WO2009142599A1

WO2009142599A1 - Device for detecting oxygen depletion in fetuses during childbirth

Info

Publication number: WO2009142599A1
Application number: PCT/SE2009/050588
Authority: WO
Inventors: Mikael Ryttinger; Johanna Lundstedt; Carina Mallard; Jan SÖDERLUND; Henrik Hagberg; Maria Olsson
Original assignee: Syspiro Diagnostics Ab
Priority date: 2008-05-22
Filing date: 2009-05-22
Publication date: 2009-11-26

Abstract

The invention relates to a diagnostic device for the monitoring of markers of global metabolomic status in the tissue of a fetus during birth, comprising a probe (101) containing an inlet tube (105), an outlet tube (106), and a membrane portion (104), said membrane portion (104) allowing the passage of markers of global metabolomic status from the tissue, said probe containing one or more anchoring means (110) at the distal end of the probe in close proximity to the membrane portion (104). The device can be attached to the presenting part of the fetus (usually the head) through the birth-canal of the pregnant woman. The probe, which is a part of a disposable device, allows certain metabolites to perfuse from the tissues through the membrane of the probe. The metabolites are then transported by the microdialysis fluid to an analysis unit. The analysis performed on the fluid determines the concentration of certain metabolites such as lactate or pH. CTG functionality is be added to the disposable device for additional monitoring of the status of the fetus.

Description

TITLE

DEVICE FOR DETECTING OXYGEN DEPLETION IN FETUSES DURING CHILDBIRTH

DESCRIPTION

TECHNICAL FIELD

The present invention relates to a device for fetal monitoring, and more particularly a device for determining the global metabolomic status of the fetus during labor and delivery. The device will assist the obstetrician in diagnosing whether an acute caesarean is necessary. The innovation may utilize a combination of two technologies, microdialysis and cardiotocography (CTG), both providing important information regarding the status of the fetus.

BACKGROUND OF THE INVENTION

In approximately 25 out of 1000 live births the infants suffer from fetal asphyxia, a pathological condition caused by oxygen depletion, which occurs when the oxygen supply of the fetus is interrupted for a period of time. In about one in every 1000 births fetal asphyxia results in neurological damages or death if no actions are taken. Every year, this condition leads to the death of thousands of children and just as many are so severely damaged by the condition that they obtain irreversible brain damage, leading to cerebral palsy. The consequences resulting from brain damage are often severe disabilities and the need for lifelong attendance.

Today's fetal monitoring methods lack specificity and/or provide only intermittent information. This leads to an uncertain situation and two types of serious consequences; first, some cases of asphyxia are not detected, which sometimes lead to severe irreversible brain damage or death; second and much more common, operative interventions (cesarean section, ventous or forceps) are performed unnecessarily. An acute caesarean section may not be necessary; however it is often chosen when the physician is in doubt of the status of the fetus, i.e. when there is not sufficient information is available to exclude severe asphyxia with reasonable certainty. Acute caesareans are not only very costly procedures for the healthcare systems, but more importantly they also increase the risk for both mother and child than a planned caesarean section Therefore, there is both a clear and outspoken need on the market for a diagnostic device that is better at detecting fetal asphyxia than today's methods

The electronic fetal monitoring system (EFM) most frequently used around the world is Cardiotocography (CTG) CTG measures both the contractions of the uterus as well as the fetal heart rate The fetal heart rate can be measured externally, through ultrasound, as well as internally, via a scalp electrode which generally gives more accurate information When a complicated childbirth is expected, the internal measurement is generally preferred

Fetal electrodes are well established in obstetric care Such electrodes are designed to be connected to an amplifier and a cardiotachometer in order to record the fetal electrocardiogram and heart rate during the labor and delivery process It is not necessary to penetrate the tissue in order to get a signal

Instead of just analyzing the fetal heart rate like in CTG, the other EFM method, STAN performs an analysis of the fetal electrocardiogram STAN combines CTG with ST waveform analysis, i e analysis of that part of the fetal ECG called the ST segment, which changes if the fetus experiences hypoxia (oxygen deficiency) Hence, STAN technology uses CTG to identify a high-risk group The fetal electrocardiogram is recorded through a scalp electrode and the data obtained is then analyzed by a computer Even if the information obtained through STAN is more specific than the information from regular CTG, both methods provide the medical staff with information that sometimes is difficult to interpret

While the EFM methods have the benefit of being able to give a continuous flow of data, they have problems with specificity, and both CTG and STAN have been criticized Since the fetal heart rate can be affected by a wide range of factors and should be considered as an indirect variable, the EFM methods sometimes give inconclusive information regarding the status of the child This is also why some studies have shown that there is no detectable difference in fetal outcomes in using STAN over regular CTG Another problem is that if the child is already in a state of asphyxia when it arrives at the clinic, the EFM is unable to detect the condition Another method used for detection of asphyxia is fetal blood sampling, which is achieved by puncturing the skin of the fetal scalp during the birth process. Fetal scalp blood sampling is a method in which a small sample of the child's blood is taken out for analysis. The sample can be analyzed with regards to pH and/or lactate content of the blood. These methods are considered to give quite a specific assessment of the state of the child but can only provide a snapshot of the situation. This means that repeated skin punctures have to be made in the scalp of the child during the birth process, in order to obtain a clear picture of the child's condition. The sample of blood must also be transported from the delivery room to the analysis unit, which leads to an unwanted time delay before the result is obtained. There are several other disadvantages as well with using this method. For instance, it can also be difficult to actually obtain blood from the scalp, especially blood that is free from contamination. This procedure puts the mother under a lot of stress since she has to change position in order to let the obstetrician get access to the head of the baby. She might also interpret the situation as if there is something is wrong with her baby or that the repeated sampling is hurting her child.

Another technique which quite the opposite to giving a snapshot picture of the blood status would be microdialysis, which instead provides a continuous status of the tissue being monitored. Microdialysis is a well established technique in measuring metabolites in blood and tissues with several applications in humans. Microdialysis enables the in vivo measurement of tissue chemistry in humans and is feasible in virtually every human organ. Microdialysis probes are currently available for applications in peripheral subcutaneous tissue, brain and heart, where it is used to monitor the biochemistry of the tissue. The technique is also often used for metabolic monitoring and as a monitoring device in clinical research, drug monitoring, and drug development.

Many other, less successful, methods have been developed, like pulse oximetry. Pulse oximetry is a method that utilizes the fact that blood with a low oxygen level has a slightly different red color than oxygenated blood. The blood is illuminated by light of two different wavelengths, with the same colors as the blood. The intensity of the reflected light is then measured. Depending on the intensity of the light of the two wavelengths reflected back it is possible to estimate the relative oxygenation of the blood. This method has not gained much acceptance since studies have shown that using pulse oximetry in combination with CTG has no measurable effect on operative interventions or the fetal outcome compared to CTG alone. Another unsuccessful method that has been developed is the pH probe. It has been proven either unpractical, unable to operate well or unable to give a stable signal. Also the combination of EFM and pH probe has proven to be unsuccessful. This method is perceived as having practical problems such as difficult to fixate in the fetal scalp. Combining the pH and fetal heart fate (FHR) electrodes in one mechanical assembly facilitated application to the fetal scalp in early labor but the combined assembly electrode was found to have other disadvantages. Hence these methods have not been successfully commercialized.

The present invention comprises a device for fetal monitoring that will solve many of the problems that are associated with known monitoring systems. The device utilizes a combination of two technologies, microdialysis and cardiotocography (CTG), to determine the global metabolomic status of the fetus during labor and delivery. The innovation offers a monitoring system providing important information regarding the status of the fetus that is both specific and continuous. Bringing such a solution to the market would not only save huge costs for the society, but also reduce a lot of human suffering and, most importantly, save lives.

SUMMARY OF THE INVENTION

More specifically the present invention relates to a diagnostic device for the monitoring of markers of global metabolomic status in tissue, and diagnosing the need for an acute caesarean section. The invention comprises a probe containing an inlet tube, an outlet tube, and a membrane portion, said membrane portion allowing the passage of markers of global metabolomic status from the tissue, said probe containing one or more anchoring means at the distal end of the probe in close proximity to the membrane portion.

In a preferred embodiment of the invention the diagnostic device further comprises electrodes for Electro Fetal Monitoring (EFM).

In a further embodiment of the invention the electrodes for Electro Fetal Monitoring (EFM) are combined with the membrane portion.

In a further embodiment of the invention the EFM comprises measurement of Cardiotocography (CTG) and/or STAN. In a preferred embodiment of the invention the markers of global metabolomic status are monitored in the tissue of a fetus.

In a further embodiment of the invention the tissue is located on the scalp of a fetus.

In a further embodiment of the invention the markers of global metabolomic status are of the group comprising lactate, pyruvate, pH, purine catabolites, xanthine, and hypoxanthine.

In a preferred embodiment of the invention the markers of global metabolomic status are of the group comprising lactate, pyruvate, and pH.

In a preferred embodiment of the invention the marker of global metabolomic status is lactate.

In a further embodiment of the invention the membrane portion has a length of 1-15 mm, more preferably 1.5-10 mm and most preferably 2-5 mm.

In a further embodiment of the invention the membrane portion has an inner diameter of about 0.1 -1.0 mm, preferably 0.2-0.9 mm, most preferably 3-0.8 mm.

In a further embodiment of the invention the anchoring means are provided with one to eight blades/wings or wires.

In a further embodiment of the invention the blades/wings or wires of the anchoring means have a length of 1 mm up to 15mm, preferably 2-6mm.

In a further embodiment of the invention the anchoring means have a stopping disc.

In a further embodiment of the invention the anchoring means are provided as one or more discs.

A further aspect of the invention relates to a method for supervising the course of childbirth by monitoring markers of global metabolomic status in the tissue of a fetus, wherein a diagnostic device according to the invention is applied to the tissue of a fetus during birth and continuously determines at least one marker of global metabolomic status, and in case the concentration of such a marker exceeds a preset value one takes appropriate action. DETAILED DESCRIPTION OF THE INVENTION

In the following examples the invention will be described in more detail. However, the described embodiments mentioned below are only given as examples and should not be limiting to the present invention. Other solutions, uses, objectives, and functions within the scope of the invention as claimed in the below described patent claims should be apparent for the person skilled in the art.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 shows one embodiment of the probe of the present invention; and

Fig. 2a-f shows different embodiments of the anchoring means according to the present invention; and

Fig. 3 is a schematic view of the introducer cannula and puncturing means of the present invention; and Fig. 4 is a schematic view of the probe of the invention when located in the lumen of the introducer cannula; and

Fig. 5 is a schematic view of how the probe with the anchoring means attaches to a tissue.

The technical solution chosen for the present invention is to use microdialysis to detect certain metabolites in the scalp tissue of children during the process of birth, in combination with cardiotocography. This solution gives the innovation its completely unique characteristic of being able to provide the user with a continuous as well as specific monitoring of the status of the child's condition.

By using the microdialysis technology, it is possible to provide both continuous and specific monitoring of metabolites related to oxygen depletion without having to take repeated blood samples. Microdialysis is a technique which can be used to determine the chemical components of the fluid in the extracellular space of tissues. It is mostly used as a research tool in order to study the chemistry of the tissues and has never before been used in detecting fetal asphyxia. The microdialysis method provides a direct profile of substances in the subcutaneous fluid as a reflection of those in the blood. A microdialysis probe is a device that is introduced into the tissue and designed to mimic a blood capillary in function. A microdialysis probe can be designed in different ways but generally a microdialysis probe consists of a thin tube wherein a perfusion solution (a salt solution that mimics physiological salt conditions in vivo) is transported. The perfusion solution is transported towards the distal end of the tube where there is provided a semi permeable microdialysis membrane, which is inserted into the tissues (in this case into the scalp tissue). The perfusion solution is transported past the microdialysis membrane which allows chemical substances present in the extracellular fluid (ECF) to pass across the membrane in order to even out the difference in concentration between the perfusion solution and the ECF. Thereafter the dialysate (perfusion solution which now contains substances present in the ECF) is transported away from the membrane probe and is collected for analysis. When the dialysate leaves the probe, it contains a representative concentration of different substances found in the tissues, but in a lower concentration. Since the perfusion solution is transported with a certain speed, complete equilibrium is not reached. The amount of time that the perfusion solution remains in the probe determines the concentration of chemical substances in the resulting dialysate. Slower transportation speed of the dialysate allows for more molecules to pass across the membrane and results in a higher concentration of this substance. The resulting concentration in the dialysate is also dependent on the characteristics of the chemical compound, such as size and electrical charge, and on the characteristics of the membrane. With a various range of microdialysis membranes it is possible to sample molecules in size ranging from a few hundred Daltons up to about 100,000 Daltons making it feasible to monitor metabolites peptides or even proteins. In general, larger molecules require longer time in order to be transported across the membrane than smaller molecules.

At the opposite end of the microdialysis probe is a connection system that puts the two tubes of the disposable device in contact with the analysis unit and allows for an easy change of disposables. The dialysate pumped out from the probe can then be analyzed by any technique known to the person skilled in the art in order to determine a certain chemical compound.

According to one embodiment of the invention, the disposable device of the invention comprises three different parts: a probe, an introducer cannula and a puncturing means. Figure 1 discloses one embodiment of a probe 101 according to the invention. The probe 101 is comprised of a membrane portion 104 at the distal end; an inlet (inner) tube 105 for supplying the perfusion solution to the membrane portion 104; and an outlet (outer) tube 106 disposed at the outside of the inner tube 105 transporting the perfusion solution away from the membrane portion 104 (see inset of Figure 1). Alternatively the perfusion solution is transported to the membrane portion through the outer tube 106 and exits the probe 101 through the inner tube 105. The transportation rate for the perfusion solution is 0.5-5 μl/min, preferably 1 -3 μl/min. The membrane portion 104 can be any shape such as a flat or curved sheet, or tubular. Preferably the membrane is shaped as a tube or a cylinder which is closed at one end and the opposite end is opened enclosing the outlet/inlet of the inner and outer tubes. The membrane can be a dialysis membrane that functions on the basis of molecular weight, size, charge and/or other suitable criteria. A longer membrane i.e. a larger membrane area recovers more substance(s) of interest, but will be limited by the depth of the probe in the fetal tissue. The membrane portion 104 used in this invention can have a length of about 1 -15 mm in length, more preferably 1.5-10 mm and most preferably 2-5 mm, and have an inner diameter of about 0.1-1.0 mm, more preferably 0.2-0.9 mm, most preferably 0.3-0.8 mm. The membrane is preferably semi-permeable and preferably composed of a biocompatible material such as polyamide or Cuprophan®. These are materials known for their semi-permeability which can be adjusted depending on the chosen density of the fibers. The inlet tube used in this invenstion can have a length of about 100 mm - 1000 mm, preferably 200 mm - 700 mm and the outlet tube can have a length of 20 mm - 200 mm, preferably 30 mm - 70 mm. The shaft of the probe can have a length of 20 mm - 300 mm. The diameter of the tubes can be about 0.6 - 1.5 mm.

The probe further comprises electrically conductive wires 107/108. The electrically conducting wires 107/108 are extended along the full length of the probe, from the membrane portion 104 (onto which they are attached), to the connectors 109 that are attached to a monitoring unit. These wires 107/108 provide the invention with the properties needed in order to perform the EFM (Electrical Fetal Monitoring) including fetal heart rate and uterus contraction measurements. One of the electrically conductive wires 107 (or metallic foil) will record electrical signals from the scalp of the fetus, while the other functions as an earthing electrode 108, picking up signals from the birth canal or leg of the mother. The electrically conductive wires 107/108 are separated from each other by an insulating material.

One or more anchoring means 110 is provided at the distal end of the probe in close proximity to the membrane portion 104 of the probe. Each anchoring member comprises one to eight blades/wings or wires 118 made from e.g. metal, metal alloys, plastic polymers, metal covered in polymeric material or carbon materials, which protrudes out from the device at an angle (Fig. 2a-c,e). The anchoring means can be located in one or more locations along the shaft of the probe. The blades/wings or wires 218 can be of a length of about 1 mm up to about 15mm, preferably 2-6 mm. The wings/blades or wires 218 prevent the device from unintentionally exiting the tissue of the fetus throughout the entire process of birth. In an alternative embodiment the anchoring means 210 is provided with a disc 219 that will prevent the probe from moving further into the tissue (Fig 2d). Alternatively the disc 219 is located between the membrane portion 204 and the anchoring means 210. In a further alternative embodiment of the anchoring means it consists of two discs 219, 220, one disc 219 that will prevent the probe from moving into the tissue and one disc 220 that will prevent the probe from moving out of the tissue (Figure 2f).

The disposable device of the invention further comprises an introducer cannula 302 for inserting the probe into the scalp of the fetus. The introducer cannula 302 has proximal end 311 at which a handle means 312 is provided, a distal end 313 and a lumen 314. The distal end 313 of the introducer cannula 302 is slightly narrowing in order to simplify insertion of the introducer cannula into the tissue. Preferably the wall of the insertion cannula is provided with a rupturable seam 315 to permit the introducer cannula to be pulled a part into two or more pieces and eliminated. A puncturing means 303 such as a needle may be inserted into the lumen 314 of the introducer cannula 302. The puncturing means 303 is provided with a pointed end 316 that can be used to puncture the tissue of the fetus. When the puncturing means 303 is introduced into the introducer cannula 302 the pointed end 316 protrudes out 1-15 mm, preferably 2-10 mm, most preferably 2.5-5 the distal end 313 of the introducer cannula 302. Suitable materials for the puncturing means 303 are e.g. metal or metal alloys, including those containing titanium, and/or polymers, carbon. The end opposite the pointed end 316 of the puncturing means is furnished with a plastic head 317 in order to prevent the puncturing means from penetrating too far into the tissue of the fetus. The puncturing means can be hollow or solid. In an alternative embodiment, the introducer cannula 302 is formed as a needle with a rupturable seam and able to penetrate tissue.

Insertion of the probe 101 of the invention into the fetus will now be described. The introducer cannula 302 containing the puncturing means 303 in the lumen is inserted through the birth canal and placed against a body part of the fetus. Preferably it is placed against the scalp of the fetus inside the uterus. After it is made sure that the distal end 313 of the introducer cannula 302 is in correct position the skin is punctured by the pointed end 316 of the puncturing means 303 and the distal end 313 of the introducer cannula 302 is inserted through the puncture hole a few millimeters. Once the introducer cannula 302 is inside the tissue, the puncturing means 103 can be removed from the lumen of the introducer cannula 302, leaving the introducer cannula 302 within the tissue. The probe 401 can thereafter be inserted into the lumen of the introducer cannula 402, while the introducer cannula 402 is still inserted in the tissue. The probe 401 is slightly longer than the introducer cannula 402 and when the probe 401 is fully inserted into the introducer cannula 402, the membrane portion 404 and the anchoring means 410 extend past the distal end 413 of the introducer cannula 402 (Figure 4). The membrane portion 504 of the probe is carefully inserted subcutaneously into the fetal tissue (521 of Figure 5a). The membrane portion 504 of the probe now fills the space that the pointed end 316 of the puncturing means 303 previously filled. Once the probe 501 has passed through the length of the introducer cannula 502, the blades/wings or wires 518 of the anchoring means 510 is extended, protruding into the surrounding tissue, and thereby preventing the probe 501 from exiting the fetal skin (Figure 5b). It should be noted that the probe does not necessarily have to be inserted straight (that is at an angle of 90°) into the tissue as illustrated in Fig. 5a-b. The person skilled in the art realizes that the probe should be inserted at an angle to the surface of the tissue, preferable at an angle of only a few degrees to the tissue. The wall of the introducer cannula is thereafter split along the rupturable seam 315 to permit removal of the introducer cannula 502, leaving the probe 501 in place.

Measurements

Previous methodologies of fetal monitoring are limited to the measurement of one or a few variables. The present methodology can measure hundreds of compounds and can therefore take full advantage of the rapid development of global profiling techniques as metabolomics and subsequently also proteomics. The measurements performed by the invention will make it possible to obtain a global metabolomic profile of the fetus. Primarily the technique will be used to detect asphyxia but can subsequently also be used to detect infection/inflammation and intrauterine growth restriction during early and late labor. The technique can also be used to monitor the metabolic status of the fetus in order to determine if it has to be delivered by an acute caesarean section. An acute caesarean will be performed if the concentrations of the measured substances are too high or if slope of the concentration gradient is to steep. The metabolomic profile will show the status of the fetus through a reflection of whole body intermediary metabolism as well as activation of the fetal immune system It is possible to attain information about the fetal health by measuring substances of the group comprising lactate, pyruvate, pH, purine catabolites, xanthine, and hypoxanthine Metabolomic and proteomic techniques will be used to obtain a broader screening of fetal intermediary metabolism and /or activation of the immune system which may be an important part of the next generation of fetal monitoring

The substances from the microdialysate can be analyzed by e g spectrophotometric methods, biosensors, mass spectrometry or kinetic enzymatic analysis However, the person skilled in the art is aware that there exist other possible techniques for analysis and therefore the invention is not limited to the methods stated above The measurements can be done by sampling in different time intervals or by continuous analysis Interpretation of the analysis can be done by evaluation of the slope of the concentration gradient or the net change in concentration

Example

The following describes a study made on sheep that was made to investigate the changes in blood lactate and pH during repeated, severe fetal asphyxia A probe according to the invention was inserted in the subcutaneous tissue of fetal sheep scalp

Pregnant sheep were anesthetized, and subjected to laparotomy and hysterotomy The umbilical cord was exposed and an occlusion cuff was applied around the umbilical cord to allow subsequent induction of asphyxia A catheter was placed in the brachial artery for sampling of blood During the study the fetal body remained in utero and only the fetal head was exposed This procedure allowed the umbilical cord and the placenta to be kept in the uterus securing a normal blood supply to the fetus The probes were perfused at 1 μL/tnin or 2 5μL/mιn The monitoring lasted for about 3 hours per sheep

Lactate and pyruvate and acid base / blood gas status were analysed with a Radiometer apparatus Eight asphyxia-episodes were induced of various durations through occlusion of the umbilical cord Umbilical cord occlusion resulted in the development of metabolic acidosis (lowering of pH, increase of pCO₂ and base deficit) and increase of blood lactate levels In response to all insults lactate increased in the microdialysates with a delay of 5-10 mm The delay is mostly due to the dead volume in the outlet tube of the probe There was a good correlation between lactate in blood and lactate in the microdialysates As expected there was a lower concentration of lactate in the dialysate from the shorter probes. The concentration correlates well with the smaller membrane surface of the shorter probes. There was a good correlation between lactate in microdialysate and development of metabolic acidosis.

The following data, from the animal studies that have been performed, is a comparison between microdialysis probes with 4 mm respectively 10 mm membrane. During this study the microdialysis probe was perfused with a flow of 2.5μl/min.

The lactate levels in blood in all experiments correlate well with the lactate levels found during birth asphyxia in the clinical setting. The dialysate has also been analysed for the purine catabolites, xanthine and hypoxanthine and these metabolites also seem to reflect the asphyxia process, but with more fluctuations and delay as compared to lactate. The speed of perfusion (1 vs. 2.5μL/min) did not influence the results.

While embodiments of the present invention have been shown and described, various modifications may be made without departing from the scope of the present invention, and all such modifications and equivalents are intended to be covered.

It should be noted that the word "comprising" does not exclude the presence of other elements or steps than those listed and the words "a" or "an" preceding an element do not exclude the presence of a plurality of such elements. It should further be noted that any reference signs do not limit the scope of the claims, that the invention may be implemented by means of both hardware and software, and that several "means" may be represented by the same item of hardware.

Claims

1. Diagnostic device for the monitoring of markers of global metabolomic status in tissue, comprising a probe (101 ) containing an inlet tube (105), an outlet tube (106), and a membrane portion (104), said membrane portion (104) allowing the passage of markers of global metabolomic status from the tissue, characterized in that one or more anchoring means (110) are provided at the distal end of the probe in close proximity to the membrane portion (104).

2. Diagnostic device according to claim 1 , wherein the device further comprises electrodes for Electro Fetal Monitoring (EFM) (107,108).

3. Diagnostic device according to claim 2, wherein the electrodes for Electro Fetal Monitoring (EFM) (107,108) are combined with the membrane portion (104).

4. Diagnostic device according to claim 2, wherein the EFM comprises measurement of Cardiotocography (CTG) and/or STAN.

5. Diagnostic device according to claim 1 , wherein the markers of global metabolomic status are monitored in the tissue of a fetus.

6. Diagnostic device according to claim 1 , wherein the tissue is located on the scalp of a fetus.

7. Diagnostic device according to claim 1 , wherein the markers of global metabolomic status are of the group comprising lactate, pyruvate, pH, purine catabolites, xanthine, and hypoxanthine.

8. Diagnostic device according to claim 7, wherein the markers of global metabolomic status are of the group comprising lactate, pyruvate, and pH.

9. Diagnostic device according to claim 8, wherein the marker of global metabolomic status is lactate.

10. Diagnostic device according to claim 1 , wherein the membrane portion (104) has a length of 1-15 mm, more preferably 1.5-10 mm and most preferably 2-5 mm.

11. Diagnostic device according to claim 1 , wherein the membrane portion (104) has an inner diameter of about 0.1-1.0 mm, preferably 0.2-0.9 mm, most preferably 3-0.8 mm.

12. Diagnostic device according to claim 1 , wherein the anchoring means (110) are provided with one to eight blades/wings or wires.

13. Diagnostic device according to claim 1 , wherein the blades/wings or wires (118) of the anchoring means (110) have a length of 1 mm up to 15mm, preferably 2-6mm.

14. Diagnostic device according to claim 1 , wherein the anchoring means (210) have a stopping disc (219).

15. Diagnostic device according to claim 1 , wherein the anchoring means (110) are provided as one or more discs (119, 120).

16. A method for supervising the course of childbirth by monitoring markers of global metabolomic status in the tissue of a fetus, characterized in that a diagnostic device according to claims 1 -15 is applied to the tissue of a fetus during birth and continuously determines at least one marker of global metabolomic status, and in case the concentration of such a marker exceeds a preset value one takes appropriate action.