This study, based on daily recordings of infant feeding, comprised 506 infants from Uppsala, Sweden. All mothers had had previous breastfeeding experience of at least 4 months, and were planning to breastfeed the index child for ≥6 months. Among exclusively breastfed infants there were wide variations in breastfeeding frequency and suckling duration per 24 hours both between infants and in the individual infant over time in the first 6 months. Most infants had an average of 1.0-2.9 feeds per night. Infants using a pacifier had fewer feeds and a shorter total suckling duration per 24 hours, and stopped breastfeeding earlier than infants not using a pacifier. These associations were not found for thumb sucking. Accustoming the infants to solids was a lengthy process, the longer the younger the infant at introduction, and was associated with small changes in pattern and duration of breastfeeding. In contrast, formula was usually given in large amounts from the beginning, and when formula was given regularly the daily breastfeeding frequency and suckling duration declined swiftly. The younger an infant at the start of regular formula feeds, the shorter the breastfeeding duration. Occasional formula feeds did not affect the breastfeeding duration. It is important for health personnel and parents to keep in mind that exclusively breastfed infants are not a homogeneous group, but rather members of distinct 'breastfeeding entities'. Moreover, if the aim is to introduce other foods 'under the protection of breast milk' it is important to realise that formula is also 'another food' and needs to be treated as such.

Studies were performed on methodological issues on vitamin A intake, status and improvement in three Asian countries, to improve the dietary approach recommended by FAO/WHO to alleviate vitamin A deficiency in low-income countries. The reliability of the practical 24-hour dietary recall method to assess individual intake of vitamin A during pregnancy was investigated in Central Java, Indonesia. The usual mean intake of vitamin A can be reliably measured, but data on attenuation of simple regression coefficients suggest that it is difficult to establish associations between vitamin A intake and some health outcome. The majority of women was below the recommended daily intake of vitamin A in all three trimesters and strategies to improve vitamin A intake in all women are thus needed. The applicability of the simplified "Helen Keller International Food Frequency Method" to assess community risk of vitamin A deficiency in South Asia, even though it excludes breastmilk and animal milk, was tested in rural Bangladesh and rural India. Breast milk was found to be an important source of vitamin A even in the second and third years of life in rural areas of Bangladesh. Similarly, animal milk is likely to be an important source of vitamin A among preschoolers in certain areas of India. The method should be revalidated to make it a useful tool even in settings where breastmilk and animal milk are common in the diets of preschool children. Whether it is possible to improve vitamin A status with dark green leafy vegetables in children free of Ascaris lumbricoides was investigated in northern Bangladesh. A substantial increase in serum β-carotene was seen after supplementary feeding of these vegetables for 6 weeks. The impact on serum retinol concentrations was less substantial.

From January, 1988, to December, 1993, 113 patients with FIGO stage IA-IIC epithelial ovarian carcinoma were treated with postoperative radiotherapy. The median follow-up period was 74 months. Tumor recurrences were recorded in 33 cases (30%). The cancer-specific survival rate was 72%. Tumor grade was a significant (P = 0.007) and independent prognostic factor in the multivariate analysis. In a smaller series of 106 patients, a number of prognostic factors (age, FIGO stage, histopathological type, and tumor grade) were studied in relation to regulators of apoptosis (p53, bcl-2, and bax) and growth factor receptors (HER-2/neu and EGFR). Immunohistochemical techniques were used. In a separate series of 103 patients, the DNA content (flow cytometry) and p53 status of the tumors were also studied and related to the same clinicopathological factors. P53 was associated with tumor grade (P = 0.007) and survival status (P = 0.046). In a Cox multivariate analysis, tumor grade (P = 0.0006), bax status (P = 0.020), and EGFR status (P = 0.018) were significant and independent prognostic factors. DNA ploidy of the tumors was strongly associated with tumor grade. From January, 1994, to December, 1998, a series of 109 patients with ovarian carcinomas (FIGO IA-IIC) were treated with postoperative adjuvant chemotherapy. The same prognostic factors were studied in this series. The median follow-up was 48 months and the cancer-specific survival rate was 75%. Twenty-five (25%) tumor recurrences were recorded. The most favorable survival rate was seen in patients with tumors negative for p53 and positive for bcl-2 or bax. In a multivariate analysis, tumor grade (P = 0.014) and p53 status (P = 0.020) were independent prognostic factors. Clinical, histopathological and biological prognostic factors should be combined in prognostic models to render patient-tailored therapy possible and to define different prognostic groups for future clinical studies of adjuvant therapy in early stage ovarian carcinomas.

Men’s violence against women is a universal issue affecting health, human rights and gender-equality. In pregnancy, violence is a risk for both the mother and her unborn child. The overall aims were: to determine the prevalence of such violence in a Swedish pregnant population, to investigate pregnant women’s attitudes to questioning about exposure to violence, and to evaluate experience gained by antenatal care midwives having routinely questioned pregnant women regarding violence. All women registered for antenatal care in Uppsala, Sweden, during 6 months were assessed regarding acts of violence. The Abuse Assessment Screen (AAS) was used twice during pregnancy and again after delivery when the women were asked an open-ended written question regarding attitudes to questioning about violence. Midwives’ experiences regarding routine assessment were evaluated in focus group discussions. The AAS questions were answered by 93% (1,038) of those eligible. Physical abuse by a partner or relative during or shortly after pregnancy was reported by 1.3%, and by 2.8% when the year preceding pregnancy was included. Lifetime sexual abuse was reported by 8.1%. Repeated questioning increased the abuse detection rate. Abused women reported more previous ill-health, and women physically abused during pregnancy more pregnancy terminations than did non-abused women. Abuse assessment was found entirely acceptable by 80%, both acceptable and unacceptable/disagreeable by 5% and solely unacceptable/ disagreeable by 3%, while 12% were neural. Abused and non-abused women did not differ regarding disinclination to answer the abuse questions. According to the midwives the delicacy of the subject and the male partners’ presence were the most prominent remaining obstacles to routine determination of violence. Routines are required to make questioning about violence an integral part of antenatal care. This would necessitate a private appointment for the woman, knowledge among care providers about the nature of men’s violence, and awareness of referral options.

<p>Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of pre-eclampsia (PE). It has recently been pointed out that PE might be more than one disease and may have several different pathogeneses. This thesis describes a new animal model for PE and examines the role of oxidative stress in early respective late onset PE. </p><p>The effects of Suramin injections on day 10 and 11 of pregnancy were investigated in normal and diabetic rats of two strains (U and H), with or without additional vitamin E treatment. Suramin caused placental dysfunction in both rat strains: foetal growth restriction, increased resorption rate, reduced placental blood flow, and decreased maternal blood volume in the placenta. In the U strain Suramin also caused maternal hypertension and reduced renal blood flow. Oxidative stress in the Suramin treated rats was indicated by increased levels of isoprostane 8-iso-PGF_2α in the placenta. Antioxidative treatment with vitamin E partly protected against the effects of Suramin. Streptozotocin-induced diabetes seemed to cause similar placental effects as Suramin, and in the diabetic rats the additional effects of Suramin were only moderate. In conclusion, Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction (U and H rats) and PE (U rats). </p><p>Oxidative stress was estimated in women with early onset (≤ 32 weeks) or late onset (≥ 35 weeks) PE, in normotensive pregnant women of respective gestational length, and in healthy non-pregnant women. The ratio of PAI-1/PAI-2 was measured in serum, and the amount of isoprostane 8-iso-PGF_2α was measured in placenta, serum, and urine. The ratio of PAI-1/PAI-2 and placental isoprostane levels were higher in women with early onset PE compared with all other groups. Serum levels of isoprostane were similar between groups. Urinary levels of isoprostane were similar in all pregnant women, but lower in non-pregnant women. These data indicate that pregnancy increases general oxidative stress, and that early onset, but not late onset PE, causes increased oxidative stress also in placental tissue. The pathogeneses of early and late onset PE are, therefore, not likely to be identical.</p>

<p>These studies were undertaken to investigate risks of maternal and perinatal complications in pregnant women with chronic hypertensive disease, and to investigate future risk of preeclampsia in women born small for gestational age (SGA). Population based cohort studies using the Swedish Medical Birth Register from different years were performed.</p><p>The maternal complications mild and severe preeclampsia, gestational diabetes and abruptio placenta were studied in a population of 681 515 women, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics as age, parity, BMI, ethnicity and smoking habits. Chronic hypertensive women wore found to have significantly increased risks of all complications. </p><p>The perinatal complication SGA was studied in a population of 560 188, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the secondary complications mild and severe preeclampsia. Chronic hypertensive women were found to suffer a significantly increased risk of giving birth to an offspring that is SGA. </p><p>The perinatal complication fetal/infant mortality was studied in a population of 1 222 952 with a prevalence of 0,6% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the complications mild and severe preeclampsia, gestational diabetes, abruptio placenta and offspring being SGA In the analysis an effect modification by gender was included. Chronic hypertensive women were found to have a significantly increased risk for stillbirth and neonatal death in male, but not in female, offspring. Thus a clear gender difference in mortality was revealed. The risk of mortality of offspring was mediated by severe preeclampsia, abruptio placenta and offspring being SGA. Mild preeclampsia and gestational diabetes did not affect the risk. No increased risk of post neonatal mortality was found.</p><p>A generation study was performed in 118 634 girls of which 5.8% were born SGA. Their future risk for mild and severe preeclampsia in first pregnancy was analysed. Risk estimates were adjusted for age, smoking, BMI and for preeclampsia in the mothers while pregnant with the study population. Women who were born SGA were shown to have a significantly increased risk for severe preeclampsia, but not for mild preeclampsia. </p>

<p>The effects of environmental contaminants in humans and animals are of great concern. Some contaminants are endocrine disruptors that may interfere with the endogenous hormonal signalling and disturb, for example, reproductive organs and functions.</p><p>Primary uterine myometrial cells originating from women and Baltic grey seals were exposed to some polychlorinated biphenyls (PCBs) and their metabolites. Even though human and Baltic grey seal myometrial cells responded differently to the tested PCBs, the results indicate that PCBs can influence myometrial cell proliferation <i>in vitro</i>.</p><p>The prevalence of uterine leiomyomas was investigated among 257 Baltic grey seals. Leiomyomas were only present in females older than 22 years, at a prevalence of 65%. Proliferation in leiomyoma cells was detected in individuals lacking ovarian proliferation support, suggesting the presence of an exogenous stimulant. By taking into account temporal alterations in the contaminant burden of the seals, PCB exposure was found to be associated with leiomyoma prevalence. In conclusion, PCB exposure may be related to uterine leiomyoma development and proliferation in Baltic grey seals <i>in vivo</i>.</p><p>Human endometrial endothelial cells (HEECs) were exposed to some endocrine disruptors, and the effects of the endocrine disruptors on cell proliferation and viability were studied. All evaluated endocrine disruptors decreased HEEC proliferation and most also decreased HEEC viability. Further studies revealed that the reduction in HEEC proliferation after exposure to o,p’-DDT was associated with differential expression of mRNA involved in proliferation, defence response, and lipid and cholesterol metabolism compared to untreated HEEC. </p><p>In conclusion, these studies suggest that endocrine disruptors affect cultured cells from the female reproductive tract of humans and grey seals, and may have deleterious effects on proliferation, viability, and genes involved in defence response, and lipid or cholesterol metabolism.</p>

The effects of environmental contaminants in humans and animals are of great concern. Some contaminants are endocrine disruptors that may interfere with the endogenous hormonal signalling and disturb, for example, reproductive organs and functions. Primary uterine myometrial cells originating from women and Baltic grey seals were exposed to some polychlorinated biphenyls (PCBs) and their metabolites. Even though human and Baltic grey seal myometrial cells responded differently to the tested PCBs, the results indicate that PCBs can influence myometrial cell proliferation in vitro. The prevalence of uterine leiomyomas was investigated among 257 Baltic grey seals. Leiomyomas were only present in females older than 22 years, at a prevalence of 65%. Proliferation in leiomyoma cells was detected in individuals lacking ovarian proliferation support, suggesting the presence of an exogenous stimulant. By taking into account temporal alterations in the contaminant burden of the seals, PCB exposure was found to be associated with leiomyoma prevalence. In conclusion, PCB exposure may be related to uterine leiomyoma development and proliferation in Baltic grey seals in vivo. Human endometrial endothelial cells (HEECs) were exposed to some endocrine disruptors, and the effects of the endocrine disruptors on cell proliferation and viability were studied. All evaluated endocrine disruptors decreased HEEC proliferation and most also decreased HEEC viability. Further studies revealed that the reduction in HEEC proliferation after exposure to o,p’-DDT was associated with differential expression of mRNA involved in proliferation, defence response, and lipid and cholesterol metabolism compared to untreated HEEC. In conclusion, these studies suggest that endocrine disruptors affect cultured cells from the female reproductive tract of humans and grey seals, and may have deleterious effects on proliferation, viability, and genes involved in defence response, and lipid or cholesterol metabolism.

Introduction: Hormone therapy (HT) has been considered as a safe treatment for menopausal symptoms. Use of HT increased dramatically in the 1980s and 1990s. Results from large randomized clinical trials (RCT) could, around the turn of the century, however not find evidence for long-term benefits with HT. These results attracted great attention from media and the scientific community leading to changed treatment guidelines and decreased use of HT. Aim: The overall aim of this thesis was to explore Swedish women’s conceptions, knowledge, management, and attitudes regarding the menopausal transition and HT. Material and methods: To explore and describe women’s conceptions of the menopausal transition women seeking medical advice due to climacteric symptoms were interviewed (n=20) and their statements were analyzed with a qualitative method (paper I). In 1999 (n=1760) and 2003 (n=1733) attitudes to (paper II) and knowledge of (paper III) the menopausal transition and HT among 53- and 54 year old women were investigated with a cross-sectional design using postal questionnaires. We also analyzed if attitudes differed before and after new scientific findings were published on risks and benefits of HT and if knowledge differed between educational levels. Since many women try to abandon use of HT a RCT was performed to study the effect of two different methods to discontinue HT, on recurrence of hot flushes, resumption of HT and on health related quality of life (HRQoL). Women (n=87) with vasomotor symptoms before initiating HT participated. Results: We found that the majority of the middle aged women in our study viewed the menopausal transition as a natural process the nature of which is affected by both hormonal changes and by ageing. Each woman seems to experience a set of psychological and physical symptoms that are in some sense unique to her experience. Women’s answers to the questions about HT demonstrate that attitudes towards HT held by women going through menopause have changed rather dramatically between 1999 and 2003. These changes probably reflect the influence on the women of media reports based on research that identified risks associated with HT that had not been identified before 1998. Women’s knowledge of the effects of HT seems to be unsatisfactory from a clinical perspective. No differences in hot flush frequency and resumption of HT were found between the women randomized to two different modes of discontinuation of HT. Almost 50 % of the women restarted HT within one year after discontinuation. Deteriorated wellbeing and severity of hot flushes were important predicting factors for resumption of HT. Conclusion: It is important to be aware of the individual woman’s conceptions and attitudes about and knowledge of the menopausal transition and HT to be able to individualize the counselling situation. Women who initiate HT due to hot flushes may experience recurrence of vasomotor symptoms and deteriorated HRQoL after discontinuation. A great proportion of them may resume HT. At present knowledge of possible advantages for the taper-down method when discontinuing HT is still lacking.

These studies were undertaken to investigate risks of maternal and perinatal complications in pregnant women with chronic hypertensive disease, and to investigate future risk of preeclampsia in women born small for gestational age (SGA). Population based cohort studies using the Swedish Medical Birth Register from different years were performed. The maternal complications mild and severe preeclampsia, gestational diabetes and abruptio placenta were studied in a population of 681 515 women, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics as age, parity, BMI, ethnicity and smoking habits. Chronic hypertensive women wore found to have significantly increased risks of all complications. The perinatal complication SGA was studied in a population of 560 188, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the secondary complications mild and severe preeclampsia. Chronic hypertensive women were found to suffer a significantly increased risk of giving birth to an offspring that is SGA. The perinatal complication fetal/infant mortality was studied in a population of 1 222 952 with a prevalence of 0,6% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the complications mild and severe preeclampsia, gestational diabetes, abruptio placenta and offspring being SGA In the analysis an effect modification by gender was included. Chronic hypertensive women were found to have a significantly increased risk for stillbirth and neonatal death in male, but not in female, offspring. Thus a clear gender difference in mortality was revealed. The risk of mortality of offspring was mediated by severe preeclampsia, abruptio placenta and offspring being SGA. Mild preeclampsia and gestational diabetes did not affect the risk. No increased risk of post neonatal mortality was found. A generation study was performed in 118 634 girls of which 5.8% were born SGA. Their future risk for mild and severe preeclampsia in first pregnancy was analysed. Risk estimates were adjusted for age, smoking, BMI and for preeclampsia in the mothers while pregnant with the study population. Women who were born SGA were shown to have a significantly increased risk for severe preeclampsia, but not for mild preeclampsia.