Wildfires pose a significant and growing threat to human health. Current trends in climate change predict that wildfire occurrence and severity will increase in the near future, and therefore the adverse health effects associated with wildfire and its air quality effects are becoming increasingly relevant. Even with current efforts to stem future rises in temperature, wildfire activity will continue to increase due to lags in the climate system itself. Thus, in addition to the known increase in mortality, respiratory, and cardiovascular risks, there is a growing need to investigate other health outcomes associated with wildfire smoke exposure, especially their effect on pregnancy and birth outcomes. In order to provide a broad overview of the state of wildfire research on the topic of pregnancy and birth outcomes, this narrative review will summarize the existing literature on pregnancy and birth outcomes associated with wildfire smoke exposure, with consideration for the ambient air pollution literature that informs wildfire research. As research in this specific topic is still developing, a pattern of limitations to study designs is beginning to emerge, which will guide future research needs. Finally, practical considerations for implementing research findings into land management and public health policies that reduce wildfire exposure in order to mitigate the health risks associated with it will be explained.

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Background Overweight and obesity are global health problems with several adverse health effects that threaten public health. In Sweden, almost four of ten pregnant women are overweight or obese, conditions that are associated with adverse pregnancy outcomes, including gestational diabetes mellitus (GDM), a metabolic disorder that complicates pregnancy. Globally, physical inactivity is the fourth leading risk factor for mortality. The recommendation for physical activity (i.e., ≥150 minutes/week) issued by the Professional Associations for Physical Activity and the Swedish National Board of Health and Welfare is in line with the recommendations by the WHO. Physical activity during pregnancy is generally safe and beneficial for both the pregnant woman and her fetus and can maintain or improve fitness and may further improve pregnancy outcomes. However, pregnant women tend to lower their physical activity when entering pregnancy. Midwives working in antenatal care (ANC) in Sweden play a prominent role in promoting a healthy lifestyle through counselling pregnant women on lifestyle, including physical activity during pregnancy. Individual counselling on physical activity encourages pregnant women to maintain their pre-pregnant leisure time physical activity throughout their pregnancy. Aims This thesis has three main aims. First, this thesis investigated guidelines for screening of GDM, risk factors, and pregnancy outcomes in relation to GDM. Second, it investigated physical activity during pregnancy and pregnancy outcomes. Third, it explored midwives’ and pregnant women’s experiences with counselling that addressed physical activity during pregnancy. Methods Study I and III are cross-sectional studies using data from the Maternal Health Care Register and the Salut Register. A total of 184,183 pregnant women were included in Study I (2011-2012) and 3,868 in Study III (2011-2012). Several statistical analyses were used: two-independent samples t-test, Pearson’s Chi-Square test, and univariate and multivariate logistic regression analyses. Study II and IV are qualitative studies applying qualitative content analysis. Study II included 41 midwives who were interviewed in eight focus group discussions (FGD). Study IV included 14 pregnant women who participated in individual in-depth interviews. Main findings There was no consensus in Sweden regarding clinical guidelines for screening regimes or 2-hour cut-off value for diagnosis of GDM from 2011 through 2012. Four screening regimes were applied in Sweden during this time period: A) universal screening with a 2-hour cut-off value of 10.0 mmol/L; B) selective screening with a 2-hour cut-off value of
8.9 mmol/L; C) selective screening with a 2-hour cut-off value of 10.0 mmol/L; and D) selective screening with
a 2-hour cut-off value of 12.2 mmol/L. The highest prevalence of GDM was found where selective screening was applied with a 2-hour cut-off value of 8.9 mmol/L. Unemployment, low educational level, and non-Nordic origin were all risk factors for GDM, and a BMI ≥30 kg/m2 almost four-doubled the risk for GDM compared to pregnant women with BMI <30 kg/m2. Increasing OGTT-values were associated with increasing risk of adverse pregnancy outcomes (Paper I). Midwives in antenatal care perceived counselling as both challenging and as an opportunity to promote a healthy lifestyle for pregnant women. As the theme “An on-going individual adjustment” revealed, the midwives tried to adjust their counselling to each pregnant woman’s individual needs. Counselling pregnant women on physical activity was seen as complex and ambiguous with a risk of being rejected by the women if the advice was delivered too straightforward. Instead, the midwives were “tiptoeing” around the sensitive topics (Paper II). Almost half of pregnant women reported that they achieved the recommended level of physical activity during pregnancy (i.e., ≥150 minutes/week). These pregnant women were characterized by lower BMI, higher educational level, and very good or good self-rated health (SRH) compared to the pregnant women who did not achieve the recommended level (Paper III). Pregnant women reported a desire for individual counselling on physical activity during pregnancy. The theme that emerged was “Longing for fulfilment of individual needs and expectations”, which reflected the wish that midwives’ counselling on physical activity should be based on pregnant women’s individual needs instead of merely providing general advice. Some participants reported receiving encouragement and support, but others believed they were provided insufficient counselling on physical activity and that the midwife had her own agenda focusing mostly on medical surveillance (Paper IV). Conclusions No consensus regarding clinical guidelines and diagnostic criterion for GDM existed in Sweden during 2011 to 2012. Obesity was a strong risk factor for development of GDM, and low socio-economic status and non-Nordic origin were also demonstrated as significant risk factors. Positively, almost half of the pregnant women reached the recommended level of physical activity during pregnancy. Participants fulfilling the recommendation were characterized by lower BMI, higher education, and very good or good self-rated health. Midwives strived to adjust and individualize their counselling on physical activity; however, some of the pregnant women could experience the counselling on physical activity being too general. Clearly, healthcare professionals should encourage fertile and pregnant women to be physically active, especially overweight and obese pregnant women who report low levels of physical activity, in order to improve overall health in this population. / Bakgrund Övervikt och fetma är ett stort hälsoproblem globalt med flera negativa hälsoeffekter som utgör ett hot mot folkhälsan. Nästan 40% av de gravida i Sverige har övervikt eller fetma vilket är associerat med flera negativa graviditetsutfall där graviditetsdiabetes (GDM) är en metabolisk sjukdom som komplicerar graviditeten. Fysisk inaktivitet är den fjärde ledande riskfaktorn för dödlighet i ett globalt perspektiv. Att vara fysiskt aktiv förbättrar välbefinnandet och livskvaliteten, främjar stabil vikt, insulinkänslighet och normalt blodtryck. Vidare sänker fysisk aktivitet risken för diabetes mellitus typ 2, fetma och hjärt-och kärlsjukdomar. Fysisk aktivitet under en okomplicerad graviditet är generellt att betrakta som utan risk och ökar välbefinnandet för både kvinnan och fostret. Fysisk aktivitet bidrar till att bibehålla eller förbättra fysisk kondition och kan förbättra graviditetsutfall. Trots dessa fördelar tenderar gravida att sänka sin fysiska aktivitet under graviditeten. De svenska rekommendationerna följer de internationella riktlinjerna som innebär ≥150 minuter/vecka av måttlig fysisk aktivitet alternativt 75 minuter/vecka av intensiv fysisk aktivitet eller en kombination av dessa. Svenska barnmorskor som arbetar inom mödrahälsovården i Sverige har en central, rådgivande roll gentemot gravida kvinnor när det gäller att verka för en hälsosam livsstil inkluderande fysisk aktivitet. Individuell rådgivning i fysisk aktivitet kan uppmuntra och stödja gravida kvinnor att fortsätta vara fysiskt aktiva under hela graviditeten. Syfte Att kartlägga riktlinjer för graviditetsdiabetes i Sverige samt riskfaktorer och graviditetsutfall i relation till GDM. Vidare att undersöka fysisk aktivitet under graviditeten samt associationer till graviditetsutfall och slutligen att utforska barnmorskor och gravida kvinnors upplevelser av rådgivning i fysisk aktivitet. Metod Studie I och III var tvärsnittsstudier där data från Mödrahälsovårds-registret och Salutregistret nyttjades. Totalt 184,183 gravida kvinnor inkluderades i Studie I och 3,868 inkluderades i Studie III (tidsperiod 2011-2012). Statistiska analyser som genomfördes var t-test, Pearson’s Chi-2-test och univariat samt multivariat logistisk regressionsanalys. Studie II och IV var kvalitativa studier där intervjuerna analyserades med manifest och latent kvalitativ innehållsanalys. Studie II inkluderade 41 barnmorskor i åtta fokusgrupper och 14 gravida omföderskor djupintervjuades individuellt i Studie IV. Resultat Under perioden 2011-2012 förelåg inte någon enighet gällande riktlinjer för screening och gränsvärde för diagnosen GDM i Sveriges 43 mödrahälsovårdsområden. Fyra olika screeningregimer identifierades; A) generell screening och 2-timmar gränsvärde på 10,0 mmol/L i plasmaglukos, B) selektiv screening och 2-timmar gränsvärde på 8,9 mmol/L i plasmaglukos, C) selektiv screening och 2-timmar gränsvärde på 10,0 mmol/L i plasmaglukos och D) selektiv screening och 2-timmar gränsvärde på 12,2 mmol/L i plasmaglukos. Den högsta prevalensen av GDM återfanns i det område som hade 8,9 mmol/L som gränsvärde och den lägsta där 12,2 mmol/L var gränsvärdet för GDM. Arbetslöshet, låg utbildningsnivå och ett utom-nordiskt ursprung utgjorde alla riskfaktorer för utveckling av GDM. Fetma, BMI ≥30 kg/m2, utgjorde den riskfaktor med högst risk för att utveckla GDM under graviditet med en nästan fyrdubblad risk jämfört med en kvinna med BMI <30kg/m2. Ökande 2-timmarsvärden av blodglukos var associerat med ökande negativa graviditetsutfall såsom kejsarsnitt och instrumentell vaginal förlossning (Artikel I). Barnmorskorna i mödrahälsovården upplevde rådgivningen i fysisk aktivitet som å ena sidan utmanande men å andra sidan som en möjlighet att verka för en hälsosam livsstil hos de gravida kvinnorna. Temat ”En ständigt pågående anpassning” visar barnmorskornas försök att anpassa sin rådgivning efter varje enskild gravid kvinnas behov och situation. Rådgivningen i fysisk aktivitet till gravida upplevdes som komplex och mångfacetterad. Det uttrycktes en oro för att bli avvisad av den gravida kvinnan om de givna råden förmedlades för uppriktigt. Detta ledde ibland till att barnmorskorna ”trippade på tå” och försiktigt närmade sig känsliga ämnen såsom övervikt och råd om fysisk aktivitet. Barnmorskorna försökte även finna individuella lösningar och anpassa råden utifrån varje enskild gravid kvinnas möjligheter. Detta var särskilt tydligt i mötet med kvinnor som immigrerat till Sverige, där barnmorskorna upplevde att en del av rådgivningen bestod i att slå hål på myter om fysisk aktivitet såsom något riskfyllt samt att informera om de positiva hälsoeffekterna med fysisk aktivitet under graviditeten (Artikel II). Nästan hälften av de gravida kvinnorna uppnådde Socialstyrelsens rekommendationer avseende fysisk aktivitet under graviditet och dessa kvinnor karakteriserades av lägre BMI, högre utbildningsnivå samt mycket bra/bra självskattad hälsa jämfört med de gravida som inte uppnådde rekommendationerna Artikel III). Temat som framkom i Artikel IV var ”Längtan efter tillfredsställelse av individuella behov och förväntningar” och speglar de gravidas önskan att erhålla en individuellt anpassad rådgivning i fysisk aktivitet av barnmorskorna istället för en generell rådgivning avsedd för alla. Några gravida hade erfarenheter av barnmorskan som stöttande och uppmuntrande i sin rådgivning i fysisk aktivitet. Andra kunde uppleva rådgivningen som otillräcklig, att barnmorskan exempelvis inte hade tillräckligt med kunskap i fysisk aktivitet samt att barnmorskan hade en egen agenda för deras möten som i huvudsak fokuserade på den medicinska övervakningen av graviditeten. Slutsats Under perioden 2011-2012 förelåg ingen consensus angående de nationella riktlinjerna och diagnostiska värdet för GDM i Sverige. Fetma var den riskfaktor med högst risk för utvecklande av GDM och låg socio-ekonomi, maternell ålder >35 år samt utom-nordiskt ursprung utgjorde även riskfaktorer för GDM. Positivt var att nästan hälften av de gravida uppnådde Socialstyrelsens rekommendationer för fysisk aktivitet under graviditeten och dessa karakteriserades av signifikant lägre BMI, högre utbildningsnivå samt mycket god/god självskattad hälsa. Trots att barnmorskorna beskrev hur de strävade efter att anpassa rådgivningen i fysisk aktivitet till varje enskild kvinna, kunde de gravida kvinnorna uppleva att rådgivningen var otillräcklig, för generell och främst fokuserad på den medicinska övervakningen. Det är av största vikt att hälso- och sjukvårdspersonal som möter fertila och gravida kvinnor verkar för en hälsosam livsstil, särskilt avseende kvinnor med en inaktiv livsstil och de som har övervikt eller fetma för att på så sätt förbättra hälsan hos denna del av befolkningen. För att uppnå detta krävs resurser gällande personal, tidsutrymme samt fortbildning inom hälsa och rådgivning för barnmorskor och annan hälso- och sjukvårdspersonal som möter dessa kvinnor. Slutligen, för att möjliggöra rådgivning som avser att stödja fysisk aktivitet för de kvinnor som immigrerat till Sverige behövs mer kunskap och utbildning i mötet med dessa kvinnor.

This thesis aims to undertake health technology assessments in high risk pregnancies through the following objectives: 1. In women with pre-eclampsia, a) To evaluate the association of maternal genotype and severe pre-eclampsia b) To assess the accuracy of tests in predicting adverse pregnancy outcomes c) To develop composite outcomes for reporting in trials on late onset pre-eclampsia 2. In women with multiple pregnancy, a) To study the association between chorionicity and stillbirth b) To identify the optimal timing of delivery in monochorionic and dichorionic twin pregnancies 3. In the field of prediction research in obstetrics a) To provide an overview of the existing prognostic models and their qualities b) To evaluate the methodological challenges and potential solutions in developing a prognostic model for complications in pre-eclampsia Methods The following research methodologies were used: Delphi survey, systematic reviews and meta-analyses. Results 1. a) Maternal genotype and severe pre-eclampsia: 57 studies evaluated 50 genotypes; increased risk of severe pre-eclampsia with thromobophilic genes. b) Accuracy of tests in predicting pre-eclampsia complications: 37 studies evaluated 13 tests. No single test showed high sensitivity and specificity. c) Delphi survey of 18/20 obstetricians and 18/24 neonatologists identified clinically important maternal and neonatal outcomes and maternal and neonatal composite outcomes were developed. 2. Prospective risk of stillbirth and neonatal deaths in uncomplicated monochorionic and dichorionic twin pregnancies: 32 studies were included. In dichorionic twin pregnancies, the risk of stillbirths was balanced against neonatal death at 37 weeks' gestation. In monochorionic pregnancies, there was a trend towards increase in stillbirths after 36 weeks but this was not significant. 3. a) From 177 studies included, 263 obstetric prediction models were developed for 40 different outcomes, most commonly pre-eclampsia, preterm delivery, mode of delivery and small for gestational age neonates. b) The obstetric prognostic model challenge of dealing with treatment paradox was explored and seven potential solutions proposed by expert consensus. Conclusion I have identified the strength of association for genes associated with complications in pre-eclampsia, components for composite outcomes for reporting in studies on pre-eclampsia, and the optimal timing of delivery for twin pregnancies. My work has highlighted the gaps in prediction research in obstetrics and the limitations of individual tests in pre-eclampsia.

The epidemic of maternal obesity is increasing worldwide. Simple, effective and acceptable interventions are needed to combat obesity and improve pregnancy outcomes in women with metabolic risk factors such as dyslipidaemia and obesity. Dietary and lifestyle interventions reduce gestational weight gain, however, their effect on maternal and fetal outcomes is not clearly known. I conducted a large pragmatic randomised trial to evaluate the effectiveness of a Mediterranean-based dietary intervention to reduce the risk of adverse maternal and fetal outcomes in pregnant women with metabolic risk factors (The ESTEEM trial). The intervention significantly reduced gestational diabetes and gestational weight gain by an average of 1.2 Kg with some protective effect on fetal outcomes. I analysed the methodological challenges encountered in the trial and discussed applied solutions. I conducted a systematic review on the commonly used dietary assessment tools in trials involving pregnant women to assess their characteristics, validity, and applicability. Self-reporting dietary tools were the most commonly used to assess dietary intake in pregnancy such as food frequency questionnaires. Only 8% of studies validated the chosen tools and applied a defined adherence criterion. I applied the findings of this review to develop and validate a custom designed food frequency questionnaire, and a short 12 items questionnaire, to assess the participants' adherence in the ESTEEM study. I assessed the dietary intake in a randomised cohort from the ESTEEM study and compared the questionnaires' accuracy to 24 hour dietary recalls as the reference method. Both the FFQ and the short questionnaire performed well for assessing the adherence to and the intake of key foods in the Mediterranean diet. I systematically reviewed available online information sources on the risks and management of obesity in pregnancy in the English language. I assessed 53 websites for their information credibility, accuracy, readability, content and technological quality. Overall I found that non-governmental funded websites that are obesity-specific and targeting healthcare users presented better overall information quality.

Inappropriate weight gain during pregnancy is a widespread problem associated with adverse maternal and newborn outcomes. This study’s objective was to examine the impact of gestational weight gain (GWG) above and below the Institute of Medicine (IOM) guidelines on pregnancy, delivery, and newborn outcomes in a rural population. Women were recruited at the first prenatal visit, and data was collected through research interviews and examination of prenatal and delivery medical records. Prepregnancy weight and weight at delivery were obtained, and the final sample (n=913) was restricted to women with singleton pregnancies. Participants were categorized by prepregnancy body mass index (BMI) and GWG above, within, or below IOM guidelines based on gestational length. After controlling for pregnancy smoking, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to identify significant outcomes associated with high or low weight gain, with normal GWG as the control. Of the 913 participants, 208 (22.8%) had inadequate GWG, 255 (27.9%) gained within the recommended range, and 450 (49.3%) gained more than recommended. Inadequate GWG was associated with delivery before 39 weeks, oxygen administration to the infant, admission to the neonatal intensive care unit (NICU), and a hospital stay longer than seven days. Excess GWG was associated with preeclampsia, pregnancy-induced hypertension (PIH), gestational diabetes mellitus, cesarean delivery, labor longer than 12 hours, macrosomia, and large-for-gestational-age (LGA) infants. GWG outside IOM guidelines was prevalent in the sample and associated with numerous adverse outcomes, suggesting a need for increased awareness and improved management of GWG in this population.

Pregnancy in women with hemoglobinopathy has been associated with an increased risk of adverse pregnancy outcomes. We conducted a historical cohort study using Discharge Abstract Database for the fiscal year 1991-1992 through 2007-2008. We estimated the frequency of pregnant women with hemoglobinopathy and examined their associations with adverse pregnancy outcomes. Women with sickle cell disease are more likely to develop pre-eclampsia and preterm labor, and to undergo cesarean delivery than women with nutritional deficiency anemia, suggesting that there are other mechanisms beyond anemia that may be responsible for an increased risk of adverse pregnancy outcomes. The data suggested a synergistic effect of hemoglobinopathy and pre-eclampsia on preterm labor and cesarean delivery. Prediction models for pre-eclampsia, preterm labor and cesarean delivery were created and internally validated for women with hemoglobinopathy, with satisfactory discrimination and calibration.

Pregnancy in women with hemoglobinopathy has been associated with an increased risk of adverse pregnancy outcomes. We conducted a historical cohort study using Discharge Abstract Database for the fiscal year 1991-1992 through 2007-2008. We estimated the frequency of pregnant women with hemoglobinopathy and examined their associations with adverse pregnancy outcomes. Women with sickle cell disease are more likely to develop pre-eclampsia and preterm labor, and to undergo cesarean delivery than women with nutritional deficiency anemia, suggesting that there are other mechanisms beyond anemia that may be responsible for an increased risk of adverse pregnancy outcomes. The data suggested a synergistic effect of hemoglobinopathy and pre-eclampsia on preterm labor and cesarean delivery. Prediction models for pre-eclampsia, preterm labor and cesarean delivery were created and internally validated for women with hemoglobinopathy, with satisfactory discrimination and calibration.

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Pregnancy in women with hemoglobinopathy has been associated with an increased risk of adverse pregnancy outcomes. We conducted a historical cohort study using Discharge Abstract Database for the fiscal year 1991-1992 through 2007-2008. We estimated the frequency of pregnant women with hemoglobinopathy and examined their associations with adverse pregnancy outcomes. Women with sickle cell disease are more likely to develop pre-eclampsia and preterm labor, and to undergo cesarean delivery than women with nutritional deficiency anemia, suggesting that there are other mechanisms beyond anemia that may be responsible for an increased risk of adverse pregnancy outcomes. The data suggested a synergistic effect of hemoglobinopathy and pre-eclampsia on preterm labor and cesarean delivery. Prediction models for pre-eclampsia, preterm labor and cesarean delivery were created and internally validated for women with hemoglobinopathy, with satisfactory discrimination and calibration.