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SpR Study Day
Maternal Medicine
W i t h y b u s h G e n e r a l H o s p i t a l H a v e r f o r d w e s t
2 0 A p r i l 2 0 1 2
M r R i c h a r d H u s i c k a
Gestational Diabetes Mellitus
GDM - WHO definition
carbohydrate intolerance resulting in hyperglycaemia of variable severity with onset or first recognition during pregnancy (whether or not insulin is used and regardless of whether diabetes persists after pregnancy)
World Health Organization and Department of Noncommunicable Disease Surveillance. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; 1999.
2
Incidence of DM in pregnancy
3-6% pregnancies with DM in England & Wales around 65 000 births/year
Pre-existing DM 0.37% (12.5% of DM in pregnancy)
Type 1 - 7.5%
Type 2 - 5%
GDM 3.5% in E&W (87.5% of DM in pregnancy) True GDM
Pre-existing DM (1:1000)
Office for National Statistics. Key Population and Vital Statistics 2005. Local and Health Authority Areas. No. Series VS, No 32. Basingstoke: Palgrave Macmillan; 2007.
CEMACH. Confidential Enquiry into Maternal and Child Health: Pregnancy in Women with Type 1 and Type 2 Diabetes in 2002–03, England, Wales and Northern Ireland. London: CEMACH; 2005.
King H. Epidemiology of glucose intolerance and gestational diabetes in women of childbearing age. Diabetes Care 1998;21(Suppl 2): B9–13.
Department of Health. National Service Framework for Diabetes: Standards. London: Department of Health; 2002.
3
Clinical features of GDM
Asymptomatic develops in the 2nd or 3rd trimester
Diagnosed by routine biochemical screening
or after suspicious findings
macrosomia, polyhydramnios, persistent glycosuria, recurrent infections
Rarely diagnosed retrospectively after IUD
birth of macrosomic baby
random plasma glucose or HbA1c
4
Impact of GDM on pregnancy
increased perinatal morbidity and mortality same way but to a much lesser degree than pre-existing DM
maternal hyperglycaemia
excess transfer of glucose to the fetus
fetal hyperinsulinaemia
Pedersen J. Weight and length at birth of infants of diabetic mothers. Acta Endocrinologica 1954;16(4):330–42.
5
Fetal hyperinsulinaemia
An overgrowth of insulin sensitive tissue adipose tissue – chest, shoulders, abdomen
shoulder dystocia, birth trauma, CS, perinatal death
Neonatal metabolic complications hypoglycaemia, RDS, hypocalcemia
A hypoxaemic state in utero risk of IUD, polycythaemia, hyperbilirubinaemia and renal vein
thrombosis
Pedersen J. Weight and length at birth of infants of diabetic mothers. Acta Endocrinologica 1954;16(4):330–42.
Hod M, Rabinerson D and Peled Y. Gestational diabetes mellitus: Is it a clinical entity? Diabetes Reviews 1995;3(4):602–13.
Freinkel N, Metzger BE. Pregnancy as a tissue culture experience: the critical implications of maternal metabolism for fetal development. In:
Pregnancy, Metabolism, Diabetes and the Fetus. CIBA Foundation Symposium 63 (New Series). London: CIBA Foundation; 1979. p. 3–23.
6
What to tell women?
All women healthy diet, optimal body weight, exercise
Women with risk factors explain the nature of GDM and impact on pregnancy
risks
importance of the screening
advantages of having GDM diagnosed
7
Screening and diagnosis
Original work by O’Sullivan (1964) 100g oral glucose challenge test
O’Sullivan JB, Mahan CM:Criteria for the oral glucose tolerance test in pregnancy.Diabetes 1964;13:278-285
Key questions: What level of maternal hyperglycemia measurably worsens
pregnancy outcome?
Does intervention improve outcome?
Is such intervention cost effective?
What is the optimum screening and/or diagnostic test?
Coustan DR:Management of gestational diabetes mellitus: A self-fulfilling prophecy? JAMA 1996;275:1199-1200
8
National Collaborating Centre for
Women’s and Children’s Health
Diabetes in pregnancymanagement of diabetes and its complications
from preconception to the postnatal period
Clinical GuidelineMarch 2008 (revised reprint July 2008)Funded to produce guidelines for the NHS by NICE
RCOG
Press
2008RCOG Press
Published by the Royal College of
Obstetricians and Gynaecologists.
To purchase further copies and for
a complete list of RCOG Press titles,
visit: www.rcogbookshop.com
Diab
etesin
pregn
ancy
Diabetes in pregnancymanagement of diabetes and its complications
from preconception to the postnatal period
ClinicalGuideline
Ma
rch200
8ClinicalGuideline
Ma
rch200
8D
iabetes
inpregn
ancy
Other NICE guidelines produced by the National Collaborating Centre for
Women’sand Children’sHealth include:
• Antenatal care: routine care for the healthy pregnant woman
• Fertility: assessment and treatment for people with fertility problems
• Caesarean section
• Type 1 diabetes: diagnosis and management of type 1 diabetes in children
and young people
• Long-acting reversible contraception: the effective and appropriate use of
long-acting reversible contraception
• Urinary incontinence: the management of urinary incontinence in women
• Heavy menstrual bleeding
• Feverish illness in children: assessment and initial management in children
younger than 5 years
• Urinary tract infection in children: diagnosis, treatment and long-term
management
• Intrapartum care: care of healthy women and their babies during childbirth
• Atopic eczema in children: management of atopic eczema in children from
birth up to the age of 12 years
• Surgical management of otitis media with effusion in children
Guidelines in production include:
• Induction of labour (update)
• Surgical site infection
• Diarrhoea and vomiting in children under 5
• When to suspect child maltreatment
• Meningitis and meningococcal disease in children
• Neonatal jaundice
• Idiopathic constipation in children
• Hypertension in pregnancy
• Socially complex pregnancies
• Autism in children and adolescents
Enquiries regarding the above guidelines can be addressed to:
National Collaborating Centre for Women’sand Children’sHealth
King’s Court
Fourth Floor
2–16 Goodge Street
London
W1T 2QA
enquiries@ncc-wch.org.uk
A version of this guideline for women with diabetes and the public is available from the NICE
website (www.nice.org.uk/CG063) or from NICE publications on 0845 003 7783; quote reference
number N1485.
9
NICE 2008
The 2 hour 75g oral glucose tolerance test (OGTT) should be used to test for GDM WHO criteria
Women with any risk factor OGTT at 24-28 weeks
GDM in previous pregnancy early self monitoring of blood glucose or
OGTT at 16-18 weeks and
OGTT at 28 weeks if results normal
10
NICE 2008
The WHO definition of GDM encompasses both impaired glucose tolerance (IGT) and diabetes.
World Health Organization and Department of Noncommunicable Disease Surveillance. Definition, diagnosis and classification of diabetes
mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health
Organization; 1999.
IGT: fasting < 7.0 mmol/l, 2 hour ≥ 7.8 mmol/l Diabetes: fasting ≥ 7.0 mmol/l, 2 hour ≥ 11.1 mmol/l
11
Risk factors for GDM
BMI > 30 kg/m2
Previous baby ≥ 4.5 kg
Previous GDM
Family history of DM (first-degree relative with DM)
Family origin with a high prevalence of DM: South Asian
specifically women whose country of family origin is India, Pakistan or Bangladesh
Black Caribbean
Middle Eastern family origin
specifically Saudi Arabia, United Arab Emirates, Iraq, Jordan, Syria, Oman, Qatar, Kuwait, Lebanon or Egypt
12
NICE 2008
Approximately 20–50% of women will have a positive screening result using these risk factors
Proportions will be varying considerably from one geographical area to another
13
Ethnicity
Systematic review of 13 studies:
Non-white race/ethnicity most consistent predictor of future recurrence
Recurrence rates
52–69% in the minority ethnic populations
30–37% in non-Hispanic white populations
Kim C, Berger DK and Chamany S. Recurrence of gestational diabetes mellitus: a systematic review. Diabetes Care 2007;30(5):1314–19.
14
Ethnic risk of GDM
11x in Indians
8x in South East Asians
6x in Arabs/Mediterraneans
3x in Afro-Caribbeans
highest prevalence of GDM in inner city areas
Nelson-Piercy C.Diabetes mellitus in Handbook of Obstetric Medicine, Fourth Edition, 2010
15
Previous GDM and recurrence rate
Recurrence of the GDM is 30–84%
75–77% in case of insulin-treatment in a previous pregnancy
Major CA, DeVeciana M, Weeks J, et al. Recurrence of gestational diabetes: who is at risk? American Journal of Obstetrics and Gynecology
1998;179(4):1038–42.
Spong CY, Guillermo L, Kuboshige J, et al. Recurrence of gestational diabetes mellitus: identification of risk factors. American Journal of
Perinatology 1998;15(1):29–33.
16
Age – risk factor?
….. new research shows that maternal age, alone and
in correlation with the maternal racial origin, may also be a significant factor contributing to the development of GDM.
Makgoba M, Savvidou M, Steer P. An analysis of the interrelationship between maternal age, body mass index and racial origin in the development of gestational diabetes mellitus. BJOG 2011; DOI: 10.1111/j.1471-0528.2011.03156.x.
17
Easy to prevent?
Mike Marsh, Deputy Editor-in-Chief of BJOG:
“It is crucial that women are aware of the benefits of healthy eating and weight control prior to pregnancy as this may reduce the risk of them developing diabetes in pregnancy.
Avoiding being overweight prior to pregnancy is particularly important for older women of South Asian and Black African racial origin.”
18
Does treatment help ?
ACHOIS trial RCT, 2005 (GDM defined as per WHO)
490 women with IGT in the treatment group
510 women with IGT receiving routine care
Treating GDM improves outcomes for women and babies
the rate of serious perinatal outcomes
1% intervention group vs. 4% controls, P = 0.01
34 needed to treat to prevent a serious outcome in a baby
Crowther CA, Hiller JE, Moss JR, et al.; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of
treatment of gestational diabetes mellitus on pregnancy outcomes. New England Journal of Medicine 2005;352(24):2477–86.
19
Counseling for GDM
Good glycaemic control reduces risk of fetal macrosomia
trauma during birth (to themselves and the baby)
induction of labour or caesarean section
neonatal hypoglycaemia and perinatal death
Crowther CA, Hiller JE, Moss JR, et al.; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. New England Journal of Medicine 2005;352(24):2477–86.
The role of diet, body weight and exercise may prevent or delay development of DM 2 in later life
risk doubled for each stone gained
risk 40-60% in next 10-15 years
Nelson-Piercy C. Diabetes mellitus in Handbook of Obstetric Medicine, Fourth Edition, 2010
20
Counseling - Blood glucose monitoring
Blood glucose targets during pregnancy for women with DM (including GDM) preprandial 3.5–5.9 mmol/l
1 hour postprandial < 7.8 mmol/l
Recommended self-monitoring of blood glucose fasting blood glucose and 1 hour after meal
in insulin-treated DM advise to test blood glucose before going to bed at night
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008.
21
Counseling - Diet
The goals - optimisation of glycaemic control
Avoid postprandial hyperglycaemia ! an important aim of dietary therapy is reducing postprandial
glucose levels
de Veciana M, Major CA, Morgan MA, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational
diabetes mellitus requiring insulin therapy. New England Journal of Medicine 1995;333(19):1237–41.
22
GDM - Diet
82% - 93% of women with GDM will achieve blood glucose targets on diet alone carbohydrates from low glycaemic index sources
lean proteins including oily fish
balance of polyunsaturated fats and monounsaturated fats
If BMI > 27 kg/m2 restrict calorie intake to 25 kcal/kg/day or less
does not result in ketonemia
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008.
Moses RG, Barker M, Winter M, Petocz P, Brand-Miller JC. Can a low- glycemic index diet reduce the need for insulin in gestational diabetes
mellitus? A randomized trial. Diabetes Care 2009;32:996–1000. doi:10.2337/dc09-0007
23
Diet in pre – existing DM
Women with pre-existing DM will have received extensive advice about dietary management
Women with DM 1 will have been on a structured education course Dose Adjustment for Normal Eating (DAFNE) Offer course to those not trained as a matter of urgency
6/12 after the course the mean HbA1c fell by 1%
Structured education programmes for DM 2 X-PERT
DAFNE Study Group. Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes: dose adjustment for normal eating (DAFNE) randomised controlled trial. BMJ 2002;325:746–8. doi:10.1136/bmj.325.7367.746 Deakin TA, Cade JE, Williams R, Greenwood DC. Structured patient education: the Diabetes X-PERT Programme makes a difference. Diabet Med 2006;23:944–54. doi:10.1111/j.1464-5491.2006.01906.x
24
Composition of the diet
Dietary advice for pregnant women with DM
(modified from Nutrition Subcommittee
of the Diabetes Care Advisory Committee
of Diabetes UK)
Nutrition Subcommittee of the Diabetes Care Advisory Committee of Diabetes UK. The implementation of nutritional advice for people with diabetes. Diabet Med 2003;20:786–807. doi:10.1046j.1464-5491.2003.01104.x
25
When to start hypoglycemic therapy?
Diet and exercise fail to maintain blood glucose targets during a period of 1–2 weeks
Ultrasound investigation suggests incipient fetal macrosomia AC > 70th percentile
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008.
26
What treatment? NICE 2008
Clinically effective therapy includes oral agents (metformin and glibenclamide)
insulin therapy
regular human insulin or rapid- acting insulin analogues
Health economic analysis glibenclamide is cost- effective
lack of clinical evidence from NHS setting
RCT investigating metformin is due to report (MiG)
Therapy should be individually tailored
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008
27
Treatment - Oral agents (update)
Glibenclamide (Glyburide) shorter-acting sulfonylurea in 2000 - same outcomes as insulin treatment (4% switched to insulin)
safe for most GDM and some DM 2 less episodes of hypoglycaemia than insulin and more convenient
new RCT 2010
women with GDM randomised to metformin or glibenclamide 35% of the metformin group required insulin 16% of the glibenclamide group required insulin
Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134–8. Moore LE, Clokey D, Rappaport VJ, Curet LB. Metformin compared with glyburide in gestational diabetes. A randomised controlled trial. Obstet Gynecol 2010;115:55–9. doi:10.1097/AOG.0b013e3181c52132
28
Treatment - Oral agents (update)
MiG trial 2008 Metformin – biguanide
safe and effective in GDM in the second half of pregnancy
perinatal outcomes similar
lower incidence of
PIH, pre-eclampsia, hypoglycaemia
lower postprandial glucose, lower maternal weight
46% needed insulin to achieve adequate control
With lower glycaemic targets achieved = less complication
birth weight >4kg, pre-eclampsia, prematurity
Follow-up after 2 years
better subcutaneous to visceral fat ratio
Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational
diabetes. N Engl J Med 2008;358:2003–15.
Rowan JA, Gao W, Hague WM, McIntyre HD. Glycemia and its relationship to outcomes in the metformin in gestational diabetes trial. Diabetes
Care 2010;33:9–16
Rowan JA et al. Diabetes Care 2011;34:2279
29
Insulin. NICE 2008
Rapid-acting insulin analogues aspart and lispro – benefits compared with regular insulin
outside pregnancy (also demonstrated in the pregnant population)
fewer episodes of hypoglycaemia
reduction in postprandial glucose excursions
improvement in overall glycaemic control
Long-acting insulin analogues Still unclear safety of the long actin insulin analogue – glargin
isophane insulin (NPH) remains the first choice in pregnancy
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008.
30
Insulin regimen
RCT (392 patients) insulin four times daily vs. insulin twice daily four-times-daily insulin
improves glycaemic control and perinatal outcomes does not increase the risks of maternal hypoglycaemia and caesarean
section
CSII should be offered if adequate control is not obtained
without disabling hypoglycaemia
In insulin-treated DM - provide concentrated glucose solution
in type 1 DM give also glucagon
Nachum Z, Ben Shlomo I, Weiner E, et al. Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. British Medical Journal 1999;319(7219):1223–7.
31
Fetal growth and wellbeing
USS 4 weekly fetal growth and AFI from 28 to 36 weeks
Monitoring of fetal wellbeing before 38 weeks is not recommended (unless IUGR)
Contact with the diabetes care team every 1–2 weeks throughout pregnancy
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008
32
Preterm labour and DM
Steroids and tocolysis can be used
additional insulin and close monitoring if treated by steroids
sliding scale vs. outpatient regimes
betamimetic drugs should not be used for tocolysis
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception
to the Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008
33
Timing and mode of birth
Elective IOL or CS (if indicated) after 38 weeks if uncomplicated pregnancy
reduces the risk of stillbirth and shoulder dystocia
does not increase CS rate
VBAC – no contraindication
Macrosomia discuss the risks and benefits of vaginal birth, IOL and CS
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008
34
Hyperglycaemia intrapartum
Risk of fetal hypoglycaemia post partum response to poorly controlled DM
response to maternal hyperglycaemia during the labour
Maternal hyperglycaemia associated with fetal distress
CEMACH 47% of the women with DM 1 and 41% with DM 2 had sub-
optimal glycaemic control during labour and birth (P = 0.28)
Confidential Enquiry into Maternal and Child Health. Diabetes in pregnancy: are we providing the best care? Findings of a national enquiry:
England, Wales and Northern Ireland. London: CEMACH; 2007.
35
Glycaemic control during labour and birth
Women with DM monitor capillary blood glucose on an hourly basis
aim for blood glucose 4 - 7 mmol/l
Women with DM 1 i.v. dextrose and insulin if blood glucose is not 4 - 7 mmol/l
National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the
Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008
36
Post partum - Breastfeeding
Breastfeeding probably doesn't affect glycaemic control
no high-quality studies
lower FBG 6/52 post partum in those exclusively breastfeeding
compared with those who stopped breastfeeding before 6/52 post partum or with those who bottle - fed
Ferris AM, Dalidowitz CK, Ingardia CM, et al. Lactation outcome in insulin-dependent diabetic women. Journal of the American Dietetic Association 1988;88(3):317–22.
37
Post partum - Management
GDM stop hypoglycaemic treatment immediately after birth
Insulin-treated pre-existing DM reduce insulin immediately after birth and monitor blood glucose levels
carefully to establish the appropriate dose inform about risk of hypoglycaemia in the postnatal period
especially when breastfeeding advise to have a meal or snack available before or during feeds
DM 2 and breastfeeding can resume or continue to take metformin/glibenclamide immediately
but other oral hypoglycaemic agents should be avoided while breastfeeding
Women with diabetes who are breastfeeding avoid any drugs for the treatment of DM complications that were
discontinued for safety reasons in the preconception period National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008
38
Follow - up after birth
Pre-existing DM refer back to their routine diabetes care arrangements
GDM exclude persisting hyperglycaemia before transfer to community care
remind of the symptoms of hyperglycaemia
offer lifestyle advice
including weight control, diet and exercise
FBG 6/52 post partum and annually thereafter
inform about the risks of GDM in future pregnancies
screening for DM when planning future pregnancies
OGTT or fasting plasma glucose
early blood glucose self-monitoring or an OGTT in future pregnancies
subsequent OGTT at 28/40 if normal results
39
Planning of pregnancy
importance of contraception
need for preconception care
40
Update since NICE 2008 guideline - HAPO
The multinational Hyperglycaemia and Pregnancy Outcome (HAPO) study defined the relationship of maternal glucose tolerance to
neonatal outcomes in over 23000 women
linear relationship between maternal fasting and postprandial glucose level and birth weight above 90th centile
same apply to adiposity
no apparent threshold effect
HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and
adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.
41
Update since NICE 2008 guideline - IADPSG
The International Association of Diabetes and Pregnancy Study Groups
consensus report 2010
effort to achieve international consensus
radical redrawing of diagnosis and screening
dg levels set at the levels of blood glucose at which adverse outcomes (LGA, cord C
peptide and newborn fat >90th C) are increased 1.75 fold over the mean from HAPO
test for all population
expected incidence of GDM over 16% !!!
International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano
PA, Damm P, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of
hyperglycemia in pregnancy. Diabetes Care 2010;33:676–82.
42
Update since NICE 2008 guideline - SIGN
Scottish guidelines adopted IADPSG criteria oGTT for high risk women
fasting glucose for low risk women
Scotish Intercollegiate Guidelines Network. National clinical guideline 116: Management of diabetes. Edinburgh: SIGN; 2010
[http://www.sign.ac.uk/pdf/sign116.pdf].
43
Current challenges
How to translate the results of trials into the practice? probably no more studies without dg or treatment of diabetes
Major increase in incidence but probably only 8-20% would need insulin or oral treatment
Can we indicate high risk women for intensive intervention?
low risk group which does not need testing?
Dietary changes in larger proportion of pregnant women Would it be beneficial?
Would it prevent GDM and complications?
Can we influence the health of the next generation?
Diagnosis and Treatment of Gestational Diabetes, RCOG, Scientific Advisory Committee Opinion Paper 23, January 2011
44
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