The clinical performance and population health impact of birthweight-for-gestational age indices at term gestation.

BACKGROUND: The assessment of birthweight for gestational age and the identification of small- and large-for-gestational age (SGA and LGA) infants remain contentious, despite the recent creation of the Intergrowth 21st Project and World Health Organisation (WHO) birthweight-for-gestational age standards. OBJECTIVE: We carried out a study to identify birthweight-for-gestational age cut-offs, and corresponding population-based, Intergrowth 21st and WHO centiles associated with higher risks of adverse neonatal outcomes, and to evaluate their ability to predict serious neonatal morbidity and neonatal mortality (SNMM) at term gestation. METHODS: The study population was based on non-anomalous, singleton live births between 37 and 41 weeks' gestation in the United States from 2003 to 2017. SNMM included 5-min Apgar score <4, neonatal seizures, need for assisted ventilation, and neonatal death. Birthweight-specific SNMM was modelled by gestational week using penalised B-splines. The birthweights at which SNMM odds were minimised (and higher by 10%, 50% and 100%) were estimated, and the corresponding population, Intergrowth 21st, and WHO centiles were identified. The clinical performance and population impact of these cut-offs for predicting SNMM were evaluated. RESULTS: The study included 40,179,663 live births and 991,486 SNMM cases. Among female singletons at 39 weeks' gestation, SNMM odds was lowest at 3203 g birthweight, and 10% higher at 2835 g and 3685 g (population centiles 11th and 82nd, Intergrowth centiles 17th and 88th and WHO centiles 15th and 85th). Birthweight cut-offs were poor predictors of SNMM, for example, the cut-offs associated with 10% and 50% higher odds of SNMM among female singletons at 39 weeks' gestation resulted in a sensitivity, specificity, and population attributable fraction of 12.5%, 89.4%, and 2.1%, and 2.9%, 98.4% and 1.3%, respectively. CONCLUSIONS: Reference- and standard-based birthweight-for-gestational age indices and centiles perform poorly for predicting adverse neonatal outcomes in individual infants, and their associated population impact is also small.

Antenatal Corticosteroid Prophylaxis at Late Preterm Gestation: Clinical Guidelines Versus Clinical Practice.

OBJECTIVE: We investigated how the Antenatal Late Preterm Steroids (ALPS) trial findings have been translated into clinical practice in Canada and the United States (U.S.). METHODS: The study included all live births in Nova Scotia, Canada, and the U.S. from 2007 to 2020. Antenatal corticosteroids (ACS) administration within specific categories of gestational age was assessed by calculating rates per 100 live births, and temporal changes were quantified using odds ratio (OR) and 95% confidence intervals (CI). Temporal trends in optimal and suboptimal ACS use were also assessed. RESULTS: In Nova Scotia, the rate of any ACS administration increased significantly among women delivering at 350 to 366 weeks, from 15.2% in 2007-2016 to 19.6% in 2017-2020 (OR 1.36, 95% CI 1.14-1.62). Overall, the U.S. rates were lower than the rates in Nova Scotia. In the U.S., rates of any ACS administration increased significantly across all gestational age categories: among live births at 350 to 366 weeks gestation, any ACS use increased from 4.1% in 2007-2016 to 18.5% in 2017-2020 (OR 5.33, 95% CI 5.28-5.38). Among infants between 240 and 346 weeks gestation in Nova Scotia, 32% received optimally timed ACS, while 47% received ACS with suboptimal timing. Of the women who received ACS in 2020, 34% in Canada and 20% in the U.S. delivered at ≥37 weeks. CONCLUSION: Publication of the ALPS trial resulted in increased ACS administration at late preterm gestation in Nova Scotia, Canada, and the U.S. However, a significant fraction of women receiving ACS prophylaxis delivered at term gestation.

Maternal cannabis use during pregnancy and maternal and neonatal outcomes: A retrospective cohort study.

OBJECTIVE: To examine the relationship between reported prenatal cannabis use and neonatal and maternal outcomes and whether the legalisation of cannabis in Canada affected the rates of reported use or the association with maternal and neonatal outcomes. DESIGN: Population-based retrospective cohort study. SETTING: Routinely collected data in a real-world setting. POPULATION: All women in the Canadian province of Nova Scotia with singleton births between 1 January 2004 and 30 June 2021. METHODS: The association between cannabis use and maternal and neonatal outcomes was examined using generalised linear models with inverse probability weighting. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes in the peripartum and postpartum period. RESULTS: Rates of reported cannabis use in pregnancy increased from 1.3% to 7.5% over the study period with no appreciable change in slope after legalisation in 2018. Infants of mothers reporting cannabis use in pregnancy were more likely to have major anomalies and a 5-minute Apgar score ≤7, require neonatal intensive care unit admission, and had lower birthweight, head circumference and birth length than infants of mothers not reporting cannabis use. These associations did not differ before and after legalisation. CONCLUSIONS: Reported cannabis use during pregnancy is associated with early postnatal complications and reduced fetal growth, even after taking into account a range of confounding factors. Rates of reported cannabis use during pregnancy increased over the past 5 years in Nova Scotia with no apparent additional effect of legalisation.

The 3G Multigenerational Cohort of Nova Scotian women and their mothers and offspring.

BACKGROUND: The negative impact of exposures such as maternal obesity, excessive gestational weight gain, and hypertension in pregnancy on the health of the next generation has been well studied. Evidence from animal studies suggests that the effects of in utero exposures may persist into the second generation, but the epidemiological literature on the influence of pregnancy-related exposures across three generations in humans is sparse. OBJECTIVES: This cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring. POPULATION: The cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward. DESIGN: Intergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort. METHODS: The cohort has prospectively collected information on sociodemographics, maternal health and health behaviours, pregnancy health and complications, and obstetrical and neonatal outcomes for two generations of women and their offspring. PRELIMINARY RESULTS: As of October 2018, the 3G cohort included 14 978 grandmothers (born 1939-1986), 16 766 mothers or cohort women (born 1981-2003), and 28 638 children (born 1996-2018). The cohort women were generally younger than Nova Scotian women born after 1980, and as a result, characteristics associated with pregnancy at a younger age were more frequently seen in the cohort women; sampling weights will be created to account for this design effect. The cohort will be updated annually to capture future deliveries to women who are already in the cohort and women who become eligible for inclusion when they deliver their first child. CONCLUSIONS: The 3G Multigenerational Cohort is a population-based cohort of women and their mothers and offspring, spanning a time period of 38 years, and provides the opportunity to study inter- and transgenerational associations across the maternal line.

Physical activity barriers, preferences, and beliefs in childhood cancer patients.

PURPOSE: Childhood cancer patients report low physical activity levels despite the risk for long-term complications that may benefit from exercise. Research is lacking regarding exercise barriers, preferences, and beliefs among patients (1) on- and off-therapy and (2) across the age spectrum. METHODS: Cross-sectional study in the Yale Pediatric Hematology-Oncology Clinic (October 2013-October 2014). Participants were ≥ 4 years old, > 1 month after cancer diagnosis at < 20 years, not acutely ill, expected to live > 6 months, and received chemotherapy and/or radiation. Participants (or parents if < 13 years) completed a survey. RESULTS: The 162 patients (99% participated) were 34% children (4.0-12.9 years), 31% adolescents (13.0-17.9 years), and 35% adults (≥ 18 years). Most had leukemia/lymphoma (66%); 32% were on-therapy. On-therapy patients were more likely than off-therapy patients (73 vs. 48%; p = 0.003) to report ≥ 1 barrier related to physical complaints, such as "just too tired" (46 vs. 28%; p = 0.021) or "afraid" of injury (22 vs. 9%; p = 0.027). The majority preferred walking (73%), exercising at home (91%), exercising in the afternoon (79%), and a maximum travel time of 10-20 min (54%); preferences did not vary significantly by therapy status or age. Most respondents (94%) recognized the benefits of exercise after cancer, but 50% of on- vs. 12% of off-therapy patients believed "their cancer diagnosis made it unsafe to exercise regularly" (p < 0.001). CONCLUSIONS: Physical activity barriers pertaining to physical complaints and safety concerns were more pronounced in on-therapy childhood cancer patients but persisted off-therapy. Preferences and beliefs were relatively consistent. Our data can inform interventions in different patient subgroups.

Fetal Echocardiographic Measures to Improve the Prenatal Diagnosis of Coarctation of the Aorta.

The objective of this study is to identify fetal echocardiographic measures that predict postnatal coarctation of the aorta (CoA). A retrospective review of patients from 2013 to 2017 identified 13 cases of prenatal diagnosis of CoA confirmed postnatally and 14 cases of prenatal diagnosis of CoA with normal arches postnatally. There were 30 controls. Measurements were made and indices applied on all available longitudinal fetal echocardiograms for each patient. Linear mixed effects models were used to examine the between-group differences in the trajectories of the measurements. Significant differences were seen in the true CoA group for the following: smaller distal transverse arch diameter to distance between the left common carotid and left subclavian arteries (DT/LCA-LSCA) index (p = 0.04), smaller distal transverse arch diameter (p = 0.005), and longer brachiocephalic to left common carotid artery (LCA) (p = 0.004) and LCA-left subclavian artery (LSCA) distances (p < 0.0001). Additionally, the LCA/DT index trend appears to differentiate false positives from true coarctations (p < 0.03). The fetal echocardiographic DT/LCA-LSCA index, brachiocephalic-LCA distance and LCA-LSCA distance are significant predictors of postnatal coarctation. The LCA/DT index trend over time may differentiate which of those patients with prenatal concern for coarctation are more likely to develop coarctation postnatally. The use of fetal echocardiographic measures may improve prenatal detection and predication of postnatal coarctation.

A home-based physical activity intervention using activity trackers in survivors of childhood cancer: A pilot study.

BACKGROUND: Over 70% of childhood cancer survivors develop late complications from therapy, many of which can be mitigated by physical activity. Survivors engage in exercise at similar or lower rates than their sedentary healthy peers. We piloted a novel home-based exercise intervention with a motivational activity tracker. We evaluated (i) feasibility, (ii) impact on activity levels and physical fitness, and (iii) barriers, preferences, and beliefs regarding physical activity. METHODS: Childhood cancer survivors currently 15 years or older and not meeting the Centers for Disease Control and Prevention physical activity guidelines were enrolled and instructed to wear the Fitbit One, a 4.8 cm × 1.8 cm motivational activity tracker, daily for 6 months. Baseline and follow-up evaluations included self-report surveys, an Actigraph accelerometer for 7 days, and a VO2 maximum test by cardiac stress test. RESULTS: Nineteen participants were enrolled (13.4% participation rate) with a mean age of 24.3 ± 5.8 years (range 15-35). Four participants withdrew with a 79% retention rate. Participants wore the Fitbit an average of 19.0 ± 4.7 days per month during months 1-3 and 15.0 ± 7.9 days per month during months 4-6. Total weekly moderate to vigorous physical activity increased from 265.6 ± 117.0 to 301.4 ± 135.4 min and VO2 maximum increased from 25.7 ± 7.7 to 27.2 ± 7.4 ml/kg/min. These changes were not statistically significant (P = 0.47 and 0.30, respectively). Survey responses indicated no change in barriers, preferences, and beliefs regarding physical activity. CONCLUSIONS: This pilot study of a motivational activity tracker demonstrated feasibility as measured by participant retention, receptivity, and belief of utility. Future studies with a large sample size are needed to demonstrate the efficacy and sustainability of this intervention.

Vitamin D Status After Cardiopulmonary Bypass in Children With Congenital Heart Disease.

Deficiency in 25-hydroxyvitamin D (25OHD) is associated with increased morbidity and mortality in the critically ill. Children who underwent surgery for congenital heart disease under cardiopulmonary bypass (CPB) are typically deficient in 25OHD. It is unclear whether this deficiency is due to CPB. We hypothesized that CPB reduces the levels of 25OHD in children with congenital heart disease. We conducted a prospective observational study on children aged 2 months to 17 years who underwent CPB. Serum was collected at 3 time points: immediately before, immediately after surgery, and 24 hours after surgery. 25-Hydroxyvitamin D, 1,25-dihydroxyvitamin D, 1,25(OH)2D, vitamin D binding protein, and albumin levels were measured. Levels were compared using repeated measures analysis of variance. We enrolled 20 patients, 40% were deficient in 25OHD with levels <20 ng/mL prior to surgery. Mean (±standard deviation) of 25OHD at the 3 time points was 21.3 ± 8 ng/mL, 19 ± 5.8 ng/mL, and 19.5 ± 6.6 ng/mL, respectively ( P = .02). The decrease in 25OHD was observed primarily in children with sufficient levels of 25OHD, with mean levels at the 3 time points: 26.8 ± 4.2 ng/mL, 21.5 ± 5.7 ng/mL, and 23.0 ± 4.9 ng/mL, respectively ( P < .001). Calculated means of free fraction of 25OHD at the 3 time points were 6.2 ± 2.8 pg/mL, 5.8 ± 2.2 pg/mL, and 5.5 ± 2.4 pg/mL, respectively, ( P = .04). Mean levels of 1,25(OH)2D were 63.7 ± 34.9 ng/mL, 53.2 ± 30.6 ng/mL, and 67.7 ± 23.5 ng/mL ( P = .04). Vitamin D binding protein and albumin levels did not significantly change. Cardiopulmonary bypass decreases 25OHD by reducing the free fraction. Current investigations are geared to establish whether vitamin D deficiency is associated with outcomes and if treatment is appropriate.

Contribution of prepregnancy body mass index and gestational weight gain to adverse neonatal outcomes: population attributable fractions for Canada.

BACKGROUND: Low or high prepregnancy body mass index (BMI) and inadequate or excess gestational weight gain (GWG) are associated with adverse neonatal outcomes. This study estimates the contribution of these risk factors to preterm births (PTBs), small-for-gestational age (SGA) and large-for-gestational age (LGA) births in Canada compared to the contribution of prenatal smoking, a recognized perinatal risk factor. METHODS: We analyzed data from the Canadian Maternity Experiences Survey. A sample of 5,930 women who had a singleton live birth in 2005-2006 was weighted to a nationally representative population of 71,200 women. From adjusted odds ratios, we calculated population attributable fractions to estimate the contribution of BMI, GWG and prenatal smoking to PTB, SGA and LGA infants overall and across four obstetric groups. RESULTS: Overall, 6% of women were underweight (<18.5 kg/m(2)) and 34.4% were overweight or obese (≥25.0 kg/m(2)). More than half (59.4%) gained above the recommended weight for their BMI, 18.6% gained less than the recommended weight and 10.4% smoked prenatally. Excess GWG contributed more to adverse outcomes than BMI, contributing to 18.2% of PTB and 15.9% of LGA. Although the distribution of BMI and GWG was similar across obstetric groups, their impact was greater among primigravid women and multigravid women without a previous PTB or pregnancy loss. The contributions of BMI and GWG to PTB and SGA exceeded that of prenatal smoking. CONCLUSIONS: Maternal weight, and GWG in particular, contributes significantly to the occurrence of adverse neonatal outcomes in Canada. Indeed, this contribution exceeds that of prenatal smoking for PTB and SGA, highlighting its public health importance.

The safety of Canadian rural maternity services: a multi-jurisdictional cohort analysis.

BACKGROUND: Small Canadian rural maternity services are struggling to maintain core staffing and remain open. Existing evidence states that having to travel to access maternity services is associated with adverse outcomes. The goal of this study is to systematically examine rural maternal and newborn outcomes across three Canadian provinces. METHODS: We analyzed maternal newborn outcomes data through provincial perinatal registries in British Columbia, Alberta and Nova Scotia for deliveries that occurred between April 1st 2003 and March 31st 2008. All births were allocated to maternity service catchments based on the residence of the mothers. Individual catchments were stratified to service levels based on distance to access intrapartum maternity services or the model of maternity services available in the community. The amalgamation of analyses from each jurisdiction involved comparison of logistic regression effect estimates. RESULTS: The number of singleton births included in the study is 150,797. Perinatal mortality is highest in communities that are greater than 4 h from maternity services overall. Rates of prematurity at less than 37 weeks gestation are higher for rural women without local access to services. Caesarean section rates are highest in communities served by general surgical models. CONCLUSION: Composite analysis of data from three Canadian provinces provides the strongest evidence to date demonstrating that we need to sustain small community maternity services with and without caesarean section capability.

Effects of tenofovir on cytokines and nucleotidases in HIV-1 target cells and the mucosal tissue environment in the female reproductive tract.

Tenofovir (TFV) is a reverse transcriptase inhibitor used in microbicide preexposure prophylaxis trials to prevent HIV infection. Recognizing that changes in cytokine/chemokine secretion and nucleotidase biological activity can influence female reproductive tract (FRT) immune protection against HIV infection, we tested the hypothesis that TFV regulates immune protection in the FRT. Epithelial cells, fibroblasts, CD4(+) T cells, and CD14(+) cells were isolated from the endometrium (Em), endocervix (Cx), and ectocervix (Ecx) following hysterectomy. The levels of proinflammatory cytokines (macrophage inflammatory protein 3α [MIP-3α], interleukin 8 [IL-8], and tumor necrosis factor alpha [TNF-α]), the expression levels of specific nucleotidases, and nucleotidase biological activities were analyzed in the presence or absence of TFV. TFV influenced mRNA and/or protein cytokines and nucleotidases in a cell- and site-specific manner. TFV significantly enhanced IL-8 and TNF-α secretion by epithelial cells from the Em and Ecx but not from the Cx. In contrast, in response to TFV, IL-8 secretion was significantly decreased in Em and Cx fibroblasts but increased with fibroblasts from the Ecx. When incubated with CD4(+) T cells from the FRT, TFV increased IL-8 (Em and Ecx) and TNF-α (Cx and Ecx) secretion levels. Moreover, when incubated with Em CD14(+) cells, TFV significantly increased MIP-3α, IL-8, and TNF-α secretion levels relative to those of the controls. In contrast, nucleotidase biological activities were significantly decreased by TFV in epithelial (Cx) and CD4(+) T cells (Em) but increased in fibroblasts (Em). Our findings indicate that TFV modulates proinflammatory cytokines, nucleotidase gene expression, and nucleotidase biological activity in epithelial cells, fibroblasts, CD4(+) T cells, and CD14(+) cells at distinct sites within the FRT.

Magnitude of income-related disparities in adverse perinatal outcomes.

BACKGROUND: To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. METHODS: A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. RESULTS: The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. CONCLUSIONS: This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases.

Effects of socioeconomic position and clinical risk factors on spontaneous and iatrogenic preterm birth.

BACKGROUND: The literature shows a variable and inconsistent relationship between socioeconomic position and preterm birth. We examined risk factors for spontaneous and iatrogenic preterm birth, with a focus on socioeconomic position and clinical risk factors, in order to explain the observed inconsistency. METHODS: We carried out a retrospective population-based cohort study of all singleton deliveries in Nova Scotia from 1988 to 2003. Data were obtained from the Nova Scotia Atlee Perinatal Database and the federal income tax T1 Family Files. Separate logistic models were used to quantify the association between socioeconomic position, clinical risk factors and spontaneous preterm birth and iatrogenic preterm birth. RESULTS: The study population included 132,714 singleton deliveries and the rate of preterm birth was 5.5%. Preterm birth rates were significantly higher among the women in the lowest (versus the highest) family income group for spontaneous (rate ratio 1.14, 95% confidence interval (CI) 1.03, 1.25) but not iatrogenic preterm birth (rate ratio 0.95, 95% CI 0.75, 1.19). Adjustment for maternal characteristics attenuated the family income-spontaneous preterm birth relationship but strengthened the relationship with iatrogenic preterm birth. Clinical risk factors such as hypertension were differentially associated with spontaneous (rate ratio 3.92, 95% CI 3.47, 4.44) and iatrogenic preterm (rate ratio 14.1, 95% CI 11.4, 17.4) but factors such as diabetes mellitus were not (rate ratio 4.38, 95% CI 3.21, 5.99 for spontaneous and 4.02, 95% CI 2.07, 7.80 for iatrogenic preterm birth). CONCLUSIONS: Socioeconomic position and clinical risk factors have different effects on spontaneous and iatrogenic preterm. Recent temporal increases in iatrogenic preterm birth appear to be responsible for the inconsistent relationship between socioeconomic position and preterm birth.

Contribution of prepregnancy body mass index and gestational weight gain to caesarean birth in Canada.

BACKGROUND: Overweight and obese women are known to be at increased risk of caesarean birth. This study estimates the contribution of prepregnancy body mass index (BMI) and gestational weight gain (GWG) to caesarean births in Canada. METHODS: We analyzed data from women in the Canadian Maternity Experiences Survey who had a singleton term live birth in 2005-2006. Adjusted odds ratios for caesarean birth across BMI and GWG groups were derived, separately for nulliparous women and parous women with and without a prior caesarean. Population attributable fractions of caesarean births associated with above normal BMI and excess GWG were calculated. RESULTS: The overall caesarean birth rate was 25.7%. Among nulliparous and parous women without a previous caesarean birth, rates in obese women were 45.1% and 9.7% respectively, and rates in women who gained above their recommended GWG were 33.5% and 8.0% respectively. Caesarean birth was more strongly associated with BMI than with GWG. However, due to the high prevalence of excess GWG (48.8%), the proportion of caesareans associated with above normal BMI and excess GWG was similar [10.1% (95% CI: 9.9-10.2) and 10.9% (95% CI: 10.7-11.1) respectively]. Overall, one in five (20.2%, 95% CI: 20.0-20.4) caesarean births was associated with above normal BMI or excess GWG. CONCLUSIONS: Overweight and obese BMI and above recommended GWG are significantly associated with caesarean birth in singleton term pregnancies in Canada. Strategies to reduce caesarean births must include measures to prevent overweight and obese BMI prior to conception and promote recommended weight gain throughout pregnancy.

Examining caesarean section rates in Canada using the Robson classification system.

OBJECTIVE: To determine the groups within the obstetric population contributing most substantially to the Caesarean section rate in five Canadian provinces. METHODS: Hospital births from five participating provinces were grouped into Robson's 10 mutually exclusive and totally inclusive classification categories. The relative contribution of each group to the overall CS rate, relative size of group, and CS rate were calculated for British Columbia, Alberta, Ontario, Nova Scotia, and Newfoundland and Labrador for the four-year period from 2007-2008 to 2010-2011. RESULTS: In all five provinces (accounting for approximately 64% of births in Canada), and for all years examined, the group making the largest relative contribution to the CS rate was women with at least one previous CS and a term, singleton, cephalic-presenting pregnancy (Robson Group 5). The CS rate for this group ranged from 76.1% in Alberta to 89.9% in Newfoundland and Labrador in 2010 to 2011, accounting for 11.3% of all deliveries. The rate of CS for Group 5 decreased slightly over the four years, except in Ontario. The next largest contributing group was nulliparous women with a term, singleton, cephalic-presenting pregnancy. Those with induced labour or Caesarean section before labour (Robson Group 2) had CS rates ranging from 34.4% in Nova Scotia to 44.6% in British Columbia (accounting for 13.1% of all deliveries), and those with spontaneous onset of labour (Robson Group 1) had CS rates of 14.5% to 20.3% in 2010 to 2011 (accounting for 23.6% of all deliveries). CONCLUSION: All hospitals and health authorities can use this standardized classification system as part of a quality improvement initiative to monitor Caesarean section rates. This classification system identifies relevant areas for interventions and resources to reduce rates of Caesarean section.

Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.

BACKGROUND: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. METHODS: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. RESULTS AND DISCUSSION: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.

In vitro anti-HIV-1 activity in cervicovaginal secretions from pregnant and nonpregnant women.

OBJECTIVE: To evaluate whether cervicovaginal secretions inhibit HIV-1 infectivity in an in vitro model, and estimate concentration of immune mediators. STUDY DESIGN: We enrolled midtrimester pregnant and regularly menstruating (nonpregnant) women. Cervicovaginal lavage was collected at 2 visits and incubated with HIV-1 and TZM-bl cells. Infectivity was compared with positive controls. Concentrations of immune mediators were compared between groups. RESULTS: At enrollment, cervicovaginal lavage inhibited IIIB virus 88.2% and 82.4%, and BaL virus 72.8% and 77.9%, among pregnant (n = 13) and nonpregnant women (n = 9), respectively. At second visit, cervicovaginal lavage inhibited IIIB 89.7% and 82.5%, and BaL 77.4% and 69.9% among pregnant (n = 15) and nonpregnant women (n = 8), respectively (all P ≤ .04). Adjusting for body mass index, race, and protein content of cervicovaginal lavage, antimicrobials were suppressed but cytokines and chemokines were not markedly different in pregnancy. CONCLUSION: Cervicovaginal secretions significantly suppress HIV-1 infectivity in this model. Concentrations of certain immune mediators are altered in pregnancy.

Intra- and inter-brand accuracy of four dental radiometers.

This study measured the accuracy and precision of four commercial dental radiometers. The intra-brand accuracy was also determined. The light outputs from 14 different curing lights were measured three times using four brands of dental radiometers and the results were compared to two laboratory-grade power meters that were used as the "gold standard". To ensure proper representation, three examples of each brand of dental radiometer were used. Data collected was analyzed using ANOVA, with 95% confidence intervals, comparing the laboratory-grade meters to the dental radiometers. Bioequivalence was established where the confidence interval for the irradiance values was within ±20% of the "gold standard" reading. Forest plots were used to highlight bioequivalence values. The two laboratory-grade meters differed by less than 0.6%. Overall, all three examples of the Bluephase and SDI radiometers as well as two examples of the LEDRadiometer and one CureRite meter were bioequivalent to the gold standard. However, the type of curing light measured had a significant effect on the accuracy of the radiometer. There was significant variability of the irradiance readings between radiometer brands, and between irradiance values recorded by the three samples of each brand studied. This made it impossible to definitively rank the radiometer brands for accuracy. Within the ±20% bioequivalence limits of this study, there was a clinically significant difference in the irradiance readings between radiometer brands and the choice of curing light affected the results. There was also significant variation in irradiance readings reported by different examples of the same brand of radiometer. Whether in clinical practice or in research, dental radiometers should not be used when either the irradiance or energy delivered needs to be accurately known.