Thyroid dysfunction is one of the most common endocrine disorders in women of childbearing age and the obstetric consequences of abnormal thyroid hormone levels during pregnancy have been established. Less understood is the implication of the presence of maternal thyroid autoantibodies on infant outcomes among women who are euthyroid during pregnancy. The objective of this study was two-fold: 1) to examine the influence of antenatal thyroperioxidase (TPO) status on fetal/infant brain and body growth measurements at delivery and 2) to explore the relationship of antenatal TPO status and maternal postpartum thyroid dysfunction (PPTD) on early infant growth and neurocognitive development. Six-hundred thirty-one (631) euthyroid pregnant women were recruited from prenatal clinics in Tampa Bay, Florida and the surrounding area between November 2007 and December 2010. TPO status was determined during pregnancy and fetal/infant brain and body growth variables were assessed at delivery. A subsample of forty-one (41) mother-infant dyads participated in a 6-month longitudinal supplemental study. Infant growth assessments were conducted at 3, 4, 5 and 6 months postpartum. Regression analysis revealed maternal TPO positivity was significantly associated with smaller head circumference, reduced brain weight and lower brain-body-ratio; however maternal race/ethnicity was identified as an effect modifier in the relationship. No significant differences were noted in birth weight, birth length, abdominal circumference or chest circumference measurements among infants born to TPO positive mothers of any racial/ethnic group as compared to their negative counterparts. Mixed model analysis of the smaller subset (n=41) revealed infants of TPO+ mothers were smaller at birth but experienced accelerated growth between birth to 3 months when compared to infants born to TPO- mothers. This acceleration led to their catch-up in growth to their TPO negative counterparts by 3 months of age. No significant differences were noted in neurocognitive outcomes between infants born to TPO+ mothers compared to those born to TPO- mothers. The findings in this dissertation indicate that maternal/race ethnicity modifies the relationship between TPO positivity and reduced fetal/infant brain growth. Additionally, the analyses suggest that maternal autoantibody status could lead to variations in early infant growth and development. The end-result of these variations is unclear. Further research is needed to determine the potential impact of reduced head circumference and accelerated growth as it relates to long-term neurocognitive consequences. Currently, TPO antibody status is not assessed as part of the standard prenatal care laboratory work-up, but findings from this study suggest that fetal brain growth may be impaired by TPO positivity among certain populations, therefore autoantibody screening among high-risk sub-groups may be useful for clinicians to determine whether prenatal thyroid treatment is warranted.

Background. Right cerebellar-left frontal (RC-LF) white matter integrity (WMI) has been associated with working memory. Right Superior Longitudinal Fasciculus II (SLF II) WMI has been associated with visual attention. These relationships have held true for neurotypical controls and brain tumor survivors. The current study examined the relationships between RC-LF WMI and processing speed, attention, and working memory. SLF II WMI and visual attention were included as a control tract and task to demonstrate a correlational double dissociation. This study also examined the relationship between the volume of brain regions within the RC-LF network and RC-LF WMI. Methods. Adult survivors of childhood brain tumors (n= 29, age: M=22 years (SD= 5), 45% female) were treated with neurosurgery, and combinations of radiation therapy and chemotherapy. Age- and gender-matched controls (n=29) were also included. Tests of auditory attention span, working memory, visual attention, and processing speed served as cognitive measures. Participants completed a 3T MRI diffusion imaging scan. WMI (FA, RD) and volume served as neuroimaging measures. In the survivor group, partial correlations between WMI and cognitive scores included controlling for type of treatment. Results. A correlational double dissociation was found. RC-LF WMI was associated with auditory attention span (FA: r=.42, p=.03; RD: r=-.50, p=.01), and was not associated with visual attention (FA: r=-.11, p=.59; RD: r=-.11, p=.57). SLF II FA WMI was associated with visual attention (FA: r=.44, p=.02; RD: r=-.17, p=.40), and was not associated with auditory attention span (FA: r=.24, p=.22; RD: r=-.10, p=.62). The relationship between RC-LF WMI and auditory attention span robustly dissociated from working memory and visual attention. In the radiation group, thalamic-frontal segment of RC-LF WMI associated with the volumetric measures of each structure of the RC-LF pathway, whereas in the no radiation group cerebellar-rubral segment of RC-LF WMI associated with the volumetric measures. Conclusions. The current study advances the understanding of structural brain changes following cerebellar tumor resection and treatment because the results show that RC-LF WMI is associated with auditory attention span rather that working memory, provide evidence for a correlational double dissociation, and suggest distinct relationships between WMI and volume based on treatment.