Jennifer Salati

Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects

BACKGROUND The uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. OBJECTIVE We demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. STUDY DESIGN Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n = 6/group). Human subjects were recruited immediately before scheduled first-trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition with a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. RESULTS In macaques, the rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and heat shock protein 70 as markers of apoptosis, nitrative, and oxidative stress, respectively, were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11 weeks gestation, and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast after first-trimester ultrasound studies. CONCLUSIONS Use of contrast-enhanced ultrasound did not result in placental structural damage and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound imaging may offer a safe clinical tool for the identification of pregnancies that are at risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes.

Outcomes of pregnancies complicated by liver cirrhosis, portal hypertension, or esophageal varices

Abstract Objective: To evaluate pregnancy outcomes in women with liver cirrhosis, portal hypertension, or esophageal varices. Study design: We analyzed a retrospective cohort of 2 284 218 pregnancies in 2005–2009 recorded in the California Birth Registry database. Utilizing ICD-9 codes we analyzed the following outcomes for liver cirrhosis, portal hypertension, or esophageal varices in pregnancy: preeclampsia (PET), preterm delivery (PTD; <37 weeks), cesarean section, low birth weight (LBW; <2500 g), small for gestational age (SGA; <10th percentile), neonatal death (NND), and postpartum hemorrhage (PPH). Results: Cirrhosis in pregnancy conferred an increased risk of PET, PTD, CS in multiparous women, LBW, and NND. Portal hypertension in pregnancy was associated with PTD, LBW, NND, and PPH. Non-bleeding esophageal varices in pregnancy were not associated with the outcomes assessed in a statistically significant manner. One case of bleeding esophageal varices was observed, resulting in PTD with a LBW infant. There were three cases of concomitant portal hypertension or concomitant esophageal varices with cirrhosis in pregnancy. Conclusion: Pregnancy in women with concomitant liver cirrhosis, portal hypertension, or esophageal varices can be successful. However, pregnancy outcomes are worse and may warrant closer antenatal monitoring and patient counseling. Cirrhosis in pregnancy with concomitant portal hypertension or esophageal varices is rare.

Racial and Ethnic Differences in Pregnancy Outcomes in Women With Chronic Hypertension

INTRODUCTION: This study evaluates the association between race and ethnicity and obstetric outcomes in women with chronic hypertension. METHODS: A retrospective cohort study of African American, Hispanic, Asian, and white California residents who delivered live, singleton, nonanomalous neonates from 2005 to 2008. The data consisted of birth records linked to hospital discharge data; chronic hypertension was identified by International Classification of Diseases, 9th Revision codes. Univariate and multivariable analyses were conducted to examine the association between chronic hypertension and preeclampsia, gestational diabetes, preterm delivery, birth weight, intrauterine fetal demise, neonatal death, and postneonatal death. RESULTS: After accounting for education level, socioeconomic status, maternal age, and parity, African American, Hispanic, and Asian women with chronic hypertension were significantly more likely than whites to develop preeclampsia and deliver preterm (P<.001). African American women had a significantly elevated risk of intrauterine fetal demise (P<.001) and postneonatal death (P<.05). Hispanic and Asian women were significantly more likely to develop gestational diabetes (P<.001). There were no significant differences in neonatal death (Table 1). Mean birth weights were significantly less for each race and ethnicity: African American (2,891 g), Hispanic (3,053 g), and Asian (2,933 g) when compared with whites (3,221 g) (P<.001). Table 1 Perinatal Outcomes by Race and Ethnicity in Women With Chronic Hypertension (Sabol, p. 168–9S) CONCLUSION: Racial and ethnic disparities affect maternal and neonatal outcomes in women whose pregnancies are complicated by chronic hypertension. Whether this represents disparities in quality of care compared with biologic differences requires further investigation.

Maternal high-fat diet reversal improves placental hemodynamics in a nonhuman primate model of diet-induced obesity

BackgroundIn a Japanese macaque model of diet-induced obesity, we have previously demonstrated that consumption of a high-fat, “Western-style” diet (WSD) is associated with placental dysfunction and adverse pregnancy outcomes, independent of an obese maternal phenotype. Specifically, we have reported decreased uterine placental blood flow and increased inflammation with maternal WSD consumption. We also previously investigated the use of a promising therapeutic intervention that mitigated the adverse placental effects of a WSD but had unexpected detrimental effects on fetal pancreatic development. Thus, the objective of the current study was to determine whether simple preconception diet reversal (REV) would improve placental function.MethodsFemale Japanese macaques were divided into three groups: REV animals (n = 5) were switched from a chronic WSD (36% fat) to a low fat, CON diet (14% fat) prior to conception and throughout pregnancy. The CON (n = 6) and WSD (n = 6) cohorts were maintained on their respective diets throughout pregnancy. Maternal body weight and composition were regularly assessed and advanced noninvasive imaging was performed at midgestation (gestational day 90, G90, or 0.5 of gestation, where full term is G175), and G129, 1 day prior to C-section delivery at G130 (0.75 of gestation). Imaging studies comprised Doppler ultrasound (US), contrast-enhanced US, and dynamic contrast-enhanced magnetic resonance imaging to assess uteroplacental hemodynamics and maternal-side placental perfusion.ResultsDietary intervention resulted in significant maternal weight loss prior to pregnancy, and improved lean to fat mass ratio. By advanced imaging we demonstrated that a chronic WSD led to decreased blood flow velocity in the intervillous space, delayed blood flow transfer through the maternal spiral arteries, and reduced total placental blood flow compared to CON fed animals. Dietary reversal ameliorated these concerning derangements, restoring these hemodynamic parameters to CON levels.ConclusionsPreconception dietary modification has beneficial effects on the maternal metabolic phenotype, and results in improved placental hemodynamics.

Intrauterine Fetal Demise and Postneonatal Death Stratified by Maternal Education Level and Gestational Age [152]

INTRODUCTION: To evaluate the association between maternal education and the rates of intrauterine fetal demise and postneonatal death stratified by gestational age in a cohort of otherwise healthy women. METHODS: A retrospective cohort study was conducted using 2005 U.S. national linked birth certificate and death certificate data. Maternal education was defined as less than or equal to some level of high school education compared with college education or beyond. Intrauterine fetal demise was defined as death occurring at or after 20 weeks of gestation. Postneonatal death was defined as death from day 29 to 365 of life. Results were expressed as number of deaths per 10,000 live births. RESULTS: Overall, perinatal death rates per 10,000 were at least double in women receiving a high school education or less compared with the more educated cohort. Specifically, the rate of intrauterine fetal demise was 0.0029 compared with 0.0018 (P<.001), neonatal death was 0.0021 compared with 0.0012 (P<.001), postneonatal death was 0.0028 compared with 0.0011 (P<.001), and infant death was 0.0049 compared with 0.0024 (P<.001). However, when examined by week of gestation, although the rates of intrauterine fetal demise and postneonatal death were greater at every gestational age in those with a high school education or less, rates of neonatal death and infant death were quite similar between the two educational groups. CONCLUSION AND IMPLICATION: Rates of intrauterine fetal demise and post neonatal death were greater for every gestational age in less educated women when compared with their more educated cohort. Given that rates of neonatal death were approximately the same regardless of level of education brings up an interesting discrepancy. Environmental factors, inability to navigate the health care system, or lack of education in prenatal and postnatal care may all be contributing factors and would require further investigation.