Should We Screen Preterm Infants for Nephrocalcinosis?

Table 1. Criterion for screening and appraisal based on available evidence.
Criteria for screening	Judgment: criteria met?			Level of evidence
Criteria for screening	Yes	Somewhat	No	1	2	3	4	5
The natural history of nephrocalcinosis is known and it is an important health problem?		×		×	×
Is there a suitable test to diagnose nephrocalcinosis?		×				×	×
Is there effective evidence-based treatment(s) for nephrocalcinosis? (e.g., citrate therapy for prevention)			×	×
Is there a recognizable latent or early symptomatic stage and does treatment in this phase lead to better outcomes?			×	×	×
Are there screening programs for nephrocalcinosis?	×							×

Table 2. Oxford Centre for Evidence-Based Medicine level of evidence guidelines.
Level	Types of studies
1	Systematic review of randomized controlled trials, inception cohort studies, level 1 diagnostic studies, or prospective cohort studies. Individual randomized controlled trial (with narrow confidence interval), cohort study with greater than 80% follow-up, validating cohort study with good reference standards, prospective cohort study with good follow-up.
2	Systematic review of cohort studies, retrospective cohort studies, untreated control groups in randomized controlled trials, or level greater than 2 diagnostic studies. Individual cohort study with less than 80% follow-up, retrospective cohort study or follow-up of untreated control patients in a randomized controlled trial, exploratory cohort study with good reference standards. Outcome research, ecological studies.
3	Systematic review of case–control studies, or nonconsecutive study. Individual case–control study, nonconsecutive study or without consistently applied reference standards, or very limited population.
4	Case-series (and poor quality cohort and case–control studies or prognostic cohort studies), case–control study, poor or nonindependent reference standard.
5	Expert opinion without explicit critical appraisal, or based on physiology, bench research or 'first principle'.

Adapted with permission from ^[102].

What is the natural history of nephrocalcinosis in premature infants & is it an important health problem?

Most cases of nephrocalcinosis will resolve spontaneously with time.
The etiology of nephrocalcinosis is multifactorial and includes low gestational age and low birth weight.
It is not clear whether renal dysfunction on follow-up reflects prematurity rather than morbidity associated with nephrocalcinosis.
There are significant gaps in our understanding and the evidence equivocal to determine whether nephrocalcinosis is an important health problem in the long-term.

How is nephrocalcinosis diagnosed in preterm infants?

At present, no gold-standard exists for diagnosing nephrocalcinosis.
Despite improvements in technology, ultrasound has been criticized for its lack of specificity in visualizing the parenchymal changes; hence, it may not be the ideal test.

Are there effective evidence-based treatments for nephrocalcinosis?

In a small randomized, controlled trial, citrate therapy was not an effective preventative therapy for nephrocalcinosis in premature infants.
Extracorporeal shock wave lithotripsy has been effective in treating cases with persistent nephrocalcinosis; however, long-term outcomes are unknown.

Is there a recognizable latent or early symptomatic stage & does treatment in this phase lead to better health outcomes?

There is a paucity of literature to determine whether the calcium:creatinine ratio is a recognizable latent or early symptomatic stage.

Are there screening programs for nephrocalcinosis & what has been their experience?

A nephrocalcinosis screening programme was implemented in 2003 in the Neonatal Intensive Care Unit of National Women's Health in Auckland, New Zealand.
Anecdotal reports indicate the screening programme was a source of distress and anxiety for parents given that nephrocalcinosis may resolve spontaneously and as such may not be a problem.

Should We Screen Preterm Infants for Nephrocalcinosis? An Evidence-based Decision