Overview

• Pregnancy may precipitate diabetes in previously healthy but susceptible individuals

• Diabetes raises the risk of a complicated pregnancy, increasing both maternal and perinatal mortality, and the risk of congenital malformations

• Pregnancy may cause deterioration of established diabetic complications and should be avoided in those with poor glycaemic control

• Tight control of diabetes during pregnancy reduces adverse outcomes substantially

• Most patients with pre-existing diabetes will require insulin during pregnancy to achieve optimal targets if they are not already using it

• Management should be coordinated through close liaison and frequent review by the diabetes, obstetric and midwifery teams

• Follow-up of women with gestational diabetes after pregnancy is important to exclude persistent hyperglycaemia and because the lifetime risk of type 2 diabetes is high

Introduction

The standard of obstetric care for women with diabetes has seen dramatic improvements over the past few decades. Several areas however, continue to cause concern. This is reflected by morbidity and mortality in this cohort of individuals, which remains unacceptably high (Table 17.1).

Good pregnancy care starts before conception and finishes long after the birth of the baby. This form of proactive approach has been shown to help reduce the risk of complications.

Women who already have diabetes and are of childbearing age, should have pre-pregnancy counselling and optimisation of glycaemic control prior to the pregnancy. All such patients should be managed in joint diabetic pregnancy clinics where there is input from both diabetes specialist teams and obstetricians with a team of midwives. Diabetic pregnancies are considered high-risk pregnancies (Tables 17.1 and 17.5) and deliveries should be planned in units with appropriate neonatal care facilities.

Preconceptual management in women with pre-existing diabetes

As congenital malformations remain a major cause of morbidity, it is critical that optimal metabolic control is achieved before conception (Table 17.3). Unplanned pregnancies in women with diabetes should be avoided and therefore it is important to address contraception in all such women of childbearing age. This will help in planning pregnancy and optimising conditions for the best pregnancy outcome. In those mothers with evidence of diabetic complications it is important these are treated optimally prior to pregnancy. Diabetic women planning pregnancy should be helped to achieve optimal glycaemic control, preferably with HbA1c below 6.1%,

Table 17.1 Increased risks for babies of women with diabetes compared to the non-diabetic population.

Stillbirths

4.7 x

Death of baby in first 4 weeks

2.6 x

Major congenital anomaly

2x

Table 17.2 Classification of diabetes

in pregnancy.

Pregnancy in patients Diagnosis of diabetes predates pregnancy with type 1 and type 2 diabetes

Gestational diabetes Diabetes first diagnosed in pregnancy Normally develops in second trimester

(24-28 weeks) Diagnosed by oral glucose tolerance test giving a 2 hour post-challenge level >7.8mmol/l

Pregnancy in patients Diagnosis of diabetes predates pregnancy with type 1 and type 2 diabetes

Gestational diabetes Diabetes first diagnosed in pregnancy Normally develops in second trimester

(24-28 weeks) Diagnosed by oral glucose tolerance test giving a 2 hour post-challenge level >7.8mmol/l

Table 17.3 Preconception checklist.

Contraception until tight control achieved (<6.1-6.5%) Folic acid 5 mg per day

Stop teratogenic drugs - ACE inhibitors and statins in particular Screen for complications - retinal screen, creatinine, ACR Check thyroid function and rubella antibodies Provide some literature - Diabetes UK website and pregnancy guide

Prepregnancy advice for diabetes

Clinics run on a regular basis at participating hospitals

> Counselling regarding benefit of prepregnancy care and importance of good glycaemic control

> Assessment of glucose control over preceding 3 months (education on importance of good control)

> Capillary blood glucose testing qds -pre breakfast and either 1 or 2 hours post meals

> Glucose targets:

• 1 hrs post meals 4-8 mmols/L or 2 hr post meals 4-7 mmol/l

> Bloods 3 monthly:

> Rubella status - ensure active immunity

> Urine for Microalbuminuria

> Folic Acid 5 mgs

Micro and Macrovascular complications discussed with referral to appropriate medical team if needed

Medication discussed: diuretics, statins and other contraindicated medication to be stopped/changed

Full retinal assessment with their optician and referred to ophthalmologist if needed

Height, weight and BMI documented, dietary advice and support from Dietician

Smoking cessation & referral if needed

Contraception discussed and encouraged until good glucose control achieved

Advice to contact Diabetes Specialist Nurse or Diabetes Midwife and GP after a +ve pregnancy test

Relevant contact numbers documented for patient (eg written in glucose testing diary)

WANDA guidelines No:6. Version 2. Dated Jan 07.

Figure 17.1 Preconceptual advice for women with diabetes planning a pregnancy (provided by Dr Aresh Anwar, University Hospital, Coventry).

although this is often difficult to achieve despite intensive insulin therapy management. Women with diabetes are currently advised to take a dose of folic acid that is over ten times higher than that of women who do not have diabetes, i.e. 5 mg/day. If the above conditions are met, the congenital malformation rate is dramatically reduced to nearly that of control population levels (Figure 17.1).

Patients exposed to poor glycaemic control in the first trimester are at risk of congenital malformations although a more common scenario is for the patient with poor glycaemic control to experience recurrent miscarriages.

Those whose HbA1c is greater than 10% preconceptually should be strongly advised to avoid pregnancy. Otherwise there is a two- to fourfold increase in the congenital abnormality rate. Abnormalities include spina bifida, congenital heart disease, microcephaly and anencephaly. In women of South Asian origin in particular, consanguinity is still a major issue and this will of course increase the risk of congenital malformations by itself.

Gestational diabetes

Diabetes detected for the first time during pregnancy is known as gestational diabetes. Pregnancy is potentially 'diabetogenic' and may trigger hyperglycaemia, particularly if the patient is already at risk, for instance through family history. Babies born to women with gestational diabetes, like those with pre-existing diabetes, are larger than normal and this may affect both foetal and maternal outcomes.

These women are also therefore managed by close monitoring in a joint diabetes antenatal clinic. The WHO definition of gestational diabetes now includes those with impaired glucose tolerance during pregnancy (see Table 17.2).

Screening for gestational diabetes

Screening for gestational diabetes by glucose tolerance test is recommended in certain risk factor groups (see Box 17.1). These include obesity, family history of diabetes, older women and also women in ethnic minorities particularly South Asians, as it accounts for high rates of gestational diabetes. In those with risk factors, a glucose tolerance test is offered usually between 24 and 28 weeks of gestation. Those with a history of previous gestational diabetes should be treated as having gestational diabetes during subsequent pregnancies.

Box 17.1 Screening for gestational diabetes At 28 weeks

First degree relative with diabetes (any type) Body mass index >35 kg/m2 Maternal age >35 years

Ethnic minority - South Asian, Afro-Caribbean, Black African

Polycystic ovary syndrome

Long-term steroids

Previous unexplained stillbirth

Previous history of macrosomia (birth weight >4.5 kg or >90th centile for gestation (on customised growth chart if available)) Polyhydramnios or foetal macrosomia in current pregnancy (>90th centile on customised growth chart)

Early screening

Previous history of gestational diabetes should have a glucose tolerance test arranged for 16-20 weeks with a repeat at 28 weeks if the first is normal

Immediate screening

Glycosuria ++ or above on two occasions (second sample within 1 week) or +++ on single occasion Urgent blood glucose if significant ketonuria

Treatment of gestational diabetes

Gestational diabetes is initially treated with diet alone and mild exercise is also encouraged. Options for treatment may include oral hypoglycaemics such as glibenclamide or metformin, but often patients require insulin. In these cases insulin or the oral hypoglycaemic agents can be stopped upon delivery.

Monitoring of the pregnant patient with diabetes

Organisation of antenatal care and frequency of reviews are summarised in Figure 17.2. HbAlc measures are important precon-ceptually and in the first trimester, but less useful later in pregnancy,

Diabetic Antenatal Care

Progestational diabetes 1st Visit

Pregestational diabetes

• Bloods - HbAlc, U&E's, Urine for microalbuminuria

• Accurate Medical + Obstetric history

■ Medication - STOP Statins, Diuretics, ACE Inhibiters.

■ If on Oral Hypoglycaemic Agents transfer to Insulin

• Full assessment of glucose control and adjustments made

• Glucose Targets: pre-meals

4-6 mmols/L (fasting 3.5-5.5) 1hr post meal < 8mmol/l OR

2hrs post meals <7 mmols/L

• BP + Urinalysis for Protein/Ketones Scan arranged for 7-9 wks gestation to con. rm viability. Fundal screening for retinopathy Hypostop/ Glucagon/ instructions for treatment of hypoglycaemia

• Dietetic Advice low fat/sugar high fibre

• Smoking cessation

Check glucose meter, check ketone testing Review sick day rules

1 2 wkly visits or tailored to patient needs

1 Scans - Detailed fetal and cardiac scan at

20 weeks, Fetal growth at 28 weeks. ■ Bloods - 4wkly HbAlc + RBS

Retinal screening each trimester (or opthalmologist review) 1 Prompt diagnosis & treatment of: raised BP/ Pre-eclampsia/ urine and vaginal infections 1 Ketoacidosis requires admission estational diabetes estational diabetes

> 2 weekly visits tailored to individual needs

> Growth scans, bloods and screening for bp/Pre-Eclampsia as above

Pregestational diabetes

Up to 20 wks

1 Formal dating scan (at 11-14 weeks)

Pregnancy booking bloods 1 Review of glycaemic targets ■ 4 weekly HbAlc + RBS

Gestational Diabetes

Shown self blood glucose monitoring ■ Bloods HbAlc, U&E's Dietetic Advice low fat/sugar high fibre Follow guidelines at appropriate gestation

> 1-2 weekly visits Close monitoring of fetal movements

> Weekly assessment of fetal wellbeingeg liquor vol + umbilical artery Doppler scan/CTGs Growth scans at 34 wks then as needed

> 4 weekly HbA1c

• Prompt diagnosis & treatment of: ketoacidosis/raised BP//pre-eclampsia /urine and vaginal Infections

• Discuss delivery plan, involving Consultant Obstetrician with aim to deliver at <40 wks.

• Obstetric anaesthetic review at 34 wks

• Plan glycaemic management during and after delivery

N.B. Regime may vary slightly for each person

WANDA guidelines No:1. Version 2. Dated Jan 07.

Figure 17.2 Organisation of antenatal care for women with diabetes (provided by Dr Aresh Anwar, University Hospital, Coventry).

Table 17.4 Monitoring targets.

Fasting/pre-meal target 3.9-5.9 mmol/l

Post-prandial target (1 hour post meal) <7.8 mmol/l and frequent self-monitoring is required. The patient should visit a joint clinic in the outpatients department every 2 weeks. Patients are encouraged to check glucose levels post-prandially as well as fasting and pre-prandially, as better control of post-prandial hyperglycaemia can help achieve optimal control (Table 17.4).

Patients with type 2 diabetes who were previously on metformin alone will usually require insulin during pregnancy but in some cases, especially when they are needle-phobic they are managed safely with glibenclamide as it does not cross the placental barrier and is not associated with neonatal hypoglycaemia. Metformin has also been shown to be safe in pregnancy and can be used as a lone agent or with insulin.

The new rapid-acting insulin analogues such as aspart and lispro have been found to be particularly useful in pregnancy, and have advantages over soluble insulins. Whilst there is limited data on long-acting analogues, they have slowly become part of routine practice. Many units, however, continue to advocate the use of iso-phane in pregnancy. Patients who fail to achieve adequate glycaemic control despite multiple dose regimens should be considered for continuous subcutaneous insulin infusion (an insulin pump).

following the pregnancy. Hypertension in pregnancy should be managed using methyldopa, together with labetalol or amlodipine if needed. Those on angiotensin converting enzyme inhibitors should ideally be changed to the above agents before pregnancy. Statins should be stopped 3 months prior to planned conception.

Monitoring the foetus during pregnancy

The true value of foetal monitoring continues to be debated. A standard regime will start with a dating scan as soon as possible in pregnancy. This is normally followed by a more accurate dating scan at 11-12 weeks of gestation. There will then be a detailed scan at 20-21 weeks specifically examining the foetus for cardiac and central nervous system abnormalities. Serial scans assessing foetal growth normally start at 27 weeks with units varying the frequency with which they scan patients. A major risk to the foetus from diabetes is macrosomia (21% >4000 g versus 11% in general population) and a twofold increase in shoulder dystocia (7.9% versus around 3%). Assessment of foetal size, weight and health are important in determining the timing and mode of delivery.

There remains a high risk of unexplained late intrauterine death. The risk of this increases as the pregnancy progresses. As a consequence pregnancies of patients with diabetes are rarely allowed to progress to full term and patients are assessed for an appropriate delivery date from 38 weeks. Growth retardation is serious and requires specialist investigation.

Managing diabetic complications during pregnancy (Table 17.5)

Women with pre-existing diabetic retinopathy may experience quite dramatic worsening of this complication with intensifying glycaemic control, especially if they have had poor control before. Therefore, regular examinations are required and they may require laser treatment. Women with hypertension and/or proteinuria are at great risk of accelerated hypertension and renal failure. In those patients with nephropathy and serum creatinine greater than 200 ^mol/l, outcome is likely to be poor and the patient should be strongly advised not to get pregnant. Women with renal impairment can expect some deterioration of renal function

Table 17.5 Inter-relationship of diabetes and pregnancy.

Impact of diabetes on the baby

Increased miscarriage rate Increased risk of congenital anomalies Increased risk of macrosomia Increased risk of stillbirth Increased perinatal mortality

Impact of pregnancy on diabetes

Progression of retinopathy Progression of nephropathy Progression of neuropathy

Impact of diabetes on pregnancy

Increased risk of pre-eclampsia Increased risk of polyhydramnios Increased risk of Caesarean section

Management in labour

Pregnant women with diabetes are usually admitted for a short period before the planned delivery or for a longer period when there are complications present. Monitoring of hyperglycaemia and also of the foetal heart rate is carried out. Although the aim is for a vaginal delivery in most cases, it is still by Caesarean section in many cases, at around 38 weeks gestation (Figure 17.3).

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