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Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum. Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound. Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P =. 034), higher calculated ASCVD risk (0.6 vs 0.4, P =. 02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P =. 0004; diastolic: 75.2 vs 69.8 mm Hg, P =. 0004), and higher augmentation index values (7.7 vs 2.3, P =. 03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P =. 29) or reactive hyperemia index (2.1 vs 2.1, P =. 93), nor in pulse wave amplitude (416 vs 326, P =. 11), carotid elastic modulus (445 vs 426, P =. 36), or carotid beta stiffness (2.8 vs 2.8, P =. 86). Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Although most pregnancies after assisted reproduction are associated with a favorable outcome for the mother and infant, reports of abnormal vascular adaptation in early pregnancy and emerging maternal and perinatal pathology warrant further investigations. Herein we extended our previous work and further examined whether perturbations of blood pressure and endothelial function during the first trimester in conceptions with nonphysiological corpus luteum (CL) numbers would persist through the third trimester of pregnancy and into the postpartum period. We investigated both maternal and perinatal outcomes. Participants were grouped according to CL number and method of conception: 0 CL (programmed autologous frozen-thawed embryo transfer, N=10-18); 1 CL (spontaneous conception [N=16] and natural cycle frozen-thawed embryo transfer [N=12]); or >3 CL associated with autologous fresh embryo transfer [N=8-12]. Augmentation index was higher during the third trimester in the absence of a CL compared to 1 CL (P=0.03) and in frozen-thawed embryo transfer in a programmed compared to a natural cycle (P=0.02). Moreover, baseline pulse-wave amplitude was higher in >3 CL conceptions at all time points (all P<0.05). The incidence of preeclampsia and preeclampsia with severe features was significantly higher in the absence of a CL compared to the presence of one or >3 CL (P=0.045 and P=0.03). Infants from conceptions with >3 CL had lower birth weights (P=0.02) and a higher rate of low birth weight offspring (P=0.008). Deficient vascular adaptation during early gestation in conceptions with nonphysiological CL numbers might predispose women to adverse pregnancy outcomes, for example, preeclampsia. [ABSTRACT FROM AUTHOR]

Identifying modifiable factors that contribute to preeclampsia risk associated with assisted reproduction can improve maternal health. Vascular dysfunction predates clinical presentation of preeclampsia. Therefore, we examined if a nonphysiological hormonal milieu, a modifiable state, affects maternal vascular health in early pregnancy. Blood pressure, endothelial function, circulating endothelial progenitor cell numbers, lipid levels, and corpus luteum (CL) hormones were compared in a prospective cohort of women with infertility history based on number of CL: 0 CL (programmed frozen embryo transfer [FET], N=18); 1 CL (spontaneous conception [N=16] and natural cycle FET [N=12]); or >3 CL associated with in vitro fertilization [N=11]. Women with 0 or >3 CL lacked the drop in mean arterial blood pressure compared with those with 1 CL (both P=0.05). Reactive hyperemia index was impaired in women with 0 CL compared with 1 CL ( P=0.04) while baseline pulse wave amplitude was higher with > 3 CL compared with 1 CL ( P=0.01) or 0 CL ( P=0.01). Comparing only FET cycles, a lower reactive hyperemia index and a higher augmentation index is noted in FETs with suppressed CL compared with FETs in a natural cycle (both P=0.03). The number of angiogenic and nonangiogenic circulating endothelial progenitor cell numbers was lower in the absence of a CL in FETs ( P=0.01 and P=0.03). Vascular health in early pregnancy is altered in women with aberrant numbers of CL (0 or >3) and might represent insufficient cardiovascular adaptation contributing to an increased risk of preeclampsia. [ABSTRACT FROM AUTHOR]

In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in vitro fertilization protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether in vitro fertilization pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during, and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity and transit time. In a parallel prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester were attenuated in the 0-CL compared with combined single/multiple-CL cohorts, which were similar (group-time interaction: P=0.06 and 0.03, respectively). The blunted changes of carotid-femoral pulse wave velocity and carotid-femoral transit time from prepregnancy in the 0-CL cohort were most striking at 10 to 12 weeks of gestation ( P=0.01 and 0.006, respectively, versus 1 and >1 CL). Zero CL was predictive of preeclampsia (adjusted odds ratio, 2.73; 95% CI, 1.14-6.49) and preeclampsia with severe features (6.45; 95% CI, 1.94-25.09) compared with 1 CL. Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Recent data suggest that in addition to glucose, fetal growth is related to maternal triglycerides (TG). To reach the fetus, TG must be hydrolyzed to free fatty acids (FFA) and transported across the placenta, but regulation is uncertain. Placental lipoprotein lipase (pLPL) hydrolyzes TG, both dietary chylomicron TG (CM-TG) and very-low density lipoprotein TG (VLDL-TG), to FFA. This may promote fetal fat accretion by increasing the available FFA pool for placental uptake. We tested the novel hypothesis that pLPL activity, but not maternal adipose tissue LPL activity, is associated with newborn adiposity and higher maternal TG.Methods: Twenty mothers (n = 13 normal-weight; n = 7 obese) were prospectively recruited. Maternal glucose, insulin, TG (total, CM-TG, VLDL-TG), and FFA were measured at 14-16, 26-28, and 36-37 weeks, and adipose tissue LPL was measured at 26-28 weeks. At term delivery, placental villous biopsies were immediately analyzed for pLPL enzymatic activity. Newborn percent body fat (newborn %fat) was assessed by skinfolds.Results: Placental LPL activity was positively correlated with birthweight (r = 0.48;P = 0.03) and newborn %fat (r = 0.59;P = 0.006), further strengthened by correcting for gestational age at delivery (r = 0.75;P = 0.0001), but adipose tissue LPL was not. Maternal TG and BMI were not correlated with pLPL activity. Additionally, pLPL gene expression, while modestly correlated with enzymatic activity (r = 0.53;P < 0.05), was not correlated with newborn adiposity.Discussion: This is the first study to show a positive correlation between pLPL activity and newborn %fat. Placental lipase regulation and the role of pLPL in pregnancies characterized by nutrient excess and fetal overgrowth warrant further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia.Methods: Placental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera.Results: PAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood.Discussion: PAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation. [ABSTRACT FROM AUTHOR]

Introduction: The developing fetus relies on the maternal blood supply to provide the choline it requires for making membrane lipids, synthesizing acetylcholine, and performing important methylation reactions. It is vital, therefore, that the placenta is efficient at transporting choline from the maternal to the fetal circulation. Although choline transporters have been found in term placenta samples, little is known about what cell types express specific choline transporters and how expression of the transporters may change over gestation. The objective of this study was to characterize choline transporter expression levels and localization in the human placenta throughout placental development.Methods: We analyzed CTL1 and -2 expression over gestation in human placental biopsies from 6 to 40 weeks gestation (n = 6-10 per gestational window) by immunoblot analysis. To determine the cellular expression pattern of the choline transporters throughout gestation, immunofluorescence analysis was then performed.Results: Both CTL1 and CTL2 were expressed in the chorionic villi from 6 weeks gestation to term. Labor did not alter expression levels of either transporter. CTL1 localized to the syncytial trophoblasts and the endothelium of the fetal vasculature within the chorionic villous structure. CTL2 localized mainly to the stroma early in gestation and by the second trimester co-localized with CTL1 at the fetal vasculature.Discussion: The differential expression pattern of CTL1 and CTL2 suggests that CTL1 is the key transporter involved in choline transport from maternal circulation and both transporters are likely involved in stromal and endothelial cell choline transport. [ABSTRACT FROM AUTHOR]

Objective: Placental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin. Study Design: Secondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60mg/d (n=102) or placebo (n=72), with PlGF collected at 13w 0d-16w 6d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders. Results: ROC analysis indicated 87.71pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p=0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p=0.445). Conclusions: Unlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated. Condensation: High-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) impacts 8 million mother-infant pairs worldwide each year. This human pregnancy-specific disease characterized by hypertension and proteinuria accounts for significant maternal and neonatal morbidity and mortality. The current theory of the pathogenesis of PE as reviewed by Drs. Christopher Redman and Ian Sargent is thought to occur as a 2-stage process with poor placentation in the first half of pregnancy resulting in the maternal response in the second half of pregnancy. Our studies have focused on understanding the placental contribution to this serious disease by examining the gene expression profile of the deciduas basalis or basal plate, the region of the placenta involved in the "poor placentation". In this review we present summaries of our microarray datasets both of normal placentation and those gene expression changes resulting in the context of PE. Additionally, we have taken this opportunity to combine the data sets to provide a more comprehensive view of this region of the placenta. As defects in the basal plate are, in part, at the root of the disease process, we believe that understanding the pathobiology that occurs in this region will increase our ability to alter the development and/or course of PE. [ABSTRACT FROM AUTHOR]

Abstract: Preeclampsia (PE) impacts 8 million mother–infant pairs worldwide each year. This human pregnancy-specific disease characterized by hypertension and proteinuria accounts for significant maternal and neonatal morbidity and mortality. The current theory of the pathogenesis of PE as reviewed by Dr. Christopher Redman and Dr. Ian Sargent is thought to occur as a 2-stage process with poor placentation in the first half of pregnancy resulting in the maternal response in the second half of pregnancy. Our studies have focused on understanding the placental contribution to this serious disease by examining the gene expression profile of the deciduas basalis or basal plate, the region of the placenta involved in the “poor placentation”. In this review we present summaries of our microarray datasets both of normal placentation and those of gene expression changes resulting in the context of PE. Additionally, we have taken this opportunity to combine the datasets to provide a more comprehensive view of this region of the placenta. As defects in the basal plate are, in part, at the root of the disease process, we believe that understanding the pathobiology that occurs in this region will increase our ability to alter the development and/or course of PE. [ABSTRACT FROM AUTHOR]

Placenta vascular formation is important for fetal growth and development. Proper development of the placenta ensures the exchange of oxygen/nutrients and blood flow necessary for fetal growth. In this chapter, we will discuss the processes of vasculogenesis, angiogenesis, and pseudovasculogenesis during placental development and in pregnancies complicated by intrauterine growth restriction. Some of the factors controlling these processes include oxygen, the VEGF family of growth factors, and their receptors. Disruption in the balance of these controlling factors may explain the vascular malformations seen in pregnancies complicated by intrauterine growth restriction. [Copyright &y& Elsevier]

Introduction Assisted reproductive technology is associated with an increased risk of preeclampsia, but the reasons are poorly understood. The corpus luteum (CL) produces multiple vasoactive hormones in the first trimester of pregnancy which could affect initial placentation and later development of preeclampsia. Hypothesis We hypothesized that non-physiologic states present in in-vitro fertilization (IVF) such as absence of the CL could increase the risk of preeclampsia. Methods 892 infertile women were enrolled in this prospective cohort study. Four categories based on CL status were defined: (1) absence of the CL; (2) single CL; (3) multiple CL associated with ovulation induction; (4) multiple CL associated with controlled ovarian stimulation for IVF and fresh embryo transfer. Analysis focused on singleton pregnancies conceived with autologous oocytes resulting in live birth (n = 683). Multivariable logistic regression was used to control for covariates. Results Compared with conceptions occurring in the presence of one CL, conceptions occurring in the absence of a CL were associated with a higher incidence of preeclampsia (12.8% vs 4.8%, P = 0.02) and preeclampsia with severe features (9.6% vs 1.4%, P = < 0.001). Compared with FET occurring in the presence of one CL (modified natural cycles), FET occurring in the absence of a CL (programmed cycles) were associated with a higher incidence of preeclampsia (12.8% vs 3.9%, P = 0.02) and preeclampsia with severe features (9.6% vs 0.8%, P = 0.002). Absence of CL and programmed FET were predictive in multivariable regression models for preeclampsia (OR 2.73; 1.14–6.49 and 3.55; 1.20–11.94) and preeclampsia with severe features (6.45; 1.94–25.09 and 15.05; 2.59–286.27) compared to presence of one CL or FET in a natural cycle. Discussion Among singleton pregnancies after infertility resulting in live birth, those conceived in the absence of a CL were at increased risk for development of preeclampsia and preeclampsia with severe features. [ABSTRACT FROM AUTHOR]

Introduction Pregnancies conceived after utilization of assisted reproductive technologies (ART) are associated with an increased risk for preeclampsia. The pathophysiologic reasons are mainly unknown. Objective We sought to determine if a non-physiologic hormonal milieu influenced by the number of corpora lutea (CL) and the mode of conception affects maternal vascular health in early pregnancy. Methods Blood pressure, endothelial function, circulating endothelial progenitor cell numbers (CPCs), lipid levels, and CL hormones were compared in a prospective cohort of women at 11 to 14 weeks' gestation by number of CL and mode of conception (N = 57): 0 CL (programmed frozen embryo transfer (FET), N = 18); 1 CL (spontaneous pregnancy after infertility [N = 16] and modified natural cycle FET [N = 12]); or >3 CL associated with in vitro fertilization [N = 11]. Results Women with 0 or >3 CL lacked the drop in mean arterial blood pressure compared to women with 1 CL (P = 0.05; P = 0.05). Reactive Hyperemia Index (RHI) was impaired in patients lacking a CL compared to women with 1 CL (P = 0.04). Baseline pulse wave amplitude (BPWA) was higher in subjects with >3 CL compared to 1 CL (P = 0.01) or zero (P = 0.01). Suppression of CL development in FET cycles was associated with a lower RHI compared with FETs in a natural cycle (P = 0.03). The number of angiogenic and non-angiogenic CPCs was lower in the absence of a CL in FETs (P = 0.02 and P = 0.04). Relaxin levels correlated with the number of angiogenic CPCs (r = 0.31; P = 0.03). Discussion Maternal vascular health in early pregnancy is altered in women with aberrant numbers of CL (0 or >3), and might represent insufficient cardiovascular adaption leading to an increased risk of preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Early detection of maladaptive processes underlying pregnancy-related pathologies is desirable because it will enable targeted interventions ahead of clinical manifestations. The quantitative analysis of plasma proteins features prominently among molecular approaches used to detect deviations from normal pregnancy. However, derivation of proteomic signatures sufficiently predictive of pregnancy-related outcomes has been challenging. An important obstacle hindering such efforts were limitations in assay technology, which prevented the broad examination of the plasma proteome.Objective: The recent availability of a highly multiplexed platform affording the simultaneous measurement of 1310 plasma proteins opens the door for a more explorative approach. The major aim of this study was to examine whether analysis of plasma collected during gestation of term pregnancy would allow identifying a set of proteins that tightly track gestational age. Establishing precisely timed plasma proteomic changes during term pregnancy is a critical step in identifying deviations from regular patterns caused by fetal and maternal maladaptations. A second aim was to gain insight into functional attributes of identified proteins and link such attributes to relevant immunological changes.Study Design: Pregnant women participated in this longitudinal study. In 2 subsequent sets of 21 (training cohort) and 10 (validation cohort) women, specific blood specimens were collected during the first (7-14 weeks), second (15-20 weeks), and third (24-32 weeks) trimesters and 6 weeks postpartum for analysis with a highly multiplexed aptamer-based platform. An elastic net algorithm was applied to infer a proteomic model predicting gestational age. A bootstrapping procedure and piecewise regression analysis was used to extract the minimum number of proteins required for predicting gestational age without compromising predictive power. Gene ontology analysis was applied to infer enrichment of molecular functions among proteins included in the proteomic model. Changes in abundance of proteins with such functions were linked to immune features predictive of gestational age at the time of sampling in pregnancies delivering at term.Results: An independently validated model consisting of 74 proteins strongly predicted gestational age (P = 3.8 × 10-14, R = 0.97). The model could be reduced to 8 proteins without losing its predictive power (P = 1.7 × 10-3, R = 0.91). The 3 top ranked proteins were glypican 3, chorionic somatomammotropin hormone, and granulins. Proteins activating the Janus kinase and signal transducer and activator of transcription pathway were enriched in the proteomic model, chorionic somatomammotropin hormone being the top-ranked protein. Abundance of chorionic somatomammotropin hormone strongly correlated with signal transducer and activator of transcription-5 signaling activity in CD4 T cells, the endogenous cell-signaling event most predictive of gestational age.Conclusion: Results indicate that precisely timed changes in the plasma proteome during term pregnancy mirror a proteomic clock. Importantly, the combined use of several plasma proteins was required for accurate prediction. The exciting promise of such a clock is that deviations from its regular chronological profile may assist in the early diagnoses of pregnancy-related pathologies, and point to underlying pathophysiology. Functional analysis of the proteomic model generated the novel hypothesis that chrionic somatomammotropin hormone may critically regulate T-cell function during pregnancy. [ABSTRACT FROM AUTHOR]

Introduction Assisted reproduction is associated with an increased risk for hypertensive disease in pregnancy. The underlying pathophysiology is still debated. Endothelial dysfunction is a central component of hypertensive disease and can be determined non-invasively by Pulse-Amplitude-Tonometry (PAT). Objectives We hypothesized that a non-physiologic maternal environment in early pregnancy, specifically the absence of a corpus luteum (CL), negatively impacts maternal endothelial health. Patients and methods For this ongoing study women with spontaneous conceptions and conceptions after assisted reproduction were recruited at an academic infertility clinic after confirmation of a viable intrauterine pregnancy between 7 and 10 weeks gestation. Exclusion criteria were multiples, chronic hypertension, chronic kidney disease, diabetes mellitus, autoimmune disease, age >50 years or BMI >30. Endothelial function was determined using the Endo-PAT2000 system by calculating the reactive hyperemia index (RHI) at 11–14 weeks gestation. RHI ⩽1.67 is associated with a higher cardiovascular risk. A fasting lipid panel was obtained for each participant. Statistical analysis was performed using Kruskal–Wallis-test with post hoc analysis. Results are shown as means and standard errors. Results 47 women participated in the research visit. We found a significant difference in endothelial function with lower RHI in pregnant women with no CL ( N = 10, RHI = 1.65 ± 0.08; p = 0.04) compared to women with 1 CL ( N = 21; RHI = 1.99 ± 0.11). This difference was also evident between frozen-thawed ET in programmed ( N = 10; RHI = 1.65 ± 0.03, p = 0.03) compared to natural cycles ( N = 9; RHI = 1.95 ± 0.08). There was no difference when comparing the data to the group of women with fresh ET and supraphysiologic numbers of CL. Age, blood pressure and lipid levels were not different between groups. Conclusions A non-physiologic maternal environment, which is generated by suppression of CL in programmed cycles, negatively impacts maternal endothelial health in early pregnancy. The cause could be the absence of CL products. Specifically, relaxin, a potent vasodilator, might play a crucial role. A deficiency in relaxin could therefore contribute to an increased risk of hypertensive disease in pregnancy after assisted reproduction. [ABSTRACT FROM AUTHOR]

Objective The maternal-fetal inflammatory response contributes to both preterm premature rupture of membranes (PPROM) and adverse neurological outcomes. Additionally, cytokines associated with fetal placental inflammation can be detrimental to brain development regardless of inciting infection. We investigated whether differential patterns of cytokine markers in maternal and fetal plasma samples reflect subtypes of placental inflammation and neurological outcomes at 6 months in infants born to mothers with PPROM. Study Design Within a prospective cohort study of 25 women with PPROM, plasma cytokines (interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor-α) were measured by enzyme-linked immunosorbent assay from maternal blood samples at rupture and delivery, and from fetal umbilical cord blood samples. Patterns of cytokine expression were correlated with specific placenta pathologies. Infants underwent cranial ultrasound after birth and standardized neurological examinations at 6 months’ corrected gestational age. Predictors of inflammation and adverse neurological outcome were assessed by logistic regression, adjusting for gestational age at birth. Results Inflammation of the fetal side of the placenta was associated with elevated maternal IL-6 and IL-8 at delivery and fetal IL-1β, IL-6, IL-8, and tumor necrosis factor-α. Worse neurological outcome at 6 months was associated with inflammation of the fetal side of the placenta and shorter duration from rupture of membrane to delivery, independent of gestational age at birth or cranial ultrasound results. Conclusion Our findings support the connection between fetal inflammation with adverse neurological outcome with PPROM, regardless of cranial ultrasound results. Further longitudinal studies are needed to adequately examine these patterns, and will aid in risk assessment and intervention strategies. [ABSTRACT FROM AUTHOR]

We examined vaccination rates during pregnancy against both seasonal and pandemic H1N1 influenza and reasons for nonadherence to recommended guidelines during the 2009 through 2010 influenza season. Demographic and vaccination data were collected using a cross-sectional approach. Among 813 postpartum women, 520 (64%) reported receiving the seasonal influenza vaccination and 439 (54%) reported receiving the H1N1 influenza vaccination during pregnancy. Most received vaccinations at their obstetrician''s office. Major reasons for not receiving vaccination were: not knowledgeable about the vaccine importance (25%), concerns for effects on fetal and maternal health (18% and 9%, respectively), and not knowledgeable about where to obtain vaccination (9%). Reported H1N1 influenza vaccination rates were significantly lower in blacks (37%) compared with non-Hispanic whites, Hispanics, and Asian/other (57%, 59%, and 58%, respectively; P < .0001). Subsequent campaigns for improving vaccination rates in pregnancy should focus on educating patients about vaccine importance and safety. [Copyright &y& Elsevier]