Fetal Brain Injury Following Prolonged Hypoxemia and Placental Insufficiency: A Review

Rees, Sandra; Mallard, Carina; Breen, Sibilah; Stringer, M; Cock, Megan L.; Harding, Richard

doi:10.1016/s1095-6433(98)01001-0

Cited by 94 publications

(63 citation statements)

References 52 publications

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“…13 Animal studies in a variety of models have contributed to the understanding of brain injury following hypoxia/ischaemia and other fetal insults. [14][15][16][17][18][19][20][21][22] Most of these studies have suggested a time course of cellular responses to fetal brain insult that is in line with what is known of the responses in the human fetal brain. Although previous studies have attempted to delineate clinical risk factors for pregnancy loss, few studies have correlated the clinical and neuropathological findings in the fetus.…”

Section: Introductionmentioning

confidence: 52%

The Scottish Perinatal Neuropathology Study—clinicopathological correlation in stillbirths

Becher

Bell

et al. 2006

BJOG

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Objective To examine the neuropathology of fetuses dying before birth, to determine the timing of any brain damage seen and to ascertain clinical associations of pre-existing brain damage.Design Population-based observational study.Setting All 22 delivery units within Scotland, 1995Scotland, -1998 Sample All stillborn fetuses ‡24 weeks of gestation excluding those with chromosomal abnormality or central nervous system/cardiothoracic malformation.Methods Clinical detail was collected on all stillborn fetuses. Requests for postmortem included separate request for detailed neuropathological examination. Stillborn fetuses were classified as full term antepartum (normal growth/growth restricted), preterm antepartum (normal growth/growth restricted), intrapartum (full term/preterm), multiple births and stillborn fetuses following abruptions. Clinicopathological correlation attempted to define the timing of brain insult. Placentas were examined for each case where available.Main outcome measures Presence of established and/or recent brain damage.Results Clinical details were available for 471 stillborn fetuses, and detailed neuropathology was possible in 191 cases. Of these 191, 13 were multiple births, 9 died following abruption, 12 were intrapartum deaths and 157 were antepartum stillborn fetuses (99 preterm and 58 full term). Recent or established brain damage was seen in 66% of the entire cohort. Thirty-five percent of all cases showed well-established hypoxic damage predating the last evidence of fetal life, and this was more common in preterm fetuses (P = 0.015), those fetuses with evidence of recent damage (P < 0.001), in pregnancies complicated by pregnancy-induced hypertension (P = 0.044) and those in whom the placenta was <10th centile (P = 0.002).Conclusions Brain damage is commonly seen in stillborn infants, and in around one-third of cases, damage predates the period immediately before death. Factors suggesting suboptimal placental function are associated with such damage. Early identification of placental impairment may lead to improved pregnancy outcome.

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Section: Introductionmentioning

confidence: 52%

The Scottish Perinatal Neuropathology Study—clinicopathological correlation in stillbirths

Becher

Bell

et al. 2006

BJOG

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“…Along with clinical observations, animal studies have also revealed the morphological changes and neurological impairments associated with foetal IUGR. In foetal sheep, experimental chronic placental insufficiency late in gestation impairs neural development and results in white matter damage and a reduction in the density of pyramidal cells within the hippocampus (Rees et al 1998). In pregnant guinea pigs, IUGR induced by experimentally limiting uterine blood flow to the placenta results in reduced hippocampal volume and fewer hippocampal pyramidal neurons in the foetal brain at the end of gestation (Mallard et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on fetal guinea pig brain development.

Kelleher¹,

Palliser²,

Walker³

et al. 2010

Journal of Endocrinology

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Progesterone and its neuroactive metabolite, allopregnanolone, are present in high concentrations during pregnancy, but drop significantly following birth. Allopregnanolone influences foetal arousal and enhances cognitive and behavioural recovery following traumatic brain injury. Inhibition of allopregnanolone synthesis increases cell death in foetal animal brains with experimental hypoxia. We hypothesised that complications during pregnancy, such as early or preterm loss of placental steroids and intrauterine growth restriction (IUGR), would disrupt the foetal neurosteroid system, contributing to poor neurodevelopmental outcomes. This study aimed to investigate the effects of chronic inhibition of allopregnanolone synthesis before term and IUGR on developmental processes in the foetal brain. Guinea pig foetuses were experimentally growth restricted at midgestation and treated with finasteride, an inhibitor of allopregnanolone synthesis. Finasteride treatment reduced foetal brain allopregnanolone concentrations by up to 75% and was associated with a reduction in myelin basic protein (MBP) (PZ0 . 001) and an increase in glial fibrillary acidic protein expression in the subcortical white matter brain region (P!0 . 001). IUGR resulted in decreased MBP expression (P!0 . 01) and was associated with a reduction in the expression of steroidogenic enzyme 5a-reductase (5aR) type 2 in the foetal brain (PZ0 . 061). Brain levels of 5aR1 were higher in male foetuses (PZ0 . 008). Both IUGR and reduced foetal brain concentrations of allopregnanolone were associated with altered expression of myelination and glial cell markers within the developing foetal brain. The potential role of neurosteroids in protecting and regulating neurodevelopmental processes in the foetal brain may provide new directions for treatment of neurodevelopmental disorders in infants who are exposed to perinatal insults and pathologies.

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“…Perinatal asphyxia remains a significant cause of infant death and impaired neurodevelopmental outcome and it is considered to be the cause of at least 20% of cerebral palsy cases (Patel and Edwards, 1997). Placental insufficiency and intrauterine growth restriction are chronic hypoxic states of many different etiologies which are commonly associated with increased neurological morbidity and mortality (Rees et al, 1998;Uvebrant and Hagberg, 1992;Williams and O'Brien, 1997). Selective neuronal loss is one of the most common brain injuries associated with hypoxic-ischemic insults in the term fetus.…”

Section: Introductionmentioning

confidence: 99%

Mild chronic hypoxia modifies the fetal sheep neural and cardiovascular responses to repeated umbilical cord occlusion

et al. 2007

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We have shown that five days of mild hypoxia has significant effects on fetal ECoG activity, heart rate and blood pressure. We now studied if mild prolonged hypoxemia had an adverse effect on the fetal cardiovascular and neural responses to repeated cord occlusion and on the magnitude of neuronal damage. Fetal and maternal catheters were placed at 120 days' gestation and animals allocated at random to receive intratracheal maternal administration of nitrogen (n=8) or compressed air in controls (n=7). Five days after surgery, nitrogen infusion was adjusted to reduce fetal brachial artery pO 2 by 25%. After 5 days of chronic hypoxemia the umbilical cord was completely occluded for 5 minutes every 30 minutes for a total of four occlusions. Data are presented as mean ± SEM and were analyzed by Two Way ANOVA or two sample t test. Nitrogen infusion decreased fetal pO 2 by 26% (20.5±1.7 vs. 14.3±0.8 mmHg) without changing fetal pCO 2 or pH. Pre-existing hypoxia fetuses had a greater terminal fall in heart rate in occlusions II, III and IV, and also had a more severe terminal hypotension in the final occlusion. Pre-existing hypoxia was associated with a greater fall in spectral edge frequency during occlussions from 14.4±0.9 Hz to 6.9±0.4 Hz vs. 13.6±1.64 Hz to 10.6±0.77 Hz in controls, p<0.05. In addition, during the three-day post-occlusion period the contribution of theta and alpha band frequencies to total ECoG activity was significantly lower in the pre-existing hypoxia fetuses (p<0.05). These effects were associated with increased neuronal loss in the striatum (p<0.05). In summary, the cardiovascular and neural response indicate a detrimental effect of preexisting mild hypoxia on fetal outcome following repeated umbilical cord occlusions.

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Fetal Brain Injury Following Prolonged Hypoxemia and Placental Insufficiency: A Review

Cited by 94 publications

References 52 publications

The Scottish Perinatal Neuropathology Study—clinicopathological correlation in stillbirths

The Scottish Perinatal Neuropathology Study—clinicopathological correlation in stillbirths

Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on fetal guinea pig brain development.

Mild chronic hypoxia modifies the fetal sheep neural and cardiovascular responses to repeated umbilical cord occlusion

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