<p>The experience of childbirth is an important life event for women, which may follow them throughout life. The overall aim of this thesis has been to describe and analyse these experiences from the women's perspective as well as the encounter between the woman and the midwife, and the possibility that a birth plan might improve women's experience of childbirth. The setting has been the ABC-centre (Alternative Birth Care), antenatal clinics and Sahlgrenska University hospital in Göteborg, and Karolinska hospital in Stockholm, Sweden. The studies have used both qualitative (phenomenological and hermeneutic) and quantitative approaches. The essential structure of the experiences of pregnancy and childbirth may be conceptualised under the heading ‘releasing and relieving encounters’, which for the woman constitutes an encounter with herself as well as with the midwife, and includes stillness as well as change. Stillness is expressed as being in the moment; exemplified as presence and being one's body. Change is expressed as transition; to the unknown and to motherhood. In the releasing and relieving encounter, for the midwife stillness and change equals being both anchored and a companion. To be a companion is to be an available person that listens to and follows the woman through the process of childbirth. To be anchored is to be the person that in the transition process respects the limits of the woman's ability as well as her own professional limits. The releasing and relieving encounter is not improved for women by a birth plan. Instead, in some aspects the relationship between the woman and her midwife during childbirth is reported as less satisfactory if preceded by a birth plan although some experiences of fear, pain and concerns for the child might be improved. </p>

<p>The aims of the studies described in this thesis were to investigate the pharmacokinetics of and cellular resistance to chemotherapy as causes of treatment failure in childhood acute lymphoblastic leukemia (ALL).</p><p>Leukemic cells from 370 children with newly diagnosed ALL were tested by the Fluorometric Microculture Cytotoxicity Assay to measure their resistance to each of ten standard cytotoxic drugs. In the high-risk group, increased in vitro resistance to each of the drugs dexamethasone, etoposide and doxorubicin was associated with a worse clinical outcome. Combining the results for these drugs yielded a drug resistance score, showing a relative risk of relapse in the most resistant group that was 9.8 times higher than in the most sensitive group. In the standard-risk and intermediate-risk groups, final evaluation must await longer follow-up.</p><p>The new cytotoxic agent CHS 828 was equally active in vitro in samples from children with acute myeloblastic leukemia (AML) and ALL, with 50% cell kill at concentrations achievable in vivo. In AML samples CHS 828 also displayed high frequencies of synergistic interactions with four standard drugs. The well-known differences in clinical outcome between Down´s syndrome (DS) and non-DS children with acute leukemia may partly be explained by our finding of differences in drug resistance at the cellular level.</p><p>Pharmacokinetic studies were performed at the start of induction treatment of ALL. Doxorubicin was assayed by reversed-phase liquid chromatography with fluorometric detection, and vincristine by high performance liquid chromatography with electrochemical detection. Plasma doxorubicin concentrations were measured in 107 children after 23 h of a 24-h infusion. The median steady-state concentration in children 4-6 years old, a group known to have a favorable outcome of treatment, was about 50% higher than in those 1-2 and >6 years old Vincristine pharmacokinetics was evaluated in 98 children. There was no correlation between age and total body clearance or any other pharmacokinetic parameters.</p><p>In vitro testing of cellular drug resistance might be useful in predicting the outcome in high-risk ALL. The further exploration of CHS 828 in childhood leukemia seems warranted. There is no pharmacokinetic rationale for the common practice of administering relatively lower doses of vincristine to adolescents than to younger children.</p>

<p>In this study 165 Swedish parents of young children with Downs’s syndrome (DS) were investigated regarding their perception of the quality of the first information and support received after the birth of the child. The parents’ opinions were compared with clinical routines at the paediatric clinics regarding these issues. Strong clinical ambitions fell short, however, since 70 % of the parents felt insufficiently informed; 56 % felt unsupported, and the timing of the disclosure varied between 0 hour to >5 days. On the basis of a grounded theory analysis the parents’ written narratives regarding the quality of the first information and support were analysed to better understand the reasons underlying the parental dissatisfaction. Criticisms were raised by the parents concerning: the low communication skills by professionals; the lack of privacy; too much negative information; and an unmet desire to early meet other DS parents. </p><p>The implications of being DS parents regarding their daily life were examined by measuring parental health, stress, sense of coherence, employment and sick leave rates. Results were compared with those in a randomly selected group of parents of healthy age-matched children. The similarities between the DS and control parents were more pronounced than the differences regarding divorce rates, siblings in the family, time spent on child care, employment and sick leave rates, and their self-perceived health, stress, and sense of coherence. However, self-perceived health of the DS mothers was impaired and stress was increased. A small group of DS parents (5 mothers and 1 father) had an extremely high rate of sick leave and no such group was seen in the control parents. In addition, the DS mothers stayed at home because of the child’s sickness most frequently and the DS fathers stayed at home for this reason more than control mothers.</p><p>Conclusions: Existing guidelines for optimal first information and support of new parents of children with DS are not always followed in Sweden. Qualitative clinical improvements from the parents’ perspective are proposed. Most DS parents live an ordinary family life in respect to the measured parameters, but the risk for health deterioration, particularly in DS mothers, might need attention.</p>

<p>An <i>in vitro</i> method was developed for measuring aromatase, based on binding of competitive aromatase inhibitor [¹¹C]vorozole to the active site of the enzyme. [¹¹C]Vorozole displayed high, specific binding <i>in vitro</i> to human placenta and human granulosa cells (GC), both fresh and frozen/thawed cells, provided correct procedures were used. High, specific binding was also observed in pig and rat ovaries, whereas binding in other tissues was unspecific and usually low. Aromatase concentrations measured by [¹¹C]vorozole binding correlated well to aromatase activity measured by [³H]water release from 1β[³H]androstenedione. </p><p>In human GC <i>in vitro</i>, low concentrations of 5α-dihydrotestosterone (DHT), but not of other androgens, stimulated aromatase activity measured by [³H]water release but had no effects on aromatase concentration measured by [¹¹C]vorozole binding. DHT may interact with aromatase differently than other androgens, perhaps by changing aromatase affinity to precursor. </p><p>In the rat estrous cycle, aromatase activity in ovarian homogenate, measured by [³H]water release, together with serum androstenedione and estradiol-17β, peaked between 6 and 13 h after onset of the light period of proestrus, the former activity being independent of radioactive substrate concentration. [¹¹C]Vorozole binding characteristics changed more rapidly than <i>de novo</i> synthesis of the enzyme. [¹¹C]Vorozole binding K_dshowed close inverse correlation to aromatase activity in ovarian homogenate and to serum estradiol-17β. Rapid changes in substrate affinity rather than changes in substrate concentration or <i>de novo</i> synthesis of the enzyme may thus be important for regulation of ovarian aromatase. </p><p>The [¹¹C]vorozole <i>in vivo</i> technique yields additional information compared with traditional in vitro techniques. </p>

<p>The overall aim of this thesis was to examine the adoption of emergency contraceptive pills (ECP) in Sweden. Two cross-sectional surveys and two quasi-experimental studies were used. Reasons for induced abortion, contraceptive practices and contraceptive failure were examined in a group of abortion applicants with a waiting-room questionnaire (I) and knowledge, use and practices of ECP were assessed with a postal questionnaire in a population-based sample of young women (II). One community-based information campaign was evaluated with a repeated postal questionnaire (III) and a school-based education intervention was evaluated with repeated class-room questionnaires (IV). Abortion applicants had inadequate contraceptive practices and a low use of ECP. One year after the deregulation of ECP women were highly aware of the method and preferred the pharmacy for the purchase of ECP. Correct knowledge and positive attitudes influenced the willingness to use ECP in the future. The information campaign was noticed by two-thirds of the women and there was an overall trend towards better knowledge, improved attitudes and increased use among all women at follow-up. The school-based intervention improved the students’ knowledge of, and attitudes to, ECP without jeopardizing condom use. The adoption of ECP in Sweden seems to have gone through the first stages of diffusion of an innovation, i.e., developement, dissemination, and adoption, and has reached the stage of implementation since the studies indicated a general awareness of more than 90%, an intention to use in case of need of more than 70%, and womens’ own experience of use of around 30%. The most cited information channels were media, friends and the local Youth Clinic. ECP is gradually becoming a more widely known, accepted and used contraceptive method in Sweden, but must be considered as being only one of many tools in the prevention of unintended pregnancies.</p>

<p>2-Methoxyestradiol (2-ME), a metabolite of 17β-estradiol, is a potent antitumor and antiangiogenesis agent in vitro and in vivo. This study aimed to investigate the effects of 2-ME on human cervical and endometrial cancers in vitro and in vivo. Human cervical cancer HeLaS3 cells, endometrial cancer HEC-1-A and RL-95-2 cells, and severe combined immune deficient (SCID) mice were used. On cervical cancer HeLaS3 cells, 2-ME inhibited the cell growth which is accompanied by apoptosis via iNOS pathway and by G₂/M cell cycle arrest. 2-ME had slight effects on normal cervical epithelial cells. In vivo on SCID mice, 2-ME (75 mg/kg p.o.) inhibited the growth of human cervical carcinoma by 34% (p < 0.05) and showed slight side effects to liver and spleen. On human endometrial cancer cells (HEC-1-A and RL-95-2 cells), 2-ME inhibited the growth by blocking cell cycle progress in S- and G₂/M-phase in both cell types, and by inducing apoptosis in HEC-1-A cells and by causing necrosis in RL-95-2 cells. 2-ME had no effects on normal endometrial cells. The apoptotic effect, in HEC-1-A cells, was prevented by iNOS-inhibitor 1400W and eliminated by Caspase-inhibitor Z-VAD-FMK. The necrosis, on RL-95-2 cells, was due to a severe disruption of the mitochondrial membrane potential. Unfortunately, 2-ME had no significant effects on endometrial cancer xenografts. It showed slight toxicity to liver, spleen and proliferative effect on uterus. In conclusion, 2-ME inhibits the growth of human cervical and endometrial cancer cells in vitro. However, a weaker anti-tumor effect was observed in our animal model and 2-ME was slightly toxic to liver and spleen. Considering the proliferative effect on uterus, 2-ME might not be a suitable therapeutic agent in gynecological tumors.</p>

<p>Studies were performed to improve iodine deficiency control programs. Goitre rates and cassava processing practices were compared in three Central African Republic (CAR) populations. Short-cuts in cassava processing were associated with elevated urinary thiocyanate and increased goitre rates, suggesting a goitrogenic effect in one population. While improved cassava processing may be beneficial, the priority is to correct the iodine deficiency. </p><p>The use of the urinary iodine/tiocyanate ratio as indicator of goitrogenic effects was explored using data from Tanzania and CAR. As the ratio can be calculated in four mathematically different ways and has physiological shortcomings, its use is discouraged.</p><p>Biannual iodised oil capsule (IOC) distribution in a Tanzanian population of 7 million during nine years was studied. Mean distribution coverage was 64%, mean delay of subsequent distribution 1.25 years, and only 43% of targeted person-time was covered. The cost of capsules constituted more than 90% of total program costs. It is cost-effective to invest more funds in communication, support of peripheral staff and supervision.</p><p>In a highland Tanzanian village, salt iodine content was highly variable compared to national standards. While school-children had adequate urinary iodine, women at delivery and newborns showed signs of in adequate iodine status. Salt iodine concentrations should be monitored during production and distribution down to household level, and iodine status assessed in all vulnerable groups before adjusting recommended salt iodization levels at production.</p><p>WHO's 1994 change in palpation goitre definition considerably lowered specificity and increased measured goitre rates by 25% in Tanzanian school-children compared to the previous system. Ultrasound estimation of thyroid volume under rugged field conditions requires considerable human and material resources yet had a precision only slightly better than palpation. In resource poor settings appropriately trained palpators using the 1960 WHO definition of goitre remain optimal for estimating thyroid size until precision and cost of ultrasound has improved.</p><p>Monitoring of process indicators needs to be an ongoing priority activity, separate from periodic evaluations of impact.</p>

<p>The studies were undertaken to evaluate risk factors and outcomes in small-for-gestational-age (SGA) births, in cohort studies using the population-based Swedish Birth, Twin and Education Registers. A cohort study of pregnant women from Uppsala County evaluated the effect on birthweight by caffeine.</p><p> Maternal anthropometrics influence risks of SGA at all gestational ages. Smoking increases risks of moderately preterm and term SGA, while hypertensive disorders foremost increase the risk of preterm SGA. Monozygotic twin mothers have higher concordance rates in offspring birthweight-for-gestational length than dizygotic twin mothers, indicating genetic effects on fetal growth. Caffeine is not associated with a reduction in birthweight or birthweight-for-gestational age.</p><p> The increased risk of stillbirth in postterm pregnancies is explained by increased rates of SGA in postterm pregnancies. Births with malformations account for a large part of the SGA-related increased risk of infant death. SGA, as defined by an individualised birth-weight standard, is a better predictor of adverse pregnancy outcomes than the commonly used population-based birthweight standard. </p><p> Risk factors for SGA, as well as the prognosis for the SGA infant, vary with gestational age. However, the commonly used definition of SGA is probably a poor predictor of intrauterine growth retardation.</p>

<p>General and reproductive health and reproductive outcome were described in rural women of childbearing age (15-44 years) during 1992-93 in a cross-sectional study in Zimbabwe. Through a two-stage sampling procedure twelve villages were selected at random, and 79% of the women in the villages accepted to participate (n=1213). In a structured interview women¡¯s self-reported morbidity, socio-economic conditions, use of health care and fertility regulation methods, reproductive outcome and infertility problems were assessed. The prevalence rates of anaemia, malaria and syphilis were investigated. Retrospectively, HIV serology was anonymously assessed and associations with socio-economic conditions and morbidity were analysed. </p><p>The mean age was 28 years. Family planning was currently used by 37%. Primary and secondary infertility was reported by 0.9% and 4.4%, respectively. The perinatal mortality rate for all completed pregnancies (n=3601) was 23/1000. During the latest completed pregnancy 94% had attended antenatal care and 85% had delivered in hospitals or clinics. The self-reported complications during delivery seemed to have been cared for within the health care system. </p><p>Women perceived their health as being generally good. Mean haemoglobin (Hb) was 13.5 g/dl and only 3.4% were anaemic (Hb ¡Ü11.0 g/dl). Malaria prevalence was 5.4%, but a positive malaria test was not associated with anaemia. Syphilis prevalence was 2.2%, and a positive syphilis test increased the risk of being HIV positive three-fold (OR=3.0; 95% CI: 1.4-6.2). </p><p>The prevalence of HIV was high (22%). Women aged 15-19 had the lowest prevalence (7.6%), while the highest was found in married women aged 20-29 years (30%). The differences in HIV prevalence between the villages ranged between 8.4% and 33%. HIV positive women reported no more morbidity than HIV negative women. The low morbidity found at the time of the study indicates a fairly short duration of the HIV epidemic. </p>

<p>Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease.</p><p>In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. <i>(Paper I)</i><b> </b></p><p>In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. <i>(Paper II)</i></p><p>Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF_2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF_2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. <i>(Papers III, V)</i> There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. <i>(Paper IV)</i></p><p>In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta.</p>