**7. Lactate in AF, a new diagnostic tool in labor**

No major improvement has occurred in the diagnostics of dysfunctional labor since the introduction of the "partogram" by Friedman and Philpot in the 1970´s. Dysfunctional labor is still one of the leading obstetrical problems, worldwide. About 20% of all deliveries have been shown to have an abnormal labor progress.

Dysfunctional labor is according to WHO defined as "a clinical deviation from expected progress" (no dilatation of cervix by 1 cm/hour, or no progress in 2 hours).The partogram is recommended to be used in all deliveries. Dysfunctional labor involves a long and painful delivery. The woman is in active labor, but the delivery progress ceases and the dilation of cervix does not proceed. The fetus does not pass through the birth canal, and the delivery comes to a halt. The reason behind dysfunctional labor is very little known, and several facts are probably due to a dysfunctional labor.

A prospective observational study was performed at Dept of Obstetrics and Gynaecology at South General Hospital, Stockholm, Sweden in 2002-2004 (Wiberg-Itzel et.al 2008). 75 women with a healthy and normal pregnancy and a spontaneous onset of labor were included in the study. AF was collected from an intrauterine pressure catheter and analyzed blinded every 30 minutes during the active phase of labor. The result was then related with the obstetrical outcome (spontaneous vaginal or operative delivery due to dysfunctional labor). The results showed that a high level of lactate in the amniotic fluid (>10.1mmol/l) at two consecutive measure during the active phase of delivery, had a strong association with the diagnosis of dystocia.

A second prospective observational study was carried out at the same hospital in Sweden between 2006-2008 (Wiberg-Itzel et. al 2010). AF from 850 healthy, normal deliveries was collected at every vaginal examination during labor. The samples were analyzed blinded. The purpose of this study was to evaluate if the level of lactate in amniotic fluid, together with the partogram recommended by the WHO could improve the diagnostics of an arrested labor. The study showed that the combination of the level of lactate in amniotic fluid and the partogram gives an improved tool to handling a delivery if there is a halt in labor progress. Among the women who was included in the study and delivered operatively due to dysfunctional labor, over 80% had an increased level of lactate in amniotic fluid (>10.1mmol/l) when labor arrested. The duration of labor was also prolonged within the group of women with an elevated lactate level in AF.

Is there an unknown transport of lactate from the uterine tissue to the AF? Experimental studies with the purpose of finding an explanatory model for the transportation of lactate out of the myometrium and into the amniotic fluid have been performed (Akerud et.al 2009). Biopsies from uterine muscle, amniotic fluid samples, umbilical cord blood and biopsies from placenta of 60 women delivered by caesarean section were collected. The presence of lactate carrying protein was identified by immunohistochemical analysis. The proteins MCT1 and MCT4 were for the first time identified in human uterine tissue. MCT1 was found in all samples but MCT4 was found only in samples from the group of women that were diagnosed as having a dysfunctional labor. The MCT transport proteins bring lactate from uterine tissue to AF, and MCT4 is activated only in dysfunctional labor with a hypoxia of the tissue. Studies are underway to examine whether there are more systems for transport of lactate in myometrial tissue.

Lactate Level in Amniotic Fluid, a New Diagnostic Tool 233

advised in the 1970's and 1980's. Early induction and operative intervention were suggested, especially if labor had not started within 24 hours. One problem with this aggressive approach was failed inductions with concomitant increased frequency of caesarean sections. Studies of women with PROM and unfavourable cervix status have been published (Kappy et al. 1979). A spontaneous onset of labor within 24 hours in 85% of the women with established PROM is presented. They also reported a reduced caesarean section rate with

In a large randomised trial of 5041 women with PROM they were randomly assigned to immediate induction of labor or expectant management (Hannah et al. 1996). The women were randomised to induction with oxytocin, vaginal PGE2-gel or expectant management up to four days after PROM. If labor had not started within four days, the women were induced with oxytocin or PGE2 gel. The primary outcomes were neonatal infection and women's evaluation of their treatment. They found no significant differences between the study groups, and concluded that in both management groups a similar rate of neonatal infections (2-3%) and caesarean sections (10%) were found. Women evaluated early

A Swedish PROM study was conducted in the 1990's where 1385 women were included (Ladfors et al. 1996). The result showed a 13% prevalence of PROM after 34 weeks of gestation. They compared obstetric and neonatal outcome between two different expectant management groups, expectancy for 48 or 72 hours. The result showed a higher rate of spontaneous deliveries among nulliparas in the `late´ induction group compared with `early´ induction. The rate of instrumental delivery was lower in the `late´ induction group, but the rate of caesarean sections was similar. They concluded that expectant for 72 hours was to be recommended. Digital vaginal examination before onset of labor was not allowed in this trial. Low frequencies of maternal and fetal infections were found, and there were no

False negative diagnosis with visual inspection at speculum examination was found to be 12%. No disadvantage, i.e. infections, was found for mother or child if the woman was sent home after a false negative speculum examination. They questioned the value of using biochemical tests in the management of women with suspected PROM. No comments were made on the assumed false positive diagnosis in women with suspect PROM. All women included in the trial had visible AF at examination, but 3.1% of them had intact membranes

In 1920's, it was found that vaginal pH turned from acid to neutral or alkaline when contaminated with amniotic fluid. In 1938 the nitrazine test was introduced, which measured pH in vaginal secrete within a narrower range. This method has been widely used

The crystallisation pattern of AF was first described in 1950's. The crystallisation phenomenon, also called ferning or arborisation test is dependent on the relative concentration of electrolytes, proteins and hydrocarbonates in AF. The crystallisation test is nowadays still one of the most commonly used methods in clinical practice worldwide.

expectant management, and no evidence of increased neonatal infections.

induction of labor more positively than expectant management.

differences between the groups.

**8.2 Historical review of PROM tests** 

at delivery.

all over the world.

Recently a study was published where the association between a high concentration of lactate in amniotic fluid as a possible marker of uterine tissue hypoxia during delivery, pathologic cardiotocography trace (CTG), and adverse neonatal outcome at delivery was shown (Wiberg-Itzel et.al 2011). A sample of AF was collected just before delivery and the lactate concentration was analyzed blinded. An association between high lactate value in amniotic fluid just before delivery and adverse neonatal outcome at birth was confirmed. In the group with AF lactate concentrations greater than 10.1 mmol/L at the last sampling occasion before delivery, significantly more neonates had an adverse neonatal outcome at birth, resuscitation was performed more frequently, and a higher number of newborns were admitted to the neonatal intensive care unit. Two neonates with hypoxic–ischemic encephalopathy grade 2 were found, and both belonged to the group with a high concentration of lactate in amniotic fluid, whereas there were no newborns in the group with lower amniotic fluid lactate that developed hypoxic– ischemic encephalopathy. of

In summary, it was found that the use of CTG together with an analysis of the lactate concentration in AF could be a promising and useful predictor of fetal outcome in labor. The method is easy, non-invasive, and safe for the mother and her unborn child. The findings have important clinical implications in view of the fact that children are still born with an unexpected adverse neonatal outcome, even with what is considered to be careful fetal surveillance

#### **7.1 Ongoing study**

Currently, a large collaborative prospective project between 10 European and one African clinic is running. In the "Dysfunctional labor study" data, saliva and amniotic fluid from 5000 primiparas and their deliveries is collected. This in a desire to gain more knowledge about the state called dystocia. The study is scheduled to continue until summer 2012.
