Macronutrients in pregnancy and birthweight 13 Keywords: Macronutrients: Protein: Carbohydrate: Fat: Birthweight: Birth Centile: Pregnancy: Diet

15 There is lack of evidence on the differential impact of maternal macronutrient consumption: 16 carbohydrates (CHO), fats and protein on birthweight. We investigated the association between 17 maternal dietary macronutrient intakes and their sub-components such as saccharides and fatty acids 18 and birthweight. This analyses included 1,196 women with singleton pregnancies who were part of 19 the CARE (CAffeine and REproductive health) study in Leeds, UK between 2003 and 2006. Women 20 were interviewed in each trimester. Dietary information was collected twice using a 24 hour dietary 21 recall around 8-12 weeks and 13-27 weeks of gestation. Multiple linear regression models adjusted 22 for alcohol and smoking in trimester 1, showed that each additional 10g/day CHO consumption was 23 associated with an increase of 4g (95% CI 1g to 7g; P=0.003) in birthweight. Conversely, an 24 additional 10g/day fat intake was associated with a lower birthweight of 8g (95% CI 0g to 16g; 25 P=0.04) when we accounted for energy contributing macronutrients in each model, and maternal 26 height, weight, parity, ethnicity, gestational age at delivery and sex of the baby. There was no 27 evidence of an association between protein intake and birthweight. Maternal diet in trimester 2 28 suggested that higher intakes of glucose (10g/day) and lactose (1g/day) were both associated with 29 higher birthweight of 52g (95% CI 4g to 100g; P=0.03) and 5g (95% CI 2g to 7g; P<0.001) 30 respectively. These results show that dietary macronutrient composition during pregnancy is 31 associated with birthweight outcomes. An appropriately balanced intake of dietary CHO and fat 32 during pregnancy could support optimum birthweight. 33 Introduction 34 There is increasing evidence elucidating the role of diet during pregnancy on the growing fetus 35 and subsequently, in the offspring metabolic health in adulthood. Maternal diet in pregnancy is 36 suggested to contribute in the alteration of fetal outcomes, including birthweight, preterm 37 delivery, low birthweight infants(<2500 g) and small for gestational age (SGA) births. Meta38 analyses have examined the role of micronutrients in the maternal diet, including vitamin C, 39 iron and folate in the development of adverse birth outcomes. Amongst dietary 40 macronutrients, evidence has been restricted to exploring the use of protein-energy supplementation 41 in pregnancy for improving offspring birthweight amongst low-income countries . However, 42 amongst high-income countries the prevalence of maternal and infant protein-energy under nutrition 43 is low due to sufficient macronutrient consumption during pregnancy. 44