Why does labetalol cause neonatal hypoglycemia

Sweating, sudden pallor, hypothermia, and cardiac arrest and failure may also occur Table 1. Because other conditions e. Definitions of hypoglycemia should be flexible enough to encompass all of these factors. There are four approaches to defining a safe range for blood glucose, all with limitations [ 5 ] [ 6 ]. Neonates may develop clinical signs suggestive of hypoglycemia but, as outlined above, these can be difficult to recognize or differentiate from other conditions.

Studies of exclusively breastfed, appropriate-for-gestational-age AGA , term infants have shown that blood glucose levels fall immediately after birth, from two-thirds of maternal levels to as low as 1. Preterm infants may take longer to reach this threshold. There are normal physiological responses to hypoglycemia, such as a rise in ketones, growth hormone, cortisol, and catecholamines, and the suppression of insulin [ 10 ] [ 11 ].

Other studies have linked long-term sequelae with even lower glucose level within the first 72 hours post-birth [ 17 ]. Still others have shown no harm from transient hypoglycemia [ 18 ] [ 19 ] but rather, an increased risk for long-term sequelae with recurrent episodes of hypoglycemia [ 16 ].

Conventionally, and for reasons of convenience, blood glucose is usually measured using chemical strips or portable, bedside glucose meters rather than formal laboratory analysis. Also, variations between capillary and venous blood [ 24 ] , blood and plasma, and immediate and stored samples, may confound results Level 3b. In particular, delays in processing may result in lower measurable glucose levels. While acute management can be initiated based on point-of-care samples to prevent delay, a diagnosis of persistent hypoglycemia should be confirmed by laboratory assays.

More accurate bedside technologies are being developed and will likely improve the quality and ease of screening in future. Continuous glucose monitors CGMs have looked promising and may prove to be beneficial for monitoring neonates. However, current barriers to this technology include inaccuracy at lower glucose levels, delay in obtaining results, need for frequent recalibration, a limited surface area for sensor placement on small neonates, and a lack of treatment protocols [ 26 ] [ 27 ].

The accuracy of CGMs when measuring hypoglycemia in neonates remains in question [ 26 ]. Impairment of gluconeogenesis [ 27 ] is the most common cause of hypoglycemia in infants [ 28 ]. Specific etiologies include excess insulin production, altered counter-regulatory hormone production, or inadequate substrate supply. Risk factors are listed in Table 1. Questions exist as to whether nonsyndromic LGA non-IDM infants are truly at risk for hypoglycemia, but infants with conditions such as Beckwith-Wiedemann syndrome need to be followed closely [ 34 ].

A number of additional maternal and fetal factors, including maternal labetalol use or late preterm administration of antenatal steroids [ 35 ] [ 36 ] as well as intrauterine growth restriction IUGR and perinatal asphyxia, can also cause hypoglycemia. More rarely, metabolic and endocrine disorders may lead to persistent neonatal hypoglycemia [ 28 ] , but their disease-specific investigations and management [ 37 ] are beyond the scope of this statement.

Thresholds for treating hypoglycemia may differ depending on etiology. No study evaluating optimal timing and intervals for glucose screening has been identified.

Furthermore, there is insufficient evidence to support routine screening for asymptomatic infants with no risk factors for hypoglycemia. Lack of evidence for adverse effects of glucose levels between 1. Because feeding raises blood glucose [ 39 ] and stimulates ketosis [ 40 ] , it is also reasonable to continue feeding at-risk infants at regular intervals, while screening before feeds.

One early study [ 33 ] showed that IDM and, by inference, LGA infants were the most likely to develop hypoglycemia in the first few hours post-birth. SGA and preterm infants may become hypoglycemic as late as the second day, although a decline in blood glucose levels may be prevented by establishing peroral intake.

If there are no feeding concerns and the infant is well, screening may be discontinued at 24 hours of age Level 2b.

An approach to testing frequency in at-risk infants is shown in Supplementary Figure 1. Symptomatic infants should have a blood glucose assessment without delay. Parents should be aware of the reasons for regular blood testing and the symptoms that health care providers may be watching for, so that they can help with monitoring. Population data have suggested that blood glucose levels as low as 2.

For at-risk infants, however, outcome data support raising the intervention threshold. Lucas et al. Compared with non-hypoglycemic control subjects, six or more episodes of hypoglycemia were associated with lower head circumference at 12 and 18 months as well as at 5 years of age.

It is uncertain whether these results would be similar for a cohort of more aggressively managed infants. Stenninger et al.

Using the Griffiths developmental and Movement-ABC tests, the authors discovered evidence of minimal neurological dysfunction whether the IDMs had been hypoglycemic or not Level 2b. It is worth noting that most of the hypoglycemic infants were asymptomatic. Cornblath et al. They distinguished between the threshold glucose value that requires action 2.

Recently, the 4. More randomized clinical trials to compare interventions, intervention thresholds, and long-term outcomes are needed. Recommendations for the management of hypoglycemia are outlined in Supplementary Figure 1.

Previous guidelines suggested raising threshold glucose levels and treatment goal levels for infants after the transitional period, defined as the first 48 hours and, more recently, as 3 days post-birth [ 19 ] [ 20 ]. Much of the evidence to recommend higher target levels is based on follow-up studies of children with hyperinsulinism, a major cause of persistent hypoglycemia. The aim of this guideline is to improve the standard of, and to reduce regional variation in, the care of women with CKD in the UK who are pregnant, planning a pregnancy or post-partum.

Download results. Next page. Source Filter Source options. Filter by Date Filter results by date: From Enter date in the format yyyy-mm-dd. To Enter date in the format yyyy-mm-dd. Accredited Accredited. Add this result to my export selection. Source: Specialist Pharmacy Service Add filter. Type: Prescribing and Technical Information Add filter. Type: Systematic Reviews Add filter. Source: Canadian Paediatric Society Add filter. Type: Guidance Add filter. Conclusion: Hypotension is more common after maternal labetalol exposure, regardless of the dosage and route of administration.

The need for intubation and the presence of a PDA also play a role. Hypoglycemia is a very common finding in this population and is merely related to prematurity and independent of labetalol exposure as was the incidental occurrence of bradycardia.

These findings on the neonatal side effects of maternal labetalol treatment in preeclampsia underline the importance of frequent blood glucose and blood pressure measurements in the first days of life, especially in intubated preterm infants with a PDA. Abstract Objective: Labetalol is often used in severe preeclampsia PE.