DIABETES IN PREGNANCY. Guideline for the management of diabetes and its complications from pre-conception to the postnatal period

Transcription

1 DIABETES IN PREGNANCY Guideline for the management of diabetes and its complications from pre-conception to the postnatal period

2 Diabetes in pregnancy Contents A. Introduction... 3 B. Background... 3 C. Target group... 3 D. Levels of evidence... 3 E. Methods used to collect evidence... 4 F. Guideline development... 4 G. Introduction to the guideline Pre-conception care Gestational diabetes Antenatal care Intra-partum care Neonatal care Postpartum care Protocol A: Gestational diabetes Protocol B: NIDDM Protocol C: IDDM Protocol D: Management of diabetic keto-acidosis Table 1: Specific antenatal care Table 2: Available insulin

3 A. Introduction Pregnancy has a marked effect on the carbohydrate metabolism. The most important change is a decrease in insulin sensitivity at cellular level resulting in insulin resistance. Placental hormones probably drive this process, but a whole host of secreted factors called adipokines contribute to this state. The net result is that for the same effect on glucose uptake into cells more insulin has to be secreted from the ß cells. Some mothers may lack the necessary reserve of insulin secretion to take up the challenge and insulin mediated glucose disposal therefore is reduced resulting in higher blood glucose levels (gestational diabetes). Mothers who already have pregestational diabetes (PDM) (Type 1 or Type 2) will need to increase treatment to maintain glucose homeostasis. B. Background This guideline is a priority and was identified as such by the Maternal Guidelines Committee after publication of the 2002 and 2006 Saving Mothers Report (Confidential Enquiry into Maternal Mortality in South Africa). C. Target group These guidelines are mainly intended for use by midwives and doctors conducting antenatal care and deliveries at level 1 (district hospital) and level 2 (secondary hospital) levels of care in South Africa. The ideal is that all pregnancies affected by diabetes are managed at a special diabetic clinic at a secondary or tertiary hospital. This type of care requires more individualised treatment and these guidelines can also be used at a tertiary level of care under the discretion of the managing clinician. D. Levels of evidence This guideline is based on the best available evidence from the NICE guideline and from consensus by the Western Cape Clinical Guidelines Committee; which based its findings on a full literature search and, where evidence is lacking, on expert opinion. The guideline was - 3

4 subsequently revised by a sub-committee of the Society for Maternal and Fetal Medicine in South Africa after input from all the members of that society. The full NICE guideline ( gives details of the methods and the evidence used to develop the guidance as well as the full literature review on which this was based. The NICE guideline was published in March 2008, and refers to the ongoing HAPO and ACHOIS studies, final results of which were published in May 2008 and included in this review. E. Methods used to collect evidence The MEDLINE database was searched for all English language publications using the key words Diabetes, Pregnancy, Metformin, insulin, keto-acidosis, HAPO and ACHOIS (accessed at ). Related articles were found through the linkage function inherent in the Medline search engine as well as through the reference section of accessed publications. All Cochrane reviews related to pregnancy and childbirth were perused in the Cochrane library issue 3 of 2010, (full-text accessed through Wiley InterScience at The repositories of data of the following colleges were accessed online: Royal College of Obstetrics and Gynaecology ( ), American College of Obstetrics and Gynecology ( ) the Royal Australian and New-Zealand College of Obstetrics and Gynaecology ( and the Society of Obstetricians and Gynaecologists of Canada ( The World Health Organisation resource guides were accessed at and further literature searches for reviews and consensus statements were performed using Google Scholar ( ). F. Guideline development This guideline constitutes a review of the most recent (up to June 2010) literature as well as an adaptation of the NICE guideline on diabetes in pregnancy. It was developed through a process of review by o The Maternal Guidelines Reference Group o External review by experts from both academic hospitals and secondary hospitals in the Western Cape Province. o In addition the guidelines were discussed, reviewed and submitted for endorsement by the Society for Maternal and Fetal Medicine in South Africa. - 4

5 External expert reviewers: The guideline was additionally sent for peer review to two general obstetrician gynaecologists working at secondary level hospitals, medical officers working in obstetrics at district level, midwives at all levels of care and patient representatives. The Maternal Guidelines Reference Group: Members (for this document) Coordinator/Chair: Ms E Arends: Assistant Director Maternal Child & Woman s Health Sub-Directorate. Editors: Dr S Gebhardt Principal Specialist & Head of Department Obstetrics & Gynaecology, Paarl Hospital and Clinical Coordinator, Obstetrics and Gynaecology, PGWC. Prof E Coetzee: Principal Specialist, Department of Obstetrics & Gynaecology, University of Cape Town and Groote Schuur Hospital. Members: Prof G Theron: Chief Specialist, Department of Obstetrics & Gynaecology, University of Stellenbosch and Tygerberg Hospital. Dr C Oettlé: Principal Specialist & Head of Department Obstetrics & Gynaecology, Eben Dönges Hospital Worcester. Prof S Clow: Associate Professor, Division of Nursing & Midwifery, University of Cape Town. Dr L Schoeman, Senior Specialist, Department of Obstetrics & Gynaecology, University of Cape Town and Groote Schuur Hospital. Dr F Patel: Senior Specialist and Head of Department, Obstetrics and Gynaecology, Karl Bremer Hospital. Prof C Nikodem: Senior Lecturer, University of Western Cape. Ms W Kamfer: Deputy Director Maternal Neonatal & Women s Health Westcoast Winelands Region. Ms S Neethling: Chief Professional Nurse; Maternal & Woman s Health; Boland/Overberg Region. Ms L Krynauw: Chief Professional Nurse, Obstetrics and Gynaecology, Tygerberg Hospital. Ms V Adriaans: Assistant Director Maternal Neonatal & Women s Health Metropole Regional Office. Ms M Petersen: Chief Professional Nurse, Education Deptartment Mowbray Maternity Hospital. - 5

6 The members of the sub-committee of the Society for Maternal and Fetal Medicine in South Africa were: Prof D Hall: Principal Specialist, Department of Obstetrics & Gynaecology, University of Stellenbosch and Tygerberg Hospital Dr H Lombaard: Principal Specialist, Department of Obstetrics & Gynaecology, University of Pretoria. Dr M Conradie: Principal Medical Officer, Division of Endocrinology, Tygerberg hospital and Stellenbosch University - 6

7 G. Introduction to the guideline Diabetes is a disorder of carbohydrate metabolism that requires immediate changes in lifestyle. In its chronic forms, diabetes is associated with long-term vascular complications, including retinopathy, nephropathy, neuropathy and vascular disease. Diabetes in pregnancy is associated with risks to the woman and to the developing fetus. Miscarriage, pre-eclampsia and preterm labour is more common in women with pre-existing diabetes. In addition, diabetic retinopathy can worsen rapidly during pregnancy. Stillbirth, congenital malformations, macrosomia, birth injury, perinatal mortality and postnatal adaptation problems (such as hypoglycaemia) are more common in babies born to women with preexisting diabetes. This clinical guideline contains recommendations for the management of diabetes and its complications in women who wish to conceive and those who are already pregnant. The guideline builds on existing clinical guidelines for routine care during the antenatal, intrapartum and postnatal periods. It focuses on areas where additional or different care should be offered to women with diabetes and their newborn babies. Where the evidence supports it, the guideline makes separate recommendations for women with pre-existing diabetes (type 1 diabetes, type 2 diabetes and other forms of diabetes, such as maturity onset diabetes of the young) and gestational diabetes. The term 'women' is used in the guideline to refer to all females of childbearing age, including young women who have not yet transferred from paediatric to adult services. The guideline will assume that prescribers will use a drug s summary of product characteristics to inform their decisions for individual women. Woman- and baby-centred care This guideline offers best practice advice on the care of women with diabetes who are planning to become pregnant, or who are already pregnant, and their newborn babies. Key priorities for implementation Pre-conception care Women with diabetes who are planning to become pregnant should be informed that establishing good glycaemic control before conception and continuing this throughout pregnancy will reduce the risk of miscarriage, congenital malformation, stillbirth and neonatal death. It is important to explain that these risks can be reduced but not eliminated. - 7

8 The importance of avoiding unplanned pregnancy should be an essential component of diabetes education from adolescence for women with diabetes. Women with diabetes who are planning to become pregnant should be offered preconception care and advice before discontinuing contraception. Antenatal care If it is safely achievable, women with diabetes should aim to keep fasting blood glucose between mmol/l and a 2-hour post-prandial level below 7mmol/l during pregnancy. Post-prandial monitoring should be instituted when insulin is administered 2 times per day. The HbA 1c should be measured every four weeks with the aim of maintaining this value below 6.1%. Women with insulin-treated diabetes should be advised of the risks of hypoglycaemia and hypoglycaemia unawareness in pregnancy, particularly in the first trimester. During pregnancy, women who are suspected of having diabetic ketoacidosis should be admitted immediately to a tertiary hospital (or the nearest secondary hospital in rural areas), where they can receive both medical and obstetric care. Women with pre-gestational diabetes should be offered nuchal translucency (NT) ultrasound scan at 12 weeks and a fetal anomaly scan at 20 weeks. Neonatal care Babies of women with diabetes should be kept with their mothers unless there is a clinical complication or there are abnormal clinical signs that warrant admission for intensive or high care. Postnatal care Women who were diagnosed with gestational diabetes should be offered lifestyle advice (including weight control, diet and exercise) and offered at least a glucose profile (as described on page 26) at the 6-week postnatal check and annually thereafter. - 8

9 Guidance 1.1 Pre-conception care Outcomes and risks for the woman and baby Healthcare professionals should seek to empower women with diabetes to make the experience of pregnancy and childbirth a positive one by providing information, advice and support that will help to reduce the risks of adverse pregnancy outcomes for the mother and the baby Women with diabetes who are planning to become pregnant should be informed that establishing good glycaemic control before conception and continuing this throughout pregnancy will reduce the risk of miscarriage, congenital malformation, stillbirth and neonatal death. It is important to explain that these risks can be reduced but not eliminated Women with diabetes who are planning to become pregnant and their families should be offered information about how diabetes affects pregnancy and how pregnancy affects diabetes. The information should cover: the role of diet, body weight and exercise the risks of hypoglycaemia and hypoglycaemia unawareness during pregnancy how nausea and vomiting in pregnancy can affect glycaemic control the increased risk of having a baby who is large for gestational age, which increases the likelihood of birth trauma, induction of labour and caesarean section the need for assessment of diabetic retinopathy before and during pregnancy the need for assessment of diabetic nephropathy before pregnancy the importance of maternal glycaemic control during labour and birth and early feeding of the baby in order to reduce the risk of neonatal hypoglycaemia the possibility of transient morbidity in the baby during the neonatal period, which may require admission to the neonatal unit the risk of the baby developing obesity and/or diabetes in later life. - 9

10 1.1.2 The importance of planning pregnancy and the role of contraception The importance of avoiding unplanned pregnancy should be an essential component of diabetes education from adolescence for women with diabetes Women with diabetes who are planning to become pregnant should be advised: that the risks associated with pregnancies complicated by diabetes increase with the duration of diabetes to use contraception until good glycaemic control (assessed by HbA 1c ) has been established that glycaemic targets, glucose monitoring, medications for diabetes (including insulin regimens for insulin-treated diabetes) and medications for complications of diabetes will need to be reviewed before and during pregnancy that additional time and effort is required to manage diabetes during pregnancy and that there will be frequent contact with healthcare professionals. Women should be given information about the local arrangements for support, including emergency contact numbers Diet, dietary supplements, body weight and exercise Women with diabetes who are planning to become pregnant should be offered individualised dietary advice Women with diabetes who are planning to become pregnant and who have a body mass index above 27 kg/m 2 should be offered advice on how to lose weight Women with diabetes who are planning to become pregnant should be advised to take folic acid (5 mg/day) from three months before the pregnancy until at least 12 weeks of gestation to reduce the risk of having a baby with a neural tube defect Target ranges for blood glucose in the pre-conception period Individualised targets for self-monitoring of blood glucose should be agreed with women who have diabetes and are planning to become pregnant, taking into account the risk of hypoglycaemia. - 10

11 If it is safely achievable, women with diabetes who are planning to become pregnant should aim to maintain their HbA 1c below 6.1%. Women should be reassured that any reduction in HbA 1c towards this target is likely to reduce the risk of congenital malformations Women with diabetes whose HbA 1c is above 10% should be strongly advised to avoid pregnancy Monitoring blood glucose and ketones in the pre-conception period Women with diabetes who are planning to become pregnant should be offered monthly measurement of HbA 1c Women with diabetes who are planning to become pregnant should be offered a meter for self-monitoring of blood glucose Women with diabetes who are planning to become pregnant and who require intensification of hypoglycaemic therapy should be advised to increase the frequency of self-monitoring of blood glucose (up to seven times per day) to include fasting and a mixture of pre- and postprandial levels Women with type 1 diabetes who are planning to become pregnant should be offered ketone testing strips and advised to test for ketonuria or ketonaemia if they become hyperglycaemic or unwell The safety of medications for diabetes before and during pregnancy Women with diabetes may be advised to use metformin or glibenclamide as an adjunct or alternative to insulin in the preconception period and during pregnancy, when the likely benefits from improved glycaemic control outweigh the potential for harm. All other oral hypoglycaemic agents should be discontinued before pregnancy and insulin substituted Healthcare professionals should be aware that the rapid-acting insulin analogues (e.g. insulin human lispro; only available on a named patient basis in the central hospitals) are safe to use during pregnancy. - 11

12 Women with insulin-treated diabetes who are planning to become pregnant should be informed that there is insufficient evidence about the use of long-acting insulin analogues during pregnancy. Therefore isophane insulin (Protaphane HM/ Humulin N ) remains the first choice for intermediate/long-acting insulin during pregnancy The safety of medications for diabetic complications before and during pregnancy Angiotensin-converting enzyme inhibitors and angiotensin-ii receptor antagonists should be discontinued before conception or as soon as pregnancy is confirmed. Alternative antihypertensive agents suitable for use during pregnancy should be substituted Statins should be discontinued before pregnancy or as soon as pregnancy is confirmed Removing barriers to the uptake of pre-conception care and when to offer information Women with diabetes should be informed about the benefits of pre-conception glycaemic control at every contact with healthcare professionals, including their diabetes care team, from adolescence The intentions of women with diabetes regarding pregnancy and contraceptive use should be documented at each contact with their diabetes care team from adolescence Pre-conception care for women with diabetes should be given in a supportive environment and the woman s partner or another family member should be encouraged to attend Self-management programmes Women with diabetes who are planning to become pregnant should be offered pre-conception care and advice before discontinuing contraception Retinal assessment in the pre-conception period Women with type 1 or full-blown type II diabetes seeking pre-conception care should be offered retinal assessment at that time (unless an annual retinal assessment has occurred within the previous 6 months) and annually thereafter if no diabetic retinopathy is found. - 12

13 Women with diabetes who are planning to become pregnant should be advised to defer rapid optimisation of glycaemic control until after retinal assessment and treatment have been completed Renal assessment in the pre-conception period Women with diabetes should be offered a renal assessment, including a measure of microalbuminuria, before discontinuing contraception. If serum creatinine is abnormal (120 micromol/litre or more), referral to a nephrologist should be considered before discontinuing contraception. 1.2 Gestational diabetes Risk factors for gestational diabetes Healthcare professionals should be aware that the following can be independent risk factors for gestational diabetes in a South African population: Previous gestational diabetes Unexplained intra-uterine death with a previous pregnancy Previous macrosomic baby > 4.5 kg Body Mass Index at booking >40 kg/m 2 Maternal age >40 years Family history of diabetes (first-degree relative with diabetes) Family origin with a high prevalence of diabetes (Asiatic) Acanthosis nigricans Polycystic ovarian syndrome Screening for gestational diabetes It is only worthwhile screening for any condition if an effective therapy is available and if that therapy is cost-effective and prevents morbidity and mortality. In the ACHOIS study women with IGT were randomised to treatment or no treatment. This study clearly indicated that the rate of serious perinatal complications was significantly lower among the infants of the treated (or intervention) group. Patients who had diabetes according to the criteria of the 1985 WHO technical report was not randomised and the diagnosis was revealed to their supervising physician. The ACHOIS results therefore pertain only to mothers with mild carbohydrate abnormalities (IGT) but still demonstrated a clinical improvement in perinatal results for the treated pregnancies. - 13

14 There was no statistically significant increase in the caesarean section rate of the intervention group and a postpartum assessment in a subgroup of these mothers indicated an improved health status in the intervention group. The diagnosis of GDM therefore did not provoke anxiety or have a negative effect on the mother s well-being The HAPO (Hyperglycaemia and Adverse Pregnancy Outcome) Study involved more than pregnant women. As blood glucose levels increased during pregnancy; the risk of having a large newborn and the risk of that newborn having hypoglycaemia and hyperinsulinism increased. The risks increased continuously over the entire range of blood glucose levels measured, even in ranges which were considered normal The ACHOIS and the HAPO studies show impelling data that even mild hyperglycaemia results in perinatal morbidity and it seems certain that further long-term morbidity (obesity and development of diabetes when older) would also occur. In addition there are long-term considerations for mothers with GDM as they are at increased risk for the development of overt diabetes. It therefore seems imperative that we should screen every pregnant woman for GDM while taking the priorities and capacity of the healthcare system into account. This document offers options so that the approach can be tailored according to available resources Universal Screening versus Selective Screening Universal Screening One-step approach: Perform an Oral Glucose Tolerance Test (OGTT) on all pregnant mothers Two-step approach: Perform initial screening by measuring the plasma glucose level 1 hour after a 50g glucose challenge and then perform a diagnostic OGTT on those women who have glucose level >7.8mmol/l. This cut-off level will identify approximately 80% of all GDM Selective Screening - 14

15 Identify high risk parameters (detailed in ), especially for Type 2 DM, and do 75g OGTT on those mothers Glycosuria can be used as an indication for selective screening, but the renal threshold for glucose re-absorption is frequently lower and most pregnant women will have glycosuria intermittently during their pregnancy. Repeated glycosuria or fasting glycosuria may therefore be more appropriate The argument against selective screening is that 50% of all possible GDM cases can be missed. As these studies were mainly done in the developed world this may not be correct in a population where Type 2 DM is more prevalent. It is unlikely that most poorly resourced countries would be able to afford universal screening. The following is recommended: Screening for gestational diabetes using risk factors combined with testing of the urine for glucose is recommended in resource challenged settings. Do a urine test for glucose at each antenatal visit 1+ glucose or more on diagnostic strips: do a random blood glucose test In addition, the following patients must be screened (with a glucose profile or, preferably, with the 75g OGTT at the weeks visit even if the urinary diagnostic strips remain negative for glucose): Previous gestational diabetes (do OGTT already at booking) Unexplained intra-uterine death with a previous pregnancy Previous macrosomic baby > 4.5 kg Body Mass Index at booking >40 kg/m 2 Maternal age >40 years Family history of diabetes (first-degree relative with diabetes) Family origin with a high prevalence of diabetes (Asiatic) Acanthosis nigricans Polycystic ovarian syndrome - 15

16 In order to make an informed decision about screening and testing for gestational diabetes, women should be informed that: in most women, gestational diabetes will respond to changes in diet and exercise some women (between 10% and 20%) will need oral hypoglycaemic agents or insulin therapy or both if diet and exercise are not effective in controlling gestational diabetes if gestational diabetes is not detected and controlled there is a small but increased risk of birth complications such as shoulder dystocia a diagnosis of gestational diabetes may lead to increased monitoring and interventions during both pregnancy and labour The 2-hour 75 g oral glucose tolerance test (OGTT) should be used to test for gestational diabetes. The diagnosis is made using the criteria defined by the World Health Organization (summarised below). Women who have had gestational diabetes in a previous pregnancy should be offered an OGTT at booking and a further OGTT at weeks if the results are normal. Women with any of the other risk factors for gestational diabetes (see above) should be offered an OGTT at the latest at 28 weeks. Diagnostic values: A fasting value 5.5 mmol/l (alternative 6 mmol/l) and a 2-hour value of < 7.8 mmol/l (alternative 8 mmol/l) excludes gestational diabetes. A fasting value >5.5 mmol/l (alternative 6 mmol/l) or a 2-hour value 7.8 mmol/l (alternative 8 mmol/l), venous samples after a 75g g OGTT is regarded as positive for gestational diabetes. An advantage of the above criteria is the correlation with treatment goals Women with gestational diabetes should be instructed in self-monitoring of blood glucose levels. Targets for blood glucose control should be determined in the same way as for women with pre-existing diabetes Women with gestational diabetes should be informed that good glycaemic control throughout pregnancy will reduce the risk of fetal macrosomia, trauma during birth (to themselves and the baby), induction of labour or caesarean section, neonatal hypoglycaemia and perinatal death. - 16

17 Women with gestational diabetes should be offered information covering: the role of diet, body weight and exercise the increased risk of having a baby who is large for gestational age, which increases the likelihood of birth trauma, induction of labour and caesarean section the importance of maternal glycaemic control during labour and birth and early feeding of the baby in order to reduce the risk of neonatal hypoglycaemia the possibility of transient morbidity in the baby during the neonatal period, which may require admission to the neonatal unit the risk of the baby developing obesity and/or diabetes in later life Women with gestational diabetes should be advised to choose, where possible, carbohydrates from low glycaemic index sources, lean proteins including oily fish and a balance of polyunsaturated fats and monounsaturated fats Women with gestational diabetes whose pre-pregnancy body mass index was above 27 kg/m 2 should be referred to a dietician to counsel on calorie intake and be advised to partake in moderate exercise (of at least 30 minutes daily) Hypoglycaemic therapy should be considered for women with gestational diabetes if diet and exercise fail to maintain blood glucose targets during a period of 1 2 weeks Hypoglycaemic therapy should be considered for women with gestational diabetes if ultrasound investigation suggests incipient fetal macrosomia (abdominal circumference above the 75th percentile) at diagnosis. 1.3 Antenatal care Target ranges for blood glucose during pregnancy Individualised targets for self-monitoring of blood glucose should be agreed with women with diabetes in pregnancy, taking into account the risk of hypoglycaemia If it is safely achievable, women with diabetes should aim to keep fasting blood glucose between 3.5 and 5.5 mmol/litre and 2-hour - 17

18 postprandial blood glucose below 7.0 mmol/litre during pregnancy. Alternative values are 6 and 8 mmol/litre HbA 1c should ideally be performed every 4 weeks to monitor glycaemic control with the aim of maintaining this value below 6.1% Monitoring blood glucose and ketones during pregnancy Ideally women using insulin should be advised to test fasting blood glucose levels and blood glucose levels 2 hours after every meal during pregnancy. For women using oral agents, a fasting level and measurement of HbA 1c is sufficient Women with insulin-treated diabetes should be advised to test blood glucose levels before going to bed at night during pregnancy Women with type 1 diabetes who are pregnant should be offered ketone testing strips and advised to test for ketonuria or ketonaemia if they become hyperglycaemic or feel unwell. - 18

19 1.3.3 Management of diabetes during pregnancy Women with insulin-treated diabetes should be advised of the risks of hypoglycaemia and hypoglycaemia unawareness in pregnancy, particularly in the first trimester During pregnancy, women with insulin-treated diabetes should have quick access to a concentrated glucose solution (Super-C tablets or honey) and women with type 1 diabetes should also be given a glucagon device for home administration. Women and their partners or other family members should be instructed in the use of the latter During pregnancy, women with type 1 diabetes who become unwell should have diabetic ketoacidosis excluded as a matter of urgency During pregnancy, women who are suspected of having diabetic ketoacidosis should be admitted immediately in a secondary (if in rural regions) or tertiary hospital for critical care, where they can receive both medical and obstetric care Retinal assessment during pregnancy Pregnant women with pre-existing diabetes should be offered retinal assessment If retinal assessment has not been performed in the preceding 12 months, it should be offered as soon as possible after the first contact in pregnancy in women with pre-existing diabetes Diabetic retinopathy should not be considered a contraindication to rapid optimisation of glycaemic control in women who present with a high HbA 1c in early pregnancy. However women with severe retinopathy should be closely monitored Women who have preproliferative diabetic retinopathy diagnosed during pregnancy should have ophthalmological follow-up for at least 6 months following the birth of the baby Diabetic retinopathy should not be considered a contraindication to vaginal birth. - 19

20 1.3.5 Renal assessment during pregnancy If renal assessment has not been undertaken in the preceding 12 months in women with pre-existing diabetes, it should be arranged at the first contact in pregnancy. Do a serum creatinine and urine diagnostic test for protein. If there is 1+ or more proteinuria, do a full 24- hour urinary protein quantification test. If the serum creatinine is abnormal (120 micromol/litre or more) or if total protein excretion exceeds 2 g/day, referral to a nephrologist should be considered. Thromboprophylaxis should be considered for women with proteinuria above 5 g/day (macroalbuminuria) Screening for congenital malformations Women with diabetes should be offered NT scanning at 12 weeks and a fetal anomaly scan at 20 weeks Monitoring fetal growth and well-being Pregnant women with diabetes should be offered Doppler tests of the umbilical artery at 24 weeks (if microvascular disease or pre-existing diabetes is present) as well as ultrasound monitoring of fetal growth and amniotic fluid volume at 34 weeks and an estimated fetal weight and morphometry at 38 weeks Routine monitoring of fetal well-being before 38 weeks is not recommended in pregnant women with diabetes, unless there is a risk of intra-uterine growth restriction Women with diabetes and a risk of intra-uterine growth restriction (microvascular disease and/or nephropathy) will require an individualised approach to monitoring fetal growth and well-being Timetable of antenatal appointments Women with diabetes who are pregnant should be offered immediate contact with a special diabetic clinic (if near a tertiary center) or at least refer to a high risk clinic at a secondary hospital Women with diabetes should have contact with their diabetes care team for assessment of glycaemic control every 2 weeks throughout pregnancy. - 20

21 Antenatal appointments for women with diabetes should provide care specifically for women with diabetes, in addition to the care provided routinely for healthy pregnant women. Table 1 describes where care for women with diabetes differs from routine antenatal care. At each appointment women should be offered ongoing opportunities for information and education Preterm labour in women with diabetes Diabetes should not be considered a contraindication to antenatal steroids for fetal lung maturation or to tocolysis Women with insulin-treated diabetes who are receiving steroids for fetal lung maturation should be closely monitored and provided with additional insulin as needed Betamimetic drugs should not be used for tocolysis in women with diabetes. 1.4 Intrapartum care Timing and mode of birth Pregnant women with diabetes who have a normally grown fetus should be offered elective birth through induction of labour, or by elective caesarean section if indicated, after 38 completed weeks Diabetes should not in itself be considered a contraindication to attempting vaginal birth after a previous caesarean section Pregnant women with diabetes who have an ultrasound-diagnosed macrosomic fetus should be informed of the risks and benefits of vaginal birth, induction of labour and caesarean section Analgesia and anaesthesia Women with diabetes and co-morbidities such as morbid obesity or autonomic neuropathy should be offered an anaesthetic assessment in the third trimester of pregnancy If general anaesthesia is used for the birth in women with diabetes, blood glucose should be monitored regularly (every 30 minutes) from - 21

22 induction of general anaesthesia until after the baby is born and the woman is fully conscious Glycaemic control during labour and birth During labour and birth, capillary blood glucose should be monitored on an hourly basis in women with diabetes and maintained at between 4 and 7 mmol/litre Women with type 1 diabetes should be considered for an intravenous dextrose and insulin infusion from the onset of established labour An intravenous dextrose and insulin infusion is recommended during labour and birth for women with diabetes whose blood glucose is not maintained at between 4 and 7 mmol/litre. Check urine hourly for ketones. 1.5 Neonatal care Initial assessment and criteria for admission to intensive or special care Women with diabetes should be advised to give birth in hospitals where advanced neonatal resuscitation skills are available 24 hours a day (secondary or tertiary hospitals) Babies of women with diabetes should be kept with their mothers unless there is a clinical complication or there are abnormal clinical signs that warrant admission for intensive or special care Blood glucose testing should be carried out routinely in babies of women with diabetes according to the provincial protocol for the management of a baby of a diabetic mother. Blood tests for polycythaemia, hyperbilirubinaemia, hypocalcaemia and hypomagnesaemia should be carried out for babies with clinical signs Babies of women with diabetes should have an echocardiogram performed if they show clinical signs associated with congenital heart disease or cardiomyopathy, including heart murmur. The timing of the examination will depend on the clinical circumstances Babies of women with diabetes should not be transferred to community care until they are at least 24 hours old, and not before healthcare - 22

23 professionals are satisfied that the babies are maintaining blood glucose levels and are feeding well Prevention and assessment of neonatal hypoglycaemia All maternity units should have a written policy for the prevention, detection and management of hypoglycaemia in babies of women with diabetes Babies of women with diabetes who present with clinical signs of hypoglycaemia should have their blood glucose tested and be treated with intravenous dextrose as soon as possible. 1.6 Postnatal care Breastfeeding and effects on glycaemic control Women with insulin-treated pre-existing diabetes should return to prepregnancy doses after birth and monitor their blood glucose levels carefully to establish that the dose remains appropriate Women with insulin-treated pre-existing diabetes should be informed that they are at increased risk of hypoglycaemia in the postnatal period, especially when breastfeeding, and they should be advised to have a meal or snack available before or during feeds Women who have been diagnosed with gestational diabetes should discontinue hypoglycaemic treatment immediately after birth Women with pre-existing type 2 diabetes who are breastfeeding can resume or continue to take metformin and/or glibenclamide immediately following birth but other oral hypoglycaemic agents should be avoided while breastfeeding Women with diabetes who are breastfeeding should continue to avoid any drugs for the treatment of diabetes complications that were discontinued for safety reasons in the pre-conception period Information and follow-up after birth Women with pre-existing diabetes should be referred back to their routine diabetes care arrangements. - 23

24 Women who were diagnosed with gestational diabetes should have their blood glucose tested to exclude persisting hyperglycaemia before they are transferred to community care Women who were diagnosed with gestational diabetes should be reminded of the symptoms of hyperglycaemia Women who were diagnosed with gestational diabetes should be offered lifestyle advice (including weight control, diet and exercise) and offered a glucose profile (as described on page 26) at the 6-week postnatal check-up and annually thereafter Women who were diagnosed with gestational diabetes (including those with ongoing impaired glucose regulation) should be informed about the risks of gestational diabetes in future pregnancies and they should be offered screening (OGTT or fasting plasma glucose) for diabetes when planning future pregnancies Women who were diagnosed with gestational diabetes (including those with ongoing impaired glucose regulation) should be offered early selfmonitoring of blood glucose or an OGTT in future pregnancies. A subsequent OGTT should be offered if the test results in early pregnancy are normal (see recommendation ) Women with diabetes should be reminded of the importance of contraception and the need for pre-conception care when planning future pregnancies. Further reading 1. Rowan JA, Hague WM, Gao W, Battin MR, Moore PM. Metformin versus Insulin for the treatment of gestational diabetes. N Engl J Med 2008; 358: HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med 2008; 358: Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. RCOG press March Diagnosis and treatment of diabetic ketoacidosis. Van Zyl DG, SA Fam Pract 2008; 50:

25 PROTOCOLS FOR THE SCREENING, DIAGNOSIS AND MANAGEMENT OF DIABETES MELLITUS IN PREGNANCY A. Gestational diabetes Gestational Diabetes Mellitus (GDM) is glucose intolerance with onset or first recognition during pregnancy. It therefore includes mothers who have Impaired Glucose Tolerance (IGT) or Diabetes diagnosed during the index pregnancy. The diabetes need not disappear after pregnancy and many mothers probably had unrecognised IGT or even Diabetes prior to the pregnancy. Screening for diabetes at the antenatal clinic: Do a urine test for glucose with each antenatal visit: o If 1+ glucose or more on diagnostic strips: do a random blood glucose test In addition, the following patients must be screened [with a glucose profile or, preferably, with a 75g Oral Glucose Tolerance Test (OGTT)]; preferably before the visit at 28 weeks at a doctor s clinic even if the urinary diagnostic strips remain negative for glucose: o Previous gestational diabetes (do OGTT already with booking) o Unexplained intra-uterine death in a previous pregnancy o Previous macrosomic baby > 4.5 kg o Body Mass Index at booking >40 kg/m 2 o Maternal age >40 years o Family history of diabetes (first-degree relative with diabetes) o Family origin with a high prevalence of diabetes (Asiatic) o Acanthosis nigricans o Polycystic ovarian syndrome These patients are at high risk for diabetes. Most of them would have been referred to a doctor s clinic in any case, as they do not qualify for BANC. Interpretation of a random glucose test (BANC/MOU care): <8 mmol/l is normal. Continue with BANC/MOU care. Repeat the test every time there is 1+ or more glucose on the urine strips. 8 but <11 mmol/l: return to the clinic the next morning (or as soon as possible thereafter) for a fasting blood glucose test. 11 mmol/l: Refer to the nearest specialist high-risk clinic (within 1 day). - 25

26 Interpretation of a fasting blood glucose (glucose profile) (BANC/MOU care) - do not eat or drink anything after 22h00 the previous night (except for water) Test blood glucose before breakfast (patient must bring her breakfast to the clinic) <6 mmol/l is normal- continue with BANC/MOU care 6: Put on 7600 kj diet and refer to a doctor s clinic for further management of the pregnancy. At the doctor s clinic: do a glucose profile (see below) after 2 weeks and then every 4 weeks until after delivery. If fasting still 6 mmol/l and/or 2-hour value 8 mmol/l, refer to a high-risk clinic. 8 mmol/l: Refer to the nearest specialist/ high-risk clinic (within 1 day). (In rural areas- start treatment so long and make appointment at the nearest outreach clinic) Interpretation of the 75 g OGTT (WHO definition): o GDM: Fasting value > 5.5 or 2 hour value 7.8 mmol/l How to do a glucose profile at the clinic: NPO from midnight (only water allowed) Patient brings own breakfast to clinic Test fasting blood glucose level Eat breakfast, repeat blood glucose test 2 hours later Control AIM for a fasting value of mmol/l and a 2-hour post-prandial level of below 7mmol/l. HbA 1c should ideally be performed every 4 weeks to monitor glycaemic control with the aim of maintaining this value below 6.1%. Management of gestational diabetes at the high risk clinic: Do thorough medical examination: look for complications of diabetes and for signs of long-standing diabetes. Do a baseline serum urea and creatinine determination. Start on 7600 kj diet and refer to dietician for advice. All diabetic pregnant patients must do moderate exercise for 30 minutes each day. Clinical judgement should be exercised when moving from lifestyle to medical interventions. Certain women can be given 2 weeks to assess the impact of lifestyle interventions. Correct dietary advice and compliance can lower serum glucose levels significantly. However early progression to oral agents or insulin may sometimes be necessary. - 26

27 Start on oral anti-diabetic drugs: Metformin (first choice) 500mg twice a day; increase if needed to 850mg three times a day. Alternative choice Daonil (glybenclamide) mg twice daily. Follow up in two weeks with a glucose profile. The available evidence (poor quality but all we have) does not support combining oral agents in pregnancy. If there is poor control at follow up, admit the patient to hospital for better control. While continuing with the oral medication, perform a 24 hour blood sugar monitoring profile for additional insulin requirement (determine glucose values half an hour before each main meal and 2 hours after the meal). Then add insulin to control blood sugar. The following is suggested: Begin an insulin regimen with Protophane (GREEN) [Humulin N] only. Start at a dose of 0.2u/kg. If the calculated dose comes to more than 20 units, start with 20 units. It is generally a good idea to start 2 units lower than the calculated dose if the dose is less than 20 units and the patient has not been on insulin before. Protophane should be administered 30 minutes before bedtime and the patient should have a snack just before going to sleep. Monitor the fasting glucose values and HbA 1c. When the fasting morning value remains high, Protophane (code GREEN) can be increased in a stepwise fashion until fasting values are normal. As a safety precaution monitor glucose level 4 hours after administration once protophane has been initiated or dosages modified. If fasting values are normal but HbA 1c is raised there are post-prandial excursions. Determine glucose values half an hour before each main meal and 2 hours after the main meal (three times a day) for hours before any changes and then add Actrapid (YELLOW) [Humulin R] as indicated below only once fasting values have been normalised. Identify the meal with the largest post-prandial increase and begin with Actrapid 4 units (30 minutes prior to meal). Increase by 2 units until the post-prandial value is within the target range. If necessary apply the same principle to other meals. As soon as the profile is satisfactory and the patient can inject herself, she can be discharged. Mark the antenatal card as level 3 (high risk). Follow up at a high risk/diabetic clinic according to the schedule below. Remember to offer home monitoring to any patient on insulin. Review control with HbA 1c 2-4 weeks after discharge along with home monitoring values before and after meals. Follow up of gestational diabetics at a high-risk clinic / diabetes clinic (refer to Table 1 of the guideline): - 27

28 2 weekly until 36 weeks. Thereafter weekly until delivery. Rural patients can be followed up at their own clinic in conjunction with a specialist outreach program. Perform detail ultrasound at 20 weeks including four-chamber view of the fetal heart and outflow tracts. Perform ultrasound fetal evaluation and weight estimation at weeks (weight estimation clinically or with ultrasound, if available). Perform glucose profile with each visit Offer induction of labour at 38 weeks if certain gestation (preferable option). If patient opts to continue with pregnancy, do weekly fetal surveillance until 41 weeks and then induce. If gestation uncertain, perform amniocentesis and fetal lung maturity tests. Opt for elective caesarean section if the estimated fetal weight is >4 kg at term and the baby has typical diabetic morphometry (AC >90 th centile, HC ± 50 th centile). Management of gestational diabetes in labour ALL DIABETIC PATIENTS MUST DELIVER IN A HOSPITAL WITH SPECIALIST SUPERVISION AND 24-HOUR NEONATAL RESUSCITATION FACILITIES Stop oral hypoglycaemic agents on the day of scheduled delivery or the night before an elective induction or caesarean section. Do hourly blood sugar values- aim for a value of between 4 and 7 mmol/l during delivery (if patient still eating meals). If this can be achieved without additional insulin, monitoring blood sugar may be all that is needed. As soon as patient is nil per os, start a maintenance infusion of 10 units of shortacting (Actrapid HM or Humulin R) insulin in 1 litre of 5% dextrose and administer intravenously at 100ml/hour. If hourly values not maintained between 4 and 7 mmol/l: o If blood sugar levels rise >8mmol/l, place on a maintenance infusion of units of short-acting (Actrapid HM or Humulin R) insulin in 1 litre of 5% dextrose. Administer at 100 ml per hour. (Discard any previous infusions). o If blood sugar level is <4mmol/l replace the maintenance infusion with a new infusion of 6-8U of short-acting (Actrapid HM or Humulin R) insulin in 1 litre 5% dextrose, at 100 ml/hour. (Discard any previous infusions). Perform continuous fetal heart rate monitoring with CTG during labour. Delivery in the lithotomy position is preferable. - 28

29 The labour ward doctor must be present during delivery (danger of shoulder impaction). The doctor on call for pediatrics must be present at delivery (remind them in time). Do not continue with oral anti-diabetic drugs after delivery Follow up 6 weeks 3 months after delivery to determine the long-term risk for diabetes. Women who were diagnosed with gestational diabetes should be offered lifestyle advice (including weight control, diet and exercise) and offered at least a glucose profile (as described earlier) at the 6-week postnatal check and annually thereafter. - 29

30 PROTOCOLS FOR THE SCREENING, DIAGNOSIS AND MANAGEMENT OF DIABETES MELLITUS IN PREGNANCY B. Pre-gestational (known) diabetes (non-insulin dependant) Pregestational (Known) Diabetes Mellitus (PDM) PDM mothers are usually older and overweight. They are insulin resistant, rather than insulin depleted and therefore seldom go into diabetic ketoacidosis. They usually need larger amounts of insulin to control their blood glucose values. If it is safely achievable, women with diabetes who are planning to become pregnant should aim to maintain their HbA 1c below 6.1% and take folic acid 5mg daily. Women with diabetes whose HbA 1c is above 10% should be strongly advised to avoid pregnancy. REFER ANY KNOWN TYPE 2 PREGNANT DIABETIC TO THE NEAREST HIGH RISK CLINIC DIRECTLY AFTER BOOKING. DO NOT STOP ANY ORAL ANTI-DIABETIC DRUGS BEFORE REFERRAL. Management at high risk clinic Search for the complete medical records on the management of her disease to date. Do a thorough medical examination: look for complications of diabetes and for signs of long-standing diabetes. Start on 7600 kj diet and refer to a dietician for advice. All diabetic pregnant patients must do moderate excercise for 30 minutes each day. Do renal assessment: serum creatinine and urine diagnostic strips. o If serum creatinine >120 micromol/litre, refer to a nephrologist. o If 1+ or more proteinuria on diagnostic strips- do a full 24 hour urine protein determination. If total protein excretion >2g/24 hours, refer to a nephrologist. Refer to ophthalmology for retinal check-up if long-standing type 2 diabetes and no assessment in the past year. How to do a glucose profile at the clinic: NPO from midnight (only water allowed). Patient brings own breakfast to clinic. Test fasting blood glucose level. Eat breakfast, repeat blood glucose test 2 hours later. - 30