Chapter 14 Pregnancy, neonates and children

Respiratory Function in Pregnancy ¹

Several physiological changes occur during pregnancy that affect respiratory function. Fluid retention resulting from increasing oestrogen levels causes oedema throughout the airway mucosa, and increases blood volume, substantially increasing oxygen delivery. Progesterone levels rise six-fold through pregnancy and have significant effects on the control of respiration and therefore arterial blood gases. Finally, in the last trimester of pregnancy, the enlarging uterus has a direct impact on respiratory mechanics. A summary of the changes for common respiratory measurements is shown in Table 14.1.

Table 14.1 Respiratory function throughout pregnancy

Lung volumes. During the last third of pregnancy the diaphragm becomes displaced cephalad by the expansion of the uterus into the abdomen. This reduces both the residual volume (by about 20%) and expiratory reserve volume, such that functional residual capacity is greatly reduced (Table 14.1). This is particularly true in the supine position, and effectively removes one of the largest stores of oxygen available to the body, making pregnant women very susceptible to hypoxia during anaesthesia or with respiratory disease.

Vital capacity, forced expiratory volume in one second and maximal breathing capacity are normally unchanged during pregnancy.

Oxygen consumption. Oxygen consumption increases throughout pregnancy peaking at between 15% and 30% above normal at full term.^2,⁴ The increase is mainly attributable to the demands of the fetus, uterus and placenta, such that when oxygen consumption is expressed per kg of body weight there is little change.

Ventilation. Respiratory rate remains unchanged whilst tidal volume, and therefore minute volume of ventilation, increase by up to 40% above normal at full term. The increase in ventilation is beyond the requirements of the enhanced oxygen uptake or carbon dioxide production so alveolar and arterial Pco₂ are reduced to about 4 kPa (30 mmHg).³ This must facilitate clearance of carbon dioxide by the fetus. There is also an increase in alveolar and arterial Po₂ of about 1 kPa (7.5 mmHg).

The hyperventilation is attributable to progesterone, and the mechanism is assumed to be a sensitisation of the central chemoreceptors. Pregnancy gives rise to a three-fold increase in the slope of a Pco₂/ventilation response curve.² The hypoxic ventilatory response is increased two-fold, most of the change occurring before the mid-point of gestation, at which time oxygen consumption has hardly begun to increase.⁵

Dyspnoea occurs in more than half of pregnant women, often beginning early in pregnancy, before the mass effect of the uterus becomes apparent. Dyspnoeic pregnant women, compared with non-dyspnoeic controls, show a greater degree of hyperventilation in spite of having similar plasma progesterone levels.² Dyspnoea early in pregnancy therefore seems to arise from a greater sensitivity of the chemoreceptors to the increase in progesterone levels. In the third trimester, when dyspnoea on mild exercise is almost universal, the extra effort required by the respiratory muscles to increase tidal volume is believed to be responsible for breathlessness rather than an altered perception of respiratory discomfort.⁶

The Lungs Before Birth

Embryology

The lungs develop in four stages, under the control of a host of transcriptional factors:⁷^–¹¹

1. Pseudoglandular stage (5–17 weeks of gestation). A ventral outgrowth from the foregut first appears about 24 days after fertilisation, and around week 5 of gestation this begins to form the basic airway and vascular architecture, including the branching patterns of the adult lung. Dividing epithelial cells lengthen the airways, and their ability to do this is influenced by physical factors relating to the lung liquid and fetal breathing described below.

2. Canalicular stage (16–26 weeks gestation). The primitive pulmonary capillaries now become more closely associated with the airway epithelium and the connective tissue architecture of the lung is formed. Fibroblasts and other cells involved in morphogenesis of the lung undergo apoptosis, so reducing the wall thickness of the embryonic lung structures.

3. Saccular stage (24 weeks gestation to term). Distalairways now develop primitive alveoli in their walls to become respiratory bronchi (see Figure 2.5). Saccules form at the termination of airways, these being primitive pulmonary acini.

4. Alveolar stage. Saccules on embryonic bronchioles now expand, and septation occurs to form the groups of alveoli seen in adult pulmonary acini. This phase of development begins at 36 weeks gestation and in humans continues until around 3 years of age. In humans at full term all major elements of the lungs are therefore fully formed, but the number of alveoli present is only about 15% of the adult lung. This postnatal maturation of lung structure is only seen in altricial mammals (humans, mouse, rabbit) who have the luxury of being able to remain ‘helpless’ following birth. Precocial species such as range animals are born with a structurally mature lung, ready for immediate activity.¹²

The lungs begin to contain surfactant and are first capable of function by approximately 24–26 weeks, this being a major factor in the viability of premature infants.

Lung Liquid

Fetal lungs contain ‘lung liquid’ (LL) which is secreted by the pulmonary epithelial cells and flows out through the developing airway into the amniotic fluid or gastrointestinal tract, flushing debris from the airways as it does so. A more important function of LL seems to be to prevent the developing lung tissues from collapsing. It is thought that LL maintains the lung at a slight positive pressure relative to the amniotic fluid, and that this expansion is responsible for stimulating cell division and lung growth, particularly with respect to airway branching.¹⁰ The respiratory tract in late pregnancy contains some 40 ml of LL, but its turnover is rapid, believed to be of the order of 500 ml per day. Its volume corresponds approximately with the functional residual capacity (FRC) after breathing is established.⁹

Fetal breathing movements also contribute to lung development. In humans they begin in the middle trimester of pregnancy, and are present for over 20 minutes per hour in the last trimester,¹³ normally during periods of general fetal activity. During episodes of breathing, the frequency is about 45 breaths per minute and the diaphragm seems to be the main muscle concerned, producing an estimated fluid shift of about 2 ml at each ‘breath’.

Maintenance of a positive pressure in the developing lung requires the upper airway to offer some resistance to the outflow of LL.⁹ During apnoea, elastic recoil of the lung tissue and continuous production of LL are both opposed by intrinsic laryngeal resistance and a collapsed pharynx. Fetal inspiratory activity, as in the adult, includes dilation of the upper airway. With quiet breathing this would allow increased efflux of LL from the airway, but simultaneous diaphragmatic contraction opposes this. During vigorous breathing movements with the mouth open, pharyngeal fluid may be ‘sucked’ into the airway thus contributing to the expansion of the lungs. Thus fetal breathing movements are believed to contribute to maintaining lung expansion, and their abolition is known to impair lung development.⁹

Lung Development and Lung Function Later in Life

Complications of pregnancy such as maternal hypertension, pre-eclampsia or the use of antibiotics have all been shown to increase the incidence of wheezing in childhood.¹⁴ Small abnormalities of lung development in utero or in the early post-natal phase can adversely affect lung function beyond childhood and into adult life.^10,¹⁵ For example, in genetically susceptible individuals maternal smoking causes irreversible abnormalities of airway calibre. Abnormalities of amniotic fluid turnover may impair normal lung development in utero, and premature birth alters the normal process of alveolar formation with long term impairment in lung function (see below).

The Fetal Circulation

The fetal circulation differs radically from the postnatal circulation (Figure 14.1). Blood from the right heart is deflected away from the lungs, partly through the foramen ovale and partly through the ductus arteriosus. Less than 10% of the output of the right ventricle reaches the lungs, the remainder passing to the systemic circulation and the placenta. Right atrial pressure exceeds left atrial pressure and this maintains the patency of the foramen ovale. Furthermore, because the vascular resistance of the pulmonary circulation exceeds that of the systemic circulation before birth, pressure in the right ventricle exceeds that in the left ventricle and these factors control the direction of flow through the ductus arteriosus.