PEDM [StratOG]

Preconception:

• HbA1c level >86 mmol/mol (10%) → advise against pregnancy.
• Folic acid (5 mg) is recommended pre-conceptually.
• Ischaemic heart disease is a strong contraindication to pregnancy.
• Hypoglycaemic drugs should not be stopped in early pregnancy or, preferably, pre-pregnancy.
• Advise women with diabetes who are planning to become pregnant to defer rapid optimisation of blood glucose control until after retinal assessment and treatment have been completed.
  • Tight glycaemic control is not recommended before pregnancy in women with pre-existing retinopathy in order to rapidly bring HbA1c as close to the normal range as possible.
  • Diabetic retinopathy should not a contraindication to rapid optimisation of blood glucose control in women who present with a high HbA1c in early pregnancy.
• Background retinopathy is unlikely to progress during pregnancy.
• Proliferative retinopathy may require laser treatment.
• Insulin requirements increase during pregnancy
• All oral hypoglycaemics except metformin should be switched to suitable alternatives either prepregnancy or when pregnancy is confirmed; glibenclamide can be used in certain circumstances.
• The prevalence of pre-eclampsia is reported to be 10–20% in women with diabetes.
• Severity of [DM] & [Proteinuria] at the onset of pregnancy increases the rates of:
  • Pre-eclampsia
  • PTD <35 weeks
    • 1/3 of all PTDs in women without diabetes are the result of hypertensive complications.

Key problems (antenatal)

• Pregnancy on DM (maternal “medical” complications):
  • Acute complications: hypoglycaemia, ketoacidosis, infections.
  • Exacerbation long-standing complications: microvascular, nephropathy, retinopathy.
• DM on pregnancy (obstetric complications):
  • Maternal “obstetric” complications: miscarriage, GHTN & PET, periodontal disease, UT & other infections, obstetric trauma, CS.
  • Fetal/neonatal complications: congenital anomalies (cardiac, renal, NTDs, microcephaly, sacral agenesis), birth injuries (shoulder dystocia, fractures, brachial plexus palsy, asphyxia), macrosomia/FGR, polyhydramnios, stillbirth/perinatal mortality, hypoglycaemia, postnatal adaptation syndromes.
• Fetal surveillance:
  • Risk for major malformations is up to 2x greater in diabetic pregnancies than in non-diabetic pregnancies.
  • US is not superior to clinical examination in predicting macrosomia.
  • Routine umbilical artery Doppler is not useful tool.
  • Postprandial levels are more influential to the development of macrosomia.
• IDM:
  • Stillbirth, congenital malformations, macrosomia, birth injury, perinatal mortality (about 28 / 1000) and postnatal adaptation problems (e.g. hypoglycaemia) are more common in babies born to women with PEDM.
  • Do not need routine admission to the special care neonatal unit
  • Hyperinsulinaemia inhibits the normal stimulatory effect of cortisol on lecithin synthesis (RDS is more common in IDM).
  • Hypocalcaemia is usually asymptomatic and resolves without treatment.
  • Macrosomia in 45% (vs. 8-9% in non-diabetics).
• PTD is increased, both
  • iatrogenic (22% vs. 3%)
  • spontaneous (16% vs. 11%): may be related to poor glycaemic control, polyhydramnios or infection.
• Falling insulin requirements in women with PEDM is a marker of placental dysfunction and are associated with an increased risk of pre-eclampsia and SGA fetuses.
• The COCP is not contraindicated.
• Children to parents with:
  • Type 1 DM → 5–6% increased risk
  • Type 2 DM → 10–15% increased risk
  • GDM → increased risk of obesity and/or DM in later life.

GDM

• Risk factors (determine at booking):
  • BMI >30 kg/m²
  • previous macrosomic baby ≥4.5 kg \(\geq\) 4.5
  • previous GDM
  • family history of DM (first-degree relative)
  • minority ethnic family origin with a high prevalence of DM
• Testing: by 75-g OGTT in women with:
  • any risk factor → at 24-28 week
  • previous GDM → asap after booking (and at 24-28 week if normal), or early self-monitoring of blood glucose
  • glycosuria ≥ 2+ on 1 occasion, or ≥ 1+ on ≥ 2 occasions (by reagent strip testing during routine ANC)
• Diagnosis (NICE):
  • Fasting ≥ 5.6 mmol/L, or
  • 2 h ≥ 7.8 mmol/L
• Management (10–20% will need hypogylcaemics or insulin therapy):
  1. ❶ Changes in diet and exercise.
  2. ❷ Metformin if targets are not met within 1–2 weeks.
  3. ❸ Insulin
• Consider insulin (± metformin + diet and exercise) if:
  • fasting ≥ 7.0 mmol/L at diagnosis
  • fasting 6 – <7 mmol/L + complications (e.g. macrosomia or polyhydramnios)
  • targets not met with diet and exercise + metformin
  • metformin is contraindicated or unacceptable to the woman.
• After birth: if returned to normal →
  • lifestyle advice (including weight control, diet and exercise) and
  • check fasting plasma glucose 6–13 weeks after birth to exclude diabetes (at the 6-week postnatal check):
    • Fasting <6 mmol/L → low probability of having diabetes at present, continue to follow the lifestyle advice.
    • Fasting >6 mmol/L → further testing for type 2 diabetes

Timing of delivery

• PEDM:
  • No complications → 37 – <39 weeks
  • Any (metabolic/M/F) → consider <37 weeks
• GDM <41 weeks

Preconception

• Advise women with DM who are planning to become pregnant to aim for the same CPG target ranges as recommended for all people with type 1 diabetes:
  • Fasting: 5–7 mmol/L (on waking)
  • Preprandial: 4–7 mmol/L (at other times the day)
  • HbA1c <48 mmol/mol (6.5%)

Insulin pump:

• Preconception
  • If switching to pump before pregnancy → pump use ≥ 3 months before attempting to conceive
  • Pumps ameliorate care, particularly in inadequately controlled diabetes:
    • recurrent hypoglycaemia or
    • ‘dawn phenomenon’ (requiring an increased dose of insulin for a short time in the early morning)
• In labour → continue with the pump but monitor blood glucose
  • Prerequisites:
    • Previously well controlled glucose
    • Stable basal needs
    • Team that is familiar with pumps during labour
    • Ideally the presence of an additional person who is able to take control of the pump and test glucose when appropriate.
  • If the use of her pump is not feasible → IV insulin

Breastfeeding

• Women with type 2 DM can resume or continue metformin and glibenclamide immediately after birth (avoid other oral glucose-lowering agents).

Target CPG in any form of diabetes (if achievable without problematic hypoglycaemia):

• Fasting: < 5.3 mmol/L, and
• 1 h after meals: < 7.8 mmol/L, or
• 2 h after meals: < 6.4 mmol/L.
• On insulin or glibenclamide → maintain CPG > 4 mmol/L

DKA [TOG 2017; StratOG]

• Occurs at lower glucose levels than in non-pregnant.
• The metabolic changes of pregnancy predispose to ketoacidosis:
  • increased insulin resistance
  • accelerated starvation (due to the high fetal and placental glucose demand)
  • reduced buffering capacity (due to increased ventilation, respiratory alkalosis and the resulting compensatory renal excretion of bicarbonate).
• The most common predisposing factors are infection, vomiting, poor control/non-compliance, beta sympathomimetic drugs and ACS.
• Diagnostic criteria (The Joint British Diabetes Societies Inpatient Care Group):
  • D Blood glucose >11.0 mmol/L or known DM
    
  • K Blood ketone ≥3.0 mmol/L or urine ketone >2+ (≥3+)
  • A Bicarbonate <15.0 mmol/L and/or venous pH <7.3
• Acid-base balance/ABG:
  • pH: 7.35 – 7.45 7.4 ±0.05
  • pO2: 10 – 14 kPa 12 ±2
  • pCO2: 4.5 – 6 kPa 5 +1–0.5
  • HCO3: 22 – 26 mmol/L 24 ±2
  • Base excess (BE): -2 – 2 mmol/L 0 ±2
• Initial fluid therapy → isotonic saline (0.9%), as most patients have a -ve fluid balance of about 100 mL/kg. This represents a total fluid deficit of approximately 6–10 L.
  • aggressive volume replacement is required
  • a sliding scale regimen of insulin and KCl in normal saline to regulate glycaemic control.
  • Careful attention to electrolyte balance is required.
• Normalisation of FHR after correction may require 4-8 hours.

Insulin

	Generic	Trade	Onset	Peak	Duration
Rapid	Aspart Lispro	Novorapid Humalog
Short	Regular	Actrapid	1/2 h	1 1/2 h, then steep decr.	5 1/2 h
Intermediate		NPH
Long	Glargine Detemir	Lantus Levemir	1 1/2 h	4-12 h (peakless), then steady decr.	24 h
Mixed		Mixtard