<p>The aim of this thesis was to explore the prevalence of parentally experienced infant sleep problems, with special interest in severe problems, in a total community sample of 2 518 infants aged between 6 and 18 months. Factors associated with severe sleep problems were sought. Parents reported 16 % of the infants to have difficulties in falling asleep at night, and 30 % to have frequent night waking. Severe sleep problems were associated with frequent night meals, psychosocial problems in the family, exhaustion and depression in the mother, and parental stress. An association with infant difficultness, high activity and problematic behaviour was also found. </p><p>In a five-year prospective study a group of children fulfilling specific criteria for severe sleep problems in infancy (N=27) was followed after an interventional sleep programme and compared with a control group regarding sleep characteristics, behaviour and development. One month after an interdisciplinary treatment programme, combining behavioural technique with family work, the average number of times the case babies woke up had diminished from 6.0 to 1.8 times per night. A 92 % rate of improvement was reported.</p><p>The changes were stable over time. Comparisons with the controls during five years revealed no significant group difference in sleep characteristics. Concerning behaviour and development, however, there were significant differences. At the age of 5.5 years, seven of the children in the former sleep problem group met the criteria for the diagnosis of attention-deficit/hyperactivity disorder. No control child qualified for the diagnosis.</p>

<p><i>Objectives: </i>To study indicators specifically reflecting the reproductive health of Ukrainian women and to analyse factors behind the indicators. </p><p><i>Methods:</i> Induced abortion and maternal mortality were studied in some countries/regions of the former Soviet Union, using official statistics. Abortion rates, contraceptive practices and intentions in Ukrainian women were analysed by a large self-completion survey in 1996, and by a classroom questionnaire to first year medical students in 1999 in Donetsk, Ukraine. Totally, 1694 women and 689 students participated. Perinatal mortality was studied, applying the Nordic-Baltic perinatal death classification to all cases in the Donetsk region in 1997-98 (n=1126) and in Denmark in 1996 (n=540). Clinical guidelines, use of technology and rates of interventions in the two regions were analysed. </p><p><i>Results:</i> Abortion remains a major method of fertility control and abortion-related mortality contributes to maternal deaths. Perinatal mortality rate is twice as high in the Donetsk region as in Denmark. A substantial proportion of sexually active women do not practice contraception. Modern methods of contraception are not widely used. There is a lack of knowledge in reproductive health issues and negative attitude to OCs. There is a positive attitude towards abortion as an acceptable fertility control method and of having abortion instead of using OCs or IUD. Poor economy is an obstacle to the use of contraceptive methods associated with a cost. Lack of experience with contraception reduces the intention to use any method in the future. Being single, younger than 19 years, living with parents, having a positive attitude towards abortion as fertility control method, having a history of previous childbirth and/or abortion are important factors associated with pregnancy termination. Antepartum deaths of growth-retarded fetuses, intrapartum and neonatal deaths associated with asphyxia are more common in Ukraine than in Denmark, particularly among premature infants. Lack of evidence-based clinical guidelines and adequate resources for fetal monitoring during pregnancy and labour, together with negative attitudes towards, and limited resources for, instrumental delivery, contribute to high perinatal mortality.</p><p><i>Conclusion:</i> Better reproductive education/information of all strata of society is needed. Implementation of evidence-based guidelines in perinatal medicine, where international collaboration can be of great value, should be a matter of high priority. </p>

<p>The appropriateness of universal screening for gestational diabetes mellitus (GDM) has been strongly questioned, since it does not satisfy ethical principles for screening. </p><p> 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. </p><p> 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.</p><p> 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. </p><p> 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.</p>

<p>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. </p><p>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. </p><p>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.</p>

<p>The concept of exclusive breastfeeding in relation to daily feeding practices and to health and growth of infants in an affluent society was examined. In a descriptive longitudinal prospective study 506 mother-infant pairs were followed from birth through the greater part of the first year. Feeding was recorded daily, and health and growth were recorded fortnightly. </p><p>Large individual variations were seen in breastfeeding patterns. A wide discrepancy between the exclusive breastfeeding rates obtained from "current status" data and data "since birth" was found.</p><p>Using a strict definition of exclusive breastfeeding from birth and taking into account the reasons for giving complementary feeding, the study showed that many exclusively breastfed infants had infections early in life, the incidence of which increased with age, despite continuation of exclusive breastfeeding. However, truly exclusively breastfed infants seem less likely to suffer infections than infants who receive formula in addition to breast milk. Increasing formula use was associated with an increasing likelihood of suffering respiratory illnesses. The growth of exclusively breastfed infants was similar to that of infants who were not exclusively breastfed. </p><p>The health of newborn infants during the first year of life was associated with factors other than feeding practices alone. Some of these factors may be prenatal, since increasing birth weight was associated with an increasing likelihood of having respiratory symptoms, even in exclusively breastfed infants. However, exclusive breastfeeding was shown to be beneficial for the health of the infant even in an affluent society. </p>

<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 concept of exclusive breastfeeding in relation to daily feeding practices and to health and growth of infants in an affluent society was examined. In a descriptive longitudinal prospective study 506 mother-infant pairs were followed from birth through the greater part of the first year. Feeding was recorded daily, and health and growth were recorded fortnightly. Large individual variations were seen in breastfeeding patterns. A wide discrepancy between the exclusive breastfeeding rates obtained from "current status" data and data "since birth" was found. Using a strict definition of exclusive breastfeeding from birth and taking into account the reasons for giving complementary feeding, the study showed that many exclusively breastfed infants had infections early in life, the incidence of which increased with age, despite continuation of exclusive breastfeeding. However, truly exclusively breastfed infants seem less likely to suffer infections than infants who receive formula in addition to breast milk. Increasing formula use was associated with an increasing likelihood of suffering respiratory illnesses. The growth of exclusively breastfed infants was similar to that of infants who were not exclusively breastfed. The health of newborn infants during the first year of life was associated with factors other than feeding practices alone. Some of these factors may be prenatal, since increasing birth weight was associated with an increasing likelihood of having respiratory symptoms, even in exclusively breastfed infants. However, exclusive breastfeeding was shown to be beneficial for the health of the infant even in an affluent society.

The aim of this thesis was to explore the prevalence of parentally experienced infant sleep problems, with special interest in severe problems, in a total community sample of 2 518 infants aged between 6 and 18 months. Factors associated with severe sleep problems were sought. Parents reported 16 % of the infants to have difficulties in falling asleep at night, and 30 % to have frequent night waking. Severe sleep problems were associated with frequent night meals, psychosocial problems in the family, exhaustion and depression in the mother, and parental stress. An association with infant difficultness, high activity and problematic behaviour was also found. In a five-year prospective study a group of children fulfilling specific criteria for severe sleep problems in infancy (N=27) was followed after an interventional sleep programme and compared with a control group regarding sleep characteristics, behaviour and development. One month after an interdisciplinary treatment programme, combining behavioural technique with family work, the average number of times the case babies woke up had diminished from 6.0 to 1.8 times per night. A 92 % rate of improvement was reported. The changes were stable over time. Comparisons with the controls during five years revealed no significant group difference in sleep characteristics. Concerning behaviour and development, however, there were significant differences. At the age of 5.5 years, seven of the children in the former sleep problem group met the criteria for the diagnosis of attention-deficit/hyperactivity disorder. No control child qualified for the diagnosis.