29th June 2023

Physiological changes in pregnancy

Overview

In normal pregnancy there are significant physiological adaptations across body systems. These enable the fetus to receive adequate nutrition and oxygen, as well as removing waste products. They also allow the pregnancy to continue despite containing non-host genetic material.

Pregnancy is measured in weeks, with a full-term pregnancy taken as 40/40. Term births are from 37/40 to 42/40 to allow for individual variation. The first trimester ends at 12 completed weeks, by which point most organogenesis has occurred.

Viability (the ability to survive outside the womb) is currently set at 24/40 within the late second trimester. The third trimester starts at 28/40 until delivery. In the UK, pregnancy is managed by midwives, with high-risk women under the care of obstetricians alongside community midwives. Scans are offered at 11-13/40, with trisomy screening at 19-22/40 with detailed anatomy scanning for all pregnancies with extra input and scans as required. Rhesus negative women have free fetal DNA screening in the first trimester, with prophylactic anti-D offered at 28/40 for any found to be carrying a rhesus positive fetus.

The number of pregnancies someone has experienced is the gravidity, normally shortened to G. The number of babies delivered at 24/40 onwards is the parity, shortened to P. Someone in their first pregnancy would be G1P0.

Cardiovascular

From the early stages, there is a drop in peripheral vascular resistance linked to peripheral vasodilation. Cardiac output increases by about 40% to compensate for this. Much of this increase is due to increased stroke volume, however, heart rate also increases by 10-15bpm.

The fall in peripheral vascular resistance leads to a drop in blood pressure (BP) in the first 20 weeks of pregnancy before rising to pre-pregnancy levels by term. There may be an overshoot for the first few days postpartum before settling to pre-pregnancy levels.

There is also a significant drop in serum colloid osmotic pressure with no change in pulmonary capillary wedge pressure.

Changes in stroke volume can lead to changes in examination and ECG during normal pregnancy; an ejection systolic murmur is very common, as is a loud first heart sound and an audible third heart sound. Ectopic beats, a small Q wave and an inverted T wave in lead III can be normal, as can ST depression and T wave inversion in inferior and lateral leads. The axis shifts to the left, which can also be seen on CXR, where there is an increase in cardiothoracic ratio.

Respiratory

Throughout pregnancy, there is a steady increase in oxygen consumption due to increased metabolic needs as well as the necessity of an alteration in the blood buffering system to optimise gas exchange in the placenta.

Tidal volume increases to enable this demand to be met, with an increase in rib cage circumference. Minute ventilation increases by about 45% due to the increase in tidal volume; there is usually no change in respiratory rate. At the end of pregnancy, due to diaphragmatic elevation, there is a fall in functional residual capacity.

PaO2 increases and PaCO2 decreases to enable gas exchange at the placenta. A chronic, fully compensated, respiratory alkalosis is therefore normal with pH 7.42-7.46 and a serum bicarbonate of 18-22.

Endocrinology and glycaemic control

There is an increase in peripheral insulin resistance and a subsequent increase in insulin production during normal pregnancy. Fasting glucose levels, therefore, fall with increased postprandial levels. Starvation, particularly in the third trimester, carries with it an increased risk of ketoacidosis.

Both pituitary and adrenal hormone levels are altered significantly. As well as the expected fall in FSH and LH due to the high progesterone and oestrogen levels, there is a slow increase in prolactin as pregnancy progresses.

The placenta secretes a number of hormones which are similar in structure to pituitary hormones. Placental hormones include growth hormone, cortisol releasing hormone and vasopressinase.

There is an increase in thyroid binding globulin resulting in an increase in T4 production and iodine requirements.

Renin and aldosterone levels are also significantly increased.

Renal

The increase in stroke volume results in a 50% rise in GFR and a subsequent fall in urea and creatinine. There is an increase in both proteinuria and glucosuria, along with increased bicarbonate and calcium excretion.

Renal size is increased and mild physiological hydronephrosis can be seen as the gravid uterus compresses the ureters at the pelvic brim.

Haematology

From the beginning of pregnancy until about 34/40 there is a steady increase in plasma volume by about 40%. This results in haemodilution, causing a drop in haemoglobin concentration, haematocrit, and red cell count. There is no fall in MCV, however, the increase in iron requirements may result in concurrent iron deficiency anaemia.

An increase in WCC (mostly neutrophil driven) and a drop in platelet levels are also normal (thrombocytopenia is defined as under 100 in pregnancy).

Pregnancy results in an increase in factors V, VIII, X, and von Willebrand factor, improving the coagulation ability of women with some underlying bleeding disorders but also resulting in a significantly heightened coagulable state. This increase in clotting risk is present for up to 6/52 postpartum. There is also impaired fibrinolysis, further increasing the risk of clots.

Neurology

The changes in blood pressure, peripheral vascular resistance and coagulation increase the risk of acute neurological events during pregnancy and immediately postpartum.

Many drugs used for neurological conditions have limited use in pregnancy or are teratogenic. Plasma concentrations can drop below therapeutic levels causing exacerbations in existing diseases.

Immune system and infectious diseases

To allow the pregnancy to continue, there is a change in the immune system from cellular (Th-1 mediated) to humoral (Th-2) mediated. These changes can have a positive impact on certain autoimmune diseases but result in a relatively immune-deficient state.

In the UK, women in the first trimester are screened for HIV, Hepatitis B, and syphilis.

Gastroenterology

Progesterone has several effects on gut motility, including reduced peristalsis and delayed gastric emptying. It also, unfortunately, reduces the pressure of the oesophageal sphincter. This results in reflux and constipation, which can be difficult to manage.

Liver metabolism is increased in pregnancy, further impacting on drug levels. The haemodilution seen decreases the total protein concentration due to the fall in albumin. ALT and AST fall slightly in normal pregnancy and bilirubin should remain unchanged.

Alkaline phosphatase is produced by the placenta and, therefore, will show an elevated blood level; the machine doesn’t routinely separate liver, bone, and placenta alkaline phosphatase.

Rheumatology

The fall in T-cell mediated immunity often has a positive impact on connective tissue diseases; however, the rapid reversal of this postpartum increases the risk of flare-up in the months post-delivery.

A small number of autoantibodies can cause congenital conditions; anti-Ro and anti-La antibodies can cause congenital heart block.