Hydrolysed formula is a risk factor for vitamin K deficiency in infants with unrecognised cholestasis.
OBJECTIVE
Vitamin K deficiency (VKD) may cause life-threatening haemorrhages, especially in breast-fed infants with unrecognised cholestasis. Interestingly, hypoallergenic formulas appear overrepresented in reported cases of VKD bleeding (VKDB) in formula-fed infants. We therefore assessed whether the risk of VKD in formula-fed infants with cholestasis is associated with hypoallergenic formulas.


METHODS
Infants born in the Netherlands between January 1991 and December 2006 with cholestatic jaundice due to biliary atresia (BA) or to α-1-antitrypsin deficiency (A1ATD) were identified in the Netherlands Study Group for Biliary Atresia Registry and the A1ATD registry, respectively. The relative risk (RR) of VKDB in patients with BA or A1ATD was calculated for different formula types. The influence of prior or ongoing breast-feeding on the RR of VKDB was also assessed.


RESULTS
A total of 179 infants with either BA (139) or A1ATD (40) were included. One hundred eighteen infants were formula fed; 8 presented with VKD. Six of these 8 infants (75%) received hypoallergenic formula (whey-based hydrolysate in 4). One infant on whey-based hydrolysed formula presented with VKDB. Risk factor analysis revealed that infants receiving hydrolysed, especially whey-based, formula, had a strongly increased risk of VKD (RR 25.0 [6.4-97.2], P < 0.001)) compared with infants receiving regular formula. Prior or ongoing breast-feeding was not significantly associated with VKD.


CONCLUSIONS
Infants with cholestasis receiving (whey-based) hydrolysed formula are at increased risk of developing VKD, compared with infants receiving regular formula. Because VKD may lead to serious haemorrhages, infants receiving whey-based hydrolysed formulas may need additional vitamin K supplementation.
Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands. p.vanhasselt@umcutrecht.nl
P M
PM
van Hasselt
W
W
de Vries
E
E
de Vries
K
K
Kok
E C M
EC
Cranenburg
T J
TJ
de Koning
L J
LJ
Schurgers
H J
HJ
Verkade
R H J
RH
Houwen
D001656:Biliary Atresia / Q000150:complications; D002779:Cholestasis / Q000150:complications*; D005512:Food Hypersensitivity / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D007223:Infant; D041943:Infant Formula / Q000737:chemistry*; D008894:Milk Proteins / Q000009:adverse effects*; D009426:Netherlands / Q000453:epidemiology; D011492:Protein Hydrolysates / Q000009:adverse effects*; D012307:Risk Factors; D014813:Vitamin K Deficiency / Q000453:epidemiology / Q000209:etiology*; D006475:Vitamin K Deficiency Bleeding / Q000453:epidemiology / Q000209:etiology*; D000067816:Whey Proteins; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications
D008894:Milk Proteins; D011492:Protein Hydrolysates; D000067816:Whey Proteins