GH Deficiency diagnosis feasible through newborn blood-spot screening cards

medwireNews: Severe growth hormone deficiency (GHD) can be detected with high accuracy using newborn screening cards, suggest researchers who recommend a diagnostic GH cutoff of less than 7 µg/L.

Lead investigator Gerhard Binder, from the University Children’s Hospital in Tübingen, Germany, and colleagues collated information from 61 questionnaires completed by 22 physicians who had sent newborn screening cards for GH assessment between 2010 and 2018, as well as cards for healthy infants born between 34.0 and 37.9 weeks in 2018 and 2019.

The blood was sampled on days 2 or 3 of postnatal life and placed on the cards  The GH content of punched-out paper discs from the cards was determined using a highly sensitive GH ELISA method.

Of the 43 ill newborns with recurrent hypoglycaemia, 25 were diagnosed with severe neonatal GHD, almost a third (32%) of whom were female. These newborns had normal birth length and head circumference, and a birth weight “only mildly” below the reference, the researchers say.

Specifically, cerebral magnetic resonance imaging (cMRI) showed pituitary malformations in 21 of the 25 GHD newborns, namely ectopia of the neurohypophysis (n=17), septum pellucidum agenesis and optic nerve hypoplasia (n=2) and severe pituitary gland hypoplasia or aplasia (n=2). Additional pituitary hormone deficiencies were also diagnosed in the newborn or early infant phase – adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) and/or gonadotropin deficiency.

A further four ill newborns with recurrent hypoglycaemia had deficiencies in both ACTH and TSH without cMRI findings, alongside micropenis (n=2), unmeasurable levels of serum cortisol (n=1) or childhood hypopituitarism (n=1).

Data for a further 36 ill newborns without severe GHD were also recorded, half of whom had recurrent hypoglycaemia. A quarter of this group were born before 36 weeks’ gestation, 26% were female, and their length, head circumference and weight at birth did not significantly differ from newborns with severe GHD born after 36 weeks.

In addition, the team collated information from 151 preterm newborns (34.0–36.9 weeks) and 130 very young term newborns (37.0–37.9 weeks).

The 95% reference range of GH levels for preterm newborns was 7.6–47.1 µg/L and a median 20.3 µg/L, and “[g]estational age showed a weak negative correlation with the GH concentration”, the researchers explain, so that the GH in preterm newborns was “slightly higher” than term newborns (median 17.5 µg/L).

GH content of the screening card was not influenced by sex, maternal smoking during pregnancy or use of continuous positive airway pressure.

Receiver operating characteristic curve analysis using data from 20 term newborns with severe GHD and 313 healthy term newborns determined that 7 µg/L was the most accurate cutoff for severe GHD, with 90.0% sensitivity and 98.7% specificity.

“It must be stressed that the measured GH content of newborn screening cards has to be adjusted for storage time, and storage should be performed at 6°C and not at room temperature”, Binder and team say in Clinical Endocrinology.

“The low GH content of the newborn screening card is a highly sensitive parameter for the detection of severe neonatal GHD, but it is unlikely that classical idiopathic GHD of childhood can already be detected shortly after birth”, they add.

The team also emphasises that “laboratory methods cannot supplant clinical examination and imaging” so that a GH screening card result of less than 7 µg/L only “confirms the clinically tentative diagnosis of severe GHD in term newborns” based on the presence of other pituitary hormone deficiencies or pituitary malformation on cMRI.

“The newborn screening card is a valuable source for the confirmation of GH deficiency in the newborn”, the researchers conclude.

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

Clin Endocrinol 2020; doi:10.1111/cen.14264
Martin Savage
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