Preterm-born individuals: a vulnerable population at risk of cardiovascular morbidity and mortality during thermal extremes?

NEW FINDINGS: What is the topic of this review? Thermal extremes disproportionately affect populations with cardiovascular conditions. Preterm birth, across all gestational age ranges below 37 weeks, has been identified as a non-modifiable risk factor for cardiovascular disease. The hypothesis is presented that individuals born preterm are at an increased risk of cardiovascular morbidity and mortality during thermal extremes. What advances does it highlight? Cardiovascular stress tests performed in preterm-born populations, from infancy through adulthood, highlight a progression of cardiovascular dysfunction accelerating through adolescence and adulthood. This dysfunction has many similarities with populations known to be at risk in thermal extremes. ABSTRACT: Preterm-born individuals are a uniquely vulnerable population. Preterm exposure to the extrauterine environment and the (mal)adaptations that occur during the transitional period can result in alterations to their macro- and micro-physiological state. The physiological adaptations that increase survival in the short term may place those born preterm on a trajectory of lifelong dysfunction and later-life decompensation. Cardiovascular compensation in children and adolescents, which masks this trajectory of dysfunction, is overcome under stress, such that the functional cardiovascular capacity is reduced and recovery impaired following physiological stress. This has implications for their response to thermal stress. As the Anthropocene introduces greater changes in our environment, thermal extremes will impact vulnerable populations as yet unidentified in the climate change context. Here, we present the hypothesis that individuals born preterm are a vulnerable population at an increased risk of cardiovascular morbidity and mortality during thermal extremes.

Low dose or very low dose phenylephrine and cyclopentolate microdrops for retinopathy of prematurity eye examinations (The Little Eye Drop Study): a randomised controlled non-inferiority trial.

OBJECTIVE: To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 µL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE). DESIGN: Multicentre, prospective, randomised controlled, non-inferiority clinical trial. SETTING: Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021. PATIENTS: Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE. INTERVENTIONS: The intervention: microdrop (approximately 7 µL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered. MAIN OUTCOME MEASURES: The primary outcome measure was an ophthalmologist-determined successful ROPEE. RESULTS: One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction -0.05 to 0.05) and for Maori (95% CI no continuity correction -0.02 to 0.19). CONCLUSION: VLD microdrops enable safe and effective screening for ROPEE in both Maori and non-Maori preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12619000795190.

Maternal Fructose Intake, Programmed Mitochondrial Function and Predisposition to Adult Disease.

Fructose consumption is now recognised as a major risk factor in the development of metabolic diseases, such as hyperlipidaemia, diabetes, non-alcoholic fatty liver disease and obesity. In addition to environmental, social, and genetic factors, an unfavourable intrauterine environment is now also recognised as an important factor in the progression of, or susceptibility to, metabolic disease during adulthood. Developmental trajectory in the short term, in response to nutrient restriction or excessive nutrient availability, may promote adaptation that serves to maintain organ functionality necessary for immediate survival and foetal development. Consequently, this may lead to decreased function of organ systems when presented with an unfavourable neonatal, adolescent and/or adult nutritional environment. These early events may exacerbate susceptibility to later-life disease since sub-optimal maternal nutrition increases the risk of non-communicable diseases (NCDs) in future generations. Earlier dietary interventions, implemented in pregnant mothers or those considering pregnancy, may have added benefit. Although, the mechanisms by which maternal diets high in fructose and the vertical transmission of maternal metabolic phenotype may lead to the predisposition to adult disease are poorly understood. In this review, we will discuss the potential contribution of excessive fructose intake during pregnancy and how this may lead to developmental reprogramming of mitochondrial function and predisposition to metabolic disease in offspring.

Acute liver failure secondary to therapeutic paracetamol dosing in an extremely preterm neonate.

We report the first case of standard therapeutic dose paracetamol for patent ductus arteriosus closure causing acute liver failure in an extremely preterm infant. After 5 days of treatment, he presented with jaundice, acute severe hepatitis and coagulopathy. Treatment with N-acetyl cysteine resulted in full recovery.

Palliative care in a tertiary neonatal intensive care unit: a 10-year review.

OBJECTIVES: When active treatment is no longer in the best interests of the patient, redirection of care to palliation is an important transition. We review, within a tertiary neonatal intensive care unit (NICU), the journey leading to the decision to redirect care, the means of symptom control and the provision of psychosocial supports. METHODS: A retrospective review of all 166 deaths of NICU-affiliated patients during a 10- year epoch. Medical notes were reviewed, and the provision and type of, or barriers to, effective palliative care was defined. RESULTS: Extreme prematurity accounted for 71/145 (49%) of deaths with relatively high proportions of Maori 17/71 (25%) and Pacific Islanders 9/71 (13%). Almost all eligible infants received some form of palliation. Transition from curative to palliative care was refused by the family in a single case. Median time from decision to redirect care until first recorded action was 80 min, and median time from action until death was 60 min. The majority of infants received some form of comfort cares, (128/166) most commonly morphine (94/128, 73%). Three infants had documented seizure activity or respiratory distress but did not receive any pharmacological intervention. Psychosocial supports were offered in 98/145 (67%) of cases, but only 71/145 (49%) of families were formally offered an opportunity to discuss the infant's clinical course after their death. CONCLUSIONS: Clinical documentation of care plans was often incomplete, potentially leading to inconsistent delivery of care, increased risk of symptom breakthrough and/or inadequate psychosocial supports for family. Formal individualised palliative care plans are under development to standardise documentation and improve therapeutic and psychosocial interventions available to the infant and their family.

Fructose Consumption During Pregnancy Influences Milk Lipid Composition and Offspring Lipid Profiles in Guinea Pigs.

Excess dietary fructose is a major public health concern (1-4). Evidence shows increased fructose intake can cause insulin resistance, hepatic de novo lipogenesis, hypertriglyceridemia, obesity and non-alcoholic fatty liver disease (NAFLD) (5-9). However, little is known about the effects of fructose during pregnancy and its influence on offspring development and predisposition to later-life disease. To determine whether moderately increased maternal fructose intake could have health consequences on offspring, we have investigated the effects of 10% w/v fructose water intake during preconception and pregnancy. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD;10% kcal from fructose) ad-libitum 60 days prior to mating and throughout gestation. Offspring were culled at weaning, day 21 (d21). Compared to CD dams, FD dams had altered glucose metabolism and increased milk free fatty acid content. Matsuda-DeFronzo insulin sensitivity index (M-ISI) from OGTT plasma showed no significant difference in whole-body insulin sensitivity between FD and CD dams 60 days post-dietary intervention and during midgestation. Fetal exposure to increased maternal fructose resulted in offspring with significantly altered serum free fatty acids at days 0, 7, 14, and 21 [including pentadecanoic acid (15:0), dma16:0, margaric acid (17:0) palmitoleic acid, total omega-7 and total saturates], increased levels of uric acid and triglycerides were also observed at d21. We have demonstrated that increased fructose intake during pregnancy can cause significant changes in maternal metabolic function and milk composition, which alters offspring metabolism. Taken together, these changes in pregnancy outcomes and feto-maternal condition may underlie their offspring's predisposition to metabolic dysfunction during later-life.

Outcomes of 23- and 24-weeks gestation infants in Wellington, New Zealand: A single centre experience.

Optimal perinatal care of infants born less than 24 weeks gestation remains contentious due to uncertainty about the long-term neurodevelopment of resuscitated infants. Our aim was to determine the short-term mortality and major morbidity outcomes from a cohort of inborn infants born at 23 and 24 weeks gestation and to assess if these parameters differed significantly between infants born at 23 vs. 24 weeks gestation. We report survival rates at 2-year follow-up of 22/38 (58%) at 23 weeks gestation and 36/60 (60%) at 24 weeks gestation. Neuroanatomical injury at the time of discharge (IVH ≥ Grade 3 and/or PVL) occurred in in 3/23 (13%) and 1/40 (3%) of surviving 23 and 24 weeks gestation infants respectively. Rates of disability at 2 years corrected postnatal age were not different between infants born at 23 and 24 weeks gestation. We show evidence that with maximal perinatal care in a tertiary setting it is possible to achieve comparable rates of survival free of significant neuroanatomical injury or severe disability at age 2 in infants born at 23-week and 24-weeks gestation.

Ectopia cordis: a novel palliative care technique.

Complete ectopia cordis in the newborn represents a significant management challenge. There are minimal data available to inform optimal clinical care for those infants with coexisting complex congenital heart disease who are therefore not candidates for surgical intervention. The exteriorisation of the heart and absence of the pericardial sac requires meticulous wound care to prevent desiccation of the myocardium and to minimise infection risk. Additionally, the technique selected must address the risk of occlusion of the cardiac vascular pedicle and abrasion between the mobile myocardium and dressing surface. We report a novel approach to wound management and integrated palliative care that enabled community-based care. Our patient, a full-term male infant with complete ectopia cordis was born in good condition by assisted vaginal delivery. He was discharged from hospital on day 8 and was cared for in the community until his demise from cardiac failure on day 15.

Shwachman-Diamond syndrome (SDS) in a preterm neonate.

A preterm neonate at 29-week gestational age was born with intrauterine growth restriction, severe pancytopaenia and gross skeletal dysplasia. Antenatal screening bloods, TORCH/parvovirus tests and karyotype were unremarkable. Postnatally, he had normal microarray comparative genomic hybridization and serum B12/folate levels, and human immunodeficiency virus and cytomegalovirus polymerase chain reaction and antoimmune screening were negative. Targeted gene testing for Shwachman-Diamond syndrome (SDS) revealed the pathognomic mutation (c.183_184delTAinsCT). His postnatal clinical course was complicated by: (i) Ventilator dependency because of a combination of a pathologically compliant chest wall and preterm-associated chronic lung disease. (ii) Progressive bone marrow failure, resulting in transfusion dependence and profound neutropenia associated with recurrent sepsis. (iii) Gastrointestinal failure and TPN dependency. (iv) Poor postnatal growth with weight/length/head circumference all <3rd centile. (v) Prognostication was complicated by the lack of published literature on the presentation of SDS in a preterm infant. However, because of inexorable progression of multiorgan failure, intensive care was withdrawn on day 54 of life. SDS is a rare autosomal recessive disorder characterised by haematological abnormalities, skeletal dysplasia and exocrine pancreatic dysfunction. Neonatal presentation is thought to be extremely rare. However, with the availability of genetic testing, it has now become clear that because of overlap in clinical presentation, term-born infants with skeletal dysplasia and severe respiratory distress may initially be misdiagnosed as asphyxiating thoracic dystrophy. This case report highlights the complexities of preterm birth complicating clinical manifestations of SDS.