Placental pathology in asphyxiated newborns meeting the criteria for therapeutic hypothermia

Wintermark, Pia; Boyd, Theonia K.; Gregas, Matthew; Labrecque, Michelle; Hansen, Anne

doi:10.1016/j.ajog.2010.08.024

Cited by 121 publications

(96 citation statements)

References 36 publications

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“…Our study indicated that AIUI was associated with lower r c SO 2 and higher FTOE on the second, third, and fourth days after birth. SpO 2 did not differ in the presence or absence of AIUI.…”

Section: Discussionsupporting

confidence: 49%

“…Placental lesions might also differ between twins, e.g., twin-to-twin transfusion. Finally, we studied r c SO 2 and FTOE values during a 2-h stable period each day. However, these values might be different during other moments of the Corrected for potential confounders: whether the mother had preeclampsia, whether the child was small for gestational age, whether there was preterm prelabor rupture of the membranes, whether the infant was delivered by cesarean section.…”

Section: Discussionmentioning

confidence: 99%

“…The r c SO 2 and SpO 2 values were collected every 5 s. The mean values for r c SO 2 , SpO 2 , and FTOE were calculated for the 2-h recording period. We used the Kolmogorov-Smirnov test to determine the normality of the r c SO 2 and FTOE values. Both showed a normal distribution.…”

Section: Discussionmentioning

confidence: 99%

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In preterm infants, ascending intrauterine infection is associated with lower cerebral tissue oxygen saturation and higher oxygen extraction

et al. 2015

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Background: Placental lesions are associated with neurological morbidity but the mechanism leading to morbidity is unclear. To provide insight into such a possible mechanism, we determined whether placental lesions were associated with regional cerebral tissue oxygen saturation (r c SO 2 ) and fractional tissue oxygen extraction (FTOE) in preterm infants during their first 5 d after birth. We hypothesized that as a result of cerebral hypoperfusion, r c SO 2 would be lower and FTOE would be higher. Method: In a prospective, observational study of 42 preterm infants (gestational age <32 wk), the infants' placentas were examined for histopathology. We measured r c SO 2 and transcutaneous arterial oxygen saturation (SpO 2 ) on days 1-5. FTOE was calculated as FTOE = (transcutaneous SpO 2 − r c SO 2 )/transcutaneous SpO 2 . results: Only three placentas showed no pathology. Ascending intrauterine infection (AIUI) (n = 16) was associated with lower r c SO 2 and higher FTOE values on days 2, 3, and 4 (P ≤ 0.05). Other placental lesions were not associated with r c SO 2 and FTOE. conclusion: AIUI is associated with lower r c SO 2 , and higher FTOE shortly after birth. The effect it has on cerebral oxygenation might be the mechanism leading to neurodevelopmental problems. t he placenta is the link between mother and fetus during pregnancy and as such it is an essential organ for the development of the fetus. It is the only organ that enables the exchange of nutrients and oxygen from mother to fetus and removes fetal waste products (1). Placental lesions carry the risk of fetal hypoxia, neonatal morbidity, and even perinatal death (2-6). Moreover, such lesions are associated with several neurological problems including intraventricular hemorrhage, white matter injury, cerebral palsy, and long-term neurodevelopmental problems (7-13).To date, the mechanism whereby placental lesions lead to cerebral damage is unclear. One study hypothesized that chronic placental insufficiency could induce fetal hypoxia that in turn could result in cerebral hypoperfusion, which leads to cerebral damage (14). Long-standing placental hypoperfusion can result in a non-optimal intrauterine environment. The placental underperfusion can lead to a reduction of perfusion surface and, as a consequence, nonoptimal oxygen delivery to the fetal circulation. This might result in some degree of intrauterine cerebral underperfusion, and as a consequence to a (transitional) effect on postnatal cerebral blood flow. On the other hand, cerebral hyperperfusion could also lead to cerebral damage (15). Understanding the mechanism of placental lesions leading to neurodevelopmental problems is necessary to provide possible clues for early interventions aiming to improve neurological outcome. To determine whether the disturbances in hemodynamics shortly after birth could be a possible mechanism underlying cerebral damage caused by placental lesions, it would be useful if we could measure cerebral tissue oxygen saturation and extraction. A noninvasive method of doing...

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

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In preterm infants, ascending intrauterine infection is associated with lower cerebral tissue oxygen saturation and higher oxygen extraction

et al. 2015

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“…[47][48][49][50] Funisitis was found to be a significant risk factor for moderate to severe neonatal encephalopathy (OR 9.29, 95% CI 1.36-63.06) in a retrospective case-control study carried out in Dublin. 49 These findings are supported by our previous work in Uganda, 48 suggesting that the association between funisitis and neonatal encephalopathy may be common across a variety of different resource settings.…”

Section: Observations On Placental Pathologymentioning

confidence: 99%

Inflammation‐induced sensitization of the brain in term infants

Fleiss

Tann

Degos

et al. 2015

Develop Med Child Neuro

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COXPerinatal insults are a leading cause of infant mortality and amongst survivors are frequently associated with neurocognitive impairment, cerebral palsy (CP), and seizure disorders. The events leading to perinatal brain injury are multifactorial. This review describes how one subinjurious factor affecting the brain sensitizes it to a second injurious factor, causing an exacerbated injurious cascade. We will review the clinical and experimental evidence, including observations of high rates of maternal and fetal infections in term-born infants with neonatal encephalopathy and cerebral palsy. In addition, we will discuss preclinical evidence for the sensitizing effects of inflammation on injuries, such as hypoxia-ischaemia, our current understanding of the mechanisms underpinning the sensitization process, and the possibility for neuroprotection. PERINATAL BRAIN INJURY IN THE TERM-BORN INFANTIntrapartum neonatal deaths are the third leading cause of global childhood mortality. 1 In addition, each year perinatal insults are estimated to be responsible for more than one million new cases of neonatal encephalopathy, and nearly half a million infants with impairments such as cerebral palsy (CP).2 Infants exposed to a perinatal insult typically present with encephalopathy, a descriptive term for a clinical constellation of neurological dysfunctions in the term-born that includes difficulty with initiating and maintaining respiration; depression of tone and reflexes; subnormal levels of consciousness; and seizures.3 Whilst often assumed to result solely from acute intrapartum hypoxic-ischaemia, the precise contribution of hypoxia is likely to vary according to the definition of encephalopathy used, the range of competing risks, and the care setting. 3,4 Presumed hypoxia-ischaemia is diagnosed based on reduced Apgar scores and acidosis, 5 and the combination of progressive hypoxia, hypercarbia, and acidosis is often referred to as asphyxia. 6 Encephalopathy resulting from hypoxia-ischaemia can be clearly diagnosed only in a small number of cases in which a sentinel event, such as placental abruption, uterine rupture, cord prolapse, or shoulder dystocia, is clearly present. Clinical studies have identified a number of other important antepartum and intrapartum risk factors for neonatal encephalopathy. [7][8][9][10] In low-income settings, where access to skilled birth attendants and emergency obstetric intervention is often limited, the probability of intrapartum hypoxic events contributing to neonatal encephalopathy is increased.2,9,11 However, in general, neonatal encephalopathy is likely to be a multifactorial condition with complex aetiology, encompassing several causal events, with strong evidence that fetal exposure to infection contributes. 12 CONCEPT OF INFLAMMATION-INDUCED SENSITIZATIONAn increasingly common model for the complex and multifactorial process of perinatal brain injury involves sensitization, 13-15 whereby factors not severe enough by themselves to induce significant brain damage make the developi...

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“…19,21 However, many important features of placental pathology cannot be identified by macroscopic examination. Abnormal placental histology has been reported in more than 75% of infants with neonatal encephalopathy (whether or not it is considered to be HIE) in clinical samples, 11,22 with the most common placental lesions being vasculopathy, inflammation, or both. Placental histological examination is the definitive method for establishing the presence of inflammation, its locus, severity, and acuteness or chronicity.…”

Section: The Placentamentioning

confidence: 99%

Does aetiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy influence the outcome of treatment?

McIntyre

Badawi

Blair

et al. 2015

Develop Med Child Neuro

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HIE Hypoxic-ischaemic encephalopathyNeonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates.Neonatal encephalopathy is a clinical syndrome of disordered neurological function occurring in the first days of life in term-born and late preterm neonates and is characterized by difficulty initiating and maintaining respiration, an abnormal level of consciousness, depression of tone and reflex responses, and often seizures. This symptom complex affects about 3 in every 1000 births, and is an important predictor of perinatal death and a major contributor to long-term adverse neurological outcomes, particularly cerebral palsy (CP). 1,2 Evidence from clinical and experimental studies agrees that some instances of neonatal encephalopathy are related to hypoxic-ischaemic injury, but the proportions of neonatal encephalopathy attributed to recent asphyxial events vary with the definitions used and the methodology of the investigations. Studies of infants in representative populations indicate that asphyxial complications at birth account for only a minority of neonatal encephalopathy. These population-based studies also identify other factors that contribute to increased risk of neonatal encephalopathy, such as intrauterine exposure to inflammation or fetal growth restriction, and note that some non-asphyxial factors can produce a clinical picture that closely mimics hypoxia-ischaemia. [3][4][5] In contrast, studies of neonatal cooling have approached this topic from the ...

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Placental pathology in asphyxiated newborns meeting the criteria for therapeutic hypothermia

Cited by 121 publications

References 36 publications

In preterm infants, ascending intrauterine infection is associated with lower cerebral tissue oxygen saturation and higher oxygen extraction

In preterm infants, ascending intrauterine infection is associated with lower cerebral tissue oxygen saturation and higher oxygen extraction

Inflammation‐induced sensitization of the brain in term infants

Does aetiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy influence the outcome of treatment?

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