Hydroxychloroquine in Type 2 Diabetes During Pregnancy

This is a randomised clinical trial comparing 2 groups i.e type 2 diabetes complicating pregnancies on standard treatment alone which comprises of oral hypoglycaemic agent with or without insulin and those with added hydroxychloroquine 200mg daily. They will be recruited within 14-20 weeks gestation. Randomisation will be done using computer software program. At recruitment, blood is withdrawn to measure glycated haemoglobin (HbA1c), full blood count, fructosamine, Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-alpha. These investigations will be repeated before delivery. Patients will monitor their blood glucose using staggered 7 points which consisting of pre-meals and 1 hour post-meals using their own glucometer. The optimum fasting level is 4-5.3 mmol/l, pre meal and pre bed levels of 4-6 mmol/l and 1 hour post meal level of 4-7.8 mmol/l. All participants are followed up every 2-4 weekly whereby home blood glucose monitoring will be reviewed. Fetal growth will be monitored via serial ultrasound and charted on the fetal growth chart. Patients' care will be done by the research team which consist of obstetrician, endocrinologist and diabetic educator. All patients will have eye assessment by the ophthalmologist prior to commencement of hydroxychloroquine.

All women will be delivered at 38 weeks or earlier if there are other concomitant problems such as fetal growth restriction or poorly controlled diabetes via induction of labour. The details of the delivery for both mother and neonates will be documented. At birth, the offsprings will be seen by the neonatologist who is also in the research team. After delivery, participants will be followed up in research clinic at 6 and 12 months together with the neonate. The height and weight of the infants will be measured in centimeter. Developmental milestones will be assessed according to the developmental milestones chart of Paediatric Protocols for Malaysian Hospitals 4th Edition 2019.

Compliance to hydroxychloroquine will be assessed at each follow up, whereby an indirect method of assessing adherence of participants in the hydroxychloroquine group will be made. Each participant will be asked whether they are still taking the study medication and are required to bring the remaining medication for tablet count. Participants with remaining of more than 20% of the scheduled medications will be considered as non-compliance and treated as drop-out. Participants will also be considered as drop-out when they are lost to follow-up, withdrawal of consent, non-compliance to hydroxychloroquine or a patient becomes ill due to drug adverse effects.

• To compare the gestational age at delivery between the two groups [Time frame: From recruitment up to 38 weeks of gestation]
• Type of labour [Time frame: From recruitment up to 38 weeks of gestation]
• Mode of delivery [Time frame: From recruitment up to 38 weeks of gestation]
• Postpartum haemorrhage [Time frame: Immediately from delivery up to 42 days post delivery]
• Obstetric anal sphincter injuries [Time frame: Immediately from delivery up to 24 hours]
• Neonatal birth weight at delivery [Time frame: At delivery up to 24 hours]
• Shoulder dystocia [Time frame: At delivery up to 24 hours]
• Appearance, pulse, grimace, activity and respiration score of neonate at 5 minutes [Time frame: At delivery up to 10 minutes after delivery]
• Number of neonates needing admission into neonatal intensive care unit [Time frame: At delivery up to 7 days of life]
• Height of the infant [Time frame: At six and twelve months of age after delivery]
• Weight of the infant [Time frame: At six and twelve months of age after delivery]
• Hospital admission [Time frame: From day 7 of life up to twelve months of age]