Pregnancy outcomes following home blood pressure monitoring in gestational hypertension.

OBJECTIVES: To assess the safety and efficacy of home blood pressure monitoring (HBPM) and office (traditional) blood pressure measurements in a cohort of pregnant women with gestational hypertension (GH). STUDY DESIGN: This was a cohort study at St. George's Hospital, University of London conducted between December 2013 and August 2018. The inclusion criteria was pregnant women with a diagnosis of GH. Eligible patients were counseled and trained by a specialist midwife and were provided with an automated Microlife® "WatchBP Home" BP machine. Each patient followed an individualised schedule of hospital visits and BP measurements based on the HBPM pathway or standard hospital protocol which was based on the National Institute of Health and Care Excellence (NICE) guideline. MAIN OUTCOME MEASURES: Adverse fetal, neonatal and maternal outcomes as well as number of antenatal hospital visits were recorded and compared between HBPM and office (traditional) pathways. RESULTS: 143 women with GH were included in the study (80 HBPM vs 63 standard care). There were no significant difference between the two groups in maternal high-dependency unit admission (P = 0.999), birth weight centile (P = 0.803), fetal growth restriction (p = 0.999), neonatal intensive care unit admissions (p = 0.507) and composite neonatal (p = 0.654), maternal (p = 0.999) or fetal adverse outcomes (p = 0.999). The number of Day Assessment Unit (DAU) visits was significantly lower in the HBPM group than the traditional pathway (median 4.0 vs. 5.0, P = 0.009). The difference was greater when the number of visits were adjusted for the duration of monitoring in weeks (median: 1.0 vs 1.5, P < 0.001). There were no significant difference between the two groups in the total number of outpatient (P = 0.357) and triage visits (p = 0.237). However, the total number of antenatal visits adjusted for the duration of monitoring was significantly lower for the HBPM group compared to the traditional pathway (median 1.4 vs 1.8, P = 0.020). CONCLUSIONS: HBPM in women with GH results in significantly less antenatal visits compared to women on a standard pathway of care. The two groups had comparable fetal, neonatal and maternal adverse outcomes. Large multicentre studies are needed to ascertain the safety of rare adverse pregnancy outcomes.

First trimester placental endothelial cells from pregnancies with abnormal uterine artery Doppler are more sensitive to apoptotic stimuli.

Failure of the placental capillary network to develop normally is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). Although the symptoms are observed at term, the problem begins in the first trimester. However, investigations at this clinically relevant time are hindered by difficulties in identifying earlystage pregnancies that are at risk of developing FGR/PE. Using uterine artery Doppler ultrasound in the first trimester as a proxy measure of poor placentation, we have identified pregnancies at increased risk of developing early onset FGR/PE. Placental endothelial cells (PEC) isolated from pregnancies at increased risk of developing FGR/PE grew more slowly and their basal rate of apoptosis was significantly higher than that seen in the normal group. The pro-apoptotic stimulus, TNFα, induced apoptosis in cells from both groups but this was significantly greater in the high risk group. TNF receptor expression was unaffected. Inhibition of nitric oxide (NO) production significantly increased the sensitivity of cells from the normal pregnancies to TNFα but not in the high risk group establishing a functional role for NO in this system. In conclusion, first trimester PEC from pregnancies at increased risk of developing early onset FGR/PE were inherently more sensitive to apoptotic stimuli and this was functionally linked to the synthesis of NO. This may contribute to the poor placental vascular development seen in on going pregnancies.

Increased apoptosis, altered oxygen signaling, and antioxidant defenses in first-trimester pregnancies with high-resistance uterine artery blood flow.

The mechanisms of deficient placentation in the first trimester remain poorly understood, although apoptosis, hypoxia, and oxidative stress have been implicated. High uterine artery Doppler resistance indexes (RIs) are predictive of placental complications of pregnancy, such as preeclampsia, fetal growth restriction, and stillbirth. We provide evidence that even in the first trimester, pregnancies with high uterine artery Doppler RI demonstrate alterations in placental gene and protein expression. Apoptosis was significantly higher in high RI placental tissue, as determined by Western blot analysis of cleaved poly (ADP-ribose) polymerase and caspase 3. Protein expression of the trophoblast survival factor insulin-like growth factor-2 was significantly lower. Both high and normal RI placentas showed evidence of hypoxia and oxidative stress with expression of hypoxia-inducible factors 1α and 2α, heat shock protein 70, presence of nitrotyrosine residues, and lipid peroxidation. We observed no exaggerated placental hypoxia or oxidative stress associated with high RI pregnancies. High RI placental tissue demonstrated an altered balance of antioxidant enzyme activity. Hypoxia and oxidative stress appear to be a physiological state in early pregnancy; our data did not support the hypothesis that they are associated with deficient placentation in the first trimester. Higher levels of apoptosis, reduced insulin-like growth factor-2 expression, and altered antioxidant defenses may contribute to abnormal placentation and the later development of pregnancy complications, such as preeclampsia, fetal growth restriction, and stillbirth.

Role of second-trimester uterine artery Doppler in assessing stillbirth risk.

OBJECTIVE: To estimate the association between uterine artery Doppler indices and stillbirth in routinely screened populations. METHODS: Second-trimester uterine artery Doppler indices at 19 to 23 weeks of gestation were obtained from a large cohort of women. Pregnancy losses recorded on a mandatory national register were cross-linked to the Doppler database. Kaplan-Meier curves were constructed for the risk of stillbirth based on the uterine artery Doppler resistance indices. Logistic regression analysis was used to assess the influence of uterine artery Doppler indices and other more conventional risk factors on the likelihood of stillbirth. RESULTS: Data were available from 15,835 women with 144 stillbirths (9.1 stillbirths per 1,000 births). Kaplan-Meier analysis showed that the risk of stillbirth (39.41 per 1000) in women with uterine artery Doppler indices greater than the 90th percentile was sevenfold higher (95% confidence interval 4.81-9.57) than the reference population (5.36 per 1000) with Doppler indices less than or equal to the 90th percentile. The positive predictive and negative predictive values for the 90th percentile uterine artery Doppler cutoff were 3.79% and 99.46%, respectively [corrected] The sensitivities of the 90th, 95, and 99th percentile uterine artery Doppler resistance index cut-offs for the sensitivity of stillbirth were 46.2%, 35.4%, and 15.4%, respectively. Conventional risk factors for term stillbirth such as ethnicity, body mass index (BMI), and smoking no longer contributed to stillbirth risk when uterine artery Doppler indices were included in multivariable logistic regression analysis. CONCLUSION: Elevated second-trimester Doppler indices, a proxy for impaired placentation, are more strongly associated with stillbirth than conventional risk factors. Risk factors such as ethnicity, maternal age, BMI, and smoking contribute to risk of term stillbirth through uteroplacental dysfunction. LEVEL OF EVIDENCE: II.

Early prediction and prevention of pre-eclampsia.

Pre-eclampsia remains an important cause of maternal and perinatal mortality. The ability to predict the most severe forms of pre-eclampsia would allow closer surveillance and earlier intervention to improve outcomes. Although no definitive preventative treatment has been found to date, it is likely that prospective treatments would need to start early in pregnancy to alter pathogenesis. Following recent advances in the understanding of the pathogenesis of this complex syndrome, new predictive tests are being evaluated. The most promising models incorporate biochemical and biophysical tests that combine assessments of placentation and maternal disease susceptibility.

Remodelling at the maternal-fetal interface: relevance to human pregnancy disorders.

In human pregnancy, successful placentation and remodelling of the uterine vasculature require the integration of a number of stages, which are crucial for a healthy pregnancy. As the demands of the developing fetus for nutrients and oxygen increase, the capacity of the maternal blood vessels to supply this must be altered radically, with deficiencies in this process implicated in a number of dangerous pregnancy complications. The complex signalling networks that regulate these tightly co-ordinated events are becoming clearer as more studies of early pregnancy are performed. It is the aim of this review to draw together our knowledge of events that occur to facilitate a successful pregnancy ranging from the preparation for implantation, through the invasion and differentiation of the trophoblast and the regulation of these processes by other cells within the decidual environment, to the active role that the trophoblast and maternal immune cells play in facilitating the remodelling of the uterine spiral arteries. The events involved in a healthy pregnancy will then be compared to aberrant placentation and remodelling, which are characteristics of many pregnancy disorders, and recent advances in detection of abnormal placental development will also be discussed.

Defective endovascular trophoblast invasion in the first trimester is associated with increased maternal serum ischemia-modified albumin.

BACKGROUND: Ischemia-modified albumin (IMA), a protein elevated in cardiac ischemia, is also increased to supra-physiological levels in early normal pregnancy. This finding supports the hypothesis that normal trophoblast development is stimulated by a hypoxic intrauterine environment. The aim of this study was to examine whether first trimester IMA levels are further elevated with defective trophoblast development. METHODS: Prospective study of healthy women with singleton pregnancies undergoing nuchal translucency assessment at 11-14 weeks. First trimester maternal serum IMA concentrations in those subsequently developing pre-term pre-eclampsia (n = 19) were compared to randomly chosen controls with normal pregnancy outcome (n = 69). RESULTS: Median first trimester serum IMA concentrations were significantly higher in women who subsequently developed pre-eclampsia (median 126.5 kU/L, interquartile range (IQR) 114.33-134.36 kU/L) when compared to those with normal pregnancy outcome (median 115.01 kU/L, IQR 102.29-124.81 kU/L, P = 0.02). CONCLUSIONS: Maternal serum IMA levels are elevated in the first trimester in women with pre-eclampsia, a clinical manifestation of defective endovascular trophoblast development. This suggests that abnormally high intrauterine hypoxia and subsequent reperfusion oxidative damage may be associated with defective trophoblast development. First trimester serum IMA may be a potential biomarker for abnormal placental development.

Uterine artery Doppler in the prediction of adverse pregnancy outcome.

PURPOSE OF REVIEW: To review publications, published during the past year, that have examined uterine artery Doppler findings in women with adverse pregnancy outcome. RECENT FINDINGS: Almost two-thirds of stillbirths that occur in the early preterm period (up to 32 weeks) can be predicted by uterine artery Doppler at 23 weeks. First trimester screening studies have shown that an abnormal result increases the risk of subsequent fetal growth restriction, and such women are at particularly high risk when indices remain abnormal in the second trimester. Studies combining uterine artery Doppler with maternal serum markers have demonstrated that measurement of first-trimester maternal serum pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin improve sensitivities of second-trimester Doppler. As these are frequently measured in Down syndrome screening and they lend themselves in screening for pre-eclampsia. Women with abnormal first and second-trimester serum markers constitute a high-risk group. Maternal serum placental protein 13 remains a promising method for early screening, although a recent study suggests lower sensitivities than initially reported. SUMMARY: Uterine artery Doppler screening identifies women at high risk for developing adverse pregnancy outcomes. Detection rates may be increased and false positive rates reduced by combination with maternal characteristics or serum markers.