Enmeshed in the controversies surrounding the pathophysiology of intrapartum fetal brain injury is the debate over the role of the forces of labor on the fetal head in causing or contributing to such damage [1] [2] . The debate, going back centuries, has been constrained by the widespread contemporary assumption that fetal ischemic brain injury during labor derives almost exclusively from hypoxic stress that results in severe, systemic asphyxia with marked fetal acidemia and impaired neonatal adaptation [3] [4] . Several lines of evidence do not support such a monolithic perspective.

For example, as many as 40% of neonates with a radiological diagnosis of hypoxic-ischemic encephalopathy (HIE) do not have evidence of severe asphyxia at birth [5] , casting doubt on use of the term “hypoxic” in this diagnostic rubric. Moreover, most newborns with severe acidosis have neither acute problems nor long-term neurologic dysfunction [5] . And infants with clinically mild neonatal encephalopathy (NE) have an incidence of neuroradiological markers of injury comparable to those with more severe NE, and subsequent handicap that might not be revealed until adolescence [6] [7] . Existing data permit the conclusion that neither the umbilical pH nor the severity or pattern of NE is a sufficiently sensitive clinical biomarker to define the etiology of NE reliably, to explain either the type or duration of a harmful exposure, or to identify term infants who would benefit from therapeutic hypothermia [7] [8] [9] . Thus, although hypoxia is certainly an important risk factor for neurological harm, it is neither a sensitive surrogate nor a gold standard for identifying the timing or the mechanism of intrapartum neurologic compromise.

Excessive mechanical forces acting on the fetal head during labor (Table 1) [10] - [15] would seem capable of causing serious brain damage. In this report we attempt to elucidate the impact of intracranial pressure (ICP) on cerebrospinal fluid (CSF) dynamics, fetal heart rate (FHR) patterns, and normal compensatory responses in protecting the brain exposed to increased pressures. In addition, we emphasize that such protection probably has limits, and that avoiding excessive fetal head compression during labor may have important salutary effects. Our goal is to summarize what is known about the potential effects of intrapartum increases in ICP and to stimulate further investigation of this important but relatively unexplored area.

ICP is the pressure within the skull, brain tissue and CSF. The ICP postnatally is normally 7 - 15 mm Hg. It is about 10 mm Hg higher in the fetus [16] , the passive consequence of resting intrauterine pressure (IUP) imposed on the fetal body.

The adult generally manifests a consistent relationship among ICP, intracranial volume and cerebral perfusion pressure. Referred to as the Monro-Kellie doctrine [17] [18] [19] , it holds that the contents of the cranium are incompressible and that the volume inside the skull is fixed in a state of equilibrium such that any increase in volume of one of the constituents must be compensated for by a decrease in volume of another, lest the ICP rise. For example, cerebral edema from ischemia would increase brain volume, causing a rise in ICP, unless there was a compensatory fall in CSF or intracranial blood volume. This traditional view of pressure-volume relationships has not been studied in the human fetus directly, but may help explain some interesting recent observations.

Intrapartum and neonatal MRI imaging has demonstrated marked narrowing of the lateral ventricles in vaginally delivered babies [20] [21] [22] . The latter was unrelated to cerebral edema, and was presumably caused by a reduction in or redistribution of fetal CSF volume in response to increased ICP [20] [21] [22] [23] . Babies delivered by elective cesarean showed no such changes in the CSF [20] . These findings bolster the evidence for the transmission of extracranial forces into the cranial cavity.

With the fetus floating in the amniotic cavity, the intrauterine pressure (IUP) is applied symmetrically to all its parts, including the head. Once membranes are ruptured and the fetal head descends, the IUP is no longer imposed symmetrically (Figure 1). Then, pressure on the circumferential portion of the cranium juxtaposed to the maternal pelvis exceeds that on the remainder of the head and other body parts [24] [25] . It is increased further during contractions, expulsive efforts, and operative vaginal delivery, when it may exceed 250 mm Hg [26] , far greater than any IUP generated by the contracting term uterus.

Investigations performed on experimental animals, as well as clinical observations, provide inescapable evidence that extracranial pressures acting on the fetal skull from contractions and forceps are transmitted intracranially to increase the fetal ICP [16] [25] [27] [28] [29] [30] (Figure 2).

Ethical considerations obviously preclude catheterizing the normal fetal skull during labor to obtain direct measurements of ICP. Such investigations, performed on experimental animals and in unique clinical circumstances where the human fetus had a lethal anomaly or was dead [16] [25] [27] [28] [31] provide considerable support for the notion that fetal extracranial pressure is transmitted intracranially to cause increased ICP, decelerations in the FHR, and decreases in fetal CBF and cerebral O₂ consumption, potentially to the point of ischemic injury [16] [25] [27] [28] [29] [30] (Figure 2).

In the experiments of Mann, et al., when head compression was applied to fetal lambs to mimic the effect of uterine contractions, the ICP increased, the electroencephalogram (EEG) became isoelectric, and brain blood flow diminished along with cerebral oxygen consumption [28] . Also in fetal sheep, increased ICP that was less than the systolic blood pressure triggered intense autonomic activity that elicited hypertension, cerebral vasodilation, and peripheral vasoconstriction, but not bradycardia [31] . When the ICP was made to exceed the mean blood pressure in a neonatal rabbit model, a deceleration in heart rate occurred [32] . Other studies in intact fetuses confirmed that external pressure on the skull caused alterations in FHR, CBF and cerebral oxygenation [24] [28] [29] [30] [33] as well as impairment of venous flow in the superior sagittal sinus, depending upon fetal head position and molding [34] [35] .

In the normal human fetus, studies using carotid artery Doppler flow, near

infrared spectroscopy and fetal EEG during the 2^nd stage of labor, showed changes in cerebral blood flow and EEG activity unrelated to fetal hypoxia [36] [37] [38] . Kelly, et al. showed that IUP from contractions with pushing may easily equal the pressure applied by forceps and is frequently accompanied by FHR decelerations [1] [2] [39] . Compression of the fetal head accompanied by increases in intracranial pressure is as foreseeable a development as is the reduction in uterine blood flow associated with myometrial contractions.

The increase in ICP attending the rise in IUP during a uterine contraction may be considered protective (up to a point), in that the higher the ICP, the greater is the resistance to further head compression. This benefit is potentially offset by the potential compromise of cerebral blood flow. To deal with increases in ICP that might diminish brain perfusion, the term fetus and newborn are endowed with robust, brain-centered, compensatory adaptations that are unrelated to the presence of systemic hypoxemia or acidemia. The best known is the Cushing response, which is clearly present in the fetus and the newborn [40] [41] [42] .

Depending on its severity, systemic hypoxemia induced by uterine contractions is detected by peripheral chemoreceptors and provokes a series of adaptive neurohumoral responses that serve to slow the heart rate (late decelerations), attempt to maintain cardiac output and direct it away from the peripheral circulation toward the priority organs (placenta, heart, brain and adrenals). Additional fetal adaptations to hypoxemia include a non-injurious reduction in brain oxygen consumption, and EEG changes. In this hypoxemic model of injury, when the fetus is sufficiently hypoxic and acidotic to impair cardiac output and CBF the potential for central nervous system injury from the related cerebral ischemia develops [3] [43] [44] . This is reflected in a severely compromised newborn with very low pH, persistently low Apgar scores, systemic hypotension, and multisystem organ involvement, likely to meet the criteria for moderate-severe encephalopathy and be a candidate for therapeutic hypothermia.

In addition to these well described adaptations to hypoxemia, the fetus also possesses adaptive responses to help it adjust to diminished brain perfusion, even without accompanying hypoxia. These reflexes derive from receptors centered in the fetal face and brain that are sensitive to stimulation by alterations in brain perfusion [38] [45] [46] [47] .

To maintain CBF during a contraction, the fetal BP normally rises passively with the increasing IUP. This may be accompanied by increased sympathoadrenal tone as reflected by fetal activity and FHR accelerations that commonly occur with or in anticipation of contractions early in labor. When this proportional elevation of fetal BP is inadequate to maintain perfusion, it will be bolstered by robust adaptive reflexes to protect the fetal brain from direct ischemia, unrelated to impaired cardiac output.

In adults an increased ICP, with a reduction in CBF, induces the Cushing response, which raises the BP to support cerebral perfusion, but also affects breathing and heart rate [40] [41] . At least in experimental animals, cerebral ischemia (diminished cerebral perfusion) decreases the cerebral surface pH, but at least initially, not the systemic arterial pH [42] . A secondary fall in systemic pH may ensue over time as the response to cerebral hypoperfusion contributes to peripheral hypoperfusion by increased systemic resistance as the body optimizes flow to the ischemic brain [42] .

This vagal response, unrelated to systemic hypoxia, is well developed in the term fetus via receptors within the brain [36] [41] [45] . In addition to the Cushing response, human newborns demonstrate various well-developed, innate responses to stimulation of the face and head, (trigeminal, diving reflexes) that raise blood pressure and induce vasoconstriction in the peripheral circulation. Like the Cushing response, these reflexes are maximal at birth and diminish progressively thereafter, as if they evolved specifically for the events of labor and delivery [46] [47] .

The bones of the fetal calvarium are usually relatively thin, not fully calcified, and unfused. These features increase compliance and make them vulnerable to changes in shape and position during labor according to constraints imposed by contractions, maternal pushing, and the bony and soft tissue elements of the birth canal [23] [48] . Normal molding is another means by which the fetus adapts to external pressures on its head. Extreme molding, especially in the context of ruptured membranes, however, is a risk factor for neurological injury, emphasizing the limited protection provided by this commonplace, adaptive mechanism [49] .

A failure to mold, as well as large head size, has been associated with labor abnormalities, traumatic and ischemic intracranial injury and subsequent handicap including autism [12] [49] - [54] .

As noted, contractions (especially with pushing) elevate ICP and induce hemodynamic changes even in the normally oxygenated fetus [37] [55] . They may also diminish fetal pO₂ which, if sufficient, will trigger the peripheral chemoreceptors and cause FHR decelerations. Generally, even with mild hypoxemia, the rise in fetal arterial pressure is initially sufficient to sustain cerebral perfusion [55] .

Adding maternal pushing efforts causes a more rapid onset, a greater peak pressure and a longer duration of maximum intrauterine and intracranial pressures. While facilitating molding and descent, these forces may impede CBF by further increasing the resistance to flow into the head. Distortion of brain vasculature can also reduce perfusion, contributing to the high frequencies of variable and early FHR decelerations in the 2^nd stage [56] .

Early decelerations are widely considered to be caused by fetal head compression [56] [57] . They are more common in occiput posterior presentations [58] , and appear only after an IUP threshold has been exceeded [59] . They can sometimes be produced by manual compression of the fetal head through the uterine wall, by pressure on the anterior fontanel, or during external version [57] [60] [61] [62] . Importantly, in fetal sheep, decelerations are not observed despite increased ICP as long as systemic hypertension and CBF are maintained [31] .

Early FHR decelerations appearing with contractions are associated with an increased resistance index and with absent or reversed diastolic blood flow in the fetal middle cerebral artery [33] . These decelerations in normal fetuses are most likely caused by a vagally mediated reflex response to a fall in cerebral perfusion, the result of cranial compression [33] [60] [63] [64] . The abrogation of the decelerations by the pre-administration of atropine confirms the reflex vagal nature of the response [65] . Thus, decelerations in response to head compression appear to represent an early, preemptive response to any threat to CBF and not some response to tactile stimulation of the scalp or long-standing or severely compromised CBF [29] .

Classical teaching holds that fetal head compression causes early decelerations, while umbilical cord compression results in variable decelerations [56] . These distinctions are probably moot because the morphology of decelerations and the severity of fetal head compression and the dynamics of fetal ICP change over time, especially during the 2^nd stage of labor [37] when both variable and early decelerations most often result from head compression, not cord compression [30] [62] [63] [64] .

Sometimes there may be delayed return of the deceleration to the baseline, or the secondary appearance of late decelerations after the variable deceleration has recovered. Walker et al. reported that pressure over the inferior aspect of the uterus often produced decelerations with slow resolution [57] . Similarly, Mocsary, et al. found delayed recovery of the deceleration, when ICP was experimentally increased above that produced by normal contractions [27] . In the sheep fetus manual head compression is associated with a significant reduction in carotid blood flow that continues beyond the deceleration, accompanied by profound suppression of fetal EEG activity and reduced brain metabolism [27] [28] [29] [30] .

These findings suggest it may not be the pressure on the head per se, but the impact on CBF that produces the deceleration. They further suggest that despite rapid return to normal IUP after a contraction, more time may be necessary to restore normal fetal CBF and FHR, and that abnormal recovery of the FHR may reflect a persistently elevated ICP or more severe cerebral ischemia separate from or in addition to any hypoxemia [27] [63] .

Excessive uterine contractility would be expected to compromise fetal oxygen availability as well as recovery from the effects of head compression. Indeed, Bakker, et al. showed that excessive uterine activity was more often accompanied by variable than late decelerations [66] . The fetus is generally tolerant of substantial amounts of uterine activity for many hours, especially in the first stage of labor [67] . When contractions are excessive, especially when combined with maternal pushing and limited fetal descent, the deleterious effects of hypoxia and of head compression may not permit sufficient recovery from the previous deceleration before the next contraction starts. Such deterioration is expressed on the FHR tracing in the form of recurrent variable decelerations with erratic changes during recovery of the deceleration, often with significant overshoot and a rising baseline. The variable decelerations may be followed immediately by hypoxemia-induced late decelerations [68] [69] [70] . Consistent with the notion of combined effects (head compression and hypoxia), an associated progressive reduction in fetal pH has been demonstrated. Such patterns have been described as subacute hypoxia [71] [72] with the recommendation that they be treated by the immediate reduction of pushing and uterine activity to allow the fetus to recover.

The understanding that intrapartum HI injury may occur without systemic asphyxia and neonatal depression has significant therapeutic implications for the neonate and the use of therapeutic hypothermia [73] . Most clinical trials of hypothermia involve infants with moderate to severe NE in whom there is both severe acidosis and neonatal depression. Although there have been clinical trials of hypothermia in infants with mild encephalopathy, there is yet no consistent recommendation on its use in those circumstances. It is relevant to point out that the experimental model of neurological injury used to test the value of cooling involved not systemic asphyxia, but a single, mechanical interruption of the cerebral circulation, where the exact time of the occlusion was known [74] .

The cause-effect relationship of mechanical factors to fetal neurological injury pervades almost two centuries of literature, especially in association with difficult or instrumental delivery (Table 2) [1] [2] [75] [76] [77] [78] [79] . Modern reviews of intrapartum fetal neurological injury or the effects of pushing, however, do not generally mention head compression as a possible etiology of injury [80] [81] . The finding of MRI evidence of recent ischemia in the face of near-normal umbilical pH cannot reasonably be explained by severe hypoxic acidemia during labor [72] [82] [83] while normal growth, normal fetal activity, normal amniotic fluid volume and a normal FHR tracing on admission would seem to preclude an earlier injury [4] . The diagnosis of “presumed perinatal stroke” refers to the discovery of cerebral ischemic lesion(s) in the perinatal period, but which may have become symptomatic only weeks or months later [84] [85] . Excessive uterine activity, prolonged pushing in the 2^nd stage and instrumental delivery (especially in the nullipara) are considered risk factors for HIE and subsequent neurological handicap including CP and stroke [15] [85] [86] [87] [88] . As expected, given the slow evolution of these changes, most of the cerebral lesions involve the cortex and white matter, (a prolonged, partial, HIE) and less commonly the basal ganglia (an acute, near-total HIE).

The ischemic effects of pressure on the fetal head will likely be augmented when superimposed on an already asphyxiated fetus. If, during systemic asphyxia,

the fetal BP is struggling or failing to provide sufficient cerebral perfusion pressure, then any factor that increases ICP (such as excessive uterine activity, maternal pushing) would aggravate the already impaired CBF. Instituting forceful pushing to effect delivery in the face of fetal bradycardia or decelerations with severe tachycardia, for example, may be counterproductive; reducing contractions and curtailing pushing may be far more beneficial. As mentioned above, prevention would be a better strategy. Thus, assessing the feasibility of safe vaginal delivery, maintaining a controlled rhythm and frequency of uterine contractions, not to exceed 4 contractions in 10 minutes [89] , observing the response of the FHR pattern to the mother’s pushing efforts, and discouraging pushing in those situations in which the FHR pattern does not return to its previously normal rate and variability will avoid both urgent intervention and fetal injury [89] [90] [91] [92] .

We must further our understanding of how the factors affecting head compression, including excessive uterine activity, dysfunctional labor progress, fetal head molding and various obstetric procedures, including pushing strategy, influence outcomes. There is no evidence that FHR patterns will fail to reflect impaired CBF or hypoxia. To better appreciate the impact of contractions on cerebral blood flow, FHR patterns must be used as an instrument of preventive care rather than to rescue a fetus who may already be compromised. Thus, early and variable decelerations should not be considered innocuous when they are unassociated with fetal acidemia. They are likely tolerable as long as there is prompt return to the previously normal baseline rate and variability. Abnormalities of deceleration recovery (prolonged, overshoot, rising heart rate, altered variability) are often markers of deterioration. Excessive uterine activity should be avoided, irrespective of the FHR pattern. Moderating expulsive efforts, even intermittently, may assist in the recovery of the fetus to its previously normal pattern and should be included in any list of techniques of intrauterine resuscitation. In this respect, current NICE guidelines from England recommend a limit of four contractions in ten minutes [89] .

Prevention of injury must begin with understanding its mechanisms and clinical correlates. The traditional view that intrapartum brain injury is exclusively the consequence of severe global asphyxia and acidosis and severe neonatal depression informs current protocols for interpreting FHR patterns and guiding intrapartum care, but is not consistent with the available clinical or experimental data. Such a narrow perspective of adverse outcomes underestimates both the true incidence of immediate and long-term perinatal harm, its timing, mechanism and preventability, as well as the potential role of enlightened obstetrical and neonatal care in preventing injury [98] - [103] . Recommendations that focus on protecting the fetal brain from hypoxia and excessive compression (minimizing excessive uterine activity, moderating maternal pushing as a strategy of intrauterine resuscitation, using the fetal response to decelerations to moderate the administration of oxytocin and pushing) should prevail whether the primary mechanism is ischemia from head compression or hypoxia from impaired utero-placental exchange. There is compelling evidence that the fetal head is exposed sometimes to extremely high external pressures during labor and delivery. It is also clear that these forces are transmitted into the cranial cavity, and that under normal circumstances there are physiologic countermeasures that protect brain perfusion. Like any such protective mechanisms, these can be overcome if compression of the head is well beyond normal, leading to the potential for impeding brain blood flow through intracranial pressures that exceed brain perfusion pressures or distortion of intracranial vasculature. Although the data linking excessive head compression to brain injury are strongly inferential at this time, cranial compression should be considered in the differential diagnosis of causes of ischemic encephalopathy. Further research in this dimension is needed desperately.

All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

As a review article that discloses no patient information this project was exempt from review by the local Institutional Review Board.

The authors declare no conflicts of interest regarding the publication of this paper.

Schifrin, B.S., Koos, B.J. and Cohen, W.R. (2024) Fetal Head Compression: Its Possible Role in Neurologic Injury. Open Journal of Obstetrics and Gynecology, 14, 124-143. https://doi.org/10.4236/ojog.2024.141013