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.

Severe Maternal Morbidity and Maternal Mortality Associated with Assisted Reproductive Technology.

OBJECTIVE: To assess the association between use of assisted reproductive technologies (ART) and severe maternal morbidity and maternal mortality (SMM). METHODS: We carried out a cohort study that included all hospital deliveries at ≥20 weeks gestation in Canada (excluding Québec) between April 2009 and March 2018. Outcomes of interest included composite SMM and SMM types (e.g., severe preeclampsia, HELLP syndrome, and eclampsia; severe hemorrhage; acute renal failure). Multivariable regression was used to estimate crude and adjusted rate ratios (RR and aRR) and 95% confidence intervals (CI). RESULTS: The study included 2 535 056 women, of whom 72 023 (2.8%) delivered following the use of ART. The composite SMM rate for women who used ART was 34.7 per 1000 deliveries (95% CI 33.0-36.0) versus 11.5 per 1000 deliveries (95% CI 11.4-11.6) for women who did not use ART (RR 3.01; 95% CI 2.89-3.14). ART use was associated with SMM types such as severe preeclampsia, HELLP syndrome, and eclampsia (RR 3.50; 95% CI 3.27-3.73), severe hemorrhage (RR 3.58, 95% CI 3.27-3.92), and acute renal failure (RR 6.79; 95% CI 5.78-7.98). Associations between ART and composite SMM were attenuated but remained elevated after adjusting for maternal characteristics (aRR 2.34; 95% CI 2.24-2.45). Women who used ART and had a multi-fetal pregnancy had a 4.7 times higher rate of composite SMM compared with women who did not use ART and delivered singletons. CONCLUSION: Women who deliver following the use of ART have increased risks of SMM and require counselling that includes mention of the lower risks of SMM associated with ART-conceived singleton pregnancy.

Incidence and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm and term gestation: a population-based study.

BACKGROUND: The majority of previous studies on severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome were hospital-based or included a relatively small number of women. Large, population-based studies examining gestational age-specific incidence patterns and risk factors for these severe pregnancy complications are lacking. OBJECTIVE: This study aimed to assess the gestational age-specific incidence rates and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia. STUDY DESIGN: We carried out a retrospective, population-based cohort study that included all women with a singleton hospital birth in Canada (excluding Quebec) from 2012 to 2016 (N=1,078,323). Data on the primary outcomes (ie, severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia) were obtained from delivery hospitalization records abstracted by the Canadian Institute for Health Information. A Cox regression was used to assess independent risk factors (eg, maternal age and chronic comorbidity) for each primary outcome and to assess differences in the effects at preterm vs term gestation (<37 vs ≥37 weeks). RESULTS: The rates of severe preeclampsia (n=2533), hemolysis, elevated liver enzymes, and low platelet count syndrome (n=2663), and eclampsia (n=465) were 2.35, 2.47, and 0.43 per 1000 singleton pregnancies, respectively. The cumulative incidence of term-onset severe preeclampsia was lower than that of preterm-onset severe preeclampsia (0.87 vs 1.54 per 1000; rate ratio, 0.57; 95% confidence intervals, 0.53-0.62), the rates of hemolysis, elevated liver enzymes, and low platelet count syndrome were similar (1.32 vs 1.23 per 1000; rate ratio, 0.93; 95% confidence interval, 0.86-1.00), and the preterm-onset eclampsia rate was lower than the term-onset rate (0.12 vs 0.33 per 1000; rate ratio, 2.64; 95% confidence interval, 2.16-3.23). For each primary outcome, chronic comorbidity and congenital anomalies were stronger risk factors for preterm- vs term-onset disease. Younger mothers (aged <25 years) were at higher risk for severe preeclampsia at term and for eclampsia at all gestational ages, whereas older mothers (aged ≥35 years) had elevated risks for severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Regardless of gestational age, nulliparity was a risk factor for all outcomes, whereas socioeconomic status was inversely associated with severe preeclampsia. CONCLUSION: The risk for severe preeclampsia declined at term, eclampsia risk increased at term, and hemolysis, elevated liver enzymes, and low platelet count syndrome risk was similar for preterm and term gestation. Young maternal age was associated with an increased risk for eclampsia and term-onset severe preeclampsia. Prepregnancy comorbidity and fetal congenital anomalies were more strongly associated with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm gestation.

The morbid genome of ciliopathies: an update.

PURPOSE: Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly. METHODS: Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes. RESULTS: In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet-Biedl syndrome. CONCLUSION: In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.

Timing of delivery in women with diabetes: A population-based study.

INTRODUCTION: Women with diabetes, and their infants, have an increased risk of adverse events due to excess fetal growth. Earlier delivery, when fetuses are smaller, may reduce these risks. This study aimed to evaluate the week-specific risks of maternal and neonatal morbidity/mortality to assist with obstetrical decision making. MATERIAL AND METHODS: In this population-based cohort study, women with type 1 diabetes (n = 5889), type 2 diabetes (n = 9422) and gestational diabetes (n = 138 917) and a comparison group without diabetes (n = 2 553 243) who delivered a singleton infant at ≥36 completed weeks of gestation between 2004 and 2014 were identified from the Canadian Institute of Health Information Discharge Abstract Database. Multivariate logistic regression was used to determine the week-specific rates of severe maternal and neonatal morbidity/mortality among women delivered iatrogenically vs those undergoing expectant management. RESULTS: For all women, the absolute risk of severe maternal morbidity/mortality was low, typically impacting less than 1% of women, and there was no significant difference in gestational age-specific severe maternal morbidity/mortality between iatrogenic delivery and expectant management among women with any form of diabetes. Among women with gestational diabetes, iatrogenic delivery was associated with an increased risk of neonatal morbidity/mortality compared with expectant management at 36 and 37 weeks' gestation (76.7 and 27.8 excess cases per 1000 deliveries, respectively) and a lower risk of neonatal morbidity/mortality at 38, 39 and 40 weeks' gestation (7.9, 27.3 and 15.9 fewer cases per 1000 deliveries, respectively). Increased risks of severe neonatal morbidity following iatrogenic delivery compared with expectant management were also observed for women with type 1 diabetes at 36 (98.3 excess cases per 1000 deliveries) and 37 weeks' gestation (44.5 excess cases per 1000 deliveries) and for women with type 2 diabetes at 36 weeks' gestation (77.9 excess cases per 1000 deliveries) weeks. CONCLUSIONS: The clinical decision regarding timing of delivery is complex and contingent on maternal-fetal wellbeing, including adequate glycemic control. This study suggests that delivery at 38, 39 or 40 weeks' gestation may optimize neonatal outcomes among women with diabetes.

Quality assessment of evidence-based clinical practice guidelines for the management of pregnant women with sickle cell disease using the AGREE II instrument: a systematic review.

BACKGROUND: The management of pregnant women with sickle cell disease (SCD) poses a major challenge for maternal healthcare services owing to the potential for complications associated with morbidity and mortality. Trustworthy evidence-based clinical practice guidelines (CPGs) have a major impact on the positive outcomes of appropriate healthcare. The objective of this study was to critically appraise the quality of recent CPGs for SCD in pregnant women. METHODS: Clinical questions were identified and the relevant CPG and bibliographic databases were searched and screened for eligible CPGs. Each CPG was appraised by four independent appraisers using the AGREE II Instrument. Inter-rater analysis was conducted. RESULTS: Four eligible CPGs were appraised: American College of Obstetricians and Gynecologists (ACOG), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Health and Care Excellence (NICE), and Royal College of Obstetricians and Gynaecologists (RCOG). Among them, the overall assessments of three CPGs (NICE, RCOG, NHLBI) scored greater than 70%; these findings were consistent with the high scores in the six domains of AGREE II, including:[1] scope and purpose,[2] stakeholder involvement,[3] rigor of development,[4] clarity of presentation,[5] applicability, and [6] editorial independence domains. Domain [3] scored (90%, 73%, 71%), domain [5] (90%, 46%, 47%), and domain [6] (71%, 77%, 52%) for NICE, RCOG, and NHLBI, respectively. Overall, the clinical recommendations were not significantly different between the included CPGs. CONCLUSIONS: Three evidence-based CPGs presented superior methodological quality. NICE demonstrated the highest quality followed by RCOG and NHLBI and all three CPGs were recommended for use in practice.

Association between gestational weight gain and severe adverse birth outcomes in Washington State, US: A population-based retrospective cohort study, 2004-2013.

BACKGROUND: Suboptimal weight gain during pregnancy is a potentially modifiable risk factor. We aimed to investigate the association between suboptimal gestational weight gain and severe adverse birth outcomes by pre-pregnancy body mass index (BMI) categories, including obesity class I to III. METHODS AND FINDINGS: We conducted a population-based study of pregnant women with singleton hospital births in Washington State, US, between 2004 and 2013. Optimal, low, and excess weight gain in each BMI category was calculated based on weight gain by gestational age as recommended by the American College of Obstetricians and Gynecologists and the Institute of Medicine. Primary composite outcomes were (1) maternal death and/or severe maternal morbidity (SMM) and (2) perinatal death and/or severe neonatal morbidity. Logistic regression was used to obtain adjusted odds ratios (AORs) and 95% confidence intervals. Overall, 722,839 women with information on pre-pregnancy BMI were included. Of these, 3.1% of women were underweight, 48.1% had normal pre-pregnancy BMI, 25.8% were overweight, and 23.0% were obese. Only 31.5% of women achieved optimal gestational weight gain. Women who had low weight gain were more likely to be African American and have Medicaid health insurance, while women with excess weight gain were more likely to be non-Hispanic white and younger than women with optimal weight gain in each pre-pregnancy BMI category. Compared with women who had optimal weight gain, those with low gestational weight gain had a higher rate of maternal death, 7.97 versus 2.63 per 100,000 (p = 0.027). In addition, low weight gain was associated with the composite adverse maternal outcome (death/SMM) in women with normal pre-pregnancy BMI and in overweight women (AOR 1.12, 95% CI 1.04-1.21, p = 0.004, and AOR 1.17, 95% CI 1.04-1.32, p = 0.009, respectively) compared to women in the same pre-pregnancy BMI category who had optimal weight gain. Similarly, excess gestational weight gain was associated with increased rates of death/SMM among women with normal pre-pregnancy BMI (AOR 1.20, 95% CI 1.12-1.28, p < 0.001) and obese women (AOR 1.12, 95% CI 1.01-1.23, p = 0.019). Low gestational weight gain was associated with perinatal death and severe neonatal morbidity regardless of pre-pregnancy BMI, including obesity classes I, II, and III, while excess weight gain was associated with severe neonatal morbidity only in women who were underweight or had normal BMI prior to pregnancy. Study limitations include the ascertainment of pre-pregnancy BMI using self-report, and lack of data availability for the most recent years. CONCLUSIONS: In this study, we found that most women do not achieve optimal weight gain during pregnancy. Low weight gain was associated with increased risk of severe adverse birth outcomes, and in particular with maternal death and perinatal death. Excess gestational weight gain was associated with severe adverse birth outcomes, except for women who were overweight prior to pregnancy. Weight gain recommendations for this group may need to be reassessed. It is important to counsel women during pregnancy about specific risks associated with both low and excess weight gain.

Episiotomy use among vaginal deliveries and the association with anal sphincter injury: a population-based retrospective cohort study.

BACKGROUND: The rate of obstetric anal sphincter injury has increased in recent years, particularly among operative vaginal deliveries. We sought to characterize temporal trends in episiotomy use and to quantify the association between episiotomy and obstetric anal sphincter injury. METHODS: Using a population-based retrospective cohort study design of hospital data from 2004 to 2017, we studied all vaginal deliveries of singleton infants at term gestation in Canada (excluding Quebec). Rates of obstetric anal sphincter injury were contrasted between women who had an episiotomy and those who did not. Log-binomial regression was used to estimate the association between episiotomy and obstetric anal sphincter injury among women with spontaneous and operative vaginal deliveries after controlling for confounders. RESULTS: The study population included 2 570 847 deliveries. Episiotomy use declined significantly among operative vaginal deliveries (53.1% in 2004 to 43.2% in 2017, p < 0.0001) and spontaneous vaginal deliveries (13.5% in 2004 to 6.5% in 2017, p < 0.0001). Episiotomy was associated with higher rates of obstetric anal sphincter injury among spontaneous vaginal deliveries (4.8 with episiotomy v. 2.4% without; adjusted rate ratio [RR] 2.06, 95% confidence interval [CI] 2.00-2.11) and this association remained after stratification by parity and obstetric history. In contrast, episiotomy was associated with lower rates of obstetric anal sphincter injury among forceps deliveries in nulliparous women (adjusted RR 0.63, 95% CI 0.61-0.66), and women with vaginal birth after cesarean (adjusted RR 0.71, 95% CI 0.60-0.85), but not among parous women without a previous cesarean (adjusted RR 1.16, 95% CI 1.00-1.34). INTERPRETATION: Episiotomy use has declined in Canada for all vaginal deliveries. The protective association between episiotomy and obstetric anal sphincter injury among women who gave birth by operative vaginal delivery (especially forceps) warrants reconsideration of clinical practice among nulliparous women and those attempting vaginal birth after cesarean.

Morbidity and Mortality Associated With Forceps and Vacuum Delivery at Outlet, Low, and Midpelvic Station.

OBJECTIVE: This study sought to quantify perinatal and maternal morbidity and mortality associated with forceps and vacuum delivery compared with Caesarean delivery in the second stage of labour and to estimate whether these associations differed by pelvic station. METHODS: The investigators conducted a population-based, retrospective cohort study of term singleton deliveries by operative delivery with prolonged second stage of labour in Canada (2003-2013) using national hospitalization data. The primary study outcomes were severe perinatal morbidity and mortality (i.e., seizures, assisted ventilation, severe birth trauma, and perinatal death) and severe maternal morbidity and mortality (i.e., severe postpartum hemorrhage, cardiac complication, and maternal death). Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) after stratifying by indication (dystocia or fetal distress). The Breslow-Day chi-square test for heterogeneity in ORs was used to test effect modification by pelvic station (outlet, low, or midpelvic). RESULTS: There were 61 106 deliveries included in the study. Among women with dystocia, forceps and vacuum deliveries were associated with higher rates of perinatal morbidity and mortality compared with Caesarean delivery (forceps: aOR 1.56; 95% CI 1.13-2.17; vacuum: aOR 1.44; 95% CI 1.06-1.97). Vacuum delivery was associated with lower rates of maternal morbidity and mortality compared with Caesarean delivery (dystocia: aOR 0.64; 95% CI 0.51-0.81; fetal distress: aOR 0.43; 95% CI 0.32-0.57). Pelvic station did not significantly modify the associations between forceps or vacuum and perinatal or maternal morbidity and mortality. CONCLUSION: Forceps and vacuum delivery is associated with increased rates of severe perinatal morbidity and mortality compared with Caesarean delivery among women with dystocia, whereas vacuum delivery is associated with decreased rates of severe maternal morbidity and mortality.

Expanding the phenome and variome of skeletal dysplasia.

PURPOSE: To describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized. METHODS: Detailed phenotyping and next-generation sequencing (panel and exome). RESULTS: Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average. CONCLUSION: By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.

Mode of delivery after a previous cesarean birth, and associated maternal and neonatal morbidity.

BACKGROUND: The mode of delivery for women with a previous cesarean delivery remains contentious. We conducted a study comparing maternal and infant outcomes after attempted vaginal birth after cesarean delivery versus elective repeat cesarean delivery. METHODS: We used data from the Discharge Abstract Database that includes all hospital deliveries in Canada (excluding Quebec). In our analysis, we included singleton deliveries to women between 37 and 43 weeks gestation who had a single prior cesarean delivery between April 2003 and March 2015. The primary outcomes were severe maternal morbidity and mortality, and serious neonatal morbidity and mortality. We used logistic regression to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Absolute rates of severe maternal morbidity and mortality were low but significantly higher after attempted vaginal birth after cesarean delivery compared with elective repeat cesarean delivery (10.7 v. 5.65 per 1000 deliveries, respectively; adjusted RR 1.96, 95% CI 1.76 to 2.19). Adjusted rate differences in severe maternal morbidity and mortality, and serious neonatal morbidity and mortality were small (5.42 and 7.09 per 1000 deliveries, respectively; number needed to treat 184 and 141, respectively). The association between vaginal birth after cesarean delivery, and serious neonatal morbidity and mortality showed a temporal worsening (adjusted RR 0.94, 95% CI 0.77 to 1.15 in 2003-2005; adjusted RR 2.07, 95% CI 1.83 to 2.35 in 2012-2014). INTERPRETATION: Although absolute rates of adverse outcomes are low, attempted vaginal birth after cesarean delivery continues to be associated with higher relative rates of severe morbidity and mortality in mothers and infants. Temporal worsening of infant outcomes after attempted vaginal birth after cesarean delivery highlights the need for greater care in selecting candidates, and more careful monitoring of labour and delivery.

Ecological association between operative vaginal delivery and obstetric and birth trauma.

BACKGROUND: Increased use of operative vaginal delivery (use of forceps, vacuum or other device) has been recommended to address high rates of cesarean delivery. We sought to determine the association between rates of operative vaginal delivery and obstetric trauma and severe birth trauma. METHODS: We carried out an ecological analysis of term, singleton deliveries in 4 Canadian provinces (2004-2014) using data from the Canadian Institute for Health Information. The primary exposure was mode of delivery. The primary outcomes were obstetric trauma and severe birth trauma. RESULTS: Data on 1 938 913 deliveries were analyzed. The rate of obstetric trauma was 7.2% in nulliparous women, and 2.2% and 2.7% among parous women without and with a previous cesarean delivery, respectively, and rates of severe birth trauma were 2.1, 1.7 and 0.7 per 1000, respectively. Each 1% absolute increase in rates of operative vaginal delivery was associated with a higher frequency of obstetric trauma among nulliparous women (adjusted rate ratio [ARR] 1.06, 95% confidence interval [CI] 1.05-1.06), parous women without a previous cesarean delivery (ARR 1.10, 95% CI 1.08-1.13) and parous women with a previous cesarean delivery (ARR 1.11, 95% CI 1.07-1.16). Operative vaginal delivery was associated with more frequent severe birth trauma, but only in nulliparous women (ARR 1.05, 95% CI 1.03-1.07). In nulliparous women, sequential vacuum and forceps instrumentation was associated with the largest increase in obstetric trauma (ARR 1.44, 95% CI 1.35-1.55) and birth trauma (ARR 1.53, 95% CI 1.03-2.27). INTERPRETATION: Increases in population rates of operative vaginal delivery are associated with higher population rates of obstetric trauma, and in nulliparous women with severe birth trauma.

Maternal age and severe maternal morbidity: A population-based retrospective cohort study.

BACKGROUND: One of the United Nations' Millennium Development Goals of 2000 was to reduce maternal mortality by 75% in 15 y; however, this challenge was not met by many industrialized countries. As average maternal age continues to rise in these countries, associated potentially life-threatening severe maternal morbidity has been understudied. Our primary objective was to examine the associations between maternal age and severe maternal morbidities. The secondary objective was to compare these associations with those for adverse fetal/infant outcomes. METHODS AND FINDINGS: This was a population-based retrospective cohort study, including all singleton births to women residing in Washington State, US, 1 January 2003-31 December 2013 (n = 828,269). We compared age-specific rates of maternal mortality/severe morbidity (e.g., obstetric shock) and adverse fetal/infant outcomes (e.g., perinatal death). Logistic regression was used to adjust for parity, body mass index, assisted conception, and other potential confounders. We compared crude odds ratios (ORs) and adjusted ORs (AORs) and risk differences and their 95% CIs. Severe maternal morbidity was significantly higher among teenage mothers than among those 25-29 y (crude OR = 1.5, 95% CI 1.5-1.6) and increased exponentially with maternal age over 39 y, from OR = 1.2 (95% CI 1.2-1.3) among women aged 35-39 y to OR = 5.4 (95% CI 2.4-12.5) among women aged ≥50 y. The elevated risk of severe morbidity among teen mothers disappeared after adjustment for confounders, except for maternal sepsis (AOR = 1.2, 95% CI 1.1-1.4). Adjusted rates of severe morbidity remained increased among mothers ≥35 y, namely, the rates of amniotic fluid embolism (AOR = 8.0, 95% CI 2.7-23.7) and obstetric shock (AOR = 2.9, 95% CI 1.3-6.6) among mothers ≥40 y, and renal failure (AOR = 15.9, 95% CI 4.8-52.0), complications of obstetric interventions (AOR = 4.7, 95% CI 2.3-9.5), and intensive care unit (ICU) admission (AOR = 4.8, 95% CI 2.0-11.9) among those 45-49 y. The adjusted risk difference in severe maternal morbidity compared to mothers 25-29 y was 0.9% (95% CI 0.7%-1.2%) for mothers 40-44 y, 1.6% (95% CI 0.7%-2.8%) for mothers 45-49 y, and 6.4% for mothers ≥50 y (95% CI 1.7%-18.2%). Similar associations were observed for fetal and infant outcomes; neonatal mortality was elevated in teen mothers (AOR = 1.5, 95% CI 1.2-1.7), while mothers over 29 y had higher risk of stillbirth. The rate of severe maternal morbidity among women over 49 y was higher than the rate of mortality/serious morbidity of their offspring. Despite the large sample size, statistical power was insufficient to examine the association between maternal age and maternal death or very rare severe morbidities. CONCLUSIONS: Maternal age-specific incidence of severe morbidity varied by outcome. Older women (≥40 y) had significantly elevated rates of some of the most severe, potentially life-threatening morbidities, including renal failure, shock, acute cardiac morbidity, serious complications of obstetric interventions, and ICU admission. These results should improve counselling to women who contemplate delaying childbirth until their forties and provide useful information to their health care providers. This information is also useful for preventive strategies to lower maternal mortality and severe maternal morbidity in developed countries.

Perinatal and maternal morbidity and mortality after attempted operative vaginal delivery at midpelvic station.

BACKGROUND: Increased use of operative vaginal delivery (i.e., forceps or vacuum application), of which 20% occurs at midpelvic station, has been advocated to reduce the rate of cesarean delivery. We aimed to quantify severe perinatal and maternal morbidity and mortality associated with attempted midpelvic operative vaginal delivery. METHODS: We studied all term singleton deliveries in Canada between 2003 and 2013, by attempted midpelvic operative vaginal or cesarean delivery with labour (with and without prolonged second stage). The primary outcomes were composite severe perinatal morbidity and mortality (e.g., convulsions, assisted ventilation, severe birth trauma and perinatal death), and composite severe maternal morbidity and mortality (e.g., severe postpartum hemorrhage, shock, sepsis, cardiac complications, acute renal failure and death). RESULTS: The study population included 187 234 deliveries. Among women with dystocia and prolonged second stage of labour, midpelvic operative vaginal delivery was associated with higher rates of severe perinatal morbidity and mortality compared with cesarean delivery (forceps, adjusted odds ratio [AOR] 1.81, 95% confidence interval [CI] 1.24 to 2.64; vacuum, AOR 1.81, 95% CI 1.17 to 2.80; sequential instruments, AOR 3.19, 95% CI 1.73 to 5.88), especially with higher rates of severe birth trauma. Rates of severe maternal morbidity and mortality were not significantly different after operative vaginal delivery, although rates of obstetric trauma were higher (forceps, AOR 4.51, 95% CI 4.04 to 5.02; vacuum, AOR 2.70, 95% CI 2.35 to 3.09; sequential instruments, AOR 4.24, 95% CI 3.46 to 5.19). Among women with fetal distress, similar associations were seen for severe birth trauma and obstetric trauma, although vacuum was associated with lower rates of severe maternal morbidity and mortality (AOR 0.52, 95% CI 0.33 to 0.80). Associations tended to be stronger among women without a prolonged second stage. INTERPRETATION: Midpelvic operative vaginal delivery is associated with higher rates of severe birth trauma and obstetric trauma, whereas overall rates of severe perinatal and maternal morbidity and mortality vary by indication and operative instrument.

Neonatal respiratory morbidity following exposure to chorioamnionitis.

BACKGROUND: There are conflicting results in the literature on the impact of chorioamnionitis on neonatal respiratory morbidities. However, most studies are based on small clinical samples and fail to account for the competing risk of perinatal death. This study aimed to determine whether chorioamnionitis affects the incidence of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) after accounting for the increased risk of death. METHODS: Retrospective cohort study using linked birth and infant death registration and hospitalization records from Washington State between 2002 and 2011 (n = 763,671 singleton infants and n = 56,537 singleton preterm infants). Logistic regression models based on the traditional and fetuses-at-risk approaches were used to model two composite outcomes namely RDS and perinatal death and BPD and perinatal death. Confounders adjusted for in the models included maternal age, race, diabetes, hypertension, antenatal corticosteroids, mode of delivery and infant sex. RESULTS: While models using the traditional approach found a significant association only between chorioamnionitis and composite BPD and perinatal death (OR = 1.23, 95% CI: 1.01-1.50); using the fetuses-at-risk approach, there was a significant association between chorioamnionitis and both composite outcomes (RDS and perinatal death OR = 2.74, 2.50-3.01; BPD and perinatal death OR = 5.18, 95% CI: 4.39-6.11). CONCLUSION: The fetuses-at-risk approach models the causal impact of chorioamnionitis on the development of the fetal lung and shows an increased risk of RDS, BPD and perinatal death associated with such maternal infection.

Temporal and Regional Variations in Operative Vaginal Delivery in Canada by Pelvic Station, 2004-2012.

OBJECTIVE: To describe temporal and regional variations in Canada in the use of operative vaginal delivery (OVD) at term for singleton pregnancies by pelvic station between 2004 and 2013. METHODS: Rates of OVD among term singleton pregnancies in Canada (excluding Quebec) were estimated using information from the Discharge Abstract Database of the Canadian Institute for Health Information for the years 2004-2012 (n = 2 284 109). Deliveries were stratified by pelvic station. Temporal trends were assessed using the Cochran-Armitage test for linear trend in proportions by year. Geographic variation was assessed by calculating the rate and 95% confidence interval of each mode of delivery from 2010-2012 for each province and territory. RESULTS: Among singleton pregnancies at term, the OVD rate decreased from 12.0% in 2004 to 10.7% in 2012 (P < 0.001), whereas Caesarean section rates (excluding those following failed OVDs) increased from 24.9% to 26.7%. Forceps deliveries decreased from 3.1% to 2.5%, primarily due to decreases in midpelvic forceps delivery. Vacuum-assisted delivery increased significantly at outlet and low stations (by 26.0% and 15.1%, respectively) and remained stable at midpelvic station. The failed OVD rate was 0.3% and decreased by 23.7% (P < 0.001). There were large variations in OVD rates by province. CONCLUSION: Temporal trends in OVD rates varied by pelvic station, with rates of outlet and low OVD increasing and rates of midpelvic and failed OVD decreasing. Vacuum extraction is increasingly replacing forceps deliveries at outlet and low stations, whereas Caesarean sections are replacing forceps deliveries at midpelvic stations. Variations in OVD rates across provinces suggest differences in instrument preference and/or an evolution in standards of practice.

Diagnosis of subclinical amniotic fluid infection prior to rescue cerclage using gram stain and glucose tests: an individual patient meta-analysis.

OBJECTIVES: Microbial invasion of the amniotic cavity (MIAC) can affect outcomes following rescue cerclage. We carried out a study to compare the diagnostic performance of the Gram stain and glucose tests for detecting subclinical MIAC. METHODS: We used individual-level data from published studies on Gram stain, glucose, and amniotic fluid culture among women with preterm labour. We calculated the sensitivity, specificity, area under the curve (AUC) and other indices, with amniotic fluid culture results used as the gold standard. The probability of infection using both tests as predictors was also estimated using logistic regression. RESULTS: The rate of culture-confirmed MIAC was 11.8% (34 of 288 women). The Gram stain test yielded a sensitivity of 65% (95% CI 46% to 78%) and a specificity of 99% (95% CI 98% to 100%). A positive Gram stain or glucose test had a sensitivity of 88% (95% CI 72% to 96%) and a specificity of 87% (95% CI 82% to 90%), while a positive Gram stain and a positive glucose test had a sensitivity of 62% (95% CI 44% to 77%) and a specificity of 100% (95% CI 98% to 100%). The AUC for the tests were Gram stain 0.82 (95% CI 0.74 to 0.90), glucose 0.86 (95% CI 0.80 to 0.93), and combined Gram stain and glucose 0.92 (95% CI 0.86 to 0.98). Using the tests, singly or in combination, provided greater clinically important calibration, risk-stratification, and classification accuracy than using no tests. CONCLUSION: Amniotic fluid Gram stain and/or glucose testing provides substantially improved performance for the diagnosis of subclinical MIAC compared with no testing.

Objectifs : L'invasion microbienne de la cavité amniotique (IMCA) peut affecter les issues à la suite d'un cerclage d'urgence. Nous avons mené une étude visant à comparer le rendement diagnostique de la coloration de Gram à celui de la concentration en glucose pour ce qui est du dépistage d'une IMCA subclinique. Méthodes : Nous avons utilisé des données personnelles issues d'études publiées ayant porté sur l'utilisation de la coloration de Gram, de la concentration en glucose et de la mise en culture du liquide amniotique chez des femmes connaissant un travail préterme. Nous avons calculé la sensibilité, la spécificité, la surface sous la courbe (SSC) et d'autres indices, les résultats de la mise en culture du liquide amniotique étant utilisés à titre de test de référence. La probabilité de constater une infection à la suite de l'utilisation des deux tests à titre de facteurs prédictifs a également été estimée au moyen d'une régression logistique. Résultats : Le taux d'IMCA confirmée par mise en culture était de 11,8 % (34 femmes sur 288). Le test par coloration de Gram a présenté une sensibilité de 65 % (IC à 95 %, 46 % - 78 %) et une spécificité de 99 % (IC à 95 %, 98 % - 100 %). L'obtention d'un résultat positif à la suite d'une coloration de Gram ou de la mesure de la concentration en glucose présentait une sensibilité de 88 % (IC à 95 %, 72 % - 96 %) et une spécificité de 87 % (IC à 95 %, 82 % - 90 %), tandis que l'obtention d'un résultat positif à la suite d'une coloration de Gram et de la mesure de la concentration en glucose présentait une sensibilité de 62 % (IC à 95 %, 44 % - 77 %) et une spécificité de 100 % (IC à 95 %, 98 % - 100 %). Les SSC étaient de 0,82 (IC à 95 %, 0,74 - 0,90) pour la coloration de Gram, de 0,86 (IC à 95 %, 0,80 - 0,93) pour la concentration en glucose et de 0,92 (IC à 95 %, 0,86 - 0,98) pour la combinaison « coloration de Gram-concentration en glucose ¼. L'utilisation de ces tests, de façon isolée ou en combinaison, offrait une meilleure (importante sur le plan clinique) capacité d'étalonnage, capacité de stratification du risque et précision en matière de classification que l'utilisation d'aucun de ces tests. Conclusion : La coloration de Gram et/ou la mesure de la concentration en glucose du liquide amniotique offrent un rendement substantiellement accru pour ce qui est du diagnostic de l'IMCA subclinique, par comparaison avec l'absence de tests.