In one line
Uncontrolled asthma harms a pregnancy far more than any asthma drug does, and the commonest reason a pregnant woman deteriorates is that somebody stopped her inhaled corticosteroid. Pregnancy also strips away her oxygen reserve, so when she does deteriorate she does it faster, and a normal-looking carbon dioxide in a tiring asthmatic is the finding that should frighten you.
Where this sits. The lung volumes, gas exchange and the ventilatory changes of pregnancy are taught in the Primary chapter on respiratory physiology. The woman who tires and needs ventilating is the Finals chapter on obstetric critical care.
The lungs pregnancy builds
Two changes run in opposite directions, and the interaction is the whole reason acute asthma is more dangerous in pregnancy.
Ventilation goes up. Progesterone is a direct respiratory stimulant acting on the central chemoreceptors. From early pregnancy it raises tidal volume, and therefore minute ventilation by roughly 30 to 50%, while the respiratory rate barely changes. The mother blows off carbon dioxide, so PaCO₂ falls to about 3.7 to 4.3 kPa (roughly 28 to 32 mmHg), the kidney excretes bicarbonate in compensation so bicarbonate falls to about 18 to 22 mmol/L, and the pH settles slightly alkalaemic. This is a chronic compensated respiratory alkalosis, and it is normal. See Arterial blood gas.
The purpose is a gradient. A lower maternal PaCO₂ means carbon dioxide flows from fetus to mother more readily, and the accompanying shift favours oxygen delivery across the placenta.
Reserve goes down. The diaphragm is elevated by about 4 cm at term. Functional residual capacity falls by around 20%, taking with it the reservoir of oxygen that sits in the lungs between breaths. At the same time oxygen consumption rises by roughly 20 to 30%, because of the fetus, the uterus and the increased work of maternal breathing.
Put those together. A pregnant woman has less oxygen stored and is using it faster. The time from apnoea, or from severe bronchospasm, to significant desaturation is much shorter than in a non-pregnant woman of the same size. This is the same physiology that makes rapid sequence induction dangerous in obstetric anaesthesia, and it is why acute asthma in pregnancy is treated aggressively and early rather than watchfully.
What does not change is just as useful. FEV₁, forced vital capacity and peak expiratory flow rate are essentially unaltered by normal pregnancy. So an abnormal spirometry or peak flow in a pregnant woman is abnormal, full stop. You do not need a pregnancy-adjusted normal range, and you should not attribute a reduced peak flow to the pregnancy.
The single most important number
Because the normal maternal PaCO₂ is around 4 kPa, a PaCO₂ of 5 kPa in a breathless pregnant asthmatic is not normal. It is relative carbon dioxide retention.
In any acute asthma attack, the woman initially hyperventilates and her carbon dioxide falls further. As she tires and airflow obstruction worsens, alveolar ventilation drops and the carbon dioxide climbs back towards the non-pregnant normal range. A registrar who reads "PaCO₂ 5.0, normal" has just documented impending respiratory failure and filed it as reassurance.
A normalising PaCO₂ in a tiring asthmatic is an indication to escalate, not to relax. Call for anaesthetic and intensive care help.
What pregnancy does to asthma, and asthma to pregnancy
The rule of thirds. Asthma control changes in pregnancy: in roughly one-third of women symptoms worsen, in one-third they improve, and in one-third they are unchanged. Nobody can predict which group a given woman is in, so every pregnant asthmatic needs monitoring rather than reassurance.
Exacerbations are common, and are commonest in the second trimester. The drivers are mechanical and hormonal, and, importantly, cessation or reduction of asthma medication by the woman or by her doctor. Pregnant women are also particularly susceptible to viral respiratory infection, including influenza, which is the commonest trigger.
Risk factors for exacerbation during pregnancy, as listed by GINA: severe asthma, multiparity, black ethnicity, depression and anxiety, current smoking, age over 35, and obesity. That list describes a large proportion of a South African antenatal clinic, and it should raise the intensity of follow-up rather than sit unused in a guideline.
What poor control does. Exacerbations and poor symptom control are associated with preterm delivery, low birth weight and increased perinatal mortality for the baby, and pre-eclampsia for the mother. The mechanism is not mysterious: intermittent maternal hypoxaemia, systemic inflammation, and repeated courses of systemic corticosteroid.
And the finding that should govern the consultation: if asthma is well controlled throughout pregnancy there is little or no increased risk of adverse maternal or fetal complications. Asthma is not inherently a high-risk condition in pregnancy. Uncontrolled asthma is.
The message that has to be delivered explicitly
GINA states it as plainly as a guideline can: the advantages of actively treating asthma in pregnancy markedly outweigh any potential risks of the usual asthma medications (Evidence A). Use of inhaled corticosteroids, beta₂-agonists, montelukast or theophylline is not associated with an increased incidence of fetal abnormality.
From that follow three positions that you must be able to state without hedging:
- Women who are pregnant or planning pregnancy should not stop inhaled-corticosteroid-containing therapy. ICS reduce exacerbations in pregnancy (Evidence A), and stopping ICS in pregnancy is itself a significant risk factor for exacerbation (Evidence A).
- Do not step down treatment during pregnancy. GINA places a low priority on stepping down until after delivery, however good the control looks.
- Say the reason out loud to the woman. Poorly controlled asthma and exacerbations pose a much greater risk to her baby than her asthma treatment does. Many women and many clinicians remain worried about inhalers in pregnancy, and an unspoken worry becomes a stopped prescription.
There is a further argument worth having available. ICS use in pregnancy may be protective for the child: in an intervention study with follow-up to 4 to 6 years, asthma prevalence was over 50% lower in the children of women who took ICS during pregnancy, with the largest reduction where the mother took ICS early, before about 12 to 20 weeks.