29th June 2023

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.