Maternal Hypertension-Related Genotypes and Congenital Heart Defects.

BACKGROUND: Maternal hypertension has been associated with congenital heart defect occurrence in several studies. We assessed whether maternal genotypes associated with this condition were also associated with congenital heart defect occurrence. METHODS: We used data from the National Birth Defects Prevention Study to identify non-Hispanic white (NHW) and Hispanic women with (cases) and without (controls) a pregnancy in which a select simple, isolated heart defect was present between 1999 and 2011. We genotyped 29 hypertension-related single nucleotide polymorphisms (SNPs). We conducted logistic regression analyses separately by race/ethnicity to assess the relationship between the presence of any congenital heart defect and each SNP and an overall blood pressure genetic risk score (GRS). All analyses were then repeated to assess 4 separate congenital heart defect subtypes. RESULTS: Four hypertension-related variants were associated with congenital heart defects among NHW women (N = 1,568 with affected pregnancies). For example, 1 intronic variant in ARHGAP2, rs633185, was associated with conotruncal defects (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1-1.6). Additionally, 2 variants were associated with congenital heart defects among Hispanic women (N = 489 with affected pregnancies). The GRS had a significant association with septal defects (OR: 2.1, 95% CI: 1.2-3.5) among NHW women. CONCLUSIONS: We replicated a previously reported association between rs633185 and conotruncal defects. Although additional hypertension-related SNPs were also associated with congenital heart defects, more work is needed to better understand the relationship between genetic risk for maternal hypertension and congenital heart defects occurrence.

Peripartum Cardiomyopathy Characteristics and Outcomes in Canadian Aboriginal and Non-Aboriginal Women.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a heterogeneous condition characterized by heart failure and left ventricular dysfunction (left ventricular ejection fraction [LVEF] < 45%) in the absence of an alternative cause and a previous diagnosis of cardiomyopathy. The Aboriginal population (Inuit, First Nations, Metis) of Canada often has barriers to health care, which can lead to delays in diagnosis and treatment. Our objectives are to describe PPCM in a Canadian population, and to determine if Canadian Aboriginal women have worse clinical outcomes than non-Aboriginal women. METHODS: A retrospective study was performed at a single tertiary care centre, between 2008 and 2014. Demographic characteristics, symptoms at presentation, medical history, discharge medications, blood work, echocardiographic parameters, and follow-up information were collected. RESULTS: A total of 177 women were screened, and 23 were included in the study (52% were Aboriginal). Aboriginal women were found to have higher rates of gravidity and parity, and higher incidence of tobacco smoking than non-Aboriginal women, and were more likely to be discharged with diuretic medications. At diagnosis, Aboriginal women were more likely to have a lower LVEF (20% [interquartile range (IQR), 15%-23%] vs 40% [IQR, 30%-42%]; P = 0.02) and a more dilated left ventricle (left ventricular end-diastolic diameter, 64 mm [IQR, 57-74 mm] vs 54 mm [IQR, 50-57mm]; P < 0.01). Recovery rate, defined as LVEF > 50%, was similar (46% in Aboriginal patients and 60% in non-Aboriginal patients). CONCLUSIONS: Our findings support that Aboriginal women with PPCM are more likely to present with lower LVEF and a more dilated left ventricle, as well, require more symptomatic management. To our knowledge, this is the first description and contrast of PPCM between Aboriginal and non-Aboriginal Canadians.

The interaction between maternal race/ethnicity and chronic hypertension on preterm birth.

BACKGROUND: In both the biomedical and public health literature, the risk for preterm birth has been linked to maternal racial/ethnic background, in particular African-American heritage. Despite this well-documented health disparity, the relationship of comorbid conditions, such as chronic hypertension, to maternal race/ethnicity and preterm birth has received relatively limited attention in the literature. OBJECTIVE: The objective of the study was to evaluate the interaction between chronic hypertension and maternal racial/ethnic background on preterm birth. STUDY DESIGN: This is a retrospective cohort study of singleton pregnancies among women who delivered between 2002 and 2015 at the University of California, San Francisco. The associations of chronic hypertension with both spontaneous and medically indicated preterm birth were examined by univariate and multivariate logistical regression, adjusting for confounders including for maternal age, history of preterm birth, maternal body mass index, insurance type (public vs private), smoking, substance abuse, history of pregestational diabetes mellitus, and use of assisted reproductive technologies. The interaction effect of chronic hypertension and racial/ethnicity was also evaluated. All values are reported as odds ratios, with 95% confidence intervals and significance set at P = .05. RESULTS: In this cohort of 23,425 singleton pregnancies, 8.8% had preterm deliveries (3% were medically indicated preterm birth, whereas 5.5% were spontaneous preterm births), and 3.8% of women carried the diagnosis of chronic hypertension. Chronic hypertension was significantly associated with preterm birth in general (adjusted odds ratio, 2.74, P < .001) and medically indicated preterm birth specifically (adjusted odds ratio, 5.25, P < .001). When evaluating the effect of chronic hypertension within racial/ethnic groups, there was an increased odds of a preterm birth among hypertensive, African-American women (adjusted odds ratio, 3.91, P < .001) and hypertensive, Asian-American/Pacific Islander women (adjusted odds ratio, 3.51, P < .001) when compared with their nonhypertensive counterparts within the same racial/ethnic group. These significant effects were also noted with regard to medically indicated preterm birth for hypertensive African-American women (adjusted odds ratio, 6.85, P < .001) and Asian-American/Pacific Islander women (adjusted odds ratio, 9.87, P < .001). There was no significant association of chronic hypertension with spontaneous preterm birth (adjusted odds ratio, 0.87, P = .4). CONCLUSION: The effect of chronic hypertension on overall preterm birth and medically indicated preterm birth differs by racial/ethnic group. The larger effect of chronic hypertension among African-American and Asian/Pacific Islander women on medically indicated and total preterm birth rates raises the possibility of an independent variable that is not captured in the data analysis, although data regarding the indication for medically indicated preterm delivery was limited in this data set. Further investigation into both social-structural and biological predispositions to preterm birth should accompany research focusing on the effect of chronic hypertension on birth outcomes.

Characteristics and In-Hospital Outcomes of Peripartum Cardiomyopathy Diagnosed During Delivery in the United States From the Nationwide Inpatient Sample (NIS) Database.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is associated with advanced maternal age, African-American race, hypertensive disorders of pregnancy, and multiple-gestation pregnancies. Less is known regarding racial differences in risk factors and predictors of adverse in-hospital outcomes. METHODS AND RESULTS: A total of 1,337 women with PPCM were identified with the use of the Nationwide Inpatient Sample (2004-2011). Clinical profiles and maternal outcomes in delivering mothers with and without PPCM were compared and stratified by race. In multivariate analysis, established risk factors for PPCM were confirmed. Anemia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.6-2.5; P < .0001), asthma (OR 2.2, 95% CI 1.5-3.2; P = .0002), smoking (OR 33.6, 95% CI 9.3-159.4; P < .0001), and thyroid disease (OR 5.9; 95% CI 1.5-21.3; P = .01) were associated with PPCM. Risk factors significant in whites, African Americans, and Hispanics were hypertension during pregnancy and anemia. Patients with PPCM had higher rates of in-hospital adverse outcomes (P < .0001), but no differences in race or comorbidities predicted adverse events. CONCLUSIONS: Hypertensive disorders during pregnancy and anemia were associated with PPCM in whites, African Americans, and Hispanics, providing further evidence that vascular stress may play a role in the pathogenesis of PPCM. Thyroid disorders may represent a novel risk factor for PPCM.

The Relationship between Total Fibroid Burden and First Trimester Bleeding and Pain.

BACKGROUND: Few studies comment on the association between fibroids and symptoms among pregnant women. These studies generally are retrospective and do not to assess the influence of number of tumours or their volume on risk of symptoms. METHODS: Right from the Start is a prospective cohort that enrolled pregnant women from the southeastern USA between 2000 and 2012. In the first trimester, all participants had standardised ultrasounds to determine the presence or absence of fibroids. Symptoms were queried in a telephone survey. We used polytomous logistic regression to model odds of bleeding, pain, or both symptoms in relation to increasing total fibroid number and volume among white and black women. RESULTS: Among 4509 participants, the prevalence of fibroids was 11%. Among those reporting symptoms (70%), 11% reported only bleeding, 59% reported only pain, and 30% reported both symptoms. After adjusting for age, race, parity, hypertension, smoking, alcohol use, and study site, increasing number of fibroids was associated with pain [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.00, 1.33] and both symptoms [OR 1.25, 95% CI 1.08, 1.45] but not with bleeding among all women. Fibroid volume was not associated with symptoms among black women, but white women with the smallest fibroid volumes were more likely to report both symptoms than those without fibroids [OR 1.79, 95% CI 1.17, 2.72]. CONCLUSIONS: Very large tumours are not requisite for experiencing symptoms, as small fibroids and increasing number of tumours are associated with pain and both symptoms.

Association of number of live births with left ventricular structure and function. The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Pregnancy is associated with marked maternal cardiovascular/hemodynamic changes. A greater number of pregnancies may be associated with long-term subclinical changes in left ventricular (LV) remodeling. METHODS: Among 2,234 white, black, Hispanic, and Chinese women (mean age 62 years) in the MESA, we used linear regression to relate live births and cardiac magnetic resonance imaging LV measures. Covariates included age, ethnicity, height, income, education, birth country, smoking, menopause, and oral contraceptive duration. Models were additionally adjusted for potential mediators: systolic blood pressure, antihypertensive use, total/high-density lipoprotein cholesterol, triglycerides, diabetes, and body mass index. We performed sensitivity analyses excluding 763 women in the lowest socioeconomic group: annual income <$25,000 and lower high school level of education. RESULTS: With each live birth, LV mass increased 1.26 g; LV end-diastolic volume, 0.74 mL; and LV end-systolic volume, 0.45 mL; LV ejection fraction decreased 0.18% (P trend <0.05). Changes were most notable for the category of women with ≥5 pregnancies. Upon adjustment for potential biologic mediators, live births remained positively associated with LV mass and end-systolic volume. Live births remained significantly associated with LV end-systolic, end-diastolic volumes, and LV mass (P trend ≤0.02) after excluding women in the lowest socioeconomic group. CONCLUSIONS: Number of live births is associated with key LV structural and functional measures in middle to older ages, even after adjustment for sociodemographic factors and cardiovascular disease risk factors. Hemodynamic changes during pregnancy may be associated with cardiac structure/function beyond childbearing years.

Disparities in maternal hypertension and pregnancy outcomes: evidence from North Carolina, 1994-2003.

OBJECTIVES: To better understand disparities in pregnancy outcomes, we analyzed data from North Carolina to determine how the pattern of maternal hypertensive disorders differs among non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic women across the range of maternal ages. In addition, we explored whether rates of poor birth outcomes, including low birthweight (LBW) and preterm birth (PTB), among hypertensive women differed by race. METHODS: We restricted our analyses to births occurring between 1994 and 2003, constructing six five-year maternal age categories: 15-19 years, 20-24 years, 25-29 years, 30-34 years, 35-39 years, and 40-44 years. We used logistic regression to determine the relative contribution of race and age to incidence of maternal hypertension. All analyses controlled for the standard covariates of maternal education, marital status, and tobacco use. To assess the impact of maternal hypertension on birth outcomes, we limited the dataset to women with any hypertensive disorder and used linear regression to determine how particular race-age combinations affected outcomes. We also used logistic regression to find out how particular race-age combinations affected the likelihood of LBW and PTB. RESULTS: The risk of hypertension differed by race, with NHB women exhibiting the highest risk and Hispanic women the lowest risk. Further, rates of hypertension increased with age. Among hypertensive women, pregnancy outcomes differed by race and age, with NHB women having the poorest outcomes (i.e., LBW and PTB) and age exhibiting a dose-response relationship in PTB and very PTB. CONCLUSIONS: Patterns of maternal hypertension and subsequent outcomes are important contributors to persistent disparities in pregnancy outcomes.

African-American women have a higher risk for developing peripartum cardiomyopathy.

OBJECTIVES: The purpose of this study was to assess whether African-American women are at increased risk of having peripartum cardiomyopathy. BACKGROUND: Peripartum cardiomyopathy is a heart disease of unknown cause that affects young women, often with devastating consequences. The frequency of peripartum cardiomyopathy varies markedly between African and non-African regions. METHODS: A case-control study was performed at a regional center that provides medical care to a racially heterogeneous population. For each case, 3 healthy control patients were randomly selected who delivered babies within the same month. RESULTS: African-American women had a 15.7-fold higher relative risk of peripartum cardiomyopathy than non-African Americans (odds ratio [OR]: 15.7, 95% confidence interval [CI]: 3.5 to 70.6). Other significant univariate risk factors were hypertension (OR: 10.8, 95% CI: 2.6 to 44.4), being unmarried (OR: 4.2, 95% CI: 1.4 to 12.3), and having had >2 previous pregnancies (OR: 2.9, 95% CI: 1.1 to 7.4). African-American ethnicity remained a significant risk factor for peripartum cardiomyopathy when other risk factors were considered in multivariable (OR: 31.5, 95% CI: 3.6 to 277.6) and stratified analyses (OR: 12.9 to 29.1, p < 0.001). Although the frequency of peripartum cardiomyopathy (185 of 100,000 deliveries) at this center was higher than in previous U.S. reports, it was comparable to the frequency in countries with more women of African descent (100 to 980 of 100,000). Analysis of other U.S. studies confirmed that the frequency of peripartum cardiomyopathy was significantly higher among African-American women. CONCLUSIONS: African-American women have significantly higher odds of having peripartum cardiomyopathy that could not be explained by several other factors. Further research will be necessary to determine the potential environmental and/or genetic factors associated with African descent that confer this risk.

Hostility and anomie: links to preterm delivery subtypes and ambulatory blood pressure at mid-pregnancy.

Underlying maternal vascular disease has been implicated as one of several pathways contributing to preterm delivery (PTD) and psychosocial factors such as hostility, anomie, effortful coping, and mastery may be associated with PTD by affecting maternal vascular health. Using data from the Pregnancy Outcomes and Community Health (POUCH) study, we included 2018 non-Hispanic White and 743 African American women from 52 clinics in five Michigan, USA communities. Women were interviewed at 15-27 weeks' gestation and followed to delivery. We found that relations between psychosocial factors and PTD subtypes (i.e. medically indicated, premature rupture of membranes, spontaneous labor) varied by race/ethnicity and socio-economic position (Medicaid insurance status). Among African American women not insured by Medicaid, anomie levels in mid-pregnancy were positively associated with medically indicated PTD after adjusting for maternal age and education. Among all women not insured by Medicaid, hostility levels were positively associated with spontaneous PTD after adjusting for maternal race/ethnicity, age, and education. Failure to detect links between psychosocial factors and PTD risk in poorer women may be due to their excess risk in multiple PTD pathways and/or a more complex web of contributing risk factors. In a subset of 395 women monitored for blood pressure, anomie scores were positively associated with systolic blood pressure and heart rate and hostility scores were positively associated with systolic and diastolic blood pressure, heart rate and mean arterial pressure in models that included time, awake/asleep, race/ethnicity, and age as covariates. Further adjustment for body mass index and smoking attenuated the anomie-vascular relations but had little effect on the hostility-vascular relations. Overall this study of pregnant women provides some physiologic evidence to support findings linking levels of anomie and hostility with risk of PTD.

[Dyspnoea in pregnant female immigrants due to unexpected mitral valve stenosis]. / Dyspnoe bij allochtone zwangeren door onverwachte mitralisklepstenose.

Three female patients, a 22-year-old Moroccan woman, a 25-year-old Turkish woman and a 35-year-old Iraqi woman, became increasingly dyspnoeic during their pregnancy; this was a symptom of congestive heart failure due to mitral valve stenosis. Since all patients were refractory to medical treatment, they underwent invasive therapy by percutaneous transvenous mitral balloon valvotomy (PTMV). In two patients this therapy was successful, but in one patient a closed mitral valvotomy was needed. All three women delivered healthy infants, two immediately following the PTMV; at follow-up 2-4 years later, the women and infants were all doing well. The prevalence of mitral valve stenosis in the western world is increasing because of changing immigration patterns. When pregnant patients start complaining about dyspnoea, especially if they are immigrants, one should be aware of the possibility of mitral valve stenosis. PTMV is a safe and successful treatment for these patients and is preferred above surgical therapy because of its low morbidity and mortality for both mother and foetus. PTMV must be performed in a thoracic surgery centre by an experienced team and the X-ray exposure should be minimised.

Hypertension during pregnancy in South Australia, part 2: risk factors for adverse maternal and/or perinatal outcome - results of multivariable analysis.

OBJECTIVE: To identify factors associated with adverse pregnancy outcomes among women with hypertension during pregnancy. DESIGN: A population-based retrospective multivariable analysis using the South Australian perinatal data collection. METHODS: Perinatal data on 70,386 singleton births in 1998-2001 were used in multivariable analyses on three groups: all women combined, all hypertensive women and women with pregnancy hypertension only, in order to identify independent risk factors for requirement for level II/III care, preterm birth, small for gestational age (SGA) birth and maternal length of stay greater than 7 days. RESULTS: The risks for the four morbidities were all increased among women with hypertension compared with normotensive women. Those with pre-existing hypertension had the lowest risk (with odds ratios (OR) 1.26-2.90). Pregnancy hypertension held the intermediate position (OR 1.52-5.70), while superimposed pre-eclampsia was associated with the highest risk (OR 2.00-8.75). Among women with hypertension, Aboriginality, older maternal age, nulliparity and pre-existing or gestational diabetes increased the risk for level II/III nursery care, preterm birth and prolonged hospital stay. Smokers had shorter stays, which may be related to their decreased risk of having a Caesarean section or operative vaginal delivery. Asian women, Aboriginal women, smokers and unemployed women had an increased risk for having an SGA baby, while women with pre-existing or gestational diabetes had a reduced risk. CONCLUSIONS: Among hypertensive pregnant women, nulliparity, older maternal age, Aboriginality, unemployment and diabetes are independent risk factors for one or more major adverse pregnancy outcomes. Smoking does not always worsen the outcome for hypertensive women except for SGA births.

Differential risk of hypertensive disorders of pregnancy among Hispanic women.

Preeclampsia and gestational hypertension are leading complications of pregnancy that also portend increased risk of future chronic hypertension. Although rates of chronic hypertension differ between non-Hispanic Caucasian and Hispanic women, few studies examined their relative rates of hypertensive disorders of pregnancy. The purpose of this study was to compare the risk of preeclampsia and gestational hypertension in a prospective cohort of normotensive, nulliparous Hispanic (n = 863) and non-Hispanic Caucasian women (n = 2,381). Compared with non-Hispanic Caucasian women, Hispanic women demonstrated a significantly decreased incidence of gestational hypertension (1.6% versus 8.5%; P < 0.01), but a similar incidence of preeclampsia (3.8% versus 3.7%; P = 0.9). Adjusting for age, smoking, diabetes, BP, body mass index (BMI), and multiple gestation uncovered an increased relative risk (RR) for preeclampsia among Hispanic women (RR 1.9; 95% CI, 1.1 to 3.3; P = 0.01), while their relative risk for gestational hypertension remained significantly decreased (RR 0.39; 95% CI, 0.22 to 0.72; P < 0.01). Among women who initially presented with hypertension during pregnancy, Hispanic women were over threefold (hazard ratio 3.3; 95% CI, 1.9 to 6.0; P < 0.01) more likely to develop preeclampsia than non-Hispanic Caucasian women. Besides Hispanic ethnicity, baseline BP, BMI, diabetes, and multiple gestation were independent risk factors for preeclampsia, whereas only baseline BP and BMI were associated with gestational hypertension. Socioeconomic status and access to prenatal care were not associated with either disorder. Hispanic ethnicity is independently associated with increased risk for preeclampsia and decreased risk for gestational hypertension. The initial presentation of hypertension during pregnancy in Hispanic women most likely represents early preeclampsia.

Testing the weathering hypothesis among Mexican-origin women.

OBJECTIVE: To examine the "weathering hypothesis," as proposed by Geronimus (1986; 1987; 1992; 1996), among US-born and foreign-born Mexican-origin women. This hypothesis specifically argues that the relationship between age and a variety of reproductively related heath outcomes varies by socioeconomic and environmental context. METHODS: 1989-1991 National Center for Health Statistics (NCHS) linked birth-death files. These files include all women who experienced a live birth in the United States and whose infants were issued a birth certificate during the years 1989 to 1991 (NCHS 1995). Age and nativity specific distributions on infant mortality, low birth weight, anemia, pregnancy related hypertension, and smoking were estimated for Mexican-origin women. RESULTS: For the foreign-born, levels of neonatal mortality are highest for younger women and tend to increase again in women at the oldest ages. For the US born, the lowest levels are for women aged 17 and 18 years, and 27-29 years. Levels for women aged 19-24 years and 30-34 years are higher than those for 17-and 18-year-olds. For both groups of women, giving birth to infants with low birth weight is most common at the earlier ages, declining more or less until the mid twenties when the rate begins to rise again slowly. Patterns for the maternal health indicators vary, with pregnancy related hypertension most strongly following the pattern suggested by weathering. CONCLUSION: Overall, this analysis suggests that there is evidence of weathering within the Mexican-origin population, particularly for the US-born population, and this is most clearly seen in levels of neonatal mortality and pregnancy related hypertension.

Preeclampsia and neonatal outcomes in chronic hypertension: comparison between white and black women.

We compared the incidence of preeclampsia and neonatal outcomes in 208 white (born in Canada) and 74 black (born in Haiti) women with mild chronic hypertension. Controls included 17,677 white and 2,400 black normotensive women delivered in the same center between 1987 and 1991. Superimposed preeclampsia (32.4% vs 14.9%; p < 0.01), perinatal mortality (9.5% vs 2.9%; p < 0.05) and prematurity (32.4% vs 19.7%; p < 0.05) were more frequent in black than in white women with chronic hypertension. Within both races, chronic hypertensive women with superimposed preeclampsia demonstrated higher rates of perinatal mortality and morbidity than controls. White chronic hypertensive women without preeclampsia and controls had similar rates of perinatal mortality as compared to black study participants and controls (2.3% vs 1.4%), small-for-gestational-age newborns (10.7% vs 7.8%) and prematurity (12.4% vs 15.3%). Compared to black controls, black chronic hypertensive women without preeclampsia had higher rates of perinatal mortality (1.2% vs 8.0%; p < 0.001) and prematurity (9.0% vs 18.0%; p < 0.05). These data provide evidence of ethnic differences in perinatal outcomes in chronic hypertensive women that are not explained only by superimposed preeclampsia.

Sodium transport inhibitors in pregnancy-induced hypertension.

In blacks and whites of similar socioeconomic background, the incidence of pregnancy-induced hypertension (PIH) is probably the same. In underdeveloped countries, however. PIH is often a life-threatening complication of pregnancy. Recent theories as to the etiology of PIH include the suggestion that vascular tone may be increased as a result of inhibition of active sodium transport in vascular smooth muscle. This may be the result of an inhibitor of sodium transport present in the serum. The literature concerning the demonstration of endogenous sodium transport inhibitors and endogenous digoxinlike immunoreactivity (EDLI) in PIH is reviewed and discussed.