GLYCOSYLATED FIBRONECTIN AND INHIBIN ARE LOWER AND ANTI-MÜLLERIAN HORMONE IS HIGHER IN UMBILICAL CORD BLOOD WHEN MOTHERS HAVE PREECLAMPSIA.

Objective: Preeclampsia is a common disorder of pregnancy, causing significant morbidity and mortality for mothers and infants. Several molecules, including glycosylated fibronectin (GlyFn), the inhibin-related proteins, anti-müllerian hormone (AMH), and the insulin-like growth factor axis, are altered in maternal plasma in the setting of preeclampsia; however, these molecules have not been previously measured in cord blood of infants born to mothers with preeclampsia, which may represent changes in fetal physiology. We evaluated potential biomarkers of preeclampsia in umbilical cord blood to fill the gap in knowledge. Methods: This is a case-control study of 196 neonates born at a tertiary teaching hospital in Boston from 2010-2017. Forty-nine neonates born to mothers with preeclampsia were matched 1:3 by gestational age, sex, and birth weight z-score with 147 controls. Eleven analytes were measured in cord blood by enzyme-linked immunosorbent assay. Binary logistic regression analyses were performed to evaluate associations between preeclampsia and analytes. Results: Mean cord blood levels of GlyFn and total inhibin were significantly lower in neonates born to mothers with preeclampsia compared to controls, and AMH levels were significantly higher in males born to mothers with preeclampsia than male controls. Associations remained significant after controlling for maternal and neonatal characteristics. Conclusion: Cord blood levels of GlyFn and inhibin are decreased and AMH (male) levels are increased in infants of preeclamptic mothers, which is opposite the pattern these biomarkers show in serum of mothers with preeclampsia. These molecules may be important in the pathophysiology and long-term effects of preeclampsia on the developing fetus. Abbreviations: AMH = anti-müllerian hormone; ELISA = enzyme-linked immunosorbent assay; GlyFn = glycosylated fibronectin; IGF = insulin-like growth factor; IGFBP5 = insulin-like growth factor binding protein 5; LOD = limit of detection; PAPP-A = pregnancy-associated plasma protein A; PAPP-A2 = pregnancy-associated plasma protein A2.

Placental proteases PAPP-A and PAPP-A2, the binding proteins they cleave (IGFBP-4 and -5), and IGF-I and IGF-II: Levels in umbilical cord blood and associations with birth weight and length.

BACKGROUND: A newborn's birth weight for gestational age provides important insights into his or her fetal growth and well-being. While the underlying mechanisms regulating fetal growth remain to be fully elucidated, the IGF axis plays an important role. Some components of this axis have been well-characterized in umbilical cord blood, but others have not yet been studied. We measured the proteases PAPP-A and PAPP-A2, the binding proteins they cleave (IGFBP-4 and -5), and the established molecules IGF-I and -II in umbilical cord blood to better characterize the IGF axis in relation to birth weight and length. METHODS: We performed a case-control study of 180 neonates born at a tertiary teaching hospital in Boston. To maximize power, infants were recruited in a 1:3:1 ratio with 37 SGA, 111 AGA, and 37 LGA infants matched by gestational age, sex, and delivery mode. IGF-I, IGF-II, IGFBP-4, IGFBP-5, PAPP-A, and PAPP-A2 were measured in umbilical cord blood by ELISA. Associations between birth weight and birth length Z-scores and the Z-scores of the above molecules were analyzed using linear regression models and analysis of covariance. RESULTS: Birth weight and length Z-scores were positively associated with Z-scores of IGF-I, IGF-II, total IGFBP-4, and IGFBP-5, with IGF-I having the strongest association. Birth weight and length Z-scores were negatively associated with Z-scores of intact IGFBP-4, PAPP-A, and PAPP-A2 levels. CONCLUSIONS: We confirm previous findings of significant associations between the IGFs in cord blood and newborn size and for the first time show positive associations between cord blood total IGFBP-4 and -5 and birth weight and a negative association between intact IGFBP-4 and birth weight. We also show for the first time a reciprocal relationship between cord blood levels of PAPP-A and PAPP-A2 and newborn size. The implications of these findings need to be further examined in large longitudinal studies and likely have diagnostic and therapeutic potential.

Longer-term liraglutide administration at the highest dose approved for obesity increases reward-related orbitofrontal cortex activation in response to food cues: Implications for plateauing weight loss in response to anti-obesity therapies.

AIMS: GLP-1 analogs have recently risen to the forefront as effective medications for lowering weight through actions in the central nervous system (CNS). However, their actions in the CNS have not yet been studied in the human brain after longer-term administration at the highest dose approved for obesity (liraglutide 3.0 mg). MATERIALS AND METHODS: A total of 20 participants with obesity were treated with placebo and liraglutide (3.0 mg) in the context of a randomized, placebo-controlled, double-blind, cross-over trial after 5 weeks of dose escalation. Neurocognitive and neuroimaging (fMRI) responses to food cues were examined at the clinical research center of Beth Israel Deaconess Medical Center. RESULTS: While using liraglutide, patients lost more weight (placebo-subtracted -2.7%; P < .001), had decreased fasting glucose (P < .001) and showed improved cholesterol levels. In an uncontrolled analysis, brain activation in response to food images was not altered by liraglutide vs placebo. When controlled for BMI/weight, liraglutide increased activation of the right orbitofrontal cortex (OFC) in response to food cues (P < .016, corrected for multiple comparisons). CONCLUSIONS: In contrast to prior studies, we demonstrate for the first time that liraglutide treatment, administered over a longer period at the highest doses approved for obesity, does not alter brain activation in response to food cues. A counter-regulatory increase in reward-related OFC activation in response to food cues can be observed when neuroimaging data are controlled for BMI changes, indicating changes in CNS that could lead to later plateaus of weight loss. These data point to a promising focus for additional interventions which, by contributing to the CNS reward system, could provide tangible benefits in reversing the plateauing phenomenon and promoting further weight loss.