Hima Tam

Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome

OBJECTIVE Obesity and metabolic syndrome are associated with systemic inflammation and increased perinatal morbidity. Metformin improves metabolic and inflammatory biomarkers in nonpregnant adults. Using in vivo and in vitro models, we examined the effect of metformin on maternal and fetal inflammation. STUDY DESIGN Female Wistar rats (6-7 weeks old) were fed a normal diet (NORM) or a high-fat/high-sugar diet (HCAL) for 5-6 weeks to induce obesity/metabolic syndrome. After mating with NORM-fed male rats, one-half of the HCAL-fed female rats received metformin (300 mg/kg, by mouth daily). All dams continued their respective diets until gestational day 19, at which time maternal and fetal outcomes were assessed. Maternal and fetal plasma and placentas were analyzed for metabolic and inflammatory markers. Cultured human placental JAR cells were pretreated with vehicle or metformin (10 μmol/L-2.5 mmol/L) before tumor necrosis factor α (TNF-α; 50 ng/mL), and supernatants were assayed for interleukin-6 (IL-6). RESULTS HCAL rats gained more prepregnancy weight than NORM rats (P = .03), had higher levels of plasma insulin and leptin, and exhibited dyslipidemia (P < .05). Fetuses that were exposed to the HCAL diet had elevated plasma IL-6, TNF-α, and chemokine (C-C motif) ligand 2 levels (P < .05) and enhanced placental TNF-α levels (P < .05). Maternal metformin did not impact maternal markers but significantly decreased diet-induced TNF-α and chemokine (C-C motif) ligand 2 in the fetal plasma. Finally, metformin dose-dependently reduced TNF-α-induced IL-6 and IκBα levels in cultured placental JAR cells. CONCLUSION Diet induced-obesity/metabolic syndrome during pregnancy significantly enhanced fetal and placental cytokine production; maternal metformin reduced fetal cytokine levels. Similarly, metformin treatment of a placental cell line suppressed TNF-α-induced IL-6 levels by NFκB inhibitor.

Magnesium sulfate ameliorates maternal and fetal inflammation in a rat model of maternal infection

OBJECTIVE Magnesium sulfate is proposed to have neuroprotective effects in the offspring. We examined the effects of maternal magnesium sulfate administration on maternal and fetal inflammatory responses in a rat model of maternal infection. STUDY DESIGN Pregnant rats were injected with saline, Gram-negative bacterial endotoxin lipopolysaccharide or lipopolysaccharide with magnesium sulfate (pre- and/or after lipopolysaccharide) to mimic infection. Maternal blood, amniotic fluid, fetal blood, and fetal brains were collected 4 hours after lipopolysaccharide and assayed for tumor necrosis factor, interleukin-6, monocyte chemoattractant protein-1, and growth-related oncogene-KC. In addition, the effect of magnesium sulfate on cytokine production by an astrocytoma cell line was assessed. RESULTS Lipopolysaccharide administration induced tumor necrosis factor, interleukin-6, monocyte chemoattractant protein-1, and growth-related oncogene-KC expression in maternal and fetal compartments. Maternal magnesium sulfate treatment significantly attenuated lipopolysaccharide-induced multiple proinflammatory mediator levels in maternal and fetal compartments. CONCLUSION Antenatal magnesium sulfate administration significantly ameliorated maternal, fetal, and gestational tissue-associated inflammatory responses in an experimental model of maternal infection.

Triphasic umbilical artery waveform: association with severe fetal growth restriction, fetal demise, and extreme velamentous cord insertion

Abstract Extreme Doppler abnormalities of the umbilical artery such as absent or reversed end diastolic velocity are associated with adverse perinatal outcomes. We present a case of a triphasic umbilical artery waveform identified at 24 weeks. The fetus was severely growth restricted with an estimated fetal weight of 314 g. A week later, fetal demise occurred. Placental pathology revealed a placental weight of 83 g, an extensive maternal floor infarction, and an extreme velamentous cord insertion 7 cm from the edge of the placental disc, with vessels entering at opposite poles of the placental disc and a single anastomotic bridging vessel on the chorionic plate connecting these two vascular poles. A triphasic umbilical artery waveform may be associated with a premorbid state and severe placental vascular abnormality. We hypothesize that the third and positive component in late diastole is present due to forward flow across the communicating bridging vessel into the contralateral entering vessel.