A.-K. Pesonen

Aspirin in the prevention of pre‐eclampsia in high‐risk women: a randomised placebo‐controlled PREDO Trial and a meta‐analysis of randomised trials

Objective  To study the effect of aspirin in the prevention of pre‐eclampsia in high‐risk women.

Neurocognitive abilities in young adults with very low birth weight

Objective: Although severely preterm birth has been associated with impaired neurocognitive abilities in children, follow-up studies in adulthood are scarce. We set out to study whether adults born with very low birth weight (VLBW) (<1,500 g), either small for gestational age (SGA) (birth weight ≤−2 SD) or appropriate for gestational age (AGA), differ in a range of neurocognitive abilities and academic performance from adults born at term and not SGA. Methods: As part of the Helsinki Study of Very Low Birth Weight Adults, 103 VLBW (37 SGA) and 105 term-born control adults (mean age 25.0, range 21.4–29.7 years) without major neurosensory impairments participated in the follow-up study in 2007–2008. The test battery included measures of general cognitive ability as well as executive functioning and related abilities. Academic performance was self-reported. Results: With adjustment for sex and age, the VLBW group scored lower or performed slower than the control group in some indices of all tests (these mean differences ranged from 0.3 to 0.5 SD units, p ≤ 0.03) and they had received remedial education at school more frequently; however, no differences existed in self-reported academic performance. The differences were evident in both VLBW-SGA and VLBW-AGA groups. Further covariate adjustments for parental education, current head circumference, and head circumference at birth and, in tests of executive functioning and related abilities, adjustment for IQ estimate had minor effects on the results. Conclusions: In comparison with control adults, VLBW adults scored lower on several neurocognitive tests. Poorer neurocognitive performance is associated with VLBW irrespective of the intrauterine growth pattern.

Depressive symptoms in adulthood and intrauterine exposure to pre‐eclampsia: the Helsinki Birth Cohort Study

Please cite this paper as: Tuovinen S, Räikkönen K, Kajantie E, Pesonen A, Heinonen K, Osmond C, Barker D, Eriksson J. Depressive symptoms in adulthood and intrauterine exposure to pre‐eclampsia: the Helsinki Birth Cohort Study. BJOG 2010;117:1236–1242.

Early life stress and blood pressure levels in late adulthood.

Severe stress experienced in early life may have long-term consequences on adult physiological functions. We studied the long-term effects of separation on blood pressure levels in non-obese subjects who were separated temporarily in childhood from their parents during World War II (WWII). The original clinical study cohort consists of people born during 1934–1944 in Helsinki, Finland. This substudy includes 1361 non-obese subjects (body mass index <30 kg m−2). Of these, 192 (14.1%) had been evacuated abroad during WWII. The remaining subjects served as controls. Blood pressure levels and use of blood pressure medication were studied. The separated subjects had significantly higher systolic blood pressure values than the non-separated (148.6+21.5 vs 142.2+19.6 mm Hg, P<0.0001) in adult life. Those subjects separated in early childhood had markedly higher systolic and diastolic blood pressure values in adult life compared with the non-separated (154.6 vs 142.5 mm Hg; 95% confidence interval (CI) 2.6–14.7; P<0.005 and 90.8 vs 87.7 mm Hg; 95% CI 1.0–7.3; P<0.02, respectively). Systolic blood pressure was also higher in the group separated for a duration of <1 year (151.7 vs 142.2 mm Hg; 95% CI 0.0–12.4; P<0.05) compared with the non-separated. Besides being separated, age at separation and duration of separation also influenced blood pressure levels in adult life. This could be due to early hormonal and metabolic programming, during plastic periods in early life, influencing blood pressure levels in adult life.

Depressive symptoms in adulthood and intrauterine exposure to pre-eclampsia: the Helsinki Birth Cohort Study

Please cite this paper as: Tuovinen S, Räikkönen K, Kajantie E, Pesonen A, Heinonen K, Osmond C, Barker D, Eriksson J. Depressive symptoms in adulthood and intrauterine exposure to pre‐eclampsia: the Helsinki Birth Cohort Study. BJOG 2010;117:1236–1242.

Body size at birth and cardiovascular response to and recovery from mental stress in children

Cardiovascular (CV) response to mental stress, a predictor of CV disease risk, may be determined already in utero. However, the underlying mechanisms remain unclear, and previous studies have used adult subjects and neglected CV recovery. We investigated 147 girls and 136 boys aged 8 years who underwent the Trier Social Stress Test for children to determine whether body size at birth is associated with CV activity. Blood pressure (BP), electrocardiogram and impedance-derived indices were recorded and analyzed from continuous measurements using Vasotrac APM205A and Biopac MP150 systems. Among girls, lower birth weight was associated with lower baseline systolic BP (SBP) and diastolic BP (DBP) values (1.9 mm Hg and 1.5 mm Hg per 1 s.d. birth weight for gestational age, respectively), higher SBP and DBP response to mental stress (1.6 mm Hg and 1.1 mm Hg per 1 s.d. birth weight for gestational age, respectively), slower BP recovery and overall higher cardiac sympathetic activity. In contrast, among boys lower birth weight was associated with higher baseline levels of SBP (2.1 mm Hg per 1 s.d. birth weight for gestational age) and total peripheral resistance (TPR), overall lower cardiac sympathetic activity, lower TPR response to mental stress and a more rapid BP and cardiac sympathetic recovery. In boys, the associations with baseline levels and cardiac sympathetic activity became significant only after adjusting for current body size. These sex-specific results suggest that individual differences in childhood CV response to and recovery from mental stress may have prenatal origins. This phenomenon may be important in linking smaller body size at birth to adult CV disease.

Maternal hypertensive disorders during pregnancy: adaptive functioning and psychiatric and psychological problems of the older offspring

To study whether pre‐eclampsia and hypertension without proteinuria during pregnancy are associated with adaptive functioning, and psychiatric and psychological problems, of older offspring.

Common mental disorders in young adults born late-preterm

BACKGROUND Results of adulthood mental health of those born late-preterm (34 + 0-36 + 6 weeks + days of gestation) are mixed and based on national registers. We examined if late-preterm birth was associated with a higher risk for common mental disorders in young adulthood when using a diagnostic interview, and if this risk decreased as gestational age increased. METHOD A total of 800 young adults (mean = 25.3, s.d. = 0.62 years), born 1985-1986, participated in a follow-up of the Arvo Ylppö Longitudinal Study. Common mental disorders (mood, anxiety and substance use disorders) during the past 12 months were defined using the Composite International Diagnostic Interview (Munich version). Gestational age was extracted from hospital birth records and categorized into early-preterm (<34 + 0, n = 37), late-preterm (34 + 0-36 + 6, n = 106), term (37 + 0-41 + 6, n = 617) and post-term (⩾42 + 0, n = 40). RESULTS Those born late-preterm and at term were at a similar risk for any common mental disorder [odds ratio (OR) 1.11, 95% confidence interval (CI) 0.67-1.84], for mood (OR 1.11, 95% CI 0.54-2.25), anxiety (OR 1.00, 95% CI 0.40-2.50) and substance use (OR 1.31, 95% CI 0.74-2.32) disorders, and co-morbidity of these disorders (p = 0.38). While the mental disorder risk decreased significantly as gestational age increased, the trend was driven by a higher risk in those born early-preterm. CONCLUSIONS Using a cohort born during the advanced neonatal and early childhood care, we found that not all individuals born preterm are at risk for common mental disorders in young adulthood - those born late-preterm are not, while those born early-preterm are at a higher risk. Available resources for prevention and intervention should be targeted towards the preterm group born the earliest.

Autism spectrum traits and visual processing in young adults with very low birth weight: the Helsinki Study of Very Low Birth Weight adults

Visual processing problems may be one underlying factor for cognitive impairments related to autism spectrum disorders (ASDs). We examined associations between ASD-traits (Autism-Spectrum Quotient) and visual processing performance (Rey-Osterrieth Complex Figure Test; Block Design task of the Wechsler Adult Intelligence Scale-III) in young adults (mean age=25.0, s.d.=2.1 years) born preterm at very low birth weight (VLBW; <1500 g) (n=101) or at term (n=104). A higher level of ASD-traits was associated with slower global visual processing speed among the preterm VLBW, but not among the term-born group (P<0.04 for interaction). Our findings suggest that the associations between ASD-traits and visual processing may be restricted to individuals born preterm, and related specifically to global, not local visual processing. Our findings point to cumulative social and neurocognitive problems in those born preterm at VLBW.

Aspirin in the prevention of pre-eclampsia in high-risk women.

Sir, We thank Dr Thornton for his interest in our article ‘Aspirin in the prevention of pre-eclampsia in high-risk women’ published in the January 2013 issue ofBJOG. He raises four points we would like to respond to: the strength of effect; sample size; exclusion of participants from the main analysis; and trial registration. Dr Thornton concludes the commentary by writing that the effect of aspirin we reported in the meta-analysis for women who also have abnormal uterine artery Doppler waveforms at 14 weeks of gestation differs little from its effect in other high-risk groups. We have difficulty in agreeingwith this; in our opinion the risk ratio in our meta-analysis (RR 0.55; 95% CI 0.37–0.83) differs from those reported by theCochrane review. The differences are even better encapsulated by comparing the numbers needed to treat (NNTs). In our meta-analysis, the substantial reduction in risk together with the high initial risk (36%) resulted in an NNT of six for preventing preeclampsia, whereas the Cochrane review reported an NNT for pre-eclampsia of 19 for women at high risk (20% risk) and 119 for women at moderate risk (6%), and concluded that ‘further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose’. The PARIS meta-analysis reported a 10% reduction and an NNT of 56 for women at high risk (18% risk) and 167 for women at moderate risk (6%). In other respects our study represents both the strengths and weaknesses of clinician-initiated trials. With limited funding, from non-commercial sources only, the participating clinicians in ten centres were able to screen 947 women whose history indicated an increased risk of pre-eclampsia, to find those whose uterine artery flow indicates a particularly high risk. As we discuss in the article, in hindsight the criterion chosen was too strict, and only 152women could be randomised. Although Dr Thornton is correct in stating that 31 of these women discontinued the treatment for various reasons and were excluded from the main analysis, he seems to overlook our description of the intention-to-treat analysis of all randomised women (except those who had a miscarriage), which gave a similar result. We do agree about the shortcomings of the information included in the ISRCTN registration (www.controlled-trials.com/ISRCTN140 30412/), submitted by onemember of the study team. For example, variables that were eventually listed in the outcomes section include predictor variables such as biochemical measurements during pregnancy. It should also be noted that the planned number of participants stated on the ISRCTN website, of 1000 women, refers to the women to be screened by Doppler ultrasound, and not those to be eventually randomised, as Dr Thornton stated in his commentary. In our conclusion we echoed the words of the Cochrane review that ‘further information is required to assess which women are most likely to benefit’, and proposed that emerging biochemical risk markers, possibly in combination with early uterine artery Doppler ultrasound, are promising candidates to identify such women for future trials.&