Early pregnancy loss incidence in high-income settings: a protocol for a systematic review and meta-analysis.

BACKGROUND: Early pregnancy loss (unintended pregnancy loss before 20 completed weeks of gestation) is a common adverse pregnancy outcome, with previous evidence reporting incidence ranging from 10 to 30% of detected pregnancies. The objective of this systematic review and meta-analysis is to determine the incidence and range of early pregnancy loss in contemporary pregnant populations based on studies with good internal and external validity. Findings may be useful for clinical counseling in pre-conception and family planning settings and for people who experience early pregnancy loss. METHODS: We will search MEDLINE, EMBASE, and CINAHL databases using combinations of medical subject headings and keywords. Peer-reviewed, full-text original research articles that meet the following criteria will be included: (1) human study; (2) study designs: controlled clinical trials or observational studies with at least 100 pregnancies in the denominator, or systematic reviews of studies using these designs; (3) conducted in high-income countries; (4) reporting early pregnancy loss incidence, defined as unintended early pregnancy loss occurring prior to 20 weeks' gestation expressed as the number of losses among all pregnancies in the study period; (5) among a contemporary (1990 or later) general population of pregnancies; and (6) published between January 1, 1990, and August 31, 2021. We will assess the quality of included studies according to the United States Preventive Services Task Force Criteria for Assessing Internal and External Validity of Individual Studies. If appropriate, based on methodological comparability across included studies, we will conduct meta-analyses using random effects models to estimate the pooled incidence of early pregnancy loss among all studies with both good internal and external validity, with meta-analyses stratified by study design type (survey-based or self-reported and medical record-based), by induced abortion restrictions (restricted vs. unrestricted), and by gestational age (first trimester only vs. all gestational ages before 20 weeks). DISCUSSION: This systematic review will synthesize existing evidence to calculate a current estimate of early pregnancy loss incidence and variability in reported incidence estimates in high-income settings. The findings of this review may inform updates to clinical counseling in pre-conception and family planning settings, as well as for patients experiencing early pregnancy loss. SYSTEMATIC REVIEW REGISTRATION: We have registered this review with the International Prospective Register of Systematic Reviews (PROSPERO #226267 ).

Inter-hospital variation in use of obstetrical blood transfusion: a population-based cohort study.

OBJECTIVE: To identify the extent of hospital-to-hospital variation in use of obstetrical blood transfusion. DESIGN: Population-based cohort study linking provincial perinatal and blood transfusion registries. SETTING: British Columbia, Canada, 2004-2015. POPULATION: All pregnant women delivering at or beyond 20 weeks' gestation at any British Columbia hospital. METHODS: Mixed-effects regression models were used to estimate hospital-specific transfusion rates after sequentially accounting for (1) the role of random variation, (2) maternal medical and obstetrical characteristics (i.e. patient case mix) and (3) institutional and delivery factors (such as use of instrumental or caesarean delivery). MAIN OUTCOME MEASURES: Hospital-specific use of obstetrical red blood cell transfusion. RESULTS: Among 44 hospitals, crude institutional transfusion rates across the study period ranged from 3.7 to 23.6 per 1000, with an average of 8.3 per 1000. After adjusting for maternal characteristics, institution and delivery risk factors, a nearly three-fold difference in rates between the 10th and 90th percentile remained (5.4-14.5 per 1000). Twelve sites had rates significantly higher or lower than the provincial average. Women residing in remote areas were 2.5-fold (95% CI 1.8-3.5] more likely to receive a blood transfusion than were women residing in metropolitan areas. CONCLUSIONS: Meaningful variation between hospitals in use of blood transfusion during pregnancy was not explained by differences in patient case-mix or institutional factors, suggesting that over- or under-utilisation of this resource may be occurring in obstetrical care. TWEETABLE ABSTRACT: Use of blood transfusion in pregnant women varied broadly between hospitals in British Columbia, Canada.

Pregnancy weight gain by gestational age and stillbirth: a population-based cohort study.

OBJECTIVE: To study the association between total and early pregnancy (<22 completed weeks) weight gain and risk of stillbirth, stratified by early-pregnancy body mass index (BMI). DESIGN: Population-based cohort study. SETTING: Stockholm-Gotland Region, Sweden. POPULATION: Pregnant women with singleton births (n = 160 560). METHODS: Pregnancy weight gain was standardised into gestational age-specific z-scores. For analyses of total pregnancy weight gain, a matched design with an incidence density sampling approach was used. Findings were also contrasted with current Institute of Medicine (IOM) weight gain recommendations. MAIN OUTCOME MEASURES: Stillbirth defined as fetal death at ≥22 completed weeks of gestation. RESULTS: For all BMI categories, there was no statistical association between total or early pregnancy weight gain and stillbirth within the range of a weight gain z-score of -2.0 SD to +2.0 SD. Among normal-weight women, the adjusted odds ratio of stillbirth for lower (-2.0 to -1.0 SD) and higher (+1.0 to +1.9 SD) total weight gain was 0.85 (95% CI; 0.48-1.49) and 1.03 (0.60-1.77), respectively, as compared with the reference category. Further, there were no associations between total or early pregnancy weight gain and stillbirth within the range of weight gain currently recommended by the IOM. For the majority of the BMI categories, the point estimates at the extremes of weight gain values (<-2.0SD and ≥2.0 SD) suggested protective effects of low weight gain and increased risks of high weight gain, but estimates were imprecise and not statistically significant. CONCLUSION: We found no associations between total or early pregnancy weight gain and stillbirth across the range of weight gain experienced by most women. TWEETABLE ABSTRACT: There was no association between weight gain during pregnancy and stillbirth among most women.

Cervical dilation at time of caesarean delivery in nulliparous women: a population-based cohort study.

OBJECTIVES: Our objective was to describe contemporary practice patterns in the timing of caesarean delivery in relation to cervical dilation, overall and by indication for caesarean. Our secondary objective was to examine how commonly caesarean delivery was performed for labour dystocia at dilations below 4 cm or without the use of oxytocin, overall and between hospitals. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Alberta, and British Columbia, Canada, 2008-2012. POPULATION: Nulliparous women in labour who delivered term singletons in cephalic position. METHODS: Histograms were used to examine the distribution of cervical dilation at time of caesarean delivery, overall and by indication for caesarean. Funnel plots were used to illustrate variation in hospital-level rates of caesarean deliveries for labour dystocia that were performed early (<4 cm dilation) or without the use of oxytocin. MAIN OUTCOME MEASURES: Cervical dilation (in centimetres) at time of caesarean delivery. RESULTS: The population-based cohort comprised 392 025 women, of whom 18.8% had a caesarean delivery. Of first-stage caesareans for labour dystocia in women who entered labour spontaneously, 13.6% (95% CI 12.9, 14.2) had dilations <4 cm [hospital-level inter-quartile range (IQR): 6.2% to 20.0%] and 29.5% (95% CI 28.6, 30.4) did not receive oxytocin to treat their dystocia (hospital-level IQR: 22.1-54.6%). CONCLUSIONS: The proportion of caesareans done before 4 cm dilation or without oxytocin varies substantially across hospitals and suggests the need for institutions to review their practices and ensure that management of labour practice guidelines are followed. TWEETABLE ABSTRACT: Many caesareans for labour dystocia are performed early during labour (<4 cm dilation) or without oxytocin.

Gestational weight gain, prepregnancy body mass index and offspring attention-deficit hyperactivity disorder symptoms and behaviour at age 10.

OBJECTIVE: To assess offspring attention-deficit hyperactivity disorder (ADHD) symptoms and emotional/behavioural impairments at age 10 years in relation to maternal gestational weight gain (GWG) and prepregnancy body mass index (BMI). DESIGN AND SETTING: Longitudinal birth cohort from Magee-Womens Hospital, Pittsburgh, Pennsylvania (enrolled 1983-86). POPULATION: Mother-infant dyads (n = 511) were followed through pregnancy to 10 years. METHODS: Self-reported total GWG was converted to gestational-age-standardised z-scores. Multivariable linear and negative binomial regressions were used to estimate effects of GWG and BMI on outcomes. MAIN OUTCOME MEASURES: Child ADHD symptoms were assessed with the Conners' Continuous Performance Test. Child behaviour was assessed by parent and teacher ratings on the Child Behaviour Checklist (CBCL) and Teacher Report Form, respectively. RESULTS: The mean (SD) total GWG (kg) was 14.5 (5.9), and 10% of women had a pregravid BMI ≥30 kg/m2 . Prepregnancy obesity (BMI of 30 kg/m2 ) was associated with increased offspring problem behaviours including internalising behaviours (adjusted ß 3.3 points, 95% CI 1.7-4.9), externalising behaviours (adjusted ß 2.9 points, 95% CI 1.4-4.6), and attention problems (adjusted ß 2.3 points, 95% CI 1.1-3.4) on the CBCL, compared with normal weight mothers (BMI of 22 kg/m2 ). There were nonsignificant trends towards increased offspring impulsivity with low GWG among lean mothers (adjusted incidence rate ratio 1.2, 95% CI 0.9-1.5) and high GWG among overweight mothers (adjusted incidence rate ratio 1.7, 95% CI 0.9-2.8), but additional outcomes did not differ by GWG z-score. Results were not meaningfully different after excluding high-substance users. CONCLUSIONS: In a low-income and high-risk sample, we observed a small increase in child behaviour problems among children of obese mothers, which could have an impact on child behaviour in the population. TWEETABLE ABSTRACT: Maternal obesity is associated with a small increase in child behaviour problems.

Maternal and neonatal outcomes after implementation of a hospital policy to limit low-risk planned caesarean deliveries before 39 weeks of gestation: an interrupted time-series analysis.

OBJECTIVE: To evaluate the extent to which implementing a hospital policy to limit planned caesarean deliveries before 39 weeks of gestation improved neonatal health, maternal health, and healthcare costs. DESIGN: Retrospective cohort study. SETTING: British Columbia Women's Hospital, Vancouver, Canada, in the period 2005-2012. POPULATION: Women with a low-risk planned repeat caesarean delivery. METHODS: An interrupted time series design was used to evaluate the policy to limit planned caesarean deliveries before 39 weeks of gestation, introduced on 1 April 2008. MAIN OUTCOME MEASURES: Composite adverse neonatal health outcome (respiratory morbidity, 5-minute Apgar score of <7, neonatal intensive care unit admission, mortality), postpartum haemorrhage, obstetrical wound infection, out-of-hour deliveries, length of stay, and healthcare costs. RESULTS: Between 2005 and 2008, 60% (1204/2021) of low-risk planned caesarean deliveries were performed before 39 weeks of gestation. After the introduction of the policy, the proportion of planned caesareans dropped by 20 percentage points (adjusted risk difference of 20 fewer cases per 100 deliveries; 95% CI -25.8, -14.3) to 41% (1033/2518). The policy had no detectable impact on adverse neonatal outcomes (2.2 excess cases per 100; 95% CI -0.4, 4.8), maternal complications, or healthcare costs, but increased the risk of out-of-hours delivery from 16.2 to 21.1% (adjusted risk difference 6.3 per 100; 95% CI 1.6, 10.9). CONCLUSIONS: We found little evidence that a hospital policy to limit planned caesareans before 39 weeks of gestation reduced adverse neonatal outcomes. Hospital administrators intending to introduce such policies should anticipate, and plan for, modest increases in out-of-hours and emergency-timing.

Using inter-institutional practice variation to understand the risks and benefits of routine labour induction at 41(+0) weeks.

OBJECTIVE: To evaluate the risks and benefits of routine labour induction at 41(+0) weeks' gestation for mother and newborn. DESIGN: Population-based retrospective cohort study of inter-institutional variation in labour induction practices for women at or beyond 41(+0) weeks' gestation. POPULATION: Women in British Columbia, Canada, who remained pregnant ≥41(+0) weeks and delivered at one of the province's 42 hospitals with >50 annual deliveries, 2008-2012 (n = 14,627). METHODS: The proportion of women remaining pregnant a week or more past the expected delivery date who were induced at 41(+0) or 41(+1) weeks' gestation for an indication of 'post-dates' was calculated for each institution. We used instrumental variable analysis (using the institutional rate of labour induction at 41(+0) weeks as the instrument) to estimate the effect of labour induction on maternal and neonatal health outcomes. MAIN OUTCOME MEASURES: Caesarean delivery, instrumental delivery, post-partum haemorrhage, 3rd or 4th degree lacerations, macrosomia, neonatal intensive care unit admission, and 5-minute Apgar score <7. RESULTS: Institutional rates of labour induction at 41(+0) weeks ranged from 14.3 to 46%. Institutions with higher (≥30%) and average (20-29.9%) induction rates did not have significantly different rates of caesarean delivery, instrumental delivery, or other maternal or neonatal outcomes than institutions with lower induction rates (<20%). Instrumental variable analyses also demonstrated no significantly increased (or decreased) risk of caesarean delivery (0.69 excess cases per 100 pregnancies [95% CI -10.1, 11.5]), instrumental delivery (8.9 per 100 [95% CI -2.3, 20.2]), or other maternal or neonatal outcomes in women who were induced (versus not induced). CONCLUSIONS: Within the current range of clinical practice, there was no evidence that differential use of routine induction at 41(+0) weeks affected maternal or neonatal health outcomes.

Gestational weight gain in twin pregnancies and maternal and child health: a systematic review.

Our objective was to systematically review the data interrogating the association between gestational weight gain (GWG) and maternal and child health among women with twin gestations. We identified 15 articles of twin gestations that studied GWG in relation to a maternal, perinatal or child health outcome and controlled for gestational age at delivery and prepregnancy body mass index. A positive association between GWG and fetal size was consistently found. Evidence on preterm birth and pregnancy complications was inconsistent. The existing studies suffer from serious methodological weaknesses, including not properly accounting for the strong correlation between gestational duration and GWG and not controlling for chorionicity. In addition, serious perinatal outcomes were not studied, and no research is available on the association between GWG and outcomes beyond birth. Our systematic review underscores that GWG in twin gestations is a neglected area of research. Rigorous studies are needed to inform future evidence-based guidelines.

Epidemiological investigation of a temporal increase in atonic postpartum haemorrhage: a population-based retrospective cohort study.

OBJECTIVE: Increases in atonic postpartum haemorrhage (PPH) have been reported from several countries in recent years. We attempted to determine the potential cause of the increase in atonic and severe atonic PPH. DESIGN: Population-based retrospective cohort study. SETTING: British Columbia, Canada, 2001-2009. POPULATION: All women with live births or stillbirths. METHODS: Detailed clinical information was obtained for 371 193 women from the British Columbia Perinatal Data Registry. Outcomes of interest were atonic PPH and severe atonic PPH (atonic PPH with blood transfusion ≥1 unit; atonic PPH with blood transfusion ≥3 units or procedures to control bleeding), whereas determinants studied included maternal characteristics (e.g. age, parity, and body mass index) and obstetrics practice factors (e.g. labour induction, augmentation, and caesarean delivery). Year-specific unadjusted and adjusted odds ratios for the outcomes were compared using logistic regression. MAIN OUTCOME MEASURES: Atonic PPH and severe atonic PPH. RESULTS: Atonic PPH increased from 4.8% in 2001 to 6.3% in 2009, atonic PPH with blood transfusion ≥1 unit increased from 16.6 in 2001 to 25.5 per 10 000 deliveries in 2009, and atonic PPH with blood transfusion ≥3 units or procedures to control bleeding increased from 11.9 to 17.6 per 10 000 deliveries. The crude 34% (95% CI 26-42%) increase in atonic PPH between 2001 and 2009 remained unchanged (42% increase, 95% CI 34-51%) after adjustment for determinants of PPH. Similarly, adjustment did not explain the increase in severe atonic PPH. CONCLUSIONS: Changes in maternal characteristics and obstetric practice do not explain the recent increase in atonic and severe atonic PPH.

Performance of the fullPIERS model in predicting adverse maternal outcomes in pre-eclampsia using patient data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) cohort, collected on admission.

The fullPIERS (Pre-eclampsia Integrated Estimate of RiSk) model is a promising tool for the prediction of adverse outcomes in pre-eclampsia, developed using the worst values for predictor variables measured within 48 hours of admission. We reassessed the performance of fullPIERS using predictor variables obtained within 6 and 24 hours of admission, and found that the stratification capacity, calibration ability, and classification accuracy of the model remained high. The fullPIERS model is accurate as a rule-in test for adverse maternal outcome, with a likelihood ratio of 14.8 (95% CI 9.1-24.1) or 17.5 (95% CI 11.7-26.3) based on 6- and 24-hour data, respectively, for the women identified to be at highest risk (predicted probability ≥ 30%).

Optimal timing of delivery in pregnancies with pre-existing hypertension.

OBJECTIVE: To determine the optimal timing of delivery in pregnancies with pre-existing (chronic) hypertension by quantifying the gestational age-specific risks of stillbirth associated with ongoing pregnancy and the gestational age-specific risks of neonatal mortality or serious neonatal morbidity following the induction of labour. DESIGN: Population-based cohort study. SETTING: USA. POPULATION: A total of 171 669 singleton births to women with pre-existing hypertension between 1995 and 2005. Pregnancies additionally complicated by diabetes mellitus, cardiac, pulmonary or renal disease were excluded. METHODS: The week-specific risks of stillbirth between 36 and 41 completed weeks of gestation were contrasted with the week-specific risks of neonatal mortality or serious neonatal morbidity among births following induction of labour in women with pre-existing hypertension. MAIN OUTCOME MEASURES: Stillbirth, neonatal mortality or serious neonatal morbidity (defined as a composite outcome which included any of the following: neonatal seizures, severe respiratory morbidity or 5-minute Apgar score ≤3). RESULTS: The risk of stillbirth in women with pre-existing hypertension remained stable at 1.0-1.1 per 1000 ongoing pregnancies until 38 weeks, before rising steadily to 3.5 per 1000 [95% confidence interval (CI): 2.4, 5.0] at 41 weeks. The risk of serious neonatal morbidity/neonatal mortality decreased sharply between 36 and 38 weeks from 137 [95% CI: 127, 146] to 26 [95% CI: 24, 29] per 1000 induced births, before stabilising beyond 39 weeks. CONCLUSIONS: Among women with otherwise uncomplicated pre-existing hypertension, delivery at 38 or 39 weeks appears to provide the optimal trade-off between the risk of adverse fetal and adverse neonatal outcomes.

Timing of delivery for pregnancies with congenital diaphragmatic hernia.

A recent report has suggested that delivery at early term ages may be associated with lower mortality among infants with congenital diaphragmatic hernia. We sought to confirm this finding by examining gestational age-specific mortality in the USA in term infants with isolated congenital diaphragmatic hernia, delivered following the spontaneous onset of labour. In the final population of 928 infants, neonatal and infant mortality decreased with advancing gestation, from 25 and 36% at 37 weeks of gestation, respectively, to 17 and 20% at 40 weeks of gestation, respectively. Log-binomial regression models showed that neonatal and infant mortality at 37 weeks of gestation were significantly higher than at 40 weeks. Further evidence, ideally from a randomised trial, is needed before recommendations for clinical practice on timing of delivery should be made.

Influence of ultrasound-to-delivery interval and maternal-fetal characteristics on validity of estimated fetal weight.

OBJECTIVES: To explore the effects of ultrasound-to-delivery interval and maternal-fetal characteristics on the distribution of measurement error in estimated fetal weights (EFWs), and to determine the predictive ability of EFW for diagnosis of small-for-gestational age (SGA) and large-for-gestational age (LGA) among infants delivered within 1 day of an ultrasound examination. METHODS: Percentage differences between EFW and birth weights were calculated in 3697 pregnancies. Linear regression was used to compare the accuracy of EFW for births on each of the 6 days after an ultrasound scan with the accuracy observed among births on the same day. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value for diagnosis of SGA and LGA according to EFW was assessed. RESULTS: The mean +/- SD percentage difference among deliveries within 1 day of the last ultrasound scan was 0.2 +/- 9.0%. Mean percentage differences were not significantly different from day 0 on days 1, 2 and 3; however, combining the data from these 4 days obscured a slight bias towards an overestimation of weight evident on day 0 and day 1. Among deliveries within 1 day of an ultrasound scan, the PPV was 61% for SGA diagnosis and 54% for LGA diagnosis. CONCLUSION: Combining data from births > 1 day after the last ultrasound examination may lead to a false conclusion that there is systematic underestimation of weight. EFW tended to underestimate the weight of macrosomic fetuses and overestimate that of small fetuses which limited sensitivity and PPV. Maternal-fetal characteristics are weak predictors of individual errors in EFW.

Customised birthweight percentiles: does adjusting for maternal characteristics matter?

OBJECTIVE: The objective of this study was to determine whether the improved prediction of risk for perinatal mortality obtained with the use of a customised birthweight standard can also be obtained with the use of a non-customised but intrauterine-based standard. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: Births in the Swedish Medical Birth Register between 1992 and 2001 (n = 782 303) with complete data on birthweight, gestational age, sex, maternal age, pre-pregnancy body mass index, height, parity, and ethnicity. METHODS: We calculated the relative risks (RRs) of stillbirth and early neonatal mortality among small-for-gestational-age (SGA) births as established by (1) a customised standard, (2) a population standard based on birthweights, and (3) a population standard based on a best estimate of intrauterine weights. MAIN OUTCOME MEASURES: Stillbirth and early neonatal mortality (<7 days). RESULTS: The RRs of stillbirth and early neonatal mortality among SGA births as classified by the intrauterine standard were similar to those among SGA births as classified by the customised standard and much higher than those among SGA births as classified by the birthweight standard. CONCLUSIONS: A non-customised but intrauterine-based standard has a similar ability to predict risk for stillbirth and early neonatal mortality as a customised birthweight standard. The process of customising population weight-for-gestational-age standards to account for maternal characteristics does little to improve prediction of perinatal mortality.