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The New Zealand 1986 very low birth weight cohort as young adults: mapping the road ahead



Very low birth weight (less than 1500 g) is associated with increased morbidity and costs of health care in childhood. Emerging evidence suggests these infants face a range of health and social problems as young adults. We studied all New Zealand very low birth weight infants born in 1986 (when 58 % were exposed to antenatal corticosteroids) in infancy, with later follow-up at 7 to 8 years and 23 to 24 years. We now aim to assess the cohort at 26–28 years compared with controls.


The case sample will comprise a minimum of 250 members of the 1986 New Zealand national very low birth weight cohort (77 % of survivors). Outcomes will be compared with a control group of 100 young adults born at term in 1986. Following written informed consent, participants will travel to Christchurch for 2 days of assessments undertaken by experienced staff. Medical assessments include growth measures, vision, respiratory function, blood pressure and echocardiogram, renal function, dental examination and blood tests. Cognitive and neuropsychological functioning will be assessed with standard tests, and mental health and social functioning by participant interview. A telephone interview will be conducted with a parent or significant other person nominated by the respondent to gain a further perspective on the young person’s health and functioning. All those born at less than 28 weeks’ gestation, plus a random subset of the cohort to a total of 150 cases and 50 controls, will be offered cranial magnetic-resonance imaging. Statistical analysis will examine comparison with controls and long-term trajectories for the very low birth weight cohort.


The research will provide crucial New Zealand data on the young adult outcomes for very low birth weight infants and address gaps in the international literature, particularly regarding cardiovascular, respiratory, visual and neurocognitive outcomes. These data will inform future neonatal care, provide evidence-based guidelines for care of preterm graduates transitioning to adult care, and help shape health education and social policies for this high risk group.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12612000995875. Registered 1 October 2012

Peer Review reports


Infants born very low birth weight (VLBW: <1500 g) or very preterm (VP: <32 weeks gestation) account for around 2 % of live births but between 50–75 % of the work load of neonatal intensive care units (NICUs) [1]. Whilst survival rates for these infants now exceed 90 %, [2, 3] what is most important for individuals, their families and society is the quality of that survival in the longer term. Knowledge of longer-term outcomes is also crucial to inform current neonatal care.

An extensive literature has documented increased rates of health problems amongst surviving VLBW/VP infants compared with full term infants in their early years, including sudden infant death syndrome, feeding problems, respiratory disorders, and increased hospitalisation [4]. Adverse outcomes are also common throughout childhood and include poor growth, neurosensory impairments such as cerebral palsy (CP) in up to10 % or more, and up to 50 % have behavioural problems, cognitive delay, or educational underachievement [511]. Woodward [12] reported that 72 % of VP infants have some white matter (WM) changes on cranial MRI scans at term equivalent, and that moderate or severe changes (in 21 %) were predictive of CP and neuro-cognitive problems in early childhood. These abnormalities include reduced WM volume, ventriculomegaly, thinning of the corpus callosum and delayed myelination. The impacts of these neonatal neurological abnormalities on adult brain structure and function are not known. However, findings from cross sectional studies in childhood and adolescence, [1315] and a recent cohort study, [16] suggest that abnormalities persist and may be irreversible.

Data are also now emerging on a range of functional and health related challenges faced by former VLBW/VP infants as they reach young adulthood, [17, 18] although the majority appear to do well overall [1921]. Scandinavian data show that preterm birth and particularly lower gestational age is associated with increased mortality in young adulthood, [22, 23] with congenital abnormalities, respiratory, endocrine and cardiovascular problems all increasing hazard ratios for risk of death [23]. Studies of growth of VLBW/VP children show that following early growth failure there is some catch-up that may continue through adolescence, although young adults remain shorter and often lighter than their peers [24]. Specific health issues found to be more prevalent include an increased risk of hypertension, [18, 25, 26] impaired insulin sensitivity, [27] glucose tolerance, [28] and renal function [29, 30] and abnormal respiratory function [25, 31]. VLBW children have a greater risk of asthma at school age than controls [32] and infants who had chronic lung disease have poorer lung function in late adolescence [25]. In addition, most reports to date indicate that former VLBW/VP young adults do have lower median IQ scores than their peers, even after excluding those with neurosensory impairments and controlling for confounding factors. Relatively fewer VLBW/VP survivors graduate from high school or enter tertiary education [17, 18, 33]. And even when free of major physical disability, VP young adults performed less well on tasks involving mental flexibility and response inhibition [34].

There are no New Zealand data in this crucial area and important gaps exist in the international literature. To address both these issues we will follow-up the 1986 New Zealand national cohort of VLBW infants, at age 26–28 years.

In 1986 we enrolled all 413 New Zealand VLBW infants admitted to a neonatal intensive care unit (NICU) as part of a prospective study of acute retinopathy of prematurity. Of these, 338 infants (82 %) survived to discharge home [35, 36]. Extensive perinatal data collection showed that at birth 58 % had received antenatal steroids, 132 (32 %) were <1000 g, 126 (31 %) were <28 weeks gestation, 103 (25 %) were small for gestational age, and 95 (23 %) were Maori. Survival for both those <1000 g and <28 weeks was 64 % [2, 36].

This cohort was followed-up at 7 to 8 years and assessments conducted to examine visual and developmental outcomes. By this age a further 12 children had died, 17 were traced to an overseas address, seven families declined follow-up and four were untraced. Hence we assessed 298 children (96 % survivors resident in NZ, 91 % all survivors): 5 % had severe disability, 5 % moderate disability and 15 % mild disability, which was principally an IQ between 1 to 2 SDs below the mean [9]. Compared with the Christchurch Health and Development Study cohort studied at the same age, [37] the VLBW cohort had higher rates of behavioural problems (conduct disorders, attention problems, anxiety/withdrawal), and poorer school achievement [10]. These differences increased with decreasing birthweight amongst the VLBW sample.

In 2009–10, when the members of the cohort were 23 to 24 years old, they were re-contacted as part of a feasibility study in preparation for funding applications for the current project. VLBW graduates were traced through their addresses at 7 to 8 years, grandparents’ addresses, general practitioners, National Health Index (NHI) codes (NHI – a unique person identifier used within the New Zealand health system since 1993), via the electoral rolls and, in a limited number of cases, by local advertisements. Checks were made with Statistics New Zealand to see if any individuals had died since last follow-up. A comparison group (controls) of individuals who were born full-term (FT) in New Zealand in 1986 and were not admitted for NICU care, was recruited either through peer nomination by cohort members or via random sampling from electoral rolls, ensuring balance with respect to the gender, ethnicity and regional distribution of the sample.

A total of 276 (85 % of 324) survivors were retraced and 230 (71 %) enrolled in this pilot (Phase 1) study, which comprised a face-to-face interview to collect information about each participant’s social background, health, education and social role outcomes, supplemented by information from medical records [38]. Sixty-nine controls were also recruited.

The present (Phase 2) study has two primary aims.

The first aim is to assess the health, mental status, functional outcome and quality of life in young adulthood of a NZ national VLBW cohort born in 1986 compared with a group of full-term children born in the same year.

We hypothesise that compared to their same age full term peers, adults born VLBW will, at age 26–28 years, have:

  1. 1.

    Lower levels of school attainment and tertiary educational participation, more limited occupational choice and higher levels of welfare dependence

  2. 2.

    Higher levels of inattention, impulsivity and emotional problems (i.e., symptoms of anxiety and depression), but lower levels of alcohol and drug use/abuse, antisocial behaviour and police contact.

  3. 3.

    Lower social participation and poorer social functioning

  4. 4.

    Poorer performance on measures of cognitive ability, information processing and executive functioning

  5. 5.

    Increased rates of cardiovascular, endocrine, pulmonary, renal and visual abnormalities and pathology

    • Specifically, regarding cardiovascular assessments, we anticipate:

      • Lower reactive hyperaemia consistent with more endothelial dysfunction

      • Echocardiograms that show more abnormalities in LV size and function

      • Elevation of BNP and other cardiac biomarkers and related signalling peptides, that reflect the degree of cardiovascular abnormality and will predict future cardiovascular events

    • regarding endocrine assessments, we anticipate:

      • Higher indices of insulin resistance and glucose intolerance

    • regarding pulmonary function, we anticipate:

      • Impaired pulmonary function, including reduced lung volumes and diffusing capacity, reduced exercise capacity, and higher rates of respiratory morbidity.

    • regarding renal function, we anticipate:

      • Higher microalbumin excretion and lower creatinine clearance

    • regarding vision, we anticipate:

      • Less favourable structural outcomes and impaired functional ability

  6. 6.

    Poorer dental health and dental hygiene

  7. 7.

    Increased rates of both macro- and micro-structural abnormalities on cranial MRI scans

The second aim is to assess whether childhood health and developmental outcomes are predictive of later young adult outcomes within the VLBW cohort.

We hypothesise that within the VLBW cohort:

  1. 8.

    Young adults who were characterised by significant disability/cognitive impairment at 7 to 8 years will fare less well on measures 1–4 than VLBW adults without early impairment [39].

  2. 9.

    Young adults who had retinopathy of prematurity (ROP) and visual impairments at 7 to 8 years will have more adverse visual problems than those who had no ROP.

  3. 10.

    Young adults who had neonatal chronic lung disease (CLD) will have more adverse respiratory function than those who no CLD

  4. 11.

    Increased duration of breastfeeding will be associated with a small but measurable advantage in cognitive outcomes

  5. 12.

    There will be increasing social and economic disadvantage with decreasing birthweight and increasing prematurity.

In our preliminary (Phase 1) study we re-established the cohort and began to address hypotheses 1–3. This Phase 2 study will extend the research to focus on health issues and neurocognitive outcomes but also to update the information collected as part of Phase 1.

Design and methods

Study population

The case sample will comprise a minimum of 250 members of the 1986 NZ National VLBW cohort (77 % of survivors). In Phase 1 the proportion (%) of the 230 survivors seen and other survivors not assessed (94) who were <1000 g was 25.2 and 27.1; were <28 weeks is 24.8 and 24.0; are male is 47.0 and 52.1; are Maori is 26.1 and 22.1; had moderate/severe disability at 7 to 8 years is 10.3 and 6.7 – all being not significantly different. Outcomes for the VLBW cohort will be assessed against a comparison sample of 100 same age term controls recruited via a process of peer nomination and random sampling from electoral rolls, ensuring balance with respect to the gender, ethnicity and regional distribution of the sample.


As part of Phase 1 all participants have been informed about Phase 2 of the study and have consented to being approached to participate in these assessments. The study has also obtained comprehensive contact information for each participant, plus a number of individuals not studied in Phase I, and we do not anticipate major difficulties in tracing and consenting participants for Phase 2. Following consent, participants will be brought to Christchurch for a 2 day multidisciplinary evaluation (an average of three participants a week). Provision will be made for a support person to travel with the participant if this is required. All costs of travel, accommodation and food will be met by the study. For the small number of the cohort members who are too compromised to travel to Christchurch due to disability severity and/or care needs we will seek information by means of a questionnaire and, where possible, a visit from one of the research team (Additional files 1, 2, 3, 4, 5, 6).

All research procedures will be conducted in existing facilities in the University of Otago, Christchurch or Canterbury District Health Board (CDHB). Participants will be scheduled to arrive the night before, have fasting blood tests the next morning and a series of assessments over 2 days. Study personnel will meet each participant and assist their navigation between laboratory sessions. To avoid problems of fatigue, participants will have the opportunity to take breaks as necessary and refreshments as required. Transportation will also be provided when needed.

Medical investigations will be undertaken in the University of Otago, Christchurch, Department of Medicine Nicholls Clinical Research Centre and the CDHB Respiratory Physiology Laboratory facilities.

Assessments will be conducted by appropriately trained, medically qualified staff, who will be blinded to the participant’s background (except where noted otherwise), and will include:

  • ▪ Standardised questionnaires on health, including respiratory [40] and bowel problems.

  • ▪ Growth-height (Harpenden stadiometer), weight, BMI (Weight/Height2), waist-hip ratio, head circumference.

  • ▪ Total body fat estimated by bioelectrical impedance analysis (BIA).

  • ▪ Visual assessment. Glasses prescription-measured in focimeter. Distance visual acuity using standardised ETDRS chart (with glasses if worn). Contrast sensitivity testing with Pelli-Robson charts (which reflects functional visual ability). Autorefraction. Retinal photographs to digitally record macula, optic disk, paracentral and peripheral retina.

  • ▪ Blood pressure assessed using a random zero machine (seated, after rest for 5 min, cuff size 2/3 upper arm length: mean of three readings)

  • ▪ Echocardiogram for left ventricular volume, mass and function, valves, ascending aorta dilatation. Measurement of myocardial velocities and deformation.

  • ▪ Endothelial dysfunction assessment by peripheral arterial tonometry (EndoPAT), [41] consisting of digital recording equipment and two finger thimble-like probes.

  • ▪ Respiratory Function Tests. Forced expiratory volume in 1 s (FEV1), Forced Vital Capacity (FVC) and FEV1/FVC [42]. Static lung volumes [43]. Diffusing capacity of CO [44]. Single breath nitrogen washout [45]. Maximal exercise testing [46].

  • ▪ Renal function, assessed by a) creatinine clearance (Ccl) – [Blood test for plasma creatinine in mmol/L. Ccl calculated from Cockcroft-Gault approximation] and b) early morning urine for albumin-creatinine ratio [mg/mmol: <2.2 normal; 2.2–22.6 microalbuminuria; >22.6 proteinuria].

  • ▪ Additional venous blood sample for:

Fasting insulin and glucose – (insulin sensitivity calculated from QUICKI [47]) lipids; glycated haemoglobin; cotinine.

Plasma hormones including B-Type Natriuretic Peptide (BNP), amino terminal proBNP (NT-proBNP), C-Type Natriuretic Peptide (CNP), amino terminal proCNP (NT-proCNP), high sensitivity troponin T (hsTNT), renin, aldosterone.

Stored plasma sample for future use – investigation of gene-environment interactions; biochemical assays.

Blood volume: 5 × 9 ml EDTA, plus 3 ml A2, plus 2 × 9 ml lithium heparin for hormones and storage. Plus 4 ml lithium heparin for biochemistry. Total 70 ml.

Total time for tests including breaks is estimated at about 2.5–3.5 h (medical/cardiology 1–1.5 h, respiratory tests 1–1.5 h, visual assessments 0.5 h).

Oral Health investigations will be undertaken by dentists from the oral health service of the Canterbury District Health Board using a standardised protocol from the 2009 New Zealand Oral Health Survey [48]. The examination will include assessments of the wearing of dentures; history of orthodontic treatment; the health of oral mucosa; tooth loss, presence of decay, and dental treatments; plaque, calculus, gingivitis; periodontal tissue destruction; decay experience of coronal and root surfaces; and the presence of enamel defects. Total examination time will be approximately 45 min. Dental examination will be supplemented by questionnaire data on current problems or concerns about oral health, practise of dental hygiene and use of dental health services.

Neuropsychological Functioning will be assessed in other existing facilities in the University of Otago, Christchurch, by research staff with appropriate training and qualifications in psychometric test administration. The test room will be suitably quiet. The tester will be blinded to the participants’ background. Testing will take between 2 to 3 h for each participant, including breaks as needed, and will include assessments of:

  • ▪ Global cognitive ability/IQ will be assessed using the Wechsler Abbreviated Scale of Intelligence® – Second edition (WASI-II), [49] an individually administered assessment of intelligence for people aged 6–90 years. This short form consists of four subtests including Block Design and Matrix Reasoning (which compose the Perceptual Reasoning Index) and the Vocabulary and Similarities subtests (which compose the Verbal Comprehension Index).

  • ▪ Attention will be measured using the Test of Everyday Attention (TEA), [50] which assesses selective attention, sustained attention and switching attention.

  • ▪ Working memory – Visual working memory will be assessed using a computer administered task adapted from the Sternberg Spatial Working Memory Paradigm [51]. Auditory working memory will be assessed using the two elevator counting tasks of the Test of Everyday Attention: Elevator counting with distraction; Elevator counting with reversal.

  • ▪ Cognitive flexibility will be assessed by the Comprehensive Trail Making Test (CTMT), [52] comprising a standardized set of five visual search and sequencing tasks, and the Brixton Spatial Anticipation Test, [53] which is a measure for assessing the ability to detect and follow a rule.

  • ▪ Visuo-spatial processing and planning will be assessed using the Benton Judgement of Line Orientation – Form V [54].

  • ▪ Information processing speed will be assessed using the Symbol Digit Modalities Test [55].

For participants with a physical or sensorineural disability some tests may not be possible, and where possible an alternative form of the test will be used.

Health and social functioning

Trained survey interviewers will update information from study Phase 1 on education, occupational status, health history and self-assessment of health status, quality of life measures, current mental health, substance use, family, peer and partner relationships and other aspects of social functioning. Interviews (2 to 3 h) will be conducted in private.

Parent/significant other report

To gain a further perspective on the young person’s health and functioning, a telephone interview will be conducted with a parent or significant other person nominated by the respondent. These interviews will gather a third person perspective on aspects of the young person’s health and health history, education and transition to adult roles, the young person’s behaviour and personality, social and partner relationships and related issues. Interviews will take 35–45 min and will be conducted by trained survey interviewers who are independent of the survey team interviewing the young person, but are not blinded their background.

Magnetic resonance imaging

We will undertake a cranial MRI scan on all participants who were born at <28 weeks gestation and a random sample of the VLBW cohort to bring the total having MRI scans to 150, plus a random 50 controls. Images will be acquired using a 3-Tesla GE scanner on the Christchurch campus and analyses undertaken by experienced staff blinded to the participants’ background. Scanning will take a total of 35–45 min comprising:

  • ▪ Clinical data – T2 and T2 FLAIR images as part of standard clinical protocol for purposes of a radiologist read/referral/exclusion and qualitative scoring

  • ▪ T1-weighted images will be used to assess brain growth and tissue distribution

  • ▪ Diffusion Tensor imaging (DTI) will assess white matter microstructural development (fractional anisotropy).

  • ▪ Arterial Spin Labelling (ASL) – a non-invasive functional measure of cerebral blood flow that produces quantification of cerebral perfusion and has good concordance with 15O-PET [56]

  • ▪ Resting State Functional Connectivity (fcMRI) which provides a method to evaluate regional interactions in the brain.

Both ASL and fcMRI may be clinically useful as biomarkers for individuals at increased risk of later cognitive impairment. This protocol, with the addition of ASL, is the same as that being used at 12 years of age in a cohort of former <32 week gestation children, who also had MRI scans at term equivalent, [12] and this may allow early clues as to longitudinal trajectories of brain injury and neural plasticity.

Additional studies

Although not part of the primary protocol for the New Zealand 1986 VLBW Follow-up Study, we will also undertake two additional studies with separate funding.

  1. 1.

    DNA methylation and outcomes in VLBW young adults. We will investigate whether young adults born with VLBW have differences in DNA methylation at specific sites in the genome (in peripheral blood samples), compared with a matched normal birthweight group, and whether these traits are associated with growth and metabolic health outcomes as young adults. Separate consent is required for this study, which also requires an additional 10 ml blood sample be taken.

  2. 2.

    C type Natriuretic Peptide (CNP) and vascular risk in VLBW young adults. CNP is a paracrine vasoprotective peptide secreted by the vascular endothelium, and which has anti-inflammatory actions in rodents and has been shown to be atheroprotective. Very little CNP normally enters the circulation but a stable product of the prohormone (amino terminal proCNP, NTproCNP) can be readily measured in plasma and serves as a marker of CNP production in tissues. Recent studies by the Christchurch group have defined the normal age and gender related ranges of plasma NTproCNP concentration in 250 healthy adult subjects without known history of cardiovascular disorder [57]. We will compare the plasma NTproCNP concentrations in VLBW young adults and term born controls and investigate their relationship with individual vascular risk factors and with adult height.

Statistical analysis and statistical power

The collected data will enable two types of analyses to be conducted. Between group comparisons: The principal analyses will examine between group differences in outcome (health, neurocognitive assessments, social functioning), using standard statistical analyses: chi square for differences in proportions; t-test for independent samples or analysis of variance for differences in means of continuous outcomes; Poisson or negative binomial regression for differences in rates. Where outcome data are non-normally distributed appropriate data transformations (eg logarithmic) may be conducted. The VLBW group may be further subdivided to test for differential effects by severity of disability at age 7 to 8, or by birthweight or gestation. Comparisons may be further adjusted if necessary for between group differences in family background characteristics using regression methods based on the generalised linear model [58]. Assuming a minimum of 250 recruits from the VLBW cohort and 100 controls, the study will have 80 % power at alpha = .05 to detect differences between groups of 30 SD or greater on continuous outcomes, and ORs in the region of 2.0–3.5 for dichotomous outcomes (depending on the base rate) [59]. This suggests the study will have adequate power to detect effect sizes in the small to moderate range. These differences are well within the anticipated effect sizes based on existing reports [17, 18]. Subdividing the VLBW group (for example by level of prior disability) is unlikely to compromise study power since the effect sizes are likely to increase for more extreme groups.

Outcome trajectories amongst the VLBW cohort: For a number of outcomes, for example visual, physical growth, it will be possible to examine across time continuities and/or trajectories in outcome from childhood to adulthood within the VLBW cohort. Depending on the outcome under consideration, analysis methods may range from simple tabular methods documenting outcome in young adulthood conditional on childhood status, to simple regression models predicting outcome in adulthood from measures in childhood, to more complex methods for repeated measures data based on a generalised estimating equation approach [60] to model changes in outcome trajectory.


The study has received ethics approval from the Upper South B Regional Ethics Committee (superseded by the Southern Health and Disability Committee) (ref: URB/12/05/015).


The study of adult outcomes after VLBW/VP birth is a relatively new field and one which is expanding, but there are important gaps in current knowledge. Many cohorts date from the 1970’s or early 1980’s when few infants received antenatal steroids, which reduce both mortality and morbidity [61]. Some studies are from single institutions, [17, 62] or a group of institutions, including the Helsinki Study of Very Low Birth Weight Adults based on 166 VLBW infants born in 1978–85 and which has been highly productive [26, 63]. Of the few population based studies most are regional [17, 18] or rely on constrained national registry data [19] (Swedish, [64, 65] Norwegian [66] and Danish [67] studies). The Netherlands study of VP/VLBW infants born in 1983 [68, 69] is most similar to our NZ cohort but these infants were not exposed to antenatal corticosteroids. As more data become available, understanding trends across studies as well as differences between them will become important. The New Zealand 1986 VLBW Follow-up Study investigators are committed to collaborating with other studies as part of the Adult Born Preterm International Collaboration (APIC), which has been initiated by the Helsinki, Finland group [70].



Very low birth weight


Very preterm


Neonatal intensive care unit


Cerebral palsy


White matter


Magnetic resonance imaging


Intelligence quotient


Standard deviation


National Health Index




New Zealand


Retinopathy of prematurity


Chronic lung disease


Canterbury District Health Board


Body-mass index


Bioelectrical impedance analysis


Early treatment diabetic retinal study


Peripheral arterial tonometry


Forced expiratory volume in 1 s


Forced vital capacity


Carbon monoxide


Creatinine clearance


Quantitative insulin sensitivity check index


B-Type natriuretic peptide


C-Type natriuretic peptide


High sensitivity troponin T (hsTNT)


Ethylenediaminetetraacetic acid


Wechsler Abbreviated Scale of Intelligence®


Test of everyday attention


Comprehensive trail making test


Diffusion tensor imaging


Arterial spin labelling (ASL)


Functional connectivity


Adult born preterm international collaboration


  1. Darlow BA, Mogridge N, Horwood LJ, et al. Admission of all gestations to a regional neonatal unit versus controls: Neonatal morbidity. J Paediatr Child Health. 2009;45:181–6.

    Article  PubMed  Google Scholar 

  2. Darlow BA, Cust AE, Donoghue DA. Improved outcomes for very low birthweight infants: evidence from New Zealand national population based data. Arch Dis Child. 2003;88:23–8.

    Article  Google Scholar 

  3. Chow SSW. Report of the Australian and New Zealand Neonatal Network 2011. Sydney: ANZNN; 2013.

    Google Scholar 

  4. Wilson-Costello D. Is there evidence that long-term outcomes have improved with intensive care? Semin Fetal Neonatal Med. 2007;12:344–54.

    Article  PubMed  Google Scholar 

  5. Allen MC. Preterm outcomes research: a critical component of neonatal intensive care. MRDD Res Reviews. 2002;8:221–33.

    Google Scholar 

  6. Marlow N. Neurocognitive outcome after very preterm birth. Arch Dis Child. 2004;89:F224–8.

    Article  CAS  Google Scholar 

  7. Aarnoudse-Moens GSA, Weisglas-Kuperus N, van Goudoever JB, Oosterlaan J. Meta-analysis of neurobehavioural outcomes in very preterm and/or very low birth weight children. Pediatrics. 2009;124:717–28.

    Article  PubMed  Google Scholar 

  8. Doyle LW. Evaluation of neonatal intensive care for extremely low birth weight infants in Victoria over two decades: 1. Effectiveness. Pediatrics. 2004;113:505–9.

    Article  PubMed  Google Scholar 

  9. Darlow BA, Horwood LJ, Mogridge N, Clemett RS. Prospective study of New Zealand very low birthweight infants: Outcome at 7 to 8 years. J Paediatr Child Health. 1997;33:47–51.

    Article  CAS  PubMed  Google Scholar 

  10. Horwood LJ, Mogridge N, Darlow BA. Cognitive, educational, and behavioural outcomes at 7 to 8 years in a national very low birthweight cohort. Arch Dis Child Fetal Neonatal Ed. 1998;78:F12–20.

    Article  Google Scholar 

  11. Woodward LJ, Moor S, Hood KM, et al. Very preterm children show impairments across multiple neurodevelopmental domains by age 4 years. Arch Dis Child Fetal Neonatal Ed. 2009;94:F339–44.

    Article  CAS  PubMed  Google Scholar 

  12. Woodward LJ, Anderson PJ, Austin NC, et al. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med. 2006;355:685–94.

    Article  CAS  PubMed  Google Scholar 

  13. Allin M, Nosarti C, Narberhaus A, et al. Growth of the corpus callosum in adolescent born preterm. Arch Pediatr Adolesc Med. 2007;161:1183–9.

    Article  PubMed  Google Scholar 

  14. Constable RT, Ment LR, Vohr BR, et al. Prematurely born children demonstrate white matter microstructural differences at 12 years of age, relative to term control subjects: an investigation of group and gender effects. Pediatrics. 2008;121:306–16.

    Article  PubMed  Google Scholar 

  15. Eikenes L, Lohaugen GC, Brubakk A-M, et al. Young adults born preterm with very low birth weight demonstrate widespread white matter alterations on brain DTI. Neuroimage. 2011;54:1774–85.

    Article  PubMed  Google Scholar 

  16. Allin MP, Kontis D, Walshe M, et al. White matter and cognition in adults who were born preterm. PLoS One. 2011;6(10):e24525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hack M. Adult outcomes of preterm children. J Dev Behav Pediatr. 2009;30:460–70.

    Article  PubMed  Google Scholar 

  18. Doyle LW, Anderson PJ. Adult outcomes of extremely preterm infants. Pediatrics. 2010;126:342–51.

    Article  PubMed  Google Scholar 

  19. Saigal SJ, Streiner D. Socio-economic achievements of individuals born very preterm at the age of 27 to 29 years. Dev Med Child Neurol. 2009;51:845–50.

    Article  Google Scholar 

  20. Zwicker JG, Harris SR. Quality of life of formerly preterm and very low birth weight infants from preschool age to adulthood: a systematic review. Pediatrics. 2008;121:e366–76.

    Article  PubMed  Google Scholar 

  21. Gäddlin P-O, Finnström O, Sydsjö G, Leijon I. Most very low birth weight subjects do well as adults. Acta Paediatr. 2009;98:1513–20.

    Article  PubMed  Google Scholar 

  22. Swamy GK, Ostbye T, Skjaerven R. Association of preterm birth with long-term survival, reproduction, and next-generation preterm birth. JAMA. 2008;299:1429–36.

    Article  CAS  PubMed  Google Scholar 

  23. Crump C, Sundquist K, Sundquist J, Winkleby MA. Gestational age at birth and mortality in young adulthood. JAMA. 2011;306:1233–40.

    Article  CAS  PubMed  Google Scholar 

  24. Euser AM, de Wit CC, Finken MJ, Rijken M, Wit JM. Growth of preterm born children. Hom Res. 2008;70:319–28.

    CAS  Google Scholar 

  25. Doyle LW. Cardiopulmonary outcomes of extreme prematurity. Semin Perinatol. 2008;32:28–34.

    Article  PubMed  Google Scholar 

  26. Hovi P, Andersson S, Räikkönen K, et al. Ambulatory Blood Pressure in Young Adults with Very Low Birth Weight. J Pediatr. 2010;156:54–9. e1.

    Article  PubMed  Google Scholar 

  27. Hofman P, Regan F, Jackson WE, et al. Premature birth and later insulin resistance. N Engl J Med. 2004;351:2179–86.

    Article  CAS  PubMed  Google Scholar 

  28. Hovi P, Andersson S, Eriksson JG, et al. Glucose regulation in young adults with very low birth weight. N Engl J Med. 2007;356:2053–63.

    Article  CAS  PubMed  Google Scholar 

  29. Kreijzer-Veen MG, Schrevel M, Finken MJ, et al. Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. J Am Soc Nephrol. 2005;16:2762–278.

    Article  Google Scholar 

  30. Rodriguez-Soriano J, Aguirre M, Oliveras R, Vallo A. Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol. 2005;20:579–84.

    Article  PubMed  Google Scholar 

  31. Evensen KAI, Steinshamm S, Tjønna AE, et al. Effects of preterm birth and fetal growth retardation on cardiovascular risk factors in young adulthood. Early Human Devel. 2009;85:239–45.

    Article  Google Scholar 

  32. Darlow BA, Horwood LJ, Mogridge N. Very low birthweight and asthma by age seven years in a national cohort. Pediatr Pulmonol. 2000;30:291–6.

    Article  CAS  PubMed  Google Scholar 

  33. Aylward GP. Neurodevelopmental outcomes of infants born prematurely. J Dev Behav Pediatr. 2005;26:427–40.

    Article  PubMed  Google Scholar 

  34. Nosarti C, Giouroukou E, Micali N, Rifkin L, Morris RG, Murray RM. Impaired executive functioning in young adults born very preterm. J Int Neuropsychol Soc. 2007;18:1–11.

    Google Scholar 

  35. Darlow BA. Incidence of retinopathy of prematurity in New Zealand. Arch Dis Child. 1988;63:1083–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Darlow BA, Horwood LJ, Clemett RS. Retinopathy of prematurity: Risk factors in a prospective population based study. Paediatr Perinat Epidemiol. 1992;6:62–80.

    Article  CAS  PubMed  Google Scholar 

  37. Christchurch health and Development Study (webpages). URL Accessed January 2015.

  38. Darlow BA, Horwood LJ, Pere-Bracken H, Woodward LJ. Psychosocial outcomes of young adults born very low birth weight. Pediatrics. 2013;132:e1521–8.

    Article  PubMed  Google Scholar 

  39. Fergusson DM, Horwood LJ, Ridder EM. Show me the child at seven II: Childhood intelligence and later outcomes in adolescence and young adulthood. J Child Psych Psychiatry. 2005;46:850–8.

    Article  Google Scholar 

  40. Burney PG, Luczynska C, Chinn S, Jarvis D. The European Community Respiratory Health Survey – study protocol. Eur Respir J. 1994;7:954–60.

    Article  CAS  PubMed  Google Scholar 

  41. Rubinshtein R, Kuvin JT, Soffler M, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31:1142–8.

    Article  PubMed  Google Scholar 

  42. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26:319–38.

    Article  CAS  PubMed  Google Scholar 

  43. Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. Eur Respir J. 2005;26:511–22.

    Article  CAS  PubMed  Google Scholar 

  44. MacIntyre N, Crapo RO, Viegi G, et al. Standardisation of the single breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26:720–35.

    Article  CAS  PubMed  Google Scholar 

  45. Ruppel G. Manual of pulmonary function testing. St Louis, Mo: Mosby Elsevier; 2009.

    Google Scholar 

  46. American Thoracic Society, American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167:211–77.

    Article  Google Scholar 

  47. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate use. Am J Physiol Endocrinol Metab. 2008;294:E15–26.

    Article  CAS  PubMed  Google Scholar 

  48. Ministry of Health. Methodology Report for the 2009 New Zealand Oral Health Survey. Wellington: Ministry of Health; 2010.

    Google Scholar 

  49. Wechsler D. Wechsler Abbreviated Scale of Intelligence–Second Edition Manual. Bloomington, MN: Pearson; 2011.

    Google Scholar 

  50. Robertson IH, Ward T, Ridgeway V, Nimmo-Smith I. The structure of normal human attention: The Test of Everyday Attention. J Int Neuropsychol Soc. 1996;2:525–34.

    Article  CAS  PubMed  Google Scholar 

  51. Sternberg S. High-speed scanning in human memory. Science. 1966;153:652–4.

    Article  CAS  PubMed  Google Scholar 

  52. Reynolds CR. Comprehensive Trail Making Test. Austin, TX: Pro-Ed; 2002. doi:10.1177/0734282905282415.

    Google Scholar 

  53. Burgess P, Shallice T. The Hayling and Brixton Tests. Test manual. Bury St Edmunds, UK: Thames Valley Test Company; 1997.

    Google Scholar 

  54. Benton AL, Varney N, Hamsher K. Visuospatial judgment: a clinical test. Arch Neurol. 1978;35:364–7.

    Article  CAS  PubMed  Google Scholar 

  55. Sheridan LK, Fitzgerald HE, Adams KM, et al. Normative Symbol Digit Modalities Test performance in a community-based sample. Arch Clin Neuropsychol. 2006;21:23–8.

    Article  PubMed  Google Scholar 

  56. Ye FQ, Berman KF, Ellmore T, et al. H2 15O PET validation of steady-state arterial spin tagging cerebral blood flow measurements in humans. Magn Reson Med. 2000;44:450–6.

    Article  CAS  PubMed  Google Scholar 

  57. Prickett TCR, Olney RC, Cameron VA, Ellis MJ, Richards AM, Espiner EA. Impact of age, phenotype and cardio-renal function on plasma C-type and B-type natriuretic peptide forms in healthy adults. Clin Endocrinol. 2013;78:783–9.

    Article  CAS  Google Scholar 

  58. McCullagh P, Nelder J. Generalized Linear Models. 2nd ed. Boca Raton: Chapman and Hall/CRC; 1989.

    Book  Google Scholar 

  59. Dupont WD, Plummer WD. Power and sample size calculations: A review and computer program. Control Clin Trials. 1990;11:116–28.

    Article  CAS  PubMed  Google Scholar 

  60. Diggle PJ, Heagerty P, Liang K-Y, Zeger SL (2002). Analysis of Longitudinal Data. Oxford Statistical Science Series. ISBN 9780198524847

  61. Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.pub2.

  62. Doyle LW, Faber B, Callanan C, et al. Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence. Pediatrics. 2006;118:108–13.

    Article  PubMed  Google Scholar 

  63. Kajantie E1, Strang-Karlsson S, Hovi P, Wehkalampi K, Lahti J, Kaseva N, et al. Insulin sensitivity and secretory response in adults born preterm: the Helsinkie Study of Very Low Birth Weight Adults. J Clin Endocrinol Metab. 2015;100:244-50.

  64. Lindström K, Winbladh B, Haglund B, Hjern A. Preterm infants as young adults: a Swedish national cohort study. Pediatrics. 2007;120:70–7.

    Article  PubMed  Google Scholar 

  65. Ekeus C, Lindström K, Lindblad F, et al. Preterm birth, social disadvantage, and cognitive competence in Swedish 18 to 19-year-old men. Pediatrics. 2010;125:e67–73.

    Article  PubMed  Google Scholar 

  66. Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008;359:262–73.

    Article  CAS  PubMed  Google Scholar 

  67. Mathiasen R, Hansen BOM, Nybo Anderson A-M. Socio-economic achievements of individuals born very preterm at the age of 27 to 29 years: a nationwide cohort study. Devel Med Child Neurol. 2009;51:901–8.

    Article  Google Scholar 

  68. Walther FJ, den Ouden AL, Verloove-Vanhorick SP. Looking back in time: outcome of a national cohort of very preterm infants born in the Netherlands in 1983. Early Hum Devel. 2000;59:175–91.

    Article  CAS  Google Scholar 

  69. Hille ET, Weisglas-Kuperus N, van Goudoever JB, et al. Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: the Dutch Project on Preterm and Small for Gestational Age Infants at 19 years of age. Pediatrics. 2007;120:e587–95.

    Article  PubMed  Google Scholar 

  70. Kajantie E, Hovi P. Is very preterm birth a risk factor for adult cardiometabolic disease? Semin Fetal Neonatal Med. 2014;19:112–7.

    Article  PubMed  Google Scholar 

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The Study is funded by the New Zealand Health Research Council (12/129) through a competitive project grant with some co-funding from the Cure Kids charity. Additional funding is from two project grants from the Child Health Research Foundation (Cure Kids) (CHRF 5040, 5041). The Canterbury Neonatal Unit Trust Fund has generously funded the cost of the EndoPAT machine and, as consumer stakeholders with an interest in the outcomes of this research, wrote a supportive letter at the time of grant applications. A replacement autorefractor was purchased through University of Otago capital funds. Finally, we are very grateful to all the young adult participants for their willingness to take part in this study.

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Correspondence to Brian A. Darlow.

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Competing interests

All authors declare that they have no competing interests.

Authors’ contributions

BAD conceived the study concept, led the protocol design and wrote the first draft of the manuscript. LJH contributed to the study concept and protocol design and is responsible for the statistical analysis plan. LJW, JME and RWT contributed to the study concept and protocol design. All remaining authors (MJE, ME, JS, MS, RK, TRM, VMcK, KL, MM, EAE, VC, JM) contributed to the protocol design. All authors read, revised and approved the final version of the manuscript.

Additional files

Additional file 1:

NZ 1986 VLBW FU Study Cohort Information Sheet May 2013 Final.

Additional file 2:

NZ 1986 VLBW FU Study Controls Information Sheet May 2013 Final.

Additional file 3:

NZ 1986 VLBW FU Study Information Sheet Genetics August 2012.

Additional file 4:

NZ 1986 VLBW FU Study Consent Form Genetics Jan 2013.

Additional file 5:

NZ 1986 VLBW FU Study Consent Form Genetics Jan 2013.

Additional file 6:

NZ 1986 VLBW FU Study Explanation of procedures June 2013.

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Darlow, B.A., Horwood, L.J., Woodward, L.J. et al. The New Zealand 1986 very low birth weight cohort as young adults: mapping the road ahead. BMC Pediatr 15, 90 (2015).

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