Maternal mortality in the United States: are the high and rising rates due to changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance?

BACKGROUND: National Vital Statistics System reports show that maternal mortality rates in the United States have nearly doubled, from 17.4 in 2018 to 32.9 per 100,000 live births in 2021. However, these high and rising rates could reflect issues unrelated to obstetrical factors, such as changes in maternal medical conditions or maternal mortality surveillance (eg, due to introduction of the pregnancy checkbox). OBJECTIVE: This study aimed to assess if the high and rising rates of maternal mortality in the United States reflect changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance. STUDY DESIGN: The study was based on all deaths in the United States from 1999 to 2021. Maternal deaths were identified using the following 2 approaches: (1) per National Vital Statistics System methodology, as deaths in pregnancy or in the postpartum period, including deaths identified solely because of a positive pregnancy checkbox, and (2) under an alternative formulation, as deaths in pregnancy or in the postpartum period, with at least 1 mention of pregnancy among the multiple causes of death on the death certificate. The frequencies of major cause-of-death categories among deaths of female patients aged 15 to 44 years, maternal deaths, deaths due to obstetrical causes (ie, direct obstetrical deaths), and deaths due to maternal medical conditions aggravated by pregnancy or its management (ie, indirect obstetrical deaths) were quantified. RESULTS: Maternal deaths, per National Vital Statistics System methodology, increased by 144% (95% confidence interval, 130-159) from 9.65 in 1999-2002 (n=1550) to 23.6 per 100,000 live births in 2018-2021 (n=3489), with increases occurring among all race and ethnicity groups. Direct obstetrical deaths increased from 8.41 in 1999-2002 to 14.1 per 100,000 live births in 2018-2021, whereas indirect obstetrical deaths increased from 1.24 to 9.41 per 100,000 live births: 38% of direct obstetrical deaths and 87% of indirect obstetrical deaths in 2018-2021 were identified because of a positive pregnancy checkbox. The pregnancy checkbox was associated with increases in less specific and incidental causes of death. For example, maternal deaths with malignant neoplasms listed as a multiple cause of death increased 46-fold from 0.03 in 1999-2002 to 1.42 per 100,000 live births in 2018-2021. Under the alternative formulation, the maternal mortality rate was 10.2 in 1999-2002 and 10.4 per 100,000 live births in 2018-2021; deaths from direct obstetrical causes decreased from 7.05 to 5.82 per 100,000 live births. Deaths due to preeclampsia, eclampsia, postpartum hemorrhage, puerperal sepsis, venous complications, and embolism decreased, whereas deaths due to adherent placenta, renal and unspecified causes, cardiomyopathy, and preexisting hypertension increased. Maternal mortality increased among non-Hispanic White women and decreased among non-Hispanic Black and Hispanic women. However, rates were disproportionately higher among non-Hispanic Black women, with large disparities evident in several causes of death (eg, cardiomyopathy). CONCLUSION: The high and rising rates of maternal mortality in the United States are a consequence of changes in maternal mortality surveillance, with reliance on the pregnancy checkbox leading to an increase in misclassified maternal deaths. Identifying maternal deaths by requiring mention of pregnancy among the multiple causes of death shows lower, stable maternal mortality rates and declines in maternal deaths from direct obstetrical causes.

Aspirin at 75 to 81 mg Daily for the Prevention of Preterm Pre-Eclampsia: Systematic Review and Meta-Analysis.

Background: Aspirin at 150 mg daily, initiated in the 1st trimester of pregnancy, prevents preterm pre-eclampsia. We aimed to estimate whether a dose of 75 to 81 mg daily can help to prevent preterm pre-eclampsia as well. Methods: A systematic search was conducted using multiple databases and meta-analyses of randomized controlled trials (RCTs) that compared aspirin initiated in the first trimester of pregnancy to placebo or no treatment, following the PRISMA guidelines and the Cochrane risk of bias tool. Results: We retrieved 11 RCTs involving 13,981 participants. Five RCTs had a low risk of bias, one at unclear risk, and fiver had a high risk of bias. A pooled analysis demonstrated that doses of 75 to 81 mg of aspirin, compared to a placebo or no treatment, was not associated with a significant reduction in preterm pre-eclampsia (8 studies; 12,391 participants; relative risk, 0.66; 95% confidence interval: 0.27 to 1.62; p = 0.36), but there was a significant heterogeneity across the studies (I2 = 61%, p = 0.02). Conclusion: It cannot be concluded that taking 75 to 81 mg of aspirin daily reduces the risk of preterm pre-eclampsia. However, given the significant heterogeneity between the studies, the true effect that such a dose of aspirin would have on pregnancy outcomes could not be properly estimated.

Determinants of Perioperative Complications in Day-Surgery for Endometriosis: A Retrospective Cohort.

OBJECTIVES: Endometriosis is a common gynaecologic disease for which surgery is often required. Our objective was to evaluate the potential determinants of perioperative complications in day-surgeries for endometriosis. METHODS: We conducted a retrospective cohort study of patients undergoing day-surgeries for endometriosis using Canadian administrative data from between 2015 and 2019. A multilevel logistic model with a random intercept at the centre level was created to assess the association between potential determinants, including age, site(s) of endometriosis lesion, centre-volume, surgical intervention, and a composite outcome of complications or specific complications. RESULTS: We observed a higher risk of complications associated with greater age (40-44 vs. 20-24 years, adjusted odds ratio [aOR] 1.58; 95% CI 1.26-1.98); hysterectomies (aOR 2.29; 95% CI 1.73-3.06) compared with minor conservative surgery; lesions of the bowel or urinary tract system (aOR 1.54; 95% CI 1.16-2.06), and extra-pelvic sites of endometriosis (aOR 1.24; 95% CI 1.07-1.52) compared with endometriosis of the uterus; and with comorbidities (aOR 1.59; 95% CI 1.09-2.32). Endometriosis lesions to the bowel and urinary tract system and to extra-pelvic sites (compared with no endometriosis at the site) were associated with a greater risk of accidental damages (aOR 1.84; 95% CI 1.43-2.37) and urinary system complications (aOR 1.75; 95% CI 1.24-2.48), respectively. Among patients undergoing hysterectomies compared with those undergoing minor conservative surgery, infectious complications (aOR 8.56; 95% CI 4.70-15.59) and accidental damages (aOR 2.31; 95% CI 1.70-3.14) were more frequent. CONCLUSIONS: Complications in day-surgeries for endometriosis are more frequent with older age, hysterectomy, comorbidities, and endometriosis of the bowel, urinary tract system, and extra-pelvic locations. More extensive disease is associated with more extensive surgical dissection and a higher risk of complications.

Effect of the COVID-19 Pandemic on Stillbirths in Canada and the United States.

OBJECTIVE: There is uncertainty regarding the effect of the COVID-19 pandemic on population rates of stillbirth. We quantified pandemic-associated changes in stillbirth rates in Canada and the United States. METHODS: We carried out a retrospective study that included all live births and stillbirths in Canada and the United States from 2015 to 2020. The primary analysis was based on all stillbirths and live births at ≥20 weeks gestation. Stillbirth rates were analyzed by month, with March 2020 considered to be the month of pandemic onset. Interrupted time series analyses were used to determine pandemic effects. RESULTS: The study population included 18 475 stillbirths and 2 244 240 live births in Canada and 134 883 stillbirths and 22 963 356 live births in the United States (8.2 and 5.8 stillbirths per 1000 total births, respectively). In Canada, pandemic onset was associated with an increase in stillbirths at ≥20 weeks gestation of 1.01 (95% confidence interval [CI] 0.56-1.46) per 1000 total births and an increase in stillbirths at ≥28 weeks gestation of 0.35 (95% CI 0.16-0.54) per 1000 total births. In the United States, pandemic onset was associated with an increase in stillbirths at ≥20 weeks gestation of 0.48 (95% CI 0.22-0.75) per 1000 total births and an increase in stillbirths at ≥28 weeks gestation of 0.22 (95% CI 0.12-0.32) per 1000 total births. The increase in stillbirths at pandemic onset returned to pre-pandemic levels in subsequent months. CONCLUSION: The COVID-19 pandemic's onset was associated with a transitory increase in stillbirth rates in Canada and the United States.

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

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

Obstetric Intervention and Perinatal Outcomes During the Coronavirus Disease 2019 (COVID-19) Pandemic.

OBJECTIVE: To quantify pandemic-related changes in obstetric intervention and perinatal outcomes in the United States. METHODS: We carried out a retrospective study of all live births and fetal deaths in the United States, 2015-2021, with data obtained from the natality, fetal death, and linked live birth-infant death files of the National Center for Health Statistics. Analyses were carried out among all singletons; singletons of patients with prepregnancy diabetes, prepregnancy hypertension, and hypertensive disorders of pregnancy; and twins. Outcomes of interest included preterm birth, preterm labor induction or preterm cesarean delivery, macrosomia, postterm birth, and perinatal death. Interrupted time series analyses were used to estimate changes in the prepandemic period (January 2015-February 2020), at pandemic onset (March 2020), and in the pandemic period (March 2020-December 2021). RESULTS: The study population included 26,604,392 live births and 155,214 stillbirths. The prepandemic period was characterized by temporal increases in preterm birth and preterm labor induction or cesarean delivery rates and temporal reductions in macrosomia, postterm birth, and perinatal mortality. Pandemic onset was associated with absolute decreases in preterm birth (decrease of 0.322/100 live births, 95% CI 0.506-0.139) and preterm labor induction or cesarean delivery (decrease of 0.190/100 live births, 95% CI 0.334-0.047) and absolute increases in macrosomia (increase of 0.046/100 live births), postterm birth (increase of 0.015/100 live births), and perinatal death (increase of 0.501/1,000 total births, 95% CI 0.220-0.783). These changes were larger in subpopulations at high risk (eg, among singletons of patients with prepregnancy diabetes). Among singletons of patients with prepregnancy diabetes, pandemic onset was associated with a decrease in preterm birth (decrease of 1.634/100 live births) and preterm labor induction or cesarean delivery (decrease of 1.521/100 live births) and increases in macrosomia (increase of 0.328/100 live births) and perinatal death (increase of 9.840/1,000 total births, 95% CI 3.933-15.75). Most changes were reversed in the months after pandemic onset. CONCLUSION: The onset of the coronavirus disease 2019 (COVID-19) pandemic was associated with a transient decrease in obstetric intervention (especially preterm labor induction or cesarean delivery) and a transient increase in perinatal mortality.

Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: a collaborative study protocol for an individual participant data meta-analysis.

INTRODUCTION: Severe bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose docosahexaenoic acid (DHA) supplementation on this short-term neonatal morbidity need further investigations in infants born very preterm. This study will determine whether high-dose DHA enteral supplementation during the neonatal period is associated with the risk of severe BPD at 36 weeks' postmenstrual age (PMA) compared with control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation. METHODS AND ANALYSIS: As part of an Australian-Canadian collaboration, we will conduct an individual participant data (IPD) meta-analysis of randomised controlled trials targeting infants born at less than 29 weeks of gestation and evaluating the effect of high-dose DHA enteral supplementation in the neonatal period compared with a control. Primary outcome will be severe grades of BPD (yes/no) at 36 weeks' PMA harmonised according to a recent definition that predicts early childhood morbidities. Other outcomes will be survival without severe BPD, death, BPD severity grades, serious brain injury, severe retinopathy of prematurity, patent ductus arteriosus and necrotising enterocolitis requiring surgery, sepsis, combined neonatal morbidities and growth. Severe BPD will be compared between groups using a multivariate generalised estimating equations log-binomial regression model. Subgroup analyses are planned for gestational age, sex, small-for-gestational age, presence of maternal chorioamnionitis and mode of delivery. ETHICS AND DISSEMINATION: The conduct of each trial was approved by institutional research ethics boards and written informed consent was obtained from participating parents. A collaboration and data sharing agreement will be signed between participating authors and institutions. This IPD meta-analysis will document the role of DHA in nutritional management of BPD. Findings will be disseminated through conferences, media interviews and publications to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023431063. TRIAL REGISTRATION NUMBER: NCT05915806.

Day surgery for endometriosis in Canada: A retrospective cohort of trend and regional variation in types of surgeries and their complications.

BACKGROUND: A significant proportion of patients with endometriosis require surgery for management of the disease. AIMS: We aimed to assess the trend and regional variation in day surgeries for endometriosis across Canada and to identify perioperative complications associated with types of surgeries and their temporal trend and regional variation. MATERIALS AND METHODS: We conducted a retrospective cohort study of women undergoing day surgeries for endometriosis between 2015 and 2019 using Canadian administrative data from the National Ambulatory Care Reporting System, which includes data from four provinces (Ontario (ON), Alberta (AB), Nova Scotia (NS) and Prince Edward Island (PEI)). Multivariate logistic regression models were used to compare perioperative complication rates, while adjusting for site(s) of endometriosis lesion, age, type of surgical intervention, and comorbidities. RESULTS: During the study period, the rate of day surgeries for endometriosis remained nearly constant at 80-90 cases per 100 000 women of reproductive age (P = 0.12). The rate of day surgeries was significantly different between provinces (AB = 94, NS = 93 vs ON = 85 per 100 000 women of reproductive age: P < 0.02). The odds of complications decreased with time (2019 vs 2015; adjusted odds ratio (aOR): 0.84; 95% CI: 0.73-0.98). There was a significant regional variation in the frequency of perioperative complications (PEI vs ON aOR: 4.13, 95% CI: 2.58-6.62; and NS vs ON aOR: 1.47, 95% CI: 1.11-1.95). CONCLUSION: The rates of day surgery for endometriosis remained stable and the risks of perioperative complications decreased during the five-year study period. However, there were significant regional variations in the risk of perioperative complications.

Complications following surgeries for endometriosis: A systematic review protocol.

BACKGROUND: Endometriosis is a common gynecological condition with a wide range of symptoms, including infertility, dyspareunia, intestinal disorders, and pelvic pain. Laparoscopy and laparotomy are used widely for diagnosing and managing endometriosis. We will conduct a systematic review and meta-analysis with the aims of reporting complications rates following each type of surgeries for endometriosis and determinants of complications. METHOD: We will search Medline (via PubMed), Embase, the Cochrane Library, Web of Science, and Google Scholar for both retrospective and prospective cohorts or trials of at least 30 participants reporting perioperative and postoperative complications for endometriosis surgeries. We will restrict the studies to those conducted after 2011, to be representative of current practices, and will exclude studies of surgeries for gynecological cancer, or other concomitant benign gynecologic surgeries such as myomectomy. Two reviewers will independently screen references and select eligible studies. A standardized form will be used to collect data related to the baseline characteristics, potential determinants of complications, types of interventions, and outcomes. Cumulative incidences of complications will be pooled using DerSimonian and Laird random-effects method. The relation between potential determinants and complications will be reported with risk ratios and their 95% of confidence intervals. Subgroup analysis of surgical approach, surgical procedure, superficial and deep infiltrating endometriosis, and the indication of surgery will be conducted. Sensitivity analyses restricted to studies with low risk of bias will be performed. DISCUSSION: This systematic review will provide information on the rates of complications for different surgical approaches and procedures for the treatment of endometriosis. It will contribute to inform patients when making decisions regarding their care. Identifying potential determinants of complications will also help to improve care by identifying women being at higher risk of complications. TRIAL REGISTRATION: Systematic review registration: CRD42021293865.

Understanding what patients and physicians need to improve their decision-making about antenatal corticosteroids in late preterm gestation: a qualitative framework analysis.

BACKGROUND: It is unclear whether the benefits of administration of antenatal corticosteroids in late preterm gestation outweigh its harms. We sought to understand whether patients and physicians need increased support to decide whether to administer antenatal corticosteroids in late preterm gestation, and their informational needs and preferences for decision-making roles related to this intervention; we also wanted to know if creation of a decision-support tool would be useful. METHODS: We conducted individual, semistructured interviews with pregnant people, obstetricians and pediatricians in Vancouver, Canada, in 2019. Using a qualitative framework analysis method, we coded, charted and interpreted interview transcripts into categories that formed an analytical framework. RESULTS: We included 20 pregnant participants, 10 obstetricians and 10 pediatricians. We organized codes into the following categories: informational needs to decide whether to administer antenatal corticosteroids; preferences for decision-making roles regarding this treatment; the need for support to make this treatment decision; and the preferred format and content of a decision-support tool. Pregnant participants wanted to be involved in decision-making about antenatal corticosteroids in late preterm gestation. They wanted information on the medication, respiratory distress, hypoglycemia, parent-neonate bonding and long-term neurodevelopment. There was variation in physician counselling practices, and in how patients and physicians perceived the balance of treatment harms and benefits. Responses suggested a decision-support tool may be useful. Participants desired clear descriptions of risk magnitude and uncertainty. INTERPRETATION: Pregnant people and physicians would likely benefit from increased support to consider the harms and benefits of antenatal corticosteroids in late preterm gestation. Creation of a decision-support tool may be useful.

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review and Meta-analysis.

Importance: High-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking. Objective: To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks' gestation. Data Sources: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions. Study Selection: Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death. Data Extraction and Synthesis: Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses. Main Outcomes and Measures: Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death. Results: Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%). Conclusions and Relevance: Results of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.

Hospital factors associated with maternal and neonatal outcomes of deliveries to patients with a previous cesarean delivery: an ecological study.

BACKGROUND: Recommendations for deliveries of pregnant patients with a previous cesarean delivery and the type of hospitals deemed safe for these deliveries have evolved in recent years, although no studies have examined hospital factors and associated safety. We sought to evaluate maternal and neonatal outcomes among patients with a previous cesarean delivery by hospital tier and volume. METHODS: We carried out an ecological study of singleton live births delivered at term gestation to patients with a previous cesarean delivery in all Canadian hospitals (excluding Quebec), 2013-2019. We obtained data from the Discharge Abstract Database of the Canadian Institute for Health Information. The primary outcomes were severe maternal morbidity or mortality (SMMM), and serious neonatal morbidity or mortality (SNMM). We used regression modelling to examine hospital tier (tier 4 hospitals being those that provide the highest level of care) and volume; we also identified hospitals with high rates of SMMM and SNMM using within-tier comparisons and comparisons with the overall rate. RESULTS: We included 235 442 deliveries to patients with a previous cesarean delivery; SMMM and SNMM rates were 14.6 per 1000 deliveries and 4.6 per 1000 live births, respectively. Among patients with a parity of 1, SMMM rates were lower in tier 1 hospitals (adjusted incidence rate ratio [IRR] 0.68, 95% confidence interval [CI] 0.52-0.89) and higher in tier 4 hospitals (adjusted IRR 1.41, 95% CI 1.05-1.91) than in tier 2 hospitals; SNMM rates did not differ by hospital tier. Rates of SNMM increased with increasing hospital volume (adjusted IRR 1.02, 95% CI 1.00-1.04) and increasing rates of vaginal birth after cesarean delivery (adjusted IRR 1.02, 95% CI 1.01-1.04). Most hospitals had relatively low SMMM and SNMM rates, although a few hospitals in each tier and volume category had significantly higher rates than others. INTERPRETATION: Adverse maternal and neonatal outcomes among patients with a previous cesarean delivery showed no clear pattern of decreasing SMMM and SNMM with increasing tiers of service and hospital volume. All hospitals, irrespective of tier or size, should continually review their rates of adverse maternal and neonatal outcomes.

Technical Update No. 439: Antenatal Corticosteroids at Late Preterm Gestation.

OBJECTIVE: To update recommendations for administration of antenatal corticosteroids in the late preterm period. TARGET POPULATION: Pregnant individuals at risk of preterm birth from 340 to 366 weeks gestation. OPTIONS: Administration or non-administration of a single course of antenatal corticosteroids at 340 to 366 weeks gestation. OUTCOMES: Neonatal morbidity (respiratory distress, hypoglycemia), long-term neurodevelopment, and other long-term outcomes (growth, cardiac/metabolic, respiratory). BENEFITS, HARMS, AND COSTS: Administration of antenatal corticosteroids from 340 to 366 weeks gestation decreases the risk of neonatal respiratory distress but increases the risk of neonatal hypoglycemia. The long-term impacts of antenatal corticosteroid administration from 340 to 366 weeks gestation are uncertain. EVIDENCE: For evidence on the neonatal effects of antenatal corticosteroid administration at late preterm gestation, we summarized evidence from the 2020 Cochrane review of antenatal corticosteroids and combined this with evidence from published randomized trials identified by searching Ovid MEDLINE from January 1, 2020, to May 11, 2022. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on neurodevelopmental outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on neurodevelopmental outcomes using the following sources: (1) the 2020 Cochrane review; and (2) evidence obtained by searching Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to January 5, 2022. We did not apply date or language restrictions. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on other long-term outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on other long-term outcomes by combining findings from the 2020 Cochrane review with evidence obtained by searching Ovid MEDLINE for observational studies related to long-term cardiometabolic, respiratory, and growth effects of antenatal corticosteroids from inception to October 22, 2021. We reviewed reference lists of included studies and relevant systematic reviews for additional references. See Appendix A for search terms and summaries. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix B (Tables B1 for definitions and B2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Maternity care providers, including midwives, family physicians, and obstetricians. SUMMARY STATEMENTS: RECOMMENDATIONS.

Early coronavirus disease 2019 restrictive measures and changes in maternal characteristics, use of assisted reproductive technology, and stillbirth.

BACKGROUND: The initial COVID-19 pandemic response-related effects on conceptions following the use of assisted reproductive technologies (ART), and on changes in the maternal characteristics of women who conceived during the early vs. pre-pandemic period, have been understudied. OBJECTIVES: To examine the effects of ART clinic closures in the United States (US) in March 2020 on the frequency of ART-conceived live births, multiple births and stillbirths; and to describe changes in the characteristics of women who conceived in the early pandemic period. METHODS: Population-based cohort study including all births in the US from January 2015 to December 2020 (22,907,688 live births; 134,537 stillbirths). Interrupted time series (ITS) methodology was used to estimate rate ratios (RR) of expected versus observed rates in December 2020 (i.e., among births conceived mainly in March 2020). Demographic and clinical characteristics were compared between mothers who conceived in March 2020 versus March 2015-2019. RESULTS: Overall, 1.1% of live births and 1.7% of stillbirths were conceived by ART. ART-conceived live births decreased by 57.0% in December 2020 (observed vs. expected RR 0.43, 95% confidence interval [CI] 0.40, 0.45), and these declines occurred in all subgroups of women. Multiple births also declined in December 2020. Stillbirth rates increased in December 2020 in ART-conceived births (RR 2.55, 95% CI 1.63, 3.92) but remained unchanged in the non-ART group. Maternal characteristics of women who conceived in the early pandemic versus pre-pandemic period differed and included an increased prevalence of pre-pregnancy obesity class 3 and chronic hypertension. CONCLUSIONS: The early pandemic closure of ART clinics resulted in a substantial decline in ART-conceived live births and multiple births in December 2020 and an increase in the proportion of stillbirths among ART-conceived births. Women who conceived in the early pandemic period also had an increased prevalence of obesity and chronic hypertension.

High doses of enteral docosahexaenoic acid omega-3 supplementation for prevention of bronchopulmonary dysplasia in very preterm infants: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Docosahexaenoic acid (DHA) supplementation in the neonatal period has been proposed to prevent bronchopulmonary dysplasia (BPD) in very preterm infants. We aim to determine the effects of an enteral supplementation with high doses of DHA on the risk for BPD at 36 weeks' postmenstrual age (PMA) in very preterm infants born less than 29 weeks' gestation compared with a control. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) searching PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, MedRxiv, ClinicalTrials.gov (up to 1 November 2021) as well as reference lists and citations of included articles and previous reviews. RCTs targeting infants born less than 29 weeks' gestation and evaluating the effect of high doses of DHA enteral supplementation in the neonatal period compared with a control will be eligible. Primary outcome will be BPD defined as the need for oxygen and/or ventilation at 36 weeks' PMA. Two authors will independently screen for inclusion, extract data and assess data quality using the Cochrane instrument (risk-of-bias tool 2.0). We will perform meta-analysis using random effects models. Prespecified subgroup analyses are planned for the infant gestational age and sex, the marine source of DHA, mode of administration and duration of exposure. Sensitivity analysis will be performed according to the accuracy of the BPD definition (ie, physiological definition) and according to the risk of bias of the RCTs. ETHICS AND DISSEMINATION: This protocol for a systematic review and meta-analysis does not require ethics approval, as no primary data are collected. This study will assess the effectiveness of high doses of enteral DHA supplementation on BPD and provide evidence to clinicians and families for decision-making. Findings will be disseminated through conferences, media interviews and publications to peer review journals. PROSPERO REGISTRATION NUMBER: CRD42021286705.