The appropriateness of universal screening for gestational diabetes mellitus (GDM) has been strongly questioned, since it does not satisfy ethical principles for screening. The aims of these studies were to determine the prevalence of GDM, expressed in terms of impaired glucose tolerance (IGT) and diabetes mellitus (DM), to evaluate different screening models using traditional anamnestic risk factors and repeated random B-glucose, to determine whether GDM increases risks for maternal complications such as preeclampsia, and to determine whether IGT during pregnancy, if left untreated, is associated with increased maternal or neonatal morbidity. Of 4,918 pregnant non-diabetic women attending maternal health care, 73.5% agreed to have a 75 g oral glucose tolerance test (OGTT). GDM was diagnosed in 1.7%, IGT in 1.3% and DM in 0.4%. Traditional risk factor criteria were fulfilled by 15.8%. Prior GDM and a prior macrosomic infant showed the highest association with GDM. No selective or two-step universal screening model would have detected all cases of GDM. A constructed model comprising prior GDM, a prior LGA/macrosomic infant, or a cut-off random B-glucose level of 8 mmol/l as an indication for OGTT reduced the need for OGTT to 7.3% compared to the selective screening model with traditional risk factors. Such a universal two-step screening model had 100% sensitivity for DM, and 44.7% sensitivity for IGT. The Swedish Medical Birth Register was used to evaluate GDM as risk factor for preeclampsia. GDM occurred in 0.8% and preeclampsia in 2.9% of 430,852 singleton pregnancies. There is an independent and significant association between GDM and preeclampsia. Obesity is a major confounding factor, but cannot explain the total excess risk. In a prospective population-based case-control study 213 women with untreated IGT during pregnancy were identified. For each case, four controls were recruited from the same delivery department. The analyses confirmed that maternal and fetal morbidity were increased in the cases in terms of cesarean section rate, pre-term delivery, Erb’s palsy and admission to NICU. There was a marked, independent increase in the proportion of LGA infants (OR 7.3; 95% CI 4.1-12.7). To determine whether treatment has an effect when IGT is diagnosed during pregnancy, a randomized study is required.

Antenatal care has been associated with improved maternal and perinatal outcomes but there is no agreement on the most effective model in terms of content as well as the number and timing of visits. A cluster randomised controlled trial was conducted in a rural area of Zimbabwe to assess a 5-visit goal-oriented antenatal care model against standard care. In the same population was also determined the sensitivity of factors used for risk screening to predict pregnancy complications and the effectiveness of the referral system in managing women with identified risk markers or pregnancy complications. Pregnancy records of 10 572 out of total 13 517 recruited women were available for analysis. The new model did not change the number of visits but resulted in better use of health care. The classical risk screening system had low predictive value and identified too large a risk group for referral. Nulliparous women had an increased risk for pregnancy complications whereas women with previous uncomplicated pregnancies were at low risk of complications even with high parity. Multiparous women with previous complications had an increased risk of complications but better utilisation of health care services for delivery reduced adverse perinatal outcomes. There was a functional referral system in Gutu and women complied with referral indications but efficiency of the system was reduced by failure of care providers to comply with referral recommendations. Antenatal care can be improved in a rural setting through a focussed programme and the unpredictability of many pregnancy complications limits the value of antenatal risk screening. Until universal access to essential obstetric care facilities is attained in low resource settings, a critical re-examination of risk factors could avoid overburdening the referral system.

Hyaluronan is an important component of the lung extracellular matrix, with a high capacity for water immobilization, but information on perinatal changes in the lung hyaluronan concentration and their association with changes in the lung water content is limited. In this study, conducted both in rabbit pups and in human infants, we investigated changes in the hyaluronan concentration and distribution in the lung and in the lung water content after preterm or term birth, and changes produced by common antenatal and postnatal pathological conditions and treatments. In rabbit pups, we found a gradual decrease in lung hyaluronan concentration and in the intensity of alveolar hyaluronan staining with advancing gestational age at birth in late gestation, but no further changes during the first 7-9 days of life. The lung water content was uniformly high before birth, but decreased significantly after preterm delivery or at birth at term. Postnatal exposure of newborn preterm or term rabbit pups to hyperoxia for 4-9 days resulted in an increase in both lung hyaluronan concentration and lung water content. This was accompanied by more intense hyaluronan staining, mainly in the alveolar walls. Antenatal exposure of rabbit pups to betamethasone or terbutaline resulted in a lower lung hyaluronan concentration at preterm birth, associated with less intense hyaluronan staining in alveolar walls, without altering the lung water content. Betamethasone exposure had a maximal effect at 25 days of gestation (term = 31 days), decreasing thereafter with advancing gestation, while terbutaline exposure resulted in a gradually increasing effect during late gestation, with a maximum at 29 days. In deceased infants born at a gestational age of < 32 weeks, the lung hyaluronan concentration at death was most strongly associated with the gestational age at birth. It also covaried with sex, antenatal steroid administration, intrauterine bleeding, mode of delivery, birth weight, IRDS, and surfactant treatment. In infants born at a gestational age of > 33 weeks there was a weaker association between lung hyaluronan concentration and gestational age. In this group, the lung hyaluronan concentration was associated with administration of a high concentration of oxygen, and covaried with maximal ventilatory pressure, and lung water content.

Background: Depressive and anxiety disorders are common health problems, affecting women at least twice as often as men. Although some studies have been made on pregnant women or, especially, in the postpartum period, most of these studies have been performed on small samples, mainly specific risk groups such as teenage mothers, women of low socioeconomic status and certain ethnic groups. Also, there is a lack of studies on antenatal and postpartum depression and/or anxiety using diagnostic criteria adhering to the Diagnostic and Statistical Manual of Mental disorders, fourth edition (DSM-IV). Aims and methods: The aims were to estimate the point prevalence of mood, anxiety and eating disorders, based on DSM-IV criteria, in an unselected population during the second trimester of pregnancy, and to assess the obstetric and neonatal outcome, as well as the health care consumption during pregnancy, delivery and the early postpartum period among women with a psychiatric disorder, compared to healthy subjects. Finally, we aimed to investigate depression and anxiety, and associated maternal characteristics and events through pregnancy and the postpartum period in the same group of women. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used for assessment of psychiatric disorders during the second trimester of pregnancy and three to six months after delivery. From October 2nd, 2000, to October 1st, 2001 all women attending the second trimester routine ultrasound-screening at two different hospitals in northern Sweden (at Umeå University Hospital and at Sunderby Central Hospital) were approached for participation in the study. After delivery, data were extracted from the medical records of the mothers and their offspring to evaluate obstetric and neonatal outcome. Three to six months after delivery, the women who had an antenatal depression and/or anxiety were contacted for an assessment using the PRIME-MD. The same procedure was made in a control group, consisting of 500 women, randomly selected among those who did not have any psychiatric diagnosis according to the PRIME-MD investigation during the second trimester of pregnancy. Results and conclusions: Of the 1555 women in the study population, 220 (14.1%) had one or more PRIME-MD diagnoses. Living single, low socioeconomic status, smoking, multiparity and a body mass index of 30 or more were significantly associated with a psychiatric diagnosis in the second trimester of pregnancy. Women with antenatal depression and/or anxiety more often suffered from nausea and vomiting during pregnancy were more often on sick leave, and they visited their obstetrician more often than healthy subjects, specifically because of fear of childbirth and premature contractions. Also, they were more commonly delivered by elective caesarean section, had an increased use of epidural analgesia and reported a longer self-experienced duration of labor. Severe complications of pregnancy, delivery, and the early postpartum period were not affected by antenatal depression and/or anxiety. There was no significant difference in neonatal outcome depending on antenatal depressive or anxiety disorder. Fewer cases of depressive and/or anxiety disorders were prevalent postpartum, but there was a significant shift from a majority of sub-threshold diagnoses during pregnancy to full DSM-IV diagnoses during the postpartum period. Previous psychiatric disorder and living singly were significantly associated with both a new-onset and a postpartum continuation/recurrence of depression and/or anxiety. Postpartum continuation/recurrence of a psychiatric disorder was additionally associated with smoking, obesity, and adverse obstetric events.

<p>The aim of the studies described in this thesis was to assess the association between certain perinatal factors and the risk of childhood lymphatic and myeloid leukemia and infant leukemia. </p><p>The five studies presented were all conducted in Sweden as population-based case-control studies. All cases were born and diagnosed between 1973-89 with leukemia up to the age of 16 years. A control was individually matched to each case. As Down’s syndrome entails a major risk for childhood leukemia, children with Down’s syndrome were excluded. The studies comprised a total of 652 cases, 47 of whom were diagnosed before the age of one year. Exposure data were extracted blindly from antenatal, obstetric, pediatric and other standardized medical records.</p><p>No association was found between prenatal exposure to ultrasound or diagnostic x-ray and childhood lymphatic or myeloid leukemia. Infant leukemia was associated with prenatal exposure to x-ray. A history of maternal lower genital tract infection significantly increased the risk of childhood leukemia, especially among children diagnosed at four years or older or in infancy. Factors such as young maternal age, and mothers working with children or in the health sector were associated with infant leukemia. Resuscitation with 100% oxygen with a face-mask and bag directly postpartum was associated with an increased risk of childhood lymphatic leukemia. The oxygen-related risk further increased if the manual ventilation lasted for three minutes or more. There was no association between lymphatic or infant leukemia and supplementary oxygen later in the neonatal period or other birth-related factors. Low Apgar scores at one and five minutes were associated with a non-significantly increased risk of lymphatic leukemia, and were significantly associated with infant leukemia.</p><p>Previously reported relations between childhood leukemia and exposures such as maternal diagnostic x-ray and birth related factors could not be confirmed by these studies. However, the present studies indicate that events during pregnancy or during the neonatal period are associated with increased risks of childhood and infant leukemia. These events can either be non-specific, such as exposure to maternal lower genital tract infection, or specific, such as the use of supplementary oxygen directly postpartum.</p>

<p>The experience of pregnancy and childbirth is a central life event with special implications for women at high risk. This thesis describes the meaning of pregnancy, childbirth and midwifery care in four qualitative interview studies based on the lifeworld theory. Women were interviewed during pregnancy and within one week after childbirth. Midwives were interviewed concerning midwifery care for women at high risk. In an intervention study, childbirth experience as reported through a post partum questionnaire was compared between women receiving standard care and women who had formulated a birth plan preceded by a questionnaire on their expectations and feelings about childbirth. </p><p>The findings emphasise that childbearing women at high risk live in an extremely vulnerable situation. The vulnerability is obvious in the use of an individual birth plan, where negative feelings become more frequent in women at high risk than in those with normal pregnancy and childbirth. During pregnancy the women feel a moral commitment towards the child, including feelings of objectification and of exaggerated responsibility. During an obstetrically complicated childbirth the essential meaning is the women’s desire to be recognised and affirmed as individual persons. Like women with normal pregnancy and childbirth, they need an emotionally present midwife who sees, give trust and supports. </p><p>Good midwifery care of childbearing women at high risk is synthesised as "genuine caring in caring for the genuine". The ethos of caring constitutes the basis of caring. Women’s transition during pregnancy and childbirth is described as a genuinely natural process. Midwives have a special responsibility to encourage and preserve this process within women at high risk. The caring relationship is the core and the most essential tool in the care. Distinctive features in the midwifery care are embodied knowledge, physical as well as emotional presence, sensitivity, a mutual dialogue including shared control between midwife and woman, and confirmation and support of the genuine in each woman. The midwifery care is a struggle and a balance between natural and medical perspectives.</p>

<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>