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KAJOG; Kasr Al-Aini Journal Vol. 3. Issue 2, August 2012 Of Obstetrics & Gynecology www.kajog.net Abdel Aal H., 2012 Original Research 40 Prediction of Fetal Outcome Using Glycosylated Hemoglobin Assay and Doppler Indices in Diabetic Pregnancies Hoda M. Abdel Aal, M.D Department of Obstetrics & Gynecology, Cairo University ABSTRACT Objective: to explore the role of glycosylated hemoglobin (HbA1c) between 34 -36 weeks gestation and Doppler indices in the prediction of fetal outcome in insulin controlled diabetic pregnancies. Design: prospective Case series Setting: Kasr Al-Aini Hospital. Participants & methods: Diabetic pregnant women with singleton pregnancy on insulin treatment with Gestaonal age between 34-36 weeks were included. All women had been assessed for Glycosylated Hb level, body mass index (BMI), ultrasound fetometery, amniotic fluid index (AFI), Placental grading, biophysical profile and Doppler ultrasound examination. Follow up was done for all women till delivery and neonates were examined for body weight, APGAR scoring at 1 & 5 minute and fetal blood glucose level was measured (adverse if <45mg/dl). Results: there was a stascally signicant correlaon between HbA1c and BMI, AFI and neonatal outcomes. HbA1c of 7% or more was found to be a cutoff value for prediction of prematurity with area under curve of 91.7%. There was no stascally signicant relaon between HbA1c and Doppler indices. Conclusion: HbA1c may be a useful marker for prematurity in pregnant diabec women and also for prediction of neonatal hypoglycemia and other adverse neonatal outcomes. It is recommended for the ante natal care of diabetic mothers is to keep HbA1c < 7% to decrease fetal adverse outcome. INTRODUCTION Gestational diabetes mellitus (GDM) constitutes a significant health risk for mother and offspring during pregnancy, delivery and throughout the life course. Women affected by GDM and their offspring are at increased risk for neonatal complications, in particular macrosomia, large for gestational age, respiratory distress, prematurity, hypoglycemia, polyhydramnios and death 1 . These offsprings are also at high risk for obesity, insulin resistance and Type 2 diabetes mellitus (T2DM) over their life course 2 . Thus, the diagnosis and appropriate management of GDM has the potential to greatly reduce neonatal and maternal morbidity and the burden of T2DM. Glycosylated hemoglobin is used as a marker of glycemic control in people with type 1 diabetes (T1DM) and T2DM 2 . Notably, the American Diabetes Association (ADA) recently recommended that HbA1c more than 6.5% may be used as a diagnosc measure for T2DM and that women with HbA1c more than 6.5% at their first prenatal visit be diagnosed with T2DM rather than GDM 3 . In the non-pregnant diabetic population sustained high HbA1c is associated with increased diabetes complications 4 . Therefore, optimal HbA1clevels in pregnancy should be defined by level of increased risk for adverse pregnancy outcomes. Elevated HbA1c may be an attractive option for identifying pregnant women at high risk for GDM, postpartum T2DM and macrosomia or delivering a large for gestational age infant (LGA). The aim of the present study was to explore the role of glycosylated hemoglobin between 34-36 weeks gestation and Doppler indices in prediction of fetal outcome in insulin controlled diabetic pregnancies. PARTICIPANTS AND METHODS This prospective case series study performed between April 2011 and March 2012 included 50 pregnant women recruited from the obstetric outpatient clinic and department of Obstetrics & Gynecology at Kasr El Aini hospital. It included

Prediction of Fetal Outcome Using Glycosylated Hemoglobin Assay and Doppler Indices in Diabetic Pregnancies (2)

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  • KAJOG; Kasr Al-Aini Journal Vol. 3. Issue 2, August 2012 Of Obstetrics & Gynecology www.kajog.net

    Abdel Aal H., 2012 Original Research 40

    Prediction of Fetal Outcome Using Glycosylated Hemoglobin Assay and Doppler Indices in Diabetic Pregnancies

    Hoda M. Abdel Aal, M.D

    Department of Obstetrics & Gynecology, Cairo University

    ABSTRACT

    Objective: to explore the role of glycosylated hemoglobin (HbA1c) between 34 -36 weeks gestation and Doppler indices in the prediction of fetal outcome in insulin controlled diabetic pregnancies.

    Design: prospective Case series

    Setting: Kasr Al-Aini Hospital.

    Participants & methods: Diabetic pregnant women with singleton pregnancy on insulin treatment with Gesta onal age between 34-36 weeks were included. All women had been assessed for Glycosylated Hb level, body mass index (BMI), ultrasound fetometery, amniotic fluid index (AFI), Placental grading, biophysical profile and Doppler ultrasound examination. Follow up was done for all women till delivery and neonates were examined for body weight, APGAR scoring at 1 & 5 minute and fetal blood glucose level was measured (adverse if

  • KAJOG; Kasr Al-Aini Journal Vol. 3. Issue 2, August 2012 Of Obstetrics & Gynecology www.kajog.net

    Abdel Aal H., 2012 Original Research 41

    singleton diabetic pregnant women on insulin treatment with Gestational age at time of inclusion between 34-36 weeks. It excluded women on diet control or those with medical disorders other than diabetes as SLE, thyroid disorders, hypertension and Pre-eclampsia.

    All women were subjected to detailed history taking, general examination including weight and height for calculation of BMI, full obstetric examination. Laboratory investigations were done in the form of fasting and post prandial blood sugar, and Glycosylated Hb level between 34-36 weeks. Ultrasound fetometery, amniotic fluid index, placental grading, biophysical profile and Doppler ultrasound examination were performed. Follow up was done for all women till delivery and neonates were examined for body weight, APGAR scoring at 1 & 5 minute and fetal Blood glucose level was measured. Adverse neonatal outcomes were considered when APGAR score was 4.5 kg presence of respiratory distress syndrome or fetal blood glucose

  • KAJOG; Kasr Al-Aini Journal Vol. 3. Issue 2, August 2012 Of Obstetrics & Gynecology www.kajog.net

    Abdel Aal H., 2012 Original Research 42

    Table 1: Descriptive Statistics for the Studied Parameters Minimum Maximum Mean SD EFW (kg) 1.6 4.9 3.09 0.81 AFI (cm) 6 28 17.40 5.47 BPP 4 8 7.40 1.01 UTAPI 0.6 1.2 0.78 0.14 UMAPI 0.81 1.25 0.92 0.13 HbA1c 5.8 13 8.17 1.98 FBS (mg%) 70 135 96.46 19.76 2h PPS (mg%) 120 280 186.08 59.72 APGAR (1 minute) 4 8 6.65 1.41 APGAR (5 minute) 5 10 7.87 1.84 Birth weight (kg) 2 5.2 3.30 0.74 Neonatal Glucose (mg%) 25 85 49.06 20.36 Delivery age (weeks) 35 38 36.69 1.19 EFW: estimated fetal weight, AFI: amniotic fluid index, BPP: biophysical profileUTAPI: uterine artery pulsatility index, MCA PI: Middle cerebral artery pulsatility index, UMAPI: Umbilical artery pulsatility index, HbA1c: Glycated hemoglobin, FBS: fasting blood sugar, 2H PPS: two hours post prandial sugar. Table 2: Fetal Outcome and Mode of Delivery among the Studied Patients.

    DISEASE Frequency Percent Neonatal Death 2 4% RDS 15 30% Large for gestational age 19 38% Prematurity 15 30% Hypoglycemia 20 40% Polyhydramnios 10 20% C.S. 33 66% V.D.(vaginal delivery) 17 34%

    There was no statistically significant rela onship between HbA1c levels and age of the studied patients while there was a statistically

    signicant correla on between HbA1c and BMI, AFI and other studied neonatal outcome (table 3).

    Table 3: Correlation between HbA1c and Age, BMI, AFI, EFW, Birth Weight, Neonatal Glucose, And 5 minutes APGAR Score

    HbA1c R p-value

    Age 0.244 0.088 BMI 0.432* 0.002 AFI 0.301** 0.034 EFW (kg) 0.426* 0.003 Birth Weight (kg) 0.308** 0.033 Neonatal Glucose -0.552*

  • KAJOG; Kasr Al-Aini Journal Vol. 3. Issue 2, August 2012 Of Obstetrics & Gynecology www.kajog.net

    Abdel Aal H., 2012 Original Research 43

    Table 4: Predictability of HbA1c at a Cutoff Point of 7% to Dierent Adverse Fetal Outcomes Sensitivity

    (100%) Specificity

    (100%) AUC

    (100%) Prematurity 90.5 81.5 91.7% Polyhydramnios 100 57.1 77.5% Macrosomia 82.38 63.64 72.6% Neonatal hypoglycemia 100 96 98.3% RDS 100 96 98.3%

    HbA1C

    0 20 40 60 80 100

    0

    20

    40

    60

    80

    100

    100-Specificity

    Sens

    itivi

    ty

    Figure 1: Roc Curve for Prediction of Neonatal Hypoglycemia

    at a Cuto Point Of 7% (AUC = 98.3%)

    HbA1C

    0 20 40 60 80 1000

    20

    40

    60

    80

    100

    100-Specificity

    Sen

    sitiv

    ity

    Figure 2: Roc Curve for Prediction of Prematurity at a Cuto Point of 7% (AUC = 91.7%)

  • KAJOG; Kasr Al-Aini Journal Vol. 3. Issue 2, August 2012 Of Obstetrics & Gynecology www.kajog.net

    Abdel Aal H., 2012 Original Research 44

    DISCUSSION

    In the United States, prevalence of gestational diabetes (GDM) ranges from 1 to 14% of pregnancies3. Gestational diabetes generally has few symptoms and it is most commonly diagnosed by screening during pregnancy. Diagnostic tests detect inappropriately high levels of glucose in blood samples5.

    The present study aimed at the evaluation of the use of HbA1c as a marker in gestational diabetic women between 34-36 weeks to predict fetal outcome and to follow them up. Interestingly, the present study observed a positive correlation between glycosylated hemoglobin and adverse fetal when HbA1c was >7% between 34-36 week. There was an increased frequency of adverse fetal outcomes including RDS, macrosomia, polyhydramnios, prematurity and neonatal hypoglycemia.

    The results of the current study revealed that the sensitivity of HbA1c >7% for predic ng polyhydramnios is 100% and the specicity is 57.1%. The incidence of large for gestational age was 38% and prematurity was 30% and this agrees with the result of Yang and colleagues (2006) who reported percentage of 40% and 28% for LGA and prematurity in their study6.

    In the current study, the sensi vity of HbA1c >7 %in predicting prematurity was 90% and the specificity is 81%and its incidence is 30%.

    It also showed a statistically significant positive rela on between HbA1c with FW and also with birth weight (P=0.003 and 0.033 respectively). This agreed with Jodie et al., 2011 who concluded that the association of HbA1c and birth weight was stronger when antepartum HbA1c was measured after GDM diagnosis at 34 weeks7.

    The results in the current study revealed, also sensi vity of 82% and a specificity of 63% for HbA1c >7% in prediction of macrosomia. In this study the incidence of neonatal hypoglycemia was 40% and there was highly statistically significant relation between HbA1c and neonatal glucose level (p=0.005) giving an area under the curve of 98.3%. This agrees with Arumugam and Abdul Majeed, 2011 who showed that HbA1c level >6.8% in late pregnancy is good predictors of hypoglycaemia in the newborn, giving an area under the curve of 99%8. In simple terms, this means that if there were two babies who were randomly selected, one with hypoglycaemia and the other without, the probability that the hypoglycaemic neonate would have shown

    an abnormally high maternal HbA1c would be around 99%.

    In this study, there was no statistically significant rela on between HbA1c and Doppler indices and this agrees with Pietryga et al. (2006) who concluded that there was no correlation between long-term-maternal glycemic control (HbA1c) and changes of blood flow velocity in placental circulation in pregnancy complicated with diabetes mellitus9.

    In conclusion, HbA1c may be a useful marker for prematurity in pregnant diabetic women and also for prediction of neonatal hypoglycemia and other adverse neonatal outcome. It is recommended for the antenatal care of diabetic mothers is to keep HbA1c

  • KAJOG; Kasr Al-Aini Journal Vol. 3. Issue 2, August 2012 Of Obstetrics & Gynecology www.kajog.net

    Abdel Aal H., 2012 Original Research 45

    Paediatric and Perinatal Epidemiology. 2011; 25(3):265

    8. Arumugam K, Abdul Majeed N. Glycated haemoglobin is a good predictor of neonatal hypoglycaemia in pregnancies complicated by diabetes. Malays J Pathol. 2011; 33(1):21

    9. Pietryga M, Brazert J, Wender-Ozegowska E, Dubiel M, Gudmundsson S. Placental Doppler velocimetry in gestational diabetes mellitus. J Perinat Med. 2006; 34(2):108