|Year : 2021 | Volume
| Issue : 3 | Page : 147-151
Maternal obesity affecting immediate neonatal outcomes in infants of diabetic mothers: A case–control study
Sajida Abdulla1, Manjula Velikkakath Divakaran2, Radha Kunnath Ramakrishnan3
1 Department of Pediatrics, Government Medical College, Ernakulam, Kerala, India
2 Department of Community Medicine, Government Medical College, Ernakulam, Kerala, India
3 Department of Obstetrics and Gynaecology, Government Medical College, Ernakulam, Kerala, India
|Date of Submission||19-May-2021|
|Date of Decision||09-Jun-2021|
|Date of Acceptance||09-Jun-2021|
|Date of Web Publication||28-Jul-2021|
Department of Pediatrics, Government Medical College, Ernakulam, Kerala
Source of Support: None, Conflict of Interest: None
Introduction: The association between maternal obesity and increased neonatal morbidity in infants of diabetic mothers needs to be evaluated. Aims: The objective of the study is to compare the immediate neonatal complications of obese and nonobese gestational diabetic mothers (GDM). Settings and Design: This prospective case–control study was conducted in a tertiary care center in Kerala, South India, between July 1, 2019 and January 1, 2020. Methods: Six hundred and seventy-seven obstetric patient records of deliveries conducted between July 1, 2019 and January 1, 2020 were reviewed. Neonatal outcomes of infants of obese and nonobese diabetic mothers (categorization based on prepregnancy body mass index [BMI]) were compared with the healthy neonatal controls born during the study period. Outcomes studied were neonatal intensive care unit (NICU) admission, NICU stay more than 7 days, hypoglycemia, respiratory distress, phototherapy, and proportion of small for gestational age in infants of diabetic mothers. Statistical Analysis Used: Statistical analysis used odds ratio and Chi-square tests. Results: One hundred and sixty-eight were found to be eligible to be included in the study. Eighty-four GDM cases were matched with 84 healthy control mothers. Hypoglycemia (P = 0.001), respiratory distress (P = 0.002), NICU admission (P = 0.001), prolonged NICU stay, and phototherapy were significantly associated with those mothers who had high BMI. Conclusions: Compared to infants of nonobese GDMs, infants of obese GDMs are at higher risk of hypoglycemia, respiratory distress, phototherapy, and NICU stay more than 7 days.
Keywords: Gestational diabetes, hypoglycemia, insulin, maternal obesity, neonatal, outcomes
|How to cite this article:|
Abdulla S, Divakaran MV, Ramakrishnan RK. Maternal obesity affecting immediate neonatal outcomes in infants of diabetic mothers: A case–control study. J Clin Neonatol 2021;10:147-51
|How to cite this URL:|
Abdulla S, Divakaran MV, Ramakrishnan RK. Maternal obesity affecting immediate neonatal outcomes in infants of diabetic mothers: A case–control study. J Clin Neonatol [serial online] 2021 [cited 2021 Sep 17];10:147-51. Available from: https://www.jcnonweb.com/text.asp?2021/10/3/147/322535
| Introduction|| |
India has a huge burden of more than 4 million gestational diabetic mothers (GDM) and an ethnic predilection in South Indians., Gestational diabetes and maternal obesity are known to result in adverse neonatal outcomes such as prematurity, macrosomia, and neonatal intensive care unit (NICU) admission. Maternal obesity, per se, is also a risk factor for preterm births and low birth weight babies, as well as macrosomia.,,, These studies have not investigated other neonatal outcomes such as NICU admission, NICU stay more than 7 days, neonatal hypoglycemia, respiratory distress, phototherapy, and the proportion of small for gestational age (SGA) infants of diabetic mothers in infants of obese diabetic mothers. There is not enough evidence for establishing maternal obesity as an independent risk factor for developing neonatal hypoglycemia, need for NICU admission, and prolonged NICU stay, in infants of diabetic mothers. This is important because routine NICU admission is not recommended for infants of diabetic mothers.
In our setting, we observed that the majority of infants of GDM (IGDM) are not macrosomic but are appropriate for gestational age or even SGA. Increased visceral fat mass during pregnancy is associated with SGA babies. Moreover, there are only a few studies on the subset of SGA infants born to GDM.
The study objective is to compare the neonatal complications of obese and nonobese GDMs.
| Methods|| |
This case–control study was conducted in the Department of Pediatrics and the Department of Obstetrics, Government Medical College, Kerala, South India, which caters mostly to lower and lower-middle socioeconomic strata of the population. The institutional research committee and ethics committee approved this study.
Selection of cases and controls
Gestational diabetes was defined as recommended by the international association of diabetes and pregnancy study groups criteria. Out of 677 obstetric patient record forms of deliveries conducted between July 1, 2019 and January 1, 2020, 168 mothers had documented prepregnancy weight and height. The inclusion criteria for “GDM cases” were singleton GDMs with documented prepregnancy weight and height, aged more than 18 years, and without other comorbidities. These cases received medical nutritional therapy (MNT)/metformin/insulin as per our obstetric unit treatment protocol. GDM cases were classified and analyzed based on their body mass index (BMI). Obesity was defined as BMI more than 25.0 kg/m2 according to Asian Indian consensus statement. Exclusion criteria of the cases considered for the study were pregnancy-induced hypertension (PIH), twins, Type 1 or Type 2 diabetes or toxoplasma, rubella, cytomegalovirus, herpes screen positive, or other systemic illness. The control mothers and their newborns were selected from the rest of the registered antenatal mothers with documented prepregnancy weight and height, who were screened negative after glucose tolerance test and who had normal BMI. Confounding factors such as PIH, multiple pregnancies, and intrauterine infections were taken care while selecting controls.
Cases and controls were matched in pairs by age and region of origin as this center also serves many migrants from North India. The outcome variables assessed were NICU admission, NICU stay more than 7 days, hypoglycemia requiring treatment, SGA, respiratory distress, and need for phototherapy. Hypoglycemia requiring treatment was defined as blood glucose level <47 mg/dl. Blood glucose was checked at 1, 3, 6, 12, 24, and 48 h of age in IGDM and in those at risk of hypoglycemia. Large for gestational age (LGA) was defined as more than the 90th percentile for gestational age. SGA was defined as birth weight <10th percentile for gestational age. Respiratory distress in the newborn is defined as the presence of any of the following: tachypnea, nasal flaring, chest retractions, or grunting. Need for phototherapy was determined as per guidelines. All newborns were managed as per our unit protocol. Newborn data were updated by the principal investigator, as and when complications arise, till discharge of each baby. The neonatal complications and its frequency and duration of NICU stay were compared in both GDM cases and the control group. Relevant demographic, maternal, and neonatal details were filled into a standard pro forma and analyzed using the Statistical Package for the Social Sciences -IBM SPSS Statistics for Windows, Version 23. Armonk, New York, USA: IBM Cor. Independent sample t-test was used to find mean birth weight in both GDM and control group. Odds ratio (OR) was used to assess the significance of neonatal complications in both the GDM and control groups. Chi-square tests were used to evaluate differences for categorical variables between the different groups. Level of significance was set up at P = 0.05 or less.
| Results|| |
[Figure 1] depicts the methodology of the study. Out of 677 obstetric case records reviewed during the study period, 168 were found to be eligible and therefore selected for analysis. Eighty-four GDM cases were matched with 84 healthy control mothers.
The descriptive characteristics of GDM cases and controls are described in [Table 1]. Maternal obesity was seen in 33 (40%) GDMs. About 80% of those who received insulin had high BMI. The mean birth weight in GDM group was 2.765 kg (standard deviation [SD] 0.640) versus 2.705 kg (SD 0.539) in the control group. Using independent sample t-test, it was found that there is no statistically significant difference between mean birth weights of GDM group and the control group. NICU admission is required 2.89 times more commonly in newborns of GDMs than the control group (OR = 2.89, 95% confidence interval [CI] [1.63–5.21], P = 0.001).
|Table 1: Baseline characteristics of gestational diabetic mother's cases and controls|
Click here to view
[Table 2] describes the neonatal outcomes while comparing GDM with high BMI and normal BMI. Hypoglycemia was seen in 96% of infants born to obese GDMs.
|Table 2: Comparison of neonatal outcomes with high and normal maternal body mass index|
Click here to view
Neonatal hypoglycemia was seen 2.87 times more in GDM group when compared to the control group (OR = 2.87, 95% CI [1.41–5.82], P = 0.003). Similarly, respiratory distress occurred 2.37 times in GDM group compared to control group (OR = 2.37 with 95% CI [1.17–4.81], P = 0.01).
Twenty-five (29.8%) babies in GDM group were SGA when compared to 18 SGA babies (18.2%) in control group. However, there is no statistically significant association between SGA and GDM (P = 0.06; OR 1.91; 95% CI [0.95–3.81]). Only three babies (9%) were found to be LGA in mothers with high BMI. Among the 84 cases of GDM, 27 received MNT, 10 received Metformin, and 47 received insulin. Those mothers with high BMI had 4.8 times more risk to enter into insulin group when compared with control group (OR: 4.86; 95% CI 2.10–11.5, P = 0.001). Insulin was started in the last week of pregnancy in 12 out of 47 patients of insulin group as their blood glucose was not controlled with diet and or oral hypoglycemic agent (OHA).
| Discussion|| |
As fetal metabolism in the infant of diabetic mother is complicated by insulin resistance and islet cell hyperplasia, multiple immediate neonatal sequelae including abnormal metabolism of glucose, calcium, magnesium, polycythemia, respiratory distress syndrome, hyperbilirubinemia, perinatal asphyxia, and abnormalities of growth are known to occur.
We report that neonatal hypoglycemia, respiratory distress, NICU admission, and NICU stay more than 7 days are significantly associated with maternal BMI more than 25 when compared to infants of nonobese diabetic mothers. The onset of neonatal hypoglycemia is also earlier in this group when compared to other high-risk groups such as SGA babies of mothers with PIH as per the study by Turner et al. It is recommended that not all infants of diabetic mothers (IDM) should be admitted to special care nurseries. However, our study shows that IDM born to obese mothers are at significant risk of developing hypoglycemia and respiratory distress and therefore should be closely monitored. The incidence of neonatal hypoglycemia in our setting is 28% compared to 15%–20% of hypoglycemia in infants of diabetic mothers in a meta-analysis by Pollex et al. 2017 ACOG technical bulletin strongly recommends that insulin is the primary agent in managing GDM if dietary management fails. There is evidence which shows that greater duration of hyperglycemia during pregnancy will result in greater risk of hypoglycemia in newborns. In our setting, in those GDM with poorly controlled blood sugars, especially in those whom insulin was started as late as 34 weeks, neonatal hypoglycemia was frequently seen when compared to those who did not require insulin. This would probably be due to prolonged maternal hyperglycemia and the consequent hyperinsulinemia in the fetus. In a very recent study, Voormolen et al. have found no difference in neonatal hypoglycemia, whether treated by MNT or insulin, even though there is a high incidence of neonatal hypoglycemia in their study on GDM.
Barquiel et al. have found that SGA infants in GDM have more neonatal complications such as hypoglycemia, polycythemia, and increased neonatal deaths than LGA infants.
Scientific data are scant regarding SGA in GDM. In our study, we observed that 22% of GDM with high BMI were SGA when compared with only 7% incidence of SGA in GDM with normal BMI. Classically, it is taught that all fetuses of mothers with GDM are growth promoted. In our study population, macrosomia was seen in only 3% (three LGA among GDM and two LGA among the controls) compared to 20%–35% incidence in the west.
We found that 30% of infants born to mothers with gestational diabetes, per se, were SGA, after excluding Type 1, Type 2 diabetes, and PIH which are known causes of vasculopathy. Hence, while studying the neonatal outcomes, our analysis was more focused on the hitherto less studied SGA babies in GDM, which was found to be much higher (29.8%) in our setting. Neonatal hypoglycemia was more common (22%) in babies born to obese mothers when compared with IDM born to nonobese mothers (7%). Decreased hepatic glycogen stores rather than hyperinsulinemia may be the reason for hypoglycemia in growth-retarded IDM. Esakoff et al. reports less macrosomia in Asian GDM compared to white GDM. The increased occurrence of SGA babies in our setup could be associated with the increased fat mass and truncal obesity seen in our population, which is also found by Bruno et al. in Italian pregnant women. It is postulated that abdominal visceral obesity leads to a proinflammatory state which is detrimental to the placental function, resulting in SGA babies. It is interesting to note that there is a very small proportion of LGA infants in our setting (3.5%). However, no significant difference was found in the mean birth weights between GDM and the control group. We report that high maternal BMI is associated significantly with adverse neonatal outcomes and these women eventually require insulin and or OHA. Goh et al. who observed that women treated with metformin and or insulin had significantly higher BMI.
The main strength of this work is that it is probably the first report in the Indian subcontinent on neonatal outcomes such as SGA infants born to GDM with prepregnancy obesity as a complicating factor. The focus on hitherto lesser studied immediate effects of maternal obesity in infants of gestational diabetes is novel and the comparison with a normal control group, eliminating selection bias, as far as possible, are the strengths of this study. We have excluded other known underlying diseases affecting fetal growth. It could prove that more adverse neonatal outcomes are significantly seen in those with maternal high BMI. This study has implications in improving lifestyle modifications to reduce BMI even before pregnancy, probably starting from adolescence. Ensuring adequate nutrition in GDM is equally important as trying to control hyperglycemia in the mother to prevent babies being born SGA.
| Conclusions|| |
We identified that adverse neonatal outcomes such as hypoglycemia, respiratory distress, and neonatal intensive care admissions are significantly seen in those GDMs with maternal obesity when compared to those without obesity. Newborns of obese GDMs are at much higher risk of developing hypoglycemia when compared to infants born to nonobese GDMs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mithal A, Bansal B, Kalra S. Gestational diabetes in India: Science and society. Indian J Endocrinol Metab 2015;19:701-4.
Sreekanthan K, Belicita A, Rajendran K, Vijayakumar A. Prevalence of gestational diabetes mellitus in a medical college in South India: A pilot study. Indian J Clin Pract 2014;25:342-7.
Assaf-Balut C, Familiar C, García de la Torre N, Rubio MA, Bordiú E, Del Valle L, et al.
Gestational diabetes mellitus treatment reduces obesity-induced adverse pregnancy and neonatal outcomes: The St. Carlos gestational study. BMJ Open Diabetes Res Care 2016;4:e000314.
Santos S, Voerman E, Amiano P, Barros H, Beilin LJ, Bergström A, et al.
Impact of maternal body mass index and gestational weight gain on pregnancy complications: An individual participant data meta-analysis of European, North American and Australian cohorts. BJOG 2019;126:984-95.
Bhavadharini B, Anjana RM, Deepa M, Jayashree G, Nrutya S, Shobana M, et al.
Gestational weight gain and pregnancy outcomes in relation to body mass index in Asian Indian women. Indian J Endocrinol Metab 2017;21:588-93.
Rajasingam D, Seed PT, Briley AL, Shennan AH, Poston L. A prospective study of pregnancy outcome and biomarkers of oxidative stress in nulliparous obese women. Am J Obstet Gynecol 2009;200:9.e1-9.
Baeten JM, Bukusi EA, Lambe M. Pregnancy complications and outcomes among overweight and obese nulliparous women. Am J Public Health 2001;91:436-40.
Bruno R, Petrella E, Bertarini V, Neri I, Facchinetti F. Lifestyle-induced maternal body composition changes and birth weight in overweight/obese pregnant women. J Pediatr Neonatal Individ Med 2015;4:e040227.
Leng J, Hay J, Liu G, Zhang J, Wang J, Liu H, et al.
Small-for-gestational age study among Chinese women. BMJ Open 2016;6:e01098.
International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al.
International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-82.
Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al.
Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009;57:163-70.
Kleigman R, Stanton B, St Geime JW, Schor NF, Behrman RE, editors. Nelson Textbook of Pediatrics, 21st ed. Philadelphia: Elsevier; 2020.
Turner D, Monthé-Drèze C, Cherkerzian S, Gregory K, Sen S. Maternal obesity and cesarean section delivery: Additional risk factors for neonatal hypoglycemia? J Perinatol 2019;39:1057-64.
Georgieff MK, Sasanow SR, Chockalingam UM, Pereira GR. A comparison of the mid-arm circumference/head circumference ratio and ponderal index for the evaluation of newborn infants after abnormal intrauterine growth. Acta Paediatr Scand 1988;77:214-9.
Pollex E, Moretti ME, Koren G, Feig DS. Safety of insulin glargine use in pregnancy: A systematic review and meta-analysis. Ann Pharmacother 2011;45:9-16.
Acker DB, Sachs BP, Friedman EA. Diabetes practice Bulletin No.180: Gestational diabetes mellitus, Obsteric Gynaecol 2017;130:e17-3.
Joshi T, Oldmeadow C, Attia J, Wynne K. The duration of intrapartum maternal hyperglycaemia predicts neonatal hypoglycaemia in women with pre-existing diabetes. Diabet Med 2017;34:725-31.
Voormolen DN, de Wit L, van Rijn BB, DeVries JH, Heringa MP, Franx A, et al.
Neonatal hypoglycemia following diet-controlled and insulin-treated gestational diabetes mellitus. Diabetes Care 2018;41:1385-90.
Barquiel B, Herranz L, Martínez-Sánchez N, Montes C, Hillman N, Bartha JL. Increased risk of neonatal complications or death among neonates born small for gestational age to mothers with gestational diabetes. Diabetes Res Clin Pract 2020;159:107971.
Blickstein I, Perlman S, HazanY, Olivestone C, Shinwell SE, editors. Fanaroff and Martin's Neonatal – Perinatal Medicine. 10th
ed. Philadelphia: Elsevier; 2015.
Nold JL, Georgieff MK. Infants of diabetic mothers. Pediatr Clin North Am 2004;51:619-37.
Esakoff TF, Guillet A, Caughey AB. Does small for gestational age worsen outcomes in gestational diabetics? J Matern Fetal Neonatal Med 2017;30:890-3.
Apovian CM, Bigornia S, Mott M, Meyers MR, Ulloor J, Gagua M, et al.
Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler Thromb Vasc Biol 2008;28:1654-9.
Goh JE, Sadler L, Rowan J. Metformin for gestational diabetes in routine clinical practice. Diabet Med 2011;28:1082-7.
[Table 1], [Table 2]