Amniotic fluid lactate (AFL): a new predictor of labor outcome in dystocic deliveries

Abstract

Purpose of this Review: Even today, hundreds of thousands of women die or suffer high levels of morbidity associated with childbirth. One of the most common causes is halted labor progress, or labor dystocia. There have been no developments in the diagnosis or treatment of dystocic deliveries since Friedman designed the Partogram in the 1950s. Oxytocin is the only treatment for dystocic labor. Sometimes, oxytocin is a lifesaver for the woman, especially in severe postpartum hemorrhages. At the same time, it is also one of the most overused drugs in obstetric care. This review article is meant to provide a short overview of the current knowledge of uterine metabolism during labor, uterine lactate production, and its association with labor dystocia. The article also intends to reflect new ways of thinking regarding practical recommendations for treating labor dystocia and offer a look at the future of dystocic labor management.

Keywords:

• Labor dystocia
• metabolic status
• lactate
• cesarean section
• oxytocin

Introduction

Even today, hundreds of thousands of women die or suffer high levels of morbidity associated with childbirth. In 2017, over 295,000 women died in childbirth. Though there have been recent improvements, labor dystocia remains one of the biggest dangers to women and newborns during labor.

In normal labor, uterine contractions are regular, the cervix is dilated, and the fetus descends through the birth canal. Labor dystocia is clinically defined as the slow or arrested progress of labor. The reason that labor progress is halted is still unknown, and there have been no significant advances in diagnostics of labor dystocia since the introduction of the Partogram by Friedman in the 1950s [1,2]. The Partogram is a graph of cervical dilation over time. The WHO recommends a Partogram for every delivery. One of the Partogram’s main purposes is to identify those at risk of prolonged, dystocic labor.

This review will cover the accumulated knowledge of the metabolism of the uterus, uterine lactate production, and its association with labor dystocia.

Uterus

During exertion, lactic acid is produced by glycolysis in all human cells. Glycolysis mainly occurs under hypoxic conditions, but the uterus is unique in its function and is glycolytic even under normoxic conditions. However, the production of lactate is lower when oxygen is available. For labor to end successfully, the uterus needs to produce strong, coordinated, effective contractions. During the regular pattern of labor contractions, uterine blood circulation is reduced with every contraction, and metabolism briefly becomes anaerobic. When the contraction subsides, lactate and other metabolites associated with hypoxia are expelled, and new, oxygenated blood is transported to the muscle. This process leads to an average level of lactate in the tissue and good labor progress [3]. Recent research has shown that the uterus needs these periods of hypoxia to trigger the next contraction [4].

Conversely, in abnormal, dystocic deliveries, lactate removal appears to deteriorate, and lactate and other metabolites accumulate in the tissue instead of being taken away. This leads to an acidification of the uterine muscle. Why this happens is still unknown. We know of several risk factors associated with labor dystocia, but not why the course of childbirth stops.

Acidification inhibits the Ca²⁺ channels in the myometrial cells and leads to a decreased inflow of Ca²⁺ into the muscle cells. This makes the labor contractions weaker and consequently less effective [4] (Figure 1). The woman will feel pain, but labor will not progress. New studies show a significant correlation between uterine lactate production, hypoxia in the tissue, and the effect of oxytocin [4]. This is an essential interaction if labor is to end normally.

Figure 1. Describes the metabolic reaction in the uterus during contractions. Graphics: Fuad Bahram, FB Scientific Art Design.

Experimental studies have discovered transport systems for lactate in uterine tissue [5]. It seems essential for the uterus to emit lactate in the event of overproduction (hypoxia) and to withdraw lactate back into the tissue, if necessary, as a form of energy [5]. Amniotic fluid appears to be a reservoir for lactate produced by the feto-maternal unit.

Monocarboxylate transport (MCT) proteins of the uterus are a group of transporters that have been studied experimentally in different labors, both normal and dystocic [5–7]. These transporters are a family of proteins, and some of them appear to be activated only in the event of acute hypoxia, as in dystocic labor [6,7]. In contrast, others are basic transporters of lactate that work continuously. Previously, it was believed that lactate was transported only over concentration gradients. Still, discovering these proteins in human body tissue has helped better our understanding (Figure 2).

Figure 2. The different systems of transport in uterine muscle. Graphics: Fuad Bahram, FB Scientific Art Design.

Clinical studies performed at the women’s clinic at Soder Hospital in Stockholm, Sweden, during the last 20 years have shown a close correlation between lactate produced by the uterus, the level of lactate in amniotic fluid lactate (AFL), and the outcome of labor. High levels of AFL (≥ 10.1 mmol/L) are overrepresented in dystocic deliveries compared to deliveries with normal progress, where low levels of AFL (< 10.1 mmol/L) are more common. A noninvasive method has been developed to detect AFL levels in a small sample of amniotic fluid (0.5 ml) collected from the vaginal pouch during vaginal examination during ongoing labor when the fetal membranes have been broken. The AFL can be analyzed within 15 s at the bedside in the delivery room (LMU061, Obstecare AB, Sweden) [8].

A significant clinical study of 3,000 primiparous women from various countries in Europe and Africa showed that analyzing AFL just before starting augmentation with oxytocin provides essential information about the current metabolic status of the uterus and is a good predictor of labor outcome [9]. Low levels of AFL (≤ 10.1 mmol/L) may support the decision to continue a prolonged vaginal delivery by augmentation with oxytocin, as the uterus appears to be well oxygenated and receptive to oxytocin. High levels of AFL (> 10.1 mmol/L) indicate an exhausted, hypoxic uterus with an increased risk not only for prolonged labor, which in many cases end in a cesarean section anyway, but also for acute fetal and maternal complications. Newborns delivered with asphyxia and women with significant postpartum hemorrhage are overrepresented in the group of deliveries with high AFL levels (Table 1).

Table 1. Lactate in amniotic fluid: predictor of labor outcome in oxytocin augmented primiparas deliveries [9].

Predicted	Observed		Total
	Cesarean section	Vaginal delivery
AFL > 10.1 mmol/l	32	54	86
AFL < 10.1 mmol/l	50	502	552
Total	82	556	638

Sensitivity = 32/82 = 39.0% (95% CI; 27 to 50); Specificity = 502/556 = 90.3% (95% CI; 87 to 93); NPV = 32/86 = 37.3% (95% CI; 27 to 48); PPV = 502/552 = 91.0% (95% CI; 88 to 93). Overall percentage of correct predictions: 83.7% (502 + 32 = 534/638 = 83.7%).

AFL and fetal outcome at labor

During normal labor contractions, the uteroplacental blood flow decreases but is rapidly restored when the contraction is over. When labor contractions are irregular and ineffective, the uteroplacental blood flow is reported to be reduced for a more extended period or constantly. Consequently, gas exchange in the fetal-maternal unit may be impaired in dystocic labor, resulting in fetal hypoxia-ischemia and lactic acidosis.

The goal of all obstetric care is to deliver a healthy woman and a healthy newborn. Although the fetus is monitored in a way we believe is optimal, we still see newborns deprived of oxygen. This may be because the monitoring methods are not specific enough or because the staff is drowning in information. For example, the Ctg results in a high number of false positives. Out of those with an affected Ctg trace, only a small proportion are hypoxic at birth. If in doubt over a Ctg interpretation, the recommendation is to use an additional method of fetal monitoring. Fetal blood sampling is an invasive and non-continuous method. The sampling failure is reported to be as high as 20%. Furthermore, the measurement of pH and lactate in fetal scalp blood has an unsatisfactory, low predictive value for adverse fetal outcomes at birth [10].

Since the 1970s, it has been known that amniotic fluid contains a high concentration of lactate, but this has never been used for analyzing fetal wellbeing during labor. A study performed at Soder Hospital in Stockholm in 2011 [11] included 850 primiparous women in labor. Amniotic fluid was sampled, and the AFL value was analyzed blinded within 30 min before delivery. All deliveries had a Ctg recording that was reviewed after delivery, blindly and according to FIGO guidelines.

In the group with an AFL > 10.1 mmol/L in the last sample taken before delivery, significantly more neonates had an adverse neonatal outcome (pH < 7.05 and BD > 12 in the umbilical artery, Apgar score < 7 at 5 min, meconium aspiration, hypoxic-ischemic encephalopathy grade 1–3). Resuscitation was performed more frequently, and a higher number of newborns were admitted to the NICU for more than 24 h. Two neonates were delivered with HIE grade 2; both belonged to the group with a high AFL level (>10.1 mmol/L).

Among the deliveries with a pathologic Ctg in the last 30 min and an adverse neonatal outcome, almost 80% also had an AFL level > 10.1 mmol/L in the last sample taken before delivery. High AFL levels seem to be a good marker of uterine hypoxia, and when used together with a Ctg recording, the predictive value for adverse neonatal outcomes was increased. Taken together with a high AFL level before delivery, functional bradycardia indicated an almost fourfold risk of adverse neonatal outcomes [11].

The AFL method is easy, noninvasive, and safe for the mother and her unborn child. These findings have important clinical implications, since children are still born with unexpected adverse neonatal outcomes, even with what is considered careful fetal surveillance.

Oxytocin

Oxytocin is one of the most-used obstetrical drugs. It is a peptide hormone produced in the hypothalamic part of the brain (the supraoptic and the paraventricular nuclei) and excreted into the bloodstream from nerves projecting to the pituitary gland [12,13]. Sir Henry Dale first described its relevance to support delivery in 1906, and Bell then advocated the clinical use of oxytocin in 1909 [13]. They discovered that cats in labor had stronger contractions if they received part of a cat brain as an infusion during delivery. In the mid-1950s, synthetic oxytocin was produced for the first time [14], and since then, oxytocin has been used all over the world. In Sweden, oxytocin is used in 55% of all deliveries, 75% of all first-time deliveries, and 38% of deliveries of multiples [15]. Oxytocin is an essential drug, as it can frequently be a lifesaver for the woman. Still, oxytocin is also one of the most misused and dangerous drugs in the obstetrical world if used negligently.

If labor dystocia is confirmed, oxytocin is suggested for augmentation. However, responses to oxytocin administration are variable. Many labors diagnosed as dystocic will be long, painful, and unsafe, as the use of oxytocin does not guarantee vaginal delivery—that is, labor dystocia occurs despite adequate stimulation with oxytocin. A Cochrane review was conducted in 2013 by Bugg et al. [16], who found that oxytocin shortened the length of labor. Still, despite stimulation, no more vaginal deliveries were carried out. A reasonable assumption is that increased knowledge of uterine activity and the pathophysiological processes will be the key to improving the understanding and treatment of dystocic labors with oxytocin.

The main question is whether introducing the AFL method could help obstetricians/midwives make a more informed decision in the delivery room when handling a dystocic delivery. Studies have shown that more than 90% of cases with a low AFL (≤10.1 mmol/L) will have a normal vaginal delivery after adequate stimulation with oxytocin. It would be reasonable to assume that the number of unnecessary cesarean sections in this group would be reduced if the method were implemented in clinical practice. Important information about uterine receptivity to augmentation will hopefully lead to a more individually adapted use of oxytocin in the future. A small percentage of women, approximately 15%, with arrested labor progress have high levels of AFL (>10.1 mmol/L) at the time of augmentation [9]. This group has a higher frequency of operative interventions, such as cesarean sections, and fetal and maternal complications are more common. This is probably the group described earlier, in which labor dystocia occurs despite adequate stimulation with oxytocin.

A further question is whether we can help women with high AFL levels with our new knowledge. If the delivery will end in an operation regardless, then it is better for both mother and fetus if it is performed as quickly as possible. Long, protracted labor that ends with a cesarean section is not preferable, but could we use the AFL method and high lactate values (>10.1 mmol/L) to do something besides perform a cesarean section? Could we improve the situation at the time of stimulation and help more of these women deliver vaginally?

Bicarbonate (samarin)

In sports medicine, it is well known that consuming bicarbonate before intense physical exercise lowers lactate levels in the blood. Much of our knowledge of uterine muscle function and its significance in labor progress comes from sports medicine. A long, dystocic delivery can, in many respects, be likened to an exhausting competition or training. Today, many athletes manage their anticipated lactic shock during exercise or competition by drinking baking soda dissolved in water about one hour before. Consuming bicarbonate is expected to neutralize the lactic acid produced during exercise [17,18]. The idea is to alkalize the environment slightly before acidification takes place. Bicarbonate is a harmless substance sold in stores as baking soda. Drinking baking soda water may help athletes improve their performance somewhat and cope a little better with the intense effort required. The question is whether this knowledge can be used in our clinical obstetrical care. Does oral intake of bicarbonate improve the condition of stimulation and enhance the outcome of dystocic deliveries with high AFL levels (> 10.1 mmol/L)? Are there any advantages to “buffer loading” the woman, and if so, will it affect the delivery outcome?

To answer these questions, a randomized, controlled trial was performed at Soder Hospital in Stockholm in 2014, in which 200 dystocic deliveries with arrested labor progress, as defined by the Partogram, were examined [19]. The study results showed that AFL levels fell significantly in the group that took bicarbonate orally before augmentation with oxytocin compared to the untreated group. The study also showed that those with high AFL levels benefited most from bicarbonate. The frequency of spontaneous vaginal deliveries was substantially higher in the treated group, and a difference in fetal outcome was shown between the two groups (Table 2).

Table 2. Data presented per group (Bicarbonate/no Bicarbonate), at the time of augmentation.

Characteristics	Bicarbonate (n = 90)	No Bicarbonate (n = 99)	p Value
Way of delivery
Spontaneous vaginal (%)	76 (84.4)	67 (67.7)	<0.01*
Vacuum/forceps (%)	6 (6.7)	24 (24.2)	<0.01*
Emergency cesarean section (%)	8 (8.9)	8 (8.1)	0.8
Active time of delivery > 12 h (%)	44 (49)	40 (40)	0.2
Use of epidural anesthesia (EDA, %)	72 (80)	88 (89)	0.2
Post-partum hemorrhage > 1.5 L (%)	0	16 (16.2)	<0.001*
Fetal
Apgar score < 7 at 5 min after delivery	0	2 (2)	0.3
Ph in arterial cord blood at delivery	7.27 (0.1)	7.23 (0.07)	0.01*
BE in arterial cord blood at delivery	−4.3 (3.4)	−5.6 (3,6)	0.01*
Transfer to neonatal intensive care (NICU, %)	2 (2.2)	6 (6.1)	0.01*

Data are presented as numbers (%), n = 199 .

*p-values < 0.05 were considered statistically significant.

Perhaps the use of bicarbonate is a new, useful tool for handling dystocic deliveries. However, it should be noted that the solution is not simply to give women bicarbonate. Bicarbonate itself does not cure the original cause of labor dystocia. Our suggestion is to let the uterus rest at the same time that bicarbonate is given. Then, stimulation with oxytocin can be tried again, and if progress is still not made, a cesarean section should be considered. We must never forget that a long, protracted progress of labor is always evil, for the woman as well as for her unborn child. At the same time, it is of course very tempting to use this new knowledge and possibly increase the proportion of vaginal deliveries, even if they are diagnosed as dystocic labor (Figure 3).

Figure 3. Bicarbonate in labor. Graphics: Fuad Bahram, FB Scientific Art Design.

Conclusion

We must ask ourselves whether we are currently using the correct criteria to handle a dystocic labor. Hopefully, an understanding of AFL levels can help us obtain new knowledge and a new kind of consensus when handling arrested labor. We hope to reduce the number of unnecessary interventions in obstetrical care. The goal is a healthy mother and a healthy newborn.

Future

Further work to develop methods for treating dystocic deliveries is ongoing. A large implementation project named Giving Birth, involving cooperation between multiple European countries, is underway.

Disclosure statement

The author of the article reports no conflict of interest.

Additional information

Funding

No specific funding was obtained.