Effects of Maternal Hba1c Level on Infants of Diabetic Mother: A Prospective Observational Study in a Tertiary Care Hospital
Bhabagrahi Mallick1*, Abhilipsa Acharya2, Satish Kumar3, Jasashree Choudhury4, Mamata Devi Mohanty5
1.Dr. Bhabagrahi Mallick: Associate Professor, Department of Pediatrics, IMS & SUM Hospital.
Email ID: [email protected]
2.Dr. Abhilipsa Acharya: Assistant Professor, Department of Neonatology, IMS & SUM Hospital Email ID: [email protected]
3.Dr. Satish Kumar: PG Resident, Department of Pediatrics, IMS & SUM Hospital.
Email ID: [email protected]
4.Dr. Jasashree Choudhury: Professor, Department of Pediatrics, IMS & SUM Hospital.
Email ID: [email protected]
5.Dr. Mamata Devi Mohanty: Professor, Department of Pediatrics, IMS & SUM Hospital.
Email ID: [email protected]
ABSTRACT
Background: The prevalence of diabetes in pregnancy is rising worldwide along with overweight & obesity. In- utero exposure to high blood sugar levels predisposes to numerous perinatal & neonatal complications. There is lack of available data on clinical profile and outcome of infant of diabetic mother (IDM), especially from developing nation like India. The available data in literature is from an era when HbA1c and oral hypoglycemic agents (OHA) were not recommended for diagnosis and management of diabetes complicating pregnancy.
Hence, the present study was conducted with aim to look for perinatal outcome of infant of diabetic mother with reference to HbA1c level in mother.
Purpose: The purpose of the study was to look for the clinical profile & complications in babies born to diabetic mothers and to compare various complications seen in babies in relation to maternal HBA1C level.
Material & methods: It was a prospective observational study conducted from 1st January 2019 to 31st July 2020 in the department of Pediatrics & Neonatology, IMS & SUM Hospital, Bhubaneswar. All the babies delivered from diabetic mothers and all the large for gestational age (LGA) babies, where mother found to be diabetic retrospectively, were included in the study. Outborn babies delivered from diabetic mothers were excluded from the study.
Result: Out of total 2107 deliveries during the study period 72 live births were from mothers diagnosed to be diabetic. Among 72 infants of diabetic mothers (IDM) 67 babies were included in the study population (2=referral, 3=early discharge). Out of 67 mothers 51 had gestational diabetic mellitus (GDM) & rest were type 2 diabetes mellitus. The male: female ratio was 1.2:1. Around 55% babies were appropriate for gestational age (AGA) whereas macrosomia was seen in 13.4% of babies. Respiratory distress (43.3%) & perinatal depression (20.9%) were the most common complications at birth. The major early neonatal complications were hyperbilirubinemia (47.7%), hypocalcemia (23.8%), hypoglycemia (16.4%). High maternal HBA1C level (>7%) were significantly associated with neonatal complications, ie, LGA (p< 0.0001), birth trauma(p=
0.0019), hypoglycemia (p= 0.0001), hypocalcemia (p= 0.0001), prematurity (p= 0.019), birth asphyxia (p<
0.0001), congenital anomalies (p< 0.0001), respiratory distress syndrome (p= 0.0002).
Conclusion: Most of the IDM babies were appropriate for gestational age. Hyperbilirubinemia, large for gestational age, hypocalcemia and hypoglycemia were the most common complications in the infants of diabetic mother. Glycemic control better defines the neonatal complications and outcome rather than the type of diabetes in mother..
Keywords:
Infant of diabetic mother, hypoglycemia, gestational diabetes mellitus, HBA1C
1.Introduction
Diabetes in pregnancy is associated with numerous maternal, fetal & neonatal complications.
Maternal diabetes may be gestational or pregestational diabetes mellitus. The prevalance of
diabetes in pregnancy is rising parallel with rising diabetes milletus1. This occurs mainly due to changing lifestyles, dietary pattern, increasing incidence of obesity, elder age at first conception, and changing testing methodology for the condition2. Data on clinical profile and outcome of infant of diabetic mother (IDM), especially from developing nation like India is lacking. The available data in literature is from an era when HbA1c and oral hypoglycemic agents (OHA) were not recommended for diagnosis and management of diabetes complicating pregnancy.
Hence, the present study was conducted with aim to look for neonatal outcome of infants of diabetic mother with reference to their HbA1c levels.
2. Aim & objectives
The aim & objective of the study was to look for the clinical profile & complications in babies born to diabetic mothers and to compare various complications seen in babies in relation to maternal HBA1C level.
3.. Methods
The study was commenced after getting Institutional Ethical Committee clearance. An informed consent of the mother was taken, after explaining the details of the study. It was a prospective observational study conducted from 1st January 2019 to 31st July 2020 in the department of Pediatrics & Neonatology, IMS & SUM Hospital, Bhubaneswar. All the babies delivered from diabetic mothers and all the large for gestational age (LGA) babies, where mother found to be diabetic retrospectively, were included in the study. Outborn babies delivered from diabetic mothers were excluded from the study. All large babies born to mothers without established diabetes were excluded.
Maternal history including age, weight, height, BMI, parity, history of any pregnancy loss, HBA1C level in last trimester of pregnancy, treatment taken, history of any complication like pre-eclampsia, hypothyroidism and mode of delivery were recorded. Detailed physical examination of baby, started from golden 1st minute, was done to look for clinical profile, complications & congenital anomalies. This includes need for resuscitation, respiratory distress at birth, birth trauma, birth weight of baby and any evidence of congenital anomaly. Birth weight of the baby was recorded in the labour room using digital weighing scale. The babies were grouped as SGA, AGA or LGA depending on the birth weight and gestational age according to standard growth charts. Large for gestational age (LGA) was defined as birth weight greater than 90th percentile for gestational age, macrosomia as birth weight more than 4000 gm, small for gestational age (SGA) as birth weight less than 10th percentile for gestational age. According to the protocol for the infant of diabetic mother, blood glucose level of baby was monitored at 2, 4, 6, 12, 24 and 48 hours of life using bed side glucometer. Blood glucose level less than 45 mg/dl was considered hypoglycaemia. Laboratory investigation like Hematocrit was done at 2 hours of life, by sending the 2 ml of blood sample to laboratory in EDTA vial and was done using automated cell count analyser based on principle of coulter impendance. Hematocrit value more than 65 % was considered as polycythemia. Serum calcium level was done at 24 hours of life, by automated analyser in the laboratory. Total serum calcium less than 7 mg/dl and 8 mg/dl was considered as hypocalcemia in preterm and term neonate respectively. Serum bilirubin was sent based on clinical icterus using Kramer zone, total serum bilirubin was measured in the laboratory using vanden berg reaction. Total Serum bilirubin level > 15 mg/dl was considered hyperbilirubinemia. Serum TSH was done on day 3 of life, using chemiluminescent
immunoassay for quantitative determination of human thyroid-stimulating hormone (hTSH) in human serum using the Access Immunoassay System. Based on maternal history, clinical profile, suspected and probable case of sepsis were screened by testing for total leukocyte count, absolute neutrophil count, CRP (Q), micro ESR. In case of suspected anomaly and suspected cardiac cause for respiratory distress, 2D echocardiography was done. Radiological investigation like ultrasonography of abdomen was also done in case of suspected anomaly of underlying organ, based on clinical presentation. NICU stay, need of non invasive ventilation, mechanical ventilator, inotropes and treatment of all babies were as per our hospital NICU protocol.
A predesigned proforma was prepared for taking detailed maternal history and examination of the neonate. The data obtained was tabulated in excel sheet and subjected to statistical analysis using SPSS software. Descriptive statistical analysis was done. Results on continuous variables were presented as Mean± SD (Min-Max). Results on categorical variables were presented in number (%). Chi square test was done comparing the high HbA1c values (>7%) of mother with clinical presentation and complications in the neonate. The level of significance was set at p value < 0.05.
4. Results
Total of 2106 mother delivered during the study period at Institute of Medical Sciences (IMS) &
SUM hospital, Bhubaneswar. Out of them, 72 singleton live-births were delivered from diabetic mothers. Total 67 infants were included in the study ( referral = 2, early discharge from hospital
= 2). Out of 67 neonates, 51 (76.1%) were delivered from mothers with gestational diabetes mellitus (GDM), rest (23.9%) had type 2 diabetes mellitus. Male: female ratio in the study population was 1.2:1. Table 1 depicts the demographic characteristics of the study population.
Table 2 shows the similar baseline characteristics of GDM and type 2 DM mothers given birth to the babies included in the study. Birth trauma, RDS and prematurity were more marked in mothers with type 2 DM than GDM (Table 3). In addition to that, SGA was more marked in mothers with GDM than type 2 DM (Table 3). High maternal HBA1C level > 7% has significant association with neonatal complications like hypoglycemia, hypocalcemia, large for gestational age (LGA), RDS, congenital anomalies, birth asphyxia and prematurity (p value< 0.05) (Table 4).
5. Discussion
In our study clinical profile, complication and outcome in infants of diabetic mother were evaluated with reference to maternal serumHbA1c level. Almost 50% babies were delivered through LSCS which was similar to the study by Metzger et al3.One third of babies are large for gestational age (LGA) which is in accordance with studies done by Metzger et al3 and Cordero et al4 where percentage of LGA babies were 29.7 % and 36 % respectively. But it is lower in comparison to studies like Ranade et al5 and Alam et al6 where it is 41.5 % and 45 % respectively, which can be explained by majority of mothers in our study had good glycemic control with having HBA1C < 7.0 %. Majority of cases in our study were born at term (67%) which is similar to studies done by Ranade et al5 and Cordero et al4. The most common complication noted at birth was respiratory distress in our study, which is higher in comparison to study done by Cordero et al4where it was 34 %. In our study most of cases being transient tachypnea of newborn did not require any major intervention apart from supportive care.
Hyperbilirubenemia was the most common metabolic complication seen in our study, which is similar to Ashraf et al7 and Senthilkumar et al8, they found hyperbilirubenemia in 52.2 % and 29
% cases respectively. Hypocalcemia was the second most common metabolic complication
(23%) in our study which is similar the Ashraf et al study7. Other complications like hypoglycemia, respiratory distress syndrome, birth asphyxia, polycythemia were similar to various other studies like Deorari et al (16.3%)9 and Hamedi et al10. Another study by Makwana et al11 has shown that incidence of hypoglycemia was 44% which was quite high. Such a high rate of hypoglycemia can be explained by suboptimal control of blood sugar in mothers. Majority of mothers in our study had good glycemic control as shown by HBA1C levels. High maternal HBA1C level (> 7 gm %) is significantly associated with most of the neonatal complications rather than the type of diabetes mellitus. Similar result was seen by Al-Nemri et al study12. Glycemic control in all the trimesters define complications in neonates. In our study HBA1C level in third trimester was only considered, rather HBA1Clevel in all the three trimesters should have been considered to better correlate with possible complications. As this study was done in a single centre with fewer number of participants, larger studies involving multiple centres are needed for better generalization of these findings.
6. Conclusion
Hyperbilirubinemia, large for gestational age, hypocalcemia and hypoglycemia and were the most common complication in infant of diabetic mother. Glycemic control better defines the neonatal complications and outcome rather than type of diabetes in mother. So, we suggests screening for diabetes in pregnant women and monitoring of HBA1C level should be mandatory in all mothers diagnosed with gestational or pregestational diabetes mellitus.
Acknowledgement: None to acknowledge.
Conflict of interest: No conflict of interest present.
Funding: No funding source for this study.
Author contribution: Satish Kumar: Study design, data collection and manuscript writing.
Bhabagrahi Mallick: study design and manuscript review. Abhilipsa Acharya: manuscript review
& statistical anlysis. Jasashree Choudhury: study design. Mamata Devi Mohanty: study design.
Bibliography
[1] Mithal A, Bansal B, Kalra S. Gestational diabetes in India: Science and society. Indian J Endocrinol Metab. 2015;19(6):701–4.
[2] Arias F, Bhide AG, S A, Damania K, Daftary SN. Practical Guide to High Risk Pregnancy and Delivery - E-Book. Elsevier Health Sciences; 2012. 583 p.
[3] Maayan-Metzger A, Lubin D, Kuint J. Hypoglycemia Rates in the First Days of Life among Term Infants Born to Diabetic Mothers. Neonatology. 2009;96(2):80–5.
[4] Cordero L, Treuer SH, Landon MB, Gabbe SG. Management of infants of diabetic mothers.
Arch Pediatr Adolesc Med. 1998 Mar;152(3):249–54.
[5] Ranade AY, Merchant RH, Bajaj RT, Joshi NC. Infants of diabetic mothers--an analysis of 50 cases. Indian Pediatr. 1989 Apr;26(4):366–70.
[6] Alam M, Raza SJ, Sherali AR, Akhtar ASM, Akhtar SM. Neonatal complications in infants born to diabetic mothers. J Coll Physicians Surg--Pak JCPSP. 2006 Mar;16(3):212–5.
[7] Ashraf S, Mushtaq S. Metabolic Complications and Outcome of Infants Born to Diabetic Mothers. :4.
[8] Senthilkumar KM, Shanthi R. Clinical profile and outcome of infant of diabetic mother in a tertiary care sick newborn care units. Int J Contemp Pediatr. 2020 Apr 24;7(5):1069.
[9] Deorari AK, Menon PS, Gupta N, Singh M. Outcome of infants born to diabetic women.
Indian Pediatr. 1985 May;22(5):375–8.
[10] Hamedi faab. comparison of maternal and fetal/neonatal complications in gestational and pre-gestational diabetes mellitus . Acta Med Iran. 2005;263–7.
[11] Makwana M, Dabi JC, Soni JP, Bhati RL, Mourya HK, Garg Y. The clinical evaluation of the infants of diabetic mothers (IDMS) born in a tertiary care hospital. Int J Contemp Pediatr. 2017 Jun 21;4(4):1228.
[12] Al-Nemri AM, Alsohime F, Shaik AH, El-Hissi GA, Al-Agha MI, Al-Abdulkarim NF, et al.
Perinatal and neonatal morbidity among infants of diabetic mothers at a university hospital in Central Saudi Arabia. Saudi Med J. 2018 Jun;39(6):592–7.
Flow Chart
Table 1: Demographic characteristics
Parameters N = 67 (%)
Male 36 (54%)
Mode of delivery
Normal Vaginal Delivery (NVD) LSCS
Assisted Vaginal Delivery
22 (32.8%) 32 (47.8%) 13 (19.4%) AGA
SGA LGA
37 (55.2%) 9 (13.4%) 21 (31.4%) Birth weight (gram)
< 1500 g 1500 – 2499 g 2500 – 4000 g
>4000 g
2 (3%) 20 (29.9%) 36 (53.7%) 9 (13.4%)
Preterm (<37 weeks) Term
22 (32.8%) 45 (67.2%) Type of diabetes mellitus
GDM
Pregestational diabetes mellitus
51 (76.1%) 16 (23.9%) Complications at birth
Birth trauma
Perinatal depression Respiratory distress Congenital anomalies
3 (4.5%) 14 (20.9%) 29 (43.3%) 6 (8.9%) Metabolic complications
Hyperbilirubinemia Hypocalcemia Hypoglycemia Polycythemia
32 (47.7%) 16 (23.8%) 11 (16.4%) 5 (7.4%) Serious complications
Birth asphyxia
Respiratory distress syndrome (RDS) Sepsis
Myocardial hypertrophy
6 (8.9%) 8 (11.9%) 7 (10.4%) 1 (1.5%) Maternal HBA1C level
≤ 7%
>7%
52 (77.6%) 15 (22.4%)
Table 2: Baseline characteristics of Diabetic mothers
Variables GDM ( n = 51) Type 2 DM ( n = 16)
Age in years (mean± SD) 30.3± 3.18 32.5 ± 3.93
BMI (mean± SD) 22.9± 3.57 23.3 ± 4.11
Gestational week (mean± SD) 36.9± 2.11 36.2 ± 2.04
HbA1c (mean± SD) 6.70± 1.30 6.78 ± 1.03
Table 3: Neonatal complications in relation to the type of diabetes in mother
Complications GDM
(n=51)
Type 2 DM (n=16)
P value
LGA 15 (29.4%) 6 (37.5%) 0.226
Birth trauma 1 (2%) 2 (12.5%) 0.003
SGA 8 (15.7%) 1 (6.3%) 0.032
Hypoglycemia 8 (15.7%) 3 (18.8%) 0.561
Hypocalcemia 13 (25.5%) 3 (18.8%) 0.254
Hyperbilirubiemia 24 (47.1%) 8 (50%) 0.681
Polycythemia 3 (5.9%) 2 (12.5%) 0.105
Prematurity 15 (29.4%) 8 (50%) 0.0024
Birth asphyxia 5 (9.8%) 2 (12.5%) 0.606
Congenital anomalies 4 (7.8%) 2 (12.5%) 0.271
RDS 4 (7.8%) 4 (25%) 0.0008
Table 4: Complications of infant of diabetic mother in relation to maternal HBA1C level
