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.

Association of health and lifestyle factors with uterine fibroids among Saudi women: A case-control study.

Objectives: The objective of this study was to measure the association between uterine fibroids (UFs) and several risk factors (parity, miscarriage, diabetes, hypertension, physical activity, smoking, family history of UF and contraceptive pill use) among Saudi women. Methods: A case-control study was conducted in 478 women at two medical centers in Riyadh. Cases were confirmed by ultrasound. Demographic and risk factor information was collected from interviews and medical records. The prevalence of risk factors was calculated with 95% confidence interval (CI). Unconditional logistic regression analysis was used to measure the associations between UFs and the risk factors. Results: More than half the participants were obese. The average body mass index (BMI) was 31.2 (±6.81) for cases and 29.4 (±7.02) for controls. Women 40 years or older had four times the odds of UFs than women younger than 40 years (adjusted odds ratio [AOR] = 4.24, 95% CI = 2.63, 6.85). Having a family history of UFs was associated with 69% greater odds of UFs (AOR = 1.69, 95% CI = 1.02, 2.81). Being obese was associated with 74% greater odds of UFs (AOR = 1.74, 95% CI = 1.00, 2.59), whereas previous live births decreased the odds of UFs by 62% (AOR = 0.38, 95% CI = 0.19, 0.75). Conclusions: This study identified risk factors associated with UFs in the Saudi population. Age over 40 years, obesity and a family history of UFs are important risk factors for UF, whereas parity appears to be protective against UF development in Saudi women. Early recognition of these risk factors is important to prevent UF complications.

Prevalence of restless legs syndrome among pregnant women: A case-control study.

BACKGROUND: This cross-sectional case-control study aimed to assess the prevalence of restless legs syndrome (RLS) and its correlates and severity among Arab (Saudi) pregnant women attending antenatal care clinics. METHODS: We interviewed 742 consecutive pregnant women attending antenatal clinics face-to-face using the International RLS Study Group (IRLSSG) criteria. We assessed the severity of RLS using the IRLSSG severity scale for RLS (IRLS). A similar number of age-matched nonpregnant women were enrolled in a control group. RESULTS: Among the cases, 104 (14%) were in the first trimester, 232 (31.3%) in the second trimester, and 406 (54.7%) in the third trimester. The RLS prevalence in cases and controls was 30% and 26.5%, respectively, (P = 0.134). Among cases, severe/very severe RLS was diagnosed in 25% and mild/moderate in 75%, compared with 15% of controls having severe/very severe RLS and 85% having mild/moderate RLS (P < 0.001). Multivariate binary logistic regression analysis identified the following parameters as independent predictors of RLS: parity (odds ratio [OR] 1.113 [confidence intervals [CI] 1.012-1.223], P = 0.027), anemia (OR 1.452 [1.033-2.042], P = 0.03), diabetes mellitus (OR 1.734 [CI 1.084-2.774], P = 0.022), Vitamin D deficiency (OR 2.376 [CI 1.488-3.794],P < 0.001), and smoking (OR 3.839 [CI 1.463-10.074], P = 0.006). None of the cases had been diagnosed or treated for RLS in the antenatal clinics. CONCLUSION: RLS is common, but underdiagnosed, among Saudi pregnant women and nonpregnant women of childbearing age. The study revealed that RLS during pregnancy is linked to parity, anemia, diabetes mellitus, Vitamin D deficiency, and smoking.

Association between fertility treatments and early placentation markers.

INTRODUCTION: Pregnancies resulting from fertility treatments are at higher risk of placenta-mediated complications. Hence, we aimed to estimate the association between fertility treatment and levels of first-trimester markers of placentation. METHODS: We conducted a cohort study in an academic center from 03/2011 to 12/2014. Adult nulliparous women with singleton pregnancies were recruited between 11 + 0 and 13 + 6 weeks of gestation. Data on maternal characteristics, medical history, and pregnancies conceived through fertility treatments (whether ovulation agents, insemination or assisted reproductive technologies) were collected. Maternal serum concentrations of PlGF, sFlt-1, PAPP-A, AFP, and free ß-hCG were obtained, and notches and UtA-PI were measured using Doppler ultrasound. Mean Multiple of the Medians (MoM) and frequencies were computed to estimate the mean differences (MD) or risk ratios (RR) comparing fertility treatment to spontaneous pregnancies. RESULTS: 427 (9%) pregnancies out of 4815 were conceived through fertility treatments, using ovulation agents (n = 233, 5%), insemination (n = 174, 4%) and/or assisted reproductive technologies (n = 85, 2%). The latter were associated with significantly lower log10PAPP-A MoM (adjusted MD: -0.02, 95%CI: -0.04 to -0.01), lower log10PlGF MoM (adjusted MD: -0.04, 95%CI: -0.06 to -0.01) and higher log10free ß-hCG MoM (adjusted MD: 0.05, 95%CI: 0.01 to 0.09) compared to spontaneous pregnancies. Ovulation agents and insemination were associated with the presence of notches (adjusted RR: 1.24, 95%CI: 1.14 to 1.35; and 1.27, 95%CI: 1.15 to 1.42, respectively) and higher log10UtA-PI MoM (adjusted MD: 0.16, 95%CI: 0.08 to 0.24; and 0.17, 95%CI: 0.07 to 0.27, respectively) than spontaneous pregnancies. CONCLUSION: Fertility treatments are associated with significant variations in markers of placentation.

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.

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.