From the Guidelines
Elevated alkaline phosphatase (ALP) in newborns is typically a normal finding and usually doesn't require treatment, with levels gradually decreasing over the first few months of life. Newborns naturally have ALP levels 2-3 times higher than adult reference ranges, with values commonly between 150-400 U/L, due to increased bone growth and osteoblast activity during rapid skeletal development, as well as the contribution of the placental isoenzyme immediately after birth 1. However, if ALP is significantly elevated (>500 U/L), additional evaluation may be warranted to rule out conditions like rickets, liver disorders, or certain genetic conditions, such as neonatal cholestasis, which can be caused by genetic and/or metabolic causes in about 25% to 30% of affected patients 1.
In cases of significantly elevated ALP, a pediatrician should order additional tests, including:
- Calcium, phosphorus, and vitamin D levels to assess bone health
- Liver function tests to evaluate for liver disorders
- Possibly bone imaging to rule out conditions like rickets or other bone diseases
- Measurements of GGT to indicate whether pathologically elevated ALP is of hepatic or nonhepatic origin 1
Most cases of mildly elevated ALP in otherwise healthy newborns require only observation with follow-up testing in 1-3 months to confirm normalization. Parents should ensure adequate vitamin D intake, either through supplements (400 IU daily) or sufficient sun exposure, as this supports proper bone mineralization during this period of rapid growth. It is essential to note that concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis, and imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis 1.
From the Research
Elevated Alkaline Phosphatase in Newborns
- Elevated alkaline phosphatase (ALP) in newborns can be caused by various factors, including benign transient hyperphosphatasemia, a condition characterized by greatly increased serum ALP without laboratory or clinical evidence of underlying bone or liver disease 2.
- This condition is usually identified incidentally during routine blood testing and resolves spontaneously, with no intervention 2.
- In some cases, elevated ALP can be due to parenteral nutrition-associated liver disease (PNALD) or metabolic bone disease (MBD) 3.
- However, studies have shown that elevated ALP in infants with PNALD is predominantly of bone rather than hepatic origin 3.
Diagnosis and Management
- When benign transient hyperphosphatasemia is suspected, a "wait and see" approach is optimal in order to avoid unnecessary investigations and parental anxiety 2, 4.
- An algorithm can be utilized as a guide in a primary care setting to arrive at the diagnosis of transient hyperphosphatasemia and avoid further tests or referrals 4.
- In cases where elevated ALP is suspected to be due to bone disease, further investigation and management may be necessary, including monitoring of vitamin D levels and adjustment of calcium and phosphate intake 5, 6.
Clinical Implications
- High alkaline phosphatase activity in preterm neonates has been associated with slower growth rate and reduced attained length at 9 and 18 months post term 6.
- This suggests that even silent early bone disease may interfere with the control of subsequent linear growth, emphasizing the importance of providing preterm infants with adequate substrate for bone mineralization 6.