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



The aim of this study was to assess whether maternal antihypertensive drugs affect multisite oxygenation levels of the neonate.



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.



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.



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.
Department of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Anne E
AE
Richter
Trijntje E
TE
Schat
Koenraad N J A
KN
Van Braeckel
Sicco A
SA
Scherjon
Arend F
AF
Bos
Elisabeth M W
EM
Kooi
D000959:Antihypertensive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007668:Kidney / Q000187:drug effects; D007741:Labetalol / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009426:Netherlands; D000066829:Neuroprotection / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011225:Pre-Eclampsia / Q000188:drug therapy; D011247:Pregnancy; D019265:Spectroscopy, Near-Infrared; D013997:Time Factors; D015145:Tocolysis / Q000379:methods
D000959:Antihypertensive Agents; D008278:Magnesium Sulfate; D009543:Nifedipine; D007741:Labetalol