BACKGROUND:Studies show that foetal and birthweight-for-gestational age centiles are poor predictors of serious neonatal morbidity and neonatal mortality (SNMM) in univariable models. OBJECTIVE:We assessed the predictive performance of multivariable SNMM models based on maternal/pregnancy characteristics, with and without birthweight centiles. METHODS:The study was based on all live births in the United States, 2019-2021, with data obtained from the period live birth-infant death files of the National Center for Health Statistics. SNMM was defined as any one or more of the following: 5-minute Apgar score < 4, seizures, assisted ventilation for> 30 or neonatal death. SNMM was modelled by log-linear regression on maternal/pregnancy characteristics as predictors, with and without birthweight centiles. Models were developed for live births at 24-42 weeks' and 39 weeks' gestation to all women and those with hypertensive disorders or pre-existing diabetes. Model performance was assessed using area under the curve (AUC). RESULTS:The study population included 10,487,243 live births and 221,728 SNMM cases (2.1 per 100 live births). The models with all live births at 24-42 weeks' gestation had AUCs of 0.83 (95% confidence interval [CI] 0.82, 0.83) based on maternal/pregnancy characteristics and 0.83 (95% CI 0.83, 0.84) based on maternal/pregnancy characteristics and birthweight centiles. However, AUCs of models based on all live births at 39 weeks' gestation were 0.66 (95% CI 0.64, 0.68) with maternal/pregnancy characteristics and 0.69 (95% CI 0.68, 0.71) with maternal/pregnancy characteristics and birthweight centiles. AUCs of the models with live births at 39 weeks' gestation to women with pre-existing diabetes were 0.69 (95% CI 0.66, 0.72) based on maternal/pregnancy characteristics, and 0.77 (95% CI 0.74, 0.79) with the addition of birthweight centiles. CONCLUSIONS:Birthweight centiles improve multivariable SNMM predictive performance in specific subpopulations, although evaluation of decision thresholds is required to determine the clinical importance of improvement in predictive ability.

From 2002 to 2023, palivizumab was the only intervention to reduce respiratory syncytial virus (RSV)-associated hospitalizations in high-risk infants in Canada but advances in RSV prevention are drastically changing this landscape. Eligibility criteria for this monoclonal antibody for preterm infants varied over time across each of 10 Canadian provinces and 3 territories. The National Professional Pediatric Association (Canadian Pediatric Society) revised its eligibility recommendations in 2015, removing access for preterm infants 30 to 32 weeks gestation (WG). The province of Nova Scotia followed these recommendations the next season. This study aimed to determine if the removal of access to palivizumab in these previously eligible infants was associated with a change in hospital admissions, deaths, or ambulatory visits associated with RSV. We identified a retrospective cohort of Nova Scotia infants born between 30 and 32 WG, without other risk factors for RSV-H, from April 2012 to September 2019 by linking six population-based provincial databases, and followed each infant through the first year of life. Episodes of RSV-associated hospitalization (RSV-H), ambulatory visits (RSV-A), or death were identified by the International Statistical Classification of Diseases and Related Health Disorders (ICD) RSV-associated diagnostic codes. Of 4,835 infants born during the study period, 250 were 30 to 32 WG and eligible for the cohort. RSV-H increased approximately 10-fold following restricted access to palivizumab (from no RSV-H (0/123) to 9.4%; 95% CI 5.0, 15.9; risk difference 9.4), but no RSV-associated deaths occurred. RSV-A also increased from 5.7 to 17.3% (risk difference 11.6). Discontinuation of access to a prophylactic anti-RSV monoclonal antibody in very preterm infants was associated with a higher risk of RSV-H and RSV-A. Evaluation of health care policy change on patient well-being is essential to assess the impact and guide future decision-making at the population level. · Discontinuation of access to a prophylactic anti-RSV monoclonal antibody in very preterm infants 30 to 32 WG was associated with a higher risk of RSV-H and RSV-A. Evaluation of changes to health care policy on patient well-being is essential to assess impact and guide future decision-making at the population level.. · Removing access to palivizumab led to higher RSV admissions in 30 to 32 WG infants.. · The effect of health care policy changes on child well-being should be assessed routinely.. · No deaths associated with RSV were identified prior to or after the policy change..

OBJECTIVES:To describe annual trends in the incidence of stillbirth and infant mortality in Nova Scotia over a 35-year period. METHODS:A population-based cohort study of deliveries between 1988 and 2022 was conducted using data from the provincial, clinically oriented Nova Scotia Atlee Perinatal Database. All pregnancies ≥200 weeks gestation or ≥500 g were included. Rates of fetal death (per 1000 births) and neonatal and infant mortality (per 1000 live births) were calculated by birth year. Rates were reported for the entire cohort and stratified by birth parent age, birthweight for gestational age and sex, and number of fetuses. RESULTS:A total of 334 776 deliveries were included, with 332 975 of these being live births; there were 1801 stillbirths, 1082 neonatal deaths, and 1579 infant deaths. Rates of fetal, neonatal, and infant death decreased between 1988-1992 and 2018-2022 (6.8-4.8, 4.0-2.5, and 6.3-4.0 per 1000 births, respectively). Rates increased somewhat in later 5-year epochs among those ≥35 years of age. Rates in the <10th percentile of birthweight for gestational age were highest in earlier epochs and showed a general downward trend with each epoch except the last. Marked temporal reductions in rates among multiple gestations were observed. CONCLUSIONS:Increases in mortality in later epochs, and among select birth parents and infant factors, suggest that patient characteristics and clinical practice changes may play a role in these increases. The observed temporal changes are important in informing the evaluation of factors associated with stillbirth and infant mortality.

Objective: To investigate whether the Antenatal Late Preterm Steroids (ALPS) trial, has been translated into clinical practice in Canada and the United States. Temporal trends in optimal and suboptimal antenatal corticosteroid (ACS) use among late preterm deliveries were also assessed. Design: A retrospective cohort study. Setting: USA and Canada, 2007 to 2020. Population: All live births in the US (n= 32,476,039) and Nova Scotia, Canada (n= 116,575). Methods and Main outcome measured: Using data from the Natality database and the Nova Scotia Atlee Perinatal Database, ACS administration within specific categories of gestational age was assessed by calculating rates per 100 live births. 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 35-36 weeks, from 15.2% in 2007-2016 to 19.6% in 2017-2020 (OR 1.36, 95%CI 1.14, 1.62). In the U.S., among live births at 35-36 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 24 and 34 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 United States 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.

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.

Hocquette and Zeitlin1 and Grantz and Zhang2 highlight a few issues with regard to our paper3 on the performance of birthweight-for-gestational age charts and birthweight centiles at term gestation. In this counterpoint, we discuss the points raised, including the choice of outcome for evaluating birthweight-for-gestational age charts, the potential impact of obstetrical intervention(s) on such assessments, and the emerging perspective on the utility of abnormal fetal and newborn growth indices. The choice of outcome for assessing fetal and newborn weight-for-gestational age charts requires consideration of the purpose of monitoring fetal and newborn growth status. In fact, the rationale varies depending on when growth is assessed, whether in utero or at birth. In utero estimation of fetal weight-for-gestational age provides information on general fetal health status and malnutrition, including restricted and excessive growth. Such assessment occurs in real-time and permits remedial intervention, although assessment is limited by potential inaccuracies in the estimation of fetal weight. On the other hand, birthweight-for-gestational age enables several assessments, including (i) a retrospective assessment of the cumulative in-utero growth experience; (ii) a cross-sectional assessment of general health status at birth; (iii) setting prognosis with regard to neonatal complications (e.g. hypoglycaemia and hyperbilirubinaemia); and (iv) obtaining a population perspective which addresses newborn growth distributions in different subpopulations. Whereas the retrospective outlook deals with obstetrical issues (e.g. by relating pregnancy complications to growth status at birth), and the prognostic viewpoint addresses the neonatal outlook (e.g. by relating growth status at birth to subsequent complications), the cross-sectional assessment at birth permits a more accurate quantification of the relationship between newborn growth status and general health status (as opposed to the in utero assessment since weight and health status are more accurately ascertained in infants). The utility of the latter assessment is predicated on two assumptions: (i) that health status at birth is best assessed using immediate findings (e.g. low 5-min Apgar score) and delayed manifestations (e.g. neonatal seizures or death) to comprehensively identify overt and hidden health conditions; and (ii) that the relation between birthweight-for-gestational age and newborn health status is generalisable, at least partly, to the estimated fetal weight-for-age and health status relation. No single outcome can address all the purposes of monitoring fetal and newborn growth, and assessments of (multi-dimensional) general health status are best achieved using a composite outcome. For our study,3 which focused on the assessment of health status at birth, we used a composite outcome that included 5-min Apgar <4, need for assisted ventilation, neonatal seizures, and neonatal death. Hocquette and Zeitlin1 advocate the evaluation of fetal and newborn growth charts based on neonatal morbidity and mortality but restrict that evaluation to small for gestational age (SGA) and large for gestational age (LGA) infants. However, as they point out,1 such evaluation excludes neonatal morbidity and mortality among appropriate-for-gestational age (AGA) infants. This is problematic because the majority of neonatal morbidity and mortality occurs among AGA infants,3 and the restriction to fetuses or infants deemed SGA and LGA fails to address the health status of all fetuses or infants. Grantz and Zhang2 also highlight the need to assess specific morbidity such as neonatal hypoglycaemia. Using information on infant growth status at birth for predicting neonatal hypoglycaemia and other morbidity is a legitimate clinical objective. However, we suspect that SGA and LGA, while risk factors for hypoglycaemia, will fail to identify the majority of hypoglycaemia cases, which will likely occur among the substantially larger population of AGA infants. One epidemiologic study4 that routinely screened 3595 newborn infants for early hypoglycaemia showed that only 13 of 124 infants with a blood glucose <40 mg/dL were SGA and 16 were LGA, while 95 were AGA. Both commentaries1, 2 provide a cautionary note regarding potential modification of the association between birthweight-for-gestational age and adverse perinatal outcomes by obstetrical and other interventions. This is a pervasive problem in non-experimental perinatal research, although some relationships are likely more impacted than others. For instance, evidence suggests that preeclampsia rates in specific populations have decreased in recent years owing to increases in iatrogenic early delivery. On the other hand, it is uncommon for iatrogenic early delivery to be based solely on SGA status. Both the GRIT randomised trial, which contrasted immediate or deferred delivery following signs of impaired foetal health in the presence of suspected growth restriction at 24–36 weeks' gestation, and the DIGITAT randomised trial, which examined the effect of labour induction versus expectant management for suspected intrauterine growth restriction at 36 weeks' gestation, showed no difference in neonatal morbidity/mortality or long-term developmental outcomes. Current clinical guidelines5 advocate iatrogenic early delivery only in the small subset of cases in whom suspected foetal growth restriction is associated with additional risk factors (such as ultrasound demonstrated absent or reversed umbilical artery blood flow), as this is associated with a reduction in perinatal death. Foetal growth restriction and excessive growth are considered 'pathological' conditions, although they are defined in abstract terms—as conditions affecting foetuses that fail to reach their biological growth potential or who exceed their growth potential, respectively, for their gestational age. Operationalisation of these concepts typically involves the use of foetal growth indices, namely, SGA and LGA, based on weight-for-gestational age cut-offs obtained from references/standards. However, recent studies (e.g. 3, 6, 7) have raised fundamental questions about SGA and LGA: Do they define diseases? Should they be used as screening criteria? Are they predictors of neonatal morbidity and mortality? Or, as some experts have argued—is it time to abandon SGA altogether?8 SGA and LGA fetuses and infants comprise a heterogeneous group with diverse aetiologies, including chromosomal abnormalities, other congenital anomalies, placental dysfunction, and constitutionally small (normal) foetuses and infants. Although such heterogeneity means that abnormal foetal and newborn growth indices do not represent diseases (which are characterised by an overt or hidden somatic anomaly9), a case can be made that they represent disease heuristics, that is, they identify individuals at high risk for disease based on empirically derived biomarker cut-offs. Hypertension and osteoporosis are examples of such heuristically defined diseases,9 which according to contemporary medical practice warrant specific therapy. Alternatively, it could be argued that abnormal fetal and newborn growth indices can be used as a first-step surveillance screen to identify fetuses and newborns at high risk for perinatal mortality or serious neonatal morbidity. This implies that screen-positive individuals are at risk of serious morbidity or mortality, but true- and false-positive individuals need to be identified through a second-stage diagnostic procedure. Unfortunately, as many recent studies have shown (e.g. 6, 7) and our study3 confirms, SGA and LGA indices fit neither the disease nor the screening criteria profile as they cannot discriminate between fetuses and infants who are, and who are not, at high risk of perinatal death or serious neonatal morbidity. The ability of a dichotomised biomarker to discriminate between individuals who have (or will develop) a disease, and those who do not, can be illustrated by contrasting systolic hypertension in relation to stroke death versus birthweight-for-gestational age in relation to serious neonatal morbidity or neonatal mortality (SNMM). Systolic hypertension is a risk factor for stroke: the 12-year follow-up of the Multiple Risk Factor Intervention Trial10 showed that stroke mortality was 4.2 times higher among males with a systolic blood pressure (SBP) of 140–149 mm Hg, 6.5 times higher among males with a SBP of 150–159 mm Hg, etc., compared with those with a SBP <110 mm Hg. Similarly, low birthweight-for-gestational age is a risk factor for SNMM: in our study,3 SNMM rates were 1.6 times higher among female singleton infants at 39 weeks' gestation with birthweights between 2283 and 2509 g, and 2.9 times higher among infants whose birthweights were <2283 g (compared with infants whose birthweights were 2850 to 3670 g). Figure 1A shows that the distribution of SBP among adults who suffered a stroke death differs substantially from the SBP distribution among all adults. In contrast, Figure 1B shows that the birthweight-for-gestational age distribution of infants with low 5-min Apgar scores differs only marginally from the same distribution among all infants. The overlapping distributions of birthweight-for-gestational age among infants with a low versus normal 5-min Apgar mean that birthweight-for-gestational age cut-offs have a limited ability to discriminate between infants at high versus low risk for such SNMM. Nevertheless, these differences only partly address the reasons why hypertension is viewed as a 'disease', while SGA and LGA face a more uncertain status. Pertinent issues in this context include the strong relationship between hypertension and other common diseases of older adults (including coronary heart disease and death from coronary heart disease10), and also evidence showing reductions in stroke and coronary heart disease mortality following anti-hypertensive therapy. This contrasts with the results of the GRIT and DIGITAT trials, which failed to show the benefit of intervention for SGA in terms of short- and long-term pregnancy and child outcomes. The accumulating evidence on abnormal fetal and newborn growth indices shows that growth centiles are 'dose-dependent' predictors of perinatal mortality and serious neonatal morbidity, although they perform poorly when used in isolation as disease proxies or screening criteria (e.g. 3, 6, 7). Nevertheless, estimated fetal weight and birthweight centiles in multivariable prediction functions3 could aid in the accurate identification of compromised fetuses and newborns at high risk of perinatal death or serious neonatal mortality, and facilitate the rational use of iatrogenic early delivery,8 and intensive neonatal care. Additionally, scientific and clinical communication and universal use of such multivariable prognostic functions would be facilitated if the same estimated fetal weight and birthweight-for-gestational age charts were used globally. KSJ and SJ proposed the response and wrote the first draft of the Counterpoint. JF, SL and MSK provided critically feedback and all authors approved the final version of the manuscript. The authors declare that they have no conflicts of interest in connection with this artilce. The data that support the findings of this study are openly available in the cited manuscripts (Reference 10) and in the NCHS linked births-infant death files (https://www.cdc.gov/nchs/data_access/vitalstatsonline.htm).

There is a concern that uterine rupture captured through hospital discharge codes without concurrent chart review may not be valid. 1 Porreco R.P. Clark S.L. Belfort M.A. et al. The changing specter of uterine rupture. Am J Obstet Gynecol. 2009; 200: 269 e1-4 Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar In particular, many identified cases are “silent/occult” cases without full division of all three uterine layers. 1 Porreco R.P. Clark S.L. Belfort M.A. et al. The changing specter of uterine rupture. Am J Obstet Gynecol. 2009; 200: 269 e1-4 Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar We set out to evaluate the accuracy of uterine rupture diagnosis captured in hospitalization records as compared to a chart review among pregnancies with a previous caesarean delivery, eligible for a trial of labour, as this target population is a key priority for surveillance efforts.

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.

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.

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.

BACKGROUNDThe 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.OBJECTIVESThis cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring.POPULATIONThe cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward.DESIGNIntergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort.METHODSThe 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 RESULTSAs 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.CONCLUSIONSThe 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.

Objectives To evaluate whether cervical dysplasia with or without loop electrosurgical excision procedure (LEEP) was associated with risk of preterm delivery. Methods This retrospective cohort study linked a provincial perinatal database and a provincial colposcopy database. All women aged ? 45years with a singleton delivery > 20 weeks’ gestation between 1995 and 2012 were included. The exposure groups included women with dysplasia treated with LEEP (Group 1) and women with dysplasia who were not treated (Group 2). The comparison group included women who did not have dysplasia or LEEP (Group 3). The primary outcome was rate of spontaneous preterm birth < 37 weeks’ gestation (sPTB) in a subsequent pregnancy. Cox proportional hazards regression was conducted to estimate hazard ratios (aHR) with 95% confidence intervals (CI) for sPTB risk, adjusted for confounders. We assessed whether the association was heterogeneous by histological grade (CIN1vs CIN2-3/AIS). Results There were 4265 women in Group 1, 3147 women in Group 2, and 63345 unexposed (Group 3) women. Relative to the unexposed women, women in Group 1 were more likely to deliver preterm (aHR 1.22; CI 1.06-1.39), but women in Group 2 were not (aHR 1.01; CI 0.86-1.19). Subgroup analysis showed that untreated high grade dysplasia, but not low grade dysplasia, was not associated with sPTB (aHR 0.67, 95% CI 0.52-0.88). Conclusions Treatment with LEEP was associated with a higher risk of sPTB, and this association was not heterogeneous by grade. High grade dysplasia, but not low grade dysplasia, was associated with a higher risk of sPTB. To evaluate whether cervical dysplasia with or without loop electrosurgical excision procedure (LEEP) was associated with risk of preterm delivery. This retrospective cohort study linked a provincial perinatal database and a provincial colposcopy database. All women aged ? 45years with a singleton delivery > 20 weeks’ gestation between 1995 and 2012 were included. The exposure groups included women with dysplasia treated with LEEP (Group 1) and women with dysplasia who were not treated (Group 2). The comparison group included women who did not have dysplasia or LEEP (Group 3). The primary outcome was rate of spontaneous preterm birth < 37 weeks’ gestation (sPTB) in a subsequent pregnancy. Cox proportional hazards regression was conducted to estimate hazard ratios (aHR) with 95% confidence intervals (CI) for sPTB risk, adjusted for confounders. We assessed whether the association was heterogeneous by histological grade (CIN1vs CIN2-3/AIS). There were 4265 women in Group 1, 3147 women in Group 2, and 63345 unexposed (Group 3) women. Relative to the unexposed women, women in Group 1 were more likely to deliver preterm (aHR 1.22; CI 1.06-1.39), but women in Group 2 were not (aHR 1.01; CI 0.86-1.19). Subgroup analysis showed that untreated high grade dysplasia, but not low grade dysplasia, was not associated with sPTB (aHR 0.67, 95% CI 0.52-0.88). Treatment with LEEP was associated with a higher risk of sPTB, and this association was not heterogeneous by grade. High grade dysplasia, but not low grade dysplasia, was associated with a higher risk of sPTB.

Objectives Delineate the changes in 12 perinatal indicators of maternal demographics, behaviour, delivery experience and infant outcome, by examining every birth in the province for 30years. Methods Descriptive analysis for each of 30years of maternal characteristics held within the Nova Scotia Atlee Perinatal Database. An interactive web page allows the user to select any of a set of 12 small animations, each presenting a time lapse of a perinatal indicator and its evolving distribution - with each yearly histogram appearing briefly to denote the mother's age, weight, presence of GDM, marital status, smoking and breastfeeding behaviour, type of care provider, delivery method, labour, and their infant's weight, gestational age, and vital status. Results A group of 40 mothers giving birth in Nova Scotia in 1988 would have included three younger than 20, one who was a diagnosed gestational diabetic, four who weighed more than 170 lbs., 13 who were cigarette smokers, and five who gave birth at a community hospital. Conclusions Thirty years later these characteristics are dramatically different, with substantial implications for the care that's required and the outcomes for them and their infants. All have been recorded in the Nova Scotia Atlee Perinatal Database and this descriptive study mines this data to provide a comprehensive, evolving snapshot of maternal demographics and behaviours, and the accompanying perinatal outcomes. Delineate the changes in 12 perinatal indicators of maternal demographics, behaviour, delivery experience and infant outcome, by examining every birth in the province for 30years. Descriptive analysis for each of 30years of maternal characteristics held within the Nova Scotia Atlee Perinatal Database. An interactive web page allows the user to select any of a set of 12 small animations, each presenting a time lapse of a perinatal indicator and its evolving distribution - with each yearly histogram appearing briefly to denote the mother's age, weight, presence of GDM, marital status, smoking and breastfeeding behaviour, type of care provider, delivery method, labour, and their infant's weight, gestational age, and vital status. A group of 40 mothers giving birth in Nova Scotia in 1988 would have included three younger than 20, one who was a diagnosed gestational diabetic, four who weighed more than 170 lbs., 13 who were cigarette smokers, and five who gave birth at a community hospital. Thirty years later these characteristics are dramatically different, with substantial implications for the care that's required and the outcomes for them and their infants. All have been recorded in the Nova Scotia Atlee Perinatal Database and this descriptive study mines this data to provide a comprehensive, evolving snapshot of maternal demographics and behaviours, and the accompanying perinatal outcomes.

Objectives: To compare neonatal and maternal outcomes, and the relative risk of interventions between mothers attended to by midwives, general practitioners, and obstetricians, and to assess the cost-effectiveness of the employee-model of midwifery-led care in Nova Scotia, Canada, when compared with general practitioners. Design, setting, and participants: The study was a retrospective cohort study involving routinely collected clinical and administrative data from all low-risk births from January 1st, 2013 to December 31st, 2017. There were 24,662 observations. Measurements: Descriptive statistics were used to summarise the mother's socio-demographic characteristics. We used a nearest-neighbour matching estimator in assessing differences in outcomes, and generalized linear models in the estimation of the risks of interventions, adjusting for potential confounders. An analytic decision tree served as the vehicle for the cost-effectiveness analysis, assessed using the net monetary benefit approach. All health care resources utilized were measured and valued. Neonatal intensive care admissions avoided was the measure of outcome. We performed probabilistic sensitivity and subgroup analyses. Findings: Mothers attended to by midwives spent less time at the hospital during birth admissions, were less likely to have interventions, instrumental births, and more likely to have exclusive breastfeeding at discharge from birth admission. There were no differences in Apgar scores and neonatal intensive care unit admissions. The employee-model of midwifery-led care was found to be cost-effective. Key conclusions: The midwifery program is both effective and cost-effective for low-risk pregnancies Implications for practice: Increasing the number of midwives will increase access and represents value for money. (C) 2019 Elsevier Ltd. All rights reserved.

PROBLEM:Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection worldwide and known to increase the risk for HIV acquisition. Few studies have investigated how infection of epithelial cells compromises barrier integrity and antimicrobial response. METHOD OF STUDY:ECC-1 cells, a human uterine epithelial cell line, were treated with live and heat-killed C. trachomatis. Epithelial barrier integrity measured as transepithelial resistance (TER), chemokines antimicrobial levels, and antimicrobial mRNA expression was measured by ELISA and Real-time RT-PCR. RESULTS:Epithelial barrier integrity was compromised when cells were infected with live, but not with heat-killed, C. trachomatis. IL-8 secretion by ECC-1 cells increased in response to live and heat-killed C. trachomatis, while MCP-1, HBD2 and trappin2/elafin secretion decreased with live C. trachomatis. CONCLUSION:Live C. trachomatis suppresses ECC-1 innate immune responses by compromising the barrier integrity, inhibiting secretion of MCP-1, HBD2, and trappin-2/elafin. Differential responses between live and heat-killed Chlamydia indicate which immune responses are dependent on ECC-1 infection rather than the extracellular presence of Chlamydia.

The mucosal immune system in the human female reproductive tract is unique and distinct from all other mucosal surfaces. Consisting of the innate and adaptive immune systems, immune protection has evolved to meet the constraints of protecting against potential viral, bacterial and fungal pathogens while ensuring reproductive success of an allogeneic conceptus. In this review, we focus on our current understanding of role of sex hormones in regulating mucosal immunity throughout the female reproductive tract. Consisting of several compartments including the Fallopian tubes, uterus, endocervix, ectocervix, and vagina, each site is precisely and independently regulated by the ovarian production of estradiol and progesterone. These hormones act both directly and indirectly through cytokines, chemokines, and growth factors, to regulate immune cell phenotype and function as well as immune protection in reproductive tract secretions. Understanding the immune system in the female reproductive tract is essential for the development of appropriate immunoprophylaxis to regulate fertility, deal with those challenges that prevent successful pregnancies, and control sexually transmitted diseases that compromise reproductive health and the lives of women and children worldwide.

OBJECTIVE: To conduct a population-based study to assess rates of optimal, suboptimal, and questionably appropriate administration of antenatal corticosteroid (betamethasone or dexamethasone) use.METHODS: All live births in Nova Scotia, Canada, from 1988 to 2012 were included in the study. Temporal trends in optimal (proportion of live births at 24-34 weeks of gestation exposed to antenatal corticosteroids between 24 hours and 7 days before delivery), suboptimal (proportion of live births at 24-34 weeks of gestation exposed to antenatal corticosteroids less than 24 hours or more than 7 days before delivery), and questionably appropriate exposure to antenatal corticosteroids (proportion of live births 35 weeks of gestation or greater exposed to antenatal corticosteroids) were quantified using odds ratios (ORs) and 95% confidence intervals (CIs).RESULTS: Among 246,459 live births between 1988 and 2012, 2.5% received a partial or a full course of antenatal corticosteroids. The rate of antenatal corticosteroid exposure for neonates born between 28 and 32 weeks of gestation increased from 39.5% in 1988-1992 to 79.3% in 2008-2012, whereas exposure for those born at 33-34 weeks of gestation increased from 14.3 to 49.7%. Optimal antenatal corticosteroid receipt increased from 10% in 1988 to 23% in 2012 (OR 2.7, 95% CI 1.6-4.5), suboptimal administration increased from 7 to 34% (OR 6.7, 95% CI 3.9-11.6), and questionably appropriate administration increased from 0.2% in 1988 to 1.7% in 2012 (OR 7.5, 95% CI 4.9-11.3). Of the women who received antenatal corticosteroids in 2012, 52% delivered at 35 weeks of gestation or greater.CONCLUSION: Temporal increases in optimal exposure to antenatal corticosteroids have been matched by increases in suboptimal and questionably appropriate receipt of antenatal corticosteroids, highlighting the need for accurate preterm delivery prognostic models.

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.

Whether the concentrations of antiviral proteins, and anti‐HIV activity, within human vaginal secretions change across the menstrual cycle is unknown.