Sex differences in cerebral blood flow following chorioamnionitis in healthy term infants

Koch, Frances R.; Wagner, Carol L.; Jenkins, Dorothea; Caplan, Michael J.; Perkel, Jessica; Rollins, Laura Grace; Katikaneni, Lakshmi D.; Mulvihill, Denise

doi:10.1038/jp.2013.179

Cited by 15 publications

(15 citation statements)

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“…Resistive indices and blood flow velocities are normally tightly correlated in the major cerebral vessels of an individual. 24 Chorioamnionitis disrupts this tight correlation in term infants, 26 and blood flow in different regions of the brain may be affected by neuroinflammatory factors and increased metabolic demand. NAC can restore cerebral autoregulation and nitric oxide (NO) responsiveness.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the immediate loss of correlation of CBF and resistance between the 3 major cerebral vessels after birth is consistent with intrauterine onset of neuroinflammation and vascular dysfunction. 26 , 39 Although we did not include a control group of preterm and term infants without chorioamnionitis exposure, another report has found uncoupling of CBF and resistance in term neonates exposed to chorioamnionitis, compared with term infants not exposed to chorioamnionitis. 26 Also, abnormal CBF has been documented in early onset sepsis and in preterm infants who develop IVH.…”

Section: Discussionmentioning

confidence: 99%

“… 26 , 39 Although we did not include a control group of preterm and term infants without chorioamnionitis exposure, another report has found uncoupling of CBF and resistance in term neonates exposed to chorioamnionitis, compared with term infants not exposed to chorioamnionitis. 26 Also, abnormal CBF has been documented in early onset sepsis and in preterm infants who develop IVH. 25 , 30 Fetal inflammatory cascades also predispose term and preterm infants to significant morbidities of IVH, HIE, white matter injury, and NEC, in which vascular insufficiency may be a contributing factor.…”

Section: Discussionmentioning

confidence: 99%

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Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis

Jenkins

Wiest

Mulvihill

et al. 2016

The Journal of Pediatrics

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ObjectiveTo evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial.Study designTwenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5–25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age.ResultsCardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted.ConclusionsIn this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein.Trial registrationClinicalTrials.gov: NCT00724594.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis

Jenkins

Wiest

Mulvihill

et al. 2016

The Journal of Pediatrics

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“…11 In addition, Gray et al demonstrated sex-specific differences in the vasodilatory effects of MgSO 4 on preterm placental vessels, and Koch et al recently showed sex-specific differences in cerebral blood flow in neonates with histologically confirmed chorioamnionitis. 25,26 These findings, in addition to known differences in gene and protein expression in male and female placentas, suggest possible mechanisms for the sex-specific differences seen in this study. [11][12][13][14] Given the study design and lack of placental samples, we were unable to address this issue.…”

Section: Discussionmentioning

confidence: 50%

Antenatal Magnesium Sulfate Exposure and Ponderal Index in Preterm Infants

Deihl

Simhan

2018

Amer J Perinatol

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“…It is known that inflammatory responses are sex-dependent; for example, studies in vivo demonstrated greater release of proinflammatory cytokines after in vivo lipopolysaccharide stimulation in male foetuses than in female foetuses (Kim-Fine et al, 2012;Koch et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Influence of foetal inflammation on the development of meconium aspiration syndrome in term neonates with meconium-stained amniotic fluid (v0.1)"

Ramaswamy¹

2019

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Background: Meconium-stained amniotic fluid is observed in approximately 10-15% of all deliveries, however, only 5% of neonates with meconium-stained amniotic fluid develop meconium aspiration syndrome (MAS). Although foetal distress and subsequent sympathetic stimulation have been considered as the primary upstream events of MAS, this clinical complication sometimes occurs due to other pathologies, such as intraamniotic inflammation. The aim of this study was to investigate whether the incidence of MAS is associated with the presence of funisitis and chorioamnionitis in term neonates with meconium-stained amniotic fluid. Methods: Between April 2013 and March 2015, 95 term neonates with meconium-stained amniotic fluid, who were hospitalized at a neonatal intensive care unit, were enrolled in the study. The placenta and umbilical cord were histopathologically examined. Clinical variables and histopathological findings associated with the incidence of MAS were studied. Results: A total of 36 neonates developed MAS. Univariate logistic regression analysis revealed that a heavier birth weight, male sex, 1-min Apgar score ≤ 7, funisitis (but not chorioamnionitis), and elevated acute-phase inflammatory reaction score were associated with increased incidence of MAS (all p < 0.05). The multivariate model comprised funisitis (OR=5.03, 95%CI, 1.63-15.5), 1-min Apgar score ≤ 7 (OR=2.74,95%CI, 1.06-7.09), and male sex (OR=3.4, 95%CI, 1.24-9.34). Conclusion: In neonates with meconium-stained amniotic fluid, funisitis, as well as low 1-min Apgar score and male sex, was identified as an independent variable for MAS development. Intraamniotic inflammation might be involved in the pathological mechanisms of MAS.

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Sex differences in cerebral blood flow following chorioamnionitis in healthy term infants

Cited by 15 publications

References 40 publications

Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis

Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis

Antenatal Magnesium Sulfate Exposure and Ponderal Index in Preterm Infants

Peer Review #2 of "Influence of foetal inflammation on the development of meconium aspiration syndrome in term neonates with meconium-stained amniotic fluid (v0.1)"

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