Discussion
This
is the first study since the original study in the 60’s, that defines
cut-offs from neonatal outcomes, without referring and comparing to
previously published cut-offs (5). Based on our results we suggest the
interventional cut-off for fetal acidaemia to be 5.2mmol/L, when
analysing the scalp blood lactate with StatstripLactate® or
StatstripXpress®. The argument for the chosen cut-off of 5.2mmol/L is
the balance between obtaining the best sensitivity and specificity for
common recognized prognostic factors of intrapartum asphyxia. By
increasing the cut-off to more than 5.2mmol/L the sensitivity will
decrease for AS <7 at 5 minutes and for the composite outcome.
On the other hand, by choosing a lower cut-off than 5.2mmol/L the
intervention rate will be unnecessarily high. We have previously shown
that the mean value for LP + 2SD equals 5.2mmol/L in the second stage,
although it is not known whether that cut-off is associated with an
increased risk for adverse outcomes. It has been previously shown that
the risk for disability at 4 years increases with increasing scalp blood
lactate levels (20,21).
Lactate accumulates in tissues, blood and cerebral spinal fluid as a
result of anaerobic metabolism due to hypoxia. Lactate levels, which are
normally within a narrow range, can therefore be used to monitor tissue
hypoxia since increased levels are associated with a high risk of
compromised vital organ function (22,23). In the 90s, after valuable
work with the POC measurement of lactate in scalp blood, Swedish
scientists published cut-offs for normality and acidaemia for LP (6–8).
These are the cut-offs recognized and used worldwide today (1,2,6).
Drawbacks of that study are that the time intervals from FBS to delivery
are not mentioned and that the cut-offs are partly based on the
pre-existing cut-offs for pH (5,6).
Recently, it was shown that the scalp blood lactate level is closely
associated to the level in central circulating blood (24). Not
surprisingly, the correlation between FBS-lactate and cord blood lactate
improves as the sampling-to-delivery time interval shortens (25). It is
important to emphasize that the FBS-lactate level reflects the metabolic
status of the fetus at the moment of FBS and depending on the fetal
reserve and other factors the metabolic status can rapidly deteriorate.
Consequently, comparing the FBS-lactate value to the fetal outcome will
always be biased by the time-lag from FBS to delivery. To avoid
preanalytical errors, it is important to ensure correct sampling
technique and if there is any doubt about contamination with amniotic
fluid or fetal products, sampling and analysing must be repeated
directly (26).
For this study, we chose 25 minutes from FBS to delivery because it
showed the highest correlation between SSLX and cord blood values and
based on the reasoning above. In addition, 25 minutes is appropriate
given that repeat sampling is recommended within 20-30 minutes if the
CTG is still non-reassuring and it is also an expected interval from
recognizing a high lactate value until expediated delivery, either by
caesarean section or vacuum extraction (16,17).
There is no ideal outcome variable specifically indicating intrapartum
asphyxia. Analysing cord blood provides the clinician with the most
objective and accurate measurement of the metabolic status of the
new-born, although the majority of babies with deteriorated cord blood
gases will be vigorous and manifest no obvious short- or long-term
neurological sequelae (27,28). Analysis of cord blood requires
meticulous technique and knowledge of pitfalls such as timing of
sampling/analysis and the different equations in the setting of the BGAs
(2,29–31). There is no international consensus of the definition of
fetal MA in cord blood, which compared to respiratory acidosis is a
serious threat to the cell function (32–35). The ACOG definition of
metabolic acidosis is pH < 7.0 + BDblood> 12 mmol/L, whereas the FIGO guideline uses a threshold of
pH < 7.05 + BDecf >10mmol/L or
lactate > 10mmol/L, because an association with adverse
neonatal outcome is recognized at that level (18,22,36). Note that the
value of BD is significantly dependent on the compartment used for
calculation - blood or extracellular fluid - with highest values when
calculated in blood (31). The lactate value in cord blood correlates
with the lactate concentration in the fetal brain, which in turn is an
established marker for the severity of cell damage and thereby for the
degree of hypoxic ischemic encephalopathy. This supports the use of
lactate in the definition of MA (22,23,37).
Low Apgar Scores, for most neonates, are likely to be due to hypoxia
whereas an intermediate score often is due to other reasons, such as
medications given to the mother, gestational age, or malformations (38).
If the one-minute Apgar is low and the baby needs respiratory support or
other intervention, then the five- and ten-minute Apgar will be affected
by resuscitation procedures undertaken. This makes the AS an unreliable
and nonspecific single marker for intrapartum hypoxia. In accordance
with Kruger et al ., we found that the predictive ability of SSLX
for low Apgar scores was relatively low (6).
In the pursuit of the optimal predictor of intrapartum hypoxia we
created a parameter based on a pH < 2SD in a normal population
plus one of the following outcomes: admission to neonatal intensive care
unit, continuous positive airway pressure therapy, bilevel positive
airway pressure, manual ventilation or AS < 7 at 5 minutes. In
that context, it is notable that the negative LR were lowest for the
three outcomes: MA, pH < 7.05 + BD ≥ 12mmol/L and pH
< 7.05 plus lactate > 10mmol/L implying that an
intervention cut-off of 5.2mmol/L can safely rule out intrapartum fetal
acidaemia.
The high false positive rate of CTG remains a limitation in obstetrics
and to achieve an appropriate intervention rate a secondary test is
necessary. There is emerging evidence of the negative consequences of
operative deliveries for both the mother and the baby (39,40). In our
study, of all fetuses with a concerning CTG, only 16% of the FBS
lactate were above the recommended cut-off for intervention, thus
principally allowing 84% of all cases with a non-reassuring CTG to
continue. A randomized controlled study to evaluate the effectiveness of
FBS to reduce interventions without an increase in adverse neonatal
outcomes is still lacking. The study by Haverkamp et al . was
underpowered and the results from the Flamingo trial are not yet
published (1,41).
Strengths of this study include the large sample size, which enabled
cut-offs to be derived from lactate samples with a wide range and
obtained close to birth, the routine of FBS and for umbilical cord blood
sampling and use of continuous CTG in the second stage of labour.
The main limitation of the study is that, despite the large number of
included patients, the numbers of adverse outcomes were low, resulting
in relatively wide confidence intervals regarding the sensitivity. Also,
not all cases had a successful blood gas analysis.
In conclusion, we suggest the scalp blood lactate cut-off for
intervention to be ≥5.2mmol/L. If the test result is normal, labour can
continue, but we recommend repeated FBS after 20 to 25 minutes if the
CTG is still non-reassuring. To evaluate the efficacy of FBS, a
randomized controlled trial is warranted with the use of the
StatstripLactate®/StatstripXpress® Lactate system and the cut-off of
5.2mmol/L.