Birth hospital and racial and ethnic differences in severe maternal morbidity in the state of California.

BACKGROUND: Birth hospital has recently emerged as a potential key contributor to disparities in severe maternal morbidity, but investigations on its contribution to racial and ethnic differences remain limited. OBJECTIVE: We leveraged statewide data from California to examine whether birth hospital explained racial and ethnic differences in severe maternal morbidity. STUDY DESIGN: This cohort study used data on all births at ≥20 weeks gestation in California (2007-2012). Severe maternal morbidity during birth hospitalization was measured using the Centers for Disease Control and Prevention index of having at least 1 of the 21 diagnoses and procedures (eg, eclampsia, blood transfusion, hysterectomy). Mixed-effects logistic regression models (ie, women nested within hospitals) were used to compare racial and ethnic differences in severe maternal morbidity before and after adjustment for maternal sociodemographic and pregnancy-related factors, comorbidities, and hospital characteristics. We also estimated the risk-standardized severe maternal morbidity rates for each hospital (N=245) and the percentage reduction in severe maternal morbidity if each group of racially and ethnically minoritized women gave birth at the same distribution of hospitals as non-Hispanic white women. RESULTS: Of the 3,020,525 women who gave birth, 39,192 (1.3%) had severe maternal morbidity (2.1% Black; 1.3% US-born Hispanic; 1.3% foreign-born Hispanic; 1.3% Asian and Pacific Islander; 1.1% white; 1.6% American Indian and Alaska Native, and Mixed-race referred to as Other). Risk-standardized rates of severe maternal morbidity ranged from 0.3 to 4.0 per 100 births across hospitals. After adjusting for covariates, the odds of severe maternal morbidity were greater among nonwhite women than white women in a given hospital (Black: odds ratio, 1.25; 95% confidence interval, 1.19-1.31); US-born Hispanic: odds ratio, 1.25; 95% confidence interval, 1.20-1.29; foreign-born Hispanic: odds ratio, 1.17; 95% confidence interval, 1.11-1.24; Asian and Pacific Islander: odds ratio, 1.26; 95% confidence interval, 1.21-1.32; Other: odds ratio, 1.31; 95% confidence interval, 1.15-1.50). Among the studied hospital factors, only teaching status was associated with severe maternal morbidity in fully adjusted models. Although 33% of white women delivered in hospitals with the highest tertile of severe maternal morbidity rates compared with 53% of Black women, birth hospital only accounted for 7.8% of the differences in severe maternal morbidity comparing Black and white women and accounted for 16.1% to 24.2% of the differences for all other racial and ethnic groups. CONCLUSION: In California, excess odds of severe maternal morbidity among racially and ethnically minoritized women were not fully explained by birth hospital. Structural causes of racial and ethnic disparities in severe maternal morbidity may vary by region, which warrants further examination to inform effective policies.

Angiotensin II receptor 1 gene variants are associated with high-altitude pulmonary edema risk.

Previous studies demonstrated that Angiotensin II Receptor 1 (AGTR1) may play an important role in the development of high-altitude pulmonary edema. We envisaged a role for AGTR1 gene variants in the pathogenesis of HAPE and investigated their potential associations with HAPE in a Han Chinese population. We genotyped seven AGTR1 polymorphisms in 267 patients with diagnosed HAPE and 304 controls and evaluated their association with risk of HAPE. Statistically significant associations were found for the single nucleotide polymorphisms (SNPs) rs275651 (p = 0.017; odds ratio [OR] = 0.65) and rs275652 (p = 0.016; OR = 0.64). Another SNP rs10941679 showed a marginally significant association after adjusting for age and sex in the additive genetic model (adjusted OR = 1.44, 95% CI = 1.01-2.04, p = 0.040). Haplotype analysis confirmed that the haplotype "AG" was associated with a 35% reduction in the risk of developing HAPE, while the haplotype "AA" increased the risk of developing HAPE by 44%. These results provide the first evidence linking genetic variations in AGTR1 with HAPE risk in Han Chinese individuals.

Genetic differences and aberrant methylation in the apelin system predict the risk of high-altitude pulmonary edema.

Hypoxia-inducible factor stimulates the expression of apelin, a potent vasodilator, in response to reduced blood arterial oxygen saturation. However, aberrations in the apelin system impair pulmonary vascular function, potentially resulting in the development of high-altitude (HA)-related disorders. This study aimed to elucidate the genetic and epigenetic regulation of apelin, apelin receptor (APLNR), and endothelial nitric oxide synthase (NOS3) in HA adaptation and HA pulmonary edema (HAPE). A genome-wide association study and sequencing identified variants of apelin, APLNR, and NOS3 that were validated in a larger sample size of HAPE-patients (HAPE-p), HAPE-free controls (HAPE-f), and healthy highland natives (HLs). Apelin-13 and nitrite levels and apelin and NOS3 expression were down-regulated in HAPE-p (P < 0.001). Among the several studied polymorphisms, apelin rs3761581, rs2235312, and rs3115757; APLNR rs11544374 and rs2282623; and NOS3 4b/4a, rs1799983, and rs7830 were associated with HAPE (P < 0.03). The risk allele rs3761581G was associated with a 58.6% reduction in gene expression (P = 0.017), and the risk alleles rs3761581G and rs2235312T were associated with low levels of apelin-13 and nitrite (P < 0.05). The latter two levels decreased further when both of these risk alleles were present in the patients (P < 0.05). Methylation of the apelin CpG island was significantly higher in HAPE-p at 11.92% than in HAPE-f and HLs at ≤ 7.1% (P < 0.05). Moreover, the methylation effect was 9% stronger in the 5' UTR and was associated with decreased apelin expression and apelin-13 levels. The rs3761581 and rs2235312 polymorphisms and methylation of the CpG island influence the expression of apelin in HAPE.

Polymorphisms of human vascular endothelial growth factor gene in high-altitude pulmonary oedema susceptible subjects.

BACKGROUND AND OBJECTIVE: Based on the reported biological properties and function of vascular endothelial growth factor (VEGF) in hypoxic conditions, many investigations have studied the hypothesis that VEGF has an important role in the pathogenesis of high altitude sicknesses, including high-altitude pulmonary oedema (HAPE). Unfortunately, the results are inconsistent. Therefore, the association of VEGF gene single nucleotide polymorphisms (SNP) with being susceptible to HAPE was investigated. METHODS: The study included 53 HAPE-susceptible subjects (HAPE-s) and 69 HAPE-resistant mountaineer controls (HAPE-r). Subjects were Japanese and the two groups were comparable in terms of age and gender. The SNP of the VEGF gene, namely C-2578A, G-1154A and T-460C in the promoter, G + 405C in the 5'-untranslated region and C936T in the 3'-untranslated region, were examined by allele discrimination experiments. In addition, arterial oxygen tension (PaO(2)) and pulmonary haemodynamic data were available for 21 of the HAPE-s subjects. RESULTS: There were no statistically significant differences in the allele frequencies, genotype distributions or haplotype frequencies of VEGF SNP between the HAPE-s and HAPE-r groups. Furthermore, neither PaO(2) nor pulmonary haemodynamic parameters were associated with the VEGF SNP in the 21 HAPE-s subjects. CONCLUSIONS: This genetic study did not provide evidence that functional SNP of the VEGF gene are associated with susceptibility to HAPE in a Japanese population.