Incidence of Adverse Pregnancy Outcomes Based on the Degree of Short Interpregnancy Interval in Urban Milwaukee Population.

INTRODUCTION: Short interpregnancy interval is defined as conception occurring within 18 months of a previous live birth. Studies show increased risks of preterm birth, low birth weight, and small for gestational age with short interpregnancy intervals; however, it is unclear if these risks are higher for all short interpregnancy intervals or only for those less than 6 months. The objective of this study was to evaluate prevalence of adverse pregnancy outcomes among people with short interpregnancy intervals, stratified by degree: less than 6 months, 6 to 11 months, and 12 to 17 months. METHODS: We conducted a retrospective cohort study of people with 2 singleton pregnancies between 2015 and 2018 at a single academic center. The following outcomes were compared between patients with interpregnancy intervals of less than 6 months, 6 to 11 months, 12 to 17 months, and 18 months or more; hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), preterm birth at less than 37 weeks, low birth weight ( < 2500 g), congenital anomalies, and gestational diabetes. Bivariate and multivariate analyses were done to examine the independent role of the degree of short interpregnancy interval and each outcome. RESULTS: A total of 1,462 patients were included in the analysis, with 80 pregnancies occurring at interpregnancy intervals less than 6 months, 181 at 6 to 11 months, 223 at 12 to 17 months, and 978 at 18 months or more. In unadjusted analysis, patients with interpregnancy intervals less than 6 months had the highest rate of preterm birth at 15.0%. In addition, patients with interpregnancy intervals less than 6 months and 12 to 17 months had higher rates of congenital anomalies versus those with interpregnancy intervals of 18 months or more. In multivariate analysis, controlling for sociodemographic and clinical confounding factors, interpregnancy intervals less than 6 months were associated with 2.3 higher odds of preterm birth (95% CI, 1.13-4.68), and those 12 to 17 months were associated with 2.52 higher odds of congenital anomalies (95% CI, 1.22-5.20). The odds of gestational diabetes were lower with interpregnancy intervals of 6 to 11 months compared to those 18 months or more (aOR 0.26; 95% CI, 0.08-0.85). CONCLUSIONS: In this single-site cohort, people with interpregnancy intervals less than 6 months had higher odds of preterm birth, while those with interpregnancy intervals 12 to 17 months had higher odds of congenital anomalies, compared with the control group with interpregnancy intervals greater than or equal to 18 months. Future research should focus on identifying modifiable risk factors for short interpregnancy intervals and interventions to reduce them.

Quantitative Comparison of Dense-Core Amyloid Plaque Accumulation in Amyloid-ß Protein Precursor Transgenic Mice.

There exist several dozen lines of transgenic mice that express human amyloid-ß protein precursor (AßPP) with Alzheimer's disease (AD)-linked mutations. AßPP transgenic mouse lines differ in the types and amounts of Aß that they generate and in their spatiotemporal patterns of expression of Aß assemblies, providing a toolkit to study Aß amyloidosis and the influence of Aß aggregation on brain function. More complete quantitative descriptions of the types of Aß assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how Aß toxicity in mice relates to the pathogenesis of AD. Here, we provide a direct quantitative comparison of amyloid plaque burdens and plaque sizes in four lines of AßPP transgenic mice. We measured the fraction of cortex and hippocampus occupied by dense-core plaques, visualized by staining with Thioflavin S, in mice from young adulthood through advanced age. We found that the plaque burdens among the transgenic lines varied by an order of magnitude: at 15 months of age, the oldest age studied, the median cortical plaque burden in 5XFAD mice was already ∼4.5 times that of 21-month-old Tg2576 mice and ∼15 times that of 21-24-month-old rTg9191 mice. Plaque-size distributions changed across the lifespan in a line- and region-dependent manner. We also compared the dense-core plaque burdens in the mice to those measured in a set of pathologically-confirmed AD cases from the Nun Study. Cortical plaque burdens in Tg2576, APPSwePS1ΔE9, and 5XFAD mice eventually far exceeded those measured in the human cohort.