Methods and devices for reducing risk of nerve injury in human fetus and identifying presence of nerve injury during and prior to childbirth

Abstract

Methods and devices for reducing the risk of human fetal nerve injury during and prior to delivery are disclosed. The method comprises the steps of: (1) identifying the risk of nerve injury in a fetus during delivery by analyzing the blood of the fetus to determine at least a first excess alkali (BE) value of the fetus during a first period of time of a first delivery process; (2) determining a median multiple of the BE value for the first period of time by dividing the BE value by a median BE value of a dataset comprising a population of fetal BE values established during the first birth process for the same period of time as the first period of time, indicating that the fetus has a risk of nerve injury; (3) treating the fetus indicated by the identification step to be at risk of said nerve injury, where said treatment step comprises intervening in delivery by any conventional therapeutic measures to reduce or eliminate the risk of said nerve injury in said fetus.

Description

[0001] This application is a divisional application of the applicant’s patent application 202080069820.X (based on PCT application No. PCT / US2020 / 044768), filed on August 3, 2020, entitled “Method and apparatus for reducing the risk of neural injury in human fetus during and before delivery and for identifying the presence of neural injury”.

[0002] Cross-references to related applications

[0003] This application relates to and claims priority to U.S. Provisional Application Serial No. 62 / 881,701, filed August 1, 2019, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0004] This invention relates to the field of obstetrics, and more specifically, to methods and apparatus for reducing the risk of neural damage in human fetuses during and before delivery. Background Technology

[0005] The current method using the American College of Obstetricians and Gynecologists (ACOG) “classification system” to assess fetal health and predict the risk of neurological damage is extremely poor, missing up to 50% of cerebral palsy (CP) cases. Its use has led to a significant increase in cesarean section rates (CDR) with little impact on reducing serious complications such as CP. The statistical performance metrics of this classification system essentially violate all the key criteria principles required for an effective screening procedure. ACOG category III is an action point requiring delivery or at least treatment, with the fetus positioned so far to the right on the numerical distribution curve that it has a very high positive predictive value for damage—most of which may have already occurred. It also has a very high and unacceptably high false negative rate—missing 50% of serious cases (as reported in several publications). Conversely, ACOG category II is defined as “of concern” (but without explicitly accepted mandatory action), positioned so far to the left on the case distribution curve that up to 75% of patients reach this level. This renders category II useless as a screening test.

[0006] Electronic fetal monitoring (EFM) was introduced into practice in the late 1960s in an attempt to intervene promptly in cases where the fetus has been or is about to be harmed (e.g., to expedite delivery via cesarean section, vacuum extraction, or forceps). Over the past few decades, EFM has been widely adopted and used in the vast majority of deliveries in the United States.

[0007] EFM is predicated on the identification of asphyxia associated with metabolic acidosis. The response to fetal heart rate (FHR) patterns is based on the identification and “rescue” of the asphyxiated fetus, hoping to prevent further injury. Conventionally, when EFM data give an overall impression of “safety,” labor is permitted to continue, while intervention is reserved only when EFM is abnormal, suggests severe asphyxia (from metabolic acidosis), or an acute emergency (e.g., fetal bradycardia). This interpretation is often highly subjective; even distinguished experts frequently disagree on the importance of individual patterns.

[0008] In an improvement upon conventional methods for interpreting EFM data and improving delivery and fetal outcomes during labor, the inventors disclose an apparatus for identifying fetal risk levels during labor in U.S. Patent 9,131,860 (the disclosure of which is incorporated herein by reference in its entirety). The apparatus includes at least one computer operable to receive input signals indicating at least the patient's FHR and maternal uterine activity, the at least one computer also 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) FHR, (b) FHR baseline variability, (c) FHR acceleration, (d) FHR deceleration, and (e) maternal uterine activity exhibits at least one unsafe characteristic from a plurality of predefined unsafe characteristics, at least parameters (a) through (e). The at least one computer is also operable to (iii) receive user input indicating the presence of one or more pre-clinical parameters in the patient that would increase the risk level of the fetus during labor, and (iv) determine the current risk level of the fetus at a given time point during labor, taking into account only: the total number of one or more pre-clinical parameters that increase the risk level of the fetus during labor; and the total number of parameters (a) to (e) that each independently and simultaneously exhibit at least one unsafe characteristic at a given time point during labor. The present invention has demonstrated the ability to produce consistent assessments of EFM data and, consequently, consistent identification of fetuses at risk of neurological injury. The Fetal Reserve Index (FRI) provides a more meaningful alternative to the ACOG classification system. The FRI incorporates multiple risk factors and increased uterine contractions present during labor to produce a statistically significant prediction of fetal cerebral palsy risk. The risk indicators of the FRI take effect earlier in pathophysiology than the ACOG classification system. By identifying potential problems early in the process, it has been shown that adverse outcomes can be reduced through appropriate clinical interventions, and indeed, emergency CDRs, overall emergency labor, and total CDRs can be reduced.

[0009] In a further improvement on conventional means of interpreting EFM data and improving fetal outcomes during labor and delivery, the inventors disclose an apparatus for identifying fetal risk levels during labor in published international application WO / 2018 / 094398, the apparatus comprising: at least one computer operable to receive input signals indicating at least the patient's FHR and maternal uterine activity, the computer operable to determine (i) FHR baseline variability, FHR acceleration, and FHR deceleration, and (ii) 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 of a plurality of predefined unsafe characteristics of at least parameters (a) to (e). The computer is also operable to (iii) receive user input indicating the presence of one or more (f) maternal risk factors, (g) obstetric risk factors, and (h) fetal risk factors in the patient that increase the risk level of the fetus during labor, and (iv) determine the current risk level of the fetus at a given time point during labor, taking into account only: the total number of parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe characteristic at a given time point during labor, and the total number of parameters (f) to (h) present. The output depicts one or more parameters (a) to (h) changing over time during labor in a single graphical user interface, and the appearance of the single graphical user interface includes markers indicating the current risk level of the fetus at any given time point during labor and signaling that intervention in labor may be necessary. The disclosure of published International Application WO / 2018 / 094398 (which is correspondingly disclosed in published U.S. Application 2019 / 0274618) is incorporated herein by reference in its entirety.

[0010] In a further step, the inventors analyzed data from before birth and one hour after birth. Surprisingly and unexpectedly (contrary to popular belief), the adaptation process from fetal to neonatal circulation differed significantly from conventional wisdom. Acid / base balance did not improve linearly but typically deteriorated sharply at different time points. Using this dataset, the FRI was able to differentiate three independent groups of infants based on their last FRI score before delivery, indicating low, intermediate, and high risk of developing metabolic acidosis (typically defined as a base excess of ≤-12 mMol / L, a recognized predictor of cerebral palsy from birth complications). The study also found that neonatal heart rate monitoring showed severe tachycardia with loss of responsiveness and variability in 85% of patients within the first 10 minutes or longer. If this pattern were present prenatally, it would generally be classified as Category III under the ACOG classification system. To some extent, these findings help explain the poor performance of the ACOG classification system, as abnormalities often go unnoticed when they occur. The above content is discussed in the published international application WO / 2020 / 102524, the entire contents of which are incorporated herein by reference.

[0011] While these advances promise to improve delivery and birth outcomes, the ongoing neurological damage to newborns due to progressive hypoxia and acidosis remains a problem that needs further attention. Summary of the Invention

[0012] Acidosis as reflected by the BE value is often the closest approximation of the risk of harm, although experience to date is insufficient to accurately estimate the risk for any given fetus. This paper demonstrates the correlation between FRI and BE scores within cervical dilation and between adjacent cervical dilation (CDx) groups. These correlations are strong enough to justify using FRI as a surrogate indicator, especially under the same cervical dilation conditions. Combining the information available in the FRI can infer the risk of acidosis at the start of stage two and suggest when FSS can be considered. In summary, this is an improvement on CTG in predicting acidosis and its sequelae.

[0013] This article discloses methods for reducing the risk of neural damage in human fetuses during labor and for identifying the presence of neural damage in human fetuses.

[0014] In one embodiment, a method for reducing the risk of neural damage in a human fetus during childbirth is disclosed, comprising the following steps:

[0015] The risk of fetal neural damage during delivery can be assessed using the following methods:

[0016] During the first stage of labor, fetal blood is analyzed to determine the fetus's at least first alkali excess (BE) value;

[0017] The median multiple of the BE value for the first time period is determined by dividing the BE value by the median BE value of the dataset, which includes a population of fetal BE values ​​established during the same time period as the first time period during the first stage of labor, wherein a BE value that is a predefined median multiple (MoM) BE value indicates a risk of neurological damage in the fetus; and

[0018] Treatment is given to fetuses indicated by the identification steps to present with the risk of said neurological damage, wherein said treatment steps include intervention during delivery through any routine treatment measures to reduce or eliminate the risk of said neurological damage to the fetus.

[0019] In one respect, the first time period during labor is characterized by cervical dilation of 0-3 cm.

[0020] According to another embodiment, a method for reducing the risk of neural damage in a human fetus during childbirth is disclosed, comprising the following steps:

[0021] The risk of fetal neural damage during delivery is assessed using the following methods:

[0022] During the first stage of labor, fetal blood is analyzed to determine at least a primary alkali excess (BE) value in the fetus, wherein a BE value ≤ -5 indicates a risk of neurological damage in the fetus; and

[0023] Treatment is given to fetuses indicated by the identification steps to present with the risk of said neurological damage, wherein said treatment steps include intervention during delivery through any routine treatment measures to reduce or eliminate the risk of said neurological damage to the fetus.

[0024] In one respect, the first time period during labor is characterized by cervical dilation of 0-3 cm.

[0025] According to a further embodiment, a method for reducing the risk of neural damage in a human fetus before or during delivery is disclosed, comprising the following steps:

[0026] (a) The fetus is monitored for at least a first set of concurrent clinical parameters, which indicate the current risk level of neural damage in the fetus;

[0027] (b) Before or during the first stage of labor, at a first time point, the current risk level of the fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (FRI value).

[0028] (c) Determining the median multiple (MoM) of the FRI values ​​for the first time period by dividing the FRI value by the median FRI value of the dataset, the dataset comprising a group of FRI values ​​established during or before the first labor stage at the same time period as the first time period, wherein a MoM of the FRI value being a predefined median multiple of the FRI value indicates the presence of the risk of the neurological injury; and

[0029] (d) Treating the fetus indicated by step (c) as having the risk of said nerve damage, wherein said treatment steps include interventions before or during delivery by any routine treatment measures to reduce or eliminate the risk of said fetal nerve damage.

[0030] According to one characteristic, the first time period is the period of cervical dilation from 0cm to 3cm during labor.

[0031] According to another feature, when step (c) indicates the presence of the risk of the nerve injury, the method includes a further step of analyzing fetal blood during at least a second time period during the first stage of labor to determine at least an excess alkali (BE) value.

[0032] According to another aspect, the steps of analyzing fetal blood include performing the analysis during a third time period during the first stage of labor, the third time period being later than the second time point, and determining the alkali excess (BE) value for at least each of the second and third time periods.

[0033] According to another aspect, the first time period during labor is characterized by cervical dilation of 0cm-3cm, and the second and third time periods during labor are each characterized by cervical dilation of less than 10cm.

[0034] 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 in 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, the current risk level of the fetus corresponding to the number of the parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature.

[0035] According to another embodiment, a method for reducing the risk of neural damage in a human fetus during childbirth is disclosed, comprising the following steps:

[0036] The risk of fetal neural damage during delivery is assessed using the following methods:

[0037] During the first stage of labor, fetal blood is analyzed to determine the fetus's at least first alkali excess (BE) value;

[0038] During the second time period of the first stage of labor, which is later than the first time point, fetal blood is analyzed to determine at least the second alkali excess (BE) value of the fetus.

[0039] Determine the rate of decrease from the first BE value to at least the second BE value, wherein a rate of decrease greater than a predefined value indicates a risk of neurological damage in the fetus; and

[0040] Treatment is given to fetuses indicated by the identification steps to present with the risk of said neurological damage, wherein said treatment steps include intervention during delivery through any routine treatment measures to reduce or eliminate the risk of said neurological damage to the fetus.

[0041] According to one perspective, the first time period during labor is characterized by cervical dilation of 0cm-3cm.

[0042] According to another perspective, the second time period during labor is characterized by cervical dilation of less than or equal to 10 cm.

[0043] According to another characteristic, when the decline rate is 46% or higher, it indicates that the fetus has the risk of the aforementioned nerve damage.

[0044] According to yet another implementation, a method for reducing the risk of neural damage in a human fetus during childbirth is disclosed, comprising the following steps:

[0045] The risk of fetal neural damage during delivery is assessed using the following methods:

[0046] During the first stage of labor, fetal blood is analyzed to determine the fetus's at least first alkali excess (BE) value;

[0047] During the second time segment of the first stage of labor, which is later than the first time segment, fetal blood is analyzed to determine at least the second alkali excess (BE) value of the fetus.

[0048] Determine the rate of decrease from the first BE value to the second BE value;

[0049] The median multiple (MoM) of the decline rate is determined by dividing the decline rate by the median decline rate of the dataset, which includes a population of fetal BE value decline rates established during the first labor stage at the same time period as the first and second time periods. A MoM of the decline rate that is a predefined median multiple of the decline rate indicates a risk of neurological damage in the fetus.

[0050] Treatment is given to fetuses indicated by the identification steps to present with the risk of said neurological damage, wherein said treatment steps include intervention during delivery through any routine treatment measures to reduce or eliminate the risk of said neurological damage to the fetus.

[0051] According to one aspect, the first time period during labor is characterized by cervical dilation of 0-3 cm.

[0052] According to another aspect, the second time period during labor is characterized by cervical dilation of less than or equal to 10 cm.

[0053] 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 following steps:

[0054] (a) The fetus is monitored for at least a first set of concurrent clinical parameters, which indicate the current risk level of neural damage in the fetus;

[0055] (b) During labor or in the first time period prior to labor, the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein said determined current risk level is expressed as a numerical value (FRI value).

[0056] (c) During or before delivery, in a second time period later than the first time period, the current risk level of the fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as an FRI value;

[0057] (d) Determine the rate of decrease from the first FRI value to the second FRI value;

[0058] (e) Determining the median multiple (MoM) of the FRI values ​​for the first time period by dividing the FRI value by the median FRI value of the dataset, the dataset comprising a group of FRI values ​​established during or before the first labor stage for the same time period as the first time period, wherein a MoM of the FRI value being a predefined median multiple of the FRI value indicates the presence of the risk of the neurological injury; and

[0059] (f) The MoM of the decline rate is determined by dividing the decline rate by the median decline rate of the dataset, which includes a population of FRI value decline rates established during or before the first labor stage, at the same time period as the first and second time periods, wherein the MoM of the decline rate indicates the presence of neurological damage in the fetus when it is a predefined MoM decline rate.

[0060] According to one characteristic, 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 in 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 said 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, the current risk level of the fetus corresponding to the number of said parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature.

[0061] According to another characteristic, the second time period is at most one hour later than the first time period.

[0062] According to another feature, when step (b) and / or step (c) indicates the presence of the risk of said nerve damage, the method includes a further step of analyzing fetal blood during or before the first stage of labor to determine at least an excess alkali (BE) value.

[0063] In another embodiment, a method for reducing the risk of neural damage in a human fetus during childbirth is disclosed, comprising the following steps:

[0064] (a) Monitor at least a first set of concurrent clinical parameters of the fetus, the concurrent clinical parameters indicating the current risk level of neural damage in the fetus;

[0065] (b) During labor or in the first time period prior to labor, the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein said determined current risk level is expressed as a numerical value (FRI value).

[0066] (c) During or before delivery, in a second time period later than the first time period, the current risk level of the fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as an FRI value;

[0067] (d) Determine the rate of decline from a first FRI value to a second FRI value, wherein a rate of decline greater than a predefined value indicates a risk of neurological damage in the fetus; and

[0068] Treatment is given to fetuses indicated by the identification steps to present with the risk of said neurological damage, wherein said treatment steps include intervention during delivery through any routine treatment measures to reduce or eliminate the risk of said neurological damage to the fetus.

[0069] According to one characteristic, the first time period during labor is characterized by cervical dilation of 0cm-3cm.

[0070] According to further characteristics, the second time period during labor is characterized by cervical dilation of less than or equal to 10 cm.

[0071] According to another characteristic, when the decline rate is 46% or higher, it indicates that the fetus is at risk of the aforementioned neurological damage.

[0072] The apparatus for performing the methods disclosed herein is also disclosed. Attached Figure Description

[0073] The present invention will be understood from the following description and drawings, wherein:

[0074] Figure 1 The figure illustrates the sensitivity of detecting BE values ​​below -12 mMol / L under various cervical dilation conditions, obtained from infant population data.

[0075] Figure 2 The graph shows the FRI score, from... Figure 1 The same data was obtained under the same cervical dilation conditions.

[0076] Figure 3 The decrease in BE value and FRI score during the first stage of labor was depicted graphically (box plot).

[0077] Figure 4 The decrease in intermediate BE values ​​during the first stage of labor is described.

[0078] Figure 5 This is a schematic diagram of a model showing the significance of the initial BE value and its rate of decline in relation to the risk of acidosis.

[0079] Figure 6 The sensitivity and specificity of the previously obtained initial BE values ​​and BE decline rate were compared using ROC analysis.

[0080] Figure 7 It is a summary logistic regression analysis table used to predict the 30% of members with the lowest BE scores at the start of the second stage of labor.

[0081] Figure 8 This is a summary logistic regression analysis table used to predict the 30% of members with the lowest pH readings at the start of the second stage of labor.

[0082] Figure 9 This is a schematic diagram of a model showing the significance of variables related to the initial BE value and its rate of decline in relation to the risk of acidosis.

[0083] Figure 10 This is a schematic diagram of the second model, showing the significance of the variables initial FRI score, FRI score decline rate, initial BE value, and BE decline rate in relation to the risk of acidosis.

[0084] Figure 11 ROC curve analysis was used to plot the initial BE decline rate (i.e., the decline rate between the first and second BE values). The straight line represents the correspondence, i.e., the relationship, between sensitivity and specificity.

[0085] Figure 12 The graphs depict the BE value relative to cervical dilation and postpartum time for each of the 25th, 50th, and 75th percentiles of the BE value measurement.

[0086] Figure 13 The graphs depict the BE value relative to cervical dilation and postpartum time for each of the 10th (bottom line), 20th (second line from the bottom), 30th (third line from the bottom), 40th (second line from the top), and 50th (top line) percentiles of the BE value measurement.

[0087] Figure 14 The graphs depict the 90th percentile of the BE value measurement, the BE value relative to cervical dilation and postpartum time, and the FRI score.

[0088] Figure 15 The graphs depict the 75th percentile of the BE value measurement, the BE value relative to cervical dilation and postpartum time, and the FRI score.

[0089] Figure 16 The graphs depict the 25th percentile of the BE value measurement, the BE value relative to cervical dilation and postpartum time, and the FRI score.

[0090] Figure 17 The graphs depict the 10th percentile of the BE value measurement, the BE value relative to cervical dilation and postpartum time, and the FRI score.

[0091] Figure 18The median and lowest quartile of BE and FRI were plotted throughout the active phase of labor.

[0092] Figure 19 The median and lowest quartile of pH and FRI were plotted throughout the active phase of labor.

[0093] Figure 20 The median and lowest quartile of BE and pH were plotted throughout the active phase of labor.

[0094] Figure 21 This is a schematic diagram of an exemplary structure of an apparatus for implementing the method of the present invention.

[0095] Figure 22 This is a schematic diagram of a second exemplary construction of a device for implementing the method of the present invention.

[0096] Figure 23 This is a schematic diagram of an embodiment of an apparatus for implementing the method of the present invention that provides remote monitoring and / or feedback. Detailed Implementation

[0097] The following describes methods and devices for reducing the risk of neural damage in human fetuses during labor. These methods and devices are based on the analysis of a dataset of fetal scalp samples, all 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 MoM, the degree of deviation from the median at discrete points—defined here as the amount of cervical dilation at a specific time—is used as an independent variable to predict the likelihood of neural damage risk.

[0098] Specific embodiments of the invention are disclosed herein as needed. However, it should be understood that the disclosed embodiments are merely examples of the invention, which can 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 construed as limiting, but rather serve as a representative basis for teaching those skilled in the art to use the invention in various ways.

[0099] As used herein, “child” is intended to include human children before delivery (i.e., children as fetuses) and human children after delivery (i.e., newborns). 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 children as fetuses and newborns.

[0100] As used in this article, “base excess” (BE) refers to the amount of base or acid that must be added to a newborn’s blood at 98.6°F (37°C) and pCO2 of 40 mmHg to restore 1 liter of newborn blood to a physiological level of 7.4. BE below average is unsafe, and values ​​≤ -12 mMol / L are considered to indicate a high risk of neurological damage.

[0101] As used herein, “computer” means a device capable of storing, retrieving and processing data, including any of a general-purpose computer, a handheld computing device (e.g., a smartphone, tablet, portable computer, etc.), and / or a special-purpose computer.

[0102] Fetal monitoring

[0103] In an exemplary embodiment of the invention described herein, at least a first set of parameters of the patient are monitored during labor to determine the level of risk for neurological injury in the child. These parameters include multiple variable dynamic parameters related to EFM, including (a) baseline FHR, (b) baseline FHR variability, (c) FHR acceleration, and (d) FHR deceleration. Optionally, these parameters also include dynamic parameters related to intrauterine activity (“IUA”) (e) maternal uterine activity (i.e., uterine contractions). In this context, the patient being monitored 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.

[0104] Table 1 - EFM and IUA Variables

[0105]

[0106] Optionally, the monitored parameters may also include certain additional maternal, obstetric, and fetal risk (“MOFR”) factors (separate from EFM variables), as follows: (f) maternal risk factors, (g) obstetric risk factors, and (h) fetal risk factors (separate from EFM). According to this embodiment, parameter (f) of the “maternal risk factors” includes the following unsafe characteristics:

[0107] 1) Decreased cardiac output / decreased placental vascular perfusion

[0108] a. Heart disease at risk of decreased cardiac output during pregnancy

[0109] b. Hypertension (chronic hypertension and pregnancy-induced hypertension)

[0110] c. SLE (Systemic Lupus Erythematosus), etc.

[0111] 2) Oxygen-carrying capacity

[0112] a. Lung diseases (e.g., asthma)

[0113] b. Anemia and hemoglobinopathies

[0114] 3) Infections (chronic and acute infections)

[0115] 4) Chronic debilitating diseases

[0116] 5) Poor absorption / poor weight gain

[0117] 6) Endocrine disorders – diabetes and thyroid diseases

[0118] 7) Advanced maternal age

[0119] 8) Drug abuse, addiction and smoking

[0120] 9) Obesity – BMI (Body Mass Index) > 35

[0121] 10) Short stature (≤5'2")

[0122] 11) Epidural anesthesia

[0123] According to this embodiment, the parameter (g) of "obstetric risk factors" includes the following unsafe characteristics:

[0124] 1) IUGR (Intrauterine Growth Restriction) / Macrosomia

[0125] 2) Oligohydramnios

[0126] 3) Excessive amniotic fluid

[0127] 4) Bleeding and premature abruption

[0128] 5) Previous cesarean section

[0129] 6) Placental and umbilical cord abnormalities

[0130] 7) Rupture of membranes (PPROM - premature birth or premature rupture of membranes, SROM - spontaneous rupture of membranes, AROM - artificial rupture of membranes)

[0131] 8) Dystocia (prolonged labor and labor arrest)

[0132] 9) Malpresentation leading to dystocia

[0133] Finally, according to this embodiment, the parameter (h) of "fetal risk factors" includes the following unsafe characteristics:

[0134] 1) Abnormal Doppler / BPP (physiological assessment)

[0135] 2) Hereditary diseases

[0136] 3) Fetal arrhythmia

[0137] 4) Meconium expulsion

[0138] 5) Chorioamnionitis

[0139] 6) Second stage of labor – pushing

[0140] 7) Amniocentesis

[0141] 8) Discontinuation of oxytocin due to fetal intolerance

[0142] 9) Switching modes (acute sustained tachycardia (>170 bpm))

[0143] 10) Ominous overshoots

[0144] 11) Bradycardia (<100 bpm)

[0145] 12) Loss of important data during labor (e.g., missing EFM of the second stage of labor)

[0146] The interpretation of the various parameters described above can be carried out conventionally, including, optionally, using the methods disclosed by the inventors in U.S. Patent No. 9,131,860 and U.S. Application No. 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 characteristic, such as the aforementioned unsafe characteristics; and obtaining an indication of the current risk level, referred to as the "Fetal Reserve Index" (FRI) score, which corresponds to the number of parameters that simultaneously and independently exhibit at least one unsafe characteristic. According to this exemplary method, the number of parameters that simultaneously and independently exhibit at least one unsafe characteristic and the indication of the current risk level of neurological injury are directly related. Therefore, for example, according to the method of monitoring parameters (a) to (e), the highest level of risk of nerve injury corresponds to the simultaneous and independent manifestation / presence of at least one unsafe feature in the patient for each of parameters (a) to (e), while the lowest level of risk of nerve injury corresponds to the absence of any unsafe feature manifested / absence of any of these parameters in the patient.

[0147] It should be understood that parameters (a) through (e) are dynamic parameters; that is, they may change in either direction during monitoring (e.g., from normal or safe, to abnormal or unsafe, and then back to normal). On the other hand, MOFR parameters (f) through (h) are inherently unidirectional; that is, once they occur (whether during or before labor), they negatively impact the FRI score. It should also be understood that, according to the exemplary implementation, the presence of an unsafe characteristic of each parameter (f) through (h) is sufficient to negatively impact the FRI score. For example, parameter (f) for “maternal risk factors” does not need to show more than one of the 11 exemplary unsafe characteristics listed above.

[0148] In the context of this disclosure, "simultaneously" means at exactly the same point in time, or at least overlapping points in time when determining the safety / unsafety of each monitoring parameter during labor. In an exemplary embodiment, this risk assessment is performed at 20-minute intervals, consistent with determining the safety / unsafety of IUA parameter(e).

[0149] In the context of this disclosure, "independence" means that the performance / non-performance of each monitoring parameter of one or more unsafe characteristics affects the determination of the current risk level, without considering the performance / non-performance of one or more unsafe characteristics of any other monitoring parameter. In other words, while the performance / non-performance of each monitoring parameter will collectively affect the determined current risk level, each monitoring parameter is considered independently of the other parameters in terms of exhibiting safe / unsafe characteristics.

[0150] The FRI score is derived as follows: If each monitored parameter is considered normal (i.e., safe), a first value (e.g., "1") is assigned to that parameter (e.g., (a) through (h)), and if a parameter is considered abnormal (i.e., unsafe), a second value (e.g., "0") is assigned to that parameter. The first and second values ​​are the same for each parameter. That is, only two values ​​(e.g., 1 or 0) are used. In this embodiment, the FRI score is calculated as a percentage by dividing the number of points by the number of parameters involved (e.g., 5) and multiplying by 100. For example, a total of 5 monitored parameters ((a) through (e)) will produce an FRI score, which is calculated as a percentage by dividing the number of points by 5 and then multiplying by 100. A total of 5 parameters ((a) to (e)) being normal will result in an FRI score of 100% (5 / 5), while point loss—which is a function of any abnormal or unsafe characteristics of any monitored FRI parameter (a) to (e)—will result in FRI scores of 80% (4 / 5), 60% (3 / 5), 40% (2 / 5), 20% (1 / 5), and 0% (0 / 5). Alternatively, all eight parameters ((a) through (h)) being normal will result in an FRI score of 100 (8 / 8), while point loss—which is a function of any abnormal or unsafe characteristics of any monitored FRI parameter (a) through (h)—will 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).

[0151] The current risk level of neurological injury is determined by considering each parameter (when present) independently of other parameters. Therefore, the scheme for determining the current risk level within the scope of this invention is not, as some conventional methods, a result of interdependence between any parameters, but rather strictly a function of the number of parameters present in the patient and / or simultaneously but independently exhibiting unsafe characteristics. Consistent with the foregoing, this method differs further 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 such that any unsafe manifestation of a predetermined unsafe characteristic according to the parameter (e.g., (a) to (e) or (a) to (h)) will cause each such parameter to contribute equally to the currently determined risk level.

[0152] Exemplary embodiments also contemplate that the method of the present invention includes assigning predefined risk categories to children, wherein the predefined risk categories correspond to determined current risk levels. For example, the current risk level of neurological damage can be identified by specific FRI scores and / or easily interpretable grades as described above. For example, but not limited to, the “grades” of the embodiments take the form of arbitrary color zones, similar to traffic lights. In embodiments of this disclosure, the lowest current risk level is identified as a “green zone” and includes an FRI score >50%. An increase in the current risk level of the fetus (relative to the lowest level) is identified as a “yellow zone” and includes an FRI score ≤50% and >26%. The highest current risk level is identified as a “red zone” and includes an FRI score ≤25%. The lower the score, the greater the risk of acidosis and adverse consequences.

[0153] Experimental data

[0154] Fetal Reserve Index (FRI) scores were derived from FHR tracking datasets and BE value datasets (both collected during the first stage of labor) of fetal scalp samples and analyzed together with BE measurements at the corresponding time points during labor. Using available measurements from these datasets, FRI scores were 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 various parameters (e.g., FHR, NHR, pH, alkalinity excess, etc.) validated the inventors' hypotheses and demonstrated the practicality of the invention in reducing the risk of neurological damage to the fetus.

[0155] More specifically, data from 475 high-risk, full-term singleton pregnancies were used to assess the relationship between FRI and EFM tracking, delivery process, and neonatal outcomes in the first hour after birth. These data were collected in the 1970s, mostly at UCLA County Hospital, with some at Yale New Haven Hospital. Each case was supervised by an attending physician in the MFM department. Monitoring strips had five data lines (EFM, contraction pattern, extended variation tracking, maternal respiration, and maternal heart rate). Postpartum, continuous neonatal heart rate (NHR), respiration, ECG, blood pressure, pH, and BE and pO2 analysis of umbilical artery core blood (CB) via indwelling catheter were continued. Concurrent notes were included throughout the scalp sampling record, along with results (e.g., pH, alkali excess, pO2), blood pressure, administered medications, provided anesthesia, and other relevant data. Prenatally, scalp sampling was performed as instructed and recorded on monitoring strips. Postnatally, umbilical cord gas was typically obtained at 1, 4, 8, 16, 32, and 64 minutes. Neonatal observations included: Apgar scores at 1 minute and 5 minutes, NHR (new heart rate) and responsiveness as the neonatal rate returned to pre-delivery levels, and umbilical artery pH, BE (body temperature), and pO2. Most of these records contained all of the above measurements.

[0156] All monitoring was initiated in the presence of ruptured membranes, with placement of a fetal scalp electrode (FSE) and an intrauterine pressure catheter (IUPC). Continuous non-hospital heart rate (NHR) was recorded—similar to intrapartum fetal heart rate (FHR).

[0157] For further analysis, the FRI scores were divided into three groups. As mentioned above, the lowest risk level was identified as the "green zone" and included >50% of the FRI scores; an increase in the current fetal risk level (relative to the lowest level) was identified as the "yellow zone" and included ≤50% and >26% of the FRI scores; the highest risk level was identified as the "red zone" and included ≤25% of the FRI scores. Approximately 10% of the cases in the assessment records were in the red zone, 30% were in the yellow zone, and 60% were in the green zone. Table 2 below summarizes the relevant characteristics of the above sample groups.

[0158] Table 2

[0159]

[0160] These data show that as labor progresses and the fetus experiences more stress, both the FRI score and BE value deteriorate (i.e., decrease). Based on this, the inventors have demonstrated that a given measurement taken early in labor can have very different meanings than the same measurement taken later (e.g., during the second stage of labor).

[0161] These data were analyzed using their actual measurements—for example, the BE values ​​themselves—along with their mean and standard deviation. They were also converted to nonparametric “multiples of the median” (MoM) instead of the parametric mean and standard deviation. Using MoM, the degree of deviation from the median at discrete points—defined here as the amount of cervical dilation at a specific time—was used as an independent variable to predict the likelihood of a cord blood BE ≤12 mMol / L (the definition of metabolic acidosis risk). Based on this measurement, a -7BE at 4 cm cervical dilation was more likely to be below -12 mMol / L in late pregnancy or cord blood compared to the same -7BE mMol / L reading at 10 cm cervical dilation (i.e., in the second stage of labor). Actual measurements of these data confirmed this conclusion.

[0162] Data analysis showed that the median and mean values ​​of the mean fetal scalp sample (FSS) BE and pH decreased gradually with an approximately linear slope during the first stage of labor (p < .000 for ANOVA tests of the significance of the difference in means and the linear component). The median values ​​of both BE and pH decreased with increasing cervical dilation. The decrease in BE and pH during the first stage of labor typically began gradually and accelerated as full cervical dilation approached. The decline accelerated during labor, continuing until four minutes postpartum.

[0163] A more detailed discussion of the above analysis results is as follows:

[0164] refer to Figure 1 The graph shows the percentage of infants in the dataset with BE values ​​below -12 mMol / L at cervical dilation of 4-5 cm, 6-7 cm, and 8-9 cm. Specifically, the bottom line plots the results for infants in the dataset with a 20% positivity rate for metabolic acidosis screening, while the top line plots the results for infants in the dataset with a 40% positivity rate for metabolic acidosis screening. As shown, at 4-5 cm cervical dilation, 40% of the infants from the 20% positivity group showed BE values ​​below -12 mMol / L, while 80% of the infants from the 40% positivity group showed such a percentage. For the 20% positivity group, this percentage increased to approximately 60% at 8-9 cm cervical dilation. For the 40% positivity group, this percentage was approximately 80% at 8-9 cm cervical dilation.

[0165] Next reference Figure 2 Under the same cervical dilation conditions (i.e., 4cm-5cm, 6cm-7cm, 8cm-9cm), the calculated infant FRI score, rather than the BE value, was used. Figure 1The same dataset was analyzed. In this figure, the bottom line plots the results for the infant population with a 20% positivity rate for metabolic acidosis screening in the dataset, while the top line plots the results for the infant population with a 40% positivity rate for metabolic acidosis screening in the dataset. Although the FRI score was not as good as the BE result (the BE result is a direct measure of fetal acidosis, unlike the FRI, which is an indirect predictor of fetal acidosis), it was parallel to the BE result.

[0166] Now for reference Figure 3 The decline in BE and FRI scores during the first stage of labor (i.e., cervical dilation between 0 cm and 10 cm) was assessed. Figure 3 The box plots show the middle 50% of the scores, with parentheses around them representing the 99th percentile. Some outliers are visible in certain expansion categories. These data suggest that fetal acidosis gradually increases during labor—possibly due to prolonged fetal contractions.

[0167] The data above were then converted from parameter mean and standard deviation to MoM for each expansion cohort. Since the baseline shifts with expansion, the MoM for any given BE measurement will vary based on the expansion. However, this allows for a standardized interpretation as a function of the MoM value without requiring constant manual adjustment of the expansion.

[0168] The MoM score reflects downward progression (i.e., the MoM increases as the score worsens).

[0169] It is worth noting that the original BE values ​​were negative. Since the FRI score is positive, the results presented in this paper can arbitrarily use positive numbers as the MoM of BE. Otherwise, allowing the MoM (FRI and BE) to progress in different directions would be very confusing. Furthermore, for most clinicians, the significance of differences greater than 1 is easier to visualize than negative numbers.

[0170] Table 3: MoM conversion of fetal scalp BE score

[0171]

[0172] As can be seen from Table 3 above, in early dilation (e.g., 0cm-3cm), the original value of -8 (left column) is close to twice (negative) of the median score (MoM 2.0), thus implying a relatively high risk. On the other hand, in the later stages of labor, the original BE value of -8 is "normal" in the sense that it is very close to the median score (MoM 1.1).

[0173] Using the median for comparison, the BE decreased by 46% for an expansion from 0cm-3cm to 10cm. The decrease in the mean was very similar and linear, decreasing proportionally by 38%. See also Figure 4 .

[0174] Using a median decrease in BE proportionally of 46% during cervical dilation from 0cm to 3cm to 10cm (see Table 3), a simple equation X = (0.46)(-12) indicates that, on average, the risk of a birth BE value of -12 is high when cervical dilation is 0cm to 3cm and the BE value is -5.52 or greater.

[0175] The corresponding figures derived from the decrease in the average value indicate that when the cervix is ​​dilated to 0-3 cm, and the BE value is at least -4.56 or worse, the average BE value at birth will drop to -12.

[0176] This new score (hereinafter referred to as the “Initial Decline Rate” (IDR) or “Initial Decline Trajectory”) will help provide an early warning of the risk of birth acidosis (operated as a BE of -12 mMol / L umbilical cord gas reading at birth). In this analysis, the proportional reduction of the first scalp sample reading (BE1) and the BE from the first scalp sample reading to the second scalp sample reading (BE_decline_1_2) were used as variables of interest. Table 4 below shows the logistic regression output:

[0177] Table 4: Logistic Regression Results for BE Variables

[0178]

[0179] Logistic regression focuses on the partial logarithm, which is the natural logarithm of the probability of the outcome (in this case, the probability of exposure to the risk of acidosis at birth). B(β) represents the partial logarithmic change for each unit change in the predictor variable. If both predictor variables are equal to 0, the constant represents the log odds of acidosis.

[0180] 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 number of predictors increases, while an odds ratio greater than 1 indicates that the outcome becomes more likely as the number of predictors increases.

[0181] Table 4 shows that the initial BE level and its trajectory, reflected by the decrease in BE levels from the first to the second reading, are crucial for predicting the risk of acidosis at birth: as BE values ​​become increasingly negative, the risk of fetal acidosis at birth increases; similarly, with initial BE levels controlled, a greater rate of decrease in BE between the first and second scalp sampling indicates a greater risk of acidosis at birth. These findings can be represented graphically, such as... Figure 5 As shown.

[0182] Summary Figure 5 The model in this paper is useful for visualizing the influence of variables considered sufficiently important in the model. As a whole, the model can be evaluated both empirically and conceptually. From an empirical perspective, the Hosmer-Lemeshow test (if significant) lets us know if anything truly important is being overlooked outside the equations. Here it is significant (<0.02) – indicating that the model is flawed and that examining the model from both clinical and theoretical perspectives should be fruitful.

[0183] The second empirical approach is to look at the analogy of R-squared, known as Nagelkerke R-squared. Its value of 0.32 indicates that approximately one-third of the variance of the birth-dichotomous BE values ​​(risk of acidosis) can be explained solely by these two variables. Internally, both variables (BE1 and the percentage decrease from BE1 to BE2) are highly significant.

[0184] These empirical results can be further studied in several ways. One is to examine the summary classification table, as shown in Table 4 below.

[0185] Table 4: Classification table of MoM conversions; FRI and BE scalp sample readings for risk of birth acidosis.

[0186]

[0187] In Table 4, the "Sensitivity" (true positive / (true positive + false negative) is 32%; the "Specificity" (true negative / (true negative + false positive) is 98%; the "Positive Likelihood Ratio" (sensitivity / 1 - specificity) is 23 [this is a single statistic measure using ROC (Receiver Operating Characteristic) curves—and this equation varies considerably between true and false positives]; the "Negative Likelihood Ratio" (1 - sensitivity / specificity) is 0.70; the PPV (true positive / all positive cases) is 81%; the NPV (true negative / all negative cases) is 88%; and the accuracy = (true positives and true negatives) / total is 88%.

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

[0189] Next reference Figure 6The results were compared using ROC curve analysis. This was achieved by preserving the predicted probabilities from the logistic regression analysis and using them as predictors in the ROC analysis. The area under the curve was 0.82 (significance < 0.000), reflecting early BE readings and the rate at which these readings decrease as birth approaches, which are important factors in predicting the risk of acidosis at birth.

[0190] The correlations between unconverted FRI and BE scores within the same cervical dilation group and between adjacent CxD groups were also calculated. The results are shown in Table 5 below. In Table 5, the following labels indicate significance levels: ^=<.05; *=<.01; **=<.001; ***=<.000. These correlations are strong enough to justify using FRI as a surrogate indicator, especially under the same cervical dilation conditions. In the later stages of the first labor, the association between FRI and BE and pH showed a moderately increasing trend, indicating that the changes in scores increased as changes began to occur.

[0191] Table 5

[0192]

[0193] Multiple regression analysis was used to improve these associations to include information about FRI levels and their trajectory over previous time periods. Table 6 below shows the BE results of regression analysis on FRI and FRI decline within grouped cervical dilation. Four types of analysis are provided in the table. The first row analyzes the BE level at dilation of 6-7 cm; the second row analyzes the decline in BE at two points (i.e., from cervical dilation of 4-5 cm to 6-7 cm); the next two rows repeat this analysis of the BE at 8-9 cm dilation and the decline in BE from 6-7 cm to 8-9 cm dilation.

[0194] Table 6

[0195]

[0196] Fetal scalp readings were available in 38 cases at 4-5 cm and 6-7 cm. Only FRI was used. 4-5cm The FRI decreased from readings in the 6-7 cm to 4-5 cm range, with an R value of .50 (p < .007). 4-5cm The coefficients were close to significant (<.099), but the decrease in FRI between two consecutive ranges was highly significant (p<.002). Similarly, the degree of decrease in BE predicted could itself serve as a management tool. 4-5cm The coefficients did not reach significance (β = .10, p < .526), ​​but the FRI trajectory was highly significant (β = -.48, p < .005).

[0197] FSS was present in 35 cases at both the 6cm-7cm and 8cm-9cm intervals. Repeating this analysis, the corresponding decreases, along with the initial FRI variable, yielded a multivariate R of .69. The initial level at 6cm-7cm and the decrease from 6cm-7cm to 8cm-9cm were highly significant. Correlation and regression analyses aimed at simultaneously predicting BE were compatible.

[0198] After successfully predicting BE levels within and between adjacent cervical dilations, the relationship between FRI scores (levels and trajectories) in 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 was assessed. Logistic regression equations were used to analyze two sources of information derived from cervical dilations of 5 cm to 7 cm. Figure 7 These results from BE are shown; Figure 8 These pH results are shown. In summary, the decrease was 50% at cervical dilation of 4-10 cm; 41% at cervical dilation of 5 cm; and 27% at cervical dilation of 6-7 cm. In each comparison, a small number of cases actually showed improvement (approximately 10%).

[0199] 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 and 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 represents the natural logarithmic change in the probability of being in the low BE category when the independent variable changes by one unit. There are two independent variables here: the initial FRI score at a given dilation and the degree of change in FRI between this dilation and the 10 cm dilation. Additionally, "N's R" represents the change in the probability of being in the low BE category. 2 "" indicates that R is derived from ordinary least squares regression 2 The Nagelkerke approximation; "HL" is an 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 has not been missed in the model).

[0200] A larger question is to what extent the logarithmic odds of the fetus 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) in 5-7 all have sufficiently large N's and are consistent and highly significant in their estimates. The higher the initial FRI score, the smaller the negative value of the trajectory, and the lower the probability that the fetus will reach the lowest 30%. Figure 9 ROC curve analysis confirmed the potential utility of this method as a screening tool for assessing the risk of acidosis at the beginning of the second stage of labor.

[0201] Surprisingly, the impact of intrauterine resuscitation (IR) was taken into account. Figure 5 In the model (by assessing the extent to which the use of IR has additive and / or interactive effects when paired with the base excess variable), neither additiveness nor as an interaction term combined with BE1 or BE decrease adds anything to the analysis; none of the additive coefficients are significant. It is noteworthy that 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 the correlation between BE decrease and IR use (r = -0.06) reveals little correlation between them, suggesting that the attending physician's decision to use IR is not influenced by BE1 levels or their short-term fluctuations.

[0202] Tables 7 and 8 below show the results of further incorporating the Fetal Reserve Index (FRI) assessment into the acidosis risk model.

[0203] Table 7: Regression results of acidosis risk models including BE, FRI, and IR

[0204]

[0205]

[0206] Table 8: Summary classification table of the models in Table 4 and observed test features

[0207] Equation prediction <-12BE Normal BE <-12BE 15 8 23 Normal BE 38 287 325 53 295 348

[0208] In the table above, "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 positive cases) is 65%*; NPV (true negative / all negative cases) is 88%; and "Accuracy" (true positive and true negative) / total is 87%.

[0209] These features are very good, except for low sensitivity. The total R-squared simulation was not significantly different from the earlier model (R-squared = 0.33), but the Homer-Lemeshow statistic (sig < 0.63) indicates that the model did not miss too much.

[0210] Figure 9 It indicates Figure 5 The variant of the model shown also includes the FRI score.

[0211] Models can also be constructed without scalp sampling BE readings—a method that has become obsolete over the past few decades. Table 9 presents these results. Although the explained variance (R-squared simulation = 0.11) is about one-third that of the composite model, the patterns are very similar.

[0212] Table 9: Regression results of the acidosis risk model including FRI and IR

[0213]

[0214]

[0215] Figure 10 It indicates Figure 9 The variant of the model shown does not include BE data.

[0216] IR combination has additive and interactive effects in reducing the risk of birth acidosis (in conjunction with a decrease in FRI), but the decrease in FRI itself does not have a separate additive effect. Regarding the characteristics of the model shown as a classification table (Table 10), the sensitivity is very low, but the PPV is much better.

[0217] Table 10: Classification table and observed test features of the models in Table 6

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

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

[0220] Next, turn to Figure 11 The table below shows the ROC curves describing the comparison of acidosis (umbilical cord blood). Table 11 summarizes the results. Figure 11 The area under the curve.

[0221] Table 11

[0222] Area under the curve

[0223] Test outcome variable: Predicted probability

[0224]

[0225]

[0226] a. Under nonparametric assumptions

[0227] b. Null hypothesis: True area = 0.5

[0228] Next reference Figure 12 The BE value is represented by three lines: the 75th (top line), 50th (middle line), and 25th (bottom line) percentiles of the BE measurement at a given dilation, cord blood, and postpartum time (from early labor to the second stage of labor, delivery, and 1 hour postpartum). The BE value creates three parallel lines of variation. Importantly, the IDR (not shown in the figure) can be used to predict the likelihood of the fetus / infant reaching a high risk of acidosis levels for injury and damage in early labor. Improving the assessment of acidosis risk may lead to changes in obstetric care, such as earlier initiation of IR and possible transfer of patients to high-risk centers early in labor, where such transfer is feasible.

[0229] Same reference Figure 13 Further analysis of the lower portion of the curve revealed that for the 10th percentile (the bottom line), the birth BE (based on cord blood) was -12.5—entering the risk zone. The BE then dropped sharply to -14.5 over the next four minutes and remained in the danger zone until the 16th minute. This is the period of greatest risk for infant injury. By definition, 9% of cases are actually worse than this.

[0230] The data presented in this article demonstrate that FRI (indirect assessment of acidosis risk) is significantly associated with BE, which can help in the timely recommendation of which patients should undergo fetal scalp or other fetal blood sampling for BE analysis. These data also suggest that both outcomes (BE and FRI) can predict fetal risk levels and allow for earlier intervention than currently possible.

[0231] To verify the above, Figures 14-17Three graphs were plotted, showing the 90th, 75th, 25th, and 10th percentiles of BE results (bottom line in each graph) at different cervical dilation and time periods, plotted against the FRI results (top line in each graph) for the same data. Similarly, these data suggest that the FRI score (top line) can be used as a screening test in early labor to determine who should have their fetal scalp sampled to obtain the BE value (bottom line).

[0232] In further confirmation of the above, Figure 18 BE and FRI values ​​for cervical dilation at 4-5 (leftmost point on the X-axis), 6-7, 8-9, 10, and at birth (rightmost point on the X-axis) were plotted. These plots show measurements of the median BE value, the lowest quartile BE value, the median FRI score, and the lowest quartile FRI score. It is worth noting that the FRI score... Figure 18 The score is displayed as a number from 0 to 1, where 1 represents an FRI score of 100.

[0233] Similarly, Figure 19 The graphs show FRI scores and pH measurements at cervical dilation points 4-5 (leftmost point on the X-axis), 6-7, 8-9, 10, and at birth (rightmost point on the X-axis). These graphs also show the median pH, lowest quartile pH, median FRI score, and lowest quartile FRI score measurements. It is noteworthy that the FRI score at... Figure 19 The score is displayed as a number from 0 to 1, where 1 represents an FRI score of 100.

[0234] at last, Figure 20 The figures show pH and BE measurements at cervical dilation 4–5 (leftmost point on the X-axis), 6–7, 8–9, 10, and at birth (rightmost point on the X-axis). These figures show the median BE value, the lowest quartile BE value, the median pH fraction, and the lowest quartile pH fraction measurements.

[0235] Acidosis as reflected by the BE value is generally the closest approximation for determining the risk of injury, although experience to date is insufficient to accurately estimate the risk for any given fetus. The MoM classification makes immediate risk assessment easier to understand. Adding a trajectory improves the accuracy of risk level progression. Since the likelihood of continuous BE or pH measurements starting early in labor, especially before the active phase of labor (<6cm), the FRI and its trajectory appear to be a reasonable alternative indicator. Combining the available information in the FRI allows for inference of the risk of acidosis at the onset of the second stage of labor and can also suggest when to consider FSS. In summary, this is an improvement over CTG in predicting acidosis and its sequelae.

[0236] The above results support several methods for identifying and reducing the risk of fetal neural damage.

[0237] The first such method involves analyzing fetal blood during a first time period of labor (e.g., when the cervix is ​​dilated to 0-3 cm) to determine at least a first alkali excess (BE) value in the fetus; then, the median multiple of the BE value for the first time period is determined by dividing the BE value by the median BE value of a dataset (e.g., used in the analysis described herein), which includes a population of fetal BE values ​​established during the same time period as the first time period during the first stage of labor. As discussed herein, a BE value that is a predefined median multiple (MoM) BE value (e.g., 1.5 at dilation of 0-3 cm) indicates a risk of neurological injury in the fetus. When the identification step indicates a risk of neurological injury in the fetus, labor is intervened with any routine treatment measures to treat the fetus and reduce or eliminate the risk of neurological injury.

[0238] Another method supported by this 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 cervical dilation is 0-3 cm) to at least determine a first BE value for the fetus. A BE value ≤ -5 (determined by the above analysis) indicates a risk of fetal neurological injury. If the identification step indicates a risk of fetal neurological injury, treatment is administered by intervening in labor with any routine medical measures (whether intrauterine or in a decision to expedite delivery) to reduce or eliminate the risk of fetal neurological injury.

[0239] Another method supported by this disclosure includes the following steps:

[0240] (a) Monitor at least a first set of concurrent clinical parameters of the fetus, the concurrent clinical parameters indicating the current risk level of neural damage in the fetus;

[0241] (b) During a first time period in the first stage of labor (e.g., when the cervix is ​​dilated to 0-3 cm), the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as an FRI value;

[0242] (c) Determining the median multiple (MoM) of the FRI values ​​for the first time period by dividing the FRI value by the median FRI value of a dataset (e.g., used in the analysis described herein), the dataset comprising a population of FRI values ​​established during or before the first labor period at the same time as the first time period, wherein a MoM of the FRI value being a predefined median multiple of the FRI value indicates the presence of the risk of the neurological injury; and

[0243] (d) Treating the fetus indicated by step (c) as having the risk of said nerve damage, wherein said treatment step includes intervening in delivery through any conventional treatment measures to reduce or eliminate the risk of said fetal nerve damage.

[0244] When step (c) indicates a risk of the aforementioned neurological injury in the fetus, the data disclosed herein support a further step: analyzing fetal blood at least during a second time period in the first stage of labor (e.g., when cervical dilation is less than 10 cm) to determine at least an excess alkali (BE) value. As previously mentioned, the BE value is a more accurate indicator of the risk of acidosis. Therefore, determining the FRI in early labor helps differentiate which infants require more invasive fetal blood testing and which do not.

[0245] The data disclosed in this article also supports further steps such as fetal blood analysis during a third time period in the first stage of labor, which is later than the second time point.

[0246] Another method supported by this disclosure utilizes the rate of decline in BE values ​​determined during the first stage of labor to identify and treat the risk of nerve injury. The method includes the following steps:

[0247] The risk of fetal neurological injury during labor is identified by: (i) analyzing fetal blood at a first time point of the first stage of labor (e.g., when cervical dilation is 0-3 cm) to determine at least a first BE value for the fetus; (ii) analyzing fetal blood at a second time point of the first stage of labor, later than the first time point (e.g., after the first stage of labor but before cervical dilation reaches 10 cm) to determine at least a second BE value for the fetus; and (iii) determining the rate of decrease from the first BE value to at least the second BE value, wherein a rate of decrease of at least a predefined value (e.g., 46% or higher by a non-limiting embodiment) indicates a risk of fetal neurological injury. When the identification steps indicate the presence of the risk of neurological injury, labor is intervened to treat the fetus to reduce or eliminate the risk of neurological injury.

[0248] Instead of comparing the BE decline rate to a predefined percentage, the aforementioned method may alternatively include the step of determining the MoM of 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 fetal BE decline rates established during the first labor stage for the same time period as the first and second time periods. According to this variant, when the MoM of the decline rate is a multiple of the predefined median decline rate, it indicates a risk of neurological damage to the fetus. When the risk of neurological damage is indicated, labor is intervened to treat the fetus using any conventional treatment measures.

[0249] Another approach supported by the data described in this article includes the following steps:

[0250] (a) The fetus is monitored for at least a first set of concurrent clinical parameters, which indicate the current risk level of neural damage in the fetus;

[0251] (b) During labor or in the first time period prior to labor, the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (FRI value).

[0252] (c) During or before delivery, in a second time period later than the first time period, the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the risk of the determined current level is expressed as an FRI value;

[0253] (d) Determine the rate of decrease from the first FRI value to the second FRI value;

[0254] (e) Determining the median multiple (MoM) of the FRI values ​​for the first time period by dividing the FRI value by the median FRI value of the dataset, the dataset comprising a population of FRI values ​​established during or before the first labor period at the same time as the first time period, wherein a MoM of the FRI value being a predefined median multiple of the FRI value indicates the presence of the risk of the neurological injury; and

[0255] (f) The MoM of the decline rate is determined by dividing the decline rate by the median decline rate of the dataset, which includes a total population of FRI value decline rates established during or before the first labor stage, at the same time period as the first and second time periods, wherein when the MoM of the decline rate is a predefined MoM decline rate, it indicates that the fetus has neurological damage.

[0256] Another approach supported by the data described in this article for reducing the risk of neural damage in human fetuses during childbirth includes the following steps:

[0257] (a) Monitor at least a first set of concurrent clinical parameters of the fetus, the concurrent clinical parameters indicating the current risk level of neural damage in the fetus;

[0258] (b) During labor or in the first time period before labor (e.g., when the cervix is ​​dilated to 0-3 cm), the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (FRI value).

[0259] (c) During or before delivery, at a second time period (e.g., when the cervix is ​​dilated to less than or equal to 10 cm), the second time period being later than the first time period, the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as an FRI value;

[0260] (d) Determine the rate of decline from a first FRI value to a second FRI value, wherein a rate of decline greater than a predefined value (e.g., but not limited to a rate of decline of 46% or higher) indicates a risk of neurological damage in the fetus; and

[0261] Treatment is given to fetuses indicated by the identification steps to present with the risk of said neurological damage, wherein said treatment steps include intervention during delivery through any routine treatment measures to reduce or eliminate the risk of said neurological damage to the fetus.

[0262] The MoM method described herein can be viewed as an "amplification" of the increased metabolic risk assessment. The method disclosed herein allows for immediate understanding of the risk of measurements without immediately linking them to the progress of labor. Furthermore, according to the invention, focusing on early data collection during labor helps to identify fetuses delivered "healthily," while for fetuses experiencing deteriorating labor conditions, FRI and MoM can prevent harm to fetuses that may already be compromised at admission.

[0263] A significant medical-legal issue in obstetrics is determining whether an infant is harmed during delivery or at the moment of arrival at delivery. Because the interpretation of EFM (Expected Fetal Development) is highly subjective and lacks broad consensus, practitioners lack reliable guidance in making this decision. In medical-legal contexts, this often leads to conflicting opinions from different medical experts. Understandably, the assessment methods for admission and care discussed in this article provide objective guidance for making these decisions.

[0264] The data presented here demonstrate that combining BE assessment during early labor with the rate of subsequent BE decline provides a sensitive method for early prediction of metabolic acidosis risk. This is performed before any abnormalities are observed in the EFM. Furthermore, these data suggest that the initial FRI and the initial rate of FRI decline provide a useful screening tool to determine who should undergo fetal scalp sampling or other fetal blood analyses, and then determine the risk level of acidosis at birth. This early risk assessment can allow for earlier initiation of intrauterine resuscitation, which has been shown to reduce the likelihood and duration of metabolic acidosis, the risk of neurological damage, and the need for emergency delivery.

[0265] The implementation of the aforementioned method is envisioned to utilize dedicated equipment or general-purpose computers, tablets, smartphones, etc., to receive various sensor inputs (manual and / or automatic reception), perform various determining steps of the method described herein, and provide visual and / or audio instructions for risks and / or intervention recommendations.

[0266] It is conceivable that the methods described above can be implemented using devices such as those comprising at least one computer.

[0267] In one embodiment, such a device includes at least one computer operable to determine a first alkali excess (BE) value of the fetus established during a first time period in the first stage of labor, and to determine 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 comprising a group of fetal BE values ​​established during the same time period as the first time period in the first stage of labor. When the BE value is a predefined median multiple of the BE value, the at least one computer is further operable to indicate a risk of neurological damage in the fetus.

[0268] Those skilled in the art will understand that the at least one computer, or even another computer operatively connected to the at least one computer, can be programmed with a dataset including a fetal BE value population established during the same time period as the first time period during the first stage of labor.

[0269] In another embodiment, the device includes at least one computer operable to: receive input signals 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, during or before labor, a first time period based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (first FRI value); determine a median multiple (MoM) of the first FRI value by dividing the first FRI value by the median FRI value of a dataset comprising a group of FRI values ​​established during or before a first labor period at the same time period as the first time period; and provide an output indicating (i) the presence of a risk of neurological injury when the determined MoM of the first FRI value is a predefined median multiple of the FRI value, and / or (ii) the presence of a neurological injury in the fetus when the MoM of the rate of decline is a predefined rate of decline of MoM.

[0270] Similarly, those skilled in the art will understand that the at least one computer, or even another computer operatively connected to the at least one computer, can be programmed with a dataset that includes a population of FRI values ​​established during the same time period as the first time period during the first labor process.

[0271] Furthermore, the at least one computer in this embodiment is operable to: receive input indicating the excess alkali (BE) value of the fetus during at least a second and a third time period during a first labor process, wherein the third time period is later than the second time point; determine the rate of decrease of the BE value during the second and third time periods; and provide an output indicating the risk of nerve damage when the rate of decrease reflected by the BE value during the second and third time periods 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 the excess alkali (BE) value of the fetus during at least a first time period and a second time period during a first labor process, wherein the second time period is later than the first time point, to determine the rate of decline of the BE values ​​during the first and second time periods, and to provide an output indicating the risk of neurological damage when the rate of decline reflected by the BE values ​​during the second and third time periods is greater than a predefined value (e.g., 46%).

[0273] In another embodiment, the device includes at least one computer operable to: receive input indicating alkali excess (BE) values ​​of the fetus during 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; determine the rate of decline from the first BE value to the second BE value; determine a median multiple (MoM) of the rate of decline by dividing the rate of decline by a dataset comprising a population of fetal BE value decline rates established during the first stage of labor for the same time periods as the first and second time periods; and provide an output indicating a risk of neurological damage when the MoM of the rate of decline is a predefined median multiple of the rate of decline.

[0274] In another embodiment, the device includes at least one computer operable to receive input signals indicating at least a first set of concurrent clinical parameters, the first set of concurrent clinical parameters indicating a current risk level of fetal neural injury; determining the current risk level of fetal neural injury based on the first set of concurrent clinical parameters during or before delivery, wherein the determined current risk level is expressed as a numerical value (a first FRI value); determining the current risk level of fetal neural injury based on the first set of concurrent clinical parameters 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; determining a rate of decrease from the first FRI value to the second FRI value; and providing an output indicating the presence of a risk of neural 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.

[0275] In another embodiment, the device includes at least one computer operable to:

[0276] Receive an input signal indicating at least a first set of concurrent clinical parameters, the first set of concurrent clinical parameters indicating the current risk level of said fetal neural injury;

[0277] During labor or in the first time period prior to labor, the current risk level of the fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (first FRI value).

[0278] During or before delivery, in a second time period later than the first time period, the current risk level of neural damage in the fetus is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a second FRI value.

[0279] Determine the rate of decrease from the first FRI value to the second FRI value;

[0280] The median multiple (MoM) of the first FRI value is determined by dividing the first FRI value by the median FRI value of the dataset, which includes a group of FRI values ​​established during or before the first labor process in the same time period as the first time period.

[0281] The MoM of the decline rate is determined by dividing the decline rate by the median decline rate of the dataset, which includes a population of FRI value decline rates established during or before the first labor stage, corresponding to the first and second time periods; and

[0282] Provide (i) an output indicating a risk of neurological damage when the MoM of the determined first FRI value is a multiple of the median of a predefined FRI value, and / or (ii) an output indicating a risk of neurological damage to the fetus when the MoM of the rate of decrease is a predefined rate of decrease of MoM.

[0283] In an exemplary form, the first time period during labor is characterized by cervical dilation of 0-3 cm; the second time period during labor is characterized by cervical dilation of less than or equal to 10 cm.

[0284] In one embodiment, a decrease rate of 46% or higher indicates a risk of neurological damage in the fetus.

[0285] 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. When using these parameters, the at least one computer is further operable to determine, during the first time period, whether each concurrent clinical parameter (a) through (e) independently exhibits at least one unsafe characteristic, and to convert the number of concurrent clinical parameters (a) through (e) simultaneously and independently exhibiting at least one unsafe characteristic into the first FRI value. For example, this can be achieved by executing a simple algorithm that sums the number of parameters (a) through (e) simultaneously and independently unsafe by using arbitrarily assigned values ​​(e.g., 1 or 0) for each parameter.

[0286] The output of the aforementioned embodiments can take any conventional form, including one or more of graphic displays, warning lights, and / or sounds. These outputs can be provided by the device itself. They can also, or alternatively, be provided by peripheral devices such as video displays and / or printers.

[0287] It is also conceivable that the devices included in this disclosure may alternatively or additionally operate to provide other information, including FHR tracking, uterine activity tracking, and / or further information relating to the current indicated level of fetal risk, as a non-limiting example, including instructions to clinicians or physicians regarding predetermined actions required or recommended for the identified level of risk. Such additional information may, for example, be provided through at least one output.

[0288] The at least one computer is further operable to receive (e.g., by conventional means, such as a keyboard or mouse in conjunction with a graphical user interface) user input indicating the BE value obtained according to the method described above.

[0289] It is conceivable that the device according to the invention may include a self-contained unit comprising one or more sensors capable of monitoring / receiving user input indicating the aforementioned parameters, or a separate unit receiving input corresponding to these parameters from other separate sensors. If the former, as described above, the at least one output may also provide the capability to include one or more display and / or printouts showing FHR and maternal uterine activity tracking, provided, for example, by conventional FHM and uterine contraction sensors. If the latter, the device for implementing the method of the invention may be a separate device connectable to an FHM device and capable of receiving data therefrom.

[0290] According to another embodiment of the device of the invention, the assessment of the fetal risk level can be provided remotely, for example via the Internet or other computer networks. According to this embodiment, it is envisioned to provide one or more individuals, such as one or more doctors and / or nurses in geographically remote locations, with a display / interface operable to the device at the patient's location, to provide the assessment of the fetal risk level to one or more individuals in remote locations, and to provide FHM and / or other monitored parameters as needed, in order to assist those giving birth in the delivery room (including via the interface and / or via other means, such as telephone, video conferencing equipment, etc.). For example, the system could be implemented in a community hospital where there is a lack of sufficient obstetricians in the delivery room.

[0291] In an exemplary embodiment, the aforementioned device or other device operable to perform the method of the present invention is operatively connected to the patient (directly or via other monitoring devices) to monitor FHR. FHR baseline variability, FHR acceleration, and FHR deceleration are determined continuously or periodically from the FHR according to a desired schedule, and parameters (a) through (d) are compared with known unsafe characteristics (e.g., those specified herein), 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) through (d), this determination results in an indication of the corresponding risk level for the fetus via one or more outputs. Furthermore, the device will preferably provide instructions for actions requested / recommended by a clinician or other user.

[0292] Figures 21 to 23 An exemplary, but by no means limiting, device for performing the above methods is schematically depicted.

[0293] More specifically, Figure 21 A device 10 is shown, comprising at least one computer 20 operable to receive input signals, such as input signals 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 operative connections of these different elements 20, 30, and 50, which can 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., multiple score-specific lights, each corresponding to a different risk level), warning sounds, etc. 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; non-limiting embodiments may include instructions to a clinician or physician relating to predetermined actions required or recommended for the identified risk level. For example, such additional information may be provided via at least one output 50. The at least one computer 20 may also be operable to receive user input (e.g., via conventional means, such as a keyboard or mouse combined with a graphical user interface). It is contemplated that the device 10 may include an integrated unit or a standalone unit 10', the integrated unit including the one or more sensors 30 capable of monitoring / receiving user input indicating the aforementioned parameters, for example… Figure 22 As illustrated schematically, the independent unit 10' receives signals from other independent sensors 30', 30'', ... Figure X It receives inputs corresponding to these parameters.

[0294] According to another implementation plan ( Figure 23The device 110, which can be remotely provided to assess the level of fetal risk, can be used, for example, via the Internet or other computer networks (shown in 300). According to this embodiment, it is envisioned to provide a display / interface 210 operably connected to the device 110 at the patient's location 100 to one or more people, such as one or more doctors and / or nurses at a geographically remote location 200, to provide assessment of the level of fetal risk to one or more people in remote locations, thereby enabling assistance to those giving birth in the delivery room (including via the interface and / or via other means, such as telephone, video conferencing equipment, etc.). For example, the system could be implemented in a community hospital where there is a shortage of obstetricians in the delivery room. For purposes of illustration and description, the foregoing description of exemplary embodiments of the invention has been presented. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed, and modifications and variations are possible based on the foregoing teachings or from practice of the invention. The embodiments shown and described are intended to explain the principles of the invention and its practical application, enabling those skilled in the art to utilize the invention in various embodiments and with various modifications suitable for the intended particular use. Although only a few embodiments of the invention have been described in detail in this disclosure, those skilled in the art will readily understand that many modifications are possible without substantially 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 invention. Other substitutions, modifications, alterations, and deletions may be made to the design, operating conditions, and arrangement of the exemplary embodiments without departing from the spirit of the invention.

Claims

1. A device for reducing the risk of neural damage in a human fetus before or during delivery, the device comprising: At least one computer, said computer being operable to: Receive input indicating the alkali excess value of the fetus during 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 period; Determine the rate of decline from the first alkali surplus value to the second alkali surplus value; as well as Provides an output indicating a risk of nerve damage when the determined rate of decline from the first base excess value to the second base excess value is at least a predefined rate of decline.

2. The device of claim 1, wherein the predefined decrease rate is 46%.

3. The device of claim 1, wherein the first time period during labor is characterized by cervical dilation of 0-3 cm.

4. The device of claim 3, wherein the second time period during labor is characterized by cervical dilation of less than or equal to 10 cm.

5. The device according to claim 1, wherein, The at least one computer is further operable to: The median multiple of the decline rate is determined by dividing the decline rate by the median decline rate of the dataset, which includes a group of fetal alkali excess decline rates established during the same time period as the first and second time periods during labor; as well as Provides an output indicating a risk of nerve damage when the median multiple of the decline rate is a predefined median multiple of the decline rate.

6. The apparatus of claim 1, wherein the at least one computer is further operable to: Receive an input signal indicating at least a first set of concurrent clinical parameters, the first set of concurrent clinical parameters indicating the current risk level of said fetal neural injury; During labor or in the first time period prior to labor, the current risk level of said fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a numerical value (first FRI value). During labor or in a second time period later than the first time period, later than the first time period, the current risk level of the fetal neurological injury is determined based on the first set of concurrent clinical parameters, wherein the determined current risk level is expressed as a second FRI value; Determine the rate of decrease from the first FRI value to the second FRI value; The median multiple of the first FRI value is determined by dividing the first FRI value by the median FRI value of the dataset, which includes a group of FRI values ​​established during or before the first labor period in the same time period as the first time period. The median multiple of the decline rate is determined by dividing the decline rate by the median decline rate of the dataset, which includes a group of decline rates of FRI values ​​established during or before the first labor phase, in the same time period as the first and second time periods. as well as Provide (i) an output indicating a risk of neurological damage when the median multiple of the determined first FRI value is a predefined median multiple of the FRI value, and / or (ii) an output indicating that the fetus has neurological damage when the median multiple of the decline rate is a predefined median multiple of the decline rate.

7. The device of claim 6, wherein: The first set of concurrent clinical parameters includes (a) FHR, (b) baseline FHR variability, (c) FHR acceleration, (d) FHR deceleration, and (e) maternal uterine activity; and The at least one computer is operable to determine, during the first time period, whether each of the concurrent clinical parameters (a) to (e) independently exhibits at least one unsafe feature, and to convert the number of concurrent clinical parameters (a) to (e) that simultaneously and independently exhibit at least one unsafe feature into the first FRI value.

8. The device of claim 6, wherein the second time period is at most one hour later than the first time period.

9. An apparatus for reducing the risk of neurological injury in a human fetus during labor, the apparatus comprising at least one computer operable to determine a first alkali excess value of the fetus established during a first time period in a first stage of labor, to determine a median multiple of the alkali excess value of the first time period by dividing the alkali excess value by a median alkali excess value of a dataset, the dataset comprising a group of fetal alkali excess values ​​established during the same time period as the first time period in the first stage of labor, and wherein the at least one computer is further operable to indicate a risk of neurological injury in the fetus when the alkali excess value is a predefined median multiple of the alkali excess value.

10. A device for reducing the risk of neural damage in a human fetus before or during delivery, the device comprising: At least one computer, said computer being operable to: Receive input indicating the alkali excess value of the fetus during 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 period; Determine the rate of decline from the first alkali surplus value to the second alkali surplus value; The median multiple of the alkali excess reduction rate is determined by dividing the reduction rate by the median reduction rate of the dataset, which includes a group of fetal alkali excess reduction rates established during the first labor process, at the same time period as the first and second time periods. as well as Provides an output indicating a risk of nerve damage when the median multiple of the rate of decrease of the base excess is a predefined median multiple of the rate of decrease.

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