There is limited evidence that plasma homocysteine (Hcy) is increased in women with adverse pregnancy outcomes, such as low birth weight (LBW). We examined the relationship between maternal Hcy at the first prenatal visit and birth weight. In a prospective observational study, women were recruited during their first prenatal visit after sonographic confirmation of gestational age. Along with the standard tests, blood was also taken for the measurement of maternal serum and red blood cell (RBC) folate, vitamin B12, and Hcy. In addition to collecting standard clinical and sociodemographic details, a detailed questionnaire on vitamin supplementation was completed under supervision. Birth outcomes were collected immediately after delivery. Of 498 women recruited, 213 (42.8%) were nulliparous, 97 (19.4%) were obese, 64 (12.9%) selfreported as current smokers, and 489 (98.2%) were taking folic acid (FA) supplements at presentation. The mean (SD) birth weight was 3426.3 g (600.7), 14.0% of infants were small for gestational age, and 7.4% were large for gestational age. Mean (SD) plasma Hcy was 7.1 (2.1) µmol/l. On multiple linear regression, higher plasma Hcy was associated with selfreported smoking ( = .009), relative income poverty ( = .037) and Irish nativity ( = .009). There was no relationship between maternal plasma Hcy and birth weight centile, either overall or when analyzed separately for either smokers ( = 0.0001,  = .98) and nonsmokers ( = -0.007,  = .097). Plasma Hcy was correlated negatively with serum folate, RBC folate, and serum vitamin B12. There was no association between maternal Hcy and the duration of FA supplementation in weeks ( = -0.08,  = .083) or between maternal Hcy and gestational age at phlebotomy ( = -0.54,  = .35). In this well-characterized cohort of women in early pregnancy, there was no correlation between maternal plasma Hcy and birth weight. However, higher Hcy was associated with maternal smoking and social deprivation which may explain the association reported previously between an increased Hcy and LBW.RationaleThis study was conducted to investigate the relationship between maternal homocysteine in early pregnancy and infant birth weight. Increased plasma homocysteine in early pregnancy was not associated with a lower birth weight. However, there was a positive correlation between increasing plasma homocysteine and maternal smoking and social disadvantage which are risk factors for lower birth weight. This study highlights the importance of correcting for confounding variables, such as smoking and social disadvantage, when evaluating the relationship maternal nutritional biomarkers and intrauterine fetal development.This study was conducted to investigate the relationship between maternal homocysteine in early pregnancy and infant birth weight. Increased plasma homocysteine in early pregnancy was not associated with a lower birth weight. However, there was a positive correlation between increasing plasma homocysteine and maternal smoking and social disadvantage which are risk factors for lower birth weight. This study highlights the importance of correcting for confounding variables, such as smoking and social disadvantage, when evaluating the relationship maternal nutritional biomarkers and intrauterine fetal development.