The potential impact of the fetal genotype on maternal blood pressure during pregnancy.

The heritability of pregnancy-induced hypertension (encompassing both gestational hypertension and preeclampsia) is around 0.47, suggesting that there is a genetic component to its development. However, the maternal genetic risk variants discovered so far only account for a small proportion of the heritability. Other genetic variants that may affect maternal blood pressure in pregnancy arise from the fetal genome, for example wild-type pregnant mice carrying offspring with Cdkn1c or Stox1 disrupted develop hypertension and proteinuria. In humans, there is a higher risk for preeclampsia in women carrying fetuses with Beckwith-Wiedemann syndrome (including those fetuses with CDKN1C mutations) and a lower risk for women carrying babies with trisomy 21. Other risk may be associated with imprinted fetal growth genes and genes that are highly expressed in the placenta such as GCM1. This article reviews the current state of knowledge linking the fetal genotype with maternal blood pressure in pregnancy.MRCThis is the Author Accepted Manuscript of Petry CJ, Beardsall K, Dunger DB. "The potential impact of the fetal genotype on maternal blood pressure during pregnancy". published in the Journal of Hypertension. The published version is available at http://dx.doi.org/10.1097/HJH.000000000000021

Hyperglycaemia in the Newborn Infant. Physiology Verses Pathology.

Hyperglycemia is common in newborns requiring intensive care, particularly in preterm infants, in sepsis and following perinatal hypoxia. The clinical significance, and optimal intervention strategy varies with context, but hyperglycaemia is associated with increased mortality and morbidity. The limited evidence for optimal clinical targets mean controversy remains regarding thresholds for intervention, and management strategies. The first consideration in the management of hyperglycaemia must be to ascertain potentially treatable causes. Calculation of the glucose infusion rate (GIR) to insure this is not excessive, is critical but the use of insulin is often helpful in the extremely preterm infant, but is associated with an increased risk of hypoglycaemia. The use of continuous glucose monitoring (CGM) has recently been demonstrated to be helpful in targeting glucose control, and reducing the risk from hypoglycaemia in the preterm infant. Its use in other at risk infants remains to be explored, and further studies are needed to provide a better understanding of the optimal glucose targets for different clinical conditions. In the future the combination of CGM and advances in computer algorithms, to provide intelligent closed loop systems, could allow a safer and more personalized approached to management

A feasibility study of paired Continuous Glucose Monitoring (CGM) intra-partum and in the newborn in pregnancies complicated by Type 1 Diabetes

Aim: To describe the continuous glucose monitoring (CGM) profiles of type 1 diabetes (T1D) offspring in the early neonatal period and its association with maternal intrapartum glucose control. Methods: A prospective observational study of T1D pregnant women and their neonatal offspring. Women had a CGM sensor inserted 2-3 days prior to delivery. Infants had a masked CGM sensor inserted as soon as possible following delivery. Maternal glycaemic outcomes were time-in-target (70-140 mg/dL [3.9-7.8 mmol/L]), hyperglycaemia >140 mg/dL (7.8 mmol/L) and mean CGM glucose during the 24 hours preceding delivery. Neonatal outcomes included lowest recorded blood glucose concentration, and CGM measures (glucose 140 mg/dL (7.8 mmol/L), and 9 (9) % time < 70 mg/dL (3.9 mmol/L) with mean (SD) CGM glucose 113 (9) mg/dL (6.3 [0.7] mmol/L). 15 infants (93.8%) had ≥1 blood glucose concentration < 47 mg/dL (2.6 mmol/L) and five had ≥1 blood glucose concentration < 18 mg/dL (1.0 mmol/L). The mean infant CGM glucose on days 1, 2, and 3 of life was 63 (14), 67 (13), 76 (11) mg/dL (3.5 [0.8], 3.7 [0.7], and 4.2 [0.6] mmol/L). Four infants (25%) spent more than 50% time with CGM glucose levels < 47 mg/dL (2.6 mmol/L) on day 1. Conclusions: CGM detected widespread neonatal hypoglycaemia, even among mothers with good intrapartum glucose control

Thresholds for hypoglycaemic screening-a cause for concern?

The new Framework for Practice highlights the limited evidence for our current clinical practice (1). It is helpful in emphasising the importance of accurate measurement of glucose concentrations, listening to the concerns of parents and acknowledging that untreated hypoglycaemia can have devastating longterm consequences. However we have the following concerns: Screening thresholds The Framework recommends lowering a commonly accepted screening threshold in infants considered to be at risk of hypoglycaemia to a level that at any other time of life would be considered harmful. It fails to acknowledge the differences between screening and diagnostic thresholds; something neonatologists are very familiar with in the management of babies with jaundice. Phototherapy is provided to many babies with bilirubin levels well below a harmful level to prevent a harmful level being reached. Screening interventions are intended to prevent harmful events. Such thresholds will inevitably mean many individuals are treated ‘unnecessarily’ to avoid the risk of significant harm. In 2000 Cornblath et al published guidance on ‘operational thresholds’ in keeping with the current BAPM framework (2). However, and possibly reflecting concerns about the lack of evidence for the safety of this lower operational threshold, in 2017 in the UK, >80% of neonatal units still used <2.6mmol/ as their defined hypoglycaemic threshold (3). A threshold of <2.6mmol/l provides an opportunity for intervention before damaging neuroglycopaenia occurs

Feasibility of Automated Insulin Delivery Guided by Continuous Glucose Monitoring in preterm infants

Abstract: Objective: Closed-loop systems have been used to optimise insulin delivery in children with diabetes, but they have not been tested in neonatal intensive care. Extremely preterm infants are prone to hyperglycaemia and hypoglycaemia; both of which have been associated with adverse outcomes. Insulin sensitivity is notoriously variable in these babies and glucose control is time-consuming, with management requiring frequent changes of dextrose-containing fluids and careful monitoring of insulin treatment. We aimed to evaluate the feasibility of closed-loop management of glucose control in these infants. Design and Setting: Single centre feasibility study with a randomized parallel design in a neonatal intensive care unit. Eligibility criteria included birth weight <1200g and <48hours of age. All infants had subcutaneous continuous glucose monitoring for the first week of life, with those in the intervention group receiving closed-loop insulin delivery in a pre-specified window, between 48 and 72hours of age during which time the primary outcome was percentage of time in target (sensor glucose 4-8mmol/l). Results: The mean (SD) gestational age and birth weight of intervention and control study arms were 27.0(2.4) weeks, 962(164) g and 27.5(2.8) weeks, 823(282) g respectively, and were not significantly different. The time in target was dramatically increased from median (IQR) 26%(6, 64) with paper guidance to 91%(78, 99) during closed loop (p<0.001). There were no serious adverse events and no difference in total insulin infused. Conclusions: Closed-loop glucose control based on subcutaneous glucose measurements appears feasible as a potential method of optimizing glucose control in extremely preterm infants.Funding was provided by the Evelyn Trust, the National Institute of Health Research EME Program and the National Institute of Health Research Cambridge Biomedical Research Centre. Medtronic provided the continuous glucose monitoring system and sensors. Medtronic had no role in design of the study, the gathering of data, access to data, preparation of the manuscript or decision to publish the results

Research & Communication Skills (RCS) Weekly sessions (2013/14)

Slides and materials from each weeks session in one handy locatio

‘There were more wires than him’: The potential for wireless patient monitoring in neonatal intensive care

$\textbf{Background:}$ The neonatal intensive care unit (NICU) can be one of the most stressful hospital environments. Alongside providing intensive clinical care, it is important that parents have the opportunity for regular physical contact with their babies because the neonatal period is critical for parent–child bonding. At present, monitoring technology in the NICU requires multiple wired sensors to track each baby's vital signs. This study describes the experiences that parents and nurses have with the current monitoring methods, and reports on their responses to the concept of a wireless monitoring system. $\textbf{Methods: }$ Semistructured interviews were conducted with six parents, each of whom had babies on the unit, and seven nurses who cared for those babies. The interviews initially focused on the participants’ experiences of the current wired system and then on their responses to the concept of a wireless system. The transcripts were analysed using a general inductive approach to identify relevant themes. $\textbf{Results:}$ Participants reported on physical and psychological barriers to parental care, the ways in which the current system obstructed the efficient delivery of clinical care and the perceived benefits and risks of a wireless system. The parents and nurses identified that the wires impeded baby–parent bonding; physically and psychologically. While a wireless system was viewed as potentially enabling greater interaction, staff and parents highlighted potential concerns, including the size, weight and battery life of any new device. $\textbf{Conclusions:}$ The many wires required to safely monitor babies within the NICU creates a negative environment for parents at a critical developmental period, in terms of physical and psychological interactions. Nurses also experience challenges with the existing system, which could negatively impact the clinical care delivery. Developing a wireless system could overcome these barriers, but there remain challenges in designing a device suitable for this unique environment.This project was funded by the EPSRC CDT in Sensor Technologies and Applications (grant number EP/L015889/1)

Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial

Aims: To examine the relationship between maternal glycaemic control and risk of neonatal hypoglycaemia using conventional and continuous glucose monitoring (CGM) metrics in the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT) participants. Methods: A secondary analysis of CONCEPTT involving 225 pregnant women and their liveborn infants. Antenatal glycaemia was assessed at 12, 24 and 34 weeks gestation. Intrapartum glycaemia was assessed by CGM measures 24 hours prior to delivery. The primary outcome was neonatal hypoglycaemia defined as glucose concentration 97.7th centile (63.2% vs 33.9%; p<0.0001) and skinfold thickness (p≤0.02). Intrapartum CGM was available for 33 participants, with no differences between mothers of neonates with and without hypoglycaemia. Conclusions: Modest increments in CGM time-in-target (5-7% increase) during the second and third trimesters are associated with reduced risk for neonatal hypoglycaemia. While more intrapartum CGM data are needed, the higher birthweight and skinfold measures associated with neonatal hypoglycaemia, suggest that risk is related to fetal hyperinsulinemia preceding the immediate intrapartum period

Short and long term outcome of neonatal hyperglycemia in very preterm infants: a retrospective follow-up study

<p>Abstract</p> <p>Background</p> <p>Hyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose ≥ 10 mmol/l, treated with insulin for ≥ 12 hours) on growth and neurobehavioral outcome at 2 years of age.</p> <p>Methods</p> <p>Retrospective follow-up study at 2 years of age among 859 infants ≤32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006. Thirty-three survivors treated with insulin for hyperglycemia and 63 matched controls without hyperglycemia were evaluated at a corrected age of 2 years. Outcome measures consisted of growth (weight, length, and head circumference) and neurological and behavioural development.</p> <p>Results</p> <p>66/859 (8%) infants ≤ 32 weeks of gestation developed hyperglycemia. Mortality during admission was 27/66 (41%) in the hyperglycemia group versus 62/793 (8%) in those without hyperglycemia (p < 0.001). Mortality was higher in infants with hyperglycemia with a birth weight ≤1,000 gram (p = 0.005) and/or gestational age of 24-28 weeks (p = 0.009) than in control infants without hyperglycemia. Sepsis was more prominent in infants with hyperglycemia and a birth weight of >1,000 gram (p = 0.002) and/or gestational age of 29-32 weeks (p = 0.009) than in control infants without hyperglycemia. Growth at 2 years of age was similar, but neurological and behavioural development was more frequently abnormal among those with neonatal hyperglycemia (p = 0.036 and 0.021 respectively).</p> <p>Conclusions</p> <p>Mortality was higher in very preterm infants with hyperglycemia treated with insulin during the neonatal period. At 2 years of age survivors showed normal growth, but a higher incidence of neurological and behavioural problems. Better strategies to manage hyperglycemia may improve outcome of very preterm infants.</p