Seminars in Fetal & Neonatal Medicine 19 (2014) 125e130

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Seminars in Fetal & Neonatal Medicine

journal homepage: www.elsevier.com/locate/siny

Review

Functional outcomes of very premature infants into adulthood

Saroj Saigal*
Neonatal Follow-up Program, McMaster University, Hamilton, Ontario, Canada

s u m m a r y
Keywords:
Adulthood
Functional abilities
Quality of life
Very low birth weight
Very preterm

The outcomes of very low birth weight survivors born in the early post-neonatal intensive care era have
now been reported to young adulthood in several longitudinal cohort studies, and more recently from
large Scandinavian national databases. The latter reports corroborate the ndings that despite disabilities, a signicant majority of very low birth weight survivors are leading productive lives, and are
functioning better than expected. This is reassuring, but there are still concerns about future psychopathology, cardiovascular and metabolic problems as they approach middle age. Although these ndings
may not be directly applicable to the current survivors of modern neonatal intensive care, they do
provide a yardstick by which to project the outcomes of future survivors until more contemporaneous
data are available.
2013 Elsevier Ltd. All rights reserved.

1. Introduction
Neonatal intensive care started in the late 1960s in most
industrialised countries. The next decade was a transitional period
when neonatal intensive care units (NICUs) were being established.
It was not until the 1980s that survival of very premature infants
started to improve and approached 50%. Reports of the outcomes at
adulthood of very low birth weight (VLBW) and extremely low
birth weight (ELBW) infants started to emerge in the early 21st
century [1,2].
An important reason to determine the life course of these highrisk infants is that children are moving targets, and their outcomes,
experiences and expectations change over time [3]. Many limitations stabilise, or improve, and newer problems may emerge
depending on the academic and social challenges that they may
face. Further, with increasing age, there are fears that they may
encounter a higher prevalence of cardiovascular and metabolic
problems than the normal term population [4e9]. Thus, the
emergence of problems is age-dependent and not necessarily cumulative. Physicians who will assume their subsequent care need
to be aware of the special challenges that the aging premature
infants may face in the future, some of which might still be
unknown.
This issue is devoted to the long-term outcome of the tiniest or
most immature babies. Several eminent international investigators
are presenting a broad array of outcomes. Although many outcomes

* Address: 1280 Main St West, Room HSC 4F, Hamilton, Ontario, Canada L8S 4K1.
Tel.: 1 905 521 2100x76959; fax: 1 905 521 5007.
E-mail address: saigal@mcmaster.ca.
1744-165X/$ e see front matter 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.siny.2013.11.001

are interrelated, in the interest of avoiding overlap, this chapter will

focus on the residual limitations and challenges, adult role functioning, life achievements, social functioning, and self-perceived
quality of life (QoL). Since there are very few studies of exclusively ELBW infants, this chapter will also include former VLBW or
very preterm (VP) infants <29 weeks of gestation who have
reached adulthood.
2. Methodological limitations
Due to the lack of ultrasound conrmation to determine the
accuracy of gestational age, cohort studies from the earlier era have
reported the outcomes mainly by birth weight categories of
<1001 g or 1000e1500 g. The bias in this articial cut-off is well
recognised, and the assumption is that the majority of ELBW infants
were <29 weeks of gestation. The incidence of small for gestational
age varied between the diverse populations and by the growth
curves used, and ranged between 18% and 24%. The longitudinal
cohort studies reported are from a single hospital, or from regional
centres, and may or may not include children with disabilities.
Because of the low survival in that era, there are limited studies of
exclusively ELBW infants to adulthood. The current studies of
extremely preterm infants are gestational-age-based, and the oldest will soon be reaching adulthood. Outcomes from the earlier
studies will therefore be reported by birth weight, unless specied
otherwise.
In the last decade, there have been several studies of premature
infants to adulthood using two different designs. Until recently, the
majority of studies to adulthood were descriptive cohort studies
with matched controls that were followed longitudinally. These

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S. Saigal / Seminars in Fetal & Neonatal Medicine 19 (2014) 125e130

studies provide meticulously collected information using validated

standardised tests, self-completed questionnaires, and interviews,
and allow us to observe changes in outcomes over time. On the
negative side, they are time-consuming and very expensive to
conduct, attrition rates can be quite high, and they are limited by
small sample sizes that do not permit further exploratory analyses
[2,10]. However, the information collected is rich, and provides a
more accurate account of the diagnoses and severity of disabilities,
behavioral and emotional problems, and self-perception of the
health-related quality of life (HRQL).
Recently, the Scandinavians have taken a more innovative
approach by using data from large epidemiological National Registries that have resulted in an explosion of publications to adulthood [11e14]. These databases have unique identiers that link
birth data with subsequent vital statistics, allowing a wealth of
information to be collected on various aspects of the individual. Not
only are they cheaper than longitudinal cohort studies, but also
there are minimal losses to follow-up. These large sample sizes
provide the power for subgroup analyses, exploration of confounders, and the impact of gestational age gradients on outcomes
(the gestational ages in these large databases before the use of
routine ultrasound may also be imprecise, particularly for infants
<30 weeks of gestation) [14,15]. The survival rates of very premature infants in Europe in the 1970s and 1980s was lower than for
the corresponding gestational ages in North American cohorts,
partly because of differences in intervention policies for offering
intensive care at lower gestational ages [16]. This strategy may have
resulted in both lower rates of survival and lower prevalences of
disabilities.
Additionally, some concerns have been expressed about the
accuracy of the diagnosis of cerebral palsy (CP) in the Danish National Patient Register [14]. Other limitations include the inability
to elicit the personal perspectives of individuals in terms of
emotional and mental health, and quality of life. Also, with large
sample sizes, it is necessary to temper interpretations of statistical
signicance with questions about clinical relevance [2,10]. Nevertheless, these studies provide valuable information that can be
complementary to support, or to refute, the ndings in the smaller
sample studies.
Interestingly, social scientists are questioning the very denition
of adulthood, and it appears that these days adulthood does not
necessarily begin where adolescence ends. Arnett [17] has coined a
new phase in life, termed emerging adulthood, for the period
between the late teen years through to the early 20s, when individuals may have shed dependency, but have not yet assumed the
full responsibilities of adulthood according to societal expectations.
In fact, the age of young adulthood has shifted to beyond 25 years.
It is well accepted that even when compared to 30 years ago, the
responsibilities of adulthood in terms of employment, marriage,
and parenthood are considerably delayed. This poses a problem as
several published follow-up studies have reported adult outcomes
starting from age 18 years upwards. For the purpose of the current
report, only studies above a mean age of 19 years will be
considered.
3. Neurodevelopmental outcomes
3.1. Neurosensory impairments
Overall, there appears to be stability in the incidence of neurological impairments from school age to adulthood [18]. Data from
both cohort studies and National Registries conrm that there is a
gradient in all neurosensory impairments based on gestational age:
higher impairments are found at lower gestational ages [11,12].
These impairments include CP, blindness, deafness, or cognitive

decits, and some also include seizures/epilepsy. CP is one of the

most common disabilities among premature survivors in adulthood. Fortunately, despite the improved survival of very immature
infants, the prevalence of CP has been declining in recent years
[16,19]. In addition, the severity of functional limitations has also
improved, reportedly due to the reduction of grade III cystic periventricular leukomalacia [16]. It remains to be seen if these current
improvements in brain pathology translate into better outcomes for
the future.
Using the Norwegian Medical Birth Registry of births between
1967 and 1983, Moster et al. [11] conducted a large-scale study of
premature infants with a wide range of gestational ages, who
were followed to a minimum age of 20 years. They reported the
rate of CP for infants between 23 and 27 completed weeks of
gestation of 9.1% compared to 0.1% in those born 37 weeks of
gestation [relative risk (RR): 78.9; 95% condence interval (CI):
56.1e110.0] [11].
Saigal et al. [20] reported an overall rate of 27% with neurosensory impairments among ELBW young adults (10% had multiple
impairments) at a mean age of 23 years, compared to 2% in normal
birth weight (NBW) controls. Of these, 13.4% had CP (2.6% were
non-ambulatory), compared to 0.8% of controls. In another Canadian study of ELBW young adults at age 19 years, the overall rate of
neurosensory impairments was 12%, of which 7% had CP [21]. Hack
et al. [22] reported a CP rate of 6.2% among VLBW adults at age 20
years. The prevalence of CP was 6.9% in VLBW males at the medical
examination for the Swedish National Service [23].
3.2. Ophthalmological problems
Most studies report a high prevalence of various ophthalmological problems after preterm birth that is dependent on both the
survival rates and the level of immaturity. Before the implementation of the National Screening Programs for ROP and the
advent of laser therapy, the prevalence of blindness among ELBW
young adults ranged between 0% [21] and 13% [24] (of these, 7% had
bilateral blindness). Moster et al. [11] reported a combined incidence of blindness, low vision and hearing loss of 4.1% for those
born between 23 and 28 weeks of gestation. Blindness was lower in
VLBW infants: 1.6% (0.4% bilateral) in the Cleveland cohort [22], and
severely reduced vision was present in 7% of Swedish VLBW 19year-old males [23]. Errors of refraction, however, are very common, and at young adulthood 64% of ELBW versus 37% NBW subjects required prescription glasses [24].
A serious nding that bears highlighting is the risk of late retinal
detachment (RD) reported in 4% of 149 ELBW (95% CI: 0.87, 7.19)
young adults in their early 20s [24]. In addition, three other young
adults had retinal tears that required surgery. Further follow-up
into their 30s in the ongoing study elicited a few more cases of
RD as well as development of cataracts in two cases (S. Saigal et al.,
unpublished data). These ndings are limited by the small sample
size, but have not been reported in other longitudinal cohort
studies. However, a recent Swedish population-based registry of 3
million children and young adults found late RD in 42 cases out of
20 470 subjects (0.2%) born before 32 weeks of gestation [25].
Compared to subjects born at term, the adjusted hazard ratio (HR)
for RD for infants born <28 weeks of gestation was 19.2 (95% CI:
10.3e35.8); it was lower for those born between 28 and 31 weeks of
gestation with HR of 4.3 (95% CI: 2.7e6.9). The gestational age of the
cohort followed by Saigal et al. [24] was likely lower than that in the
Swedish report, accounting for the higher prevalence of RD in the
former study. These ndings suggest a causal relationship between
short gestational age and the risk of RD. Despite careful monitoring,
there is still a 3e9-fold increase in the risk of RD in the current
survivors born extremely prematurely. As the risk of retinal

S. Saigal / Seminars in Fetal & Neonatal Medicine 19 (2014) 125e130

detachment increases with age, it is imperative that these young

adults be followed through life.
3.3. Audiological problems
The reported incidence of deafness is quite variable and ranges
from 0% [24] to 7% [21] in ELBW young adults. The incidence of
deafness in VLBW young adults was 1.2% in the Cleveland study
[22], 7.4% in the Dutch study [26], and 5.8% in Swedish VLBW males
[23].
4. Adult functioning
4.1. Educational achievements
In terms of school completion, a gestational age gradient was
again observed in the Norwegian study [11]: at 23e27 completed
weeks of gestation 68% had completed high school, and 25% had
completed a bachelors degree: the corresponding gures for 28e
30 weeks of gestation were 70% and 28%, compared with 75% and
35% for those born at term. Although Lefebvre et al. [21] reported
that fewer ELBW subjects had obtained a secondary school
diploma compared to normal birth weight group (56% vs 85%),
this was related to the fathers socio-economic score. Some
studies have reported no statistically signicant differences between ELBW and controls in the proportion that graduated from
high school (82% vs 87%) [20]. Sex differences were observed
within this ELBW group, with a higher proportion of male participants with less than high school education (25% vs 10%,
P 0.01), and fewer males enrolled in, or graduated from, postsecondary education (49% vs 71%, P 0.01). Also, a signicantly
lower proportion of ELBW young adults was enrolled in postsecondary education (23% vs 37%, P 0.01). A similar nding
was reported in the Swedish National cohort study [12], with 26%
of those born with a gestational age of 28 weeks who had
completed university education, compared to 38% of those born at
NBW; there were no differences in high school attainment by
gestational age. In a much smaller, geographically dened Swedish cohort born in the late 1980s, information was elicited through
mailed questionnaires at age 20 years. No differences were noted
in education, occupation, or social situation compared to controls
[27]. Similar to the ndings by Saigal et al. [20], Hack et al. [22]
reported a female advantage, with 66% of VLBW males and 81%
of VLBW females who completed high school, compared with 75%
of term males and 90% of term females. Ironically, the rates of
completion of high school education among ELBW young adults in
the Ontario study [20] and in a Minnesota single hospital report of
births between 23 and 26 weeks of gestation [28] were similar to
that of the NBW controls in the Cleveland study [22], demonstrating the powerful effect of social class on educational
attainment.
4.2. Employment
As a group, adults born very preterm or very low birth weight
have higher rates of unemployment and lower net income, partly as
a consequence of being disabled. Moster et al. [11] showed that
although unemployment rates were not different, Norwegian
young adults born between 23 and 27 completed weeks of gestation had lower job-related income (23%) than those born at term
(20%) and a higher proportion received social security benets
(19.9% versus 17.6%), but the differences were not statistically signicant (RR: 1.2; 95% CI: 0.9e1.5). When people with disabilities
were excluded, there was still a signicant, though weaker, association between lower gestational age overall and the proportions

127

who attained a higher education, obtained a better-paying job, or

who received social benets. Similar ndings were reported from
the Swedish National Cohort study [12]. A higher proportion of
adults born between 24 and 28 weeks of gestation compared with
those born at term were receiving social welfare (5% vs 1.8%) and
disability assistance (0.6% vs 0.1%). However, overall a signicant
proportion of all those born between 24 and 28 weeks of gestation
were employed and more were paying taxes than receiving
benets.
At a mean age of 23 years, 48% of Ontario ELBW subjects vs 57%
of controls had permanent employment, and there were no differences in occupational prestige between the groups [20].
However, in a sub-analysis, a higher proportion of ELBW than
NBW participants were neither employed, nor at school (26% vs
15%, P 0.02), largely due to chronic illnesses or permanent
disability (46% vs 15%, P 0.03). Female ELBW subjects were more
disadvantaged in terms of employment. In the Dutch study [26],
three times as many VLBW 19-year-olds than controls were neither
employed nor at school (7.6% and 2.6%, respectively).
4.3. Living arrangements, dating and marriage
A higher proportion of 24e28-week gestation young adults than
controls were living at home with their parents between 23 and 29
years of age in the Swedish National Study (18.3% vs 15.0%,
P 0.001).12 In the Helsinki study, VLBW young adults who were
free of major disabilities (age range: 18e27 years) were 1.7-fold
more likely to be living in the parental home than controls (95%
CI: 1.01e3.05; P 0.05); this association was signicant only for
men [29]. Interestingly, although Finnish and Canadian cohorts had
similar socio-demographic background and access to health care,
no statistically signicant differences were observed in the proportion of ELBW young adults compared with controls still living at
home (55% vs 47%) in the latter study [20].
Moster [11] reported that a lower proportion of Norwegian
young adults born between 23 and 27 weeks of gestation than
controls were either married or cohabiting (10.0% vs 18.3%,
respectively; RR: 0.7; CI: 0.5e1.0). This was also true for the
Swedish [12] and the Finnish cohorts [29]. Further, several studies
have reported that VLBW young adults were less likely to experience sexual intercourse, and they had fewer sexual partners
compared with controls [22,29,30]. In another Swedish regional
cohort study of infants born between 1987 to 1988, no differences
were observed at age 20 years between VLBW and NBW young
adults in employment, living independently or cohabiting, as
elicited through postal questionnaires [27]. Cooke [31] also reported no differences in sexual experiences or intimate relationships between the VLBW and control subjects for either
gender.
4.4. Reproduction
Who would have thought that one day we would be discussing
reproduction as an outcome in our extremely premature survivors?
Biological parenthood was reported in 28.7% of subjects born 23e
27 weeks, but was lower than the rate of 43.1% in term controls (RR:
0.8; 0.6e1.0) in the Norwegian study [11]. Hack et al. [22] reported
fewer pregnancies in women, but not in the partners of men, at age
20 years. Saigal et al. [20] reported no differences in reproductive
rates or parenthood in a longitudinal cohort study of ELBW infants
compared to term-born controls. However, the power to detect
such differences was limited by the small sample sizes and the
young age of the participants.
The Norwegian Medical Birth Registry study [13] of births between 1967 and 1976 reported strong evidence of lower

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S. Saigal / Seminars in Fetal & Neonatal Medicine 19 (2014) 125e130

reproductive rates for both men and women who had been born
very preterm. Only 25% of women and 13.9% of men who had been
born between 22 and 27 weeks of gestation had subsequently
reproduced, in contrast to 68% of women and 50% of men born at
term. Interestingly, only female premature participants were at
increased risk of recurrent preterm birth, with a dose response
based on the degree of maternal prematurity. The risk of having a
preterm offspring was 14% for women born between 22 and 27
weeks of gestation compared to 6.4% for NBW women. A subsequent Swedish population-based registry [32] has conrmed the
above nding of reduced probability of reproduction by very premature males and females (HR: 0.78; 95% CI: 0.70e0.86 for males;
HR: 0.81; 95% CI: 0.75e0.88 for females). Without these large databases, the evidence for reduced reproductive rates would have
been very weak.
Apart from the biological and physiological factors for the
reduced reproductive rates, psychosocial, nutritional, and economic factors may affect the ability to reproduce. As Swamy et al.
[13] point out, survivors born preterm may have more difculties in
nding a partner because of medical factors, disabilities and
cognitive decits. Moreover, several studies have shown that fewer
premature infants, and particularly those with disabilities, experience sexual intercourse [22,29,30,33]. Also, in western societies the
mean age of parenting is increasing, and this may additionally
contribute to decreased fertility and possible childlessness in the
future.
4.5. Social relationships and risk-taking behaviours
A Swiss study [34] reported poorer social relations in VLBW
young adults: there were fewer visits from friends and family
(P 0.04); VLBW young adults spent less time with friends
(P 0.001), and had lower mean number of friends than controls.
Cooke [31] reported that VLBW young adults in Liverpool participated similarly to controls in social activities. Saigal et al. [33] reported similar peer, partner and family relationships, including
mean number of friends, and involvement in clubs and social activities, among ELBW young adults and term controls. The rates of
overall criminality in the Norwegian National Study were similar in
those born 23e27 weeks (9.6%) than in those born at term (8.7%;
RR: 1.1; 0.8e1.6) [11].
Most studies, however, are consistent in the nding of lower
risk-taking behaviours among premature young adults compared
to their term-born peers [12,22,30,31,33]. These include a lower
proportion that used drugs or consumed alcohol, smoked cigarettes
or marijuana, exhibited delinquent behaviours, rates of crime
conviction or incarceration, or contact with police. It is not entirely
clear, but the reasons for these behaviours may be due to increased
parental monitoring [22], shy personality [35,36], and possibly
fewer social opportunities.
5. Functional status and quality of life
How do we dene functional outcomes, and what variables and
measurement tools should we consider in assessing the same? In
the past, the ability of a person to perform the routine activities of
daily living, as well as leisure and socially allocated roles, was
considered as an acceptable functional outcome. Functional status
is therefore a way of reporting the limitations resulting from a
disease or illness in an objective manner.
Although most studies show that the general health of former
premature infants improves by adulthood, they are still left with
some residual functional limitations. These include visual and
hearing decits (described above), dexterity and clumsiness; and,
in a minority, reduced self-care abilities [24]. These limitations

remained signicant, even when young adults with disabilities

were excluded. Consistent with this study, several investigators
have reported that VLBW young adults lead a more sedentary
lifestyle, and have limited participation in strenuous physical activities [22e24,37].
The above traditional biomedical model of reporting functional
limitations per se is no longer considered sufcient. With the current broader approach in dening patient outcomes, this denition
has been expanded to combine biomedical factors with social science approaches to obtain a more holistic picture of an individuals
functioning. It is therefore recommended that the subjective
views e how a person feels e should be elicited directly from the
person most affected by the process. Yet, there are few studies that
address the personal perspectives of the individual in question at
adulthood.
Several reviews of the denition and conceptual framework of
QoL have been published [38,39]. However, in the context of health
care, most studies report the health-related quality of life (HRQL),
that allows an individual to implicitly weigh aspects of their health
and provide a personal valuation of the same. It is this personal
valuation that distinguishes HRQL from other measures of health
and function [38,39].
Many different techniques and measures have been used to
assess the HRQL of premature infants at adulthood. Using a
structured questionnaire that included both objective and subjective measures, Danish investigators [40,41] reported that on
both these variables, non-impaired VLBW 18e20-year-olds were
similar to their NBW peers. However, the QoL was lower in those
with impairments. Three studies used the SF36, a mailed health
questionnaire. In the British study [31], VLBW 19e22-year-old
males rated themselves lower only in physical functioning and
health perception compared to their NBW peers. The Swiss study
[37] reported no differences in both physical and psychological
functioning in their 23-year-old young adults <1250 g birth weight
compared to their peers born at NBW. In another Swiss study [42]
of 55 ELBW young adults, lower self-perceived mental health and
lower socio-emotional functioning was noted compared to European norms.
HRQL was assessed longitudinally in Canadian ELBW subjects
at adolescence [43] and at young adulthood [44], using directly
measured preferences with the standard gamble method. Contrary to expectations, there were no differences in the mean
utility scores between the overall ELBW young adults and their
NBW counterparts; nor were there any differences between
those with and without disabilities [44]. The Collaborative
Project on Preterm and Small for Gestational Age Infants (POPS)
in The Netherlands used the HUI3 utility formula applied to the
self-reported health status of VLBW young adults at age 19 years
[45]. They reported fairly high HRQL (0.87, on a scale of 0e1),
and remarkable stability from adolescence to young adulthood.
HRQL was negatively associated with internalising problems and
with physical disabilities. Further follow-up to age 28 years
showed that the HRQL increased from 0.83 at age 19 years to
0.85 at age 28 years [46]. A major limitation was that only onethird of the cohort participated at age 28 years, and data for the
remaining two-thirds were imputed. Nor did they have a control
group.
Thus, despite impairments and varying methods of eliciting
QoL, it appears that former premature young adults report
their QoL to be fairly high d comparable to their term-born
counterparts. This phenomenon of discordance between functional limitations and high valuation has been termed disability
paradox by Albrecht and Devleiger [47], and has been reported
in many non-premature adult populations. The explanation
for the discordance remains elusive. Self-reported QoL

S. Saigal / Seminars in Fetal & Neonatal Medicine 19 (2014) 125e130

provides complementary information to traditional biomedical

outcomes, and should be elicited from individuals to obtain their
personal perceptions, and to tailor their care to their perceived
needs.
6. Prematurity, aging, and mortality in young adulthood
In a Norwegian meta-analysis, an inverse relationship was
found between birth weight and mortality in adulthood [48].
There was a 6% lower risk of deaths per kilogram among higher
birth weights (adjusted HR: 0.94; 95% CI: 0.92e0.97). However,
the rst large study to gauge the effects of gestational age on
mortality at young adulthood was derived from the National Birth
and Death Registry from Sweden [15]. Included in this study were
singletons born between 1973 and 1979 and who survived the
rst year of life. Mortality rates (per 1000 person-years) by
gestational age at birth were 0.94 for 22e27 weeks and 0.86 for
28e33 weeks of gestation. There was an independent, stepwise
inverse relationship between gestational age and mortality, and it
affected both sexes similarly. Preterm birth was associated with
increased mortality even among those born late preterm. The
underlying mechanisms are unknown, but may be related to fetal
and postnatal nutritional abnormalities, hormonal alterations or
genetic factors. Prematurity rates in Sweden are only 5%, and
mortality risk will no doubt have a larger impact in countries
where the prematurity rates are higher. This may be further
compounded by the current survival of more and more immature
infants.
7. Conclusion
Although most VLBW infants go through signicant difculties in childhood and adolescence, by and large, by the time
they reach adulthood, they do better than expected in terms of
adult functioning. Many young adults may still have chronic
health conditions and some functional limitations, but despite
that, they seem to be fairly resilient and lead relatively normal
lives [1e3,11,29]. A most rewarding nding is that a signicant
majority of VLBW and ELBW participants rated their QoL equivalent to that of their peers. Certainly, although there is a gestational age gradient in the incidence and severity of disabilities,
there is no such difference in terms of subjective valuation of
their QoL. Whether these ndings are generalisable to the more
recent survivors remains to be seen. One might anticipate that
their outcomes might be substantially better, as these infants are
the beneciaries of technological and social advances in care.
However, there are also some reservations as increasing numbers
of extremely immature infants are surviving, and disability rates
have not declined correspondingly.
The mean age of follow-up of the studies reported to adulthood
so far is still fairly young. It is likely that the disparity in occupational prestige and income may widen signicantly when they are
in their 30s or 40s. There is also some suggestion of higher rates of
psychopathology as they become older [49,50]. In addition, there
are concerns that other problems, such as diabetes, hypertension,
atherosclerosis and cardiovascular diseases may manifest as they
reach middle-age [4,8]. There is already some evidence of insulin
resistance [5e7], and higher blood pressure among VLBW young
adults [7,9,51,52].
Thus, we need to be vigilant regarding the long-term outlook
for the former preemies in their middle age, and ensure that
further follow-up of the above populations is continued. In
addition, the current cohorts who are now adolescents from the
recent era of neonatal intensive care need to be monitored to
adulthood.

129

Practice points
 Residual neurodevelopmental disabilities and functional
limitations persist to adulthood.
 Most studies report lower educational attainment and
lower income.
 The proportions married or cohabiting and reproductive
rates are lower.
 The quality of life is similar to term-born peers.
 There is early evidence of more psychopathology, higher
blood pressure and insulin resistance.

Research directions
 Longer-term follow-up to monitor the cardiovascular and
metabolic sequelae until middle age.
 Monitor and treat psychopathology, particularly in
females.
 Collect data to middle adulthood on the current survivors.

Conict of interest statement

None declared.
Funding sources
None.
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