Along with other metabolic disorders, Diabetes mellitus in association with pregnancy as well as one developed during pregnancy is one of the very common disorders in obstetric practice and neonatology; prevalence of this disease is on the rise across South Asia due to increasing maternal age, obesity, sedentary lifestyle etc. [2] The burden of GDM in Pakistan is amongst the highest in the region and babies of GDM mothers face significantly higher risks of complications in the course of pregnancy, most importantly neonatal hypoglycaemia.

Prenatal and fetal physiological mechanisms are well described as glucose is normally transferred across the placenta to the fetus and during chronic hyperglycaemia of the mother, the fetal pancreatic beta-cells will become hyperplastic, with the fetus then becoming

hyperinsulinemic. After the baby has been born, when the mother is unable to give an uninterrupted supply of glucose, while the baby's insulin is still high, blood glucose level may drop suddenly and greatly in the newborn during the first few hours of life [3].

Vitiation of the milieu is caused by neonatal Hypoglycemia and if not recognised may lead to serious neurologic sequelae including seizures, apnea and permanent neurodevelopmental imbalance following severe or recurrent episodes [4]. Given that the disease occurs without symptoms early in life, screening is recommended for all infants born to a diabetic mother irrespective of birth weight or apparent status of wellbeing and is structured and time bound [5].

Although there is a good amount of data available on hypoglycemia in IDM in literature, no local data is available from these tertiary hospitals in Pakistan and the screening practices differ from hospital to hospital. This study has thus been designed to gauge the prevalence of neonatal hypoglycaemia in Pakistan in several tertiary health care centres and to find the most closely related factors.

The study design and setting It was a multi-center and prospective observational study undertaken in Neonatology and Pediatrics departments in tertiary care teaching hospitals of Pakistan such as Nishtar Medical University Hospital, Multan and Jinnah Hospital Lahore. Data collection was carried out from August 2025 to January 2026. Ethical Approval Ethical approval for the study was obtained from the Institutional Ethical Review Committees of the participating hospitals prior to enrollment, in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all enrolled neonates. Inclusion Criteria ● Neonates born to mother with Gestational Diabetes Mellitus GDM ● Born from mothers who have pre-existing (Type-1 or Type-2) Diabetes mellitus (DM) ● Late prematures (gestational age less than 37 weeks) who attend the neonatal unit/nursery for the routine post-natal observation. Exclusion Criteria ● Newborns with major congenital anomalies ● Infants of mothers undiagnosed with DM. Study Procedure Monitoring of capillary glucose levels was done at 1 hr, 2 hrs, 4 hrs and 24 hrs of life since it is a routine practice for babies born to diabetic mother in the institutional setting by using the calibrated glucometer. Hypoglycemia was considered to be reading < 40mg/dl at any of these time points during the first 24 hours of life. Those neonates who were considered having hypoglycemia were treated as per standard institutional feed and in case of need intravenous dextrose, as per institutional policy. Maternal information gathered were type of diabetes, glycemic control (utilizing the last available antenatal glycated hemoglobin (HbA1c); good glycemic control defined as below or equal to 6.5%), gestational age at birth and delivery mode. The neonatal parameters were weight at birth, sex and macrosomia (weight at birth > 4 kg). Outcome Measures The main outcome were the overall occurrence of neonatal hypoglycemia during the first 24 hours of life. Secondary outcomes comprised of proportion of hypoglycemic episodes occurring at each of the serial screening time points, and association of hypoglycemia with maternal glycemic control, type of delivery, type of diabetes and macrosomia. Statistical Analysis All the data were analysed using SPSS 26.0 software. All the continuous variables were included and expressed as mean (SD) and compared using Independent samples t test. Categorical data was presented as numbers and percentages and the comparison of these data was done with Chi-square test. Statistically significant differences were set at p < 0.05 level.

During the study period of six months, 210 neonates born of DM were enrolled. The mean maternal age was 29.4 ± 4.6 years and the majority of cases were of gestational diabetes mellitus (77.1%) and the remaining were cases of pre-existing diabetes mellitus. Good glycemic control was defined as serum glucose of 60–105 mg/dl in 61.4% while poor glycemic control was defined as below or above this range in 38.6%. The basic maternal and neonatal characteristics are shown in Table 1.

Of 210 neonates, 57 developed hypoglycaemia in the first 24 hours with the overall prevalence being 27.1%. For transient hyperinsulinemic hypoglycemia in this population, the prevalence, as shown in figure 1, was highest for the 1 hour screen, and progressively lower in the subsequent time points, reaching a nadir of 3.3% for the 24 hour screen.

On comparison to look at the occurrence of hypoglycemia between the babies born of poor glycemic control and good, it is found that more babies born to poor glycemic control mothers experienced hypoglycemia than good glycemic control mothers (48.1% vs. 14.0%, p < 0.001) as shown in Table 2. Macrosomic neonates also had a higher incidence of hypoglycemia compared to non-macrosomic neonates (51.0% vs. 19.5%, p < .001). The difference between the cesarean and vaginal delivery groups and between the pre-existing diabetes group and the GDM group in the incidence of hypoglycemia were both statistically significant (33.3% vs. 19.8%, p = 0.023 and 39.6% vs. 23.5%, p = 0.031, respectively).

Table 1: Shows the baseline characteristics of the mother and neonates (n = 210).

Table 2: Association Between Neonatal Hypoglycemia and Maternal/Neonatal Risk Factors

In this multi-center observational study, over 25% of neonates born to diabetic mothers experienced hypoglycemia within the first 24 hours of life with highest risk in the first hour of life. This phenomenon mirrors well-known physiological adaptation from a hyperglycaemic intrauterine state to extrauterine independence, and emphasises the importance of early, structured, glucose screening in this patient group [3,5]. Poor glycemic control in mothers is highly associated with neonatal hypoglycemia, which is similar to other studies carried out in tertiary care hospitals in Pakistan. A study at a public sector teaching hospital in Karachi also found significantly higher incidence of neonatal hypoglycemia among infants born to mothers who had suboptimal antenatal glycemic control [6]. A cohort of infants born to DMs in Lahore found a similar overall prevalence, with two factors—macrosomia and cesarean delivery—independently associated, similar to those found here [7]. Leading risk factors reported in a similarly designed study done in Islamabad were macrosomia and poor control in the antenatal period [14]. There was an increased risk of these infants in the macrosomic category, consistent with the fetal hyperinsulinemia hypothesis that excess transplacental glucose delivery results in accelerated fetal growth and exaggerated insulin mediated glucose clearance during the postnatal period [4]. These could be attributed to the greater incidence of cesarean-delivered neonates, who had a greater incidence of poor glucose homeostasis, due to delayed breast-feeding, glycemic changes during the surgical procedure, and decreased early skin-to-skin contact all linked to poor neonatal glucose homeostasis after Cesarean delivery [8]. The immediate clinical implications of these findings are as follows: Hypoglycemic events in this cohort were mostly detected at the first screening time, which was mostly within hour 1 of life; longer delays in time to first glucose check may miss a critical window for intervention. It is necessary to implement the structured and time bound screening along with early feeding practices and close monitoring of high-risk groups as part of routine neonatal care. This study does have some limitations. It is an observational study and, therefore, causal relationships cannot be determined with certainty. The assessment period did not include episodes beyond 24 hours or long-term neurodevelopmental outcomes. Large multi-center longitudinal studies, including longer follow-up, are encouraged. Finally, these results have immediate relevance for health-systems as resources in settings under health monitoring are constrained with intermittent point-of-care glucose testing serving as the primary source of information. With such settings, a well-timed screening schedule based on least time-consuming clinical protocols focused around the first few hours of life will likely yield considerably more than screening distributed evenly across the lighting hours, and provide an opportunity to apply limited nursing and laboratory resources where there is the greatest likelihood to be of clinical use. Immersing such a straightforward, uniform screening checklist in the admission order set for infants born to diabetic mothers, along with education for staff regarding the subtle symptoms and signs of hypoglycaemia, may change the bed-side practice of screening for hypoglycaemia and translate this into consistent practice without any significant additional financial investment. The results also support the importance of a multi-disciplinary approach from the antenatal to the postnatal period. The combination of obstetric teams who are optimizing maternal glycemic control in pregnancy, and neonatal teams who implement structured postnatal screening and feeding plans is a continuum of care that seems to have important effects in bringing down hypoglycemia and its consequences in this cohort of children. Increased communication between the antenatal clinic and neonatal unit, focussed on bringing to the attention of the neonatal team the status of a mother's glycemic control at birth, could further enhance the neonatal team's prioritization process with a stronger focus on high-risk infants within the kick-off period of postnatal care.

Despite new scientific information, hypoglycemia in the newborn period continues to be quite a common complication in infants born to mothers with diabetes, with the highest prevalence occurring in the first hour of life and it is associated with non-optimal glycemic control and/or macrosomia during gestation, cesarean delivery. These results argue strongly for early, routine, serial glucose screening for all neonates born to diabetic mothers in tertiary care setting with a specific emphasis on the first hour, when there is peak risk of hypoglycemia. Better glycemic control during pregnancy, early breastfeeding, and closer postnatal surveillance of the high-risk populations such as macrosomic infants and cesarean-section babies also may decrease the morbidity from this largely preventable condition. In summary, using simple algorithm screening of situations in a protocol-driven fashion in a setting with limited resources like most of the tertiary care centres of Pakistan can be a great practical and cost-effective way of improving the detection of such situations and the outcomes. These efforts also could be complemented at little extra cost by closer collaboration between the teams providing antenatal and neonatal care; and by routine for all staff to be alert for signs and symptoms of neonatal hypoglycemia. Future multi-center studies with longer follow-up should be done to elucidate the downstream neurodevelopmental effects of neonatal hypoglycaemia in the population and to determine if any further improvement is measurable if there will be uniform screening and management protocols for this high-risk group across tertiary care hospitals in Pakistan.

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