Mining the Gap: Deriving Pregnancy Reference Intervals for Hematology Parameters Using Clinical Datasets.

BACKGROUND: Physiological changes during pregnancy invalidate use of general population reference intervals (RIs) for pregnant people. The complete blood count (CBC) is commonly ordered during pregnancy, but few studies have established pregnancy RIs suitable for contemporary Canadian mothers. Prospective RI studies are challenging to perform during pregnancy while retrospective techniques fall short as pregnancy and health status are not readily available in the laboratory information system (LIS). This study derived pregnancy RIs retrospectively using LIS data linked to provincial perinatal registry data. METHODS: A 5-year healthy pregnancy cohort was defined from the British Columbia Perinatal Data Registry and linked to laboratory data from two laboratories. CBC and differential RIs were calculated using direct and indirect approaches. Impacts of maternal and pregnancy characteristics, such as age, body mass index, and ethnicity, on laboratory values were also assessed. RESULTS: The cohort contained 143 106 unique term singleton pregnancies, linked to >972 000 CBC results. RIs were calculated by trimester and gestational week. Result trends throughout gestation aligned with previous reports in the literature, although differences in exact RI limits were seen for many tests. Trimester-specific bins may not be appropriate for several CBC parameters that change rapidly within trimesters, including red blood cells (RBCs), some leukocyte parameters, and platelet counts. CONCLUSIONS: Combining information from comprehensive clinical databases with LIS data provides a robust and reliable means for deriving pregnancy RIs. The present analysis also illustrates limitations of using conventional trimester bins during pregnancy, supporting use of gestational age or empirically derived bins for defining CBC normal values during pregnancy.

Upgrade Rate of Flat Epithelial Atypia Diagnosed at Stereotactic Core Needle Biopsy of Microcalcifications: Is Excisional Biopsy Indicated?

OBJECTIVE: Whether the optimal management of pure flat epithelial atypia (FEA) found on core needle biopsy (CNB) specimens is surgical excision or imaging follow-up remains controversial. This study aimed to determine the upgrade rate to ductal carcinoma in situ (DCIS), invasive carcinoma or a high-risk lesion (atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in situ), and it explored the relationship between a family history of breast cancer and the risk of upgrade. METHODS: Cases with pure FEA found on stereotactic CNB of microcalcifications between March 2011 to December 2017 were followed by excisional biopsy or periodic imaging. The proportion of cases upgraded to a high-risk lesion and the odds of upgrade as related to a family history of breast cancer were determined with 95% confidence intervals (CIs). RESULTS: We identified 622 cases of pure FEA; 101 (16.2%) underwent surgical excision and 269 (43.2%) had imaging follow-up of ≥ 24 months. There were no upgrades to DCIS or invasive cancer in any of these 370 individuals (0%), and 4.6% (17/370; 95% CI: 2.9%-7.2%) were upgraded to a high-risk lesion. There was a nonstatistically significant trend between family history and upgrade to high-risk lesion (odds ratio 1.72 [95% CI: 0.65%-4.57%]). CONCLUSION: In our study, the upgrade rate of pure FEA to malignancy was 0%. We suggest that regular imaging follow-up is an appropriate alternative to surgery. Because of potential differences in biopsy techniques and pathologist interpretation of the primary biopsy, individual institutions should audit their own results prior to altering their management of FEA.

Maternal and Perinatal Morbidity and Mortality Associated With Anemia in Pregnancy.

OBJECTIVE: To estimate the incidence of anemia in pregnancy and compare the maternal and perinatal outcomes of women with and without anemia. METHODS: We conducted a population-based retrospective cohort study on all pregnant women in British Columbia who had a live birth or stillbirth at or after 20 weeks of gestation between 2004 and 2016. Women were diagnosed with anemia based on two criteria: third-trimester hemoglobin value or a delivery admission diagnosis of anemia (made before delivery). Anemia was categorized into no anemia (hemoglobin 11 g/dL or greater), mild (9-10.9 g/dL), moderate (7-8.9 g/dL), severe (less than 7 g/dL), or anemia of unspecified severity (with diagnosis made before delivery). Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs expressing the association between anemia and maternal and perinatal outcomes. RESULTS: Of 515,270 women in the study population, 65,906 (12.8%) had anemia: 11.8%, 0.43%, and 0.02% had mild, moderate, and severe anemia, respectively, and 0.58% had anemia of unspecified severity. Anemic women had longer hospitalization duration and more antenatal admissions, and rates of preeclampsia, placenta previa and cesarean delivery were higher among women with anemia. The intrapartum-postpartum blood transfusion rate was 5.1 per 1,000 among women without anemia, and higher among women with anemia (aOR 2.45, 95% CI 1.74-3.45 for mild anemia; 21.3, 95% CI 12.2-37.3 for moderate anemia; not analyzable for severe anemia; and 48.3, 95% CI 6.60-353.9 for anemia of unspecified severity). Anemia was associated with preterm birth (mild anemia, aOR 1.09, 95% CI 1.05-1.12; moderate anemia, aOR 2.26, 95% CI 2.02-2.54; anemia of unspecified severity, aOR 2.27, 95% CI 2.06-2.50), small-for-gestational-age live birth, low 5-minute Apgar score, neonatal death, and perinatal death. CONCLUSION: Maternal anemia in pregnancy represents a common and potentially reversible risk factor associated with antepartum, intrapartum, and postpartum maternal morbidity and perinatal morbidity and mortality.