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.

OS103. Hypertensive disorders during pregnancy and cognitive decline of the offspring up to old age: the helsinki birth cohort study.

INTRODUCTION: Hypertensive disorders affect the fetal developmental milieu and may point to mechanisms by which prenatal adversity is associated with lower cognitive ability in subsequent life. OBJECTIVES: We tested whether hypertensive disorders during pregnancy predict age-related change in cognitive ability in the offspring up to old age. METHODS: Using mothers' blood pressure and urinary protein measurements from the maternity clinics and birth hospitals, we defined normotensive or hypertensive pregnancies in mothers of 398 men, who participated in the Helsinki Birth Cohort 1934-44 Study. The men underwent the Finnish Defense Forces basic ability test twice, first, during compulsory military service at age 20.1 (SD=1.4) years and, then, in a re-test at age 68.5 (SD=2.9) years. The test yields a total score and subscores for tests measuring verbal, arithmetic and visuospatial reasoning. Scores were standardized with a mean of 100 and standard deviation of 15. RESULTS: Men born after pregnancies complicated by a hypertensive disorder, compared with men born after normotensive pregnancies, scored 3.84 (95% Confidence Interval, 0.77 to 6.91) points lower on total cognitive ability at 68.5 years, and displayed a greater decline in total cognitive ability (2.31, 0.23 to 4.39) after 20.1 years. Of the subscores, associations were strongest for arithmetic reasoning. CONCLUSION: Maternal hypertensive disorders in pregnancy predict lower cognitive ability and greater cognitive decline up to old age. Multidisciplinary research is essential in order to uncover the mechanisms linking hypertensive pregnancy disorders with lower cognitive abilities in the offspring.

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.

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.

Romantic attachment in young adults with very low birth weight - The Helsinki Study of Very Low Birth Weight Adults.

Early attachment relationships from infancy onward contribute to attachment patterns later in life, to the ability to build up close relationships and to well-being in general. Severely preterm birth may challenge the development of these attachment relationships. We studied whether there are differences in attachment patterns related to romantic relationships between young adults (mean age 22.4 years, s.d. 2.2 years) with very low birth weight (VLBW, <1500 g; n = 162) and their peers born at term (n = 172), who completed the Experiences in Close Relationships Questionnaire - Revised. Young adults born at VLBW showed lower attachment-related anxiety than their peers born at term (mean difference -9.5%, 95% CI -16.0 to -2.6) when adjusted for sex, age, parental education and being in a romantic relationship currently. The groups did not differ in attachment-related avoidance. In subgroup analyses, the VLBW women born small for gestational age (SGA, birth weight <-2 s.d.) scored on average 14.8% (95% CI 3.1-26.6) higher than the control women on attachment avoidance. The effects remained after the exclusion of 18 participants with neurosensory deficits. We found no evidence for a compromised attachment pattern in young adults born at VLBW, with a possible exception of women born SGA at VLBW. VLBW adults were rather characterized by a lower level of attachment-related anxiety.

Influenza A/Fujian/411/02(H3N2)-lineage viruses in Finland: genetic diversity, epidemic activity and vaccination-induced antibody response.

The first sporadic cases of Fujian/411/02-lineage viruses were recorded in Finland in winter 2001-2002. The first protracted but low-intensity outbreak occurred here during the first half of 2003, and the second outbreak early in autumn 2003, after detection of sporadic influenza A cases in the summer. The calculated incidence of influenza A in the Finnish army was 515/10000 during the first outbreak and 2066/10000 during the second outbreak. During the 2003-2004 epidemic season, the isolates fell into three groups for their haemagglutinin (HA1) sequences. In groups I and II, the strains were reassortants which differed for their neuraminidase (NA) sequences from the viruses of the previous spring. Group II viruses, which predominated in Finland during the 2003-2004 season, were characterized by loss of the glycosylation site at position 126 in HA1. The relevance of this loss to the epidemiology is discussed, as well as the frequent appearance of codominant amino acid mixtures at position 151 lining the catalytic cavity of the NA. Group III viruses, genetically related to Wellington/1/2004, the drift variant predominant in 2004 in the southern hemisphere, caused some localized outbreaks in Finland towards the end of the 2003-2004 epidemic. The antigenic match between the vaccine virus (Panama/2007/99) and the Fujian-lineage epidemic viruses in winter 2003-2004 was far from optimal. Nevertheless, high levels of prevaccination and postvaccination antibodies to the predomi- nant group II virus were recorded. Lower antibody levels were detected to the group III virus, which turned out to be a herald strain that reappeared in Finland during the following epidemic season.

Reappearance of influenza B/Victoria/2/87-lineage viruses: epidemic activity, genetic diversity and vaccination efficacy in the Finnish Defence Forces.

A new B/Shangdong/7/97-like influenza virus (Victoria/2/87 lineage) predominated during the 2002/2003 epidemic season in Finland and was estimated to account for 2246 of the 13,496 feverish upper respiratory tract infections (URIs) occurring among conscripts in the Finnish army. The incidence (1716/10,000 conscripts) was indicative of moderate epidemic activity at most. Analysis of the cross-reactive antibodies induced in 1988 suggests that the basis of the protection was probably established during the childhood of the conscripts. Vaccination in autumn 2002 prevented 42% of the URIs during the influenza B outbreak and 71% (95% CI 42-85) of infections interpreted as influenza B. Despite the low genetic variability of the Shangdong/7/97-like viruses, breakages of a potential glycosylation site in haemagglutinin (HA1, position 197) were frequent; their biological significance is discussed. The Shangdong/7/97-like strains were HA1/NA reassortants, as were also the less abundant strains that for HA1 belonged to the B/Yamagata/16/88 lineage. A further reassortment, which probably emerged during the outbreak in one of the garrisons, supports our hypothesis that circumstances in these settings may especially favour the emergence of diversity by reassortment.

Phylogenetic and antigenic analysis of influenza A(H3N2) viruses isolated from conscripts receiving influenza vaccine prior to the epidemic season of 1998/9.

Roughly half (54%) of the 910 young conscripts at a garrison in Finland were vaccinated with commercial influenza vaccines in autumn 1998. During the influenza outbreak in February 1999, 12 H3N2-subtype virus strains were isolated from vaccinated patients, and 11 such strains were isolated from unvaccinated patients. The isolates were related to the vaccine strain A/Sydney/5/97 and could be classified into three subgroups based on sequence variation in the HA1 gene coding for the variable domain of viral haemagglutinin (HA). A total of 6-10 amino-acid substitutions in HA1, three of these in the receptor-binding site, differentiated the field strains from the vaccine virus. In haemagglutination inhibition (HI) tests, eight strains from the study population exhibited reduced reactivity with a variety of antisera including human post-vaccination sera. Six of these strains were isolated from vaccinated and two from unvaccinated patients. The reduced reactivity did not correlate with particular amino-acid changes in HA1. We suggest that low-reactivity viruses may have an advantage over other co-circulating variants under some circumstances characterized by enhanced immunity-mediated selection and high infection pressure. Whether the frequency of these viruses increased in our vaccinated study population cannot be determined, nor can their effect on vaccine efficacy.

Vaccination-induced HI antibody response to intraepidemic influenza A(H3N2) virus variants of the 1996-1997 epidemic season.

Intraepidemic antigenic and genetic variation was indicated when H3N2-subtype influenza A virus strains isolated during the 1996-1997 epidemic season in Finland were studied for reactivity in the haemagglutination inhibition (HI) assay and for nucleotide sequences coding for the variable HA1 domain of viral haemagglutinin. Thirty prevaccination- and postvaccination-paired sera taken from subjects who had been vaccinated against influenza during the previous autumn were studied for the presence of HI antibody to the homologous vaccine virus A/Nanchang/933/95, and five field strains representing the genetic and antigenic variability of the 1996-1997 epidemic season. The lowest vaccination-induced HI titres in each of the three age groups were detected in the two field strains that had been isolated from vaccinated patients and belonged to two different genetic sublineages. The intraepidemic variability of the 1996-1997 field strains in HI reactivity may be indicative of circulation of virus strains that may be capable of breaking through vaccination-induced immunity better than the other strains.

Acceptable protective efficacy of influenza vaccination in young military conscripts under circumstances of incomplete antigenic and genetic match.

Commercial inactivated parenteral influenza vaccines reduced febrile (> or = 38 degrees C) respiratory illness by 53% (95% CL: 41-63%) during a 3 week outbreak in 1998 when A/Sydney/5/97(H3N2)-like influenza viruses were shown to be the predominant etiological agents and an older antigenic variant, A/Nanchang/933/95, served as the vaccine virus. The calculatory efficacy for preventing virologically diagnosed influenza infections was 57% (95% CL: 40-68%). The study population consisted of 1374 young male military conscripts. Vaccination coverage on a voluntary basis was 67%. Vaccination was ineffective in preventing febrile illness during a second epidemic wave lasting 2 weeks when mainly adenoviruses were shown to have been circulating in the garrison. Out of the 36 nasopharyngeal aspirates positive for influenza A by antigen detection, 18 A/Sydney/5/97-like strains (10 from non-vaccinated and eight from vaccinated subjects) and two A/Nanchang/933/95-like strains (both from non-vaccinated subjects) were isolated in MDCK cell cultures. Intraepidemic variation was detected among the A/Sydney/5/97-like field strains in their HA1 sequences and reactivity in HI tests, but no evidence was obtained that this variation would have been of significance to the virus in breaking through the vaccination-induced immunity.

Adequate seroresponse to influenza vaccination in dialysis patients.

BACKGROUND: Hemodialysis (HD) patients are immunocompromised, and they have been shown to react suboptimally to recommended vaccinations. Advances in dialysis therapy and other supportive measures may theoretically result in better immune system functions. Clinical evidence supporting this theory has, however, not been presented. With influenza vaccination response, we tried to address this question. METHODS: 42 HD and 15 continuous ambulatory peritoneal dialysis (CAPD) patients were vaccinated with a trivalent influenza vaccine, and the seroresponses at 5 weeks were measured. The results were compared with those of similarly vaccinated 20 nephrology outpatient clinic patients with varying degrees of renal insufficiency and those of 31 cardiac patients with normal renal function. RESULTS: The dialysis patients had higher prevaccination titers of hemagglutination-inhibiting (HI) antibodies to all three vaccine virus antigens than the other groups due to more frequent previous vaccinations. The dialysis patients exhibited lower antibody increases, but an almost comparable proportion of them reached a protective antibody level (HI titers > or =40) 5 weeks after vaccination [A/H3N2: 61% (cardiac patients), 35% (nephrology outpatient clinic patients), 67% (CAPD), and 36% (HD); A/H1N1: 71, 70, 80 and 60; B: 97, 90, 80, and 76%, respectively]. Among the HD group, all patients receiving parenteral calcitriol except 1 (83%), but only 50% of the other HD patients produced protective antibody titers at least to two out of three vaccine virus antigens. No other patient- or HD treatment-associated parameter was significantly related to the vaccination-induced antibody response. CONCLUSIONS: We conclude that influenza vaccination of dialysis patients according to current recommendations may be effective. Additionally, our results suggest that parenteral calcitriol treatment may augment the immune response of HD patients even in a clinically relevant way, an effect so far shown only in in vitro studies.

Expansion of a novel pulmonary CD3(-) CD4(+) CD8(+) cell population in mice during Chlamydia pneumoniae infection.

A new pulmonary T-cell-like lymphocyte population with the phenotype CD3(-) CD4(+) CD8(+) was discovered in mice. CD4(+) CD8(+) but CD3(+) cells among murine intestinal intraepithelial lymphocytes have previously been described. We describe herein a dramatic expansion of the CD3(-) CD4(+) CD8(+) cell population in response to experimental respiratory infection. After intranasal Chlamydia pneumoniae infection, CD4(+) CD8(+) cells became transiently the dominant lymphocyte type (maximum of 87% of all lymphocytes) in the lungs of NIH/S mice but remained virtually undetectable in spleen and blood. The enrichment of these cells was not a C. pneumoniae-specific event, since infection of NIH/S mice with influenza A virus also resulted in an increase in the number of CD4(+) CD8(+) cells (maximum of 42% of all lymphocytes). In addition to outbred NIH/S mice, two other mouse strains were studied: BALB/c (H-2(d)) and C57BL/6 (H-2(b)). C. pneumoniae-infected BALB/c mice responded with an intermediate increase in the number of CD4(+) CD8(+) cells in lungs, whereas C57BL/6 mice did not respond. The double-positive CD4(+) CD8(+) cells lacked a major part of the T-cell receptor complex, being both CD3(-) and TCR alpha beta-. However, when they were stimulated in vitro with a T-cell mitogen, they responded by proliferation but did not secrete gamma interferon. The dramatic expansion of this cell population at the infection site suggests an active role for them in respiratory infection, but the specification of this requires further study.

Associations of prevaccination antibody levels with adverse reactions to pneumococcal and influenza vaccines administered simultaneously in the elderly.

The association of prevaccination antibodies with the adverse reactions seen after vaccination was studied in 85 elderly subjects (65-90 years) vaccinated simultaneously with pneumococcal and influenza vaccines. The subjects with a temperature rise (9% of vaccinees) had significantly higher prevaccination antibody levels to pneumococcal capsular polysaccharides (PPSs) than those without a temperature rise; no difference was seen in their haemagglutination inhibiting (HI) influenza virus antibody levels. Pain in the left arm (the pneumococcal vaccine injection site) occurred in 45% of the subjects and was likewise associated with elevated PPS antibody levels. Pain at the site of influenza vaccine injection (the right arm) seen in 33% of the vaccinees was significantly more common among those who had previously received influenza vaccine, but was not associated with elevated HI antibody levels. In conclusion, prevaccination pneumococcal but not influenza antibodies were associated with both systemic and local reactions following vaccination.

Myelitis associated with influenza A virus infection.

We report a patient presenting with myelitis after respiratory symptoms. A high level of antibodies to influenza A virus was measured in serum and cerebrospinal fluid (CSF), and the serum/CSF antibody ratio was 1.7, suggesting specific antibody production in the central nervous system. Magnetic resonance imaging of the spinal canal showed a contrast-enhanced swelling on the cervical medulla. Such a case would have warranted the use of antiviral therapy and calls to mind the neurotropic potential of influenza A viruses.

Recent influenza B viruses in Europe: a phylogenetic analysis.

BACKGROUND: Influenza B virus evolution is currently in a unique situation having two cocirculating main lineages B/Yamagata/16/88 (YM/88)-like and B/Victoria/2/87 (VI/87)-like viruses. Continuation of this bifurcation would mean development towards distinct forms resembling the HA subtypes of influenza A viruses. OBJECTIVE: We wanted to examine both intraepidemic heterogeneity and recent evolution in these two lineages. The initial purpose was to determine the geographic distribution of the two sublineages of the VI/87-like viruses in Europe in 1989-1990 under circumstances of low epidemic activity. Due to the outbreaks of YM/88-like viruses since 1991, the study was extended to contain the evolution of these viruses and their genetic relationship with the vaccine strains of that time. STUDY DESIGN: The HA1 gene sequences of 33 influenza B strains isolated in ten European countries since 1989 were determined and compared with those available through databases or personal contacts. RESULTS: The two main lineages, YM/88-like and VI/87-like viruses, both continued to circulate. In both lineages, changes in the potential glycosylation sites were observed. Two sublineages of the VI/87 lineage cocirculated during the 1989-1990 season with somewhat different geographic distributions. A high degree of intraepidemic heterogeneity was observed, as well as examples of conserved nucleotide sequences. CONCLUSIONS: It is important to follow the evolution and circulation of VI/87-like viruses. Current vaccines give poor or no protection against VI/87-like viruses in immunologically unprimed children or even in primed adults (Levandowski et al., 1991, Pyhala et al., 1994). Changes in the potential glycosylation pattern in the latest virus isolates of both main lineages have occurred and it is interesting to see the significance of these changes to viral evolution.

HA1 domain of influenza A (H3N2) viruses in Finland in 1989-1995: evolution, egg-adaptation and relationship to vaccine strains.

The HA1 gene sequences of 22 MDCK cell-derived influenza A (H3N2) strains, ten of their egg-derived counterparts and three vaccine strains were determined. Antigenic and sequence differences between the epidemic and vaccine strains were recorded, most striking in 1992/93; a minority of the amino acid differences in 1989-95 was involved in egg-adaptation. Changes in the assortment of amino acid substitutions produced during egg-adaptation of field strains may account for the difficulty encountered in isolating these viruses in embryonated eggs. Six revertant amino acids, characteristic of field strains prevalent in 1969-71 were recorded in 1994/95. Their genome sequence was interpreted to have been maintained over the interval years among low abundant sequences of the viral quasispecies. Potential changes of carbohydrate moieties were recorded in two glycosylation sites, suggesting that oligosaccharides at these sites are not necessarily advantageous for the H3N2 subtype virus currently.