scholarly journals Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation—A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial

2020 ◽  
Vol 8 ◽  
Author(s):  
Fieke Terstappen ◽  
Anne E. Richter ◽  
A. Titia Lely ◽  
Freek E. Hoebeek ◽  
Ayten Elvan-Taspinar ◽  
...  

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth.Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests.Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69–72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two.Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis.

2020 ◽  
Vol 56 (1) ◽  
pp. 51-60 ◽  
Author(s):  
H. Wolf ◽  
S. J. Gordijn ◽  
W. Onland ◽  
R. J. S. Vliegenthart ◽  
J. W. Ganzevoort

Author(s):  
Nathan R. Blue ◽  
Matthew Hoffman ◽  
Amanda A. Allshouse ◽  
William A. Grobman ◽  
Hyagriv N. Simhan ◽  
...  

Objective Our objective was to test the association of fetal adrenal size with perinatal morbidity among fetuses with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile). Study Design This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) adrenal study, which measured fetal adrenal gland size at 22 to 30 weeks' gestation. We analyzed the transverse adrenal area (TAA) and fetal zone area (absolute measurements and corrected for fetal size) and the ratio of the fetal zone area to the total transverse area using a composite perinatal outcome of stillbirth, neonatal intensive care unit admission, respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, sepsis, mechanical ventilation, seizure, or death. Among fetuses with FGR, adrenal measurements were compared between those that did and did not experience the composite perinatal outcome. Results There were 1,709 eligible neonates. Seven percent (n = 120) were diagnosed with FGR at the time of adrenal measurement, and 14.7% (n = 251) experienced perinatal morbidity. EFW-corrected and absolute adrenal measurements were similar among fetuses with and without FGR as well as among those who did and did not experience morbidity. The area under the curve for corrected TAA was 0.52 (95% confidence interval 0.38–0.67). Conclusion In our cohort, adrenal size was not associated with risk of morbidity among fetuses with FGR.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mark W. Cunningham ◽  
Lorena M. Amaral ◽  
Nathan E. Campbell ◽  
Denise C. Cornelius ◽  
Tarek Ibrahim ◽  
...  

AbstractTwo important clinical features of preeclampsia (PE) are hypertension and fetal growth restriction. The reduced uterine perfusion pressure (RUPP) preclinical rat model of PE exhibits both of these features. Moreover, RUPP and PE women have elevated vasoconstrictor peptide endothelin-1 (ET-1) and inflammation. Interleukin-2 (IL-2) is a cytokine that regulates NK cell activity and is elevated in miscarriage, PE, and RUPP rats. The objective of this study was to examine a role for IL-2 in NK cell activation, fetal growth restriction, and hypertension during pregnancy by either infusion of IL-2 or blockade of IL-2 (basiliximab) in normal pregnant (NP) and RUPP rats. On gestational day 14, NP and RUPP rats received low (LD), middle (MD), or high dose (HD) IL-2 (0.05, 0.10, or 0.20 ng/ml) IP or basiliximab (0.07 mg per rat) by IV infusion. On day 19, blood pressure (MAP), pup weights, and blood were collected. Basiliximab had no effect on blood pressure, however, significantly lowered NK cells and may have worsened overall fetal survival in RUPP rats. However, IL-2 LD (102 ± 4 mmHg) and IL-2 HD (105 ± 6 mmHg) significantly lowered blood pressure, ET-1, and activated NK cells compared to control RUPPs (124 ± 3 mmHg, p < 0.05). Importantly, IL-2 in RUPP rats significantly reduced fetal weight and survival. These data indicate that although maternal benefits may have occurred with low dose IL-2 infusion, negative effects were seen in the fetus. Moreover, inhibition of IL-2 signaling did not have favorable outcome for the mother or fetus.


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