Developmental origins of psychological vulnerability factors for mental disorders

Premature birth and associated small body size are known to affect health over the life course. Moreover, compelling evidence suggests that birth size throughout its whole range of variation is inversely associated with risk for cardiovascular disease and type 2 diabetes in subsequent life. To explain these findings, the Developmental Origins of Health and Disease (DOHaD) model has been introduced. Within this framework, restricted physical growth is, to a large extent, considered either a product of harmful environmental influences, such as suboptimal nutrition and alterations in the foetal hormonal milieu, or an adaptive reaction to the environment. Whether inverse associations exist between body size at birth and psychological vulnerability factors for mental disorders is poorly known. Thus, the aim of this thesis was to study in three large prospective cohorts whether prenatal and postnatal physical growth, across the whole range of variation, is associated with subsequent temperament/personality traits and psychological symptoms that are considered vulnerability factors for mental disorders. Weight and length at birth in full term infants showed quadratic associations with the temperamental trait of harm avoidance (Study I). The highest scores were characteristic of the smallest individuals, followed by the heaviest/longest. Linear associations between birth size and psychological outcomes were found such that lower weight and thinness at birth predicted more pronounced trait anxiety in late adulthood (Study II); lower birth weight, placental size, and head circumference at 12 months predicted a more pronounced positive schitzotypal trait in women (Study III); and thinness and smaller head circumference at birth associated with symptoms of attention-deficit hyperactivity disorder (ADHD) in children who were born at term (Study IV). These associations occured across the whole variation in birth size and after adjusting for several confounders. With respect to growth after birth, individuals with high trait anxiety scores in late adulthood were lighter in weight and thinner in infancy, and gained weight more rapidly between 7 and 11 years of age, but weighed less and were shorter in late adulthood in relation to weight and height measured at 11 years of age (Study II). These results suggest that a suboptimal prenatal environment reflected in smaller birth size may affect a variety of psychological vulnerability factors for mental disorders, such as the temperamental trait of harm avoidance, trait anxiety, schizotypal traits, and symptoms of ADHD. The smaller the birth size across the whole range of variation, the more pronounced were these psychological vulnerability factors. Moreover, some of these outcomes, such as trait anxiety, were also predicted by patterns of growth after birth. The findings are concordant with the DOHaD model, and emphasise the importance of prenatal factors in the aetiology of not only mental disorders but also their psychological vulnerability factors.

Kuka on potilas? : Suomalaisen sikiöseulontakäytännön sosiaalieettistä tarkastelua

Who is the patient? A social-ethical study of the Finnish practice of prenatal screening. The aim of this study is to examine the Finnish practice of prenatal screening from a social-ethical perspective. Analyzing ethical problems in medicine and medical practice only on a general scale may conceal relevant ethical dilemmas. Previous studies have suggested that many pregnant women view the prenatal screening practices customary in the Finnish maternal care system as intimidating and oppressive. This study analyzes the ethical questions of prenatal screening by focusing on the experiences and decision-making of a pregnant woman. Finnish women s experiences of and decision-making on the most common prenatal screening methods are reflected in the basic principles of biomedical ethics described by Tom L. Beauchamp and James F. Childress in Principles of Biomedical Ethics. To concretize women s experiences I refer to studies of Finnish women s experiences of prenatal screenings. This study shows that the principles of autonomy, non-maleficence and beneficence seem to materialize rather poorly in the Finnish practice of prenatal screening. The main ethical problem with prenatal screening is that the likelihood of a foetal cure is very limited and, upon detection of an affected foetus, the choice is usually whether to continue with the pregnancy or to undergo an abortion. Although informed consent should be required, women s participation in prenatal testing is, in many cases at least, not based on their active decision. Many women experience severe anxiety when they receive a positive screening result and must wait for the final results. Medical studies indicate that long- term anxiety may negatively influence the foetus and the mother-child relationship. This study shows that the practice of prenatal screening as such may cause more harm than benefit to many pregnant women and their foetuses. This study examines the decision-making process of a pregnant woman by using the theory of medical casuistry described in Jonsen, Siegler and Winslade s Clinical Ethics. This study focuses on each of the four points of view recommended by the theory. The main problem seems to be the question of whom the patient of prenatal screening is and whom the practice is intended to benefit: the mother, the foetus, the family or society? This study shows that the concepts of health in Finnish maternal care in general, and of the prenatal screening system in particular, differ considerably. It also demonstrates that the purpose and the aims of prenatal screening, aside from the woman s right to choose, has been expressed neither in Finnish public health programmes nor in the public recommendations of prenatal screening. This study suggests that the practice of prenatal screening is a statement, though unexpressed, of public health policy and as such comprises part of the policy of disability. This study further demonstrates that through a single explicit aim (the woman s right to choose) society actually evades its obligation to women by saddling pregnant women with the entire moral responsibility as well as the possible negative consequences of her choice, such as sorrow, regrets and moral balancing. The study reveals several ethical problems in the Finnish practice of prenatal screening. Such problems should be dealt with as the Finnish practice of prenatal screening advances.

Regulation of Osteoblast Differentiation and Gene Expression by Phosphodiesterases and Bioactive Peptides

Bone is a mineralized tissue that enables multiple mechanical and metabolic functions to be carried out in the skeleton. Bone contains distinct cell types: osteoblasts (bone-forming cells), osteocytes (mature osteoblast that embedded in mineralized bone matrix) and the osteoclasts (bone-resorbing cells). Remodelling of bone begins early in foetal life, and once the skeleton is fully formed in young adults, almost all of the metabolic activity is in this form. Bone is constantly destroyed or resorbed by osteoclasts and then replaced by osteoblasts. Many bone diseases, i.e. osteoporosis, also known as bone loss, typically reflect an imbalance in skeletal turnover. The cyclic adenosine monophosphate (cAMP) and the cyclic guanosine monophosphate (cGMP) are second messengers involved in a variety of cellular responses to such extracellular agents as hormones and neurotransmitters. In the hormonal regulation of bone metabolism, i.e. via parathyroid hormone (PTH), parathyroid hormone-related peptide (PTHrp) and prostaglandin E2 signal via cAMP. cAMP and cGMP are formed by adenylate and guanylate cyclases and are degraded by phosphodiesterases (PDEs). PDEs determine the amplitudes of cyclic nucleotide-mediated hormonal responses and modulate the duration of the signal. The activities of the PDEs are regulated by multiple inputs from other signalling systems and are crucial points of cross-talk between the pathways. Food-derived bioactive peptides are reported to express a variety of functions in vivo. The angiotensin-converting enzymes (ACEs) are involved in the regulation of the specific maturation or degradation of a number of mammalian bioactive peptides. The bioactive peptides offer also a nutriceutical and a nutrigenomic aspect to bone cell biology. The aim of this study was to investigate the influence of PDEs and bioactive peptides on the activation and the differentiation of human osteoblast cells. The profile of PDEs in human osteoblast-like cells and the effect of glucocorticoids on the function of cAMP PDEs, were investigated at the mRNA and enzyme levels. The effects of PDEs on bone formation and osteoblast gene expression were determined with chemical inhibitors and siRNAs (short interfering RNAs). The influence of bioactive peptides on osteoblast gene expression and proliferation was studied at the mRNA and cellular levels. This work provides information on how PDEs are involved in the function and the differentiation of osteoblasts. The findings illustrate that gene-specific silencing with an RNA interference (RNAi) method is useful in inhibiting, the gene expression of specific PDEs and further, PDE7 inhibition upregulates several osteogenic genes and increases bALP activity and mineralization in human mesenchymal stem cells-derived osteoblasts. PDEs appear to be involved in a mechanism by which glucocorticoids affect cAMP signaling. This may provide a potential route in the formation of glucocorticoid-induced bone loss, involving the down-regulation of cAMP-PDE. PDEs may play an important role in the regulation of osteoblastic differentiation. Isoleucine-proline-proline (IPP), a bioactive peptide, possesses the potential to increase osteoblast proliferation, differentiation and signalling.

Long-term results of obstetric brachial plexus surgery

Background: Brachial plexus birth palsy (BPBP) most often occurs as a result of foetal-maternal disproportion. The C5 and C6 nerve roots of the brachial plexus are most frequently affected. In contrast, roots from the C7 to Th1 that result in total injury together with C5 and C6 injury, are affected in fewer than half of the patients. BPBP was first described by Smellie in 1764. Erb published his classical description of the injury in 1874 and his name became linked with the paralysis that is associated with upper root injury. Since then, early results of brachial plexus surgery have been reasonably well documented. However, from a clinical point of view not all primary results are maintained and there is also a need for later follow-up results. In addition most of the studies that are published emanate from highly specialized clinics and no nation wide epidemiological reports are available. One of the plexus injuries is the avulsion type, in which the nerve root or roots are ruptured at the neural cord. It has been speculated whether this might cause injury to the whole neural system or whether shoulder asymmetry and upper limb inequality results in postural deformities of the spine. Alternatively, avulsion could manifest as other signs and symptoms of the whole musculoskeletal system. In addition, there is no available information covering activities of daily living after obstetric brachial plexus surgery. Patients and methods: This was a population-based cross-sectional study on all patients who had undergone brachial plexus surgery with at least 5 years of follow-up. An incidence of 3.05/1000 for BPBP was obtained from the registers for this study period. A total of 1706 BPBP patients needing hospital treatment out of 1 717 057 newborns were registered in Finland between 1971 and 1997 inclusive. Of these BPBP patients, 124 (7.3%) underwent brachial plexus surgery at a mean age of 2.8 months (range: 0.4―13.2 months). Surgery was most often performed by direct neuroraphy after neuroma resection (53%). Depending on the phase of the study, 105 to 112 patients (85-90%) participated in a clinical and radiological follow-up assessment. The mean follow up time exceeded 13 years (range: 5.0―31.5 years). Functional status of the upper extremity was evaluated using Mallet, Gilbert and Raimondi scales. Isometric strength of the upper limb, sensation of the hand and stereognosis were evaluated for both the affected and unaffected sides then the differences and their ratios were calculated and recorded. In addition to the upper extremity, assessment of the spine and lower extremities were performed. Activities of daily living (ADL), participation in normal physical activities, and the use of physiotherapy and occupational therapy were recorded in a questionnaire. Results: The unaffected limb functioned as the dominant hand in all, except four patients. The mean length of the affected upper limb was 6 cm (range: 1-13.5 cm) shorter in 106 (95%) patients. Shoulder function was recorded as a mean Mallet score of 3 (range: 2―4) which was moderate. Both elbow function and hand function were good. The mean Gilbert elbow scale value was 3 (range: -1―5) and the mean Raimondi hand scale was 4 (range:1―5). One-third of the patients experienced pain in the affected limb including all those patients (n=9) who had clavicular non-union resulting from surgery. A total of 61 patients (57%) had an active shoulder external rotation of less than 0° and an active elbow extension deficiency was noted in 82 patients (77%) giving a mean of 26° (range: 5°―80°). In all, expect two patients, shoulder external rotation strength at a mean ratio 35% (range: 0―83%) and in all patients elbow flexion strength at a mean ratio of 41% (range: 0―79%) were impaired compared to the unaffected side. According to radiographs, incongruence of the glenohumeral joint was noted in 15 (16%) patients, whereas incongruence of the radiohumeral joint was found in 20 (21%) patients. Fine sensation was normal for 34/49 (69%) patients with C5-6 injury, for 15/31 (48%) with C5-7 and for only 8/25 (32%) of patients with total injury. Loss of protective sensation or absent sensation was noted in some palmar areas of the hand for 12/105 patients (11%). Normal stereognosis was recorded for 88/105 patients (84%). No significant inequalities in leg length were found and the incidence of structural scoliosis (1.7%) did not differ from that of the reference population. Nearly half of the patients (43%) had asynchronous motion of the upper limbs during gait, which was associated with impaired upper limb function. Data obtained from the completed questionnaires indicated that two thirds (63%) of the patients were satisfied with the functional outcome of the affected hand although one third of all patients needed help with ADL. Only a few patients were unable to participate in physical activities such as: bicycling, cross-country skiing or swimming. However, 71% of the patients reported problems related to the affected upper limb, such as muscle weakness and/or joint stiffness during the aforementioned activities. Incongruity of the radiohumeral joints, extent of the injury, avulsion type injury, age less than three months of age at the time of plexus surgery and inexperience of the surgeon was related to poor results as determined by multivariate analyses. Conclusions: Most of the patients had persistent sequelae, especially of shoulder function. Almost all measurements for the total injury group were poorer compared with those of the C5-6 type injury group. Most of the patients had asymmetry of the shoulder region and a shorter affected upper limb, which is a probable reason for having an abnormal gait. However, BPBP did not have an effect on normal growth of the lower extremities or the spine. Although, participation in physical activities was similar to that of the normal population, two-thirds of the patients reported problems. One-third of the patients needed help with ADL. During the period covered by this study, 7.3% BPBP of patients that needed hospital treatment had a brachial plexus operation, which amounts to fewer than 10 operations per year in Finland. It seems that better results of obstetric plexus surgery and more careful follow-up including opportunities for late reconstructive procedures will be expected, if the treatment is solely concentrated on by a few specialised teams.

Sikiöaikana päihteille altistuneiden lasten kasvuympäristö ja kehitys

Life of children exposed to alcohol or drugs in utero This study focused on the growth environment, physical development and socio-emotional development of children, aged 16 and under, who had been exposed to alcohol (n=78) or drugs (n=15) in utero. The aim of the study was to obtain a comprehensive picture of the living conditions of these children and to examine the role of the growth environment in their development. The study was carried out using questionnaires, written life stories and interviews. Attachment theory was used as a background theory in the study. Over half of the children exposed to alcohol were diagnosed with foetal alcohol syndrome (FAS), one quarter was diagnosed with foetal alcohol effects (FAE), and one fifth had no diagnosis. Most of the children exposed to drugs had been exposed to either amphetamines or cannabis, and a smaller number to heroin. Some of the children exposed to alcohol were mentally handicapped or intellectually impaired. The children exposed to drugs did not exhibit any serious learning difficulties but a considerable number of them had socio-emotional development problems. Language and speech problems and attention, concentration and social interaction problems were typical among both the children exposed to alcohol and those exposed to drugs. Only one child had been placed into long-term foster care in a family immediately after leaving the maternity hospital. In biological families there had been neglect, violence, mental health problems, crime and unemployment, and many parents were already dead. Two of the children had been sexually abused and four were suspected of having been abused. From the point of view of the children's development, the three most critical issues were 1) the range of illnesses and handicaps that had impaired their functional capacity as a result of their prenatal exposure to alcohol, 2) child's age at the time of placement on a long-term basis, and 3) the number of their traumatic experiences. The relationship with their biological parents after placement also played a role. Children with symptoms were found in all diagnosis categories and types of exposure. Children with the smallest number of symptoms were found among those who had never lived with their biological parents. Almost all children were exhibiting strong symptoms at the time of placement in foster care. In most cases, they were behaving in a disorderly manner towards others, but some children were withdrawn. The most conspicuous feature among those with the most severe symptoms was their disorganized behaviour. Placement in a foster family enhanced the children's development, but did not solve the problems. The foster parents who brought these children up did not receive as much therapy for the children and support for the upbringing as they appear to have needed. In Finland, transfer to long-term custody is based on strict criteria. The rights of children prescribed in the child protection law are not fulfilled in practice. Key words: FASD, FAS, FAE, alcohol exposure, drugs exposure, illegal drugs, early interaction, child development, attachment

Magnetic resonance imaging and ultrasonography in brachial plexus birth injury

Brachial plexus birth injury (BPBI) is caused by stretching, tearing or avulsion of the C5-C8 or Th1 nerve roots during delivery. Foetal-maternal disproportion is the main reason for BPBI. The goal of this study was to find out the incidence of posterior subluxation of the humeral head during first year of life in BPBI and optimal timing of the ultrasonographic screening of the glenohumeral joint. The glenohumeral congruity and posterior subluxation of the humeral head associated to muscle atrophy were assessed and surgical treatment of the shoulder girdle as well as muscle changes in elbow flexion contracture were evaluated. The prospective, population based part of the study included all neonates born in Helsinki area during years 2003-2006. Patients with BPBI sent to the Hospital for Children and Adolescents because of decreased external rotation, internal rotation contracture or deformation of the glenohumeral joint as well as patients with elbow flexion contracture were also included in this prospective study. The incidence of BPBI was calculated to be 3.1/1000 newborns in Helsinki area. About 80% of the patients with BPBI recover totally during the follow-up within the first year of life. Permanent plexus injury at the age of one year was noted in 20% of the patients (0.64/1000 newborns). Muscle imbalance resulted in sonographically detected posterior subluxation in one third of the patients with permanent BPBI. If muscle imbalance and posterior subluxation are left untreated bony deformities will develop. All patients with internal rotation contracture of the glenohumeral joint presented muscle atrophy of the rotator cuff muscles. Especially subscapular and infraspinous muscles were affected. A correlation was found particularly between greatest thickness of subscapular muscle and subluxation of the humeral head, degree of glenoid retroversion, as well as amount of internal rotation contracture. Supinator muscle atrophy was evident among all the studied patients with elbow flexion contracture. Brachial muscle pathology seemed to be an important factor for elbow flexion contracture in BPBI. Residual dysfunction of the upper extremity may require operative treatment such as tendon lengthening, tendon transfers, relocation of the humeral head or osteotomy of the humerus. Relocation of the humeral head improved the glenohumeral congruency among patients under 5 years of age. Functional improvement without remodeling of the glenohumeral joint was achieved by other reconstructive procedures. In conclusion: Shoulder screening by US should be done to all patients with permanent BPBI at the age of 3 and 6 months. Especially atrophy of the subscapular muscle correlates with glenohumeral deformity and posterior subluxation of the humeral head, which has not been reported in previous studies. Permanent muscle changes are the main reason for diminished range of motion of the elbow and forearm. Relocation of the humeral head, when needed, should be performed under the age of 5 years.

Precarious Pregnancies : Alcohol, drugs and the regulation of risks

Since the 1970s alcohol and drug use by pregnant women has become a target of political, professional and personal concern. The present study focuses on prenatal substance use and the regulation of risks by examining different kinds of societal responses to prenatal alcohol and drug use. The study analyses face-to-face encounters between professionals and service users at a specialised maternity clinic for pregnant women with substance abuse problems, medical and political discourses on the compulsory treatment of pregnant women as a means of FAS prevention and official recommendations on alcohol intake during pregnancy. Moreover, the study addresses the women s perspective by asking how women who have used illicit drugs during pregnancy perceive and rank the dangers linked to drug use. The study consists of five empirical sub-studies and a summary article. Sub-study I was written in collaboration with Dorte Hecksher and Sub-study IV with Riikka Perälä. Theoretically the study builds on the one hand, on the socio-cultural approach to the selection and perception of risks and on the other on governmentality studies which focus on the use of power in contemporary Western societies. The study is based on an ethnographic approach and makes use of the principles of multi-sited ethnography. The empirical sub-studies are based on three different types of qualitative data: ethnographic field notes from a maternity clinic from a period of 7 months, documentary material (medical journals, political documents, health education materials, government reports) and 3) interviews from maternity clinics with clients and members of staff. The study demonstrates that the logic of the regulation of prenatal alcohol use in Finland is characterised by the rise of the foetus , a process in which the urgency of protecting the foetus has gradually gained a more prominent role in the discourses on alcohol-related foetal damage. An increasing unwillingness to accept any kinds of risks when foetal health is at stake is manifested in the public debate on the compulsory treatment of pregnant women with alcohol problems and in the health authorities decision to advise pregnant women to refrain from alcohol use during pregnancy (Sub-studies I and II). Secondly, the study suggests that maternity care professionals have an ambivalent role in their mundane encounters with their pregnant clients: on the one hand professionals focus on the well-being of the foetus, but on the other, they need to take into account the women s needs and agency. The professionals daily encounters with their clients are thus characterised by hybridisation: the simultaneous use of technologies of domination and technologies of agency (Sub-studies III and IV). Finally, the study draws attention to the women s understanding of the risks of illicit drug during pregnancy, and shows that the women s understanding of risk differs from the bio-medical view. The study suggests that when drug-using pregnant women seek professional help they can feel that their moral worth is threatened by professionals negative attitudes which can make service-use challenging.