Neurodevelopmental Outcome in Infants of Gestational Diabetic Mother in a Tertiary Care Hospital, Dhaka, Bangladesh

Maria Mahabub¹, Rumpa Mani Chowdhury², Mohammad Kamrul Hassan Shabuj³, Sadeka Choudhury Moni⁴, Ismat Jahan⁵, M A Mannan^6*, Sanjoy Kumer Dey⁷, M Shahidullah⁸

¹Resident, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University Shahbag, Dhaka, Bangladesh
²Assistant Professor, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University Shahbag, Dhaka, Bangladesh
³Associate Professor, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University Shahbag, Dhaka, Bangladesh
⁴Associate Professor, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University Shahbag, Dhaka, Bangladesh
⁵Associate Professor, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University Shahbag, Dhaka, Bangladesh
⁶Professor, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University Shahbag, Dhaka, Bangladesh
⁷Professor and Chairman, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh
⁸Founder and Professor, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University Shahbag, Dhaka, Bangladesh

*Correspondence author: MA Mannan, Professor, Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; Email: [email protected]

Citation: Mannan MA, et al. Neurodevelopmental Outcome in Infants of Gestational Diabetic Mother in a Tertiary Care Hospital, Dhaka, Bangladesh. Jour Clin Med Res. 2024;5(3):1-14.

Copyright^© 2024 by Mannan MA, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Table 1: Maternal baseline characteristics of neonates (N=52).

Baseline characteristics of the studied neonates were presented in Table 2. Mean gestational age was 36.54 ± 1.63 weeks and mean birth weight was 2722.5 ± 660 gram. Most of the neonates belonged to term (51.9%) and normal birth weight (> 2500 g). Male and female ratio was 1.1:1. Most of them were appropriate for gestational age (65.4%). Five newborns had intrauterine growth restriction, about one third (34.6%) neonates needed neonatal intensive care admission, eight newborn had APGAR score less than 7/10 at 1^st minute after birth.

Table 2: Neonatal baseline characteristics of studied neonates (N=52).

Clinical characteristics of enrolled neonates were shown in Table 3. Near about one third had hyperbilirubinemia (31%), thereafter hypoglycemia and polycythemia was found in 15% neonates, hypocalcemia was in 13.5% and few neonates had hypomagnesemia (9.6%). The most common morbidity of the studied newborns was sepsis (17.3%), thereafter respiratory distress (11.5%), around 4% patients had seizure and 2% newborn developed shock as a complication. Fig. 2 is showing the percentage of metabolic, hematological and clinical findings among studied neonates.

Table 3: Laboratory parameters and Clinical characteristics of neonates (N=52).

Figure 2: Metabolic, hematological and clinical findings among studied neonates (N=52).

The overall neurodevelopmental outcome of the infants of diabetic mother is shown in Fig. 3. Most of the infants (n=38) had favorable outcome, which is 73.1% of studied neonates. More than one fourth (26.9%) infants (n=14) had adverse neurodevelopmental outcome.

Figure 3: Neurodevelopmental outcome of studied neonates (N=52).

Most of the newborns had favorable outcome, 98% in cognition, 79% in language and 90% in motor development. Among the adverse outcome of three domain, 2% had cognitive delay, around one fourth had language delay (21.2%) and few had delay in motor domain (9.6%). (Table 4). In Fig. 4 is showing the difference between adverse and favorable outcome among the three domains.

Table 4: Neurodevelopmental Outcome of enrolled neonates in follow up at 9 months of age (N= 52).

Figure 4: Neurodevelopmental outcome of infants at 9 months follow up.

Qualitative data were presented as number and percentage, Quantitative data were presented as mean ± SD. Statistical test: Chi square test and Independent t-test.

Maternal parameters were compared between the favorable and adverse outcome group. There were significant difference between two groups in respect to drugs (insulin or OHA) used in gestational diabetes mellitus and maternal glycemic control. (p-value- 0.041 and 0.000). Regarding other parameters such as maternal age, mode of delivery and hypertension there were no significant difference found (Table 5).

Table 5: Comparison of Maternal factors between adverse and favorable outcome group (N= 52).

Qualitative data were presented as number and percentage, Quantitative data were presented as mean ± SD.

Statistical Test

Chi square test and Independent t-test Neonatal baseline characteristics were compared between the favorable and adverse outcome group. There were no significant difference between two groups in respect to birth weight, gestational age category, fetal growth at birth, intrauterine growth restriction, gender distribution, APGAR score and need for NICU admission (Table 6).

Table 6: Comparison of neonatal baseline characteristics between adverse and favorable outcome group (N= 52).

Multivariate regression analysis of factors affecting neurodevelopmental outcome in the studied newborns showed only maternal glycemic control was significantly associated with adverse neurodevelopmental outcome among the studied neonates. (p-value=0.001) (Table 7).

Table 7: Multivariate logistic regression analysis of factors affecting neurodevelopmental outcome in enrolled neonates (N=52).

Discussion

It is well established that diabetes has been associated with maternal and perinatal morbidity and mortality both in short and long term. In this prospective observational study, 52 infants of gestational diabetic mother were recruited to see the association between GDM and child’s neurodevelopment and they were followed up at their 9 months of age. To justify whether any maternal factors and neonatal complications affecting the neurodevelopment of infant, some maternal factors and newborn’s clinical, metabolic and hematological profile were seen. Newborn who developed any co-morbidities like sepsis, jaundice and/or respiratory distress were admitted in NICU and other’s were kept mother’s side in the postnatal ward. Both were followed up according to NICU protocol during hospital stay. Neonatal hypoglycemia, maternal poor glycemic control and maternal use of drugs for GDM was the predictive factors of adverse neurodevelopment. Among the predictive factors such as hypoglycemia, no baby developed symptomatic hypoglycemia as because early introduction of frequent feeding was ensured. Mother who needed drugs Mother who needed drugs for GDM either took insulin or Metformin as oral hypoglycemic agent. Though most of the mother had good glycemic control, adverse outcome was mostly found among the infants of mother who had poor glycemic control and it was significantly associated with adverse developmental outcome in this study. This study includes newborn with gestation 34 weeks or more, as less than 34 weeks neonates are more vulnerable to develop several serious co morbidities like sepsis, respiratory distress, jaundice, perinatal asphyxia, congenital anomalies, specially in this subcontinent. Similarly, in a multicenter study done in Montreal, Canada and Dublin, Ireland, they also excluded gestation of less than 32 weeks to avoid poor developmental outcome due to other co-morbidities [5]. In this study, the mean gestational age was 36.54 ±1.63 weeks. It is close to a previous study, where the mean gestational age was 37.92 ± 1.65 [19]. In the present study, the mean birth weight was 2722.5 ± 660 g which was lower than the previous study where the mean birth weight was 3596 ± 494 g [22]. This difference can be explained by that, in their study they recruited more number of obese mother getting insulin. In this study, lower segment cesarean section was needed in 90.4% cases which was quite higher than the previous study where LSCS was needed only for 51.1% cases [15]. This higher percentage of the LSCS may be explained by the fact, that this study was conducted in a tertiary care hospital, where most of the complicated pregnancies were dealt by the Feto-maternal medicine unit, with necessitating LSCS. However, a study explained that if LSCS done electively, it is associated with improved neonatal outcomes in terms of better APGAR scores at 5 minutes [15]. This findings was consistent with the present study, that this study found no low 5 min APGAR score among studied neonates.

In this study, more than half neonates were delivered at term (51.9 %), on the other hand a previous study found preterm deliveries were higher (51.1%) [20]. This difference can be explained by the fact that, in their study all diabetic mothers were with coexisting medical complications like pregnancy induced hypertension, chronic heart and renal disease. In this study 65.4% babies were AGA which is quite similar to a previous study done in Tamil Nadu, India, where they found 68% babies were age appropriate [21]. Maternal factors responsible for poor neurodevelopmental outcome in infants were evaluated in this study. As maternal complications, this study found (34.6 %) mother were hypertensive which is consistent with a previous study which showed that up to 10-30 % of women with gestational diabetes may develop hypertension in pregnancy [22]. In this study, 11.5 % mother had polyhydramnios which is similar to a previous study where they found that incidence of polyhydramnios is 11.6% [23]. In this study, 48.1% mother needed insulin or oral hypoglycemic agent as medication, where a study showed 57.1% mother needed insulin [24]. This contradictory findings can be explained by higher number of obese mother were included in their study. This study showed 13% diabetic mother had poor glycemic control which is differed from the previous study done in Tamil Nadu, India in 2018, where they got 58.1% mother had poor glycemic control [21]. This difference may be due to the fact that, they included all the mother getting insulin who were obese and overweight. When neonatal clinical and laboratory parameters were seen, this study found hypoglycemia was the second most common complication present in 15.4 % of patients. This result is not consistent with the result of a study where they found hypoglycemia was the most common complication among IDM and seen in 71.4% of neonates [25]. This difference can be explained by the fact that, this study was done in a tertiary level hospital where all the babies were strictly followed up in postnatal ward and frequent feeding was ensured and blood glucose level was checked routinely, which decreased the chance of developing hypoglycemia. Several studies have agreed that the incidence of hypoglycemia in infants of gestational diabetic mother was 12.9% to 59.4% [26-28]. In the present study hyperbilirubinemia was found as the most common complication seen in 30.8% of neonate where in a previous study they found 66.7% hyperbilirubinemia in IDM [25]. This larger difference may be due to strict monitoring of jaundice by measuring serial transcutaneous bilirubin and frequent follow up in this tertiary level hospital reduce the severity of jaundice. This study found polycythemia in 15.4 % cases, this findings was quite near to a study where they found 11% cases of polycythemia in IDMs [15]. In the present study 13.5% IDMs developed hypocalcemia, where in another study they found hypocalcemia in 22% of IDMs [15]. This difference may be explained by the fact, that they included most of the preterm babies in their study. Regarding clinical parameter this study found sepsis was the most common (17.3%) and respiratory distress was the second most common (11.5%) morbidities among IDMs, which differed from the study done in California, Los Angeles, where they showed respiratory distress was more common and near about 48%, this bigger difference can be explained by the fact that they recruited all the newborns below 34 weeks in their study and respiratory distress is common in preterm babies [29]. This study showed neurodevelopmental outcome at 9 months by BSID III where cognitive, expressive and receptive language, fine and gross motor development was seen. There are several studies done in different subcontinent to see the neurodevelopmental outcome but they use other scale to assess the outcome like Bruininks Oseretzky test, Wechsler Preschool and Primary Scale of Intelligence, Ages and Stages Questionnaire (ASQ), TanakaBinet IQ scores and BSID II(mental developmental index and psychomotor developmental index). So far, only two studies used BSID III to see the outcome among diabetic mother.

This study found overall adverse outcome in 26.9% infants among them 1.9% had cognitive delay, which differed from the study where they found 6.5% delay in cognitive skills [12]. This difference may be in respect to the fact, that in this study more number of mother had good glycemic control. Also some author given this explanation that cognitive ability of offspring born to mothers with well controlled  diabetes  is  usually  normal  unless complicated by other comorbidities [30]. The present study got 9.6% infants with motor delay, which was also lower from a study, where they found 14.6% and another study found 12.6% delay in motor development [12,31]. This lower percentage in this study also can be explained by this fact that having more number of mother with good glycemic control in this study. This study found language delay in 11% infants, this result differed in respect of lower percentage from the study where they found 26% of children born to diabetic mothers having low language abilities [19]. But this findings was in agreement with some studies in terms of that all these studies including the present study found a higher incidence of developmental language delay in infants born to diabetic mothers [19,24,32]. This finding was contradicting by a study where they found that children born to mothers with diabetes had a higher risk of developmental delay mainly in gross motor skills [33]. In a contrary, when some studies done with older children, showed no significant differences in developmental outcomes among the diabetic mother [32]. This can be explained by the statement given by a study where they stated that, younger children have poorer neurological functions as there is a gap in maturation of central nervous system, but older children can compensate for slight motor impairment as because this gap will compensate with age [30]. This statement was established in some studies as they didn’t find any difference in cognitive scores in older children from 4 to 13 years born to GDM mothers [34,35]. When neonatal factors were compared with adverse and favorable outcome only hypoglycemia was found significantly associated with adverse outcome. This findings was consistent with a systematic review by where they found that neonatal hypoglycemia was significantly associated with developing long lasting adverse neurodevelopmental outcome.36 When maternal factors were compared with adverse and favorable outcome, maternal poor glycemic control and maternal use of drugs for GDM where found significantly associated with adverse outcome. In contrast with this findings a study showed that no significant difference was associated with maternal use of drugs for GDM [37]. This can be explained by the fact, that they only studied with the mother where on medication either oral (metformin) or insulin. When multivariate logistic regression was done among these factors only poor glycemic control was found significantly associated with adverse neurodevelopmental outcome. This finding was in agreement with several studies and systematic review [7,11,19]. Like this study, several studies were done to see the neurodevelopmental outcome among infants born to mother with gestational diabetes and most of the study was consistent with this statement that maternal gestational diabetes can adversely effect neurodevelopmental outcome of infants. Which is consistent with the findings of present study.

Conclusion

Maternal gestational diabetes can adversely affect on their infants neurodevelopment. Among the adverse outcome of three domains language delay was most common. Neonatal hypoglycemia, maternal poor glycemic control and use of drugs for GDM are significant predictors of adverse neurodevelopmental outcome in infants of gestational diabetic mother. Among them maternal poor glycemic control was significantly associated with adverse neurodevelopmental outcome.

Limitations of the Study

Long term follow-up couldn’t be done. BSID III was not done by single clinical psychologist. Single follow up was done.

Recommendations

Further multicenter prospective studies with larger sample size and longer follow up can be done to give better insight of neurodevelopmental outcome of infants of diabetic mother. Each and every diabetic mother should enrolled in follow up clinic to identify the later co-morbidities of infant as well as neurodevelopment at earliest possible time hence intervention can be provided for better quality of life of the infants of diabetic mother.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author Contribution

Contributed to concept and design, analysis and interpretation of data and drafting and revising of article; analysis and interpretation of data and revising article for intellectual content. All authors contributed to final approval of version to be published.

Funding

University research grant, BSMMU.

Acknowledgment

The authors thank all the newborns on whom they conducted our study. The authors also express all their appreciation to their colleagues and nurses in the neonatology unit who facilitated this work.

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