Causes and consequences of fetal acidosis

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  1. Catherine South Bobrow,
  2. Peter W Soothill
  1. Fetal Medicine Research Unit, University of Bristol, Department of Obstetrics, St Michael's Hospital, Bristol BS2 8EG
  1. Professor Peter Soothill.

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The fetus depends on the mother for placental commutation of oxygen and carbon dioxide. This in plow relies on adequate maternal blood gas concentrations, uterine blood supply, placental transfer and fetal gas ship. Disruption of any of these can crusade fetal hypoxia, which, despite compensatory mechanisms, may lead to acidosis. When severe and acute (lasting hours), merely especially if prolonged (days or weeks), hypoxia and therefore acidosis, are associated with significant morbidity and mortality with potential long term sequelae. Whether this impairment is primarily due to reduced cell energy availability, equally a outcome of hypoxia, or secondary to jail cell poisoning, as a result of acidosis, is unclear and indeed acidosis could simply be a marker of the cause and severity of the hypoxia.

Key points

  • The causes and consequences ofacute (minutes or hours) andchronic (days or weeks) fetal acidosis are different

  • In the by much attention has been paid to acute acidosis during labour, but in previously normal fetuses this israrely associated with subsequent damage

  • In contrast, chronic acidosis, which is oftentimes not detected antenatally, is associated with a pregnant increment in neurodevelopmental delay

  • The identification of small for gestational age fetuses by ultrasound scans and the use of Doppler waveforms to detect which of these have placental dysfunction mean that these fetuses tin be monitored antenatally

  • Delivery before hypoxia has produced chronic acidosis, may prevent subsequent harm and good timing of commitment remains the only direction choice at present.

The very different aetiologies of acute vschronic acidosis and the possible consequences will exist reviewed, whether direct caused by the acidosis or indirectly by the hypoxia

What is acidosis?

Acidosis ways a high hydrogen ion concentration in the tissues. Acidaemia refers to a high hydrogen ion concentration in the blood and is the almost easily measured indication of tissue acidosis. The unit most usually used is pH, which is log to base ten of the reciprocal of the hydrogen ion concentration. Whereas blood pH can change quickly, tissue pH is more stable. The cut off taken to define acidaemia in adults is a pH of less than 7.36, only later on labour and normal commitment much lower values normally occur in the fetus (pH 7.00), often with no subsequent sick furnishings. Studies looking at the pH of fetuses from cord blood samples taken antenatally and at commitment have established reference ranges. Other indices sometimes used to assess acidosis are the base backlog or bicarbonate. Neither of these is measured by conventional blood gas machines but is calculated from the measured pH and pCO2.

The major sources of hydrogen ions in the fetus are carbonic and lactic acids from aerobic and anaerobic metabolism, respectively. The removal of COtwo (and so carbonic acid) from the fetus depends almost entirely on the placenta. Unlike in sheep, lactate does non normally seem to be an important substrate for the man fetus and lactic acrid is normally either further metabolised or excreted transplacentally. The latter has been shown past analyses of arterial and venous cord blood samples from human fetuses with low claret oxygen content due to anaemia secondary to severe Rhesus isoimmunisation. Lactate concentration was higher in the umbilical artery than the umbilical vein. The increased lactate is explained by increasing production from anaerobic metabolism and the difference in concentration betwixt the umbilical artery and vein suggests that the placental circulation clears lactate from the fetal claret so helping to "repay" a fetal oxygen debt.1

The causes of fetal hypoxia and therefore acidosis can be divided into maternal, placental, or fetal. The consequences of acidosis depend on its severity and elapsing and also the status of the fetus earlier the insult, and we allocate the causes of fetal acidosis into astute (hours) or chronic (days). In postnatal medicine acidosis is often described as respiratory (predominantly due to increased pCO2) or metabolic (predominantly due to increased lactic acid). However, while acute fetal acidosis is almost always initially respiratory, this is rapidly followed by mixed respiratory and metabolic acidosis if there is no improvement in oxygenation. Furthermore, the chronic acidosis of fetal life is also mixed,ii (fig 1) and nosotros therefore prefer to use the terms acute and chronic.

Figure 1

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Effigy 1

Relations between umbilical venous hypoxaemia (pO2) and umbilical hypercapnia (pCO2), hyperlacticaemia (blood lactate), or acidosis (pH); these are all expressed in multiples of SD from the appropriate mean for gestational historic period). Reproduced with permission from Nicolaides et al. Am J Obstet Gynecol;1989;161:996-100.

Aetiology

ACUTE

Maternal

Anything that causes hypotension or hypovolaemia such as bleeding, a vasovagal attack, or epidural anaesthesia volition reduce the maternal blood supply and so oxygen delivery to the uterus. Uterine contractions can also interrupt the uterine blood flow by a pressure rise and if prolonged, as in hypertonus, may cause hypoxia and and so acidosis.

Placental

Abruption can disrupt the utero-placental apportionment by separating and so tearing the uterine spiral arteries from the placenta.

Fetal

Blood flow from the placenta to the fetus is often affected during labour and commitment past umbilical string compression and this can sometimes happen earlier labour if there is reduced liquor or a truthful knot in the cord. Creature experiments have shown that at that place is significant reserve considering the fetus can compensate by increased oxygen extraction,3 meaning blood menstruation to the fetus must exist reduced by at least fifty% to crusade hypoxia.iv

CHRONIC

Maternal

Maternal causes of chronic fetal acidosis include reduced oxygenation of maternal blood, such as in severe respiratory or cardiac disease, or reduced blood flow to the placenta as in connective tissue diseases—for instance, systemic lupus erythematosus—and pre-eclampsia.

Placental

Antenatal fetal blood sampling by ultrasound guided needle aspiration from the umbilical cord (cordocentesis) in pregnancies with fetal growth restriction (FGR) has shown hypoxia as a result of impaired placental transfer of oxygen.5 This is idea to issue from inadequate trophoblast invasion of the myometrium in early pregnancy,6 leading to reduced perfusion of the intervillous spaces. In creature experiments, like astute string pinch studies, utero-placental blood flow besides needs to be reduced by at least 50% to produce fetal hypoxia.7 This indicates that the reduction in placental transfer seen in human FGR must exist substantial to produce the hypoxia and acidosis found at cordocentesis in such cases.

Fetal

Fifty-fifty with normal placental function, conditions within the fetus can cause acidosis. Anaemia from rhesus disease, parvovirus infection, α-thalassaemia or feto-maternal bleeding, when severe enough to reduce fetal haemoglobin concentrations beneath 40 chiliad/l (equivalent to an oxygen content below 2 mmol/fifty), can lead to a fall in pH.viii 9 Arterio-venous shunting in fetal tumours, serious cardiac structural abnormalities, or arrhythmias are other weather which tin can atomic number 82 to chronic acidosis by decreased oxygenation equally a issue of reduced feto-placental blood flow.

Diagnosis of acidosis

ANTENATALLY

The utilise of ultrasound imaging to assess fetal size and wellbeing, Doppler studies of the fetal circulation, and cordocentesis have helped us to empathize some of the mysteries of life before birth. During the 1980s cordocentesis was used to study the acid base condition of the fetus and create reference ranges for umbilical arterial and venous claret gases in the second and third trimesters (fig 2).ii 10These studies provided the outset straight evidence of chronic acidosis.5 However, cordocentesis carries a procedure related chance of ane% and cannot therefore exist used routinely or repeatedly for monitoring. To overcome this, fetal medicine specialists take searched for not-invasive techniques to observe acidosis.

Figure 2

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Figure 2

Reference ranges (hateful and 95% confidence intervals), of umbilical venous and arterial pH with gestation. Dots represent pH values from FGR fetuses, many with chronic acidosis. Reproduced with permission from Nicolaides et al. Am J Obstet Gynecol.two

In acute situations where severe hypoxia and acidosis are suspected, the not-invasive techniques used are fetal middle rate monitoring or biophysical contour score (fetal breathing/movements, gross body motion, tone and amniotic fluid volume). However, in pregnancies with placental dysfunction earlier labour, the onset of hypoxia and acidosis is more gradual and results of these tests are often normal until a preterminal stage11 where urgent delivery is required to foreclose an intrauterine death.

An important quantum in antenatal surveillance was the sit-in that increased resistance in placental vasculature in pregnancies with hypoxia and acidosis due to placental dysfunction acquired aberrant menses patterns in the umbilical artery, demonstrable using Doppler ultrasonography. Umbilical artery Doppler velocimetry is a sensitive and specific non-invasive way of detecting chronic acidosis. This was confirmed by the demonstration of significant associations between umbilical artery Doppler waveforms and blood gases at commitment.12 xiii Farther piece of work has besides shown a characteristic blueprint of redistribution of blood flow to the most essential organs at the expense of the peripheral ones. This occurs with increasing acidosis, and is followed by progressive cardiac dysfunction, leading to abnormal venous blood flow patterns. Doppler is now the nearly widely used technique to find chronic acidosis in practiced U.k. clinical practice.

INTRAPARTUM

Fetal heart rate monitoring during labour can give us an indication of fetal hypoxia and acidosis, simply although sensitive, this method is non very specific. Measurements of acid base condition intrapartum obtained from sampling fetal blood from the presenting role later on cervical dilatation and rupture of membranes help decrease operative deliveries following fake positive fetal heart rate traces.14 In contrast to antenatal blood gas results, the value of a single event in labour is limited as the acid base interactions are dynamic and may change speedily, and repeated samples are often needed. Several methods of continuous blood gas monitoring using an electrode fastened to the fetus sub- or transcutaneously have been tried for pOii,15 pCOtwo, and pH.16 Intrapartum fetal oxygen saturation monitoring past pulse oximetry is beingness adult and seems to exist a practiced predictor of pO2 and acrid base status,17 and this has of import implications for monitoring in labour.

Fetal pH falls during normal labour but this is constitute earlier in pregnancies afflicted by complications such as pre-eclampsia and growth restriction.xviii We believe this result is not only because of "reduced reserve" for labour but that some of these cases are acidotic before labour onset (every bit described to a higher place).

AT Delivery

Studies of acid base status in string claret at nascence take provided normal ranges.19 Every bit in labour, neonates from pregnancies with antenatal (growth retardation) or intrapartum (meconium staining) complications, are more probable to be hypoxic20 and acidotic at birth. In our view the important distinction is whether the acidosis resulted from chronic (present before labour) or acute hypoxia. The difference in umbilical artery and vein gases may give farther information on its elapsing. In placental dysfunction where hypoxia is due to reduced placental transfer, umbilical artery and vein values will both be abnormal and like, whereas in acute cord compression or fetal bradycardia the hypoxia and acidosis will be predominantly in the umbilical avenue, leading to a large arteriovenous departure. This is because a irksome passage of blood through the placenta allows time for maximum gas exchange despite reduced total blood flow.

Consequences of acidosis

Acidosis occurs as a outcome of tissue hypoxia and it is unclear whether the consequences of this process are due primarily to the acidosis or the hypoxia. What has become articulate over the past decade is that the consequences of hypoxia/acidosis are very different, depending on whether this is acute or chronic. The normal human fetus is adjusted to survive labour and has compensatory mechanisms that permit it to withstand even severe hypoxia and acidosis for short periods of time. Several studies have looked at the neurological outcome of neonates who were severely asphyxiated at delivery.21-24 Although the cutoff of pH used to define severe acidosis and the historic period at follow upwards varied, conclusions were similar from all the studies: although bloodshed may be slightly increased, the predictive value of acidosis at birth for neurological sequelae, especially in term neonates, is poor.

In contrast, the fetus exposed antenatally to chronic hypoxia and acidosis is much more at run a risk of associated long term morbidity. In 1994 Low et al reported a written report of neonates following respiratory or metabolic acidosis at delivery.25Umbilical arterial buffer base was used and they found that complications were not increased with a pure respiratory acidosis merely they were with metabolic acidosis, and these neonates were more probable to accept passed meconium and take had instrumental deliveries. An increased proportion of undiagnosed chronically acidotic fetuses in this group could explain this. In a large study of the antecedents of cerebral palsy in 1986 Nelson et alconcluded that antenatal events were much more than of import than intra- or postpartum ones.26 This was supported past a study by Adamson et al in 1995 where all term, singleton neonates born over an 8 month period with a well defined diagnosis of encephalopathy within the kickoff calendar week of life were identified prospectively and matched with a well neonate.27 Antenatal and intrapartum factors in both groups were compared and but 6% of cases had intrapartum run a risk factors alone. They concluded that in most of their cases intrapartum acidosis was non the cause and events occurring in the antenatal period were more than oftentimes implicated. Further evidence for this association comes from a follow upwardly study of infants with acid base of operations status assessed as fetuses by cordocentesis. To remove the complications of extreme prematurity just cases delivered afterward 32 weeks were studied. Neurodevelopmental assessment showed a reduction in developmental caliber following chronic fetal acidaemia (fig 3).28

Figure 3

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Figure 3

Fetal blood pH (expressed in multiples of SD from the normal hateful) at cordocentesis in chromosomally normal small for gestational historic period fetuses and subsequent Griffiths neurodevelopmental quotient (DQ); r= 0.41, n = 65, p= 0.0008. Squares signal three children with cognitive palsy. Reproduced with permission from Soothill et al. Eur J Obstet Gynaecol Reprod Biol, 1995; 59:21-four.

Determination

Prevention of severe acute acidosis depends on good labour ward monitoring and intendance. Prevention of chronic fetal acidosis, which is probably a much more common crusade of impairment, depends on detection of placental dysfunction antenatally by clinical fetal growth cess, ultrasound scanning and Doppler ultrasonography. At that place is nevertheless no overall consensus on the best balance between keeping the fetus in an hypoxic/acidotic environs or very premature delivery.29In fetuses with aberrant Doppler waveforms delivery should usually be by Caesarean department to avoid acute on chronic acidosis. Much current research is concentrating on improving placental transfer to develop a futurity in utero treatment for this group.

References

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