Methods and apparatus for reducing the risk of and identifying the presence of neurological injury in a human fetus during and prior to delivery

Abstract

Methods and apparatus for reducing the risk of neurological injury to a human fetus during and before labor are disclosed. According to one embodiment, the method comprises the following steps: (1) identifying a risk of neurological injury to a fetus during labor by analyzing fetal blood during a first time period of a first stage of labor to determine at least a first base excess (BE) value for the fetus; (2) determining a median multiple of the BE value for the first time period by dividing the BE value by the median BE value of a data set, the data set comprising a population of fetal BE values established for a time period during the first stage of labor that is the same as the first time period, wherein a BE value that is a predefined median multiple of the BE value indicates that the fetus is at risk of neurological injury; and (3) treating the fetus indicated by the identifying step to be at risk of neurological injury, wherein the treating step comprises intervening in labor by any conventional treatment measure to reduce or eliminate the risk of neurological injury to the fetus.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is related to and claims the benefit of priority to U.S. Provisional Application Serial No. 62 / 881,701, filed on August 1, 2019, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention relates to the field of obstetrics and, more particularly, to methods and devices for reducing the risk of neurological injury to a human fetus during and before delivery. Background Art

[0004] The current American College of Obstetricians and Gynecologists (ACOG) classification system for assessing fetal well-being and predicting risk of neurologic impairment is extremely poor, missing up to 50% of cerebral palsy (CP) cases. Its use has led to a significant increase in cesarean delivery rates (CDRs) while having little impact on reducing serious complications such as CP. The statistical performance metrics of this classification system violate essentially all the key criteria required for an effective screening program. ACOG Category III, the action point for delivery or at least treatment, is so far to the right on the fetal distribution curve that it has a high positive predictive value for injury—most of which may have already occurred. It also has a very high and unacceptable false-negative rate—missing 50% of severe cases (as reported in multiple publications). In contrast, ACOG Category II, defined as "concern" (but without a clearly accepted mandatory action), is so far to the left on the case distribution curve that it is achieved in up to 75% of patients. This renders Category II useless as a screening test.

[0005] Electronic fetal monitoring (EFM) was introduced into practice in the late 1960s in an attempt to allow for timely intervention (eg, by cesarean section, or by expedited delivery using a vacuum extractor or forceps) in cases of fetal compromise or impending compromise. Over the past few decades, EFM has become widely adopted and used in the vast majority of deliveries in the United States.

[0006] The premise of EFM is the recognition of asphyxia associated with metabolic acidemia. The response to fetal heart rate (FHR) patterns is based on the identification and "rescue" of the asphyxiated fetus, hopefully before it suffers any harm. Traditionally, delivery is allowed to continue when EFM data indicate an overall impression of "safety," and intervention is reserved for abnormal EFM data, suggesting severe asphyxia (from metabolic acidosis), or an acute emergency (eg, fetal bradycardia). This interpretation is often highly subjective; even prominent experts often disagree on the significance of individual patterns.

[0007] In an improvement over conventional approaches for interpreting EFM data and improving fetal outcomes during labor and delivery, the inventors disclosed in U.S. Patent No. 9,131,860 (the disclosure of which is incorporated herein by reference in its entirety) an apparatus for identifying a fetal risk level during labor. The apparatus comprises at least one computer operable to receive input signals indicative of at least a patient's FHR and maternal uterine activity, the at least one computer further operable to (i) determine at least FHR baseline variability, FHR acceleration, and FHR deceleration from the FHR, and (ii) determine when each of at least (a) the FHR, (b) the FHR baseline variability, (c) the FHR acceleration, (d) the FHR deceleration, and (e) the maternal uterine activity exhibits at least one unsafe characteristic from a plurality of predefined unsafe characteristics of at least parameters (a) through (e). The at least one computer is further operable to (iii) receive user input indicating the presence of one or more prior clinical parameters in the patient that increase the risk level for the fetus during labor, and (iv) determine a current risk level for the fetus at a given time point during labor, the risk level taking into account only: the total number of the one or more prior clinical parameters that increase the risk level for the fetus during labor; and the total number of parameters (a) through (e) that each independently and simultaneously exhibit at least one unsafe characteristic at the given time point during labor. The present invention has been demonstrated to produce consistent assessments of EFM data and, therefore, consistent identification of fetuses at risk for neurological injury. The Fetal Reserve Index (FRI) provides a more meaningful alternative to the ACOG classification system. The FRI combines multiple risk factors and the presence of increased uterine contractions during labor to produce a statistically significant prediction of fetal risk for cerebral palsy. The FRI's risk indicators are validated earlier in the pathophysiology than the ACOG classification system. By identifying potential problems early in the process, appropriate clinical intervention has been shown to reduce adverse outcomes and can actually reduce emergency CDRs, overall emergency deliveries, and total CDRs.

[0008] In a further improvement to conventional means for interpreting EFM data and improving fetal outcomes in labor and delivery, the inventors disclosed in published international application WO / 2018 / 094398 an apparatus for identifying the level of fetal risk during labor, the apparatus comprising: at least one computer operable to receive input signals indicative of at least a patient's FHR and maternal uterine activity, the computer operable to determine (i) FHR baseline variability, FHR acceleration, and FHR deceleration, and (ii) determining when each parameter of at least (a) FHR, (b) FHR baseline variability, (c) FHR acceleration, (d) FHR deceleration, and (e) maternal uterine activity exhibits at least one unsafe characteristic of a plurality of predefined unsafe characteristics of at least parameters (a) to (e). The computer is further operable to (iii) receive user input indicating the presence in the patient of one or more (f) maternal risk factors, (g) obstetric risk factors, and (h) fetal risk factors that increase the risk level of the fetus during labor, and (iv) determine a current risk level for the fetus at a given time point during labor, the risk level taking into account only: the total number of parameters (a) to (e) that each independently and simultaneously exhibit at least one unsafe characteristic at the given time point during labor, and the total number of parameters (f) to (h) that are present. The output depicts one or more parameters (a) to (h) as they change over time during labor in a single graphical user interface, and the appearance of the single graphical user interface includes a marker for indicating the current risk level of the fetus at any given time point during labor and signals that intervention in labor may be necessary. The disclosure of published international application WO / 2018 / 094398 (disclosed in published U.S. application 2019 / 0274618, respectively) is incorporated herein by reference in its entirety.

[0009] In a further approach, the inventors analyzed data from before and one hour after birth. Surprisingly and unexpectedly (contrary to popular belief), the adaptation process from fetal to neonatal circulation was found to be very different from what is generally believed. Acid / base balance does not improve linearly, but rather deteriorates significantly over varying time periods. Using this dataset, the FRI was able to distinguish three separate groups of infants at low, intermediate, and high risk for developing metabolic acidosis (generally defined as a base excess of ≤-12 mMol / L, a widely accepted predictor of cerebral palsy due to birth complications) based on their last FRI score before delivery. The study also found that neonatal heart rate measurements revealed severe tachycardia with loss of responsiveness and variability during the first 10 minutes or longer in 85% of patients. If this pattern were present prenatally, it would generally be considered Class III under the ACOG classification system. These findings, in part, help explain the poor performance of the ACOG classification system, as abnormalities often go unnoticed when they occur. The above content is discussed in published international application WO / 2020 / 102524, the entire content of which is incorporated herein by reference.

[0010] Although these advances hold promise for improving labor and delivery outcomes, neurological damage to the neonate due to progressive hypoxia and acidemia continues and remains a problem that needs further resolution. Summary of the Invention

[0011] Acidosis, as reflected by the BE score, is often the closest measure of risk of compromise, although experience to date is insufficient to provide a precise estimate of risk for any given fetus. This article demonstrates correlations between the FRI and BE scores within cervical dilation and between adjacent cervical dilation (CDx) groups. These correlations are strong enough to justify considering the FRI as a surrogate marker, particularly within the same cervical dilation setting. Combining the information available in the FRI allows inferences about the risk of acidosis at the start of the second stage and also suggests when FSS should be considered. In summary, this represents an improvement over CTG in predicting acidosis and its sequelae.

[0012] Disclosed herein are methods for reducing the risk of and identifying the presence of neurological injury in a human fetus during labor.

[0013] In one embodiment, a method for reducing the risk of neurological injury in a human fetus during labor is disclosed, comprising the steps of:

[0014] Identify the risk of fetal neurological injury during labor by:

[0015] During a first period of a first stage of labor, analyzing fetal blood to determine at least a first base excess (BE) value of the fetus;

[0016] determining a median multiple of the BE value for the first time period by dividing the BE value by a median BE value of a dataset, the dataset comprising a population of fetal BE values established at a time period during the first stage of labor that is the same as the first time period, wherein a predefined multiple of the median (MoM) BE value indicates that the fetus is at risk of neurological injury; and

[0017] Treating the fetus indicated by the identification step as being at risk of neural damage, wherein the treating step comprises intervening in delivery by any conventional treatment measure to reduce or eliminate the risk of neural damage to the fetus.

[0018] In one aspect, said first period of time during labor is characterized by a cervical dilation of 0-3 cm.

[0019] According to another embodiment, a method for reducing the risk of neurological injury in a human fetus during labor is disclosed, comprising the steps of:

[0020] The risk of fetal neurological injury during labor is identified by:

[0021] During a first period of the first stage of labor, analyzing fetal blood to determine at least a first base excess (BE) value of the fetus, wherein a BE value of ≤-5 indicates that the fetus is at risk of neurological damage; and

[0022] Treating the fetus indicated by the identification step as being at risk of neural damage, wherein the treating step comprises intervening in delivery by any conventional treatment measure to reduce or eliminate the risk of neural damage to the fetus.

[0023] In one aspect, said first period of time during labor is characterized by a cervical dilation of 0-3 cm.

[0024] According to a further embodiment, a method for reducing the risk of neurological injury in a human fetus before or during labor is disclosed, comprising the steps of:

[0025] (a) monitoring the fetus for at least a first set of concurrent clinical parameters, the concurrent clinical parameters indicating a current risk level of neurological impairment in the fetus;

[0026] (b) determining a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters at a first time period before or during the first stage of labor, wherein the determined current risk level is expressed as a numerical value (FRI value);

[0027] (c) determining a multiple of a median (MoM) of the FRI value for the first time period by dividing the FRI value by a median FRI value of a dataset, the dataset comprising a population of FRI values established during or before the first stage of labor for the same time period as the first time period, wherein the presence of the risk of neurological injury is indicated when the MoM of the FRI value is a predefined multiple of the median FRI value; and

[0028] (d) treating the fetus indicated by step (c) to be at risk of neural damage, wherein the treating step comprises intervening by any conventional treatment measure before or during delivery to reduce or eliminate the risk of neural damage to the fetus.

[0029] According to one feature, the first time period is a time period during labor characterized by a cervical dilation of 0 cm-3 cm.

[0030] According to another feature, when said step (c) indicates the presence of said risk of neurological damage, said method comprises the further step of analyzing fetal blood to determine at least a base excess (BE) value during at least a second period of time during the first stage of labor.

[0031] According to another aspect, the step of analyzing fetal blood includes performing the analysis at a third time period during the first stage of labor, the third time period being later than the second time point, and determining a base excess (BE) value for at least each of the second and third time periods.

[0032] According to yet another aspect, the first time period during labor is characterized by a cervical dilation of 0-3 cm, and the second and third time periods during labor are each characterized by a cervical dilation of less than 10 cm.

[0033] According to another aspect, the first set of concurrent clinical parameters includes (a) FHR, (b) FHR baseline variability, (c) FHR acceleration, (d) FHR deceleration and (e) maternal uterine activity, and the step of determining the current risk level of neurological injury to the child includes determining whether each of the concurrent clinical parameters (a) to (e) independently exhibits at least one unsafe feature, and converting the number of the concurrent clinical parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature into an indication of the current risk level of the fetus, and the current risk level of the fetus corresponds to the number of the parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature.

[0034] According to yet another embodiment, a method for reducing the risk of neurological injury in a human fetus during labor is disclosed, comprising the steps of:

[0035] The risk of fetal neurological injury during labor is identified by:

[0036] During a first period of a first stage of labor, analyzing fetal blood to determine at least a first base excess (BE) value of the fetus;

[0037] analyzing fetal blood during a second time period of the first stage of labor, the second time period being later than the first time point, to determine at least a second base excess (BE) value of the fetus;

[0038] determining a rate of decrease from the first BE value to at least the second BE value, wherein the rate of decrease, when greater than a predefined value, indicates that the fetus is at risk of neurological damage; and

[0039] Treating the fetus indicated by the identification step as being at risk of neural damage, wherein the treating step comprises intervening in delivery by any conventional treatment measure to reduce or eliminate the risk of neural damage to the fetus.

[0040] According to one aspect, said first period of time during labor is characterized by a cervical dilation of 0-3 cm.

[0041] According to another aspect, the second period of time during labor is characterized by a cervical dilation of less than or equal to 10 cm.

[0042] According to another feature, when the rate of decrease is 46% or higher, it indicates that the fetus is at risk of neurological damage.

[0043] According to yet another embodiment, a method for reducing the risk of neurological injury in a human fetus during labor is disclosed, comprising the steps of:

[0044] The risk of fetal neurological injury during labor is identified by:

[0045] During a first period of a first stage of labor, analyzing fetal blood to determine at least a first base excess (BE) value of the fetus;

[0046] analyzing fetal blood during a second time period of the first stage of labor, the second time period being later than the first time period, to determine at least a second base excess (BE) value of the fetus;

[0047] determining a rate of decrease from the first BE value to the second BE value;

[0048] determining a multiple of median (MoM) of the descent rate by dividing the descent rate by a median descent rate of a dataset, the dataset comprising a population of descent rates of fetal BE values established for a time period identical to the first time period and the second time period during the first stage of labor, wherein when the MoM of the descent rate is a predefined multiple of median descent rate, it indicates that the fetus is at risk of neurological injury; and

[0049] Treating the fetus indicated by the identification step as being at risk of neural damage, wherein the treating step comprises intervening in delivery by any conventional treatment measure to reduce or eliminate the risk of neural damage to the fetus.

[0050] According to one aspect, said first period of time during labor is characterized by a cervical dilation of 0-3 cm.

[0051] According to yet another aspect, the second period of time during labor is characterized by a cervical dilation of less than or equal to 10 cm.

[0052] According to yet another embodiment, a method for identifying the presence of neurological damage in a human fetus during or before delivery is disclosed, comprising the steps of:

[0053] (a) monitoring the fetus for at least a first set of concurrent clinical parameters, the concurrent clinical parameters indicating a current risk level of neurological impairment in the fetus;

[0054] (b) determining, during a first time period during or before labor, a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (FRI value);

[0055] (c) determining a current level of risk of fetal neurological injury based on the first set of concurrent clinical parameters during a second time period during or before labor, the second time period being later than the first time period, wherein the determined current level of risk is expressed as a FRI value;

[0056] (d) determining a rate of decrease from the first FRI value to the second FRI value;

[0057] (e) determining a multiple of a median (MoM) of the FRI value for the first time period by dividing the FRI value by a median FRI value of a dataset, the dataset comprising a population of FRI values established for a time period that is the same as the first time period during or before the first stage of labor, wherein the presence of the risk of neurological injury is indicated when the MoM of the FRI value is a predefined multiple of the median FRI value; and

[0058] (f) determining a MoM for the rate of decline by dividing the rate of decline by a median rate of decline of a dataset, the dataset comprising a population of rates of decline of FRI values established for a time period identical to the first and second time periods during or before the first stage of labor, wherein when the MoM for the rate of decline is a predefined MoM rate of decline, it indicates that the fetus has a neurological injury.

[0059] According to one feature, the first set of concurrent clinical parameters includes (a) FHR, (b) FHR baseline variability, (c) FHR acceleration, (d) FHR deceleration and (e) maternal uterine activity, and the step of determining the current risk level of neurological injury to the child includes determining whether each of the concurrent clinical parameters (a) to (e) independently exhibits at least one unsafe feature, and converting the number of the concurrent clinical parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature into an indication of the current risk level of the fetus, and the current risk level of the fetus corresponds to the number of the parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature.

[0060] According to another feature, the second time period is at most one hour later than the first time period.

[0061] According to yet another feature, when step (b) and / or step (c) indicates the presence of the risk of neurological damage, the method comprises the further step of analyzing fetal blood for at least a third time period during or before the first stage of labor to determine at least a base excess (BE) value.

[0062] In another embodiment, a method for reducing the risk of neurological injury in a human fetus during labor is disclosed, comprising the steps of:

[0063] (a) monitoring at least a first set of concurrent clinical parameters of the fetus, the concurrent clinical parameters indicating a current risk level of neurological impairment in the fetus;

[0064] (b) determining, during a first time period during or before labor, a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (FRI value);

[0065] (c) determining a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters during a second time period during or before labor, the second time period being later than the first time period, wherein the determined current risk level is expressed as a FRI value;

[0066] (d) determining a rate of decrease from a first FRI value to a second FRI value, wherein when the rate of decrease is greater than a predefined value, it indicates that the fetus is at risk of neurological damage; and

[0067] Treating the fetus indicated by the identification step as being at risk of neural damage, wherein the treating step comprises intervening in delivery by any conventional treatment measure to reduce or eliminate the risk of neural damage to the fetus.

[0068] According to one feature, said first period of time during labor is characterized by a cervical dilation of 0 cm-3 cm.

[0069] According to further features, the second period of time during labor is characterized by a cervical dilation of less than or equal to 10 cm.

[0070] According to yet another feature, when the decrease rate is 46% or higher, it indicates that the fetus is at risk of neurological damage.

[0071] Also disclosed are apparatuses for performing the methods of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0072] The present invention will be understood from the following description and accompanying drawings, in which:

[0073] Figure 1 Figure 2 illustrates the sensitivity of the test to achieve BE values below -12 mMol / L at various cervical dilations, obtained from infant population data.

[0074] Figure 2 The FRI scores are shown in Figure 2. Figure 1 The same data were obtained under the same cervical dilation conditions.

[0075] Figure 3 The decrease in BE and FRI scores during the first stage of labor is depicted graphically (box plots).

[0076] Figure 4 The decrease in the median BE value during the first stage of labor is depicted.

[0077] Figure 5 Schematic diagram of the model showing the significance of the variables of initial BE value and its rate of decline in association with the risk of acidemia.

[0078] Figure 6 The sensitivity and specificity of the previously obtained initial BE value and BE decline rate were compared using receiver operating characteristic (ROC) analysis.

[0079] Figure 7 Table 2 summarizes the logistic regression analysis for predicting membership in the lowest 30% of BE scores at the start of the second stage of labor.

[0080] Figure 8 Table 2 summarizes the logistic regression analysis for predicting membership in the lowest 30% of pH readings at the start of the second stage of labor.

[0081] Figure 9 Schematic diagram of the model showing the significance of the initial BE value and its rate of decline as variables associated with the risk of acidemia.

[0082] Figure 10 is a schematic diagram of the second model, showing the significance of the variables of initial FRI score, FRI score decline rate, initial BE value, and BE decline rate in association with the risk of acidemia.

[0083] Figure 11 The ROC curve analysis of the initial BE reduction rate (i.e., the reduction rate between the first BE value and the second BE value) is depicted. The straight line represents the corresponding relationship, i.e., the connection, between sensitivity and specificity.

[0084] Figure 12 Plots of BE value versus cervical dilation and postpartum time are depicted for each of the 25th, 50th, and 75th percentiles of BE value measurements.

[0085] Figure 13 Plots of BE value versus cervical dilation and postpartum time are depicted for each of the 10th (lowest line), 20th (second line from the bottom), 30th (third line from the bottom), 40th (second line from the top), and 50th (upper line) percentiles of BE value measurements.

[0086] Figure 14 Depicted are graphs of BE values versus cervical dilation and postpartum time, and FRI scores for the 90th percentile of BE value measurements.

[0087] Figure 15 Depicted are graphs of BE values versus cervical dilation and postpartum time, and FRI scores for the 75th percentile of BE value measurements.

[0088] Figure 16 Depicted are graphs of BE values versus cervical dilation and postpartum time, and FRI scores for the 25th percentile of BE value measurements.

[0089] Figure 17 Depicted are graphs of BE values versus cervical dilation and postpartum time, and FRI scores for the 10th percentile of BE value measurements.

[0090] Figure 18The median and lowest quartiles of BE and FRI throughout the active phase of labor are depicted.

[0091] Figure 19 The median and lowest quartiles of pH and FRI throughout the active phase of labor are depicted.

[0092] Figure 20 The median and lowest quartiles of BE and pH throughout the active phase of labor are depicted.

[0093] Figure 21 is a schematic diagram of an exemplary configuration of an apparatus for carrying out the method of the present invention.

[0094] Figure 22 is a schematic diagram of a second exemplary configuration of an apparatus for carrying out the method of the present invention.

[0095] Figure 23 is a schematic diagram of an embodiment of an apparatus for carrying out the method of the present invention for providing remote monitoring and / or feedback. DETAILED DESCRIPTION

[0096] Methods and apparatus for reducing the risk of neurological injury in a human fetus during labor are described below. These methods and apparatus are based on the analysis of a dataset of fetal scalp samples, all of which were obtained during the first stage of labor, as described below. More specifically, the analysis involves converting certain results into nonparametric "multiples of the median" (MoM). By using the MoM, the degree of deviation from the median at a discrete point—here, the amount of cervical dilation at a specific time—is used as an independent variable to predict the likelihood of neurological injury risk.

[0097] As required, specific embodiments of the present invention are disclosed herein. However, it should be understood that the disclosed embodiments are merely examples of the present invention, and the present invention may be implemented in various forms and alternative forms. The drawings are not necessarily drawn to scale, and some features may be enlarged or reduced to show details of specific components. Therefore, the specific structural and functional details disclosed herein should not be interpreted as limiting, but merely as a representative basis for teaching those skilled in the art to use the present invention in various ways.

[0098] As used herein, "child" is intended to include a human child prior to birth (i.e., a child as a fetus) and a human child after birth (i.e., a newborn). The terms "fetus" and "child as a fetus" are used interchangeably, as are the terms "newborn" and "infant." In this context, "child" also refers to a child as a fetus and a newborn.

[0099] As used herein, "base excess" (BE) refers to the amount of base or acid that must be added to a newborn's blood to restore 1 liter of blood to a physiological level of 7.4 at 98.6°F (37°C) and a pCO2 of 40 mmHg. A BE below average is unsafe, and values ≤ -12 mMol / L are considered to carry a high risk of neurological damage.

[0100] As used herein, "computer" refers to a device that can store, retrieve, and process data, including any general-purpose computer, handheld computing device (e.g., smartphone, tablet, laptop, etc.), and / or special-purpose computer.

[0101] Fetal monitoring

[0102] In an exemplary embodiment of the invention described herein, at least a first set of parameters of a patient are monitored during labor and delivery, and these parameters are used to determine the risk level of neurological injury in the child. These parameters include multiple variable dynamic parameters related to EFM, including (a) baseline FHR, (b) FHR baseline variability, (c) FHR acceleration, and (d) FHR deceleration. Optionally, these parameters also include a dynamic parameter (e) maternal uterine activity (i.e., uterine contractions) related to intrauterine activity ("IUA"). In this case, the monitored patient refers to the mother and / or fetus, depending on the monitored parameters. In an exemplary embodiment, these monitored parameters are assessed as safe or unsafe based on the characteristics listed in Table 1 below.

[0103] Table 1 - EFM and IUA variables

[0104]

[0105] Optionally, the monitored parameters may also include certain additional maternal, obstetric, and fetal risk ("MOFR") factors (separate from the EFM variables), as follows: (f) maternal risk factors, (g) obstetric risk factors, (h) fetal risk factors (separate from EFM). According to this embodiment, parameter (f) of "maternal risk factors" includes the following unsafe characteristics:

[0106] 1) Decreased cardiac output / decreased placental vascular perfusion

[0107] a. Heart disease with a risk of decreased cardiac output during pregnancy

[0108] b. Hypertension (chronic hypertension and pregnancy-induced hypertension)

[0109] c.SLE (systemic lupus erythematosus), etc.

[0110] 2) Oxygen carrying capacity

[0111] a. Lung diseases (such as asthma)

[0112] b. Anemia and hemoglobinopathy

[0113] 3) Infection (chronic infection and acute infection)

[0114] 4) Chronic debilitating diseases

[0115] 5) Malabsorption / Poor Weight Gain

[0116] 6) Endocrine disease - diabetes and thyroid disease

[0117] 7) Older mothers

[0118] 8) Substance abuse, addiction, and smoking

[0119] 9) Obesity – BMI (body mass index) > 35

[0120] 10) Short stature (≤5'2")

[0121] 11) Epidural anesthesia

[0122] According to this embodiment, the parameter (g) of "obstetric risk factors" includes the following unsafe features:

[0123] 1) IUGR (intrauterine growth restriction) / macrosomia

[0124] 2) Oligohydramnios

[0125] 3) Polyhydramnios

[0126] 4) Bleeding and premature abruption

[0127] 5) Previous cesarean section

[0128] 6) Placental and umbilical cord abnormalities

[0129] 7) Rupture of membranes (PPROM – preterm labor or premature rupture of membranes, SROM – spontaneous rupture of membranes, AROM – artificial rupture of membranes)

[0130] 8) Dystocia (prolonged labor and labor arrest)

[0131] 9) Malposition of the fetus

[0132] Finally, according to this embodiment, the parameter (h) of "fetal risk factor" includes the following unsafe features:

[0133] 1) Abnormal Doppler / BPP (physiological assessment)

[0134] 2) Genetic diseases

[0135] 3) Fetal arrhythmia

[0136] 4) Meconium discharge

[0137] 5) Chorioamnionitis

[0138] 6) Second stage of labor – pushing

[0139] 7) Amnioinfusion

[0140] 8) Withdrawal of oxytocin due to fetal intolerance

[0141] 9) Conversion mode (acute sustained tachycardia (>170 bpm))

[0142] 10) Ominous overshoots

[0143] 11) Bradycardia (<100 bpm)

[0144] 12) Loss of important data during labor (e.g., missing EFM of the second stage of labor)

[0145] Interpretation of the various parameters described above can be performed conventionally, including, optionally, using the methods disclosed by the inventors in U.S. Patent No. 9,131,860 and published U.S. Application 2019 / 0274618. More specifically, according to one embodiment disclosed in those references, the method most generally includes determining whether each monitored or assessed parameter independently exhibits at least one unsafe feature, e.g., the unsafe features described above; and obtaining an indication of the current risk level, referred to as a "fetal reserve index" (FRI) score, the risk level corresponding to the number of these parameters that simultaneously and independently exhibit at least one unsafe feature / the number of these parameters that exist simultaneously and independently. According to this exemplary method, the number of parameters that simultaneously and independently exhibit at least one unsafe feature, on the one hand, and the indication of the current risk level of neurological damage, on the other hand, are directly related. Thus, for example, according to a method in which parameters (a) to (e) are monitored, the highest level of risk of neurological injury corresponds to the simultaneous, independent manifestation of at least one unsafe characteristic in the patient for each of parameters (a) to (e) / the simultaneous, independent presence in the patient, while the lowest level of risk of neurological injury corresponds to the absence of any manifestation of any unsafe characteristic for any of these parameters / the absence of any of these parameters in the patient.

[0146] It should be understood that parameters (a) through (e) are dynamic parameters; that is, they may change in either direction during the monitoring process (e.g., from normal or safe, to abnormal or unsafe, and then back again). On the other hand, MOFR parameters (f) through (h) are unidirectional in nature; that is, they will negatively affect the FRI score once (if) they occur (whether during or before delivery). It should also be understood that, according to exemplary embodiments, the presence of an unsafe characteristic for each of parameters (f) through (h) is sufficient to negatively affect the FRI score. For example, parameter (f) of "Maternal Risk Factors" need not exhibit more than one of the 11 exemplary unsafe characteristics listed above.

[0147] In the context of the present disclosure, "simultaneously" means at exactly the same time point, or at least overlapping time points during labor when determining the safety / unsafety of each monitored parameter. In an exemplary embodiment, this risk assessment is performed at 20-minute intervals, consistent with determining the safety / unsafety of IUA parameter (e).

[0148] In the context of this disclosure, "independent" means that the presence / absence of one or more unsafe characteristics by each monitored parameter will affect the determination of the current risk level, regardless of the presence / absence of one or more unsafe characteristics by any other monitored parameter. In other words, while the presence / absence of each monitored parameter will collectively affect the determined current risk level, each monitored parameter is considered independent of the other parameters in terms of exhibiting safe / unsafe characteristics.

[0149] The FRI score is derived as follows: if each monitored parameter is considered normal (i.e., safe), a first numerical value (e.g., "1") is assigned to the parameter (e.g., (a) to (h)), and if the parameter is considered abnormal (i.e., unsafe), a second numerical value (e.g., "0") is assigned to the parameter. The first and second numerical values for each parameter are the same. That is, only two values (e.g., 1 or 0) are used. The FRI score of this embodiment is calculated based on the number of points divided by the number of parameters involved (e.g., 5) and multiplied by 100 to obtain a percentage. For example, a total of 5 monitored parameters ((a) to (e)) will produce a FRI score, which is calculated by dividing the number of points by 5 and multiplying by 100 to obtain a percentage. Normality of all five parameters ((a) to (e)) would result in a FRI score of 100% (5 / 5), while loss of points - as a function of the presence of abnormalities or unsafe characteristics in any of the monitored FRI parameters (a) to (e) - would result in FRI scores of 80% (4 / 5), 60% (3 / 5), 40% (2 / 5), 20% (1 / 5) and 0% (0 / 5). Alternatively, normality of all eight parameters ((a) to (h)) would result in an FRI score of 100 (8 / 8), while a loss of points—as a function of the presence of abnormalities or unsafe characteristics in any of the monitored FRI parameters (a) to (h)—would result in FRI scores of 100% (8 / 8), 87.5% (7 / 8), 75.0% (6 / 8), 62.5% (5 / 8), 50.0% (4 / 8), 37.5% (3 / 8), 25.0% (2 / 8), 12.5% (1 / 8), and 0% (0 / 8).

[0150] The current level of risk of neurological injury is identified by considering each parameter (when present) independently of the other parameters. Thus, the scheme for identifying the current risk level within the scope of the present invention is not the result of any interdependence between parameters, as is the case with some conventional methods, but is strictly a function of the number of parameters that are present in the patient and / or that exhibit unsafe characteristics simultaneously but independently. Consistent with the foregoing, this method is also distinguished in that it does not consider the degree of unsafety indicated by one or more characteristics of any monitored parameter. Instead, preferably, the parameters are equally weighted so that any unsafe manifestation of a predetermined unsafe characteristic according to the parameters (e.g., (a) to (e) or (a) to (h)) will cause each such parameter to contribute equally to the currently determined risk level.

[0151] Exemplary embodiments also contemplate that the methods of the present invention include assigning predefined risk categories to children, wherein the predefined risk categories correspond to determined current risk levels. For example, the current risk level for neurological damage can be identified by a specific FRI score and / or an easily interpretable scale as described above. For example, but not limited to, the "scale" of the embodiments takes the form of arbitrary color areas, similar to traffic lights. In the embodiments of the present disclosure, the lowest current risk level is identified as a "green zone" and includes FRI scores of >50%. Increased current risk levels for the fetus (relative to the lowest level) are identified as a "yellow zone" and include FRI scores of ≤50% and >26%. The highest current risk level is identified as a "red zone" and includes FRI scores of ≤25%. The lower the score, the greater the risk of acidosis and adverse outcomes.

[0152] Experimental data

[0153] From a dataset of FHR tracings and BE values from fetal scalp samples (both collected during the first stage of labor), a fetal reserve index (FRI) score was derived and analyzed together with BE measurements taken at corresponding times during labor. Using the available measurements from this dataset, the FRI score was calculated according to the methods described above and the disclosures of U.S. Patent 9,131,860, published international application WO / 2020 / 102524, and published international application WO / 2018 / 094398. Evaluation of historical fetal and neonatal data corresponding to a variety of parameters (e.g., FHR, NHR, pH, base excess, etc.) validated the inventors' hypotheses and demonstrated the utility of the present invention in reducing the risk of neurological damage to the fetus.

[0154] More specifically, data from 475 high-risk, term singleton pregnancies were used to assess the relationship between FRI and EFM tracing, delivery process, and neonatal outcomes in the first hour after birth. These data were collected in the 1970s, mostly at the University of Southern California Los Angeles County Hospital and some at Yale New Haven Hospital. Each case was supervised by an attending physician in the MFM department. The monitoring strip had five data lines (EFM, contraction pattern, extension variability tracing, maternal respirations, and maternal heart rate). After delivery, continuous neonatal heart rate (NHR), respirations, ECG, and blood pressure from an indwelling catheter, pH, and umbilical artery core blood (CB) blood pressure and pO2 analysis were performed. Scalp sampling, its results (e.g., pH, base excess, pO2), blood pressure, medications administered, anesthesia provided, and other relevant data were contemporaneously annotated throughout the record. Antenatally, scalp sampling was performed as directed and recorded on the monitoring strip. After birth, umbilical cord gas was typically obtained at 1, 4, 8, 16, 32, and 64 minutes. Neonatal observations included: Apgar scores at 1 and 5 minutes, NHR with return to predelivery rate and responsiveness over time, and umbilical artery pH, BE, and pO2. Most of these records had all of the above measurements.

[0155] All monitoring is initiated in the presence of ruptured membranes with placement of fetal scalp electrodes (FSE) and an intrauterine pressure catheter (IUPC). The NHR is recorded continuously—similar to the intrapartum FHR.

[0156] For further analysis, the results of the FRI score were divided into three groups. As described above, the lowest risk level was identified as the "green zone" and included FRI scores of >50%; the increased current risk level of the fetus (relative to the lowest level) was identified as the "yellow zone" and included FRI scores of ≤50% and >26%; the highest risk level was identified as the "red zone" and included FRI scores of ≤25%. Approximately 10% of the cases in the evaluation records were in the red zone, 30% of the cases were in the yellow zone, and 60% of the cases were in the green zone. Table 2 below summarizes the relevant characteristics of the above sample population.

[0157] Table 2

[0158]

[0159] From these data, it was determined that both the FRI score and the BE value worsened (i.e., decreased) as labor progressed and the fetus was subjected to more stress. On this basis, the inventors demonstrated that a given measurement taken early in labor could have a very different meaning than the same measurement taken later (e.g., in the second stage of labor).

[0160] These data were analyzed by their actual measured values—i.e., the BE values themselves—as well as their means and standard deviations. They were also converted to nonparametric “multiples of the median” (MoM) rather than parametric means and standard deviations. By using the MoM, the degree of deviation from the median at a discrete point—here defined as the amount of cervical dilation at a specific time—served as an independent variable to predict the likelihood of having a cord blood BE of ≤12 mMol / L (a definition of risk for metabolic acidosis). Based on this measure, a -7 BE at a cervical dilation of 4 cm was more likely to be less than -12 BE mMol / L in late pregnancy or cord blood than the same -7 BE mMol / L reading at a cervical dilation of 10 cm (i.e., during the second stage of labor). The actual measurements of these data confirmed this conclusion.

[0161] Data analysis showed that mean fetal scalp sample (FSS) BE and pH values (median and mean) decreased gradually during the first stage of labor with a nearly linear slope (p < .000 for the difference in means and the significance of the linear component by ANOVA). Both median BE and pH decreased with increasing cervical dilation. The decrease in BE and pH during the first stage of labor generally began gradually and decreased more rapidly as full cervical dilation approached. The decrease accelerated during labor until four minutes after delivery.

[0162] A more detailed discussion of the above analysis results follows:

[0163] refer to Figure 1 , shows a graph depicting the percentage of infants in a particular population in the data set who had BE values below -12 mMol / L at cervical dilations of 4 cm-5 cm, 6 cm-7 cm, and 8 cm-9 cm. Specifically, the bottom line plots the results for the population of infants in the data set whose metabolic acidosis screened positive at 20%, while the top line plots the results for the population of infants in the data set whose metabolic acidosis screened positive at 40%. As shown, at a cervical dilation of 4 cm-5 cm, 40% of infants from the 20% screening-positive population exhibited BE values below -12 mMol / L, while 80% of infants from the 40% screening-positive population exhibited such a score. For the 20% screening-positive population, this percentage increased to approximately 60% at a cervical dilation of 8 cm-9 cm. For the 40% screening-positive population, this percentage was approximately 80% at a cervical dilation of 8 cm-9 cm.

[0164] Next reference Figure 2 , under the same cervical dilation (ie 4cm-5cm, 6cm-7cm, 8cm-9cm) conditions, the calculated infant FRI score was used instead of the BE value. Figure 1The same data set was analyzed in . In this figure, the bottom line plots the results for the population of infants in the data set where 20% of infants screened positive for metabolic acidosis, while the top line plots the results for the population of infants in the data set where 40% of infants screened positive for metabolic acidosis. Although the FRI score was not as good as the BE result (the BE result is a direct measure of fetal acidosis, as opposed to the FRI, which is an indirect predictor of fetal acidosis), it showed a parallel pattern with the BE result.

[0165] Now refer to Figure 3 , assessed the decline in BE and FRI scores during the first stage of labor (i.e., between 0 cm and 10 cm of cervical dilation). Figure 3 The box plot shows the middle 50% of scores, with brackets around them representing the 99th percentile. Some outliers can be seen in certain dilation categories. These data suggest that fetal acidosis gradually increases during labor—possibly because the fetus is in prolonged uterine contractions.

[0166] The above data were then converted from parameter means and standard deviations to MoMs for each expansion cohort. Because the baseline shifts with expansion, the MoM for any given BE measurement will vary based on expansion. However, this allows for standardized interpretation as a function of MoM values without the need for constant manual adjustment for expansion.

[0167] The MoM score reflects downward progression (ie, MoM increases as the score gets worse).

[0168] It is important to note that the raw BE values are negative. Because FRI scores are positive, the results presented in this article arbitrarily use positive numbers as the MoM for BE. Otherwise, it would be very confusing to have the MoMs (FRI and BE) progress in different directions. Furthermore, for most clinicians, the significance of a difference is easier to visualize with numbers greater than 1 than with negative numbers.

[0169] Table 3: MoM conversion of fetal scalp BE scores

[0170]

[0171] As can be seen in Table 3 above, at early dilation (e.g., 0 cm-3 cm), a raw BE value of -8 (left column) is close to twice (negative) the mid-point (MoM of 2.0), and therefore the risk implied by this value is relatively high. On the other hand, later in the labor process, a raw BE value of -8 is "normal" in the sense that it is very close to the mid-point (MoM of 1.1).

[0172] Using median comparisons, BE decreased by 46% from 0-3 cm to 10 cm dilation. The reduction in mean values was very similar and linear, with a proportional decrease of 38%. Figure 4 .

[0173] Using the proportional median BE decrease of 46% during cervical dilation from 0 cm to 3 cm to 10 cm (see Table 3), a simple equation X = (0.46)(-12) indicates that when the cervix is dilated from 0 cm to 3 cm and the BE value is -5.52 or greater, on average, there is a high risk of a BE value of -12 at birth.

[0174] The corresponding figures derived from the mean decreases indicate that the mean BE at birth would decrease to -12 when the BE value is at least -4.56 or worse at a cervical dilation of 0 cm to 3 cm.

[0175] This new score (hereafter referred to as the "Initial Decline Rate" (IDR) or "Initial Decline Trajectory") will help provide an early warning of the risk of acidemia at birth (operationalized as a BE of -12 mMol / L on an umbilical cord gas reading at birth). In this analysis, the first scalp sample reading (BE1) and the proportional decrease in BE from the first to the second scalp sample reading (BE_Drop_1_2) were used as variables of interest. Table 4 below shows the logistic regression output:

[0176] Table 4: Logistic regression results of BE variables

[0177]

[0178] Logistic regression focuses on the logit, which is the natural logarithm of the odds of the outcome occurring (in this case, the odds of being exposed to acidemia at birth). B(β) represents the change in the logit for each unit change in the predictor variable. If both predictors are equal to 0, the constant represents the log odds of acidemia.

[0179] In Table 4, Exp(B)'s are B's converted to odds ratios, where the other variables in the regression equation remain constant. An odds ratio less than 1 indicates that the outcome becomes less likely as the predictor variable increases, while an odds ratio greater than 1 indicates that the outcome becomes more likely as the predictor variable increases.

[0180] Table 4 shows that the initial BE level and its trajectory, as reflected by the decline in BE levels from the first to the second reading, are important in predicting the risk of acidemia at birth: as BE values become more negative, the risk of acidemia at birth increases; similarly, when the initial BE level is controlled, the greater the rate of decline in BE between the first and second scalp sampling, the greater the risk of acidemia at birth. These findings can be graphically represented as Figure 5 shown.

[0181] Summary Figure 5 The model in [ ] is useful for visualizing the nature of the effects of variables deemed sufficiently important in the model. The model as a whole can be evaluated both empirically and conceptually. From an empirical perspective, the Hosmer-Lemeshow test (if significant) tells us whether something truly important has been left out of the equation. Here, it is significant (< 0.02), suggesting that the model is incorrect and that examining it from both clinical and theoretical perspectives would be fruitful.

[0182] The second empirical approach is to look at an analogy of R-squared, called the Nagelkerke R-squared. Its value is 0.32, indicating that approximately one-third of the variance in BE values dichotomized at birth (risk of acidemia) can be explained by these two variables alone. Internally, both variables (BE1 and the proportion of the decline from BE1 to BE2) are highly significant.

[0183] These empirical results can be further investigated in several ways. One is by looking at the summary classification table, see Table 4 below.

[0184] Table 4: Classification of MoM conversions

[0185] FRI and BE scalp sample readings for acidosis risk at birth

[0186]

[0187] In Table 4, the "Sensitivity" (true positives / (true positives + false negatives)) is 32%; the "Specificity" (true negatives / (true negatives + false positives)) is 98%; the "Positive Likelihood Ratio" (sensitivity / 1-specificity) is 23 [this is a single statistic measured using the coordinates of the ROC (receiver operating characteristic) curve - and this equation has a large difference between true and false positives]; the "Negative Likelihood Ratio" (1-sensitivity / specificity) is 0.70; the PPV (true positives / all cases that tested positive) is 81%; the NPV (true negatives / all cases that tested negative) is 88%; and the Accuracy = (true positives and true negatives) / total is 88%.

[0188] It is important to note that in samples that do not accurately reflect the population distribution, the interpretation of PPV and NPV must be cautious. If the incidence of the outcome is higher than the population, the actual PPV will be higher than expected.

[0189] Next reference Figure 6, ROC curve analysis was used to compare the above results. This was achieved by saving the predicted probabilities from the logistic regression analysis and using them as predictor variables in the ROC analysis. The area under the curve was 0.82 (significance < 0.000), reflecting that early BE readings, and the rate at which these readings decline as birth approaches, are important factors in predicting the risk of acidemia at birth.

[0190] Correlations between untransformed FRI and BE scores were also calculated within the same cervical dilation group and between adjacent CxD groups. The results are shown in Table 5 below. In Table 5, the following symbols indicate the significance level: ^ = <.05; * = <.01; ** = <.001; *** = <.000. These correlations are strong enough to justify considering FRI as a surrogate marker, especially when the cervical dilation is the same. In the late first stage of labor, the associations between FRI and BE and pH showed a modest upward trend, indicating that the change in scores increases as changes begin to occur.

[0191] Table 5

[0192]

[0193] Multiple regression analysis was used to refine these associations to include information about FRI levels and their trajectories over the preceding time period. Table 6 below shows the BE results for regression analysis of FRI and FRI decline within grouped cervical dilations. Four analyses are presented in this table. Row 1 analyzes BE levels at 6-7 cm dilation; row 2 analyzes the decline in BE at two points (i.e., from 4-5 cm dilation to 6-7 cm dilation); the next two rows repeat this analysis for BE at 8-9 cm dilation and for the decline in BE from 6-7 cm dilation to 8-9 cm dilation.

[0194] Table 6

[0195]

[0196]

[0197] 38 cases had fetal scalp sample readings at 4cm-5cm and 6cm-7cm. Only FRI was used 4-5cm And the FRI decreased from readings at 6-7 cm to 4-5 cm with an R of .50 (p < .007). 4-5cm The coefficient approaches significance (<.099), but the decrease in FRI between the two consecutive ranges is highly significant (p <.002). Again, we predict that the degree of BE decrease can itself be a management tool. 4-5cmThe coefficient did not reach significance (β = .10, p < .526), but the FRI trajectory was highly significant (β = -.48, p < .005).

[0198] Thirty-five cases had FSS at both 6-7 cm and 8-9 cm. Repeating this analysis, the corresponding decline and the initial FRI variable yielded a multivariate R of .69. The initial level of 6-7 cm and the decline from 6-7 cm to 8-9 cm were highly significant. Correlation and regression analyses designed to simultaneously predict BE were compatible.

[0199] After successfully predicting BE levels within and between adjacent cervical dilations, we evaluated the relationship between FRI scores (level and trajectory) during the first stage of labor and the risk of being in the lowest 30% of BE scores at the start of the second stage of labor. Using logistic regression equations, we analyzed the two sources of information derived from cervical dilations of 5 cm to 7 cm. Figure 7 These results for BE are shown; Figure 8 These results for pH are shown. In summary, the decrease was 50% at 4 to 10 cm cervical dilation, 41% at 5 cm cervical dilation, and 27% at 6 and 7 cm cervical dilation. In each comparison, a minority of cases actually improved (approximately 10%).

[0200] In front Figure 7 and Figure 8 In the equation: "FRI5" represents the FRI measured near the beginning of the period defined by cervical dilation to 5 cm; "FRI10-5chg" represents the difference between the FRI at 10 cm dilation and the FRI at 5 cm dilation; "PIOI" represents the predicted low BE and the observed low BE; "PhOh" represents the predicted high BE and the observed high BE; "B's" in the equation represent the natural logarithm of the change in the probability of being in the low BE category for a unit change in the independent variable. There are two independent variables here, the initial FRI score at a certain dilation and the degree of change in FRI between this dilation and 10 cm dilation. In addition, "N's R 2 ” represents the R derived from ordinary least squares regression 2 Nagelkerke approximation of ; "HL" is the abbreviation for the Hosmer Lemshaw coefficient. Nagelkerke R 2 The more significant the better; the less significant the Hosmer-Lemeshow coefficient the better (because it indicates that something important is not missing from the model).

[0201] The larger question is to what extent the log odds of being in the lowest 30% of BE cases at the start of the second stage of labor can be predicted. The equations for cervical dilation (CD) values of 5-7 all have sufficiently large N's and are consistent and highly significant in their estimates. The higher the initial FRI score, the less negative the trajectory, and the less likely the fetus is to be in the lowest 30%. Figure 9 ROC curve analysis confirmed the potential utility of this method as a screening tool to assess the risk of acidosis at the beginning of the second stage of labor.

[0202] Surprisingly, the impact of intrauterine resuscitation (IR) was considered Figure 5 In the model (which assessed the extent to which IR use had additive and / or interactive effects when paired with the base excess variable), neither additive nor interactive terms combined with BE1 or BE decline added anything to the analysis; none of the additive coefficients were significant. Of note, this raises questions about IR in practice, as using IR as a strategy to address fetal blood oxygenation problems is an obvious choice. However, observing the correlation between BE1 and IR use (r = 0.08) or between BE decline and IR use (r = -0.06) revealed little correlation, suggesting that the treating physician's decision to use IR is not influenced by BE1 levels or their fluctuations over short periods of time.

[0203] Tables 7 and 8 below show the results of further introducing the fetal reserve index (FRI) assessment into the acidosis risk model.

[0204] Table 7: Regression results of the acidosis risk model including BE, FRI, and IR

[0205]

[0206]

[0207] Table 8: Summary of the models in Table 4 and their observed characteristics

[0208] Equation prediction <-12BE Normal BE <-12BE 15 8 23 Normal BE 38 287 325 53 295 348

[0209] In the above table, "Sensitivity" (true positive / (true positive + false negative) is 17%; "Specificity" (true negative / (true negative + false positive) is 97%; positive likelihood ratio (sensitivity / 1-specificity)) is 10.44; "Negative likelihood ratio" (1-sensitivity / specificity) is 0.88; PPV (true positive / all cases that test positive) is 65%*; NPV (true negative / all cases that test negative) is 88%; and "Accuracy" (true positive and true negative) / total is 87%.

[0210] These characteristics are very good, except for the low sensitivity. The overall R squared simulation is not significantly different from the earlier model (R squared = 0.33), but the Homer-Lemeshow statistic (sig < 0.63) suggests that the model does not miss much.

[0211] Figure 9 Expressed Figure 5 A variation of the model shown that additionally includes the FRI score.

[0212] It is also possible to construct a model without scalp-sampled BE readings—an approach that has fallen out of favor over the past few decades. These results are presented in Table 9. Although the amount of variance explained (R-squared simulated = 0.11) is about one-third that of the comprehensive model, the patterns are very similar.

[0213] Table 9: Regression results of the acidemia risk model including FRI and IR

[0214]

[0215] Figure 10 Expressed Figure 9 A variation of the model shown that does not include BE data.

[0216] The combined IR had both an additive and interactive effect (combined with a decrease in FRI) in reducing the risk of acidemia at birth, but a decrease in FRI itself had no additive effect. Regarding the characteristics of the model presented as a classification table (Table 10), the sensitivity was very low, but the PPV was much better.

[0217] Table 10: Classification table and test characteristics of the model in Table 6 Observed

[0218] Equation prediction <-12BE Normal BE <-12BE 2 2 4 Normal BE 52 293 345 54 295 349

[0219] In the foregoing, "Sensitivity" (true positives / (true positives + false negatives) is 4%; "Specificity" (true negatives / (true negatives + false positives) is 99%; positive likelihood ratio (sensitivity / 1-specificity)) is 5.46; negative likelihood ratio (1-sensitivity / specificity) is 0.97; PPV (true positives / all cases that test positive) is 50%*; NPV (true negatives / all cases that test negative) is 85%; accuracy (true positives and true negatives) / total is 85%.

[0220] Next go to Figure 11 , which shows the ROC curve describing the comparison of acidemia (cord blood). The following Table 11 summarizes Figure 11 The area under the curve.

[0221] Table 11

[0222] Area under the curve

[0223] Test outcome variable: predicted probability

[0224]

[0225] a. Under nonparametric assumptions

[0226] b. Null hypothesis: True area = 0.5

[0227] Next reference Figure 12 BE values are represented by three lines: the 75th (top line), 50th (middle line), and 25th (bottom line) percentiles of BE measurements at given dilation, cord blood, and postpartum time (from early labor to the second stage of labor, delivery, and 1 hour postpartum). The BE values create three parallel lines of variation. Importantly, the IDR (not shown) can be used to predict early in labor the likelihood that the fetus / infant will reach a high-risk acidemia level that puts them at risk for injury and compromise. Enhanced assessment of acidemia risk may lead to changes in obstetric care, such as earlier initiation of IR and potentially transfer of patients to a high-risk center early in labor, when such transfer is feasible.

[0228] Also refer to Figure 13 Further analysis of the lower portion of the curve shows that for the 10th percentile (the bottom line), the BE (based on cord blood) at birth is -12.5—entering the risk zone. The BE then plummets to -14.5 over the next four minutes and remains in the risk zone until the 16th minute. This is the period of greatest risk for harm to the infant. By definition, 9% of cases are actually worse than this.

[0229] The data presented here demonstrate that the FRI (an indirect assessment of acidemia risk) is significantly associated with BE, which could help inform immediate recommendations about which patients should undergo fetal scalp or other fetal blood sampling for analysis of BE. These data also suggest that both outcomes (BE and FRI) could predict the level of fetal risk and allow for earlier intervention than is currently possible.

[0230] To confirm the above, Figure 14-17 Three graphs are depicted showing the 90th, 75th, 25th, and 10th percentiles of BE results at different cervical dilations and time periods (the lowermost line in each graph), plotted against the FRI results for these same data (the uppermost line in each graph). Again, these data suggest that the FRI score (uppermost line) could be used as a screening test early in labor to decide who should undergo fetal scalp sampling for BE values (lowermost line).

[0231] In further confirmation of the above, Figure 18BE and FRI values were plotted at cervical dilations 4-5 (leftmost point on the X-axis), 6-7, 8-9, 10, and at birth (rightmost point on the X-axis). The graphs show the median BE value, the lowest quartile of BE values, the median FRI score, and the lowest quartile of FRI scores. It is noteworthy that the FRI score was Figure 18 The FRI score is displayed as a score from 0 to 1, where 1 represents a FRI score of 100.

[0232] Similarly, Figure 19 The FRI scores and pH measurements at cervical dilations 4-5 (leftmost point on the X-axis), 6-7, 8-9, 10, and birth (rightmost point on the X-axis) are shown. The graphs show the median pH, the lowest quartile of pH, the median FRI score, and the lowest quartile of FRI score measurements. Of note, the FRI score at Figure 19 The FRI score is displayed as a score from 0 to 1, where 1 represents a FRI score of 100.

[0233] at last, Figure 20 pH and BE measurements are shown at cervical dilations 4-5 (leftmost point on the X-axis), 6-7, 8-9, 10, and birth (rightmost point on the X-axis). The graphs show the median BE value, the lowest quartile BE value, the median pH score, and the lowest quartile pH score measurements.

[0234] Acidosis, as reflected by the BE value, is generally the closest approximation to determining the risk of injury, although experience to date is insufficient to provide a precise estimate of risk for any given fetus. The MoM classification makes immediate risk assessment more understandable. The addition of a trajectory improves the accuracy of the progression of risk levels. Because serial BE or pH measurements are rarely available from early labor onward, especially before the active phase of labor (<6 cm), the FRI and its trajectory appear to be a reasonable surrogate. Combining the available information in the FRI allows inferences about the risk of acidosis at the onset of the second stage of labor and may also suggest when to consider FSS. In summary, this is an improvement over CTG in predicting acidosis and its sequelae.

[0235] These results support several approaches for identifying and reducing the risk of fetal neurological injury.

[0236] A first such method includes analyzing fetal blood during a first time period during labor (e.g., when the cervix is 0-3 cm dilated), determining at least a first base excess (BE) value for the fetus; and then determining a median multiple of the BE value for the first time period by dividing the BE value by the median BE value of a dataset (e.g., such as used in the analysis described herein), the dataset including a population of fetal BE values established for the same time period during the first stage of labor as the first time period. As discussed herein, when the BE value is a predefined multiple of the median (MoM) BE value (e.g., 1.5 at a dilation of 0-3 cm), it indicates that the fetus is at risk for neurological injury. When the identifying step indicates that the fetus is at risk for neurological injury, then intervening in labor to treat the fetus by any conventional treatment measure to reduce or eliminate the risk of neurological injury to the fetus.

[0237] Another method supported by the present disclosure includes identifying the risk of fetal neurological injury during labor by: (i) analyzing fetal blood during a first period of the first stage of labor (e.g., when the cervix is dilated between 0 cm and 3 cm) to determine at least a first BE value for the fetus. When the BE value is ≤ -5 (as determined by the above analysis), it indicates that the fetus is at risk of neurological injury. If the identification step indicates the risk of neurological injury, intervening in labor to treat the risk by any conventional treatment measure (whether in utero or by deciding to deliver promptly) to reduce or eliminate the risk of fetal neurological injury.

[0238] Another method supported by the present disclosure includes the following steps:

[0239] (a) monitoring at least a first set of concurrent clinical parameters of the fetus, the concurrent clinical parameters indicating a current risk level of neurological impairment in the fetus;

[0240] (b) determining a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters during a first time period during the first stage of labor (e.g., when the cervix is dilated between 0 cm and 3 cm), wherein the determined current risk level is expressed as a FRI value;

[0241] (c) determining a multiple of a median (MoM) of the FRI value for the first time period by dividing the FRI value by a median FRI value of a dataset (e.g., such as used in the analyses described herein), the dataset comprising a population of FRI values established for a time period that is the same as the first time period during or before the first stage of labor, wherein the presence of the risk of neurological injury is indicated when the MoM of the FRI value is a predefined multiple of the median FRI value; and

[0242] (d) treating the fetus indicated by step (c) as being at risk of neural damage, wherein the treating step comprises intervening in labor by any conventional treatment measure to reduce or eliminate the risk of neural damage to the fetus.

[0243] When step (c) indicates that the fetus is at risk for neurological damage, the data disclosed herein support the further step of analyzing fetal blood to determine at least a base excess (BE) value during at least a second period of time during the first stage of labor (e.g., when the cervix is less than 10 cm dilated). As previously discussed, the BE value is a more accurate indicator of acidosis risk. Therefore, determining the FRI early in labor can help distinguish which infants require more invasive fetal blood testing and which infants do not.

[0244] The data disclosed herein also support the further step of performing fetal blood analysis at a third time period during the first stage of labor, said third time period being later than the second time point.

[0245] Another method supported by the present disclosure utilizes the rate of decline of BE values determined during the first stage of labor to identify and treat the risk of neurological injury. The method comprises the following steps:

[0246] The risk of fetal neurological injury during labor is identified by: (i) analyzing fetal blood during a first time period of the first stage of labor (e.g., when the cervix is dilated between 0 cm and 3 cm) to determine at least a first BE value for the fetus; (ii) analyzing fetal blood during a second time period of the first stage of labor, the second time period being later than the first time point (e.g., after the first stage of labor but before the cervix reaches 10 cm dilation), to determine at least a second base excess (BE) value for the fetus; and (iii) determining a rate of decrease from the first BE value to the at least second BE value, wherein when the rate of decrease is at least a predefined value (e.g., by way of non-limiting example, 46% or greater), it indicates that the fetus is at risk of neurological injury. When the identifying step indicates the risk of neurological injury, intervening in labor to treat the fetus to reduce or eliminate the risk of neurological injury.

[0247] Instead of comparing the BE decline rate to a predefined percentage, the aforementioned method may alternatively include the step of determining a MoM for the decline rate by dividing the decline rate by the median decline rate of a dataset (e.g., as described herein), the dataset comprising a population of decline rates for fetal BE values established over a time period during the first stage of labor that is the same as the first and second time periods. According to this variant, when the MoM for the decline rate is a multiple of the predefined median decline rate, it indicates that the fetus is at risk for neurological damage. When the risk of neurological damage is indicated, labor is intervened to treat the fetus by any conventional treatment measure.

[0248] Another approach supported by the data presented herein includes the following steps:

[0249] (a) monitoring the fetus for at least a first set of concurrent clinical parameters, the concurrent clinical parameters indicating a current risk level of neurological impairment in the fetus;

[0250] (b) determining a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters during or before labor, wherein the determined current risk level is expressed as a numerical value (FRI value);

[0251] (c) determining a current level of risk of fetal neurological injury based on the first set of concurrent clinical parameters during a second time period during or before labor, the second time period being later than the first time period, wherein the determined current level of risk is expressed as a FRI value;

[0252] (d) determining a rate of decrease from the first FRI value to the second FRI value;

[0253] (e) determining a multiple of a median (MoM) of the FRI value for the first time period by dividing the FRI value by a median FRI value of a dataset, the dataset comprising a population of FRI values established for a time period same as the first time period during or before the first stage of labor, wherein the presence of the risk of neurological injury is indicated when the MoM of the FRI value is a predefined multiple of the median FRI value; and

[0254] (f) determining a MoM for the rate of decline by dividing the rate of decline by a median rate of decline for a dataset comprising a population of rates of decline for FRI values established for a time period identical to the first and second time periods during or before the first stage of labor, wherein the MoM for the rate of decline is indicative of a neurological impairment in the fetus when the MoM for the rate of decline is a predefined MoM rate of decline.

[0255] Another approach supported by the data presented herein for reducing the risk of neurologic injury in a human fetus during labor and delivery includes the following steps:

[0256] (a) monitoring at least a first set of concurrent clinical parameters of the fetus, the concurrent clinical parameters indicating a current risk level of neurological impairment in the fetus;

[0257] (b) determining a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters during or before labor (e.g., when the cervix is dilated from 0 cm to 3 cm), wherein the determined current risk level is expressed as a numerical value (FRI value);

[0258] (c) determining a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters during a second time period (e.g., when the cervix is less than or equal to 10 cm) before or during labor, the second time period being later than the first time period, wherein the determined current risk level is expressed as a FRI value;

[0259] (d) determining a rate of decrease from a first FRI value to a second FRI value, wherein when the rate of decrease is greater than a predefined value (for example, but not limited to, a rate of decrease of 46% or greater), it indicates that the fetus is at risk of neurological damage; and

[0260] Treating the fetus indicated by the identification step as being at risk of neural damage, wherein the treating step comprises intervening in delivery by any conventional treatment measure to reduce or eliminate the risk of neural damage to the fetus.

[0261] The MoM approach described herein can be viewed as an incremental "amplification" of metabolic risk assessment. Through the methods disclosed herein, the risk of a measured value can be immediately understood without having to immediately correlate it with the course of labor. Furthermore, focusing data collection early in labor, according to the present invention, helps clarify which fetuses are delivered "healthy," while for those whose labor deteriorates, FRI and MoM can prevent damage to fetuses that may already be compromised upon admission.

[0262] A significant medico-legal issue in obstetrics is the attempt to determine whether a baby is damaged during labor or already damaged upon entering labor. Because the interpretation of EFM is subjective and lacks widespread consensus, practitioners lack reliable guidance for making this determination. In medico-legal situations, this often leads to diametrically opposed opinions among different medical specialists. Understandably, the admission and maintenance assessment methods discussed in this article provide objective guidance for making these decisions.

[0263] The data presented here suggest that combining BE assessed early in labor and the subsequent rate of decline in BE provides a sensitive method for early prediction of the risk of metabolic acidosis. This occurs before any abnormalities are observed on EFM. Furthermore, these data suggest that the initial FRI and the rate of initial decline in FRI provide a useful screen for deciding who should undergo fetal scalp sampling or other fetal blood analysis and then determine the level of risk for acidosis at birth. This early risk identification may allow for earlier initiation of intrauterine resuscitation, which has been shown to reduce the likelihood and duration of metabolic acidosis, the risk of neurologic compromise, and the need for emergency delivery.

[0264] Embodiments of the foregoing method are contemplated as utilizing a dedicated device or a general-purpose computer, tablet, smartphone, etc. to receive various sensor inputs (manually and / or automatically), perform the various determination steps of the method described herein, and provide visual and / or audio indications of risk and / or intervention recommendations.

[0265] It is contemplated that the above-specified methods may be implemented by, for example, a device comprising at least one computer.

[0266] In one embodiment, such an apparatus includes at least one computer operable to determine a first base excess (BE) value for the fetus established at a first time period during a first stage of labor, determine a median multiple of the BE value for the first time period by dividing the BE value by a median BE value of a dataset, the dataset comprising a population of fetal BE values established at a time period during the first stage of labor that is the same as the first time period, and when the BE value is a predefined median multiple BE value, the at least one computer is further operable to indicate that the fetus is at risk for neurological injury.

[0267] Those skilled in the art will appreciate that the at least one computer, or even another computer operably connected to the at least one computer, may be programmed with a data set comprising a population of fetal BE values established during the first stage of labor over the same time period as the first time period.

[0268] In another embodiment, the device includes at least one computer operable to: receive an input signal indicating at least a first set of concurrent clinical parameters, the first set of concurrent clinical parameters indicating a current risk level of fetal neurological injury; determine the current risk level of fetal neurological injury based on the first set of concurrent clinical parameters in a first time period during or before labor, wherein the determined current risk level is expressed as a numerical value (a first FRI value); determine a multiple of the median (MoM) of the first FRI value by dividing the first FRI value by the median FRI value of a data set, the data set including a population of FRI values established for a time period that is the same as the first time period during or before the first stage of labor; and provide (i) an output indicating the presence of a risk of neurological injury when the determined MoM of the first FRI value is a predefined multiple of the median FRI value, and / or (ii) an output indicating the presence of neurological injury to the fetus when the MoM of the decline rate is a predefined MoM decline rate.

[0269] Likewise, those skilled in the art will appreciate that the at least one computer, or even another computer operatively connected to the at least one computer, may be programmed with a data set comprising a population of FRI values established over the same time period as the first time period during the first stage of labor.

[0270] Further, the at least one computer of this embodiment is operable to: receive input indicating base excess (BE) values of the fetus for at least a second time period and a third time period during the first stage of labor, wherein the third time period is later than the second time point; determine a rate of decrease of the BE values in the second time period and the third time period; and provide an output indicating a risk of neurological injury when the rate of decrease reflected by the BE values in the second time period and the third time period is greater than a predefined value (e.g., 46%).

[0271] In another embodiment, the apparatus includes at least one computer operable to receive input indicating base excess (BE) values of the fetus for at least a first time period and a second time period during a first stage of labor, wherein the second time period is later than the first time point, to determine a rate of decrease in the BE values for the first time period and the second time period, and to provide an output indicating the presence of a risk of neurological injury when the rate of decrease reflected by the BE values for the second time period and the third time period is greater than a predefined value (e.g., 46%).

[0272] In another embodiment, the device includes at least one computer operable to: receive input indicating base excess (BE) values of the fetus for at least a first time period and a second time period during the first stage of labor, wherein the second time period is later than the first time point; determine a rate of descent from the first BE value to the second BE value; determine a multiple of the median (MoM) of the rate of descent by dividing the rate of descent by the median rate of descent of a data set, the data set including a population of rates of descent for fetal BE values established for time periods during the first stage of labor that are the same as the first time period and the second time period; and provide an output indicating the presence of a risk of neurological injury when the MoM of the rate of descent is a predefined multiple of the median rate of descent.

[0273] In another embodiment, the device includes at least one computer operable to receive an input signal indicating at least a first set of concurrent clinical parameters, the first set of concurrent clinical parameters indicating a current risk level of fetal neurological injury; determine the current risk level of fetal neurological injury based on the first set of concurrent clinical parameters in a first time period during or before delivery, wherein the determined current risk level is expressed as a numerical value (a first FRI value); determine the current risk level of fetal neurological injury based on the first set of concurrent clinical parameters in a second time period during or before delivery, the second time period being later than the first time period, wherein the determined current risk level is expressed as a second FRI value; determine a rate of decrease from the first FRI value to the second FRI value; and provide an output indicating the presence of a risk of neurological injury when the determined rate of decrease from the first FRI value to the second FRI value is at least a predefined rate of decrease.

[0274] In another embodiment, the apparatus comprises at least one computer operable to:

[0275] receiving an input signal indicative of at least a first set of concurrent clinical parameters, the first set of concurrent clinical parameters indicative of a current risk level of neurological injury to the fetus;

[0276] determining, during a first time period during or before labor, a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (a first FRI value);

[0277] determining a current risk level of neurological impairment for the fetus based on the first set of concurrent clinical parameters during a second time period during or before labor, the second time period being later than the first time period, wherein the determined current risk level is represented as a second FRI value;

[0278] determining a rate of decrease from the first FRI value to the second FRI value;

[0279] determining a multiple of the median (MoM) of the first FRI value by dividing the first FRI value by a median FRI value of a dataset, the dataset comprising a population of FRI values established during a first stage of labor or prior to a time period that is the same as the first time period;

[0280] determining the MoM of the rate of decline by dividing the rate of decline by the median rate of decline of a data set including a population of rates of decline of FRI values established for a time period identical to the first and second time periods during or before the first stage of labor; and

[0281] Providing (i) an output indicating that a risk of neurological injury exists when the determined MoM of the first FRI value is a multiple of a predefined median FRI value, and / or (ii) an output indicating that the fetus exists at risk of neurological injury when the MoM of the decline rate is a predefined MoM decline rate.

[0282] In an exemplary form, said first period of time during labor is characterized by a cervical dilation of 0 cm-3 cm; and said second period of time during labor is characterized by a cervical dilation of less than or equal to 10 cm.

[0283] In one embodiment, when the decrease rate is 46% or higher, it indicates that the fetus is at risk of neurological damage.

[0284] As discussed elsewhere, the first set of concurrent clinical parameters may include (a) FHR, (b) FHR baseline variability, (c) FHR acceleration, (d) FHR deceleration, and (e) maternal uterine activity. In the case of employing these parameters, the at least one computer is further operable to determine whether each of the concurrent clinical parameters (a) to (e) independently exhibits at least one unsafe characteristic during the first time period, and to convert the number of the concurrent clinical parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe characteristic into the first FRI value. This may be achieved, for example, by executing a simple algorithm that sums the number of the concurrent clinical parameters (a) to (e) that are simultaneously and independently unsafe using an arbitrarily assigned value (e.g., 1 or 0) for each parameter.

[0285] The outputs of the aforementioned embodiments may take any conventional form, including one or more of a graphical display, a warning light, and / or a sound. These outputs may be provided by the device itself. They may also or alternatively be provided by peripheral devices such as a video display and / or a printer.

[0286] It is also contemplated that the devices encompassed by the present disclosure may alternatively or additionally be operable to provide other information, including FHR tracking, uterine activity tracking, and / or further information related to the current indicated fetal risk level, including, by way of non-limiting example, an indication to a clinician or clinician regarding a predetermined action required or recommended for the identified risk level. For example, such other information may be provided via at least one output.

[0287] The at least one computer is further operable to receive user input (eg, via conventional means such as a keyboard or mouse in conjunction with a graphical user interface) indicating a BE value obtained according to the method described above.

[0288] It is contemplated that an apparatus according to the present invention may comprise a self-contained unit including one or more sensors capable of monitoring / receiving user input indicative of the above-mentioned parameters, or a separate unit that receives input corresponding to these parameters from other separate sensors. In the former case, as described above, the at least one output may also provide the capability to include one or more of a display and / or a printout showing FHR and maternal uterine activity tracking, such as provided by a conventional FHM and uterine contraction sensor. In the latter case, the apparatus for implementing the method of the present invention may be a separate device connectable to an FHM device and capable of receiving data therefrom.

[0289] According to another embodiment of the device of the present invention, the identification of the fetal risk level can be provided remotely, for example, via the Internet or other computer network. According to this embodiment, it is envisioned that a display / interface operatively connected to the device at the patient's location is provided to one or more individuals, such as one or more doctors and / or nurses in a geographically remote location, so as to provide the identification of the fetal risk level to one or more individuals in the remote location, as well as the FHM and / or other monitored parameters as needed, so as to be able to provide assistance to those who are giving birth in the delivery room (including through the interface and / or by other means, such as telephone, video conferencing equipment, etc.). For example, the system can be implemented in a community hospital that lacks sufficient obstetricians in the delivery room.

[0290] In an exemplary embodiment, the aforementioned device or other device operable to perform the method of the present invention is operably connected to the patient (directly or via other monitoring devices) to monitor the FHR. FHR baseline variability, FHR acceleration, and FHR deceleration are determined from the FHR continuously or periodically according to a desired schedule, and parameters (a) to (d) are compared with known unsafe characteristics (such as those specified herein) and stored in the at least one computer to determine whether any one or more parameters independently exhibit at least one unsafe characteristic. When the at least one computer determines that any unsafe characteristic is present simultaneously for any one or more parameters (a) to (d), the determination results in an indication of a corresponding risk level to the fetus through one or more outputs. In addition, the device will preferably provide an indication of a requested / recommended action by a clinician or other user.

[0291] Figures 21 to 23 An exemplary, but by no means limiting, apparatus for carrying out the above-described method is schematically depicted.

[0292] More specifically, Figure 21The apparatus 10 is shown comprising at least one computer 20 operable to receive input signals, such as from one or more sensors 30 connected to a patient 40. At least one output 50 is operatively connected to the at least one computer 10. Figure 21 The bold lines indicate the operable connection of these various elements 20, 30 and 50, which may be accomplished by any known method. The at least one output 50 may include, for example, a video display and / or printer, warning lights (e.g., for example, a plurality of score-specific lights, each corresponding to a different risk level), audible warnings, and the like. It is also contemplated that the device may alternatively or additionally be operable to provide other information, including FHR tracking, uterine activity tracking and / or further information relating to the current indicated fetal risk level, including, in non-limiting embodiments, instructions to the clinician or clinician regarding predetermined actions required or recommended for the identified risk level. For example, such other information may be provided via the at least one output 50. The at least one computer 20 may also be operable to receive user input (e.g., by conventional means, such as a keyboard or mouse in conjunction with a graphical user interface). It is contemplated that the device 10 may include a self-contained unit or stand-alone unit 10', the self-contained unit including the one or more sensors 30 capable of monitoring / receiving user input indicative of the above parameters, for example Figure 22 As shown schematically, the independent unit 10' is connected to other independent sensors 30', 30" Figure X ) receives input corresponding to these parameters.

[0293] According to another embodiment ( Figure 23), the identification of the fetal risk level can be provided remotely, for example, via the Internet or other computer network (shown as 300). According to this embodiment, it is envisaged that the display / interface 210 of the device 110 operably connected to the patient's location 100 is provided to one or more people, for example, to one or more doctors and / or nurses at a geographically remote location 200, so as to provide the identification of the fetal risk level to one or more people at the remote location so as to be able to provide assistance to those who are giving birth in the delivery room (including through the interface and / or by other means, such as telephone, video conferencing equipment, etc.). For example, the system can be implemented in a community hospital that lacks sufficient obstetricians in the delivery room. For the purpose of illustration and description, the foregoing description of exemplary embodiments of the present invention has been presented. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or that can be obtained from the practice of the invention. The embodiments shown and described are intended to explain the principles of the invention and its practical application so that those skilled in the art can utilize the invention in various embodiments and with a variety of modifications suitable for the intended specific use. Although only a few embodiments of the present invention have been described in detail in this disclosure, those skilled in the art who review this disclosure will readily appreciate that many modifications are possible without materially departing from the novel teachings and advantages of the subject matter, and all such modifications are intended to be included within the scope of the present invention. Other substitutions, modifications, changes, and omissions may be made to the design, operating conditions, and arrangement of the exemplary embodiments without departing from the essence of the present invention.

Claims

1. A device for reducing the risk of neurological injury in a human fetus before or during labor, the device comprising: At least one computer operable to: receiving an input signal indicative of at least a first set of concurrent clinical parameters, the first set of concurrent clinical parameters indicative of a current risk level of neurological injury to the fetus; determining, during a first time period during or before the first stage of labor, a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value as a first FRI value; determining a median multiple of the first FRI value by dividing the first FRI value by a median FRI value of a dataset, the dataset comprising a population of FRI values established during the first stage of labor or before the first stage of labor for a time period that is the same as the first time period; as well as providing an output indicating the presence of a risk of neurological injury when the determined multiple of a median of the first FRI value is a predefined multiple of a median of FRI values; as well as The first set of concurrent clinical parameters includes (a) FHR, (b) FHR baseline variability, (c) FHR acceleration, (d) FHR deceleration and (e) maternal uterine activity.

2. The apparatus of claim 1 , wherein the at least one computer is further operable to: receiving input indicating base excess values of the fetus for at least a second time period and a third time period during a first stage of labor, wherein the third time period is later than the second time period; determining a decrease rate of the alkali excess value in the second time period and the third time period; and An output is provided indicating that a risk of nerve damage exists when the base excess values for the second and third time periods reflect a rate of decrease greater than a predefined value.

3. The apparatus of claim 2, wherein each of the second time period and the third time period during the first stage of labor is characterized by a cervical dilation of less than or equal to 10 cm.

4. The apparatus of claim 1 , wherein the at least one computer is operable to determine whether each of the concurrent clinical parameters (a) to (e) independently exhibits at least one unsafe characteristic during the first time period, and convert the number of the concurrent clinical parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe characteristic into the first FRI value.

5. The apparatus of claim 1 , wherein the at least one computer is further operable to: determining a current risk level of fetal neurological injury based on the first set of concurrent clinical parameters during a second time period during or before the first stage of labor, the second time period being later than the first time period, wherein the determined current risk level is represented as a second FRI value; determining a rate of decrease from the first FRI value to the second FRI value; determining a median multiple of the decline rate by dividing the decline rate by a median decline rate for a data set including a population of decline rates for FRI values established during or before the first stage of labor and for time periods identical to the first and second time periods; as well as An output is provided indicating that a risk of nerve damage exists when the determined rate of decrease from the first FRI value to the second FRI value is at least a predefined rate of decrease.

6. The apparatus of claim 5, wherein the first time period during the first stage of labor is characterized by a cervical dilation of 0 cm-3 cm.

7. The apparatus of claim 5 or 6, wherein the second time period during the first stage of labor is characterized by a cervical dilation of less than or equal to 10 cm or is at most one hour later than the first time period.

8. The apparatus of claim 5, wherein when the drop rate is 46% or higher, Indicating that the fetus is at risk of neurological damage.

9. An apparatus as described in claim 5 or 8, wherein the at least one computer is operable to determine whether each of the concurrent clinical parameters (a) to (e) independently exhibits at least one unsafe feature during the first time period, and convert the number of the concurrent clinical parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature into the first FRI value.

10. The apparatus of claim 5 or 8, wherein the at least one computer is further operable to: determining a median multiple of the first FRI value by dividing the first FRI value by a median FRI value of a data set, the data set including a population of FRI values established during a first stage of labor or before the first stage of labor for a time period that is the same as the first time period; determining a median multiple of the decline rate by dividing the decline rate by a median decline rate for a data set including a population of decline rates for FRI values established during or before the first stage of labor and for time periods identical to the first and second time periods; as well as Providing (i) an output indicating the presence of a risk of neurological injury when the determined median multiple of the first FRI value is a predefined median multiple of the FRI value, and / or (ii) an output indicating the presence of neurological injury in the fetus when the median multiple of the decline rate is a predefined median multiple decline rate.

11. The apparatus of claim 1 , wherein the at least one computer is further operable to: for a first base excess value for the fetus established for a time period during the first stage of labor, determine a median multiple of the base excess value for the time period by dividing the base excess value by a median base excess value of a data set, the data set comprising a population of fetal base excess values established for the same time period during the first stage of labor, and wherein when the base excess value is a predefined median multiple base excess value, the at least one computer is further operable to indicate that the fetus is at risk of neurological injury.

12. The apparatus of claim 2, wherein the predefined droop rate is 46%.

13. The apparatus of claim 2 or 12, wherein the at least one computer is further operable to: determining a median multiple of the rate of decline by dividing the rate of decline in base excess by the median rate of decline in a data set comprising a population of rates of decline in fetal base excess values established over time periods during the first stage of labor that are the same as the first and second time periods; and An output is provided indicating that a risk of nerve damage exists when the median multiple of the base excess decrease rate is a predefined median multiple of the decrease rate.

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