academic Faculty During the COVID-19 Pandemic: A Latent Class Analysis.

Background: For faculty in academic health sciences, the balance between research, education, and patient care has been impeded by the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to identify personal and professional characteristics of faculty to understand the impact of the pandemic on faculty and consequent policy implications. Methods: A 93-question survey was sent to faculty at a large urban public university and medical center. Demographic, family, and academic characteristics, work distribution and productivity before and during the pandemic, stress, and self-care data information were collected. Latent class analysis (LCA) was performed to identify classes of faculty sharing similar characteristics. Comparisons between latent classes were performed using analysis of variance and chi-square analyses. Results: Of 497 respondents, 60% were women. Four latent classes of faculty emerged based on six significant indicator variables. Class 1 individuals were more likely women, assistant professors, nontenured with high work and home stress; Class 2 faculty were more likely associate professors, women, tenured, who reported high home and work stress; Class 3 faculty were more likely men, professors, tenured with moderate work, but low home stress; and Class 4 faculty were more likely adjunct professors, nontenured, and had low home and work stress. Class 2 reported significantly increased administrative and clinical duties, decreased scholarly productivity, and deferred self-care. Conclusions: The pandemic has not affected faculty equally. Early and mid-career individuals were impacted negatively from increased workloads, stress, and decreased self-care. Academic leaders need to acknowledge these differences and be inclusive of faculty with different experiences when adjusting workplace or promotion policies.

Controversies in treatment practices of the mother-infant dyad at the limit of viability.

In the setting of threatened extreme preterm birth, balancing maternal and fetal risks and benefits in order to choose the best available treatment options is of utmost importance. Inconsistency in treatment practices for infants born between 22 and 24 weeks of gestatotional age may account for inter-hospital variation in survival rates with and without impairment. Most importantly, non-biased and accurate information must be presented to the family as soon as extremely preterm birth is suspected, including counseling on morbidities and mortality associated with delivery at the limits of viability. This review will focus on different therapeutic medical and surgical practices available for threatened extremely preterm birth to improve fetal and maternal outcomes while highlighting the importance of patient-centered approaches.

Population based cohort study of fetal deaths, and neonatal and perinatal mortality at term within a Somali diaspora.

BACKGROUND: Somali women deliver at greater gestational age with limited information on the associated perinatal mortality. Our objective is to compare perinatal mortality among Somali women with the population rates. METHODS: This is a retrospective cohort study from all births that occurred in Minnesota between 2011 and 2017. Information was obtained from certificates of birth, and neonatal and fetal death. Data was abstracted from 470,550 non-anomalous births ≥37 and ≤ 42 weeks of gestation. The study population included U.S. born White, U.S. born Black, women born in Somalia or self-identified as Somali, and women who identified as Hispanic regardless of place of birth (377,426). We excluded births < 37 weeks and > 42 weeks, > 1 fetus, age < 18 or > 45 years, or women of other ethnicities. The exposure was documented ethnicity or place of birth, and the outcomes were live birth, fetal death, neonatal death prior to 28 days, and perinatal mortality rates. These were calculated using binomial proportions with 95% confidence intervals and compared using odds ratios adjusted (aOR) for diabetes, hypertension and maternal body mass index. RESULTS: The aOR [95%CI] for stillbirth rate in the Somali cohort was greater than for U.S. born White (2.05 [1.49-2.83]) and Hispanic women (1.90 [1.30-2.79]), but similar to U.S. born Black women (0.88 [0.57-1.34]). Neonatal death rates were greater than for U.S. born White (1.84 [1.36-2.48], U.S. born Black women (1.47 [1.04-2.06]) and Hispanic women (1.47 [1.05-2.06]). This did not change after analysis was restricted to those with spontaneous onset of labor. When analyzed by week, at 42 weeks Somali aOR for neonatal death was the same as for U.S. born White women, but compared against U.S. born Black and Hispanic women, was significantly lower. CONCLUSIONS: The later mean gestational age at delivery among women of Somali ethnicity is associated with greater overall risk for stillbirth and neonatal death rates at term, except compared against U.S. born Black women with whom stillbirth rates were not different. At 42 weeks, Somali neonatal mortality decreased and was comparable to that of the U.S. born White population and was lower than that of the other minorities.

Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age.

BACKGROUND: Accurate pregnancy dating is critical for maternal and child health and for counseling on safe and effective abortion methods. While last menstrual period and first trimester ultrasound are often used together to determine gestational age (GA), they have limited accuracy and availability, respectively. Prior studies have shown that pregnancy-associated plasma protein-A (PAPP-A) increases exponentially during pregnancy and has the potential to serve as a biochemical marker of GA. We aimed to analyze the relationship between sonographically determined GA and serum PAPP-A concentration measured by different immunoassays and to derive cutoff levels informative for the 70 days GA commonly recommended limit for medical abortion in outpatient settings. METHODS: We compared technical characteristics of 4 commercially available PAPP-A immunoassays and tested 120 maternal serum samples (GA range: 34-231 days) along with contrived pool samples and traceable quality controls. These characteristics included area under the receiver operator characteristic (AUROC) plot, sensitivity and specificity based on cutoffs defined by the Youden Index, and likelihood ratios. RESULTS: All 4 immunoassays had sensitivities and specificities ≥80%, and AUROC values ranging from 0.948 to 0.968. Marked differences among absolute PAPP-A values were noted depending on immunoassay. PAPP-A cutoff values at 70 days GA for each individual immunoassay were established along with procedural recommendations that increase equivalence among immunoassays. CONCLUSIONS: Maternal serum PAPP-A levels correlated strongly with GA despite differences in immunoassay formats and absolute data output. Serum PAPP-A has biomarker potential for future development of a point-of-care test aimed at increasing access to medical abortion.