Introduction
Diabetes in pregnancy is increasing world-wide especially in the South East Asian region. The prevalence may range from 1% to 14% depending on the diagnostic criteria (ADA, 2004). In Central Women’s Hospital, Yangon, the prevalence of Gestational Diabetes Mellitus (GDM) was 12.19% in 2003 (Tint-Swe-Latt, 2003), 15% in 2016 (CWH, Yangon Registry, 2016). Diabetes in pregnancy is associated with miscarriage, pre-eclampsia and preterm labour, stillbirth, congenital malformations, macrosomia, birth injury, perinatal mortality, neonatal hypoglycaemia.
Definition and Classification
Hyperglycaemia first detected at any time during pregnancy should be classified as either GDM or diabetes mellitus (DM) in pregnancy, according to WHO criteria (2018). GDM should be diagnosed at any time in pregnancy if one or more of the following criteria are met:
- fasting plasma glucose 5.1–6.9 mmol/L (92–125 mg/dL)
- 1-hour plasma glucose 10.0 mmol/L (180 mg/dL) following a 75 g oral glucose load
- 2-hour plasmaglucose 8.5–11.0 mmol/L (153–199 mg/dL) following a 75 g oral glucose load
DM in pregnancy should be diagnosed if one or more of the following criteria are met:
- fasting plasma glucose 7.0 mmol/L (126 mg/dL)
- 2-hour plasma glucose 11.1 mmol/L (200 mg/dL) following a 75 g oral glucose load
- random plasma glucose 11.1 mmol/L (200 mg/dL) in the presence of diabetes symptoms
Pathophysiology of GDM
The elevated blood glucose level in gestational diabetes is caused by placental hormones, human placental lactogen (hPL). A pronounced physiological decrease in peripheral insulin sensitivity occurs as pregnancy proceeds as a result of increased level of hPL, oestrogen, progesterone, cortisol and prolactin. In most cases, hyperglycaemia is a result of impaired glucose tolerance due to pancreatic β cell dysfunction on a background of chronic insulin resistance (Plows et al, 2018).
Another factor in insulin requirements during pregnancy is the production of insulinase by the placenta. GDM develops when insulin secretion falls to overcome the physiologic insulin resistance during pregnancy (Berberoglu, 2019).
Management of women with exiting DM
Preconception planning and care
Women with diabetes who are planning to become pregnant should be explained good blood glucose control before conception and continuing this throughout pregnancy will reduce the risk of miscarriage, congenital malformation, stillbirth and neonatal death. An unplanned pregnancy should be avoided by using effective contraception until good blood glucose (HbA1C level below 48 mmol/mol, 6.5%). If HbA1C is > 86mmol/mol (10%), women are strongly advised not to get pregnant. Advise to lose weight if a BMI is > 27Kg/m2 and to take Folic acid 5mg/day until 12 weeks of gestation to reduce the risk of neural tube defect. ACEI and statin should be discontinued.
Antenatal care for women with diabetes
At booking visit, take a clinical history to establish the extent of diabetes-related complications (including neuropathy and vascular disease), and review medicines for diabetes and its complications. These pregnant women should be under the joint care of diabetic physician and obstetrician. They should also be offered self-monitoring of blood glucose and retinal and renal assessment unless the woman has been assessed in the last 3 months. Frequent ante-natal visit and HbA1c levels should be done to determine the level of risk for the pregnancy. Confirm viability of pregnancy and gestational age at 7–9 weeks.
At 16–20 weeks, offer retinal assessment to women if diabetic retinopathy was present at their first antenatal clinic visit. The detailed anomaly scan including fetal heart (4 chambers, outflow tracts and 3 vessels) should be done at 20 weeks. At 28, 32 and 36 weeks, ultrasound monitoring of fetal growth and amniotic fluid volume should be offered. Test of fetal wellbeing should be done at 38 and 39 weeks. Offer induction of labour, or caesarean section if indicated at 37 week or 38+6 week. Elective birth before 37+0 weeks should be considered if there are metabolic or any other maternal or fetal complications.
Intra-partum care
Capillary plasma glucose should be monitored every hour during labour and maintained between 4 and 7 mmol/litre. Intravenous dextrose and insulin infusion should be used during labour and birth if capillary plasma glucose is not maintainedbetween 4 and 7 mmol/litre.
Neonatal care
Blood glucose testing should be routinely done at 2-4 hours after birth. Early feeding starts as soon as possible after birth (within 30 minutes) and then at frequent intervals (every 2-3 hours) until feeding maintains pre-feed capillary plasma glucose levels at a minimum of 2.0mmol/litre.
Postnatal care
Women taking insulin should reduce their insulin immediately after birth and women with pre-exiting type 2 diabetes who are breastfeeding can resume or continue to take Metformin and Glibenclamide immediately after birth, but should avoid other oral hypoglycaemic agents while breastfeeding. They should be referred back to routine diabetes care.
Gestational Diabetes
All pregnant women should be asked for risk factors for gestational diabetes at booking visit. Risk factors are those with BMI ≥ 30kg/m2, previous macrosomic baby≥ 4.5kg, previous history of GDM, history of DM in 1st degree relatives, poor obstetrics outcomes: unexplained stillbirth, IUFD, congenital anomalies and suspected fetal macrosomia and polyhydramnios in current pregnancy.
Diagnosis of GDM
Those pregnant women with gestational diabetes in a previous pregnancy, a 75g 2-hour OGTT should be performed as soon as possible after booking (whether in the first or second trimester) and a further 75g OGTT at 24-28 weeks if the result of the first OGTT are normal.Those with any of the other risk factors for GDM should be offered a 75g 2-hour OGTT at 24-28 weeks.
Most commonly used guideline for Diagnosis of GDM
* One value is sufficient for diagnosis
** Two or more values are required for diagnosis
*** Two or more values required for diagnosis
**** One value is sufficient for diagnosis
75g 2-hour OGTT
A standard OGTT should be performed after overnight fasting (8–14 hours) by giving 75 g anhydrous glucose in 250–300 ml water. Plasma glucose is measured fasting and after 2 hours. Those who meet WHO criteria for diabetes mellitus or impaired glucose tolerance (IGT) are classified as having GDM.
Management of GDM
Women with GDM should be reviewed with joint care with Physician within 1 week. Then they should be explained about the implications (both short and long term) of the diagnosis and treatment including life style changes: diet, exercise (walking 30 minutes after meals) and medicines. The targeted fasting levels are below 7mmol/litre. The good glucose control through pregnancy will reduce the risks of fetal macrosomia, birth trauma, induction of labour and /or caesarean section, neonatal hypoglycaemia and perinatal death.
Medical management
The immediate treatment with insulin, ± Metformin should be offered if (a) fasting plasma glucose ≥126mg/dl (7 mmol/L) or above at diagnosis (b) fasting between 108- 124.2 mg/dl (6-6.9 mmol/L) if complications present. Self- monitoring of glucose (fasting, pre-meal, 1 hour post meal and bed time) should be done in those with a multiple daily insulin injection, and fasting and 1 hour post meal in women who are on diet & exercise or taking oral therapy. Blood glucose targets (Capillary plasma glucose) are 5.3 mmol/L (Fasting), 7.8 mmol/L (1HPP) and 6.4 mmol/L (2HPP).
Mode and Time of delivery
Women with GDM should be advised to give birth no later than 40+6 weeks, and offered elective birth (by induction of labour, or by caesarean section if indicated) to women who have not given birth by this time. If there are maternal or fetal complications, elective birth should be considered before 40+6 weeks.
Intra-partum care
Capillary plasma glucose should be monitored every hour and maintained at 4-7 mmol/L. Intravenous dextrose & insulin infusion should be given if it is not maintained between 4-7 mmol/L. Labour should be monitored by partograph. Delivery should be done by an experienced obstetrician who should be aware of shoulder dystocia. Paediatrician should attend delivery for neonatal resuscitation if necessary.
Postpartum care
Blood glucose lowering drugs should be discontinued immediately after birth. Patient should be counselled regarding life style changes, risk of GDM in subsequent pregnancy, and importance of 6 weeks post-natal follow-up and fasting blood sugar to exclude diabetes. As up to 50% of GDM cases develop type II diabetes within 5 years of the births they are advised to do HbA1c annually.
Recommendations
As prevalence of GDM is increasing worldwide especially in Asian countries, all pregnant women with or without risk factors should be offered universal screening by 75g OGTT at 24-28 weeks to exclude GDM and to reduce maternal and perinatal morbidity and mortality by an early intervention. The standardise screening method and management guideline suitable for Myanmar is urgently needed and all health care providers should be aware of the increasing trends of GDM.
References
- American Diabetes Association (2004). Gestational diabetes mellitus. Diabetic care; 27: s88-89
- Berberoglu, Z. (2019) Pathophysiology of Gestational Diabetes Mellitus. 97
- National Institute for Health and Clinical Excellence (2015). Diabetes in pregnancy: management of diabetes and its complications from pre-conception to the post-natal period, NICE, London
- Obstetrical and Gynaecological Society Myanmar Medical association (2015). Diabetes Mellitus in Pregnancy : In Obstetrics & Gynaecological management Guidelines
- Plows,J., Stanley,J., Baker,P., Reynolds,C., et al. (2018) The pathophysiology of Gestational Diabetes Mellitus. International Journal of Molecular Sciences. 19(11), 3342
- Tint-Swe-Latt (2003). A study of Gestational Diabetes Mellitus in Central Women’s Hospital, Yangon.
- WHO (2013). Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy
- WHO (2018). Recommendation on the diagnosis of gestational diabetes in pregnancy
