Hypoglycaemia in screening oral glucose tolerance test in pregnancy with low birth weight fetus

Abstract

Maternal hypoglycemia, a condition characterized by lower than normal blood glucose levels in pregnant women, has been increasingly associated with adverse pregnancy outcomes, including low birth weight (LBW) in neonates. LBW, defined as a birth weight of less than 2500 g, can result from various factors, including maternal nutrition, health status, and metabolic conditions like hypoglycemia. Maternal hypoglycemia may affect fetal growth by altering the supply of essential nutrients and oxygen to the fetus, leading to restricted fetal development and growth. This condition poses significant risks not only during pregnancy but also for the long-term health of the child, increasing the likelihood of developmental delays, health issues, and chronic conditions later in life. Research in this area has focused on understanding the mechanisms through which maternal hypoglycemia influences fetal development, with studies suggesting that alterations in placental blood flow and nutrient transport, as well as direct effects on fetal insulin levels and metabolism, may play a role. Given the potential impact of maternal hypoglycemia on neonatal health outcomes, early detection and management are crucial to minimize risks for LBW and its associated complications. Further investigations are needed to fully elucidate the complex interactions between maternal glucose levels and fetal growth, as well as to develop targeted interventions to support the health of both mother and child. Understanding these relationships is vital for improving prenatal care and outcomes for pregnancies complicated by hypoglycemia.

Key Words: Glucose tolerance test; Low birth weight; Hypoglycaemia; High-risk pregnancy; Neonatal outcome

Core Tip: Maternal hypoglycemia's association with low birth weight is a complex and nuanced issue that has garnered attention in the medical community. Emerging studies suggest a correlation between maternal blood glucose levels and birth weights, highlighting that not only hyperglycemia, but also hypoglycemia could significantly impact neonatal outcomes.

TO THE EDITOR

Neonatal low birth weight (LBW) presents a significant public health challenge worldwide. The World Health Organization estimated that in 2015, approximately one out of every seven live births globally, amounting to 20.5 million infants, were born with LBW. Furthermore, LBW is associated with over 80% of neonatal fatalities, with preterm births accounting for around two-thirds of these deaths[1]. Pregnancy hypoglycaemia arises from a relatively enhanced state of insulin action, which could be due to heightened insulin levels or an increase in insulin receptor activity, as well as a reduction in certain hormones that typically counteract insulin's effects, such as placental lactogen[2,3].

While women with gestational diabetes mellitus (GDM) often have elevated glucose levels, leading to a higher chance of birthing neonates that are large for gestational age, women experiencing low blood sugar may have a heightened risk of delivering neonates with LBW[4]. However, there has been limited research on the connection between low blood sugar during the oral glucose tolerance test (OGTT) and the subsequent effects on maternal and neonatal health, particularly in women who are normally glucose tolerant (NGT)[5,6]. Previous studies have mainly concentrated on the consequences of reactive hypoglycemia following an OGTT, with inconsistent findings regarding its influence on maternal and neonatal outcomes, such as neonatal birth weight. Furthermore, the bulk of this research has focused on hypoglycemic effects in women with GDM or obesity[7,8]. There is a lack of information on the pregnancy outcomes for NGT women who have lower or flat glycemic levels during the OGTT conducted between the 24th to 28th weeks of gestation[4,9]. A study published in 2022 concluded that hypoglycemia in OGTT is not associated with maternal or neonatal adverse outcomes[7].

Research into maternal hypoglycemia and its potential link to LBW is revealing important insights into fetal development. Unlike the well-established risks associated with GDM, where elevated maternal glucose can lead to large-for-gestational-age infants, maternal hypoglycemia represents a less understood risk factor[2,3].

We have read with great interest this observational study by Nayak et al[10] They explored the association between low glycemia during OGTT test and LBW. LBW was defined as below 2500 g and glycaemic markers were diagnostic for GDM as follows: Fasting glucose ≥ 5.6 mmol/L and/or a 2 h plasma glucose post 75 g glucose load ≥ 7.8 mmol/L. Hypoglycemia was defined by a blood glucose value ≤ 3.5 mmol/L[10]. This study has a large number of cases analyzed (n = 3537) on a 4 year period. They selected high risk women for GDM that underwent OGTT[10].

According to the authors, LBW was significantly higher in women with low plasma glucose when compared to women who delivered normal or macrosomic neonates. They have also stated that maternal age is not a significant factor[10].

The developing fetus relies on maternal glucose as its primary energy source, transported across the placenta without the need for insulin[9,11]. When a mother experiences episodes of hypoglycemia, this vital supply of glucose to the fetus may be compromised, potentially impeding fetal growth and development, leading to LBW and higher risks of admission into neonatal intensive care unit[12,13].

Most of the current literature focuses on the effects of hypoglycemia in populations of women with GDM or obesity, with scant data on otherwise healthy women with naturally lower glucose levels. This gap signifies a need for more robust, large-scale studies to better understand the potential impacts of maternal hypoglycemia on fetal growth and to establish clear clinical guidelines for managing low blood sugar levels during pregnancy to optimize neonatal outcomes.

Although studies show inconsistent data, it is important to have a different approach on women with low glucose levels at OGTT, given the fact that a large number of factors can contribute to LBW such as genetic conditions, structural abnormalities, and environmental factors[14].

So far most of the international societies recommends screening for GDM only to high risk women, it is important to think about having all women screened at 24-28 weeks not only for GDM, but also for prediction of adverse perinatal and neonatal outcomes[15].

Finally, the authors well presented, on a large number of cases, an association of low fasting plasma glucose and a low glucose response at OGTT with LBW in high risk women for GDM screened at 24-28 weeks and highlights the importance of hypolgycaemia, which otherwise it is considered to be normal.