Association of antenatal steroids with surfactant administration in moderate preterm infants born to women with diabetes mellitus and/or hypertension.

BACKGROUND: Randomized trials of antenatal steroid administration (ANS) for extreme or moderate preterm pregnancies excluded women with diabetes mellitus (DM) and included few with preeclampsia. METHODS: Cohort study (n = 1,813) including moderate preterm births [290/7-336/7wks' gestational age GA)] before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with hypertensive disorders (HTN) and/or DM. We compared surfactant administration in Group-1 (neither HTN nor DM), Group-2a (HTN not DM), Group-2b (DM not HTN) and Group-2c (DM and HTN). RESULTS: Surfactant administration was less frequent after ANS in Group-1 [adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.31, 0.93, P = 0.03], Group-2a (aOR 0.36, CI 0.22, 0.58, P < 0.001) and Group-2c (aOR 0.29, CI 0.12, 0.71, P = 0.007) but not Group-2b (P = 0.64). CONCLUSIONS: ANS administration was independently associated with less surfactant administration in moderately preterm neonates whose mothers had neither HTN nor DM, and those with HTN, but not those with DM without HTN.

Association of antenatal steroids with neonatal mortality and morbidity in preterm infants born to mothers with diabetes mellitus and hypertension.

BACKGROUND: Randomized trials of antenatal steroids (ANS) included women at 24-33 weeks gestational age (GA); however, few women had preeclampsia and women with diabetes mellitus (DM) were excluded. METHODS: Cohort study including preterm births at 230/7-286/7 weeks GA before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with DM and hypertensive disorders (HTN). We compared Group-A (neither DM nor HTN) and Group-B (DM and/or HTN). RESULTS: Among 747 neonates the adjusted odds ratio (aOR) for surfactant administration, in-hospital mortality, severe intraventricular hemorrhage (IVH) and death or severe IVH were lower in ANS-exposed neonates than unexposed neonates. In Group-B, ANS administration was independently associated with less severe IVH and less death or severe IVH, but not less surfactant use or mortality. CONCLUSIONS: Increased ANS administration in women with DM and/or HTN was independently associated with less severe IVH and less death or severe IVH but without decrease in surfactant administration.

Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases fetal amino acid oxidation.

Protein supplementation during human pregnancy does not improve fetal growth and may increase small-for-gestational-age birth rates and mortality. To define possible mechanisms, sheep with twin pregnancies were infused with amino acids (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA group, fetal arterial pH (7.365 +/- 0.007 day 0 vs. 7.336 +/- 0.012 day 4, P < 0.005), hemoglobin-oxygen saturation (46.2 +/- 2.6 vs. 37.8 +/- 3.6%, P < 0.005), and total oxygen content (3.17 +/- 0.17 vs. 2.49 +/- 0.20 mmol/l, P < 0.0001) were decreased on day 4 compared with day 0. Fetal leucine disposal did not change (9.22 +/- 0.73 vs. 8.09 +/- 0.63 micromol x min(-1) x kg(-1), AA vs. C), but the rate of leucine oxidation increased 43% in the AA group (2.63 +/- 0.16 vs. 1.84 +/- 0.24 micromol x min(-1) x kg(-1), P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 +/- 23 vs. 250 +/- 29 micromol x min(-1) x kg(-1), P = 0.06). Rates of leucine incorporation into fetal protein (5.19 +/- 0.97 vs. 5.47 +/- 0.89 micromol x min(-1) x kg(-1), AA vs. C), release from protein breakdown (4.20 +/- 0.95 vs. 4.62 +/- 0.74 micromol x min(-1) x kg(-1)), and protein accretion (1.00 +/- 0.30 vs. 0.85 +/- 0.25 micromol x min(-1) x kg(-1)) did not change. Consistent with these data, there was no change in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein synthesis regulators 4E-BP1, eEF2, eIF2alpha, and p70(S6K). Decreased concentrations of certain essential amino acids, increased amino acid oxidation, fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal toxicity during maternal amino acid supplementation.

Differential effects of chronic pulsatile versus chronic constant maternal hyperglycemia on fetal pancreatic ß-cells.

Constant maternal hyperglycemia limits, while pulsatile maternal hyperglycemia may enhance, fetal glucose-stimulated insulin secretion (GSIS) in sheep. However, the impact of such different patterns of hyperglycemia on the development of the fetal ß-cell is unknown. We measured the impact of one week of chronic constant hyperglycemia (CHG, n = 6) versus pulsatile hyperglycemia (PHG, n = 5) versus controls (n = 7) on the percentage of the fetal pancreas staining for insulin (ß-cell area), mitotic and apoptotic indices and size of fetal ß-cells, and fetal insulin secretion in sheep. Baseline insulin concentrations were higher in CHG fetuses (P < 0.05) compared to controls and PHG. GSIS was lower in the CHG group (P < 0.005) compared to controls and PHG. PHG ß-cell area was increased 50% (P < 0.05) compared to controls and CHG. CHG ß-cell apoptosis was increased over 400% (P < 0.05) compared to controls and PHG. These results indicate that late gestation constant maternal hyperglycemia leads to significant ß-cell toxicity (increased apoptosis and decreased GSIS). Furthermore, pulsatile maternal hyperglycemia increases pancreatic ß-cell area but did not increase GSIS, indicating decreased ß-cell responsiveness. These findings demonstrate differential effects that the pattern of maternal hyperglycemia has on fetal pancreatic ß-cell development, which might contribute to later life limitation in insulin secretion.