Standard Treatment Guidelines For Diabetes And Pregnancy

The prevalence of pre existing diabetes in pregnancy is increasing in parallel with the rise in the rates of obesity.

Diabetes in pregnancy is associated with risks to the mother & the developing fetus. Miscarriage, preeclampsia and preterm labor are more common in women with preexisting diabetes. In addition, diabetic retinopathy can worsen rapidly during pregnancy.Stillbirth,congenital malformations, macrosomia, birth injury, perinatal mortality & postnatal adaption problems such as hypoglycaemia are more common in babies born to women with pre existing diabetes.

Outcomes of diabetic pregnancies have improved for the mother and the newborn due to understanding of the disease process, improved education, and new treatment modalities delivered in a team approach. Nausea and vomiting of pregnancy and associated insulin resistance can make glycaemic control a challenge. Care of women with preexisting diabetes demands careful monitoring in the preconception, prenatal, and postpartum periods.

Controversies still exist in screening, management, & treatment of gestational diabetes.

Ministry of Health and Family Welfare, Government of India has issued the Standard Treatment Guidelines for Diabetes And Pregnancy. Following are the major recommendations :

Case definition:

Pre gestational diabetes: Women who present with ke to acidosis or random plasma glucose levels greater than 200 mg/dl plus classical signs and symptoms such as polyphagia, polyuria or polydipsia are labeled as pre gestational diabetes. American Diabetes Association (2004) also recommends that pregnant women with fasting glucose levels of 126mg/dl or greater be considered to have overt diabetes.

Gestational diabetes mellitus: Current practice is a 2 step testing, screening and diagnosis. Universal screening is recommended in India as Asians are a high risk group for diabetes.

 O’Sullivan 50 g glucose, 1 hour screening test cutoff ranges from 130mg/dl to 140 mg/dl.

 The next step, diagnostic 3 hour 100gm GTT has atleast 2 different algorithms for diagnosis of GDM. Diagnostic parameters for the 3 hour, 100g GTT

NDDGC CCC

time	mg/dl	mg/dl
FBS	105	95
1 hr	190	180
2 hr	165	155
3 hr	145	140

NDDGC-National diabetes data group criteria

CCC -Carpenter Coustan Criteria

 Recently, a single step 75 gm oral glucose tolerance test is also being used wherein a 2 hr plasma glucose level is measured after random administration of oral glucose.A plasma value > 140 mg% is diagnostic of GDM.It serves both as a screening &a diagnostic test. However, further studies are required before it is put to routine use in India.

II. Incidence Of The Condition In our Country:

1-2%of mothers

Differential Diagnosis

Glycosuria of pregnancy

Preconceptional Care:

Preconception Counselling

All women of reproductive age with preexisting diabetes should be advised about the potential benefits of pre pregnancy planning. They should be offered education on the role of diet, appropriate body weight, and exercise. The American Diabetes Association has defined optimal pre conceptional glucose control using insulin to include self monitored pre-prandial glucose levels of 70 to 100 mg/dL and postprandial values _ 140 mg/dL and _ 120 mg/dL at 1 and 2 hours, respectively. A reasonable target for HbA1c in pre-pregnancy counseling is to aim for 6%. An improvement in HbA1C levels can also be achieved by switching to short acting modern analogue and by enrolling the pre-pregnant subject into education programs that teach enhanced carbohydrate counting. Women with diabetes whose HbA1c is above 10% should be strongly advised to avoid pregnancy. In pre-pregnancy counseling the current drug regime should also be reviewed. Some hypoglycemic drugs and the newer long acting insulin analogues have not been evaluated for safety in pregnancy and they should be replaced. Anti-hypertensives particularly ACE inhibitors and angiotensin receptor antagonists should be discontinued prior to pregnancy. Finally, folate, 400 µg/d, is given periconceptionally and during early pregnancy to decrease the risk of neural-tube defects. When pregnancy occurs without any pre-pregnancy counseling , then an urgent assessment of all the previous factors should be undertaken as soon as possible at the antenatal clinic. Retinal & renal assessments are mandatory in all cases.

Optimal Diagnostic Criteria, Investigation.Treatment And Referral Criteria

Situation 1: At Secondary Hospital/Non-Metro situation:Optimal standards of situation where technology and resources are limited

a) Clinical diagnosis:As described in case definition. Women with risk factors for GDM should be carefully screened like the obese, prior GDM, prior macrosomic infant, elderly mothers, multiple pregnancy, south east Asians, Hispanics, African Americans, polycystic ovarian syndrome, family history of diabetes.

Such women at very high risk may benefit from early screening in the first trimester. If early screening is normal, screening is repeated at 24 to 26 weeks.

b) Investigations:

Close monitoring of blood glucose, baseline& interval glycosylated haemoglobin levels andurine sugar & ketones are helpful throughout pregnancy.Target blood glucose values are fasting 95 mg%, 1 hour 140 mg% & 2 hour 120 mg%.

If a patient is controlled on diet, blood sugar monitoring with capillary blood glucose levels 4 times a day (FBS and PPBS thrice) are enough.

Patients on pharmaceutical therapy- in addition need preprandial & 3 am values.

Other investigations required specially include ultrasound for dating, aneuploidy screening , anomaly scanning, growth profile monitoring for fetal weight, AFI and biophysical profile is necessary in poorly controlled diabetics.

Non stress test by 32 to 34 weeks. Lack of USG and NST facilities warrant referral to higher centers.

c) Treatment:

Diet and exercise are instituted first. For many patients with GDM ,oral hypoglycemic or insulin therapy may be avoided altogether with no increase in adverse perinatal outcomes on diet alone. For women of normal weight, the American Diabetes Association recommends a caloric intake of 30 to 35 kcal/kg, taken as three meals and three snacks daily. For underweight women, this is increased to 40 kcal/kg/d. For those more than 120 percent above ideal weight, it is decreased to 24 kcal/kg/d. An ideal dietary composition is 55 percent carbohydrate, 20 percent protein, and 25 percent fat with less than 10 percent as saturated fat. Generally a diet containing with CHO restriction to 45-60% preferably complex high fiber carbohydrates sources of known low Glycemic Index, lean proteins including oily fish, and a balance of polyunsaturated and monounsaturated fats is recommended. Women with a high BMI might be advised to restrict calorie intake with expert dietetic advice and consider suitable enhanced mild or moderate exercise during the pregnancy. 1 to 2 miles walk at least 3 times a week is recommended.

Pharmacotherapy with insulin is instituted when diet and exercise therapy fail as evidenced by an abnormality in more than half the self monitored glucose values or an abnormal value in those women tested weekly.

Recommended initial dose of Insulin is,

0.7-0.8 U/kg body wt in the 1st

trimester 1.0 U/kg body wt in the 2nd trimester

1.2U/kg body wt in the 3rd trimester

Dose is adjusted according to the response of hyperglycaemia to initial therapy.

Of the calculated daily dose, 2/3rds is given before breakfast, divided as 2/3rd NPH insulin and 1/3rd regular insulin, and the remaining 1/3rd of the daily dose is given as 1/2 regular insulin before dinner and 1/2 NPH insulin at bed time.

Self-monitoring of capillary glucose levels using a glucometer is recommended because this involves the woman in her own care. The goals of glucose control recommended during pregnancy are Fasting _≤95 mg/dL, Premeal _≤100 mg/dL,1-hr postprandial ≤140 mg/dL, 2-hr postprandial _≤120 mg/dL and 0200–0600 _≤60mg/dL.

Antenatal care- twice weekly visits required. Well controlled diabetics can deliver at 40 weeks

Poorly controlled non compliant patients on pharmacotherapy need antenatal testing for monitoring macrosomia or growth restriction and timely planning of delivery when fetus is optimally mature with lung maturity.

Women with pregestational diabetes with nephropathy, retinopathy may worsen and warrant earlier delivery. Preeclampsia, and IUGR may set in.

Good glycaemic control during pregnancy can avoid ketosis and sepsis.

Diabetic ke to acidosis should be suspected when a pregnant diabetic mother presents with blood sugar more than 200mg/dl, vomiting and dehydration with low serum bicarbonate and presence of acetone as it could lead to fetal loss if not intensively managed in conjunction with a physician.

Preterm labor in diabetics can be managed with antenatal steroids & tocolysis. However,women with insulin treated diabetes who are receiving steroids for fetal lung maturation should be closely monitored and receive additional insulin according to protocol.Also, betamimeticdrugs should not be used for tocolysis in such women. Labor and delivery Women with pre-gestational diabetes and GDM requiring pharmacotherapy are best managed with IV fluids(100-150ml/hr),insulin drips and 100mg% during active labor. Women with very mild GDM may not require insulin therapy but should have blood glucose assessment during labor.

It is important to considerably reduce or delete the dose of long-acting insulin given on the day of delivery. Regular insulin should be used to meet most or all of the insulin needs of the mother at this time, because insulin requirements typically drop markedly after delivery. During labor and after delivery, the woman should be adequately hydrated intravenously and given glucose in sufficient amounts to maintain normoglycemia. Capillary or plasma glucose levels should be checked frequently, and regular insulin should be administered accordingly. It is not unusual for a woman to require virtually no insulin for the first 24 hours or so postpartum and then for insulin requirements to fluctuate markedly during the next few days. Infection must be promptly detected and treated.

When estimated fetal weight is above 4.5 kg, elective caesarean is planned to avoid shoulder dystocia and birth trauma. In those where the EFW ranges between 4 to 4.5 kg, other obstetric factors should be considered in decision making for caesarean section.Uncontrolled diabetes & presence of end organ disease are other indications of caesarean section.

Preparedness for the management of neonatal problems is a must.

Post partum management-A 75 g GTT should be performed at 6 to 12 weeks postpartum and other intervals thereafter for GDM mothers. Subsequently, testing can be done annually or triannually(ADA recommendation).

Contraceptive advice needs to be given as per WHO recommendations.

Referral criteria:

When careful monitoring facilities are not available.

 For expert opinion regarding anomalies and paediatric surgery and for fetal echocardiography.

 When there are comorbidities warranting multidisciplinary input especially in pregestational diabetics and poorly controlled gestational diabetics.

 When there is need for intensive neonatal care unit to manage problems in the newborn.

Situation 2: At Superspeciality Facility in Metro location where higher end technology is available.

a) Clinical diagnosis: As described in situation 1

b) Investigations: As described in situation I.Fetal echocardiography & periodic doppler studiesif growth retardation present.

c) Treatment: As described in situation 1. A multidisciplinary team is involved early in care and planned delivery is carried out in the presence of anomalies to facilitate optimal care in a tertiary center with good nicu and paediatricsurgeons.An endocrinologist is necessary for the management of DKA.

d) Referral Criteria: Even in a metro situation not all centers will be equipped with the multiple specialists, skilled hands and facilities. The decision to refer to a better facility should be taken if it warrants to give the best care to the mother and the newborn.

Visit	Measures
Preconceptional/ 1 st visit	-Offer information, advice and support in relation to establishing glycaemic control& effects of diabetes on pregnancy. -Review medications for diabetes and its complications. -Folic acid supplementation. -Take a clinical history to ascertain the extent of diabetes-related complications. -Offer retinal and renal assessment if these have not been undertaken in the previous 12 months.
5-6 weeks	Confirm viability of pregnancy and gestational age. -Establish glycaemic control
16 weeks	Offer retinal assessment at 16–20 weeks to women with pre-existing diabetes who showed signs of diabetic retinopathy at the first antenatal visit.
22-24 weeks	Offer four-chamber view of the fetal heart and outflow tracts plus scans that would be offered at 18–20 weeks as part of routine antenatal care.
28 weeks	-Offer ultrasound monitoring of fetal growth and amniotic fluid volume. -Offer retinal assessment to women with pre-existing diabetes who showed no diabetic retinopathy at their first antenatal clinic visit.
32 weeks	Offer ultrasound monitoring of fetal growth and amniotic fluid volume.
36 weeks	-Offer ultrasound monitoring of fetal growth and amniotic fluid volume. -Offer information and advice about: i. timing, mode and management of birth ii. analgesia and anaesthesia iii. changes to hypoglycaemic therapy during and after birth iv. management of the baby after birth v. initiation of breastfeeding and the effect of breastfeeding on glycaemic control vi. contraception and follow-up
38 weeks	Offer induction of labour, or caesarean section if indicated, and start regular tests of fetal well-being for women with diabetes who are awaiting spontaneous labour.
39 weeks	Offer tests of fetal well-being.

40 weeks

Termination of pregnancy in diet controlled diabetics.

*All women with diabetes should also receive routine antenatal care.

V. Further Reading And References:

Williams

Obstetrics Obstetrics and Gynaecology

clinics of North America, June 2010, Vol 37, No 2 NICE clinical guideline 63: March 2008

Current Progress in Obstetrics &Gynaecology, 2012, Vol 1