Objective. To determine relative influences of intrauterine growth restriction (IUGR) and preterm birth on risks of cardiovascular, renal, or metabolic dysfunction in adolescent children. Study Design. Retrospective cohort study. 71 periadolescent children were classified into four groups: premature small for gestational age (SGA), premature appropriate for gestational age (AGA), term SGA, and term AGA. Outcome Measures. Systolic blood pressure (SBP), augmentation index (Al), glomerular filtration rate (GFR) following protein load; plasma glucose and serum insulin levels. Results. SGA had higher SBP (average 4.6 mmHg) and lower GFR following protein load (average 28.5 mL/min/1.73 m2) than AGA. There was no effect of prematurity on SBP (P = .4) or GFR (P = .9). Both prematurity and SGA were associated with higher AI (average 9.7%) and higher serum insulin levels 2 hr after glucose load (average 15.5 mIU/L) than all other groups. Conclusion. IUGR is a more significant risk factor than preterm birth for later systolic hypertension and renal dysfunction. Among children born preterm, those who are also SGA are at increased risk of arterial stiffness and metabolic dysfunction.

It is accepted that human pregnancy is associated with a shift away from Th1 type and a bias toward Th2-type immune responses. The molecular mechanisms that regulate this shift are as yet unknown. We assessed the expression and activity of NF-κB, a transcription factor that plays a central role in regulating immune responses. We isolated T cells from PBMCs from nonpregnant and pregnant females and demonstrated that the NF-κB/IκB signaling pathway is down-regulated in T cells in pregnancy. Using Western blotting, high levels of NF-κB (p65) were detected in all nuclear fractions of T cells from nonpregnant females. In contrast, low levels of p65 were detected in nuclear fractions from T cells from pregnant females. Levels of IκBα and -β were also higher in cytoplasmic fractions from T cells from nonpregnant than from pregnant females. The reduction in p65 levels in pregnancy was reflected in the activity of NF-κB in EMSA; T cells from pregnant females contain less active NF-κB than from nonpregnant females. Stimulation of T cells from nonpregnant females with PMA/ionomycin resulted in IκBα degradation, p65 translocation, and subsequent production of the Th1 cytokines IFN-γ and IL-2. In contrast, PMA stimulation had no effect on NF-κB activity in T cells from pregnant females, and this was reflected in reduced Th1 cytokine production. Using the inhibitor of NF-κB activity, SN50, we were able to show that NF-κB activity was essential for the production of Th1 cytokines, suggesting that specific down-regulation of NF-κB in T cells throughout gestation is paramount to pregnancy success through specific regulation of cytokine production.

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