Brenda Kelly

Cardiovascular Risk Factors in Children and Young Adults Born to Preeclamptic Pregnancies: A Systematic Review

BACKGROUND AND OBJECTIVE: Preeclampsia is an independent cardiovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardiovascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero. METHODS: We performed a systematic review and meta-analysis on studies reporting traditional cardiovascular risk factors in those exposed to preeclampsia compared to controls. Information was extracted on the classic cardiovascular risk factors, including blood pressure, lipid profile, glucose metabolism, and BMI from articles published between 1948 and August 2011 in Medline and Embase. RESULTS: Eighteen studies provided cumulated data on 45 249 individuals. In utero exposure to preeclampsia was associated with a 2.39 mm Hg (95% confidence interval: 1.74–3.05; P < .0001) higher systolic and a 1.35 mm Hg (95% confidence interval: 0.90–1.80; P < .00001) higher diastolic blood pressure during childhood and young adulthood. BMI was increased by 0.62 kg/m2 (P < .00001). Associations were similar in children and adolescents, for different genders, and with variation in birth weight. There was insufficient evidence to identify consistent variation in lipid profile or glucose metabolism. CONCLUSIONS: Young offspring of pregnancies complicated by preeclampsia already have increased blood pressure and BMI, a finding that may need to be considered in future primary prevention strategies for cardiovascular disease.

Elevated Blood Pressure in Offspring Born Premature to Hypertensive Pregnancy: Is Endothelial Dysfunction the Underlying Vascular Mechanism?

Offspring born to mothers with hypertensive pregnancy have higher childhood blood pressure. We hypothesized this relates to prenatally programmed differences in the underlying vascular pathophysiology of the offspring and that these would be most apparent in those born preterm because of severe hypertension. We carried out a 20-year follow-up study of 71 subjects born preterm, 19 to a hypertensive pregnancy and 52 to a normotensive pregnancy. Findings were compared with 38 subjects born at term to uncomplicated pregnancies. Peripheral and central blood pressures were measured, and then central arterial stiffness was assessed by carotid-femoral pulse wave velocity using applanation tonometry. Ultrasound was used to assess flow-mediated endothelial-dependent and independent brachial artery responses and common carotid artery intima-media thickness. Offspring born preterm to either hypertensive or normotensive pregnancy had higher peripheral and central blood pressure compared with full-term born offspring (central mean arterial pressure after preterm hypertensive pregnancy: 84.92±7.0 mm Hg; preterm normotensive pregnancy: 84.13±8.9 mm Hg; full-term pregnancy: 76.24±7.96 mm Hg; P=0.0009). However, underlying vascular phenotype differed. Preterm offspring of normotensive pregnancy had greater arterial stiffness than offspring of hypertensive pregnancy (5.92±0.84 versus 5.42±0.73 m/s; P=0.039), whereas offspring of hypertensive pregnancy had greater carotid intima-media thickness (0.52±0.04 versus 0.48±0.06 mm; P=0.013) and 30% lower flow-mediated dilatation (4.25±4.02% versus 6.79±4.38%; P=0.05). Prematurity is associated with elevated blood pressure in later life. However, predominant underlying vascular phenotype depends on maternal pathology. Targeting endothelial function may be particularly important for primary prevention after hypertension in pregnancy.

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies.

Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2–5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.

Antenatal Glucocorticoid Exposure and Long-Term Alterations in Aortic Function and Glucose Metabolism

OBJECTIVE: Animal studies have demonstrated long-term effects of in utero glucocortcoid exposure on vascular development and glucose metabolism. We hypothesized that there would be a similar impact in humans. METHODS: One hundred and two young adults born preterm aged 23 to 28 years, with prospective data collection from birth, and 95 adults born term after uncomplicated pregnancies underwent cardiovascular MRI. We compared cardiac and aortic structure and function, as well as cardiovascular risk profile, in a nested case-control study of 16 participants exposed to antenatal steroids and 32 who were not, but with otherwise similar perinatal care. Outcomes were compared with normal ranges in those born term. RESULTS: Adults whose mothers had received antenatal steroids had decreased ascending aortic distensibility (9.88 ± 3.21 vs 13.62 ± 3.88 mm Hg−1 × 103, P = .002) and increased aortic arch pulse wave velocity (5.45 ± 1.41 vs 4.47 ± 0.91 m/s, P = .006). The increase in stiffness was equivalent to that of term adults a decade older. Those who had in utero exposure to antenatal steroids also had significant differences in homeostatic model assessments for β-cell function (P = .010), but in multiple regression analysis this did not explain the impact of steroids on aortic function. CONCLUSIONS: Antenatal glucocorticoid exposure in preterm infants is associated with increased aortic arch stiffness and altered glucose metabolism in early adulthood.

Unique blood pressure characteristics in mother and offspring after early onset preeclampsia.

Risk of hypertension in mother and offspring after preeclampsia is greater if preeclampsia develops early in pregnancy. We investigated whether those who develop early onset disease have unique adverse blood pressure characteristics. One hundred forty women were studied 6 to 13 years either after a pregnancy complicated by preeclampsia (45 women with early onset preeclampsia before 34 weeks gestation and 45 women with late-onset preeclampsia) or after a normotensive pregnancy (50 women). Forty-seven offspring from these pregnancies also participated. Data on maternal antenatal and postnatal blood pressures were extracted from maternity records and related to peripheral, central, and ambulatory blood pressure measurements in later life. Compared with late-onset preeclampsia, early onset preeclampsia was associated with higher diastolic blood pressure 6 weeks postnatally (86.25±13.46 versus 75.00±5.00 mm Hg, P<0.05), a greater increase in blood pressure relative to booking blood pressure over the subsequent 6 to 13 years, and higher nocturnal systolic and diastolic blood pressures in later life (111.07±13.18 versus 101.13±11.50 mm Hg, P=0.04, and 67.00±7.25 versus 58.60±5.79 mm Hg, P=0.002). Furthermore, at age 6 to 13 years their offspring had higher systolic blood pressure compared with those born to late-onset preeclampsia (96.27±7.30 versus 88.39±7.57 mm Hg, P=0.005). Mothers who developed early onset preeclampsia, and the offspring of that pregnancy display specific adverse blood pressure characteristics later in life. These are not evident in mothers and offspring after late-onset preeclampsia or normotensive pregnancy.

Short-Term Exposure to Exogenous Lipids in Premature Infants and Long-Term Changes in Aortic and Cardiac Function

Objective— Intravenous lipid use is associated with an acute hyperlipidemia, but long-term consequences have not been studied. We investigated whether elevated lipids in humans during the critical period of preterm neonatal life have a long-term impact on aortic and myocardial function relevant to adult disease. Methods and Results— We followed up 102 subjects born prematurely and now aged 23 to 28 years. Eighteen received intravenous lipids as neonates and were matched to controls with equivalent perinatal characteristics. Global and regional aortic stiffness and left ventricular function were assessed by cardiovascular magnetic resonance. Those who received intravenous lipids had greater aortic stiffness in early adulthood (P=0.0002), with greater stiffness in the abdominal aorta (P=0.012). The relationship was graded according to the elevation in neonatal cholesterol induced by intravenous lipids (P<0.0001) but not other metabolic parameters altered by the infusion. Peak systolic circumferential strain was also reduced in the lipid group (P=0.006), which, again, was proportional to neonatal cholesterol level (P<0.01). Conclusion— Aortic and myocardial function in young adulthood is associated with intralipid exposure during neonatal life for preterm infants, in a graded manner related to the rise in cholesterol. Circulating cholesterol during critical developmental periods may have long-term impacts on the human cardiovascular system.

Prevention of Vascular Dysfunction after Preeclampsia: A Potential Long-Term Outcome Measure and an Emerging Goal for Treatment

Preeclampsia is increasingly being recognised as more than an isolated disease of pregnancy. In particular, preeclampsia has emerged as an independent risk factor for maternal cardiovascular disease and has recently been recognised as a risk factor for cardiovascular disease in children exposed in utero. Preeclampsia and cardiovascular disease may share important pathophysiological and molecular mechanisms and further investigation into these is likely to offer insight into the origins of both conditions. This paper considers the links between cardiovascular disease and preeclampsia and the implication of these findings for refinement of the management of patients whose care is complicated by preeclampsia.

Guided Random Forests for Identification of Key Fetal Anatomy and Image Categorization in Ultrasound Scans

In this paper, we propose a novel machine learning based method to categorize unlabeled fetal ultrasound images. The proposed method guides the learning of a Random Forests classifier to extract features from regions inside the images where meaningful structures exist. The new method utilizes a translation and orientation invariant feature which captures the appearance of a region at multiple spatial resolutions. Evaluated on a large real world clinical dataset (~30K images from a hospital database), our method showed very promising categorization accuracy (accuracytop1 is 75% while accuracytop2 is 91%).

Mandatory submission of patient identifiable information to third parties: FGM now, what next?

The government has done much to tackle female genital mutilation (FGM),1 2 3 but the planned rollout of FGM Enhanced Data Collection across the NHS in October 2015 is ill considered. All healthcare professionals will be legally obliged to submit highly sensitive, patient identifiable information on every woman with FGM attending the NHS for whatever reason. A woeful consultation preceded the ministerial direction, which also says patient consent is not …

A Deep Learning Solution for Automatic Fetal Neurosonographic Diagnostic Plane Verification Using Clinical Standard Constraints

During routine ultrasound assessment of the fetal brain for biometry estimation and detection of fetal abnormalities, accurate imaging planes must be found by sonologists following a well-defined imaging protocol or clinical standard, which can be difficult for non-experts to do well. This assessment helps provide accurate biometry estimation and the detection of possible brain abnormalities. We describe a machine-learning method to assess automatically that transventricular ultrasound images of the fetal brain have been correctly acquired and meet the required clinical standard. We propose a deep learning solution, which breaks the problem down into three stages: (i) accurate localization of the fetal brain, (ii) detection of regions that contain structures of interest and (iii) learning the acoustic patterns in the regions that enable plane verification. We evaluate the developed methodology on a large real-world clinical data set of 2-D mid-gestation fetal images. We show that the automatic verification method approaches human expert assessment.