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.

Pre-existing medical conditions in pregnancy

Diabetes

The impact of diabetes on pregnancy is linked to pre-pregnancy control and pre-existing complications. The outcomes for both women with diabetes and their babies are improved by tight glycaemic control in the months leading up to conception as well as during pregnancy itself.

Hyperglycaemia results in increased fetal insulin production alongside insulin-like growth factors. Chronic hyperglycaemia leads to a macrosomic fetus as the insulin converts the excess glucose for storage; polyhydramnios (excess amniotic fluid) is also seen. Target levels for fasting blood glucose in pregnancy are 5.3 – 7.8 an hour after meals.

Recent advances have resulted in all pregnant women with pre-existing diabetes meeting the criteria for continuous glucose monitoring and more are also being offered insulin pumps.

A higher HbA1c at conception is proportionately linked to an increased risk of congenital abnormalities. The background microvascular changes also increase the risk of placental insufficiency and pre-eclampsia. Women with pre-existing diabetes in pregnancy are therefore advised to take high dose folic acid (5mg) until 12/40 and 150mg aspirin until term.

Type 1 diabetes

Insulin requirements can at least double by the end of pregnancy due to the growing fetus as well as increased insulin resistance. Increased cardiac output can lead to a rapid worsening of pre-existing end organ damage.

Baseline renal function should be checked at the beginning of pregnancy, including albumin-creatinine ratio, and retinal screening should be performed at booking and 28/40 with more frequent assessment if retinopathy is present.

ACE inhibitors and angiotensin receptor blockers (ARBs) are contraindicated in pregnancy and need to be stopped pre-conception if possible. Statins should also be stopped.

Type 2 diabetes/monogenic diabetes

There is little difference between type 1 and type 2 diabetes in terms of pregnancy outcomes. As the insulin resistance increases and due to the tighter sugar control required, many women with type 2 diabetes require the addition of exogenous insulin.

Metformin is not licensed in pregnancy but is considered safe to use. Other oral blood glucose therapies should be stopped, as should ACE inhibitors, ARBs, and statins.

Women with monogenic diabetes should be seen in joint diabetic clinic, but their management depends on whether the fetus has inherited the same genetic mutation; if the mutation is present, the fetus will not be affected by the hyperglycaemia significantly, and growth will be normal.

Cardiovascular disease

Cardiovascular disease is the leading indirect cause of maternal death in the UK. The physiological changes of pregnancy can have a significant impact on pre-existing conditions, as well as resulting in new-onset symptoms.

The reduction in colloid osmotic pressure significantly increases the risk of pulmonary oedema in the presence of increased preload or increased capillary permeability due to conditions like pre-eclampsia.

Hypertension

The first line option in pregnancy is labetalol; women with chronic hypertension should be changed from ACE inhibitors and ARBs prior to conception. Thiazide and thiazide-like diuretics should also be avoided. Women on other antihypertensive treatments should be advised that there is no evidence of an increased risk of congenital malformation.

Target BP should be <135/85 if medicated. Treatment should be started if BP >140/90.

Chronic hypertension carries an increased risk of pre-eclampsia and growth restriction, so women should be advised to take aspirin 150mg until 36/40 and have growth scans from 28/40.

Ischaemic heart disease

Risk factors for ischaemic heart disease in pregnancy include increased parity as well as the usual risk factors. The risk is highest in the third trimester and peripartum. Atherosclerotic lesions are still the most common cause however the incidence of coronary artery dissection is increased compared to the non-pregnant population. The left anteriorly descending (LAD) is the most common site of dissection, followed by the right coronary artery (RCA) and the circumflex artery.

In most situations, the management of acute coronary syndrome is the same as non-pregnancy; pregnancy and recent delivery by caesarean are not contraindications for primary percutaneous coronary intervention or thrombolysis. Clopidogrel is normally used as an alternative to newer antiplatelet agents.

Adult congenital heart disease

More women are choosing to become pregnant after a diagnosis of congenital cardiac disease. The majority of women will have had successful surgery in childhood and have no long-term sequelae from their treatment. Baseline function assessments, including an echo, are helpful in risk stratification.

The presence of pulmonary hypertension is a significant risk factor for severe morbidity and mortality regardless of underlying aetiology.

Renal disease

The increased cardiac output associated with pregnancy results in a rise in creatinine clearance and eGFR during pregnancy. This often leads to an improving renal function picture on bloods in mild pre-existing renal disease; however, the long-term impact of the increased workload results in worsening of the underlying condition.

Chronic kidney disease

Women with grade 4 CKD should be warned that pregnancy may impair their function further and mean they reach the threshold for dialysis. For women already on dialysis, increased frequency is required. They are often swapped to haemodialysis if on peritoneal dialysis to reduce the risk of intra-abdominal infection, practical issues relating to space available for peritoneal dialysis with a gravid uterus, and due to improved pregnancy outcomes for haemodialysis over peritoneal dialysis.

Renal transplantation

The majority of women with a renal transplant who then go through pregnancy have good outcomes. In many cases, the transplanted kidney copes well with the increased physiological requirements and they remain stable. The best outcomes are found between 1-5 years post-transplant.

Tacrolimus and ciclosporin can be used throughout pregnancy, as can steroids. Mycophenolate mofetil and cyclophosphamide should be avoided.

Thyroid disease

Thyroid binding globulin, total T4 and T3 are all increased in pregnancy. Thyroid stimulating hormone (TSH) levels also increase in the first trimester before settling again as pregnancy progresses. Beta-hCG is similar in structure to TSH and can therefore lead to transient hyperthyroidism.

Free T3 and T4 are reduced with increased maternal iodine demands.

Due to these changes, the normal range for TSH, T3 and T4 levels are different for each trimester.

Hyperthyroid

Graves’ disease is the leading cause of hyperthyroidism seen in pregnant women, with the majority diagnosed pre-pregnancy. Carbimazole is the first line treatment outside pregnancy, however, there is a theoretical risk of aplasia cutis if used in the first trimester.

If hyperthyroidism is diagnosed in the first trimester, propylthiouracil is considered first line. Later in pregnancy either propylthiouracil or carbimazole can be used. If a woman conceives whilst taking maintenance dose carbimazole, the consensus opinion is to remain on the lowest dose possible to keep levels stable.

Graves’ is an autoimmune condition and therefore is likely to improve in pregnancy, with a potential flare postpartum. Thyrotoxicosis is rare but dangerous in pregnancy and can lead to miscarriage, preterm birth, fetal or neonatal thyrotoxicosis, and thyroid storm around delivery.

Hypothyroid

Hypothyroidism is common in women of childbearing age and can affect up to 1% of pregnancies in the UK. As in the case of hyperthyroidism, most cases will have been diagnosed pre-pregnancy and will already be on replacement therapy.

About a quarter of women will require an increase in dosing but this should be confirmed by checking for TSH and low free T4.

Untreated hypothyroidism can lead to an increase in miscarriage, low birth weights, anaemia, and pre-eclampsia. There is also a link to developmental delay in infancy.

Epilepsy

Epilepsy is a relatively common condition in women of childbearing age, with idiopathic epilepsy being the leading underlying cause. Women with well-controlled epilepsy pre-pregnancy can be reassured that, providing they continue to take their medication and the therapeutic levels of these are maintained, the pregnancy is likely to be straightforward.

SUDEP (Sudden Unexpected Death in Epilepsy) is one of the leading causes of indirect maternal death in the UK, possibly linked to the changes with drug levels and fatigue. Labour and the immediate postpartum period are the most common times for seizures.

Most epileptic seizures will not have a significant impact on the growing fetus; status epilepticus is understandably more dangerous for both mother and baby.

Anti-epileptic drugs

Due to the well-published risks of some anti-epileptic drugs, women are often concerned about continuing their medication during pregnancy. This concern can then be exacerbated by vomiting in early pregnancy leading to drug levels which are not therapeutic. Later in pregnancy, increased drug clearance and larger volumes of distribution also lead to sub-therapeutic levels, along with lower gastric absorption in labour itself.

Sodium valproate is linked to neurodevelopmental delay and neural tube defects and so should only be used by women and girls who are on the pregnancy prevention program with regular reviews and discussion about the avoidance of pregnancies.

Newer agents such as lamotrigine and levetiracetam appear to have the lowest risk of congenital abnormalities, with phenytoin and carbamazepine also at a lower level than valproate. High dose folic acid (5mg daily) seems to reduce the risk of teratogenicity, as does using a minimal dose that stabilises seizure activity and avoidance, if possible, of polytherapy.

Thrombophilia

Pregnancy itself increases the risk of venous thromboembolism (VTE). The presence of hereditary or acquired thrombophilia increases this risk further. Protein C, S or antithrombin deficiency, as well as factor V Leiden and prothrombin gene mutations, are found in the general population and all lead to an increased risk of thrombosis in pregnancy or the first six weeks postpartum. Factor V Leiden (FVL) is the most common heterozygous mutation in the general UK population and so taking a family history is important in considering VTE risk in pregnancy.

Pregnancy alters levels of anticoagulant proteins and as such no testing can be done; genetic mutations, antithrombin and antiphospholipid antibodies can be screened for if this will change management.

Antiphospholipid syndrome (APLS)

Antiphospholipid syndrome is the best-known acquired thrombophilia syndrome and has specific clinical and biochemical diagnostic criteria. Pregnancy where either obstetric history or antiphospholipid antibodies are present count as a risk factor when assessing the need for LMWH in the antenatal and postpartum period.

Other long term medical conditions

Inflammatory bowel diseases and asthma are among the most common long term medical conditions found in pregnant women. Most of the time, good control pre-pregnancy is an indicator that the disease activity during pregnancy will be minimal.

The changes in immune system activity allow many autoimmune diseases to stabilise in pregnancy but can lead to a flare postpartum. Rheumatoid conditions, as well as multiple sclerosis, fall into this category. As before, the importance of staying on treatment that has minimised symptoms and halted disease progression should be discussed with women.

Crohn’s disease has no increased risk of exacerbation in pregnancy, but the presence of perianal disease may lead to a discussion about the risk of perineal trauma with vaginal birth. There is an increased incidence of active ulcerative colitis both in pregnancy and postpartum compared to the non-pregnant population.

Biologics

Biologic agents are increasingly used to initiate disease remission and to prevent progression. We have more evidence of the safety of many monoclonal antibodies and women should be counselled about their safety and efficacy. The main risk factor around their use is the risk to the neonate of immune suppression; live vaccines should be avoided for six months after birth – in the UK, these are the BCG and rotavirus vaccines.

Infections

Women in the UK are screened for HIV, hepatitis B and syphilis. They are also asked about smear test history and HPV infection, herpes simplex and whether they have a positive history of chickenpox infection.

Hepatitis B infection should be managed as outside pregnancy; viral load guides whether the baby requires early hepatitis B vaccine or, rarely, immunoglobulin after delivery.

HIV

Most women with HIV are aware of their diagnosis prior to pregnancy. When they are on effective combination antiretroviral therapy (cART), this should be continued; if dolutegravir is included in the regimen, high dose folic acid is required to reduce the risk of neural tube defects. All pregnant women, including elite controllers, should start cART and be encouraged to continue this after pregnancy.

Viral load in the later stages of pregnancy will guide discussions about the mode of delivery. For women on cART with a viral load <50 HIV RNA copies/mL at 36/40, caesarean section should be offered for obstetric reasons only. External cephalic version and amniocentesis/chronic villous sampling are also appropriate with a non-detectable viral load.

Neonatal management in the very low risk setting is zidovudine monotherapy.

Medical complications in pregnancy

Summary

Pregnancy exerts unique physiological changes on the body. Many of these changes remain “normal for pregnancy”; however, certain conditions are unique to pregnancy or are more likely to occur in pregnancy. Hypertension, diabetes, thromboembolic disease and infections are discussed below. Intrahepatic cholestasis of pregnancy, pemphigoid gestationalis, amniotic fluid embolism, acute fatty liver of pregnancy and peripartum cardiomyopathy are further examples of conditions which only arise in pregnancy.

Diabetes

Relative insulin resistance and reduced glucose tolerance are normal for pregnancy. The placenta secretes anti-insulin hormones and so insulin production increases to overcome these changes. Low fasting glucose and high postprandial blood glucose are common.

Gestational diabetes

Gestational diabetes (GDM) is diabetes with the onset or first recognition in pregnancy; although the majority of these cases will be gestational diabetes, pregnancy can be the first time pre-existing diabetes is diagnosed.

Women with any risk factors for GDM should be screened by glucose tolerance testing between 24-28/40. Women with previous GDM should be screened as soon as practicable after booking the pregnancy. These risk factors for GDM are BMI >30, previous macrosomic baby >4.5kg, previous GDM, family history of diabetes, and ethnicity with a high prevalence of diabetes. Persistent glucosuria is also an indication for testing.

Testing should be performed using a 2-hour 75g oral glucose tolerance test, with fasting and 2-hour blood glucose levels taken. If positive, an HbA1c should be taken to screen for pre-existing diabetes.

All women who are diagnosed with gestational diabetes should be advised on how diet and exercise will improve their condition. If the fasting glucose level is under 7mmol/litre in the absence of fetal macrosomia, a trial of diet and exercise is offered.

Metformin and/or insulin should be offered to women with a fasting blood glucose of >7mmol/litre or between 6-6.9mmol/litre if there is fetal macrosomia or polyhydramnios.

Target levels for all women with diabetes in pregnancy are:

• Fasting: 5.3mmol/L
• 1hr after meals: 7.8mmol/L
• 2 hours after meals: 6.4mmol/L

Capillary plasma glucose should be kept above 4mmol/litre.

Growth scans are offered every four weeks from 28/40, with care being undertaken by joint diabetes and obstetric clinics. Women with uncomplicated gestational diabetes should be offered delivery by 40+6/40. Blood glucose measurements should be performed hourly in labour to keep levels between 4-7mmol/L.

Women with GDM should stop all blood glucose lowering therapy at delivery. Follow-up is with a fasting glucose or an HbA1c between 6-13 weeks post-delivery and an annual HbA1c thereafter.

Hypertension in pregnancy

As with diabetes, hypertensive disorders in pregnancy include new-onset hypertension and pre-existing hypertension which is recognised for the first time in pregnancy.

Hypertension in pregnancy is diagnosed at 140/90mmHg, and therapy to reduce this to 135/85mmHg should be offered if it is persistently elevated. The first line treatment is labetalol, with nifedipine second line, and methyldopa third line. Outpatient management includes BP monitoring, urine dipstick for proteinuria 1-2 times a week, and weekly bloods to screen for pre-eclampsia. Growth scans are also offered as both hypertension and beta blockers are linked to babies who are small for gestational age.

Women with BP >160/110mmHg should be admitted for initial management. This may be with oral or IV labetalol, oral nifedipine or IV hydralazine.

Post-delivery, women should continue their antihypertensive therapy; this should be reduced if BP <130/80. The exception to this is with methyldopa; this needs to be changed or stopped within two days of delivery due to the link with postnatal depression. These women should be reviewed at 2/52 postpartum and 6/52 postpartum by their GP.

Pre-eclampsia

Pre-eclampsia is a multi-system disorder with a wide variety of presentations and disease progression; the underlying cause is thought to be related to vascular endothelial dysfunction and abnormal placentation.

Risk factors for developing pre-eclampsia include hypertension in previous pregnancy, CKD, autoimmune disease, i.e. SLE or APLS, pre-existing diabetes and chronic hypertension. Women with these risk factors, as well as those with two or more moderate risk factors, should be offered 75-150mg aspirin daily from 12/40 until birth. Moderate risk factors are 1st pregnancy, age >40, pregnancy interval >10 years, BMI >35, family history of pre-eclampsia and multiple pregnancy.

The presence of new or worsening hypertension after 20/40, with either proteinuria (PCR>30) or evidence of maternal organ dysfunction or utero-placental dysfunction, makes the diagnosis of pre-eclampsia.

The management is dependent on the gestation and severity of pre-eclampsia, however, BP control and monitoring for severe pre-eclampsia form the mainstay of treatment preterm until the benefits of delivery outweigh the risks associated with preterm delivery. Diagnosis from 37/40 should lead to the offer of delivery within 24-48 hours.

Severe pre-eclampsia, HELLP and eclampsia

Severe pre-eclampsia includes BP >160/110 with significant proteinuria and/or maternal organ dysfunction. The symptoms include ongoing or recurrent severe headaches, visual scotoma, nausea or vomiting, epigastric pain and oliguria. Signs include hyperreflexia or >2 beats of clonus, liver tenderness and oedema.

HELLP (Haemolysis, Elevated Liver enzymes and Low Platelets) is diagnosed when ALT is >70 IU/L or rising, with platelets <150 x10⁹/L and falling. Immediate delivery is indicated with antihypertensive therapy and IV magnesium sulphate (bolus 4g then 1g/hr).

Eclampsia is diagnosed when a tonic-clonic seizure occurs in association with possible pre-eclampsia. Hyperreflexia may be the only preceding symptom. Most eclamptic seizures are self-limiting; mainstays of management include reducing the risk of recurrence with IV magnesium sulphate, controlling the BP and delivery of the baby if the seizure is pre-delivery.

Thromboembolic disease

The physiological changes of pregnancy increase the risk of thromboembolic disease both antenatally and, significantly, for the first six weeks after delivery. Depending on risk factors, women may be offered LMWH from booking, 28/40, or from delivery for ten days or six weeks.

Acute management of VTE

Given the increased risk of VTE in pregnancy, any woman presenting with symptoms suggestive of VTE should be started on treatment dose LMWH and have urgent investigations. The treatment dose in pregnancy is approximately 1mg/kg BD or 1.5mg/kg OD. Before starting on anticoagulants, baseline FBC, U&E, LFTs and clotting are taken. D-dimer should not be performed as pre-test probability scores are not validated in pregnancy.

DVT: if DVT is suspected, a compression duplex ultrasound should be performed. If negative but suspicion is high, LMWH should be continued, and a further scan performed on days 3 and 7. If iliac vein thrombosis is suspected MRI may be used.

PE: Women with suspected PE should have a CXR and ECG. If they also have signs of a DVT, compression duplex ultrasound should be done; if this is positive, no further investigations are required. If the CXR is abnormal, a CTPA in preference to a V/Q scan should be carried out.

Life-threatening PE: IV unfractionated heparin, thrombolysis, thoracotomy and surgical embolectomy are all options for treatment. If stable, unfractionated heparin is first line. If there is evidence of significant haemodynamic compromise, thrombolysis should be offered.

Infection

The change from cell-mediated to humoral-mediated immunity makes pregnancy a time of relative immunocompromise. Several infections are known to cause fetal and congenital complications. Alongside the more traditional TORCH organisms discussed below, zika virus, malaria, influenza, hepatitis B, HIV, gonorrhoea and chlamydia can also cause maternal and neonatal compromise. E. Coli and Group A streptococcus are the most common infections leading to severe maternal sepsis.

TORCH

Toxoplasmosis, Other (syphilis, chickenpox, parvovirus 19) Rubella, Cytomegalovirus and Herpes Simplex make up the TORCH pathogens known to cause congenital infections, developmental delay and fetal compromise.

Syphilis is screened for at booking, and a positive result should be followed up by sexual health and obstetrics with urgent treatment given. Effective treatment is highly effective in preventing congenital syphilis.

Toxoplasmosis, chickenpox, parvovirus-19, rubella and CMV are not tested on booking bloods, but if infection or exposure is suspected, IgM and IgG levels are checked. The presence of IgM indicates acute infection; IgG indicates previous exposure. Blood saved at booking is therefore checked to see if this exposure and subsequent immunity occurred prior to pregnancy.

Women are asked about herpes simplex infection at booking; primary infection at or around delivery is an indication for Caesarean section. Prophylactic acyclovir is given from 36/40 to reduce the risk of a flare of recurrent herpes.