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.

Cannabis use in pregnancy and maternal and infant outcomes: A Canadian cross-jurisdictional population-based cohort study.

BACKGROUND: With the recent legalization of cannabis in Canada, there is an urgent need to understand the effect of cannabis use in pregnancy. Our population-based study investigated the effects of prenatal cannabis use on maternal and newborn outcomes, and modification by infant sex. METHODS: The cohort included 1,280,447 singleton births from the British Columbia Perinatal Data Registry, the Better Outcomes Registry & Network Ontario, and the Perinatal Program Newfoundland Labrador from April 1st, 2012 to March 31st, 2019. Logistic regression determined the associations between prenatal cannabis use and low birth weight, small-for-gestational age, large-for-gestational age, spontaneous and medically indicated preterm birth, very preterm birth, stillbirth, major congenital anomalies, caesarean section, gestational diabetes and gestational hypertension. Models were adjusted for other substance use, socio-demographic and-economic characteristics, co-morbidities. Interaction terms were included to investigate modification by infant sex. RESULTS: The prevalence of cannabis use in our cohort was approximately 2%. Prenatal cannabis use is associated with increased risks of spontaneous and medically indicated preterm birth (1.80[1.68-1.93] and 1.94[1.77-2.12], respectively), very preterm birth (1.73[1.48-2.02]), low birth weight (1.90[1.79-2.03]), small-for-gestational age (1.21[1.16-1.27]) and large-for-gestational age (1.06[1.01-1.12]), any major congenital anomaly (1.71[1.49-1.97]), caesarean section (1.13[1.09-1.17]), and gestational diabetes (1.32[1.23-1.42]). No association was found for stillbirth or gestational hypertension. Only small-for-gestational age (p = 0.03) and spontaneous preterm birth (p = 0.04) showed evidence of modification by infant sex. CONCLUSIONS: Prenatal cannabis use increases the likelihood of preterm birth, low birth weight, small-for-gestational age and major congenital anomalies with prenatally exposed female infants showing evidence of increased susceptibility. Additional measures are needed to inform the public and providers of the inherent risks of cannabis exposure in pregnancy.

Travel Time to Delivery, Antenatal Care, and Birth Outcomes: A Population-Based Cohort of Uncomplicated Pregnancies in British Columbia, 2012-2019.

OBJECTIVE: Health policy and system leaders need to know whether long travel time to a delivery facility adversely affects birth outcomes. In this study, we estimated associations between travel time to delivery and outcomes in low-risk pregnancies. METHODS: This population-based cohort included all singleton births without obstetric comorbidities or intrapartum facility transfers in British Columbia, Canada, from 2012 to 2019. Travel time was measured from maternal residential postal code to delivery facility using road network analysis. We estimated associations between travel time and severe maternal morbidity, stillbirth, pre-term birth, and small-for-gestational age (SGA) and large-for-gestational age (LGA) status using logistic regression, adjusted for confounders (adjusted odds ratios [aORs]). To examine variations in associations between travel time and outcomes by antenatal care utilization, we stratified models by antenatal care categories. RESULTS: Of 232 698 births, 3.8% occurred at a facility ≥60 minutes from the maternal residence. Obesity, adolescent age, substance use, inadequate prenatal care, and low socioeconomic status were more frequent among those traveling farther for delivery. Travel time ≥120 minutes was associated with increased risk of stillbirth (aOR 1.8; 95% CI 1.2-2.8), pre-term birth (aOR 2.3; 95% CI 2.1-2.5), LGA (aOR 1.5; 95% CI 1.4-1.6), and severe maternal morbidity (aOR 1.5; 95% CI 1.2-1.8), but not SGA (aOR 1.0; 95% CI 0.8-1.1), when compared with a travel time of 1-29 minutes. Risk of stillbirth was greatest with inadequate and intensive (adequate plus) antenatal care but persisted for severe maternal morbidity, pre-term birth, and LGA across categories. CONCLUSION: Longer travel time to delivery was associated with increased risk of adverse outcomes in low-risk pregnancies after adjusting for confounding factors. Associations were stronger among those with inadequate antenatal care.

Cannabis Use in Pregnancy in British Columbia and Selected Birth Outcomes.

OBJECTIVE: This study sought to determine the association between cannabis use in pregnancy and stillbirth, small for gestational age (SGA) (<10th percentile), and spontaneous preterm birth (<37 weeks). METHODS: The study used abstracted obstetrical and neonatal medical records for deliveries in British Columbia from April 1, 2008 to March 31, 2016 that were contained in the Perinatal Data Registry of Perinatal Services British Columbia. Chi-square tests were conducted to compare maternal sociodemographic characteristics by cannabis use. Logistic regression was conducted to determine the association between cannabis use and SGA and spontaneous preterm births. Cox proportional hazards regression modelling was used to identify the association between cannabis use and stillbirth. Secondary analyses were conducted to ascertain differences by timing of stillbirth (Canadian Task Force Classification II-2). RESULTS: Maternal cannabis use has increased in British Columbia over the past decade. Pregnant women who use cannabis are younger and more likely to use alcohol, tobacco, and illicit substances and to have a history of mental illness. Using cannabis in pregnancy was associated with a 47% increased risk of SGA (adjusted OR 1.47; 95% CI 1.33-1.61), a 27% increased risk of spontaneous preterm birth (adjusted OR 1.27; 95% CI 1.14-1.42), and a 184% increased risk of intrapartum stillbirth (adjusted HR [aHR] 2.84; 95% CI 1.18-6.82). The association between cannabis use in pregnancy and overall stillbirth and antepartum stillbirth did not reach statistical significance, but it had comparable point estimates to other outcomes (aHR 1.38; 95% CI 0.95-1.99 and aHR 1.34; 95% CI 0.88-2.06, respectively). CONCLUSION: Cannabis use in pregnancy is associated with SGA, spontaneous preterm birth, and intrapartum stillbirth.

Gestational Weight Loss: Comparison Between the Birth Certificate and the Medical Record, Florida, 2012.

Objective Examine agreement with the medical record (MR) when gestational weight loss (GWL) on the Florida birth certificate (BC) is ≥ 0 pounds (lbs). Methods In 2012, 3923 Florida-resident women had a live, singleton birth where BC indicated GWL ≥ 0 lbs. Of these, we selected a stratified random sample of 2141 and abstracted from the MR prepregnancy and delivery weight data used to compute four estimates of GWL (delivery minus prepregnancy weight) from different sources found within the MR (first prenatal visit record, nursing admission record, labor/delivery records, BC worksheet). We assessed agreement between the BC and MR estimates for GWL categorized as 0, 1-10, 11-19, and ≥ 20 lbs. Results Prepregnancy or delivery weight was missing or source not in the MR for 23-81% of records. Overall agreement on GWL between the BC and the four MR estimates ranged from 39.1 to 57.2%. Agreement by GWL category ranged from 10.6 to 38.0% for 0 lbs, 47.6 to 64.3% for 1-10 lbs, 49.5 to 60.0% for 11-19 lbs, and 47.8 to 67.7% for ≥ 20 lbs. Conclusions Prepregnancy and delivery weight were frequently missing from the MR or inconsistently documented across the different sources. When the BC indicated GWL ≥ 0 lbs, agreement with different sources of the MR was moderate to poor revealing the need to reduce missing data and better understand the quality of weight data in the MR.

Timing of Maternal Tobacco Exposure, Hypertension, and Risk of Singleton Small-For-Gestational Age Infants.

OBJECTIVE: Small-for-gestational age infants are at an increased risk for disabilities and chronic health problems. Smoking and hypertension during pregnancy pose significant risks for fetal growth restriction. The study aims to identify whether (1) the timing of tobacco use modifies the risk of small-for-gestational age, (2) there are differences in association by percentile of small-for-gestational age (3rd, 5th, and 10th percentile), and (3) the effect of tobacco exposure on small-for-gestational age outcome is mediated by hypertension. MATERIALS AND METHODS: Data were obtained from the 2009 Natality public use file available through the National Center for Health Statistics. Women were categorized into 11 groups depending on the trimester of tobacco exposure, the number of daily cigarettes smoked, and presence of hypertension. Multivariable log-linear regression models were performed to determine the association between percentile of singleton small-for-gestational age outcome (3rd, 5th, and 10th), trimester and degree of tobacco exposure, and hypertension. RESULTS: Hypertension and smoking worked synergistically to restrict fetal growth. Hypertensive women who smoked heavily in all three trimesters were 4.34 times more likely to give birth to a 3rd percentile small-for-gestational age infant compared with nonsmoking normotensive women. CONCLUSION: The timing and duration of tobacco exposure mediates the risk and severity of fetal growth restriction.

The Impact of ART on Live Birth Outcomes: Differing Experiences across Three States.

BACKGROUND: Research has shown an association between assisted reproductive technology (ART) and adverse birth outcomes. We identified whether birth outcomes of ART-conceived pregnancies vary across states with different maternal characteristics, insurance coverage for ART services, and type of ART services provided. METHODS: CDC's National ART Surveillance System data were linked to Massachusetts, Florida, and Michigan vital records from 2000 through 2006. Maternal characteristics in ART- and non-ART-conceived live births were compared between states using chi-square tests. We performed multivariable logistic regression analyses and calculated adjusted odds ratios (aOR) to assess associations between ART use and singleton preterm delivery (<32 weeks, <37 weeks), singleton small for gestational age (SGA) (<5th and <10th percentiles) and multiple birth. RESULTS: ART use in Massachusetts was associated with significantly lower odds of twins as well as triplets and higher order births compared to Florida and Michigan (aOR 22.6 vs. 30.0 and 26.3, and aOR 37.6 vs. 92.8 and 99.2, respectively; Pinteraction < 0.001). ART use was associated with increased odds of SGA in Michigan only, and with preterm delivery (<32 and <37 weeks) in all states (aOR range: 1.60, 1.87). CONCLUSIONS: ART use was associated with an increased risk of preterm delivery among singletons that showed little variability between states. The number of twins, triplets and higher order gestations per cycle was lower in Massachusetts, which may be due to the availability of insurance coverage for ART in Massachusetts.

Postpartum Weight Retention and Subsequent Pregnancy Outcomes.

The effects of postpartum weight retention on gestational weight gain in successive pregnancies require elucidation. The purpose of the study was (1) to examine the association between postpartum weight retention and subsequent adherence to the Institute of Medicine gestational weight gain guidelines and (2) to determine whether the association varies by body mass index status and affects birth outcomes. Florida vital records for 2005-2010 were analyzed using χ tests and multivariable Poisson regression, adjusted for interpregnancy interval, tobacco use, maternal age, and race/ethnicity. Obese women who gained inadequate weight were more likely to retain weight between pregnancies than obese women who met or exceeded the recommended weight gain. Risks for preterm birth increased among women with inadequate weight and decreased among women with excessive weight gain. Gaining excessive weight was protective for small-for-gestational age infants in all body mass index categories but increased the risks for large-for-gestational age infants. Underweight and normal weight women who gained in excess were 40% more likely to develop hypertension than normal weight women who gained within the recommended amount. Obese women who retain or gain weight postpartum are at increased risk for inadequate weight gain in a successive pregnancy. Achieving Institute of Medicine-recommended gestational weight gain is essential for preventing adverse maternal and infant outcomes.

Health and economic effects from linking bedside and outpatient tobacco cessation services for hospitalized smokers in two large hospitals: study protocol for a randomized controlled trial.

BACKGROUND: Extended smoking cessation follow-up after hospital discharge significantly increases abstinence. Hospital smoke-free policies create a period of 'forced abstinence' for smokers, thus providing an opportunity to integrate tobacco dependence treatment, and to support post-discharge maintenance of hospital-acquired abstinence. This study is funded by the National Heart, Lung, and Blood Institute (1U01HL1053231). METHODS/DESIGN: The Inpatient Technology-Supported Assisted Referral study is a multi-center, randomized clinical effectiveness trial being conducted at Kaiser Permanente Northwest (KPNW) and at Oregon Health & Science University (OHSU) hospitals in Portland, Oregon. The study assesses the effectiveness and cost-effectiveness of linking a practical inpatient assisted referral to outpatient cessation services plus interactive voice recognition (AR + IVR) follow-up calls, compared to usual care inpatient counseling (UC). In November 2011, we began recruiting 900 hospital patients age ≥18 years who smoked ≥1 cigarettes in the past 30 days, willing to remain abstinent postdischarge, have a working phone, live within 50 miles of the hospital, speak English, and have no health-related barriers to participation. Each site will randomize 450 patients to AR + IVR or UC using a 2:1 assignment strategy. Participants in the AR + IVR arm will receive a brief inpatient cessation consult plus a referral to available outpatient cessation programs and medications, and four IVR follow-up calls over seven weeks postdischarge. Participants do not have to accept the referral. At KPNW, UC participants will receive brief inpatient counseling and encouragement to self-enroll in available outpatient services. The primary outcome is self-reported thirty-day smoking abstinence at six months postrandomization for AR + IVR participants compared to usual care. Additional outcomes include self-reported and biochemically confirmed seven-day abstinence at six months, self-reported seven-day, thirty-day, and continuous abstinence at twelve months, intervention dose response at six and twelve months for AR + IVR recipients, incremental cost-effectiveness of AR + IVR intervention compared to usual care at six and twelve months, and health-care utilization and expenditures at twelve months for AR + IVR recipients compared to UC. DISCUSSION: This study will provide important evidence for the effectiveness and cost-effectiveness of linking hospital-based tobacco treatment specialists' services with discharge follow-up care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01236079.

Obesity in older mothers, gestational weight gain, and risk estimates for preterm phenotypes.

OBJECTIVE: To assess whether advanced maternal age modifies the relationship between maternal pregravid weight status, gestational weight gain patterns, and the occurrence of spontaneous preterm birth (SPB) and medically indicated preterm birth (MIPB). METHODS: Retrospective cohort analysis of vital statistics data from the state of Florida for the period 2004 through 2007 comprising 311,422 singleton pregnancies (two age groups: 20-24 years old or younger women and >or=35 years or older women). Mothers were classified into five clusters based on their pre-pregnancy body mass index (BMI) values: non-obese (less than 30), class I obese (30.0or=50.0). RESULTS: MIPB occurred more frequently among older than younger women [11.8% vs. 6.4%, respectively (p<0.0001)) whereas SPB occurred more frequently among younger women [11.3% vs. 10.5%, respectively (p<0.0001)). Maternal obesity increased the risk for MIPB but not for SPB. Regardless of BMI status, the risk of MIPB was elevated among older mothers, particularly among those with suboptimal (<0.23 kg/week) and supraoptimal (>0.68 kg/week) gestational weight gain. A dose-response relationship with increasing gestational weight gain was evident (p<0.01); the greatest risk for MIPB occurred among older mothers with weekly gestational weight gain in excess of 0.79 kg (OR=7.76, 95% CI=5.73-10.5). CONCLUSION: The occurrence of medically indicated preterm birth is positively associated with increased maternal pregravid body weight, older maternal age and extremes of gestational weight gain. Targeted pre- and inter-conception weight management efforts should be particularly encouraged in older mothers.

Joint effect of obesity and teenage pregnancy on the risk of preeclampsia: a population-based study.

PURPOSE: To determine the joint effect of young maternal age and obesity status on the risk of preeclampsia and eclampsia among a large cohort of singleton pregnancies. METHODS: Data were obtained from birth cohort files recorded in the state of Florida during the years 2004-2007. The study sample consisted of mothers aged 13-24 (n = 290,807), divided into four obesity categories on the basis of prepregnancy body mass index (BMI): nonobese (BMI < 30), Class I obese (30.0 < or = BMI > or = 34.9), Class II obese (35.0 < or = BMI > or = 39.9), and extreme obesity (BMI > or = 40). Nonobese mothers (BMI < 30) between the ages of 20 and 24 years were the reference group. Logistic regression models were generated to adjust for the association between preeclampsia, obesity, and maternal age with sociodemographic variables and pregnancy complications as covariates. RESULTS: The overall prevalence of preeclampsia in the study population was 5.0%. The risk of preeclampsia and eclampsia increased significantly with increasing BMI and decreasing age. Extremely obese teenagers were almost four times as likely to develop preeclampsia and eclampsia compared with nonobese women aged 20-24 years (adjusted odds ratio [95% confidence interval] = 3.79 [3.15-4.55]). Whereas obesity elevated the risk for preeclampsia and eclampsia among all women in the study, teenagers were most at risk because of the combined effects of young age and obesity. CONCLUSION: Effective obesity prevention strategies should continue to be advocated for all teenagers, in addition to innovative approaches to teenage pregnancy prevention.

The impact of obesity on spontaneous and medically indicated preterm birth among adolescent mothers.

PURPOSE: We sought to evaluate the impact of obesity on the risk of spontaneous and medically indicated preterm birth in young women compared to adult women. METHODS: Florida vital records from 2004 to 2007 were used to obtain data. The study sample consisted of 290,807 mothers of whom 4,739 were adolescent girls < or =15 years old: 23,228 were girls 16-17 years old; 58,196 were women 18-19 years old; and 204,644 were women 20-24 years old. Adjusted estimates for spontaneous and medically indicated preterm birth were determined based on maternal BMI and weight gain during pregnancy. Subjects were categorized by BMI as follows: class I obesity (30.0 < or = BMI < or = 34.9), class II obesity (35.0 < or = BMI < or = 39.9), class III obesity (40 < or = BMI < or = 49.9), and super-obese (BMI > or = 50.0). RESULTS: Obese mothers had elevated risk for medically indicated preterm birth and lower risk for spontaneous preterm birth compared to non-obese mothers. Overall, the risk for spontaneous preterm birth increased in a dose-dependent fashion with younger age but no age-dependent trend was observed for medically indicated preterm birth (P < 0.0001). Very low weight gain (<0.12 kg/week) during pregnancy was associated with a higher risk of spontaneous preterm birth among both non-obese and obese teenagers. CONCLUSIONS: Preterm birth is a heterogeneous entity that is mediated by obesity status and maternal age. Obesity among pregnant teenagers increases the risk for medically indicated preterm birth but not the risk for spontaneous preterm birth.

Risk factors for major antenatal depression among low-income African American women.

OBJECTIVES: Data on risk factors for major antenatal depression among African American women are scant. In this study, we seek to determine the prevalence and risk factors for major antenatal depression among low-income African American women receiving prenatal services through the Central Hillsborough Healthy Start (CHHS). METHODS: Women were screened using the Edinburgh Postnatal Depression Scale (EPDS) with a cutoff of > or =13 as positive for risk of major antenatal depression. In total, 546 African American women were included in the analysis. We used logistic regression to identify risk factors for major antenatal depression. RESULTS: The prevalence of depressive symptomatology consistent with major antenatal depression was 25%. Maternal age was identified as the main risk factor for major antenatal depression. The association between maternal age and risk for major antenatal depression was biphasic, with a linear trend component lasting until age 30, at which point the slope changed markedly tracing a more pronounced likelihood for major depression with advancing age. Women aged > or =30 were about 5 times as likely to suffer from symptoms of major antenatal depression as teen mothers (OR = 4.62, 95% CI 2.23-9.95). CONCLUSIONS: The risk for major antenatal depression increases about 5-fold among low-income African American women from age 30 as compared to teen mothers. The results are consistent with the weathering effect resulting from years of cumulative stress burden due to socioeconomic marginalization and discrimination. Older African American mothers may benefit from routine antenatal depression screening for early diagnosis and intervention.

The superobese mother and ethnic disparities in preterm birth.

OBJECTIVES: We assessed the association between preterm birth and obesity subtypes across racial/ethnic groups. METHODS: We analyzed data on 540981 women from birth cohort files for the State of Florida from 2004 to 2007. Obese women were categorized using body mass index (BMI) values as class I obese (30.0 < or = BMI < or = 34.9), class II obese (35.0 < or = BMI < or = 39.9), class III or extremely obese (40 < or = BMI < or = 49.9), and superobese (BMI > or = 50.0). Logistic regression was used to obtain adjusted estimates. RESULTS: About 28% of women were obese, with the highest rate (40.9%) registered among black gravidas, while whites and Hispanics had comparable rates (24.3% vs 25.5%, respectively). Superobesity was also most prevalent in blacks (1.3%). Among obese women, the risk for preterm birth was greatest among blacks (OR, 1.71; 95% CI, 1.65-1.77), while whites (OR, 1.15; 95% CI, 1.12-1.19) and Hispanics (OR, 1.22; 95% CI, 1.18-1.27) had significantly lower and comparable risk levels. CONCLUSIONS: Extremely obese and superobese women are emerging high-risk groups for adverse birth outcomes, and black women appear to bear the heaviest burden. The disproportionately rising trend in extreme forms of obesity among black women is of utmost concern and represents a clarion call for infusion of more resources into obesity prevention programs in black communities.