0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Depression in Young Adults With Very Low Birth Weight:  The Helsinki Study of Very Low-Birth-Weight Adults FREE

Katri Räikkönen, PhD; Anu-Katriina Pesonen, PhD; Kati Heinonen, PhD; Eero Kajantie, MD, PhD; Petteri Hovi, MD; Anna-Liisa Järvenpää, MD, PhD; Johan G. Eriksson, MD, PhD; Sture Andersson, MD, PhD
[+] Author Affiliations

Author Affiliations: Departments of Psychology (Drs Räikkönen, Pesonen, and Heinonen) and Public Health (Dr Eriksson) and Institute of Clinical Medicine and Hospital for Children and Adolescents (Drs Kajantie, Hovi, Järvenpää, and Andersson), University of Helsinki; and Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute (Drs Kajantie, Hovi, and Eriksson); Helsinki, Finland.


Arch Gen Psychiatry. 2008;65(3):290-296. doi:10.1001/archgenpsychiatry.2007.40.
Text Size: A A A
Published online

Context  Little is known about the mental health outcomes of very low-birth-weight (VLBW) (<1500 g) infants in young adulthood.

Objective  To test whether young adults aged 18 to 27 years with VLBW differ from term control subjects in depressive symptoms, current use of antidepressant medication, and the rate of depression diagnosed by a physician.

Design  Retrospective longitudinal study.

Setting  Academic research.

Participants  A total of 162 VLBW young adults (response rate, 65.1%) and 172 term control subjects (response rate, 54.8%) born between February 22, 1978, and November 8, 1985, in Helsinki, Finland.

Main Outcome Measures  Antidepressant use, history of physician-diagnosed depression, Beck Depression Inventory score, and Center for Epidemiologic Studies Depression Scale score.

Results  The VLBW participants reported 20.1% (95% confidence interval [CI], −40.8% to −5.1%) lower CES-D scores than the controls (P =.02). However, this finding was confined to 110 VLBW participants who were born appropriate for gestational age (birth weight ≥−2 SDs according to Finnish birth weight charts), whose Center for Epidemiologic Studies Depression Scale scores were 29.1% (95% CI, −53.7% to −8.4%) lower than those of the controls (P =.004). Furthermore, VLBW participants born appropriate for gestational age were 4.8 (95% CI, 1.3-10.0) times less likely to report a depression diagnosis than controls (P =.02). In contrast, 52 VLBW participants born small for gestational age (birth weight <−2 SDs according to Finnish birth weight charts) reported 36.2% (95% CI, 1.1%-83.5%) higher Beck Depression Inventory scores (P =.04), were 4.0 (95% CI, 1.1-14.3) times more likely to use antidepressants (P =.03), and were 2.5 (95% CI, 1.0-6.3) times more likely to report a depression diagnosis (P =.04) compared with controls.

Conclusions  This is the first study (to our knowledge) to show that intrauterine growth pattern may modify associations between VLBW and depression. Intrauterine growth retardation rather than VLBW per se may pose a risk of depression in young adulthood.

Figures in this Article

Introduction of modern methods of neonatal intensive care in the past few decades has resulted in improvements in survival and in decreases in rates of neurosensory and neuromotor impairments of preterm infants with very low birth weight (VLBW) (<1500 g).1,2 However, studies of long-term outcomes of VLBW infants have indicated problems in mental health, psychological development, and social and academic competencies in childhood3 and adolescence.4 Accumulating evidence suggests that these problems may persist into young adulthood. Young adults with VLBW score lower on intelligence57 and academic achievement3 tests, report less satisfactory school performance and ability to learn and concentrate,8 and are less frequently enrolled in or graduate from high school5 than control subjects born at term.

Relative to the data on cognitive and academic achievements, data on mental health outcomes of VLBW young adults are scanty and inconsistent. Cooke1 found no differences between subjects aged 19 to 22 years with VLBW and term control subjects in self-reported anxiety, depression, or overall mental health. Also, Bjerager et al8 found no differences between subjects aged 18 to 20 years with VLBW and term control subjects in self-reported mental health. Hack et al7 found that (relative to term control subjects) 20-year-old subjects with VLBW were characterized by a lower level of self-reported delinquent behavior but had higher levels of parent-reported thought and attention problems and withdrawn and anxious-depressed behaviors; in addition, women with VLBW were characterized by more self-reported internalizing behaviors. Apart from these data on VLBW young adults, other data are more consistent in demonstrating that subjects with low birth weight (LBW) (≤2500 g) are prone to experiencing depressive symptoms912 and to receiving a clinical diagnosis of depression13 at various points in life compared with those with birth weights greater than 2500 g.

In the present study, we tested whether young adults aged 18 to 27 years with VLBW differ from term control subjects in depressive symptoms, current use of antidepressant medication, and the rate of depression diagnosed by a physician. Findings from a few studies7,14,15 suggest that intrauterine growth patterns reflected in being born small for gestational age (SGA) and appropriate for gestational age (AGA) may modify the developmental outcomes of VLBW infants. Therefore, we also tested whether VLBW young adults born AGA and SGA differ from term controls and from each other in depressive symptoms, current use of antidepressants, and rate of depression diagnosis. Finally, we tested whether common pregnancy-related risk factors such as maternal smoking and preeclampsia are related to the outcome measures.

PARTICIPANTS

The original study cohort consisted of 474 consecutive VLBW infants born between February 22, 1978, and November 8, 1985, in one of several maternity hospitals that serve the geographic area of the province of Uusimaa, Finland. Of these, 335 (70.7%) were discharged alive from the neonatal intensive care unit of the Children's Hospital at the Helsinki University Central Hospital, the only tertiary neonatal care center in the province of Uusimaa. Of those discharged alive and those who died, 238 (71.7%) and 94 (28.3%), respectively, were born AGA (birth weight ≥−2 SDs according to Finnish birth weight charts),16 and 97 (68.3%) and 45 (31.7%), respectively, were born SGA (birth weight <−2 SDs according to Finnish birth weight charts). The neonatal mortality rates of infants born AGA and SGA were not statistically significantly different (χ21 = 0.55, P = .49).

We selected control subjects from the records of all consecutive births of the hospitals. For each VLBW survivor, we included the next available singleton infant who was of the same sex, born at term (gestational age, ≥37 weeks), and not SGA as a control subject. We then traced these individuals in the Population Register Center as young adults. Mortality rates from hospital discharge to June 20, 2004, were 1.8% for young adults with VLBW and 1.0% for term controls; we were able to trace 95.1% and 96.8%, respectively, of the survivors. We invited 255 young adults with VLBW and 314 controls who were living in the greater Helsinki area, and 166 (65.1% [43.3% men]) young adults with VLBW and 172 (54.8% [40.6% men]) controls agreed to participate in the study as previously described.17 Of 166 VLBW participants, 162 had valid data on the main outcome measures; 2 participants did not fill out the depressive symptom scales embedded in a psychological survey, and 2 additional participants had attended special education for the developmentally delayed during school age and were excluded.

As previously described by Hovi et al,17 participants in this study and nonparticipants were similar in birth weight, standardized birth weight, gestational age, maternal preeclampsia, days of mechanical ventilation, days of oxygen, and discharge age, except that the rate of cerebral palsy at 15 months of age was lower among the VLBW participants (10 subjects [6.0%]) than among the VLBW nonparticipants (17 subjects [19.1%]) (P =.005). The study protocol was approved by the Ethics Committee for Children and Adolescents' Diseases and Psychiatry at the Helsinki University Central Hospital, and all participants gave their written informed consent. The perinatal data were derived from maternal welfare clinic and hospital records; parental, participants' developmental, and young adult characteristics were measured at a clinical examination.17

MAIN OUTCOME MEASURES

In conjunction with the clinical visit,17 participants' depressive symptoms were assessed using questionnaires, and they were asked whether they used antidepressant medication currently and if they had been diagnosed by a physician as having depression. The Beck Depression Inventory (BDI)18 and the Center for Epidemiologic Studies Depression Scale (CES-D)19 were used to measure the severity and frequency of depressive symptoms. In addition to considering the BDI and CES-D scores as continuous measures, we used the predefined and validated cut point scores of 10, 19, and 30 for defining those at risk of mild, moderate, and severe depression, respectively, according to the BDI,18 as well as a cut point score of 16 for defining those at risk of moderate-severe depression according to the CES-D.19 The internal reliability coefficient (Cronbach α) was .91 for the BDI and for the CES-D.

Sixteen participants reported that they were currently taking antidepressants. Ten were taking serotonin reuptake inhibitors, 4 were taking noradrenaline-serotonin reuptake inhibitors, 1 was taking tricyclic antidepressants, and 1 was taking an unnamed antidepressant. Thirty-four participants reported a past diagnosis of depression.

STATISTICAL ANALYSIS

As the primary data analytic tools, we used multiple linear regression analysis (depressive symptoms as continuous measures) and logistic regression analysis (categories of depressive symptoms [with those reporting no symptoms as a reference group], current use of antidepressants, and depression diagnosis). We examined differences in the main outcome measures between (1) VLBW young adults and term controls, (2) VLBW young adults born AGA and term controls, and (3) VLBW young adults born SGA and term controls, in addition to (4) differences within the VLBW group between those born AGA and those born SGA. Because women, older individuals, those with cognitive problems, those in lower socioeconomic groups, and those with higher body mass index (BMI) have been shown to demonstrate greater preponderance to depression,11 and because BMI gain is among the adverse effects of some antidepressants (eg, some noradrenaline-serotonin reuptake inhibitors that our study participants reported using), the group comparisons were conducted with the following covariates in the models: sex, age, parental level of education, BMI (calculated as weight in kilograms divided by height in meters squared), and attendance at a modified curriculum during school age (as a proxy of cognitive problems). The BDI and CES-D scores were logarithmically transformed to attain normality. Group differences are reported in percentages and in odds ratios with 95% confidence intervals (CIs).

CHARACTERISTICS OF THE SAMPLE

Table 1 gives the birth weight, gestational age, and other perinatal, parental, and adult characteristics in the VLBW group (162 subjects [93 women and 69 men], categorized as 110 born AGA [62 women and 48 men] and 52 born SGA [31 women and 21 men]) and in the term control group (172 subjects [103 women and 69 men]). In addition to differing from term control subjects, VLBW young adults born SGA compared with those born AGA were more frequently born to mothers with preeclampsia (P < .001). Further comparisons within the VLBW group showed that, compared with their VLBW counterparts born AGA, VLBW women born SGA were on average 3.3 cm shorter (P =.05) and had a 2.0 lower BMI in young adulthood (P =.02), while VLBW men born SGA had a 2.2 higher BMI in young adulthood (P =.02). There were no other statistically significant differences between the VLBW young adults born AGA and SGA.

Table Graphic Jump LocationTable 1. Characteristics of Very Low-Birth-Weight (VLBW) Infants Born Appropriate for Gestational Age (AGA) and Small for Gestational Age (SGA) and of Term Control Subjectsa
ASSOCIATIONS BETWEEN COVARIATES AND DEPRESSION

Next, we examined the associations between the covariates and depression in the VLBW and control groups. Compared with men, women in the VLBW and control groups scored 64.0% and 33.6% higher, respectively, on the CES-D and 116.2% and 40.5% higher, respectively, on the BDI (P < .01 for all). Among the VLBW group, current use of antidepressants was reported by 9 women (5 born SGA and 4 born AGA) and by no men (P =.008), while among the control group current use of antidepressants was reported by 2 women and by 5 men (P =.08). Diagnosis of depression was reported by 13 women (mean [SD] age at onset, 19.6 [2.8] years; age range, 13-25 years) and by no men (P =.001) among the VLBW group but by 14 women and by 7 men among the control group (P =.48).

We also tested whether the other covariates were associated with depression. After controlling for sex, VLBW young adults who had attended a modified curriculum reported lower CES-D and BDI scores (P < .03 for both), while none reported current use of antidepressants or a depression diagnosis. Among VLBW women, higher BMI was related to a greater likelihood of use of antidepressants (P =.06). In the control group, after controlling for sex, higher BMI in adulthood was related to higher BDI scores (P =.04), and older age was related to greater likelihood of reporting a depression diagnosis (P =.04). There were no other statistically significant associations between the covariates and depression in the VLBW and control groups.

Finally, we tested whether the depressive outcome measures were interrelated in the VLBW and control groups. All the associations were in the expected direction and were statistically significant (P < .001 for all).

DIFFERENCES BETWEEN VLBW YOUNG ADULTS AND TERM CONTROL SUBJECTS IN DEPRESSION

As summarized in Table 2, after controlling for sex, age, parental education, BMI in young adulthood, and attendance at a modified curriculum, participants in the VLBW group reported 20.1% lower CES-D scores than the controls (P =.02). Seventeen percent (n = 27) of VLBW young adults and 25.0% (n = 43) of term controls were at increased risk of moderate-severe depression according to the CES-D (odds ratio, 0.6; 95% CI, 0.3-1.0; P =.06). The groups did not differ in BDI scores. Twelve percent (20 subjects [16, 3, and 1 of mild, moderate, and severe categories, respectively]) of VLBW participants and 15.1% (26 subjects [15, 8, and 3 of mild, moderate, and severe categories, respectively]) of term controls were at increased risk of mild-severe depression according to the BDI scores (odds ratio, 0.8; 95% CI, 0.4-1.5; P =.46). The VLBW participants and control subjects did not differ from each other in their current use of antidepressants or in their rate of depression diagnosis.

Table Graphic Jump LocationTable 2. Depressive Symptoms Among Young Adults With Very Low Birth Weight (VLBW) and Among Term Control Subjectsa

Next, we tested whether VLBW young adults born AGA and those born SGA differed from term control subjects in depressive symptoms. As summarized in Table 2, after adjusting for the covariates, the VLBW participants born AGA reported 29.1% lower CES-D scores than the control subjects (P =.004). Figure 1 shows that their risk of moderate-severe depression according to the CES-D scores was 2.6 (95% CI, 1.3-5.6) times lower than that of the term controls (P =.009). The VLBW participants born AGA were also 4.8 (95% CI, 1.3-10.0) times less likely to report a depression diagnosis than the control subjects (P =.02) (Table 2 and Figure 2).

Place holder to copy figure label and caption
Figure 1.

Rates of very low-birth-weight (VLBW) young adults born appropriate for gestational age (AGA) and small for gestational age (SGA) and of term control subjects at risk of moderate-severe depression according to the Center for Epidemiological Studies Depression Scale (CES-D ≥16) and at risk of mild-moderate depression according to the Beck Depression Inventory (BDI ≥10). Error bars refer to 95% confidence intervals, and P values refer to group comparisons after adjusting for sex, age, parental educational attainment, body mass index in young adulthood, and attendance at a modified curriculum during school age.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Rates of very low-birth-weight (VLBW) young adults born appropriate for gestational age (AGA) and small for gestational age (SGA) and of term control subjects using antidepressants and reporting a depression diagnosis. Error bars refer to 95% confidence intervals, and P values refer to group comparisons after adjusting for sex, age, parental educational attainment, body mass index in young adulthood, and attendance at a modified curriculum during school age.

Graphic Jump Location

In contrast, the VLBW participants born SGA reported 36.2% higher BDI scores than the control subjects (P =.04) (Table 2). Figure 1 shows that their risk of mild-severe depression according to the BDI scores was 2.1 (95% CI, 0.9-4.9) times greater than that of the control subjects (P =.08). Furthermore, the VLBW participants born SGA were 4.0 times more likely to report current antidepressant use (P =.03) and 2.5 times more likely to report a depression diagnosis (P =.04) compared with the control subjects (Table 2 and Figure 2).

DIFFERENCES BETWEEN VLBW YOUNG ADULTS BORN AGA AND SGA IN DEPRESSION AND OTHER PERINATAL RISKS

After adjustments for the major covariates, comparisons between the VLBW young adults born AGA and SGA in depressive symptoms showed that those born SGA had 25.2% higher CES-D scores (P =.06) and 50.4% higher BDI scores (P =.007) than those born AGA (Table 2). Figure 1 shows that the risk of VLBW young adults born SGA for moderate-severe depression according to the CES-D scores was 3.8 (95% CI, 1.5-9.5) times greater (P =.006) and for mild-severe depression according to the BDI scores was 3.7 (95% CI, 1.3-10.4) times greater P =.01) compared with the risk of VLBW young adults born AGA. Furthermore, VLBW young adults born SGA were 7.3 times more likely to report current antidepressant use (P =.03) and 18.4 times more likely to report a depression diagnosis (P =.001) compared with those born AGA (Table 2 and Figure 2).

Maternal smoking during pregnancy was associated with higher BDI scores (32.5% [95% CI, 0.0%-74.5%] for offspring of smokers, (P = .05), independent of VLBW and the other covariates, but not with CES-D scores, antidepressant use, or depression diagnosis (P > .35 for all). Maternal preeclampsia was not statistically significantly associated with depression (P > .68). We then reran all the analyses contrasting VLBW participants with term controls, VLBW AGA and SGA participants with term controls, and against each other, with maternal smoking during pregnancy and preeclampsia as additional covariates. The statistically significant associations remained so (P < .05 for all).

The associations remained statistically significant (P < .05 for all) after excluding from the analyses 13 subjects with cerebral palsy and 2 subjects with mild developmental delay (despite reporting a diagnosis of developmental delay, both had attended a standard school curriculum at age-appropriate school grades and were retained in the previously described analyses). Those with and without these impairments did not differ from each other in depressive symptoms (P > .31), and none of those with impairments reported using antidepressants currently or having a depression diagnosis. In the VLBW group, twins and triplets did not differ from singletons in depressive symptoms (P > .33 for both), and adjustment for multiple pregnancy had no effect on our results.

Finally, we tested whether differences in depressive symptoms between the groups varied by sex but found no evidence for sex interaction (P > .25 for all interaction terms). Tests for sex interaction in the analyses of antidepressant use and depression diagnosis were not feasible, as these were reported by women only. However, when we restricted these analyses to women, the associations remained statistically significant (P < .05 for all).

We found that young adults with VLBW reported less depression in young adulthood than term control subjects. However, this was strongly dependent on intrauterine growth pattern of the VLBW participants: those born AGA reported fewer depressive symptoms and were less likely to report a depression diagnosis than term controls, while those born SGA reported more depressive symptoms, used antidepressants more frequently, and were more likely to report a depression diagnosis than term controls. Furthermore, not only did the VLBW participants differ from their term counterparts in depressive symptoms but also, when those born AGA and SGA were contrasted with each other, those born SGA reported more depression. We found no evidence that sex, age, maternal preeclampsia, BMI in young adulthood, parental educational attainment, maternal smoking during pregnancy, and attendance at a modified curriculum during school age explained the findings. The results did not change when participants with cerebral palsy or mild developmental delay were excluded from the analyses.

These findings are in disagreement with earlier findings on mental health outcomes of VLBW young adults, as no studies (to our knowledge) have indicated that VLBW young adults born AGA would fare better than their counterparts born SGA or at term. Two studies1,8 found no differences between young adults with VLBW and term control subjects in self-reported mental health, including depression. A third study7 found less self-reported delinquent behavior among VLBW women and men, more self-reported internalizing problem behavior among VLBW women, and a range of other problem behaviors among VLBW women and men as indicated by their parents. There are methodological differences between the present study and these previous studies such as measurements used, mental health outcomes, informants (self vs parents), diversity in ethnic backgrounds, and sample differences in the range of birth year and age at testing. However, inferences on the extent to which these differences account for the discrepant findings cannot be made. To our knowledge, ours is the first study to report that mental health outcomes of VLBW participants may be dependent on intrauterine growth pattern.

However, our findings parallel some of earlier findings that suggest that the developmental outcomes of VLBW infants may be modulated by AGA and SGA status. Hack et al7 noted that the parent-reported greater inattention that characterized VLBW young adults leveled off when VLBW infants born SGA were removed from the analyses. However, other problem behaviors characterizing VLBW young adults' self-reports or parent-reports were unaffected by AGA or SGA status. A recent study14 of VLBW adolescents indicated that SGA status was the best predictor of parent-reported behavior problems that characterized VLBW adolescents. Furthermore, a small but growing number of findings regarding SGA and AGA infants' cognitive development suggest that VLBW infants born SGA may fare worse during the course of development than those born AGA.15

Our findings also parallel recent findings among preterm adults. Preterm 31-year-old adults who weighed less than 1900 g at birth and whose standardized birth weight (−0.4 SD according to birth weight charts) is comparable to that of the VLBW AGA group in our study reported fewer depressive symptoms and experienced psychiatric disorders less frequently than term control subjects.20 Finally, our findings also parallel those among cohorts not restricted to participants born preterm.913 These findings demonstrate that adolescents and adults with LBW report increased rates of depressive symptoms and more frequently have a depression diagnosis. Studies9,1113,21 in which gestational age at birth has been available show that these associations are attributable to slow fetal growth rather than solely to prematurity. Therefore, our findings add to the literature by underlining the importance of differentiating VLBW infants born AGA from those born SGA. The results also suggest that intrauterine growth retardation, as reflected in SGA status, rather than VLBW per se may pose a risk of depression later in life.

Although the mechanisms of these associations are unknown, intrauterine glucocorticoid programming of the hypothalamic-pituitary-adrenal axis (HPAA) has been proposed as a key candidate mechanism.22,23 Findings in animals have linked reduced activity of the placental enzyme 11β-hydroxysteroid dehydrogenase type 2 (which protects the fetus from excess maternal cortisol) with intrauterine growth restriction and with increased HPAA activity and anxiety like behaviors.24 In humans, preterm25,26 and term26 SGA births have been associated with reduced activity of this placental enzyme. Small size at preterm27 and term28 birth is also linked with altered HPAA activity, which in turn is among the key biologic characteristics of depression. Obviously, the HPAA is coupled with many other hormonal systems, including the growth hormone–insulin–like growth factor system, which is a key regulator of growth and brain development29 and may be involved in the pathogenesis of depression.30

Genetic mechanisms also cannot be overlooked. There is evidence that depression and depressive symptoms are at least moderately heritable.31 Maternal distress during pregnancy may be associated with shorter length of gestation32 and with less optimal development of the offspring.33 Findings from a recent study9 of young adults with LBW suggest that the association between LBW and depression is not explained by maternal depression-anxiety during pregnancy, but we had no parental history of depression available in our study and cannot resolve the question of confounding by parental depression.

Although an obvious explanation of the findings of less depression among AGA infants compared with SGA infants is their more optimal development until delivery, we have no ready explanation of why AGA infants scored lower in depressive symptoms than term control subjects. We can only speculate that if the physiologic stress regulatory systems of the AGA infants compared with the SGA infants are less affected in utero,26 making them physiologically less vulnerable to stress-related adversities, perhaps their risk is further decreased by their lower threshold to stress and to depression-inducing environments: VLBW young adults are prone to less risk taking and delinquent adulthood compared with term control subjects.7,8 Parenting may have a role in buffering the risk further.2,34

Limitations of our study include the absence of data available on mental health outcomes during the course of development until young adulthood, such that we cannot detect continuity and change in behaviors in the VLBW and control groups over time. Because we do not have parent-reports available, comparison with previous findings relating to these outcomes cannot be made. However, there are no parent versions available for the CES-D and BDI that we used. Our study cohort included few participants who used antidepressants and reported a depression diagnosis, these being confined to women in the VLBW group, restricting assessment of the external validity and reproducibility of the findings. Furthermore, premature infants today and infants of our cohort may differ. Survival has improved, and breakthroughs in therapy have changed the character of some diseases.35 Although our original cohort comprised the entire population of VLBW infants in the area who were discharged alive after neonatal intensive care, our participants may not be representative of the original cohort. Furthermore, 65.1% of the VLBW young adults and 54.8% of the control subjects participated, introducing a potential bias toward healthier participants.36 Our results are based on internal comparisons within the study sample, and nonparticipation would introduce bias only if the effect of VLBW on young adult outcomes in nonparticipants differed.

We conclude that VLBW is associated with fewer self-reported depressive symptoms in young adulthood. However, this finding was confined to the VLBW young adults born AGA, who were also less likely to report a depression diagnosis. The VLBW young adults born SGA reported more depressive symptoms, used antidepressants more frequently, and were more likely to report a depression diagnosis than the term control subjects. Therefore, intrauterine growth retardation rather than VLBW per se may pose a risk of depression in young adulthood.

Correspondence: Katri Räikkönen, PhD, Department of Psychology, University of Helsinki, PO Box 9, FI-00014 Helsinki, Finland (katri.raikkonen@helsinki.fi).

Submitted for Publication: April 30, 2007; final revision received September 4, 2007; accepted October 11, 2007.

Author Contributions: Dr Räikkönen takes full responsibility for the integrity of the data and the accuracy of the data analysis. All authors had full access to all the data in the study.

Financial Disclosure: None reported.

Funding/Support: This study was supported by grants from the University of Helsinki, Academy of Finland, Duodecim Finnish Medical Society, Finska Läkaresällskapet, Finnish Foundation for Pediatric Research, Finnish Special Governmental Subsidiary for Health Sciences, Jalmari and Rauha Ahokas Foundation, Novo Nordisk Foundation, Päivikki and Sakari Sohlberg Foundation, Signe and Ane Gyllenberg Foundation, Yrjö Jahnsson Foundation, Juho Vainio Foundation, and Orion-Pharma Foundation.

Role of the Sponsors: The sponsors had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript.

Cooke  RW Health, lifestyle, and quality of life for young adults born very preterm. Arch Dis Child 2004;89 (3) 201- 206
PubMed Link to Article
Hack  M Young adult outcomes of very-low-birth-weight children. Semin Fetal Neonatal Med 2006;11 (2) 127- 137
PubMed Link to Article
Pharoah  POStevenson  CJWest  CR General Certificate of Secondary Education performance in very low birthweight infants. Arch Dis Child 2003;88 (4) 295- 298
PubMed Link to Article
Patton  GCCoffey  CCarlin  JBOlsson  CAMorley  R Prematurity at birth and adolescent depressive disorder. Br J Psychiatry 2004;184446- 447
PubMed Link to Article
Ericson  AKällén  B Very low birthweight boys at the age of 19. Arch Dis Child Fetal Neonatal Ed 1998;78 (3) F171- F174
PubMed Link to Article
Hack  MFlannery  DJSchluchter  MCartar  LBorawski  EKlein  N Outcomes in young adulthood for very-low-birth-weight infants. N Engl J Med 2002;346 (3) 149- 157
PubMed Link to Article
Hack  MYoungstrom  EACartar  LSchluchter  MTaylor  HGFlannery  DKlein  NBorawski  E Behavioral outcomes and evidence of psychopathology among very low birth weight infants at age 20 years. Pediatrics 2004;114 (4) 932- 940
PubMed Link to Article
Bjerager  MSteensberg  JGreisen  G Quality of life among young adults born with very low birthweights. Acta Paediatr 1995;84 (12) 1339- 1343
PubMed Link to Article
Alati  RLawlor  DAMamun  AAWilliams  GMNajman  JMO’Callaghan  MBor  W Is there a fetal origin of depression? evidence from the Mater University Study of Pregnancy and its outcomes. Am J Epidemiol 2007;165 (5) 575- 582
PubMed Link to Article
Gale  CRMartyn  CN Birth weight and later risk of depression in a national birth cohort. Br J Psychiatry 2004;18428- 33
PubMed Link to Article
Räikkönen  KPesonen  AKKajantie  EHeinonen  KForsen  TPhillips  DIOsmond  CBarker  DJEriksson  JG Length of gestation and depressive symptoms at age 60 years. Br J Psychiatry 2007;190469- 474
PubMed Link to Article
Thompson  CSyddall  HRodin  IOsmond  CBarker  DJ Birth weight and the risk of depressive disorder in late life. Br J Psychiatry 2001;179450- 455
PubMed Link to Article
Costello  EJWorthman  CErkanli  AAngold  A Prediction from low birth weight to female adolescent depression: a test of competing hypotheses. Arch Gen Psychiatry 2007;64 (3) 338- 344
PubMed Link to Article
Dahl  LBKaaresen  PITunby  JHandegård  BHKvernmo  SRønning  JA Emotional, behavioral, social, and academic outcomes in adolescents born with very low birth weight. Pediatrics 2006;118 (2) e449- e459
PubMed Link to Article
Korkman  MLiikanen  AFellman  V Neuropsychological consequences of very low birth weight and asphyxia at term: follow-up until school-age. J Clin Exp Neuropsychol 1996;18 (2) 220- 233
PubMed Link to Article
Pihkala  JHakala  TVoutilainen  PRaivio  K Characteristics of recent fetal growth curves in Finland [in Finnish] Duodecim 1989;105 (18) 1540- 1546
PubMed
Hovi  PAndersson  SEriksson  JGJärvenpää  ALStrang-Karlsson  SMäkitie  OKajantie  E Glucose regulation in young adults with very low birth weight. N Engl J Med 2007;356 (20) 2053- 2063
PubMed Link to Article
Beck  ATWard  CHMendelson  MMock  JErbaugh  J An inventory for measuring depression. Arch Gen Psychiatry 1961;4561- 571
PubMed Link to Article
Radloff  LS The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1977;1 (3) 385- 401
Link to Article
Dalziel  SRLim  VKLambert  AMcCarthy  DParag  VRodgers  AHarding  JE Psychological functioning and health-related quality of life in adulthood after preterm birth. Dev Med Child Neurol 2007;49 (8) 597- 602
PubMed Link to Article
Berle  JØMykletun  ADaltveit  AKRasmussen  SDahl  AA Outcomes in adulthood for children with foetal growth retardation: a linkage study from the Nord-Trondelag Health Study (HUNT) and the Medical Birth Registry of Norway. Acta Psychiatr Scand 2006;113 (6) 501- 509
PubMed Link to Article
Seckl  JRHolmes  MC Mechanisms of disease: glucocorticoids, their placental metabolism and fetal ‘programming’ of adult pathophysiology. Nat Clin Pract Endocrinol Metab 2007;3 (6) 479- 488
PubMed Link to Article
Seckl  JRMeaney  MJ Glucocorticoid programming. Ann N Y Acad Sci 2004;103263- 84
PubMed Link to Article
Welberg  LASeckl  JRHolmes  MC Inhibition of 11β-hydroxysteroid dehydrogenase, the foeto-placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety-like behaviour in the offspring. Eur J Neurosci 2000;12 (3) 1047- 1054
PubMed Link to Article
Kajantie  EDunkel  LTurpeinen  UStenman  UHWood  PJNuutila  MAndersson  S Placental 11β-hydroxysteroid dehydrogenase-2 and fetal cortisol/cortisone shuttle in small preterm infants. J Clin Endocrinol Metab 2003;88 (1) 493- 500
PubMed Link to Article
Shams  MKilby  MDSomerset  DAHowie  AJGupta  AWood  PJAfnan  MStewart  PM 11β-Hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction. Hum Reprod 1998;13 (4) 799- 804
PubMed Link to Article
Walker  BRIrving  RJAndrew  RBelton  NR Contrasting effects of intrauterine growth retardation and premature delivery on adult cortisol secretion and metabolism in man. Clin Endocrinol (Oxf) 2002;57 (3) 351- 355
PubMed Link to Article
Kajantie  E Fetal origins of stress-related adult disease. Ann N Y Acad Sci 2006;108311- 27
PubMed Link to Article
Russo  VCGluckman  PDFeldman  ELWerther  GA The insulin-like growth factor system and its pleiotropic functions in brain. Endocr Rev 2005;26 (7) 916- 943
PubMed Link to Article
Schneider  HJPagotto  UStalla  GK Central effects of the somatotropic system. Eur J Endocrinol 2003;149 (5) 377- 392
PubMed Link to Article
Agrawal  AJacobson  KCGardner  COPrescott  CAKendler  KS A population based twin study of sex differences in depressive symptoms. Twin Res 2004;7 (2) 176- 181
PubMed Link to Article
Glynn  LMWadhwa  PDDunkel-Schetter  CChicz-Demet  ASandman  CA When stress happens matters: effects of earthquake timing on stress responsivity in pregnancy. Am J Obstet Gynecol 2001;184 (4) 637- 642
PubMed Link to Article
Pesonen  AKRäikkönen  KStrandberg  TEJärvenpää  AL Continuity of maternal stress from the pre- to the postnatal period: associations with infant's positive, negative and overall temperamental reactivity. Infant Behav Dev 2005;2836- 47
Link to Article
Halpern  LFBrand  KLMalone  AF Parenting stress in mothers of very-low-birth-weight (VLBW) and full-term infants: a function of infant behavioral characteristics and child-rearing attitudes. J Pediatr Psychol 2001;26 (2) 93- 104
PubMed Link to Article
Fanaroff  AAHack  MWalsh  MC The NICHD Neonatal Research Network: changes in practice and outcomes during the first 15 years. Semin Perinatol 2003;27 (4) 281- 287
PubMed Link to Article
Hille  ETElbertse  LGravenhorst  JBBrand  RVerloove-Vanhorick  SP Dutch POPS-19 Collaborative Study Group. Nonresponse bias in a follow-up study of 19-year-old adolescents born as preterm infants. Pediatrics 2005;116 (5) e662- e666http://pediatrics.aappublications.org/cgi/content/full/116/6/e662. Accessed December 13, 2007
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Rates of very low-birth-weight (VLBW) young adults born appropriate for gestational age (AGA) and small for gestational age (SGA) and of term control subjects at risk of moderate-severe depression according to the Center for Epidemiological Studies Depression Scale (CES-D ≥16) and at risk of mild-moderate depression according to the Beck Depression Inventory (BDI ≥10). Error bars refer to 95% confidence intervals, and P values refer to group comparisons after adjusting for sex, age, parental educational attainment, body mass index in young adulthood, and attendance at a modified curriculum during school age.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Rates of very low-birth-weight (VLBW) young adults born appropriate for gestational age (AGA) and small for gestational age (SGA) and of term control subjects using antidepressants and reporting a depression diagnosis. Error bars refer to 95% confidence intervals, and P values refer to group comparisons after adjusting for sex, age, parental educational attainment, body mass index in young adulthood, and attendance at a modified curriculum during school age.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Characteristics of Very Low-Birth-Weight (VLBW) Infants Born Appropriate for Gestational Age (AGA) and Small for Gestational Age (SGA) and of Term Control Subjectsa
Table Graphic Jump LocationTable 2. Depressive Symptoms Among Young Adults With Very Low Birth Weight (VLBW) and Among Term Control Subjectsa

References

Cooke  RW Health, lifestyle, and quality of life for young adults born very preterm. Arch Dis Child 2004;89 (3) 201- 206
PubMed Link to Article
Hack  M Young adult outcomes of very-low-birth-weight children. Semin Fetal Neonatal Med 2006;11 (2) 127- 137
PubMed Link to Article
Pharoah  POStevenson  CJWest  CR General Certificate of Secondary Education performance in very low birthweight infants. Arch Dis Child 2003;88 (4) 295- 298
PubMed Link to Article
Patton  GCCoffey  CCarlin  JBOlsson  CAMorley  R Prematurity at birth and adolescent depressive disorder. Br J Psychiatry 2004;184446- 447
PubMed Link to Article
Ericson  AKällén  B Very low birthweight boys at the age of 19. Arch Dis Child Fetal Neonatal Ed 1998;78 (3) F171- F174
PubMed Link to Article
Hack  MFlannery  DJSchluchter  MCartar  LBorawski  EKlein  N Outcomes in young adulthood for very-low-birth-weight infants. N Engl J Med 2002;346 (3) 149- 157
PubMed Link to Article
Hack  MYoungstrom  EACartar  LSchluchter  MTaylor  HGFlannery  DKlein  NBorawski  E Behavioral outcomes and evidence of psychopathology among very low birth weight infants at age 20 years. Pediatrics 2004;114 (4) 932- 940
PubMed Link to Article
Bjerager  MSteensberg  JGreisen  G Quality of life among young adults born with very low birthweights. Acta Paediatr 1995;84 (12) 1339- 1343
PubMed Link to Article
Alati  RLawlor  DAMamun  AAWilliams  GMNajman  JMO’Callaghan  MBor  W Is there a fetal origin of depression? evidence from the Mater University Study of Pregnancy and its outcomes. Am J Epidemiol 2007;165 (5) 575- 582
PubMed Link to Article
Gale  CRMartyn  CN Birth weight and later risk of depression in a national birth cohort. Br J Psychiatry 2004;18428- 33
PubMed Link to Article
Räikkönen  KPesonen  AKKajantie  EHeinonen  KForsen  TPhillips  DIOsmond  CBarker  DJEriksson  JG Length of gestation and depressive symptoms at age 60 years. Br J Psychiatry 2007;190469- 474
PubMed Link to Article
Thompson  CSyddall  HRodin  IOsmond  CBarker  DJ Birth weight and the risk of depressive disorder in late life. Br J Psychiatry 2001;179450- 455
PubMed Link to Article
Costello  EJWorthman  CErkanli  AAngold  A Prediction from low birth weight to female adolescent depression: a test of competing hypotheses. Arch Gen Psychiatry 2007;64 (3) 338- 344
PubMed Link to Article
Dahl  LBKaaresen  PITunby  JHandegård  BHKvernmo  SRønning  JA Emotional, behavioral, social, and academic outcomes in adolescents born with very low birth weight. Pediatrics 2006;118 (2) e449- e459
PubMed Link to Article
Korkman  MLiikanen  AFellman  V Neuropsychological consequences of very low birth weight and asphyxia at term: follow-up until school-age. J Clin Exp Neuropsychol 1996;18 (2) 220- 233
PubMed Link to Article
Pihkala  JHakala  TVoutilainen  PRaivio  K Characteristics of recent fetal growth curves in Finland [in Finnish] Duodecim 1989;105 (18) 1540- 1546
PubMed
Hovi  PAndersson  SEriksson  JGJärvenpää  ALStrang-Karlsson  SMäkitie  OKajantie  E Glucose regulation in young adults with very low birth weight. N Engl J Med 2007;356 (20) 2053- 2063
PubMed Link to Article
Beck  ATWard  CHMendelson  MMock  JErbaugh  J An inventory for measuring depression. Arch Gen Psychiatry 1961;4561- 571
PubMed Link to Article
Radloff  LS The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1977;1 (3) 385- 401
Link to Article
Dalziel  SRLim  VKLambert  AMcCarthy  DParag  VRodgers  AHarding  JE Psychological functioning and health-related quality of life in adulthood after preterm birth. Dev Med Child Neurol 2007;49 (8) 597- 602
PubMed Link to Article
Berle  JØMykletun  ADaltveit  AKRasmussen  SDahl  AA Outcomes in adulthood for children with foetal growth retardation: a linkage study from the Nord-Trondelag Health Study (HUNT) and the Medical Birth Registry of Norway. Acta Psychiatr Scand 2006;113 (6) 501- 509
PubMed Link to Article
Seckl  JRHolmes  MC Mechanisms of disease: glucocorticoids, their placental metabolism and fetal ‘programming’ of adult pathophysiology. Nat Clin Pract Endocrinol Metab 2007;3 (6) 479- 488
PubMed Link to Article
Seckl  JRMeaney  MJ Glucocorticoid programming. Ann N Y Acad Sci 2004;103263- 84
PubMed Link to Article
Welberg  LASeckl  JRHolmes  MC Inhibition of 11β-hydroxysteroid dehydrogenase, the foeto-placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety-like behaviour in the offspring. Eur J Neurosci 2000;12 (3) 1047- 1054
PubMed Link to Article
Kajantie  EDunkel  LTurpeinen  UStenman  UHWood  PJNuutila  MAndersson  S Placental 11β-hydroxysteroid dehydrogenase-2 and fetal cortisol/cortisone shuttle in small preterm infants. J Clin Endocrinol Metab 2003;88 (1) 493- 500
PubMed Link to Article
Shams  MKilby  MDSomerset  DAHowie  AJGupta  AWood  PJAfnan  MStewart  PM 11β-Hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction. Hum Reprod 1998;13 (4) 799- 804
PubMed Link to Article
Walker  BRIrving  RJAndrew  RBelton  NR Contrasting effects of intrauterine growth retardation and premature delivery on adult cortisol secretion and metabolism in man. Clin Endocrinol (Oxf) 2002;57 (3) 351- 355
PubMed Link to Article
Kajantie  E Fetal origins of stress-related adult disease. Ann N Y Acad Sci 2006;108311- 27
PubMed Link to Article
Russo  VCGluckman  PDFeldman  ELWerther  GA The insulin-like growth factor system and its pleiotropic functions in brain. Endocr Rev 2005;26 (7) 916- 943
PubMed Link to Article
Schneider  HJPagotto  UStalla  GK Central effects of the somatotropic system. Eur J Endocrinol 2003;149 (5) 377- 392
PubMed Link to Article
Agrawal  AJacobson  KCGardner  COPrescott  CAKendler  KS A population based twin study of sex differences in depressive symptoms. Twin Res 2004;7 (2) 176- 181
PubMed Link to Article
Glynn  LMWadhwa  PDDunkel-Schetter  CChicz-Demet  ASandman  CA When stress happens matters: effects of earthquake timing on stress responsivity in pregnancy. Am J Obstet Gynecol 2001;184 (4) 637- 642
PubMed Link to Article
Pesonen  AKRäikkönen  KStrandberg  TEJärvenpää  AL Continuity of maternal stress from the pre- to the postnatal period: associations with infant's positive, negative and overall temperamental reactivity. Infant Behav Dev 2005;2836- 47
Link to Article
Halpern  LFBrand  KLMalone  AF Parenting stress in mothers of very-low-birth-weight (VLBW) and full-term infants: a function of infant behavioral characteristics and child-rearing attitudes. J Pediatr Psychol 2001;26 (2) 93- 104
PubMed Link to Article
Fanaroff  AAHack  MWalsh  MC The NICHD Neonatal Research Network: changes in practice and outcomes during the first 15 years. Semin Perinatol 2003;27 (4) 281- 287
PubMed Link to Article
Hille  ETElbertse  LGravenhorst  JBBrand  RVerloove-Vanhorick  SP Dutch POPS-19 Collaborative Study Group. Nonresponse bias in a follow-up study of 19-year-old adolescents born as preterm infants. Pediatrics 2005;116 (5) e662- e666http://pediatrics.aappublications.org/cgi/content/full/116/6/e662. Accessed December 13, 2007
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 63

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

The Rational Clinical Examination
Make the Diagnosis: Depression

The Rational Clinical Examination
Original Article: Is This Patient Clinically Depressed?