Pre-existing maternal cardiovascular disease and the risk of offspring cardiovascular disease from infancy to early adulthood.

BACKGROUND AND AIMS: A variety of maternal heart conditions are associated with abnormal placentation and reduced foetal growth. However, their impact on offspring's long-term cardiovascular health is poorly studied. This study aims to investigate the association between intrauterine exposure to pre-existing maternal cardiovascular disease (CVD) and offspring CVD occurring from infancy to early adulthood, using paternal CVD as a negative control. METHODS: This nationwide cohort study used register data of live singletons without major malformations or congenital heart disease born between 1992 and 2019 in Sweden. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for essential maternal characteristics. Paternal CVD served as a negative control for assessment of unmeasured genetic and environmental confounding. RESULTS: Of the 2 597 786 offspring analysed (49.1% female), 26 471 (1.0%) were born to mothers with pre-existing CVD. During a median follow-up of 14 years (range 1-29 years), 17 382 offspring were diagnosed with CVD. Offspring of mothers with CVD had 2.09 times higher adjusted HR of CVD (95% CI 1.83, 2.39) compared with offspring of mothers without CVD. Compared with maternal CVD, paternal CVD showed an association of smaller magnitude (HR 1.49, 95% CI 1.32, 1.68). Increased hazards of offspring CVD were also found when stratifying maternal CVD into maternal arrhythmia (HR 2.94, 95% CI 2.41, 3.58), vascular (HR 1.59, 95% CI 1.21, 2.10), and structural heart diseases (HR 1.48, 95% CI 1.08, 2.02). CONCLUSIONS: Maternal CVD was associated with an increased risk of CVD in offspring during childhood and young adulthood. Paternal comparison suggests that genetic or shared familial factors may not fully explain this association.

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.

Temporal changes in pre-existing health conditions five years prior to pregnancy in British Columbia, Canada, 2000-2019.

BACKGROUND: Pre-existing health conditions increase the risk of obstetric complications during pregnancy and birth. However, the prevalence and recent changes in the frequency of pre-existing health conditions in the childbearing population remain unknown. OBJECTIVES: To estimate the temporal changes in the prevalence of pre-existing health conditions among pregnant women in British Columbia, Canada. METHODS: We carried out a population-based cross-sectional study of 825,203 deliveries in BC between 2000 and 2019 and examined 17 categories of physical and psychiatric health conditions recorded within 5 years before childbirth. We also undertook age-period-cohort analyses to evaluate temporal changes in pre-existing health conditions. RESULTS: The prevalence of any pre-existing health condition was 26.2% (n = 216,214) with overall trends remaining stable during the study period. Between 2000 and 2019, the prevalence rates of anxiety (5.6%-9.6%), bipolar (1.6%-3.4%), psychosis (0.7%-0.8%), and eating disorders (0.2%-0.3%) increased. The prevalence of hypertension increased sharply from 0.06% in 2000 to 0.3% in 2019. Diabetes mellitus and stroke rates increased, as did the prevalence of systemic lupus, multiple sclerosis, and chronic kidney disease. Advanced maternal age was strongly associated with both psychiatric and circulatory/metabolic conditions. A strong birth cohort effect was evident, with rates of psychiatric conditions increasing among women born after 1985. CONCLUSIONS: In British Columbia, Canada, 1 in 4 mothers had a pre-existing health condition 5 years prior to pregnancy. These findings underscore the need for multi-disciplinary care for women with pre-existing health conditions to improve maternal, foetal, and infant health.

Severe maternal morbidity surveillance, temporal trends and regional variation: A population-based cohort study.

OBJECTIVE: To quantify temporal trends and regional variation in severe maternal morbidity (SMM) in Sweden. DESIGN: Cohort study. POPULATION: Live birth and stillbirth deliveries in Sweden, 1999-2019. METHODS: Types and subtypes of SMM were identified, based on a standard list (modified for Swedish clinical setting after considering the frequency and validity of each indicator) using diagnoses and procedure codes, among all deliveries at ≥22 weeks of gestation (including complications within 42 days of delivery). Contrasts between regions were quantified using rate ratios (RRs) and 95% confidence intervals (95% CIs). Temporal changes in SMM types and subtypes were described. MAIN OUTCOME MEASURES: Types and subtypes of SMM. RESULTS: There were 59 789 SMM cases among 2 212 576 deliveries, corresponding to 270.2 (95% CI 268.1-272.4) per 10 000 deliveries. Composite SMM rates increased from 236.6 per 10 000 deliveries in 1999 to 307.3 per 10 000 deliveries in 2006, before declining to 253.8 per 10 000 deliveries in 2019. Changes in composite SMM corresponded with temporal changes in severe haemorrhage rates, which increased from 94.9 per 10 000 deliveries in 1999 to 169.3 per 10 000 deliveries in 2006, before declining to 111.2 per 10 000 deliveries in 2019. Severe pre-eclampsia, eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome (103.8 per 10 000 deliveries), severe haemorrhage (133.7 per 10 000 deliveries), sepsis, embolism, disseminated intravascular coagulation, shock and severe mental health disorders were the most common SMM types. Rates of embolism, disseminated intravascular coagulation and shock, acute renal failure, cardiac complications, sepsis and assisted ventilation increased, whereas rates of surgical complications, severe uterine rupture and anaesthesia complications declined. CONCLUSIONS: The observed spatiotemporal variations in composite SMM and SMM types provide substantive insights and highlight regional priorities for improving maternal health.

Changes in the prevalence of maternal chronic conditions during pregnancy: A nationwide age-period-cohort analysis.

OBJECTIVE: To estimate temporal changes in the prevalence of pre-existing chronic conditions among pregnant women in Sweden and evaluate the extent to which secular changes in maternal age, birth cohorts and obesity are associated with these trends. DESIGN: Population-based cross-sectional study. SETTING: Sweden, 2002-2019. POPULATION: All women (aged 15-49 years) who delivered in Sweden (2002-2019). METHODS: An age-period-cohort analysis was used to evaluate the effects of age, calendar periods, and birth cohorts on the observed temporal trends. MAIN OUTCOME MEASURES: Pre-existing chronic conditions, including 17 disease categories of physical and psychiatric health conditions recorded within 5 years before childbirth, presented as prevalence rates and rate ratios (RRs) with 95% confidence intervals (CIs). Temporal trends were also adjusted for pre-pregnancy body mass index (BMI) and the mother's country of birth. RESULTS: The overall prevalence of at least one pre-existing chronic condition was 8.7% (147 458 of 1 703 731 women). The rates of pre-existing chronic conditions in pregnancy increased threefold between 2002-2006 and 2016-2019 (RR 2.82, 95% CI 2.77-2.87). Rates of psychiatric (RR 3.80, 95% CI 3.71-3.89), circulatory/metabolic (RR 1.62, 95% CI 1.55-1.71), autoimmune/neurological (RR 1.69, 95% CI 1.61-1.78) and other (RR 2.10, 95% CI 1.99-2.22) conditions increased substantially from 2002-2006 to 2016-2019. However, these increasing rates were less pronounced between 2012-2015 and 2016-2019. No birth cohort effect was evident for any of the pre-existing chronic conditions. Adjusting for secular changes in obesity and the mother's country of birth did not affect these associations. CONCLUSIONS: The burden of pre-existing chronic conditions in pregnancy in Sweden increased from 2002 to 2019. This increase may be associated with the improved reporting of diagnoses and advancements in chronic condition treatment among women, potentially enhancing their fecundity.

Stillbirth risk by fetal size among 126.5 million births in 15 countries from 2000 to 2020: A fetuses-at-risk approach.

OBJECTIVE: To compare stillbirth rates and risks for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies at 24-44 completed weeks of gestation using a birth-based and fetuses-at-risk approachs. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 high- and middle-income countries. POPULATION: Live births and stillbirths. METHODS: A total of 151 country-years of data, including 126 543 070 births across 15 countries from 2000 to 2020, were compiled. Births were categorised into SGA, AGA and LGA using INTERGROWTH-21st standards. Gestation-specific stillbirth rates, with total births as the denominator, and gestation-specific stillbirth risks, with fetuses still in utero as the denominator, were calculated from 24 to 44 weeks of gestation. MAIN OUTCOME MEASURES: Gestation-specific stillbirth rates and risks according to size at birth. RESULTS: The overall stillbirth rate was 4.22 per 1000 total births (95% CI 4.22-4.23) across all gestations. Applying the birth-based approach, the stillbirth rates were highest at 24 weeks of gestation, with 621.6 per 1000 total births (95% CI 620.9-622.2) for SGA pregnancies, 298.4 per 1000 total births (95% CI 298.1-298.7) for AGA pregnancies and 338.5 per 1000 total births (95% CI 337.9-339.0) for LGA pregnancies. Applying the fetuses-at-risk approach, the gestation-specific stillbirth risk was highest for SGA pregnancies (1.3-1.4 per 1000 fetuses at risk) prior to 29 weeks of gestation. The risk remained stable between 30 and 34 weeks of gestation, and then increased gradually from 35 weeks of gestation to the highest rate of 8.4 per 1000 fetuses at risk (95% CI 8.3-8.4) at ≥42 weeks of gestation. The stillbirth risk ratio (RR) was consistently high for SGA compared with AGA pregnancies, with the highest RR observed at ≥42 weeks of gestation (RR 9.2, 95% CI 15.2-13.2), and with the lowest RR observed at 24 weeks of gestation (RR 3.1, 95% CI 1.9-4.3). The stillbirth RR was also consistently high for SGA compared with AGA pregnancies across all countries, with national variability ranging from RR 0.70 (95% CI 0.43-0.97) in Mexico to RR 8.6 (95% CI 8.1-9.1) in Uruguay. No increased risk for LGA pregnancies was observed. CONCLUSIONS: Small for gestational age (SGA) was strongly associated with stillbirth risk in this study based on high-quality data from high- and middle-income countries. The highest RRs were seen in preterm gestations, with two-thirds of the stillbirths born as preterm births. To advance our understanding of stillbirth, further analyses should be conducted using high-quality data sets from low-income settings, particularly those with relatively high rates of SGA.

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.

Apgar Score and Risk of Neonatal Death among Preterm Infants.

BACKGROUND: Gestational age is the major determinant of neonatal death (death within the first 28 days of life) in preterm infants. The joint effect of gestational age and Apgar score on the risk of neonatal death is unknown. METHODS: Using data from the Swedish Medical Birth Register, we identified 113,300 preterm infants (22 weeks 0 days to 36 weeks 6 days of gestation) born from 1992 through 2016. In analyses stratified according to gestational age (22 to 24 weeks, 25 to 27 weeks, 28 to 31 weeks, 32 to 34 weeks, and 35 or 36 weeks), we estimated adjusted relative risks of neonatal death and absolute rate differences in neonatal mortality (i.e., the excess number of neonatal deaths per 100 births) according to the Apgar scores at 5 and 10 minutes and according to the change in the Apgar score between 5 minutes and 10 minutes. Scores range from 0 to 10, with higher scores indicating a better physical condition of the newborn. RESULTS: There were 1986 neonatal deaths (1.8%). The incidence of neonatal death ranged from 0.2% (at 36 weeks of gestation) to 76.5% (at 22 weeks of gestation). Lower Apgar scores were associated with higher relative risks of neonatal death and greater absolute rate differences in neonatal mortality in all gestational-age strata. For example, among infants born at 28 to 31 weeks, the adjusted absolute rate differences according to the 5-minute Apgar score, with those who had a score of 9 or 10 serving as the reference group, were 51.7 (95% confidence interval [CI], 38.1 to 65.4) for a score of 0 or 1, 25.5 (95% CI, 18.3 to 32.8) for a score of 2 or 3, 7.1 (95% CI, 5.1 to 9.1) for a score of 4 to 6, and 1.2 (95% CI, 0.5 to 1.9) for a score of 7 or 8. An increase in the Apgar score between 5 minutes and 10 minutes was associated with lower neonatal mortality than a stable Apgar score. CONCLUSIONS: In this study, Apgar scores at 5 and 10 minutes provided prognostic information about neonatal survival among preterm infants across gestational-age strata. (Funded by the Swedish Research Council for Health, Working Life, and Welfare and Karolinska Institutet.).

Multiple sclerosis, disease-modifying drugs and risk for adverse perinatal and pregnancy outcomes: Results from a population-based cohort study.

BACKGROUND: There is a paucity of information on maternal multiple sclerosis (MS) and risk of adverse pregnancy and perinatal outcomes. OBJECTIVE: The aim of this study was to determine the association between MS and risks of adverse pregnancy and perinatal outcomes in women with MS. In women with MS, the influence of exposure to disease-modifying therapy (DMT) was also investigated. METHODS: Population-based retrospective cohort study on singleton births to mothers with MS and matched MS-free mothers from the general population in Sweden between 2006 and 2020. Women with MS were identified through Swedish health care registries, with MS onset before child's birth. RESULTS: Of 29,568 births included, 3418 births were to 2310 mothers with MS. Compared with MS-free controls, maternal MS was associated with increased risks of elective caesarean sections, instrumental delivery, maternal infection and antepartum haemorrhage/ placental abruption. Compared with offspring of MS-free women, neonates of mothers with MS were at increased risks of medically indicated preterm birth and being born small for gestational age. DMT exposure was not associated with increased risks of malformations. CONCLUSIONS: While maternal MS was associated with a small increased risk of few adverse pregnancy and neonatal outcomes, DMT exposure close to pregnancy was not associated with major adverse outcomes.

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.

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.

Does maternal stature modify the association between infants who are small or large for gestational age and adverse perinatal outcomes? A retrospective cohort study.

OBJECTIVE: To investigate the effect of maternal stature on adverse birth outcomes and quantify perinatal risks associated with small- and large-for-gestational age infants (SGA and LGA, respectively) born to mothers of short, average, and tall stature. DESIGN: Retrospective cohort study. SETTING: USA, 2016-2017. POPULATION: Women with a singleton live birth (N = 7 325 741). METHODS: Using data from the National Center for Health Statistics, short and tall stature were defined as <10th and >90th centile of the maternal height distribution. Modified Poisson regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (95% CIs). MAIN OUTCOME MEASURES: Preterm birth (<37 weeks of gestation), neonatal intensive care unit (NICU) admission and severe neonatal morbidity/mortality (SNMM). RESULTS: With increased maternal height, the risk of adverse outcomes increased in SGA infants and decreased in LGA infants compared with infants appropriate-for-gestational age (AGA) (p < 0.001). Infants who were SGA born to women of tall stature had the highest risk of NICU admission (aRR 1.98, 95% CI 1.91-2.05; p < 0.001), whereas LGA infants born to women of tall stature had the lowest risk (aRR 0.85, 95% CI 0.82-0.88; p < 0.001), compared with AGA infants born to women of average stature. LGA infants born to women of short stature had an increased risk of NICU admission and SNMM, compared with AGA infants born to women of average stature (aRR 1.32, 95% CI 1.27-1.38; aRR 1.21, 95% CI 1.13-1.29, respectively). CONCLUSIONS: Maternal height modifies the association between SGA and LGA status at birth and neonatal outcomes. This quantification of risk can assist healthcare providers in monitoring fetal growth, and optimising neonatal care and follow-up.

Stillbirths: Contribution of preterm birth and size-for-gestational age for 125.4 million total births from nationwide records in 13 countries, 2000-2020.

OBJECTIVE: To examine the contribution of preterm birth and size-for-gestational age in stillbirths using six 'newborn types'. DESIGN: Population-based multi-country analyses. SETTING: Births collected through routine data systems in 13 countries. SAMPLE: 125 419 255 total births from 22+0 to 44+6 weeks' gestation identified from 2000 to 2020. METHODS: We included 635 107 stillbirths from 22+0 weeks' gestation from 13 countries. We classified all births, including stillbirths, into six 'newborn types' based on gestational age information (preterm, PT, <37+0 weeks versus term, T, ≥37+0 weeks) and size-for-gestational age defined as small (SGA, <10th centile), appropriate (AGA, 10th-90th centiles) or large (LGA, >90th centile) for gestational age, according to the international newborn size for gestational age and sex INTERGROWTH-21st standards. MAIN OUTCOME MEASURES: Distribution of stillbirths, stillbirth rates and rate ratios according to six newborn types. RESULTS: 635 107 (0.5%) of the 125 419 255 total births resulted in stillbirth after 22+0 weeks. Most stillbirths (74.3%) were preterm. Around 21.2% were SGA types (PT + SGA [16.2%], PT + AGA [48.3%], T + SGA [5.0%]) and 14.1% were LGA types (PT + LGA [9.9%], T + LGA [4.2%]). The median rate ratio (RR) for stillbirth was highest in PT + SGA babies (RR 81.1, interquartile range [IQR], 68.8-118.8) followed by PT + AGA (RR 25.0, IQR, 20.0-34.3), PT + LGA (RR 25.9, IQR, 13.8-28.7) and T + SGA (RR 5.6, IQR, 5.1-6.0) compared with T + AGA. Stillbirth rate ratios were similar for T + LGA versus T + AGA (RR 0.7, IQR, 0.7-1.1). At the population level, 25% of stillbirths were attributable to small-for-gestational-age. CONCLUSIONS: In these high-quality data from high/middle income countries, almost three-quarters of stillbirths were born preterm and a fifth small-for-gestational age, with the highest stillbirth rates associated with the coexistence of preterm and SGA. Further analyses are needed to better understand patterns of gestation-specific risk in these populations, as well as patterns in lower-income contexts, especially those with higher rates of intrapartum stillbirth and SGA.

Neonatal mortality risk of large-for-gestational-age and macrosomic live births in 15 countries, including 115.6 million nationwide linked records, 2000-2020.

OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], <10th centile, appropriate [AGA], 10th-90th centile or large [LGA], >90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Vulnerable newborn types: Analysis of population-based registries for 165 million births in 23 countries, 2000-2021.

OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.

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

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

Crude and adjusted comparisons of cesarean delivery rates using the Robson classification: A population-based cohort study in Canada and Sweden, 2004 to 2016.

BACKGROUND: The Robson classification has become a global standard for comparing and monitoring cesarean delivery (CD) rates across populations and over time; however, this classification does not account for differences in important maternal, fetal, and obstetric practice factors known to impact CD rates. The objectives of our study were to identify subgroups of women contributing to differences in the CD rate in Sweden and British Columbia (BC), Canada using the Robson classification and to estimate the contribution of maternal, fetal/infant, and obstetric practice factors to differences in CD rates between countries and over time. METHODS AND FINDINGS: We conducted a population-based cohort study of deliveries in Sweden (January 1, 2004 to December 31, 2016; n = 1,392,779) and BC (March 1, 2004 to April 31, 2017; n = 559,205). Deliveries were stratified into Robson categories and the CD rate, relative size of each group and its contribution to the overall CD rate were compared between the Swedish and the Canadian cohorts. Poisson and log-binomial regression were used to assess the contribution of maternal, fetal, and obstetric practice factors to spatiotemporal differences in Robson group-specific CD rates between Sweden and BC. Nulliparous women comprised 44.8% of the study population, while women of advanced maternal age (≥35 years) and women with overweight/obesity (≥25 kg/m2) constituted 23.5% and 32.4% of the study population, respectively. The CD rate in Sweden was stable at approximately 17.0% from 2004 to 2016 (p for trend = 0.10), while the CD rate increased in BC from 29.4% to 33.9% (p for trend < 0.001). Differences in CD rates between Sweden and BC varied by Robson group, for example, in Group 1 (nullipara with a term, single, cephalic fetus with spontaneous labor), the CD rate was 8.1% in Sweden and 20.4% in BC (rate ratio [RR] for BC versus Sweden = 2.52, 95% confidence interval [CI] 2.49 to 2.56, p < 0.001) and in Group 2 (nullipara, single, cephalic fetus, term gestation with induction of labor or prelabor CD), the rate of CD was 37.3% in Sweden and 45.9% in BC (RR = 1.23, 95% CI 1.22 to 1.25, p < 0.001). The effect of adjustment for maternal characteristics (e.g., age, body mass index), maternal comorbidity (e.g., preeclampsia), fetal characteristics (e.g., head position), and obstetric practice factors (e.g., epidural) ranged from no effect (e.g., among breech deliveries; Groups 6 and 7) to explaining up to 5.2% of the absolute difference in the CD rate (Group 2: adjusted CD rate in BC 40.7%, adjusted RR = 1.09, 95% CI 1.08 to 1.12, p < 0.001). Adjustment also explained a substantial fraction of the temporal change in CD rates among some Robson groups in BC. Limitations of the study include a lack of information on intrapartum details, such as labor duration as well as maternal and perinatal outcomes associated with the observed differences in CD rates. CONCLUSIONS: In this study, we found that several factors not included in the Robson classification explain a significant proportion of the spatiotemporal difference in CD rates in some Robson groups. These findings suggest that incorporating these factors into explanatory models using the Robson classification may be useful for ensuring that public health initiatives regarding CD rates are evidence informed.

Chorioamnionitis and risk of long-term neurodevelopmental disorders in offspring: a population-based cohort study.

BACKGROUND: Evidence indicates that in utero exposure to chorioamnionitis might increase the risk of neurodevelopmental disorders in the offspring. However, findings on this topic have been inconsistent. OBJECTIVE: To examine the association between chorioamnionitis and neurodevelopmental disorders in offspring. STUDY DESIGN: This was a retrospective population-based cohort study in Sweden. A total of 2,228,280 singleton live births and stillbirths between 1998 and 2019 were included in our study population. Data on maternal characteristics and neurodevelopmental disorders in offspring were obtained by individual record-linkages of nationwide Swedish registries. Chorioamnionitis was identified using the National Medical Birth Register. Inpatient and outpatient diagnoses were obtained for cerebral palsy, autism, attention deficit hyperactivity disorder, epilepsy, and intellectual disability. Multivariable Cox proportional hazards regression was used to estimate the association between chorioamnionitis and each neurodevelopmental disorder with adjusted hazard ratios and 95% confidence intervals. A causal mediation analysis of the relationship between chorioamnionitis and neurodevelopmental disorders with preterm delivery (<37 weeks) was performed. RESULTS: A total of 5770 (0.26%) offspring were exposed to chorioamnionitis during pregnancy. During the study's follow-up time there were 4752 (0.21%) cases of cerebral palsy, 17,897 (0.80 %) cases of epilepsy, 50,570 (2.27 %) cases of autism, 114,087 (5.12%) cases of attention deficit hyperactivity disorder, and 14,574 (0.65%) cases of intellectual disability. After adjusting for potential confounders, exposure to chorioamnionitis increased the hazard ratios of cerebral palsy (adjusted hazard ratio, 7.43; 95% confidence interval, 5.90-9.37), autism (adjusted hazard ratio, 1.43; 95% confidence interval, 1.21-1.68), attention deficit hyperactivity disorder (adjusted hazard ratio, 1.17; 95% confidence interval, 1.03-1.33), and intellectual disability (adjusted hazard ratio, 1.99; 95% confidence interval, 1.53-2.58), whereas chorioamnionitis was not significantly associated with higher rates of epilepsy in offspring. Mediation analysis revealed that these associations were mainly explained through preterm delivery; however, increased risk was also observed among term infants. CONCLUSION: Chorioamnionitis increases the risk of neurodevelopmental disorders, particularly cerebral palsy, autism, attention deficit hyperactivity disorder, and intellectual disability. These associations were mainly mediated through preterm delivery. Efforts for timely identification and appropriate interventions to treat infections during pregnancy will have sustained benefits in reducing the burden of neurologic complications in children at the population level.

Maternal and neonatal trauma following operative vaginal delivery.

BACKGROUND: Operative vaginal delivery (OVD) is considered safe if carried out by trained personnel. However, opportunities for training in OVD have declined and, given these shifts in practice, the safety of OVD is unknown. We estimated incidence rates of trauma following OVD in Canada, and quantified variation in trauma rates by instrument, region, level of obstetric care and institutional OVD volume. METHODS: We conducted a cohort study of all singleton, term deliveries in Canada between April 2013 and March 2019, excluding Quebec. Our main outcome measures were maternal trauma (e.g., obstetric anal sphincter injury, high vaginal lacerations) and neonatal trauma (e.g., subgaleal hemorrhage, brachial plexus injury). We calculated adjusted and stabilized rates of trauma using mixed-effects logistic regression. RESULTS: Of 1 326 191 deliveries, 38 500 (2.9%) were attempted forceps deliveries and 110 987 (8.4%) were attempted vacuum deliveries. The maternal trauma rate following forceps delivery was 25.3% (95% confidence interval [CI] 24.8%-25.7%) and the neonatal trauma rate was 9.6 (95% CI 8.6-10.6) per 1000 live births. Maternal and neonatal trauma rates following vacuum delivery were 13.2% (95% CI 13.0%-13.4%) and 9.6 (95% CI 9.0-10.2) per 1000 live births, respectively. Maternal trauma rates remained higher with forceps than with vacuum after adjustment for confounders (adjusted rate ratio 1.70, 95% CI 1.65-1.75) and varied by region, but not by level of obstetric care. INTERPRETATION: In Canada, rates of trauma following OVD are higher than previously reported, irrespective of region, level of obstetric care and volume of OVD among hospitals. These results support a reassessment of OVD safety in Canada.