The Effect of Maternal Antihypertensive Drugs on the Cerebral, Renal and Splanchnic Tissue Oxygen Extraction of Preterm Neonates

Abstract

Background: Drugs with antihypertensive action are frequently used in obstetrics for the treatment of preeclampsia (labetalol) and tocolysis (nifedipine) or for neuroprotection (MgSO₄), and may affect the hemodynamics of preterm born neonates. Objective: The aim of this study was to assess whether maternal antihypertensive drugs affect multisite oxygenation levels of the neonate. Methods: Eighty preterm neonates of ≤32 weeks of gestational age were monitored using near-infrared spectroscopy. Mean cerebral, renal and splanchnic fractional tissue oxygen extractions (cFTOE, rFTOE and sFTOE) were calculated for the first 5 postnatal days. We determined the effect of various maternal antihypertensive drugs on cFTOE and rFTOE using multilevel analysis, and on sFTOE using Kruskal-Wallis and Mann-Whitney U tests. Results: Eleven infants were exposed to labetalol ± MgSO₄, 7 to nifedipine ± MgSO₄, 20 to MgSO₄ only, and 42 to no maternal antihypertensive drugs. The infants exposed to labetalol ± MgSO₄ had a lower cFTOE on days 1 (0.14, p = 0.031), 2 (0.13, p = 0.035) and 4 (0.18, p = 0.046) than nonexposed infants on the corresponding days (0.22, 0.20 and 0.24, respectively). On day 2, cFTOE was also lower in infants exposed to nifedipine ± MgSO₄ (0.11, p = 0.028) and to MgSO₄ only (0.15, p = 0.047). sFTOE was higher in infants exposed to labetalol ± MgSO₄ on days 1 (µ = 0.71) and 2 (µ = 0.82) than in nonexposed infants (µ = 0.26, p = 0.04 and µ = 0.55, p = 0.007, respectively). Maternal antihypertensive drugs did not affect rFTOE. Conclusions: Low neonatal cFTOE found with maternal antihypertensive drug exposure may relate to either increased cerebral perfusion or neurologic depression induced by the medication, or preferential brain perfusion associated with preeclampsia placental insufficiency. Concomitantly high sFTOE found with labetalol exposure supports the latter, while renal autoregulation may explain rFTOE stability.

Abdominal Near-Infrared Spectroscopy Detects Low Mesenteric Perfusion Early in Preterm Infants with Hemodynamic Significant Ductus Arteriosus

“…Both the splanchnic perfusion and its reproducibility in the mesenteric territory in preterm infants using NIRS have been extensively studied [12,17,20,21,22,23,24,25,26]. Petrova et al [27] did not find significant differences in cerebral, mesenteric, or renal rSO 2 in a cohort of preterm infants <32 weeks gestation with PDA with a diameter ≥3 versus <3 mm.…”

The Effect of Antenatal Neuroprotective Magnesium Sulfate Treatment on Cerebral Oxygenation in Preterm Infants

“…There is still a lack of evidence, and conflicting results about the effect of antenatal MgSO 4 on both cerebral oxygenation and the incidence of severe IVH, and the reports suggest that outcomes may depend on the antenatal maternal magnesium dose/serum concentrations and neonatal serum magnesium concentrations. [21][22][23][24][25][26][27][28] Despite the uncertainty about the exact mechanism of fetal MgSO 4 neuroprotection, some factors have been asserted to have a role in lowering CP risk. MgSO 4 was shown to have multiple direct effects on the nervous tissue, such as blockade of NMDA (N-Methyl-d-aspartate) receptors and increasing angiogenesis.…”

“…21 There are two other studies both searching for the effect of maternal antihypertensive drugs, including MgSO 4 as it has blood pressure lowering properties, on the cFTOE in the preterm infants during the first day after birth. 22,23 Both found a lowered cFTOE in infants with antenatal MgSO 4 exposure. However, both studies were unable to entangle whether this effect resulted from underlying disease such as preeclampsia or concomitantly given labetalol.…”

Antenatal Magnesium Sulfate and Preeclampsia Differentially Affect Neonatal Cerebral Oxygenation

“…We previously reported that antenatal MgSO 4 is associated with a lower neonatal cerebral fractional tissue oxygen extraction (cFTOE), either due to reduced cerebral oxygen consumption associated with lower cerebral metabolism or increased cerebral oxygen supply through vasodilatory mechanisms [6]. Although MgSO 4 has been reported to affect cerebral blood flow (CBF), a confounding effect of maternal PE can frequently not be excluded [7][8][9].…”

“…Although MgSO 4 has been reported to affect cerebral blood flow (CBF), a confounding effect of maternal PE can frequently not be excluded [7][8][9]. Likewise, fetal brain sparing (preferential cerebral perfusion in response to placental insufficiency) may have influenced these findings [6,10].…”