Background A well-balanced nutritious diet is important for the pregnant woman and the growing fetus, as well as for their future health. Poor nutrition results from both over-consumption of energy-rich foods which can lead to a higher weight gain than is healthy and under-nutrition of essential nutrients. Food intake is regulated in complex biological systems by many factors, where steroid hormone is one factor involved. The overall aim of this thesis is to describe dietary intake, vitamin D levels, dietary information and dietary changes, and to study the relation between allopregnanolone and weight gain during pregnancy and postpartum. Methods Study I was a qualitative study with focus group interviews with 23 pregnant women. The text was analysed with content analysis. Study II was a quantitative cross-sectional study conducted in early pregnancy (n=209) with a reference group (n=206). Self-reported dietary data from a questionnaire was analysed using descriptive comparative statistics and a cluster analysis model (Partial Least Squares modelling). Study III had a quantitative longitudinal design. Vitamin D concentrations were analysed in 184 women, collected on five occasions during pregnancy and postpartum. Descriptive comparative statistics and a linear mixed model were used. Study IV was a quantitative longitudinal study with 60 women. Concentrations of allopregnanolone were analysed in gestational week 12 and 35. Descriptive and comparative statistics as well as Spearman’s correlation (rho) were used to describe the relationship between weight gain and allopregnanolone concentrations.   Results The focus group interviews showed that women wanted to know more about different foods to reduce any risk for their child but the information about foods was partly up to themselves to find out. They expressedfeelingsof insecurityand guiltif they accidentallyate something“forbidden”. The recommendationswere followedas best as possiblealong withcommon sense todeal with dietchanges. The main themes were “Finding out by oneself”, “Getting professional advice when health problems occur”, “Being uncertain” and “Being responsible with a pinch of salt”. Some differences in the dietary patterns were found among the pregnant women compared to references, with less, vegetables (47 g/day), potatoes/rice/pasta (31 g/day), meat/fish (24 g/day) and intake of alcohol and tobacco/snuff but a higher intake of supplements. Bothpregnant women and referenceshad intakes offolatethrough diet45% (pregnant) and 22% (references) lower than current recommendations(500vs400g/day). Vitamin Dintake was34% lower than the recommendationsof 10mg/day. At least a third of the participants had insufficient plasma levels below 50 nmol/L of vitamin D. Season was a strong factor influencing the longitudinal pattern. Gestational week, season, total energy intake, dietary intake of vitamin D, and multivitamin supplementation over the previous 14 days were factors related to vitamin D levels. A correlation betweenallopregnanoloneconcentrations ingestationalweek 35and weight gainin weeks12–35was seen (p = 0.016). Therewas alsoa correlation betweenthe increase inallopregnanolone(weeks12–35) andweight gain(see above) (p = 0.028).   Conclusions Dietary recommendations were described as contradictory and confusing and the dietary advice felt inadequate. The women faced their diet changes and sought information on their own but would have wished for more extensive advice from the midwife. The intake of vitamins essential for pregnancy was lower than recommended, which is also confirmed by low plasma levels of vitamin D in at least one third of the pregnant women. Vitamin D levels peaked in late pregnancy. Aside from gestational week and season which were related to plasma levels, intake from foods and supplements also affected the levels. Reasons for weight gain are complex and depend on many factors. Allopregnanolone is a factor that was seen to relate to the weight gain of the studied pregnant women. / Bakgrund En välbalanserad näringsrik kost är viktig för den gravida kvinnan och det växande fostret, så även för deras framtida hälsa. En bristfällig kost kan utgöras av både överförbrukning av energirika livsmedel vilket kan leda till högre viktuppgång än vad som är hälsosamt och bristande intag av viktiga näringsämnen. Kostintag regleras av komplexa biologiska system där flera faktorer är inblandade däribland steroidhormonet allopregnanolon. Det övergripande syftet med denna avhandling är att under och efter graviditet beskriva kostintag, vitamin D-nivåer, kostinformation och kostförändringar och att studera allopregnanolons relation till viktökning. Metod Studie I var en kvalitativ studie med fokusgruppsintervjuer med 23 gravida kvinnor. Texten analyserades med innehållsanalys. Studie II var en kvantitativ tvärsnittsstudie som genomfördes i tidig graviditet (n = 209) och med en grupp icke-gravida kvinnor (kontrollgrupp) (n=206). Självrapporterade kostdata från ett frågeformulär analyserades med beskrivande, jämförande statistik och en klusteranalysmodell (Partial Least Squares modellering). Studie III hade en kvantitativ longitudinell design. Vitamin D-koncentrationer analyserades hos 184 kvinnor, vid fem tillfällen under graviditeten och efter förlossningen. Beskrivande, jämförande statistik och en linjär mixad regressionsmodell användes. Studie IV var en kvantitativ longitudinell studie med 60 kvinnor. Koncentrationerna av allopregnanolon analyserades vid graviditetsvecka 12 och 35. Beskrivande och jämförande statistik samt Spearman’s korrelation användes för att beskriva samband mellan viktökning och koncentrationer av allopregnanolon. Resultat Intervjuerna i studie I visade att kvinnor ville veta mer om olika typer av mat för att minska en eventuell risk för sina barn men kostinformation var delvis upp till dem själva att ta reda på. De VIII uttryckte känslor av osäkerhet och skuld om de råkat äta något ”förbjudet”. Rekommendationerna följdes så väl som möjligt, tillsammans med sunt förnuft för att hantera kostförändringar. Huvudteman var ”Söka information på egen hand”, ”Få professionell rådgivning när problem uppstår”, ”Känna sig osäker” och ”Ta ansvar med en nypa salt”. I studie II kunde man se vissa skillnader i kostmönster bland de gravida kvinnorna jämfört med kontrollgruppen: mindre intag av grönsaker (47 g/dag), potatis/ris/pasta (31 g/dag), kött/fisk (24 g/dag) och alkohol och tobak/snus och ett högre intag av kosttillskott. Både gravida kvinnor och kontrollgruppen hade lägre intag av folsyra via kosten med 45 % (gravida) och 22 % (kontrollgruppen) än de gällande rekommendationer som är (500 resp 400 g/dag). I studie III såg man att inta et av vitamin D var 34 % lägre än rekommendationen på 10 µg/dag. Minst en tredjedel av deltagarna hade otillräckliga plasma nivåer av vitamin D, under 50 nmol/L. Årstid var en stark faktor som påverkar det longitudinella mönstret. Graviditetsvecka, säsong, totala energiintaget, intaget av vitamin D och multivitamintillskott under de senaste 14 dagarna var faktorer som relaterade till Dvitaminnivåer. I studie IV sågs ett samband mellan allopregnanolon-koncentrationer vid graviditetsvecka 35 och viktökning från vecka 12 till 35 (p = 0,016). Det sågs också ett samband mellan ökningen av allopregnanolon (vecka 12–35) och viktökningen (se ovan) (p = 0,028). Slutsatser Kostrekommendationer beskrevs som motsägelsefulla och förvirrande och kostråden de fick uppfattades som otillräckliga. Kvinnorna tog itu med sina kostförändringar och sökte information på egen hand men hade önskat mer omfattande råd från barnmorskan. Intaget av vitaminer viktiga för graviditeten var lägre än rekommendationerna, vilket också bekräftas av låga plasmanivåer av D-vitamin hos cirka en tredjedel av de gravida kvinnorna. D-vitaminnivåerna nådde en topp i slutet av graviditeten. Graviditetsvecka och säsong på året påverkade D vitaminnivåer, så även intag via mat och kosttillskott. Orsakertill viktökning är komplexa och beror på många faktorer. Allopregnanolon är en faktor som sågs relatera till viktökningen hos de undersökta gravida kvinnorna.

Background: Vitamin D is known to be associated with inflammatory diseases, but its relationship with allergic diseases is unclear. The study objective is to determine the association of serum vitamin D levels and markers of wheeze, asthma and atopy. Methods: Data (n = 9,463) on serum vitamin D levels and atopy were obtained from 2005-2006 National Health and Nutrition Examination Survey. Serum vitamin D level was categorized into four groups: Normal (≥30ng/ml), Insufficient (21-29ng/ml), Deficient (11-20ng/ml) and Severely Deficient (≤10ng/ml). Atopy was defined as at least 1 positive allergen-specific IgE level measured for a panel of 5 common aeroallergens- cat, dog, house dust mite, cock roach and Alternaria species. Doctor-diagnosed asthma and wheeze in the previous 12 months were assessed by means of questionnaire. Multivariable logistic regression analyses were conducted to investigate the association of serum vitamin D with wheeze, asthma and atopy adjusting for age, sex, race, smoking, outdoor physical activity, body mass index and poverty income ratio. Results: Overall, 15%, 14% and 28% of subjects had wheeze, asthma and atopy, respectively. Approximately 21% had normal serum vitamin D levels, while 35%, 28% and 5% had insufficient, deficient and severely deficient levels. Compared to subjects with normal vitamin D levels, those with insufficient, deficient and severely deficient levels had increased relative odds of wheeze and atopy with highest adjusted estimates in subjects with severe vitamin D deficiency (adjusted odds ratio [OR] 2.31, 95% Confidence Interval [CI] 1.73-3.10 for wheeze; OR 1.49, 95% CI 1.17-1.89 for atopy). Conclusion: Low serum vitamin D levels were found to be associated with wheeze and atopy. Findings contribute to ongoing efforts to understanding the role of vitamin D in atopic diseases.

This thesis looks at risk factors for multiple sclerosis (MS), a chronic, degenerative autoimmune disease which is usually diagnosed between the ages of 20 and 50 years. It is estimated to affect over 100,000 people in the UK. The research setting was Orkney and Shetland, two archipelagos situated north of mainland Scotland, and both of which have very high MS prevalence as do other countries at high latitudes. I examine genetic and environmental risk factors in Orkney and Shetland using multiple methods over four studies. I also review the vitamin D and UV exposure literatures as these are risk factors pertinent to MS in Orkney and Shetland. After devoting three chapters to introducing the purpose of the thesis, MS, and Orkney and Shetland, in the fourth chapter, I aim to establish whether the birthplace of cases show any spatial, temporal, or spatiotemporal clustering. Evidence of these kinds of clustering may indicate that there are environmental risk factors present in some areas or that were present over particular periods, which raise risk of developing MS. Although I find statistically significant temporal, spatial, and spatiotemporal clustering in Orkney, and a spatial cluster in Shetland, for multiple reasons these results need to be interpreted with caution. I conclude that the clusters are very likely to be artefacts. Furthermore, there are multiple possible alternative explanations for such clusters that could not be explored by the available data. Chapter 5 examines the heritability of MS in Orkney and Shetland to estimate the proportion of phenotypic variance attributable to additive genetic effects. I also look at the birthplaces of ancestors of cases and controls to see if any locations contribute a greater amount of ancestral DNA to the gene pool of modern MS cases, which I term ‘genetic clustering’. In Orkney I obtained a heritability estimate of 0.36 (95% CI -0.26, 0.98); in Shetland this estimate was 0.20 (95% CI -1.88, 2.28). These modest estimates are consistent with the heritability literature. The genetic clustering analyses highlight two Orkney registration districts, Kirkwall and Westray, which earlier studies identified as areas of MS clustering. I also identify three Shetland registration districts, however these locations had not shown any evidence of clustering in earlier studies. Again, I advise caution in interpreting results, particularly as all the error bars across registration districts overlap. Chapter 6 presents a scoping review to map the literature and identify evidence of an association between vitamin D and UV exposure with MS. In methodically searching the literature, I identify a large and heterogeneous evidence base comprising multiple observational, intervention, and genetic studies. Overall, many studies support an association between vitamin D deficiency and MS. There is also evidence for an association between UV exposure and MS, although UV exposure is considerably less explored than vitamin D. I finally identify gaps in the literature and make suggestions for future research. In Chapter 7 I aim to compare vitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. I firstly compare mean vitamin D and prevalence of deficiency in cross-sectional data from studies in Orkney and mainland Scotland. I secondly use multivariable regression to identify factors associated with vitamin D levels in Orkney. I find that mean (standard deviation) vitamin D is significantly higher in Orkney compared to mainland Scotland (35.3 (18.0) and 31.7 (21.2), respectively), and prevalence of severe deficiency is lower in Orkney (6.6% to 16.2% p = 1.1 x 10-15). Factors associated with higher vitamin D in Orkney include older age, farming occupations and foreign holidays. I conclude that although mean vitamin D levels are higher in Orkney compared to mainland Scotland, there is substantial variation within the Orkney population which may influence MS risk. Chapter 8 examines the correlates and determinants of UVB exposure in Shetland. I firstly construct correlation matrices to visualise how 1) personal characteristics such as sex, occupation, and skin type, 2) physical activity, and 3) body weight and fat, correlate with UVB exposure. I then use multivariable regression to identify factors associated with UVB exposure in Shetland. I run two multivariable models. The first includes the full sample size where activity data were measured by questionnaires. The second includes both questionnaire physical activity data and step-count data from pedometers, however as only a subset of participants had been supplied with pedometers, this analysis comprises a smaller sample size. I find that the amount of skin exposed was most strongly correlated with UVB exposure. Step count and activity minutes were also moderately positively correlated, and indoor occupations moderately negatively correlated, with UVB exposure. The regression analysis using the full sample with questionnaire activity data found that factors associated with greater UVB exposure were age and ambient UVB, while working indoors was significantly associated with lower UVB exposure. The model including the pedometer data found that found that age, total steps, and the amount of ambient UVB were significantly associated with greater UVB exposure. I conclude that atmospheric conditions, working outdoors and older age are important factors in UVB exposure in Shetland. It remains to be seen how UVB exposure translates to vitamin D levels in Shetland. I found evidence for environmental and genetic risk factors for MS in Orkney and Shetland. The two environmental risk factors, vitamin D deficiency and reduced UV exposure, are more likely to affect the younger population who are still within their lifetime risk of developing MS.