Publications by authors named "Frank H Bloomfield"

106 Publications

Effect of Bias Gas Flow on Tracheal Cytokine Concentrations in Ventilated Extremely Preterm Infants: A Randomized Controlled Trial.

Neonatology 2021 Apr 7:1-8. Epub 2021 Apr 7.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Background: The objective of this study was to determine whether ventilator bias gas flow affects tracheal aspirate (TA) cytokine concentrations in ventilated extremely preterm infants.

Methods: This is a randomized controlled trial in a tertiary neonatal unit in New Zealand. Preterm infants (<28 weeks' gestation/<1,000 g) requiring intubation in the first 7 days after birth were randomized to bias gas flows of 4 or 10 L/min. Cytokine concentrations in TA and plasma were measured at 24, 72, and 120 h after the onset of ventilation. The primary outcome measure was concentration of interleukin (IL)-8 in TA 24 h after the onset of mechanical ventilation.

Results: Baseline demographics were similar in babies randomized to 4 (n = 50) and 10 (n = 45) L/min bias gas flow. TA IL-8 concentrations were not different between groups. Plasma IL-8 concentrations decreased over time (p < 0.05). Respiratory support and incidence of bronchopulmonary dysplasia at 36 weeks' corrected gestational age were similar between groups. Fewer babies ventilated at 4 L/min developed necrotizing enterocolitis (NEC) ≥ stage 2 (n = 0 vs. n = 5; p = 0.02) and fewer died (n = 1 vs. n = 5, p = 0.06).

Conclusions: Lower bias gas flow in ventilated extremely preterm infants did not alter TA cytokine concentrations but the lower incidence of NEC and mortality warrants further investigation.
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http://dx.doi.org/10.1159/000515364DOI Listing
April 2021

Factors Associated With the Microbiome in Moderate-Late Preterm Babies: A Cohort Study From the DIAMOND Randomized Controlled Trial.

Front Cell Infect Microbiol 2021 1;11:595323. Epub 2021 Mar 1.

Liggins Institute, The University of Auckland, Auckland, New Zealand.

The gut microbiota of preterm infants is affected by perinatal factors and, in turn, may impact upon infant health. In this study, we collected fecal samples at Day-10 (D10) and 4-months corrected-age (4M) from 227 moderate-late preterm (MLPT) babies enrolled in a randomized controlled trial of nutritional management. A total of 320 samples underwent 16S amplicon sequencing, and shotgun metagenomic sequencing was performed on 94 samples from the 4M time point. The microbiome of babies whose families lived in lower socioeconomic status (SES) areas exhibited a significantly higher microbial alpha diversity at D10 (Wilcoxon test = 0.021), greater abundance of (linear model, q = 0.020) at D10 and (q = 0.031) at 4M. Hospital of birth explained 5.2% of the observed variance in 4M samples (PERMANOVA, = 0.038), with more abundant in fecal samples from babies born in Middlemore hospital (linear model, q = 0.016). Maternal antibiotic (Wilcoxon test, = 0.013) and probiotic ( = 0.04) usage within the four-week period before sample collection was associated with a reduction in the alpha diversity of D10 samples. Infant probiotic intake explained 2.1% (PERMANOVA, = 0.021) of the variance in the D10 microbial profile with increased (linear model, q = 1.1 × 10) levels. At 4M, the microbiome of infants who were breastmilk fed had reduced alpha diversity when compared to non-breastmilk fed infants (Wilcoxon test, < 0.05). Although causality cannot be inferred within our study, we conclude that in MLPT babies, maternal socioeconomic factors, as well as the perinatal medical environment and nutrition impact on the development of the newborn microbiome.
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http://dx.doi.org/10.3389/fcimb.2021.595323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958882PMC
March 2021

Maternal and neonatal glycaemic control after antenatal corticosteroid administration in women with diabetes in pregnancy: A retrospective cohort study.

PLoS One 2021 18;16(2):e0246175. Epub 2021 Feb 18.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Objective: To describe maternal and neonatal glycaemic control following antenatal corticosteroid administration to women with diabetes in pregnancy.

Design: Retrospective cohort study.

Setting: A tertiary hospital in Auckland, New Zealand.

Population: Women with diabetes in pregnancy who received antenatal corticosteroids from 2006-2016.

Methods: Corticosteroid administration, maternal and neonatal glycaemia data were retrieved from electronic patient records. Demographic data were downloaded from the hospital database. Relationships between variables were analysed using multivariate analysis.

Main Outcome Measures: Maternal hyperglycaemia and neonatal hypoglycaemia.

Results: Corticosteroids were administered to 647 of 7317 of women with diabetes (8.8%) who gave birth to 715 babies. After an initial course of corticosteroids, 92% and 52% of women had blood glucose concentrations > 7 and > 10 mmol/L respectively. Median peak blood glucose concentration of approximately 10 mmol/L occurred 9 hours after corticosteroid administration and hyperglycaemia lasted approximately 72 hours. Thirty percent of women gave birth within 72 hours of the last dose of corticosteroids. Babies of women who were hyperglycaemic within 24 hours of birth were more likely to develop hypoglycaemia (< 2.6 mmol/L, OR 1.51 [95% CI 1.10-2.07], p = 0.01) and severe hypoglycaemia (≤ 2.0 mmol/L, OR 2.00 [95% CI 1.41-2.85], p < 0.0001) than babies of non-hyperglycaemic mothers. There was no association between maternal glycaemia within 7 days of the last dose of corticosteroids and neonatal hypoglycaemia.

Conclusions: Hyperglycaemia is common in women with diabetes in pregnancy following antenatal corticosteroid administration. Maternal hyperglycaemia in the 24 hours prior to birth is associated with increased risk of neonatal hypoglycaemia. Limitations included the retrospective study design, so that not all data were available for all women and babies and the glucose testing schedule was variable.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246175PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891747PMC
February 2021

Multi-Round compared to Real-Time Delphi for consensus in core outcome set (COS) development: a randomised trial.

Trials 2021 Feb 15;22(1):142. Epub 2021 Feb 15.

Health Research Board - Trials Methodology Research Network (HRB-TMRN), Galway, Ireland.

Background: The Delphi method is used in a wide variety of settings as a method of building consensus on important issues. Traditionally, the Delphi method uses multiple rounds of a survey to allow for feedback of other participants' survey responses in between rounds. By informing participants about how others answer a question or prioritise specific topics, it allows for diverse opinions to inform the consensus process. For this reason, the Delphi method is popular as a consensus building approach in developing core outcome sets (COS), i.e. the minimum agreed set of standardised outcomes that should be measured and reported in studies on a specific health condition. In a COS setting, participants prioritise the importance of outcomes for inclusion in a COS. This usually involves participating in multiple rounds of a survey that can span several weeks or months. Challenges with participant retention have been highlighted in previous COS. We will compare a three-round with a Real-Time Delphi approach on prioritised outcomes. This trial is embedded within the COHESION study which is developing a COS for interventions treating neonatal encephalopathy.

Methods: One hundred and eighty stakeholders (parents/caregivers of infants diagnosed and treated with neonatal encephalopathy, healthcare providers and researchers) will be randomised using stratified randomisation to take part in either the Multi-Round or Real-Time Delphi. Stakeholders will rate the importance of the same set of outcomes in both arms. We will compare the prioritised outcomes at the end of both surveys as well as other parameters such as feedback, initial condition and iteration effects.

Discussion: This trial will provide evidence to inform decisions on the use of Multi-Round compared to Real-Time Delphi survey methods.

Trial Registration: NCT04471103 . Registered on 14 July 2020.
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http://dx.doi.org/10.1186/s13063-021-05074-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885346PMC
February 2021

COHESION: core outcomes in neonatal encephalopathy (protocol).

Trials 2021 Feb 8;22(1):125. Epub 2021 Feb 8.

Health Research Board - Trials Methodology Research Network (HRB-TMRN), Galway, Ireland.

Background: Neonatal encephalopathy is a complex syndrome in infants that predominantly affects the brain and other organs. The leading cause is a lack of oxygen in the blood reaching the brain. Neonatal encephalopathy can result in mortality or complications later in life, including seizures, movement disorders and cerebral palsy. Treatment options for neonatal encephalopathy are limited mainly to therapeutic hypothermia, although other potential treatments are emerging. However, evaluations of the effectiveness of treatments are challenging because of heterogeneity and inconsistency in outcomes measured and reported between trials. In this paper, we detail how we will develop a core outcome set to standardise outcomes measured and reported upon for interventions for the treatment of neonatal encephalopathy.

Methods: We will systematically review the literature to identify outcomes reported previously in randomised trials and systematic reviews of randomised trials. We will identify outcomes important to parents or caregivers of infants diagnosed with and who have received treatment for neonatal encephalopathy. We will do this by conducting in person or by video teleconferencing interviews with parents or caregivers in high-income and low- to middle-income countries. Stakeholders with expertise in neonatal encephalopathy (parents/caregivers, healthcare providers and researchers) will rate the importance of identified outcomes in an online Delphi survey using either a three-round Delphi survey or a "Real-Time" Delphi survey to which stakeholders will be allocated at random. Consensus meetings will take place by video conference to allow for an international group of stakeholder representatives to discuss and vote on the outcomes to include in the final core outcome set (COS).

Discussion: More research is needed on treatments for neonatal encephalopathy. Standardising outcomes measured and reported in evaluations of the effectiveness of interventions for the treatment of neonatal encephalopathy will improve evidence synthesis and improve results reported in systematic reviews and meta-analysis in this area. Overall, this COS will allow for improved treatments to be identified, heterogeneity in research to be reduced, and overall patient care to be enhanced.

Trial Registration: This study is registered in the Core Outcome Measures for Effectiveness (COMET) database http://www.comet-initiative.org/Studies/Details/1270 .
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http://dx.doi.org/10.1186/s13063-021-05030-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871638PMC
February 2021

Olfactory Cues in Infant Feeds: Volatile Profiles of Different Milks Fed to Preterm Infants.

Front Nutr 2020 15;7:603090. Epub 2021 Jan 15.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Smell is determined by odor-active volatile compounds that bind to specific olfactory receptors, allowing us to discriminate different smells. Olfactory stimulation may assist with digestion and metabolism of feeds in the neonate by activation of the cephalic phase response of digestion. Infants' physiological responses to the smell of different milks suggest they can distinguish between breastmilk and infant formula. We aimed to describe the profile of volatile compounds in preterm breastmilk and investigate how this differed from that of other preterm infant feeding options including pasteurized donor breastmilk, breastmilk with bovine milk-based fortifier, human milk-based products and various infant formulas. Forty-seven milk samples (13 different infant formulas and 34 human milk-based samples) were analyzed. Volatile compounds were extracted using Solid Phase Micro Extraction. Identification and relative quantification were carried out by Gas Chromatography with Mass Spectrometry. Principal Component Analysis (PCA) and one-way Analysis of Variance (ANOVA) with Tukey's HSD (parametric data) or Conover's test (non-parametric data) were used as appropriate to explore differences in volatile profiles among milk types. In total, 122 compounds were identified. Breastmilk containing bovine milk-based fortifier presented the highest number of compounds (109) and liquid formula the lowest (70). The profile of volatile compounds varied with 51 compounds significantly different (adjusted < 0.001) among milk types. PCA explained 47% of variability. Compared to preterm breastmilk, the profile of volatile compounds in breastmilk with added bovine milk-based fortifier was marked by presence of fatty acids and their esters, ketones and aldehydes; infant formulas were characterized by alkyls, aldehydes and furans, and human milk-based products presented high concentrations of aromatic hydrocarbons, terpenoids and specific fatty acids. Sensory-active products of fatty acid oxidation are the major contributors to olfactory cues in infant feeds. Analysis of volatile compounds might be useful for monitoring quality of milk and detection of oxidation products and environmental contaminants. Further research is needed to determine whether these different volatile compounds have biological or physiological effects in nutrition of preterm infants.
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http://dx.doi.org/10.3389/fnut.2020.603090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843498PMC
January 2021

Effects of maternal periconceptional undernutrition in sheep on offspring glucose-insulin axis function into adulthood.

J Dev Orig Health Dis 2020 Nov 20:1-7. Epub 2020 Nov 20.

Liggins Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.

Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15-20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7-10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%-58% in fetuses (P = 0.004), but decreased 39%-43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.
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http://dx.doi.org/10.1017/S2040174420001063DOI Listing
November 2020

A Core Outcome Set and minimum reporting set for intervention studies in growth restriction in the NEwbOrN: the COSNEON study.

Pediatr Res 2020 Sep 14. Epub 2020 Sep 14.

Department of Obstetrics and Gynaecology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.

Background: Different interventions and treatments are available for growth-restricted newborns to improve neonatal and long-term outcomes. Lack of outcome standardization across trials of feeding interventions limits pooled analysis of intervention effects. This study aimed to develop a core outcome set (COS) and minimum reporting set (MRS) for this research field.

Methods: A scoping search identified relevant outcomes and baseline characteristics. These outcomes were presented to two stakeholder groups (lay experience and professional experts) in three rounds of online Delphi surveys. The professional experts were involved in the development of the MRS. All items were rated for their importance on a 5-point Likert scale and re-rated in subsequent rounds after presentation of the results at the group level. During a face-to-face consensus meeting the final COS and MRS were determined.

Results: Forty-seven of 53 experts (89%) who completed the first round completed all three survey rounds. After the consensus meeting, consensus was reached on 19 outcomes and 17 baseline characteristics.

Conclusions: A COS and MRS for feeding interventions in the newborn after growth restriction were developed. Use of these sets will promote uniform reporting of study characteristics and improve data synthesis and meta-analysis of multiple studies.

Impact: Both a COS and MRS for growth restriction in the newborn were developed. This study provides the first international combined health-care professional and patient consensus on outcomes and baseline characteristics for intervention and treatment studies in growth-restricted newborns. The use of COS and MRS results in the development of more uniform study protocols, thereby facilitating data synthesis/meta-analysis of multiple studies aiming to optimize treatment and interventions in growth restriction in the newborn.
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http://dx.doi.org/10.1038/s41390-020-01119-5DOI Listing
September 2020

Preterm human milk: associations between perinatal factors and hormone concentrations throughout lactation.

Pediatr Res 2020 Jul 29. Epub 2020 Jul 29.

The Liggins Institute, University of Auckland, Auckland, New Zealand.

Background: Infants born moderate to late preterm constitute the majority of preterm births, yet guidelines for their nutritional care are unclear. Maternal milk is the most appropriate nutrition for these infants; however, its composition can be influenced by environmental factors. The present study therefore investigated perinatal predictors of human milk composition in a preterm cohort.

Methods: Milk was collected during the DIAMOND trial (DIfferent Approaches to Moderate and late preterm Nutrition: Determinants of feed tolerance, body composition and development) from 169 mothers of 191 infants at three time-points (5 and 10 days post partum and 4 months' corrected age). Leptin, adiponectin and insulin-like growth factor-1 (IGF-1) were analysed by enzyme-linked immunosorbent assay. Generalised mixed models were used to evaluate associations between milk composition and maternal/infant/perinatal factors.

Results: Most findings were independent of collection time-point. Gestational diabetes was associated with lower adiponectin. Higher adiponectin and lower leptin were associated with higher socioeconomic status, higher maternal education and ability to fully breastfeed at discharge from hospital. Higher leptin was associated with high perceived stress during hospital admission. Milk IGF-1 displayed sex-specific patterns in association with maternal social deprivation.

Conclusion: Maternal, infant and environmental factors during the perinatal period were associated with milk compositional profiles throughout lactation. Further clinical trials should investigate the impact of such changes in terms of long-term infant outcomes.

Impact: Human milk is the best nutrition for the infant. However, its composition may be susceptible to alterations determined by pathological conditions mother and infant may face throughout pregnancy and in the perinatal period.This study found that perinatal factors are associated with human milk composition from early to late lactation.If human milk composition throughout lactation is "programmed" during pregnancy or early lactation, infants who were exposed in utero to environmental insults may still be exposed to them during lactation. The impact of human milk compositional alteration on infant growth following perinatal pathological events requires further investigation.
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http://dx.doi.org/10.1038/s41390-020-1069-1DOI Listing
July 2020

Effects of Neonatal Hyperglycemia on Retinopathy of Prematurity and Visual Outcomes at 7 Years of Age: A Matched Cohort Study.

J Pediatr 2020 08;223:42-50.e2

Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand; Newborn Services, National Women's Health, Auckland City Hospital, Auckland, New Zealand.

Objective: To determine whether neonatal hyperglycemia is associated with retinopathy of prematurity (ROP), visual outcomes, and ocular growth at 7 years of age.

Study Design: Children born preterm (<30 weeks of gestational age) at a tertiary hospital in Auckland, New Zealand, who developed neonatal hyperglycemia (2 blood glucose concentrations ≥153 mg/dL [8.5 mmol/L] 4 hours apart) were matched with children who were not hyperglycemic (matching criteria: sex, gestational age, birth weight, age, socioeconomic status, and multiple birth) and assessed at 7 years of corrected age. The primary outcome, favorable overall visual outcome (visual acuity ≤0.3 logarithm of the minimum angle of resolution, no strabismus, stereoacuity ≤240 arcsec, not requiring spectacles) was compared between groups using generalized matching criteria-adjusted linear regression models.

Results: Assessments were performed on 57 children with neonatal hyperglycemia (hyperglycemia group) and 54 matched children without hyperglycemia (control group). There were no differences in overall favorable visual outcome (OR 0.95, 95% CI 0.42-2.13, P = .90) or severe ROP incidence (OR 2.20, 95% CI 0.63-7.63, P = .21) between groups. Children with hyperglycemia had poorer binocular distance visual acuity (mean difference 0.08, 95% CI 0.03-0.14 logarithm of the minimum angle of resolution, P < .01), more strabismus (OR 6.22, 95% CI 1.31-29.45, P = .02), and thicker crystalline lens (mean difference 0.14, 95% CI 0.04-0.24 mm, P < .01). Maximum blood glucose concentration was greater in the ROP-treated group compared with the ROP-not treated and no ROP groups after adjusting for sex, gestational age, and birth weight z score (P = .02).

Conclusions: Neonatal hyperglycemia was not associated with overall visual outcomes at 7 years of age. However, there were between-group differences for specific outcome measures relating to interocular lens growth and binocular vision. Further follow-up is required to determine implications on long-term visual outcome.
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http://dx.doi.org/10.1016/j.jpeds.2020.04.059DOI Listing
August 2020

The potential impact of feeding formula-fed infants according to published recommendations.

Pediatr Res 2020 10 7;88(4):526-528. Epub 2020 Jul 7.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pediatric Intermediate Care Unit, 20122, Milan, Italy.

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http://dx.doi.org/10.1038/s41390-020-1056-6DOI Listing
October 2020

Early Use of Antibiotics Is Associated with a Lower Incidence of Necrotizing Enterocolitis in Preterm, Very Low Birth Weight Infants: The NEOMUNE-NeoNutriNet Cohort Study.

J Pediatr 2020 12 14;227:128-134.e2. Epub 2020 Jun 14.

Department of Neonatology, Shenzhen Bao'an Maternal and Child Health Hospital, Shenzhen, China.

Objective: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC).

Study Design: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition.

Results: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001).

Conclusions: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686259PMC
December 2020

The microbial biogeography of the gastrointestinal tract of preterm and term lambs.

Sci Rep 2020 06 4;10(1):9113. Epub 2020 Jun 4.

Liggins Institute, The University of Auckland, Auckland, New Zealand.

Nutritional supplementation is a common clinical intervention to support the growth of preterm infants. There is little information on how nutritional supplementation interacts with the developing microbiome of the small intestine, the major site for nutrient metabolism and absorption. We investigated the effect of preterm birth and nutritional supplementation on the mucosal and luminal microbiota along the gastrointestinal tract (GIT) of preterm lambs. Preterm lambs (n = 24) were enterally supplemented with branched-chain amino acids (BCAAs), carbohydrate (maltodextrin), or water for two weeks from birth. Term lambs (n = 7) received water. Mucosal scrapings and luminal samples were collected from the duodenum, jejunum, ileum (small intestine) and colon at six weeks post-term age and analysed by 16S rRNA amplicon sequencing. Anatomical site explained 54% (q = 0.0004) of the variance and differences between the term and preterm groups explained 5.7% (q = 0.024) of the variance in microbial beta-diversities. The colon was enriched with Tenericutes and Verrucomicrobia compared to the small intestine, while Actinobacteria, and superphylum Patescibacteria were present in higher abundance in the small intestine compared to the colon. Our findings highlight that early-life short-term nutritional supplementation in preterm lambs does not alter the microbial community residing in the small intestine and colon.
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http://dx.doi.org/10.1038/s41598-020-66056-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272652PMC
June 2020

Neonatal Refeeding Syndrome and Clinical Outcome in Extremely Low-Birth-Weight Babies: Secondary Cohort Analysis From the ProVIDe Trial.

JPEN J Parenter Enteral Nutr 2021 01 4;45(1):65-78. Epub 2020 Jul 4.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Background: Refeeding syndrome (RS) following preterm birth has been linked to high intravenous (IV) protein intake in the presence of low electrolyte supply. In extremely low-birth-weight (ELBW) babies, we aimed to determine the incidence of RS and associations with birth characteristics and clinical outcomes.

Method: Prospective cohort study of ELBW ProVIDe Trial participants in 6 New Zealand neonatal intensive care units. RS was defined as serum phosphate < 1.4 mmol.L and total calcium > 2.8 mmol.L . Relationships between RS and other factors were explored using 2-sample tests and logistic regression adjusted for sex, gestation, and birth-weight z-score.

Results: Of 338 babies (mean [SD] birth-weight, 780 (134) g, gestational age, 25.9 [1.7] weeks), 68 (20%) had RS. Mortality was greater in babies with RS (32% vs 11%; P < .0001). More small- than appropriate-for-gestational-age babies developed RS (22% vs 8%; P = .001). Growth from birth to 36 weeks' corrected age was not different between babies who did and did not have RS. In logistic regression, the odds of RS decreased by 70% for each 1 mmol per kg .d IV phosphate intake (odds ratio [OR], 0.3; CI, 0.1-0.6; P = .002) and increased by 80% for each 1 g.kg .d IV protein intake (OR, 1.8; CI, 1.3-2.7; P = .002).

Conclusions: Neonatal RS is common in this cohort of ELBW babies and is associated with increased morbidity and mortality. Optimizing phosphate and calcium intakes in IV nutrition solutions may reduce RS and its consequences.
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http://dx.doi.org/10.1002/jpen.1934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891336PMC
January 2021

Utility of published skinfold thickness equations for prediction of body composition in very young New Zealand children.

Br J Nutr 2020 08 6;124(3):349-360. Epub 2020 Apr 6.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Measurement of body composition is increasingly important in research and clinical settings but is difficult in very young children. Bioelectrical impedance analysis (BIA) and air displacement plethysmography (ADP) are well-established but require specialist equipment so are not always feasible. Our aim was to determine if anthropometry and skinfold thickness measurements can be used as a substitute for BIA or ADP for assessing body composition in very young New Zealand children. We used three multi-ethnic cohorts: 217 children at a mean age of 24·2 months with skinfold and BIA measurements; seventy-nine infants at a mean age of 20·9 weeks and seventy-three infants at a mean age of 16·2 weeks, both with skinfold and ADP measurements. We used Bland-Altman plots to compare fat and fat-free mass calculated using all potentially relevant equations with measurements using BIA or ADP. We also calculated the proportion of children in the same tertile for measured fat or fat-free mass and tertiles (i) calculated using each equation, (ii) each absolute skinfold, and (iii) sum of skinfold thicknesses. We found that even for the best equation for each cohort, the 95 % limits of agreement with standard measures were wide (25-200 % of the mean) and the proportion of children whose standard measures fell in the same tertile as the skinfold estimates was ≤69 %. We conclude that none of the available published skinfold thickness equations provides good prediction of body composition in multi-ethnic cohorts of very young New Zealand children with different birth history and growth patterns.
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http://dx.doi.org/10.1017/S0007114520001221DOI Listing
August 2020

Relationships between Neonatal Nutrition and Growth to 36 Weeks' Corrected Age in ELBW Babies-Secondary Cohort Analysis from the Provide Trial.

Nutrients 2020 Mar 13;12(3). Epub 2020 Mar 13.

Liggins Institute, University of Auckland, 1142 Auckland, New Zealand.

A key modifiable factor for improving neurodevelopment in extremely low birthweight (ELBW) babies may be improving growth, especially head growth, by optimising nutrition in the early neonatal period. We aimed to investigate relationships between nutrient intakes in the 4 weeks after birth, and growth from birth to 36 weeks' corrected age (CA) in ELBW babies. We undertook a prospective cohort study of 434 participants enrolled in a randomised controlled trial (ProVIDe) in eight New Zealand and Australian neonatal intensive care units. Macronutrient intakes from birth to 4 weeks and weight, length and head circumference measurements from birth to 36 weeks' CA were collected. From birth to 36 weeks' CA, the median (IQR) z-score changes were: weight -0.48 (-1.09, 0.05); length -1.16 (-1.86, -0.43), and head circumference -0.82 (-1.51, -0.19). Changes in z-score to 4 weeks and 36 weeks' CA were correlated with protein intake. Each 1 g·Kg·d total protein intake in week 2 was associated with 0.26 z-score increase in head circumference at 36 weeks' CA. Both nutritional intake and change in z-scores to 36 weeks' CA differed widely amongst sites. Correlations between nutrition and growth, and differences in these amongst sites, indicate there may be potential to improve growth with enhanced nutrition practices.
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http://dx.doi.org/10.3390/nu12030760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146349PMC
March 2020

Patterns of antenatal corticosteroid administration in a cohort of women with diabetes in pregnancy.

PLoS One 2020 27;15(2):e0229014. Epub 2020 Feb 27.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Antenatal corticosteroids administered to the mother prior to birth decrease the risk of mortality and major morbidity in infants born at less than 35 weeks' gestation. However, the evidence relating to women with diabetes in pregnancy is limited. Clinical guidelines for antenatal corticosteroid administration recommend that women with diabetes in pregnancy are treated in the same way as women without diabetes, but there are no recent descriptions of whether contemporary practice complies with this guidance. This study is a retrospective review of antenatal corticosteroid administration at a New Zealand tertiary hospital in women with diabetes in pregnancy. We found that in this cohort, for both an initial course at less than 35 weeks' gestation and repeat courses at less than 33 weeks', the administration of antenatal corticosteroid to women with diabetes in pregnancy is largely consistent with current Australian and New Zealand recommendations. However, almost 25% of women received their last dose of antenatal corticosteroid at or beyond the latest recommended gestation of 35 weeks' gestation. Pre-existing diabetes and planned caesarean section were independently associated with an increased rate of antenatal corticosteroid administration. We conclude that diabetes in pregnancy does not appear to be a deterrent to antenatal corticosteroid administration. The high rates of administration at gestations beyond recommendations, despite the lack of evidence of benefit in this group of women, highlights the need for further research into the risks and benefits of antenatal corticosteroid administration to women with diabetes in pregnancy, particularly in the late preterm and early term periods.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229014PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046227PMC
May 2020

Growth and Clinical Outcome in Very Low-Birth-Weight Infants After the Introduction of a Multicomponent Intravenous Lipid Emulsion.

JPEN J Parenter Enteral Nutr 2020 09 28;44(7):1318-1327. Epub 2020 Jan 28.

Liggins Institute, The University of Auckland, Auckland, New Zealand.

Background: Very low-birth-weight (VLBW; birth weight < 1500 g) infants are often dependent on intravenous nutrition after birth. Conventional soy-based intravenous lipid emulsions (Soy LE) are associated with inflammatory and metabolic complications that may be harmful to preterm infants. Evidence to support any clinical benefit associated with newer multicomponent emulsions (Mixed LE), remains inconsistent and unsubstantiated in appropriate studies. This retrospective study aimed to determine whether growth and clinical outcomes differed between VLBW infants given Mixed LE vs Soy LE at Auckland City Hospital.

Methods: Data were collected on nutrition, growth, and neonatal morbidities for the first 4 weeks after birth. Outcomes were compared between 2 lipid cohorts, Soy LE (February 2013 - August 2014) and Mixed LE (August 2014 - December 2015), using univariate and multivariate analysis.

Results: 207 infants (Soy LE, 105 vs Mixed LE, 102) were included in the study. Significantly fewer infants in the Mixed LE cohort developed any stage retinopathy of prematurity (Soy LE 59% vs Mixed LE 39%, P = .005) or intraventricular hemorrhage (Soy LE 27% vs Mixed LE 15%, P = .03) during their admission. Mixed LE was also associated with significantly lower mean (P = .01), minimum (P = .03), and maximum (P = .04) total bilirubin concentrations across the first 4 weeks after birth. There was no difference in growth velocity or weight, length, and head circumference z-score change.

Conclusion: SMOFlipid may represent a favorable alternative to conventional lipid emulsions in neonatal parenteral nutrition regimens; however, long-term effects should be further evaluated.
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http://dx.doi.org/10.1002/jpen.1750DOI Listing
September 2020

Dietary Patterns and Dietary Adaptations in Women with and without Gestational Diabetes: Evidence from the Growing Up in New Zealand Study.

Nutrients 2020 Jan 15;12(1). Epub 2020 Jan 15.

The Liggins Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

Diet is a cornerstone of the management of gestational diabetes (GDM). We investigated differences in dietary patterns and dietary adaptations among pregnant women with and without GDM participating in the Growing Up in New Zealand study. Presence of GDM was determined using coded clinical data and plasma glucose results meeting the New Zealand Society for the Study of Diabetes diagnostic criteria. Women answered a food frequency questionnaire and questions regarding dietary changes and information received during pregnancy. Women with GDM had lower adherence scores than those without GDM for 'Junk' (mean (SD) score -0.28 (0.95) versus 0.02 (1.01) < 0.0005) and 'Traditional/White bread' dietary patterns (-0.18 (0.93) versus 0.01 (1.01) = 0.002). More women with GDM reported avoiding foods high in fat or sugar (25.3% versus 5.7%, < 0.05) compared to women without GDM. A greater proportion of women with GDM compared with those without GDM received information from dietitians or nutritionists (27.0% versus 1.7%, < 0.05) or obstetricians (12.6% versus 7.5%, < 0.05). More women diagnosed before the antenatal interview received advice from dietitians or nutritionists compared with those diagnosed after (46.9% versus 6.0%, < 0.05). Women with GDM appear to make positive changes to their diet in response to advice received from health care professionals.
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http://dx.doi.org/10.3390/nu12010227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019595PMC
January 2020

introduce nationwide pulse oximetry screening for the detection of critical congenital heart disease and other hypoxaemic conditions in the newborn.

N Z Med J 2020 01 17;133(1508):111-117. Epub 2020 Jan 17.

Professor of Neonatology, Liggins Institute, University of Auckland.

The mortality risk for infants with critical congenital heart disease (CCHD) unrecognised at the time of birth is high. Pulse oximetry has been utilised as a screening tool for the detection of these anomalies in the newborn as the majority will have a degree of hypoxaemia. This screening strategy has a moderate sensitivity and excellent specificity for the detection of CCHD, and a low false-positive rate. Respiratory and infective diseases are responsible for a large number of positive test results. The early recognition of these diseases can also improve health outcomes. Different approaches have been taken to introduce screening, ranging from hospital-led initiatives to mandatory state-wide policies. A study conducted in New Zealand demonstrated that sector-led screening initiatives are unlikely to result in equitable outcomes. In this midwifery-led maternity setting a nationwide pulse oximetry screening programme with adequate human and material resources should be introduced.
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January 2020

Effects of preterm birth induced with or without exogenous glucocorticoids on the ovine glucose-insulin axis.

J Dev Orig Health Dis 2021 Feb 15;12(1):58-70. Epub 2020 Jan 15.

College of Health and Medicine, ANU Medical School, The Australian National University, Canberra, ACT 2601, Australia.

Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11-14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12-13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml-1·kg-1·min-1·ng-1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%-71% in NG-Prem vs. G-Prem and 42%-80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.
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http://dx.doi.org/10.1017/S2040174419000916DOI Listing
February 2021

Plasma ammonia concentrations in extremely low birthweight infants in the first week after birth: secondary analysis from the ProVIDe randomized clinical trial.

Pediatr Res 2020 08 2;88(2):250-256. Epub 2020 Jan 2.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Background: Little is known about normative ammonia concentrations in extremely low birthweight (ELBW) babies and whether these vary with birth characteristics. We aimed to determine ammonia concentrations in ELBW babies in the first week after birth and relationships with neonatal characteristics and protein intake.

Methods: Arterial blood samples for the measurement of plasma ammonia concentration were collected within 7 days of birth from ProVIDe trial participants in six New Zealand neonatal intensive care units.

Results: Three hundred and twenty-two babies were included. Median (range) gestational age was 25.7 (22.7-31.6) weeks. Median (interquartile range (IQR)) ammonia concentration was 102 (80-131) µg/dL. There were no statistically significant associations between ammonia concentrations and birthweight or sex. Ammonia concentrations were weakly correlated with mean total (Spearman's r = 0.11, P = 0.047) and intravenous (r = 0.13, P = 0.02) protein intake from birth, gestational age at birth (r = -0.13, P = 0.02) and postnatal age (r = -0.13, P = 0.02).

Conclusions: Plasma ammonia concentrations in ELBW babies are similar to those of larger and more mature babies and only weakly correlated with protein intake. Currently, recommended thresholds for investigation of hyperammonaemia are appropriate for ELBW babies. Protein intake should not be limited by concerns about potential hyperammonaemia.
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http://dx.doi.org/10.1038/s41390-019-0730-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384986PMC
August 2020

Sex-specific relationships between early nutrition and neurodevelopment in preterm infants.

Pediatr Res 2020 04 29;87(5):872-878. Epub 2019 Nov 29.

Newborn Services, Starship Hospital, Auckland District Health Board, Auckland, New Zealand.

Background: Although early nutrition is associated with neurodevelopmental outcome at 2 years' corrected age in children born very preterm, it is not clear if these associations are different in girls and boys.

Methods: Retrospective cohort study of infants born <30 weeks' gestational age or <1500 g birth weight in Auckland, NZ. Macronutrient, energy and fluid volumes per kg per day were calculated from daily nutritional intakes and averaged over days 1-7 (week 1) and 1-28 (month 1). Primary outcome was survival without neurodevelopmental impairment at 2 years corrected age.

Results: More girls (215/478) survived without neurodevelopmental impairment at 2 years (82% vs. 72%, P = 0.02). Overall, survival without neurodevelopmental impairment was positively associated with more energy, fat, and enteral feeds in week 1, and more energy and enteral feeds in month 1 (P = 0.005-0.03), but all with sex interactions (P = 0.008-0.02). In girls but not boys, survival without neurodevelopmental impairment was positively associated with week 1 total intakes of fat (OR(95% CI) for highest vs. lowest intake quartile 62.6(6.6-1618.1), P < 0.001), energy (22.9(2.6-542.0), P = 0.03) and enteral feeds (1.9 × 10(9.5-not estimable), P < 0.001).

Conclusions: Higher early fat and enteral feed intakes are associated with improved outcome in girls, but not boys. Future research should determine sex-specific neonatal nutritional requirements.
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http://dx.doi.org/10.1038/s41390-019-0695-yDOI Listing
April 2020

Macronutrient Supplements in Preterm and Small-for-Gestational-Age Animals: A Systematic Review and Meta-analysis.

Sci Rep 2019 10 11;9(1):14715. Epub 2019 Oct 11.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Early macronutrient supplementation in preterm and/or small-for-gestational-age (SGA) infants may improve growth but have detrimental effects on later cardio-metabolic health which may be sex-specific. We systematically reviewed the long-term effects of early macronutrient supplementation in preterm and SGA animals and whether these differ by sex. Using Cochrane Neonatal and SYRCLE methodologies we included random or quasi-random studies that allocated non-human mammals to macronutrient supplements or no supplements between birth and weaning and assessed post-weaning outcomes. We used random-effects models to calculate standardized mean differences (SMD) with 95% confidence intervals (CIs). Six studies provided low to very-low-quality evidence that macronutrient supplementation increased weight in juvenile rats (SMD; 95% CI: 2.13; 1.00, 3.25; 1 study, n = 24), increased leptin concentrations in older adults (1.31; 0.12, 2.51; 1 study, n = 14 male rats), but decreased leptin concentrations in young adults (-1.13; -2.21, -0.05; 1 study, n = 16 female rats) and improved spatial learning and memory (qualitative data; 1 study). There was no evidence of sex-specific effects and no overall effect on length, serum lipids, body composition, HOMA-IR, or blood pressure. Macronutrient supplements may affect later growth, metabolism, and neurodevelopment of preterm and SGA animals, but evidence is limited and low quality.
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http://dx.doi.org/10.1038/s41598-019-51295-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789152PMC
October 2019

Prevalence of gestational diabetes according to commonly used data sources: an observational study.

BMC Pregnancy Childbirth 2019 Oct 11;19(1):349. Epub 2019 Oct 11.

The Liggins Institute, University of Auckland, Building 505, Level 2, 85 Park Road, Auckland, 1023, New Zealand.

Background: It is well recognized that prevalence of gestational diabetes mellitus (GDM) varies depending on the population studied and the diagnostic criteria used. The data source used also can lead to substantial differences in the reporting of GDM prevalence but is considered less frequently. Accurate estimation of GDM prevalence is important for service planning and evaluation, policy development, and research. We aimed to determine the prevalence of GDM in a cohort of New Zealand women using a variety of data sources and to evaluate the agreement between different data sources.

Methods: A retrospective analysis of prospectively collected data from the Growing Up in New Zealand Study, consisting of a cohort of 6822 pregnant women residing in a geographical area defined by three regional health boards in New Zealand. Prevalence of GDM was estimated using four commonly used data sources. Coded clinical data on diabetes status were collected from regional health boards and the Ministry of Health's National Minimum Dataset, plasma glucose results were collected from laboratories servicing the recruitment catchment area and coded according to the New Zealand Society for the Study of Diabetes diagnostic criteria, and self-reported diabetes status collected via interview administered questionnaires. Agreement between data sources was calculated using the proportion of agreement with 95% confidence intervals for both a positive and negative diagnosis of GDM.

Results: Prevalence of GDM combining data from all sources in the Growing Up in New Zealand cohort was 6.2%. Estimates varied from 3.8 to 6.9% depending on the data source. The proportion of agreement between data sources for presence of GDM was 0.70 (95% CI 0.65, 0.75). A third of women who had a diagnosis of GDM according to medical data reported having no diabetes in interview administered questionnaires.

Conclusion: Prevalence of GDM varies considerably depending on the data source used. Health services need to be aware of this and to understand the limitations of local data sources to ensure service planning and evaluation, policy development and research are appropriate for the local prevalence. Improved communication of the diagnosis may assist women's self-management of GDM.
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http://dx.doi.org/10.1186/s12884-019-2521-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788112PMC
October 2019

Feasibility of Standardized Human Milk Collection in Neonatal Care Units.

Sci Rep 2019 10 4;9(1):14343. Epub 2019 Oct 4.

The Liggins Institute, The University of Auckland, Auckland, New Zealand.

Research in human lactation is a growing field. However, difficulties in studying human milk originate from the dynamicity of its composition. Using standardized collection protocols is mandatory to minimize variation and warrant comparability of findings across different studies. Yet, information on the feasibility of collecting human milk with standardized procedures, especially in neonatal units, are lacking. The present study aims to report on the feasibility and difficulties to collect human milk according to a standardized protocol, during early lactation from women who gave birth to preterm infants. Human milk was collected from 129 mothers of moderate- to late-preterm infants according to two variations of a standard protocol which differed for number of collection time-points. Collection rates and adherence to the sampling protocol were evaluated together with reason for missed collection. Collection of ≥1 sample was successful for 80% of the mothers. However adherence to the standard protocol was overall low (36% and 27%). Collection rates were different between the two protocol variations (73% against 92%, p ≤ 0.001). Amongst the reason for missed collection, low milk supply was the most recurrent (40%). Our findings show that while collecting human milk in neonatal units is achievable, obtaining standard and comparable samples results challenging.
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http://dx.doi.org/10.1038/s41598-019-50560-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778269PMC
October 2019

The Influence of Early Nutrition on Brain Growth and Neurodevelopment in Extremely Preterm Babies: A Narrative Review.

Nutrients 2019 Aug 30;11(9). Epub 2019 Aug 30.

Starship Child Health, Auckland City Hospital, Auckland 1023, New Zealand.

Extremely preterm babies are at increased risk of less than optimal neurodevelopment compared with their term-born counterparts. Optimising nutrition is a promising avenue to mitigate the adverse neurodevelopmental consequences of preterm birth. In this narrative review, we summarize current knowledge on how nutrition, and in particular, protein intake, affects neurodevelopment in extremely preterm babies. Observational studies consistently report that higher intravenous and enteral protein intakes are associated with improved growth and possibly neurodevelopment, but differences in methodologies and combinations of intravenous and enteral nutrition strategies make it difficult to determine the effects of each intervention. Unfortunately, there are few randomized controlled trials of nutrition in this population conducted to determine neurodevelopmental outcomes. Substantial variation in reporting of trials, both of nutritional intakes and of outcomes, limits conclusions from meta-analyses. Future studies to determine the effects of nutritional intakes in extremely preterm babies need to be adequately powered to assess neurodevelopmental outcomes separately in boys and girls, and designed to address the many potential confounders which may have clouded research findings to date. The development of minimal reporting sets and core outcome sets for nutrition research will aid future meta-analyses.
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http://dx.doi.org/10.3390/nu11092029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770288PMC
August 2019

Relationships Between Early Neonatal Nutrition and Neurodevelopment at School Age in Children Born Very Preterm.

J Pediatr Gastroenterol Nutr 2020 01;70(1):72-78

Liggins Institute.

Objectives: The aim of this study was to determine whether a new nutrition protocol designed to increase early protein intakes while reducing fluid volume in infants born very preterm was associated with altered neurodevelopment and growth in childhood.

Methods: A retrospective, observational cohort study of children born <30 weeks' gestation or <1500 g and admitted to the neonatal unit, National Women's Hospital, Auckland, New Zealand, before and after a change in nutrition protocol. The primary outcome was neurodevelopmental impairment at 7 years (any of Wechsler Intelligence Scale for Children full scale IQ < 85, Movement Assessment Battery for Children-2 total score ≤5th centile, cerebral palsy, blind, or deaf requiring aids). Outcomes were compared between groups and for the overall cohort using generalized linear regression, adjusted for sex and birth weight z score.

Results: Of 201 eligible children, 128 (64%) were assessed (55/89 [62%] exposed to the old nutrition protocol, 73 of 112 [65%] to the new protocol). Children who experienced the new protocol received more protein, less energy, and less carbohydrate in postnatal days 1 to 7. Neurodevelopmental impairment was similar at 7 years (30/73 [41%] vs 25/55 [45%], adjusted odds ratio [AOR] [95% confidence interval] 0.78 [0.35-1.70], P = 0.55), as was the incidence of cerebral palsy (AOR 7.36 [0.88-61.40], P = 0.07). Growth and body composition were also similar between groups. An extra 1 g/kg parenteral protein intake in postnatal days 1 to 7 was associated with a 27% increased odds of cerebral palsy (AOR 1.27 [1.03-1.57], P = 0.006).

Conclusions: Higher early protein intakes do not change overall rates of neurodevelopmental impairment or growth at 7 years. Further research is needed to determine the effects of higher early parenteral protein intake on motor development.
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http://dx.doi.org/10.1097/MPG.0000000000002471DOI Listing
January 2020

Feasibility study assessing equitable delivery of newborn pulse oximetry screening in New Zealand's midwifery-led maternity setting.

BMJ Open 2019 08 18;9(8):e030506. Epub 2019 Aug 18.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Objectives: The aim of this study was to conduct New Zealand-specific research to inform the design of a pulse oximetry screening strategy that ensures equity of access for the New Zealand maternity population. Equity is an important consideration as the test has the potential to benefit some populations and socioeconomic groups more than others.

Setting: New Zealand has an ethnically diverse population and a midwifery-led maternity service. One quaternary hospital and urban primary birthing unit (Region A), two regional hospitals (Region B) and three regional primary birthing units (Region C) from three Health Boards in New Zealand's North Island participated in a feasibility study of pulse oximetry screening. Home births in these regions were also included.

Participants: There were 27 172 infants that satisfied the inclusion criteria; 16 644 (61%) were screened. The following data were collected for all well newborn infants with a gestation age ≥35 weeks: date of birth, ethnicity, type of maternity care provider, deprivation index and screening status (yes/no). The study was conducted over a 2-year period from May 2016 to April 2018.

Results: Screening rates improved over time. Infants born in Region B (adjusted OR=0.75; 95% CI 0.67 to 0.83) and C (adjusted OR=0.29; 95% CI 0.27 to 0.32) were less likely to receive screening compared with those born in Region A. There were significant associations between screening rates and deprivation, ethnicity and maternity care provider. Lack of human and material resources prohibited universal access to screening.

Conclusion: A pulse oximetry screening programme that is sector-led is likely to perpetuate inequity. Screening programmes need to be designed so that resources are distributed in the way most likely to optimise health outcomes for infants born with cardiac anomalies.

Ethics Approval: This study was approved by the Health and Disability Ethics Committees of New Zealand (15/NTA/168).
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http://dx.doi.org/10.1136/bmjopen-2019-030506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701602PMC
August 2019

Newborn pulse oximetry screening in the context of a high antenatal detection rate of critical congenital heart disease.

Acta Paediatr 2020 01 2;109(1):93-99. Epub 2019 Sep 2.

Paediatric and Congenital Cardiac Services, Starship Children's Hospital, Auckland, New Zealand.

Aim: Assess the potential additional benefit from pulse oximetry screening in the early detection of critical congenital heart disease in a country with a well-developed antenatal ultrasound screening programme.

Methods: Live-born infants, pregnancy terminations and stillbirths from 20 weeks' gestational age, between 2013 and 2015, with critical cardiac defects defined as primary or secondary targets of pulse oximetry screening were identified. Critical defects were those resulting in the death of a fetus or an infant in the first 28 days after birth, or a defect requiring intervention in the first 28 days.

Results: Two hundred and sixty-eight infants and Fetuses were identified. Antenatal detection rates improved from 69% to 77% over the study period. An associated co-morbidity improved antenatal detection rates. Twenty-seven live-born infants were diagnosed after discharge: 15 aortic arch obstruction (AAO); 10 d-loop transposition of the great arteries (d-TGA), and two total anomalous pulmonary venous drainage (TAPVD). Of these, five with AAO, nine with d-TGA and likely both with TAPVD could potentially have been detected with oximetry screening.

Conclusion: The antenatal detection of critical cardiac anomalies continues to improve in New Zealand. Despite high antenatal detection rates for most lesions, universal postnatal oximetry screening has the potential to improve early detection.
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http://dx.doi.org/10.1111/apa.14946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972642PMC
January 2020