Objectives
Pharmacological Management
Discuss the safety of continuing pre -pregnancy medications Decide when antihyperglycemic medication is required during pregnancy Determine what antihyperglycemic medication to use Discuss initial dosing and adjustment of dose Discuss insulin administration, storage
Lipids and Blood pressure
Replacements
Statins must be stopped
Dyslipidemia § Reduction of saturated fat intake, no trans fat intake, cholesterol intake < 200mg/day § Weight control § Physical activity
§ Preferably prior to pregnancy or § As soon as pregnancy determined
ACE inhibitors and ARBs (angiotensin II receptor blockers) must be stopped § Preferably prior to pregnancy or § As soon as pregnancy determined
Hypertension § Reduce salt intake § Calcium channel blockers, labetalol, hydralazine and methyldopa.
ACEI/ ARBs may cause renal failure in the fetus CDA, 2013 Kitzmiller, Block et al, 2008
CDA, 2013
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Triglycerides
Insulin
Triglycerides may double by 20 weeks
Indicated when target blood glucose levels not attained with diet and physical activity after 2 weeks
Cholesterol, LDL and HDL may increase 10 -20%
Human insulin should be used – less transfer of insulin antibodies
Initiate treatment if triglycerides over 1000mg/dl § Intensive glycemic control § Fish oil supplement
Rapid acting insulin analogues (lispro and aspart) have been shown to be safe in pregnancy
Fibrates and niacin are best avoided during pregnancy
§ Improve postprandial levels § Lower risk of postprandial hypoglycemia
Fetal outcomes the same with human insulin (soluble) or rapid acting analogues
Goldenberg, Benderly, Goldbourt, 2008 Kitzmiller, Block et al, 2008
Insulin
Starting insulin in GDM
Long acting insulin analogues
If fasting high – start NPH or detemir at bedtime
• detemir has been approved for use in pregnancy • glargine has not yet been approved
If postprandial high – start soluble or rapid acting before meal.
Few studies on safety of long acting analogues in pregnancy
§ Start with 4 units § Titrate 1-2 units/every 2 days until targets are reached
Usual recommendation is to use NPH or detemir as basal insulin
Educate § Administration § Storage § Hypoglycemia
Premix insulins are an alternative but lack the flexibility of a basal bolus regimen
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Insulin Syringe • Correct syringe must be used for the strength of the insulin • if using 100u/1 ml insulin then must have a 100u/1ml syringe, • if using 40u/1ml insulin must have a 40u/1ml syringe.
• Usually disposable – intended for 1 use only • Insulin pens are convenient alternatives to syringes but are more expensive • Easier to teach • Fewer mistakes with dosages
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Insulin Practicalities
Precautions
Storage
• Insulin strength may vary (U40, U100) • Ensure the syringe matches the strength! • Clear insulins
• One month at room temperature once the vial has been openedor kept in fridge
• • •
• Must never be frozen • Store away from source of heat
Long acting insulin analogues Regular/soluble insulin Rapid acting insulin analogues
• Cloudy insulin (should not be used if clumps do not dissolve on mixing
• If refrigerator not available, store in clay pot • May be damaged by direct sunlight or vigorous shaking
• •
• Pre-drawn syringes can be kept for one month in fridge (provided power supply reliable)
NPH or N Premixed insulin
• Identify and differentiate insulin type
Glucose lowering medications Sulfonylurea – glibenclamide (glyburide) § Minimal transfer across the placenta § Not associated with neonatal hypoglycemia § Must be balanced with meals and snacks to prevent hypoglycemia § Higher incidence of pre-eclampsia
Good control achieved…but
Jacobson et al . 2005
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However…
Glucose lowering medications
Latest evidence suggests: Ø glibenclamide is associated with worse outcomes compared to insulin and metformin Need more studies in this area
Metformin § Does cross the placenta § Does not appear to have adverse effects on the fetus § May be used in polycystic ovarian syndrome to improve fertility and decrease spontaneous abortion rate
Hence glibenclamide is not recommended in the routine management of GDM
Feig, Moses, 2011 Balsells et al, 2015
Metformin vs Insulin (MiG Trial)
However…
Neonatal complications did not vary between the 2 subject groups. • Less severe hypoglycemia in the infants of mothers on metformin. • Women on metformin gained less weight • Preterm birth was more common in themetformin group, but there was no increase in other complications. • 76% of women who used metformin were more likely to say they would use metformin in a subsequent pregnancy than were women on insulin (27.2%).
What is the effect on the babies? Unknown as to whether the use of metformin during pregnancy is § Beneficial § Neutral § Deleterious
46.3% of women on metformin had to be on supplemental insulin as well.
Need more studies in this area
The conclusion of this study was that metformin was a safe option for GDM, and it was more agreeable to the patient.
Metformin is therefore not recommended as a first line therapy for GDM Feig, Moses, 2011
Rowan Hague Gao et al. 2008
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Other oral agents
Final word on oral agents
There is insufficient data on the use of other antidiabetic agents such as • meglitinides, • alpha glucosidase inhibitors, • thiazolidinediones, • GLP-1 agonists and DPP-4 inhibitors
If a woman is on oral agents when diagnosed with GDM -Discontinue them -Start diet and exercise plan -Monitor blood glucose
The use of these agents in pregnancy cannot be recommended
-Start insulin
References Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 Clinical practice guidelines for the prevention and management of diabetes in Canada; Diabetes and pregnancy. Can J of Diabetes. 2013;37(suppl 1):S168-183. Feig DS, Moses RG. Metformin during pregnancy. Diabetes Care. 2011;34:2329 Goldenberg I, Benderly M, Goldbourt U. Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag. 2008 February;4(1):131–141. Jacobson et al - Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization, American Journal of Obstetrics and Gynecology 2005 Kitzmiller JL, Block JM, Catalano PM, et al. Managing preexisting diabetes for pregnancy: Summary of evidence and consensus recommendations for care. Diabetes Care. 2008;31(5):1060-1079. Rowan JA, Hague WM, Gao W. et al. Metformin versus Insulin for the Treatment of Gestational Diabetes. NEJM 2008;358:2003-15
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Objectives
Complications
Discuss causes, prevention strategies and treatment of hypoglycemia for those women on insulin
Hypoglycemia Premature Labour Preeclampsia
Discuss premature labour, recognizing contractions, and action to take Discuss diagnosis and treatment of preeclampsia
Definition of hypoglycemia
Risk of hypoglycemia (1 of 3)
1. The development of autonomic or neuroglycopenic symptoms
Only those taking glucose -lowering medicines or insulin are at risk
2. Low plasma glucose (less than 4.0 mmol/L or 72 mg/dl)
Risk increases with: • • • • •
3. Symptoms resolved by administration of carbohydrate
Cryer, Davis, Shamoon, 2003
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Not enough carbohydrate consumption Late or missed meal Fasting or malnourishment Too much insulin Prolonged or unplanned activity
Canadian Diabetes Association, 2013
Effect Of Hypoglycemia On Fetus
Fetal heart rate, as well as fetal movements and placental perfusion appear to be unchanged during conditions of maternal hypoglycemia in the range of 2.5 â&#x20AC;&#x201C; 3.0 mmol/L (45â&#x20AC;&#x201C;55 mg/dL)
Coustan, 2009 Diamond, Reece et al, 1992 Nisell, Persson , et al1994 Reece, Hagav, et al 1995
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Treatment Severe • 20 g glucose • Glucagon 1ml SC or IM; increases BG by 3 -12 mmol/L (54-216 mg/dl) over 60 min • IV dextrose- 20 to 50 ml of 50% dextrose over 2 to 3 minutes; immediate response is seen • Manage seizure- place person on their side if not too agitated
Canadian Diabetes Association, 2013
Premature Labour
Follow-up management
Preterm labour in GDM – can use steroids and tocolysis as for other pregnancies
• Meal or snack (15 to 20 g carbohydrate + a protein source)
Preferably avoid betamimetic as tocolytics
• Next dose of insulin taken as usual if cause is known
Nifidepine is a good choice
and hypo was mild • Consider reducing next dose of insulin if hypo was
• Assess cause and prevent recurrence
Both steroids / tocolytics can push glucose up so need to monitor closely and cover with insulin / increasing dose of insulin
• Avoid BG levels < 4 mmol/L (72 mg/dL)
Rule out UTI as a risk factor for preterm labour
severe
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Preeclampsia • Women with GDM are at increased risk of preeclampsia; this is partly due to the increased insulin resistance
Delivery
• It is possible that this increase could be accounted for by the fact that their age and BMI predispose them to GDM as well as hypertension. • Monitor BP & urine albumin every visit Hollander 2007
Timing of delivery – the same for all?
Objectives Discuss when to deliver infant
•
Women with diabetes before pregnancy are at increased risk
•
In GDM perinatal mortality rates lower
•
If insulin requiring, best to use approach similar to pregestational DM
•
GDM managed on diet and exercise alone possibly not at any greater risk from baseline
•
Depends on severity and duration of diabetes as well as co morbidities
Discuss options for inducing labour Discuss implications of Caesarian section
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Timing of delivery
Consider….
TOO EARLY
LATE?
RDS
LATE IUFD
PREMATURITY
Gestational specific risks for still birth continue to fall up to 38 weeks but increase slightly over 40 weeks In insulin dependent women most would plan delivery 38 - 39 weeks
MACROSOMIA
Between 38 and 39 weeks § No difference in incidence of cesareans § More larger babies in one study § There is as yet not enough evidence that induction in diabetic pregnancies prevents fetal macrosomia
In diet controlled GDM women most would be comfortable to 40 weeks
Mode of delivery
With good control and reassuring tests of well being some centres go on to 41 weeks
Matter of choice High section rates – 30 – 80% averaging 50% in many centres Vaginal delivery is possible and safe § Previous obstetric history § EFW § Other clinical factors
Induction of labour is a safe option
Patel, Steer, Doyle et al. 2003
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Monitoring labour
References COMPLICATIONS
Labour is a time of unpredictable glucose and insulin demands – risk of hypoglycemia
Canadian Diabetes Association Expert Committee. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diab 2013;37(suppl 1):S69-71 Coustan , D, Glob. libr. women's med., (ISSN: 1756-2228) 2009; DOI 10.3843/GLOWM.10162
Sliding scale / infusion
Cryer P.E. Davis, S.N. Shamoon , H. Hypoglycemia in diabetes. Diabetes Care, 2003;26(6):1902-1912
§ Maintain plasma glucose below 110 mg/dl to avoid maternal hyperglycemia and subsequent foetal hypoglycemia
Diamond MP, Reece EA, Caprio S et al: Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin -dependent diabetes mellitus. Am JObstet Gynecol 1992;166:70-77
Careful intrapartum FHR monitoring
Nisell H, Persson B, Hanson U, et al: Hormonal, metabolic and circulatory responses to insulin -induced hypoglycemia in pregnant and nonpregnant women with insulin -dependent diabetes. Am JPerinatol 1994;11:231-236
Pay attention to second stage – slow progress is a red flag
Reece EA, Hagay Z, Roberts AB et al: Fetal Doppler and behavioral responses during hypoglycemia induced with the insulin clamp technique in pregnant diabetic women. Am J Obstet Gynecol 1995;172:151-155.
Hollander M, Paarlberg KM, Huisjes AJM, 2007 Gestational Diabetes: A Review of the Current Literature and Guidelines Volume 62, Number 2 Obstetrical and Gynecological Survey
Saleh M., Grunberger, G. Hypoglycemia: A cause for poor glycemic control. Clinical Diabetes, 2001;19(4):161-167. DELIVERY
Caution with instrumental delivery
Jovanovic L, Knopp RH, Kim H, et al. Elevated pregnancy losses at high and low extremes of maternal glucose in early normal and diabetic pregnancy: evidence for a protective adaptation in diabetes. Diabetes Care 2005; 28:1113.
Be prepared for shoulder dystocia
Patel RR, Steer P, Doyle P, Little MP, Elliot P. Does gestation vary by ethnic group? A London-based study of over 122000 pregnancies with spontaneous onset of labour. Int J of Epid. 2003;33:107-113.DOI: 10.1093/ijc/dyg238.
Jovanovic L. 2005
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Objectives Discuss the immediate care of the infant Discuss the importance of breast feeding
Post Partum
Discuss follow up screening of the mother Discuss risk of IGT or diabetes in future Discuss follow up education for mother
After delivery – the infant
After delivery – the infant
Watch for signs of hypoglycemia
Usual care
Check blood glucose – heel prick
§ Vital signs § Apgar scores § Pre-warmed incubator § Start breast feeding within 30 minutes for better latching § Watch for jaundice – check bilirubin § If macrosomic, check calcium and magnesium on day 2
§ Within 1st hour after delivery § After each of 1st 4 feeds
Less than 2.6 mmol/L or 44 mg/dl defined as hypoglycemia Treatment of hypoglycemia § Topfeeding/glucose in water/ IV dextrose
Seshiah, Balaji, 2006
Seshiah, Balaji, 2006
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Breast feeding Encourage for all
After delivery - mother
Protects infant from over or undernutrition during early childhood
Exogenous insulin not required after placenta is delivered
May lower risk of § Obesity § Hypertension § Cardiovascular disease § Diabetes
Blood glucose usually returns to normal Check fasting within 48 hours to rule out type 1 or type 2 diabetes
Gunderson, 2007
Future pregnancies
Post partum period
Should be planned
Encourage mother to achieve healthy weight. Education regarding birth control is needed • Healthy eating • Adequate intake to sustain breast feeding • Regular activity
Encourage achieving healthy weight prior to conceiving again Check blood glucose levels well ahead of conception allowing time to normalize if necessary
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Glucose tolerance testing Contraception
Should be done 6-12 weeks post partum
Any method of contraception can be safely used in a woman with history of GDM
Fasting glucose testing is not sufficient to identify all who have IGT or type 2 diabetes
• Intrauterine devices are commonly used
§ Only 34% of women with IGT or type 2 had elevated fasting glucose levels § 44% of those with type 2 had fasting less than 5.5 mmol/L (100 mg/dL)
Progesterone-only oral contraceptives are the best choice within the first 6 weeks post partum
OGTT should be done
• They have the lowest risk of thrombosis • Preferred during breastfeeding
Metzger, Buchanan, Coustan et al. 2007
CVD risk
Postpartum education is key
Women with GDM may have many of characteristics of metabolic syndrome
OGTT at 6-12 weeks
Hypertension, dyslipidemia, obesity, IGT should all be evaluated and treated
§ Obesity § Hypertension § Dyslipidemia
Managing risk factors
Birth control Preconception screening Annual screening for diabetes – 35-60% risk of type 2 within 10 years Metzger, Buchanan, Coustan et al. 2007
Metzger, Buchanan, Coustan et al. 2007
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References Gunderson EP. Breastfeeding after gestational diabetes pregnancy. Diabetes Care. 2007;30(suppl 2):S161-168. Metzger BE, Buchanan TA, Coustan DR, De Leiva A, Hadden DR, Hod M. Summary and recommendations of the fifth international workshop-conference on gestational diabetes mellitus, Diabetes Care. 2007; 30(suppl 2):S251-260. Seshiah V, Balaji V, et al. Gestational Diabetes Mellitus â&#x20AC;&#x201C; Guidelines. J Assoc Physic of India 2006;54:622-28.
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Case study #1: Mrs. C Mrs. C is a 22 year old primigravida coming for her first antenatal checkup at 12 weeks of gestation. On examination, she is 152 cm tall and weighs 69 kg. BMI, 30 kg/m2
CASE STUDIES
She does not have a family history of diabetes.
•Does she need to be screened for diabetes? •If so, when? •What screening test is to be used?
Mrs. C. Mrs. C
Mrs. C had a fasting blood glucose done Mrs. C undergoes repeat testing at 26 weeks’ gestation.
Her results are as follows. Time
Her results on the 75 gm glucose load (fasting) are as follows.
0 hr (Fasting)
Time
Glucose mmol/L(mg/dL)
4.7 (86)
Glucose mmol/L(mg/dL)
•Does she have diabetes? •Does she have GDM? •Does she need to be tested again? •If so, when?
0 hr (Fasting)
1 hour
2 hour
4.8 (88)
10.3 (186)
8.9 (161)
•Does she have GDM? •If yes, what treatment is indicated? •When will you review her and using what tests?
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Mrs. C Mrs. C
Fasting blood glucose mmol/L (mg/dL
5.2 (93)
Mrs. C is put on 4 units of rapid acting insulin before breakfast and advised to monitor her blood glucose daily. She does well.
2 hour postprandial blood glucose mmolL (mg/dL) breakfast
8.6 (156)
After 2 weeks, her reports are as follows.
After 2 weeks, her results were as follows
Fasting blood glucose mmol/L (mg/dl) 2 hour postprandial blood glucose mmol/L(mg/dl) breakfast
•Is her glycemic control adequate? •What is the next line of treatment? •What other test can help assess level of glycemic control?
6.5 (118) 7 (126)
•Is her glycemic control adequate? •What is the next line of treatment?
Mrs. C
Mrs. C
Mrs. C is now on 6 units of NPH insulin at bedtime in addition to 4 units of rapid acting insulin before breakfast. She starts complaining of excess hunger during the early hours of the morning.
Her insulin dose has stabilized
Her reports are as follows.
Should she have been induced earlier?
§ NPH 8 units at bedtime § rapid acting insulin 6 u before breakfast, 4 units before lunch and 4 units before evening meal.
Mrs. C goes into labour at 39 weeks.
mmol/L (mg/dL) Fasting BG
3.3 (61)
2 hour postprandial BG
5.6 (102)
Should a C-Section be considered? How should her insulin be managed during labour and delivery?
•Are these values acceptable? •What is the next line of treatment?
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Case study #2: Mrs. S
Mrs. C
Mrs. S is a 35 year old nulliparous lady and has suffered two miscarriages in the last three years.
Following delivery, blood glucose levels normalised and she was able to stop insulin.
After the last miscarriage she was diagnosed with PCOS and has been on metformin since.
After 6 weeks, she underwent an OGTT, the results of which are as follows. Time Glucose mmol/L (mg/dl)
0 hour (Fasting)
2 hours
4.5 (82)
7.0 (127)
She did not test her blood glucose levels during either of her previous pregnancies. Her mother has diabetes.
•What is the diagnosis? •What is her risk of developing diabetes in the future? •When should she be tested next?
She presents at 12 weeks gestation What else do you need to know?
Mrs. S Mrs. S
Mrs S has an OGTT at 13 weeks gestation
• Does she need to be screened for diabetes? • If so, when? Glucose mmol/L(mg/dl)
• What screening test is to be used?
Fasting
2 hour
6.0 (108)
9.0 (162)
Are these results ok? • Should the metformin be continued?
Should she be retested? When?
• What is the purpose of metformin?
What management strategies should be considered?
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Mrs M
Case Study #3: Mrs M
Fasting BG at 6 weeks Fasting
Mrs. M, 30/F â&#x20AC;&#x201C; Primigravida
8.8 mmol/L (160 mg/dL)
LMP: 13/10/12 EDC : 28/07/13 Regular cycles
What would you advise now?
Spontaneous conception 10 months after marriage
Trial of MNT or medications right away? Any other tests?
No family history of DM
What risks to the pregnancy will you discuss with this lady?
Mrs M
MRS M â&#x20AC;&#x201C; Blood glucose record
Normal scan at 12 weeks with a low risk of Downs 19- 20 week scan plus fetal echo was normal
Gestational age
FBS mmol/L (mg/dL)
1 h PPBS mmol/L(mg/dL)
A1c %
Medication
15
5.9 (107)
6.9 (125)
8.1
Premix 70/30 18 - 0 - 18 + Metformin 500 BD
18
7.1 (129)
10.1 (183)
7.2
22 - 0 - 22 + Metformin BD
19
5.3 (97)
9.6 (173)
5.8 (105)
8.7 (157)
When will you advise next scan?
Glucose results as in next slide. Patient not very regular with SMBG and not following the meal plan
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26 - 0 - 20 + Metformin BD 6.5
Mrs M
Mrs M
29 week scan
She comes in with c/o discomfort and abdominal pain at 30 weeks How will you manage her now?
Ask to comment
Uterus is irritable with some tightening on and off
Mrs M Uterine contractions settle. UTI picked up and treated with appropriate antibiotics
Mrs M
She is now 37 weeks
Tocolytic â&#x20AC;&#x201C; which drug and dose
FBS 5.5mmol/L (100mg/dL) 1 hr PPBS 8.3 mmol/L (150 mg.dL) on
Steroids â&#x20AC;&#x201C; dose / concerns in GDM
Regular (soluble) 26-10-14 + NPH 0-0-12 Comes in with decreased movements What would your approach be?
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Case Study #4 Mrs. C, a 32 year old primigravida Reports for the first antenatal checkup. She is obese with a body mass index of 35kg/m 2, both her parents have diabetes. Her OGTT results are as follows. Time
0 hr (Fasting)
1 hour
2 hour
10.6 (192)
16.0 (288)
14.6 (263)
Glucose mmol/L(mg/dL)
Her HbA1c is 9.2%. • What type of diabetes does this patient have? • What is the ideal line of treatment? • What is the prognosis for the pregnancy and for future resolution of diabetes?
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Original Article
WORLD DIABETES FOUNDATION
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Can the management of blood sugar levels in gestational diabetes mellitus cases be an indicator of maternal and fetal outcomes? The results of a prospective cohort study from India. Rajesh Jain, Sanjeev Davey1, Anuradha Davey2, Santosh K. Raghav1, Jai V. Singh1 Gestational Diabetes, Prevention Control Project, Jain Hospital, Kanpur,1 Department of Community Medicine, Muzaffarnagar Medical College and Hospital, Muzaffarnagar,2 Department of Community Medicine, Subharti Medical College, Meerut, Uttar Pradesh, India. BACKGROUND: Gestational diabetes mellitus (GDM) is emerging as an important public health problem in India owing to its increasing prevalence since the last decade. The issue addressed in the study was whether the management of blood sugar levels in GDM cases can predict maternal and fetal outcomes. MATERIALS AND METHODS: A prospective cohort study was done for 2 year from October1, 2012, to September 31, 2014, at 198 diabetic screening units as a part of the Gestational Diabetes Prevention and Control Project approved by the Indian Government in the district of Kanpur, state of Uttar Pradesh. A total of 57,108 pregnant women were screened during their 24-28th weeks ofpregnancy by impaired oral glucose test. All types of maternal and perinatal outcomes were followed up in both GDM and non-GDM categories in the 2nd year (2013-2014) after blood sugar levels were controlled. RESULTS: It was seen that for all kinds of maternal and fetal outcomes, the differences between GDM cases and non-GDM cases were highly significant (P < 0.0001, relative risk > 1 in every case). Moreover, perinatal mortality also increased significantly from 5.7% to 8.9% when blood sugar levels increased from 199mg/dl and above. Perinatal and maternal outcomes in GDM cases were also significantly related to the control of blood sugar levels (P < 0.0001). CONCLUSION: Blood sugar levels can be an indicator of maternal and perinatal morbidity and mortality in GDM cases, provided unified diagnostic criteria are used by India laboratories. However, to get an accurate picture on this issue, all factors need further study. It was seen that for all kinds of maternal outcomes suchas cesarean section, pregnancy-induced bypertension (PIH), premature baby unit (PBU) care, family H/O DM and antepartum hemorrhage / postpartum hemorrhage (APH / PPH), the differences between GDM and non-GDM cases were highly statistically significant (P < 0.0001, RR > 1 in every case). This was also seen in the outcomes of neonates in terms of perinatal death, stillbirth, neonatal death, congenital malformations, low gestation for age (LGA), low birth weight (LBW), jaundice. Here also the differences between GDM and non-GDM case were statistically significant (P < 0.0001, RR > 1 in every case) [Table 1]. In terms of H/O previous birth complication, again in the category of stillbirths and perinatal deaths both in GDM and non-GDM cases, the differences were statistically significant (P < 0.0001). However, in neonatal deaths, it was not significant in both GDM and non-GDM category (P > 0.05) [Table 2] As the blood sugar level rose above 120 mg/dl, perinatal mortality rose significantly as compared to previous perinatal loss (P < 0.0001). This increased significantly from (5.7% to 8.9%) when blood sugar level was >199 mg/dl [Table 3 and Figure 1].
Table 1 : Maternal and fetal outoomes of gestational diabetes mellitus and nongestational diabetes mellitus pregnant women Outcomes
GDM cases (n=7641) N (%)
Non-GDM cases (n=8000) N (%)
RR
95% CI
p-value
247 (3.2) 128 (1.7) 375 (4.9) 382 (5) 2242 (29.3) 234 (3.06) 684 (9) 863 (11.3) 686 (9) 382 (5) 1372 (17.9) 64 (.0.84)
102 (1.3) 56 (0.7) 158 (1.97) 82 (1.03) 1814 (22.67) 85 (1.06) 67 (.83) 758 (9.4) 483 (6) 84 (1) 546 (6.8) 26 (0.32)
2.53 2.39 2.48 4.87 1.21 2.88 10.6 1.19 1.83 4.76 2.62 2.57
2.0-3.1 1.75-3.27 2.0-2.9 3.8-6.1 1.2-1.3 2.25-3.68 8.3-13.7 1.1-1.3 1.6-2.0 3.7-6.0 2.3-2.8 1.6-4.0
<0.44 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0002 <0.0001 <0.0001 <0.0001 <0.0001
Stillbirth Neonatal death Perinatal death Congenital malformation Cesarean section PBU Care LGA LBW PIH Jaundice Family history of DM APH/PPH
APH : Antepartum hemorrhage, PPH : Postpartum hemorrhage; PIH : Pregnancy-Induced hypertension; LBW: Low birth weight; LGA: Low gestaion for age; PBU: Premature baby unit; OR : Odds ratio, RR : Relative risk; DM : Diabetes mellitus; GDM : Ges : Gestational diabetes mellitus
Table 2 : Fetal outoomes in gestational diabetes mellitus versus nongestational diabetes mellitus and its relationship with history of previous birth complications p- value
GDM absent (n=8000) N (%)
Previous fetal loss present
916 (12)
<0.0001
102 (1.2)
212 (2.6)
128 (1.7)
156 (2)
<0.09
56 (0.7)
62 (9.8)
<0.5
375 (4.9)
1072 (14)
<0.0001
158 (1.9)
274 (3.4)
<0.0001
GDM cases (n=7641) N (%)
Previous fetal loss present
Stillbirth
247 (3.2)
Neonatal death Perinatal death
Outcomes in neonate
GDM : Gestational diabetes mellitus
N (%)
p- value
N (%) <0.0001
Table 3 : Perinatal mortality as a function of blood sugar (mg/dl) vbalue and its comparison with a history of previous perinatal loss Blood gugar levels (mg/dl)
Samples tested (n=57,018
Perinatal mortality present N (%)
History of previous perinatal mortality N (%)
n1=12,560 n2=31,075 n3= 5742 n4=3915 n5=1451 n6 = 940 n7=1335
776 (2.4) 137 (2.4) 137 (3.5) 65 (4.4) 54 (5.7) 119 (8.9)
768 (2.5) 214 (3.7) 417 (10) 176 (12.1) 168 (17.8) 311 (23.2)
<100 100-119 120-139 140-159 160-179 180-199 ³ 200
p-value
<0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001
The most important finding in our study was that as blood sugar levels rose above 120 mg/dl, there was significant perinatal mortality compared to previous perinatal loss (P <0.0001). This perinatal loss increased significantly from (5.7% to 8.9%), when blood sugar levels was ³ 199 mg/dl. This finding was also unique in contrast to many related [19-26] studies. It has been seen that the values of oral glucose tolerance test in the middle phase of pregnancy and antenatal random glycemia can to some extent also predict PIH, preterm births, or stillbirths. [20]
DISCUSSION DM is increasing worldwide and this rise is more prevalent in developing countries such as India, which is going to become the future "Diabetic-Capital," for which GDM is thought be a real contributor[12]. This emphasizes the importance of prevalence studies in India in pregnant women in order to reveal the exact prevalence of GDM. [12] Hence, GDM is emerging as a rising public health problem in pregnant women in India as many studies have indicated. [5,12-15] 40
8.9
5.7 4.4 3.5 24
24
% of GDM Cases with Blood Sugar levels
10 9 8 7 6 5 4 3 2 1 0
35.9
35
BS Uncontrolled (in %) Relative Risk
25 22.6 20 15.6
15 10
9.3 7.5
5
100-119
120-139
140-159
160-179
180-199
³ 200
5.2
5.1
3.3
2.7
1.8
0
Figure 1 : Perinatal mortality (%) in gestational diabetes mellitus cases in relation to the maternal blood sugar levels (in g/dl)
BS Controlled (in %)
30
irth
ath
are
ath
S c e de ean ll b U ld al sar PB ata aty Ce rin on Pe Ne
Sti
L
GA
0.8
W
LB
IH
1.1
H se DM d PP nU un H/ H/O uli AP ly Ins mi a F
P
ice
Ja
Maternal & Neonatal Outoomes
Figure 2 : Maternal and perinatal outcomes (in %) in gestations diabetes mellitus cases in relation to the maternal blood sugar levels controlled by treatment (in g/dl).
Jain, et al : Role of management of blood sugar in improving outcomes in GDM cases Table 4 : Post follow-up complications of gestational diabetes diagnosed in controlled and uncontrolled blood sugar after treatment Maternal and neonatal outcomes Stillbirth Neonatal death Perinatal death Congenital malformation Cesarean section PBU Care LGA LBW PIH Jaundice Family history of DM APH/PPH Insulin use
BS-controlled (<140mg%) (n=4589) N (%)
BS-uncontrolled (>140 mg%) (n=454) N (%)
RR
95% CI
p-value
64 (1.4) 37 (0.8) 101 (2.19) 206 (4.5) 1101 (24.0) 27 (0.59) 30 (.65) 413 (8.9) 137 (2.98) 26 (0.56) 357 (7.7) 11 (0.23) 298 (6.4)
15 (3.3) 8 (1.8) 23 (5.1) 22 (4.8) 163 (35.9) 12 (2.75) 34 (7.5) 71 (15.6) 42 (9.3) 24 (5.2) 103 (22.6) 4 (0.88) 5 (1.1)
0.42 0.04 0.43 0.93 0.67 0.22 0.087 0.57 0.32 0.11 0.34 0.27 5.89
2.0-3.1 30.28-0.98 0.28-0.68 0.60-1.4 0.58-0.76 0.11-0.44 0.054-0.14 0.46-0.73 0.23-0.45 0.062-0.18 0.28-0.41 0.087-0.85 2.4-14.1
<0.0023 <0.043 <0.0002 (<0.73 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.025 <0.0001
APH : Antepartum hemorrhage, PPH : Postpartum hemorrhage; PIH : Pregnancy-Induced hypertension; LBW: Low birth weight; LGA: Low gestation for age; PBU: Prematurebaby unit; BS : Blood Sugar; OR: Odds ratio; RR: Relative risk; DM: Diabetes mellitus
CONCLUSION Maternal and fetal outcomes in GDM cases are poor. Perinatal and maternal outcomes in GDM cases are also signficantly related to control or blood sugar levels. Therefore, blood sugar levels appear to be an important possible indicator of maternal and perinatal morbidity and mortality in Indian GDM cases. However, there is a need to unify diagnostic criteria in practices throughout the Indian subcontinent for a better validation of results from this study as well as other GDM studies conducted in India. Presented at 7th World Congress of Diabetes DIABETESINDIA 2017 Hotel Pullman & Novotel, New Delhi, India.