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A study of neonatal outcome in infants born to diabetic mothers at a tertiary care hospital

Diabetes Mellitus refers to a group of common metabolic disorders that share the common phenotype of hyperglycemia. It is the most common medical complication during pregnancy which affects about 0.5% to 5% of all pregnancies. It may be before pregnancy (pre-gestational or overt diabetes) or may be detected for the first time during pregnancy (gestational diabetes). Of these 80% are caused by gestational diabetes mellitus. Gestational diabetes (GDM) is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy.


INTRODUCTION
Diabetes Mellitus refers to a group of common metabolic disorders that share the common phenotype of hyperglycemia. 1 It is the most common medical complication during pregnancy which affects about 0.5% to 5% of all pregnancies. 2 It may be before pregnancy (pre-gestational or overt diabetes) or may be detected for the first time during pregnancy (gestational diabetes). Of these 80% are caused by gestational diabetes mellitus. 3 Gestational diabetes (GDM) is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. 4 Infants born to diabetic mother (IDM) are at increased risk of complications which may be periconceptional, fetal, neonatal and even long term. 5 GDM increases the risk of complications via a myriad of biological mechanisms. Overt maternal diabetes mellitus can adversely influence intrauterine development. Spontaneous abortions and congenital anomalies may be induced in the first trimester. Excessive foetal growth, neonatal hypoglycaemia, jaundice, polycythemia and stillbirth may be induced during the second and third trimesters. 6 Infants of diabetic mother are at higher risk of complications and congenital anomalies like macrosomia, hypoglycemia, hypocalcemia, hypomagnesemia, polycythemia, hyperbilirubinemia, prematurity, transient tachypnea of newborn, respiratory distress syndrome, birth asphyxia, congenital heart diseases like interventricular septal hypertrophy, transient hypertrophic subaortic stenosis, cardiomyopathy, cleft lip, cleft palate, sacral agenesis, jitteriness, seizures, movement disorders. [7][8][9] A strong association between congenital anomalies and maternal glycemic control has been documented. 10 Although in developed countries there has been significant improvement in the outcome of diabetic pregnancies due to better metabolic control before and during pregnancy and better neonatal care, the management in developing country still poses a major challenge. Due to increased perinatal morbidity and mortality, IDM babies should be closely monitored. Studies have shown that strict control of maternal glucose during pregnancy has a favorable perinatal outcome. 11 The present study aimed to know the perinatal outcome and its relation to maternal glycemic control.

METHODS
This prospective hospital-based study was conducted at a tertiary care hospital, Bangalore, Karnataka during the period from July 2016 to June 2017. Informed and written consent was obtained from the parents of the newborn. Ethical clearance was obtained from the institutional ethical committee.
The mothers were grouped into pre-gestational diabetes and gestational diabetes mellitus. GDM was defined as any degree of glucose intolerance with onset or first recognition during pregnancy. GDM diagnosis was made according to IADPSG criteria, if plasma glucose values: • Fasting: 92 mg/dl (5.1 mmol/l) • 1 hour: 180 mg/dl (10 mmol/l) • 2 hours: 153 mg/dl (8.5 mmol/l) 100 neonates were included in the study. Maternal history and details of glycemic control (blood glucose and HbA1c levels) was taken from maternal records. Neonatal history and detailed examination of these babies was done. Birth w eight was measured by using digital electronic weighing scale before first feed after removing clothes of the baby. Laboratory investigations like blood glucose, serum calcium, serum bilirubin, haematocrit, 2D Echo, chest X-ray was done. The mothers with HbA1c levels less than 6.5% were labelled as having a satisfactory glycemic control whereas mothers with HbA1c levels more than 6.5% were grouped as having unsatisfactory glycemic control. Results were analyzed by analysing software SPSS 21.
Hypoglycemia was seen in 54% and hypocalcemia was seen in 43% neonates. Hypoglycemia at birth was seen more in babies with macrosomia and low birth weight. Polycythemia was seen in 35% neonates and hyperbilirubinemia was seen in 42% neonates     Hypoglycemia, macrosomia, polycythemia was seen more in mothers with HbA1c more than 6.5 than mothers with HbA1c less than 6.5 (Table 5). Complications were associated with poor maternal glycemic control (p <0.01).

DISCUSSION
Diabetes mellitus is the commonest endocrine disorder during pregnancy. The duration and severity of maternal diabetes and quality of its control during pregnancy determine the outcome of the offspring. 12 In our study, the diabetic mothers constituted 2.9 % of all deliveries whereas other studies Prabhavathi et al showed an incidence of 3.5%, Shirazi H et al showed an incidence of 1.25%. 13,14 In the present study, GDM was found in 86% and pregestational diabetes in 14% cases, which was similar to other studies like Shirazi  The most common complication seen in the present study was hypoglycemia which was seen in 54% which can be dangerous. Hypoglycemia is defined as blood glucose levels <40 mg/dl in any infant regardless of gestational age and whether or not symptoms are present. Infants of diabetic mothers have hyperinsulinism at birth due to increased placental transfer of glucose and other nutrients stimulating hyperplasia of islets of Langerhans in the fetus and increased insulin secretion, increased amount of C peptide and free insulin in cord blood. Once the maternal supply of glucose is stopped by clamping the cord, the excess insulin in the baby reduces glucose during the first few hours of life.  16 Hypocalcemia was seen in 43% neonates. Hypocalcemia is defined as total serum calcium levels <7 mg/dl. Abnormalities in calcium metabolism represent a delayed transition from fetal to neonatal parathyroid control. Perinatal asphyxia that occurs in IDMs is a result of multiple factors like maternal hypertension with reduction of placental blood flow, premature labour, fetal macrosomia and maternal hyperglycemia within 6 to 8 hours preceding delivery, which supposedly reduces placental blood flow. 17 RDS was seen in 13% babies which is due to higher insulin levels which interfere with incorporation of choline into lecithin, producing deficiency in saturated phosphatidyl choline in lungs and amniotic fluid.

CONCLUSION
Poor glycemic control in the pregnancy can lead to large for gestational age babies or small babies with higher frequency of other complications. Screening for GDMs should be performed in all pregnant women. Planned pregnancy, proper antenatal care, strict glycemic control in mother and prompt treatment of diabetic mother is essential to reduce perinatal and neonatal complications.
Babies born to diabetic mothers should be monitored properly to reduce the morbidity and mortality.