Christina Aye

Clinical cardiovascular risk during young adulthood in offspring of hypertensive pregnancies: insights from a 20-year prospective follow-up birth cohort

Objectives Offspring of hypertensive pregnancies have increased cardiovascular risk factors during childhood. We hypothesised that offspring of hypertensive pregnancies would demonstrate increased clinical levels of hypertension by young adult life, which would be proportional to the severity of the pregnancy complication. Design Prospective birth cohort study Setting Tertiary obstetric hospital. Participants 2868 young adult offspring of women enrolled during pregnancy into the Western Australia Pregnancy Cohort (Raine) Study. Main outcome measures Cardiovascular risk, including incidence of hypertension and metabolic disease, in those born to hypertensive compared to normotensive pregnancies. Results Young adult offspring of hypertensive pregnancies were 2.5 times (95% CI 1.32 to 4.56, p=0.004) more likely to have global lifetime risk (QRISK) scores above the 75th centile. Thirty per cent of 20 year olds with hypertensive blood pressures were born following a hypertensive pregnancy. Pre-eclampsia or hypertension resulting in preterm birth associated with a threefold (95% CI 1.3 to 7.0, p=0.01) greater risk of being hypertensive by age 20 years, with no differences in body mass index. Whereas pregnancy-induced hypertension associated with a smaller 3±1 mm Hg blood pressure rise (p=0.001) and a twofold (95% CI 1.5 to 2.8, p=0.001) greater risk of being obese or overweight. Risk factor associations were consistent throughout early life and independent of other birth-factors. Conclusions Incidence of offspring hypertension was significantly increased in those whose mothers had a more complicated pregnancy history, including preterm birth and pre-eclampsia.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies.

Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (−17.7±16.4% versus −9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth.

Multidisciplinary management of ornithine transcarbamylase (OTC) deficiency in pregnancy: essential to prevent hyperammonemic complications.

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error in the metabolism of the urea cycle with an incidence of 1 in 14 000 live births. Pregnancy can trigger potentially fatal hyperammonemic crises. We report a successful pregnancy in a 29-year-old primiparous patient with a known diagnosis of OTC deficiency since infancy. Hyperammonemic complications were avoided due to careful multidisciplinary management which included a detailed antenatal, intrapartum and postnatal plan. Management principles include avoidance of triggers, a low-protein diet and medications which promote the removal of nitrogen by alternative pathways. Triggers include metabolic stress such as febrile illness, particularly gastroenteritis, fasting and any protein loading. In our case the patient, in addition to a restricted protein intake, was prescribed sodium benzoate 4 g four times a day, sodium phenylbutyrate 2 g four times a day and arginine 500 mg four times a day to aid excretion of ammonia and reduce flux through the urea cycle.

Aortic stiffness and blood pressure variability in young people: a multimodality investigation of central and peripheral vasculature

Introduction: Increased blood pressure (BP) variability is a cardiovascular risk marker for young individuals and may relate to the ability of their aorta to buffer cardiac output. We used a multimodality approach to determine relations between central and peripheral arterial stiffness and BP variability. Methods: We studied 152 adults (mean age of 31 years) who had BP variability measures based on SD of awake ambulatory BPs, 24-h weighted SD and average real variability (ARV). Global and regional aortic distensibility was measured by cardiovascular magnetic resonance, arterial stiffness by cardio-ankle vascular index (CAVI) and pulse wave velocity (PWV) by SphygmoCor (carotid–femoral) and Vicorder (brachial–femoral). Results: In young people, free from overt cardiovascular disease, all indices of SBP and DBP variability correlated with aortic distensibility (global aortic distensibility versus awake SBP SD: r = −0.39, P < 0.001; SBP ARV: r = −0.34, P < 0.001; weighted 24-h SBP SD: r = −0.42, P < 0.001). CAVI, which closely associated with aortic distensibility, also related to DBP variability, as well as awake SBP SD (r = 0.19, P < 0.05) and weighted 24-h SBP SD (r = 0.24, P < 0.01), with a trend for SBP ARV (r = 0.17, P = 0.06). In contrast, associations with PWV were only between carotid–femoral PWV and weighted SD of SBP (r = 0.20, P = 0.03) as well as weighted and ARV of DBP. Conclusion: Greater BP variability in young people relates to increases in central aortic stiffness, strategies to measure and protect aortic function from a young age may be important to reduce cardiovascular risk.

B Postnatal Cardiac Remodelling after Preterm Birth: Why Preterm-Born Individuals have a Unique Functional and Structural Phenotype in Young Adulthood?

Background Preterm birth leads to a switch from fetal to postnatal circulation before completion of in utero cardiac development. We hypothesised that those born preterm would have a unique adult cardiac phenotype and that this would develop during postnatal life. Methods 234 young adults underwent cardiovascular magnetic resonance, of which 102 had been followed prospectively since preterm birth. We then studied 200 infants, longitudinally from birth to three months of age using echocardiography, of which 111 were born preterm. To define cardiac shape and function in adult and neonatal life we developed in-house 3D computational approaches and applied novel deformation imaging tools. Results born preterm had increased LV and RV mass index (P < 0.001 and P < 0.001), proportional to severity of prematurity (P = 0.03 and P < 0.001), and reduced chamber volumes and length (P < 0.01). Although LV ejection fraction was preserved, RV ejection fraction was reduced (P = 0.006), as were LV systolic and diastolic myocardial deformation. At birth, preterm-born infants had similar LV mass index, appropriate for gestational body size, as term-born infants (P = 0.13). However, by three months a greater percentage increase (P = 0.01) resulted in significantly greater LV mass index in those born preterm (P = 0.04). Interestingly, their LV end-diastolic volume index was already smaller at birth (P = 0.003) and this difference persisted at three months (P = 0.05). Conclusions Birth is associated with a unique adult cardiac phenotype. Disproportionate increases in mass occur during postnatal life alongside persistent shape changes. Postnatal life may be a critical window for modification of cardiac development, relevant to the adult cardiovasculature.

Skin eruptions specific to pregnancy: an overview

Ajaya Maharajan MBBS DGO MRCOG,* Christina Aye BMBCh MA Hons MRCOG, Ravi Ratnavel DM(Oxon) FRCP(UK), Ekaterina Burova FRCP CMSc (equ. PhD) Consultant in Obstetrics and Gynaecology, Luton and Dunstable University Hospital, Lewsey Road, Luton, Bedfordshire LU4 0DZ, UK ST5 in Obstetrics and Gynaecology, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK Consultant Dermatologist, Buckinghamshire Health Care, Mandeville Road, Aylesbury, Buckinghamshire HP21 8AL, UK Consultant Dermatologist, Skin Cancer Lead for Bedford Hospital, Bedford Hospital NHS Trust, South Wing, Kempston Road, Bedford MK42 9DJ, UK *Correspondence: Ajaya Maharajan. Email: kalapushpam@yahoo.comPregnancy results in various physiological skin changes. As a consequence, some common dermatoses can present more frequently in pregnant women. In addition, there are a number of skin eruptions unique to pregnancy. The aetiology of physiological skin changes in pregnancy is uncertain but is thought to be due to hormonal and physical changes of pregnancy. The four dermatoses of pregnancy are: atopic eruption of pregnancy, pemphigoid gestationis, polymorphic eruption of pregnancy and intrahepatic cholestasis of pregnancy.Key content Pregnancy results in various physiological skin changes. As a consequence, some common dermatoses can present more frequently in pregnant women. In addition, there are a number of skin eruptions unique to pregnancy. The aetiology of physiological skin changes in pregnancy is uncertain but is thought to be due to hormonal and physical changes of pregnancy. The four dermatoses of pregnancy are: atopic eruption of pregnancy, pemphigoid gestationis, polymorphic eruption of pregnancy and intrahepatic cholestasis of pregnancy. Learning objectives To understand the physiological skin changes in pregnancy. To identify the skin conditions that require appropriate referral. To be able to take a history, to diagnose the skin eruptions unique to pregnancy, undertake appropriate investigations and first-line management, and understand the criteria for referral to a dermatologist.

Urinary incontinence: Can weight loss treat urinary incontinence in obese women?

New research confirms that weight loss is an effective first-line intervention for overweight or obese women with urinary incontinence. Such patients should be encouraged to lose weight, but must also be given access to a full range of treatment options.

Neonatal autonomic function after pregnancy complications and early cardiovascular development

BackgroundHeart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period.MethodsNinety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age.ResultsIncreasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point.ConclusionsAltered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

Arteriovenous differences in cord blood gas analysis and the prediction of adverse neonatal outcome

The aim of this paper was to determine whether arteriovenous differences of pH and pCO2 are useful predictors of adverse neonatal outcome in acidemic neonates.