Midline defects, e.g. central cleft palate and/or lip, hypotelorism or hypertelorism.

Features of recognizable syndrome, e.g. Beckwith–Wiedemann syndrome (macroglossia, ear lobe creases, exomphalos), Smith–Lemli–Opitz (microcephaly, second- and third-toe syndactyly, see below), Robinow syndrome.

Symmetrical growth retardation.

Micropenis (hypopituitarism, dysmorphic syndrome, see below).

Large-for-gestational-age, exomphalos, ear lobe creases (Beckwith–Wiedemann syndrome).

Hypoglycaemia (hormone insufficiency: e.g. cortisol, growth hormone (GH); hormone excess: i.e. insulin; metabolic abnormality).

Hypothermia (hypopituitarism; sepsis, which can be secondary to an underlying metabolic problem).

Prolonged jaundice (hypopituitarism).

Tetany or seizures (hypocalcaemia).

Consanguinity suggestive of an autosomal recessive problem.

Neonatal death suggestive of inherited disorder, e.g. metabolic disorder previously presenting as Escherichia coli septicaemia.

Underlying genetic defect

Hypopituitarism with or without septo-optic dysplasia (SOD), optic nerve hypoplasia (ONH)

Hypoadrenalism

Hypocalcaemia (hypoparathyroidism, e.g. DiGeorge syndrome)

Metabolic disorder

urgent management (Beckwith–Wiedemann, SOD, inborn errors of metabolism);

hormone balance in the newborn period (infants with Down's syndrome have an increased incidence of hypothyroidism).

Usually symptomatic hypoglycaemia which may result in convulsions.

Asymptomatic hypoglycaemia and prolonged jaundice.

Dysmorphic baby with midline anomalies.

Micropenis.

Anterior pituitary hormones

– Adrenocorticotrophic hormone (ACTH).

– Thyroid-stimulating hormone (TSH).

– Luteinizing hormone (LH) and follicle stimulating hormone (FSH).

– Growth hormone (GH).

– Prolactin.

Posterior pituitary hormone

– Antidiuretic hormone (ADH).

Anterior hypopituitarism:

– Symptoms and signs of hypoglycaemia (see Chapter 2).

– Other symptoms and signs include micropenis (see Chapter 6), hypothermia, conjugated hyperbilirubinaemia.

– Dysmorphic features such as midline defects and craniofacial anomalies (see Chapter 5).

– Ophthalmic examination may reveal optic nerve hypoplasia/dysplasia.

– Most have a birth length and weight below the mean (although usually within normal centiles).

– Some have severe growth failure, even at birth.

– Although some children may grow normally in early childhood, in others growth failure is more immediate.

Posterior hypopituitarism:

– May present with polyhydramnios.

– After birth, there may be signs of dehydration: excessive weight loss, irritability, fever, hypernatraemia, convulsions, or coma.

– Breast-fed babies may present later with failure to thrive, anorexia, vomiting, fever, constipation, or developmental delay.

Measurement of random free thyroxine (fT4) and thyroid-stimulating hormone (TSH, after the initial postnatal surge in the first 2 days of life) provides information about pituitary and thyroid function.

Baseline gonadotrophin levels (leuteinizing hormone, LH; follicle stimulation hormone, FSH) can also be informative, as they should be relatively high in the newborn period.

Measurement of cortisol and growth hormone (GH) at the time of hypoglycaemia can be helpful, but, unlike older infants and children, the normal neonate may produce a good GH response to hypoglycaemia, but a poor cortisol response.

Measurement of several (at least 3) random cortisol levels is useful, as cortisol is released in a pulsatile manner and may be low (e.g. 50 nmol/L) in normal infants if measured at the nadir. Timing is not important as diurnal variation does not appear for 8–12 weeks. All samples could be on the same day (and therefore the results could be reported together).

[…]

Neuroglycopaenic symptoms of hypoglycaemia include apnoea, hypotonia, jittering, irritability, lethargy, abnormal cry, feeding problems, convulsions, and coma.

Autonomic symptoms (pallor, sweating, tachypnoea) are generally not prominent in the newborn.

Macrosomia may be present in infants of diabetic mothers.

Macrosomia in the absence of a history of maternal diabetes suggests hyperinsulinism.

Macrosomia with magroglossia, organomegaly, exomphalos, or ear lobe creases suggests Beckwith–Wiedemann syndrome (approximately 80% demonstrate genotypic abnormalities of the distal region of chromosome 11p).

Midline defects, micropenis, and jaundice suggest hypopituitarism (see Chapter 7).

Babies can have low blood glucose levels and be completely asymptomatic.

Asymptomatic healthy term babies of normal birth weight (9th to 91st centiles) do not require blood sugar measurements.

Symptomatic hypoglycaemia in a term baby is always pathological until proved otherwise.

Preterm or intrauterine growth retardation: lack of glycogen stores, immature enzymes involved in glucose homoeostasis, inappropriately high insulin levels.

History of birth depression: lack of glycogen stores due to utilization.

Infants of diabetic mothers, large-for-dates babies, babies with Beckwith–Wiedemann syndrome, babies with rhesus disease: excessive insulin secretion.

Polycythaemia: excessive metabolism of glucose by erythrocytes.

Congenital heart disease, sepsis, hypothermia: excessive glucose demands.

[…]

widened QRS complexes or tall, tented T-waves on ECG;

dysrhythmias, such as ventricular tachycardia or fibrillation.

Is the biochemistry result true? How was the sample collected, and could it have been haemolysed? Repeat the sample as a matter of urgency.

How many hours/days old is the infant? (Mild hyperkalaemia is not uncommon in extremely low birth weight (ELBW) infants in the first few days of life).

Review history for antecedents of renal impairment (asphyxia and birth trauma).

Is there a family history of renal problems? (e.g. polycystic kidneys).

Look for contractures (suggestive of reduced fetal urine output causing oligohydramnios).

Look for genital pigmentation (see Chapter 11) or ambiguity (see Chapters 8 and 10) suggestive of congenital adrenal hyperplasia.

Spurious (haemolysed blood sample).

Renal impairment (including structural defects, e.g. urethral valves, dysplastic kidneys, and renal vascular accidents).

Tissue damage (especially in immature infants with extensive bruising).

Immaturity of renal potassium excreting capacity in ELBW infants.

Acidosis (causing shift of potassium out of cells into extracellular fluid).

[…]

This is usually secondary to Hashimoto's thyroiditis and the mother may be producing thyroid inhibiting or rarely thyroid stimulating antibodies so the baby may develop transient hypo or very rarely hyperthyroidism.

If the maternal TSH receptor antibody titre is known, the risk to the baby can be assessed. TSH receptor antibody titres do not differentiate stimulating from blocking antibodies and both may co-exist (high titres will increase risk of hypo or hyperthyroidism). The TRH receptor antibody results differ depending on laboratory methods, and so normal levels will need to be assessed with reference to the laboratory norms.

If maternal TSH receptor antibody titre is normal, a Guthrie card TSH will suffice.

If the TSH receptor antibody titre is elevated or unknown, review the baby at 10 days to 2 weeks and measure TSH and fT4.

As risk of postnatal hypo or hyperthyroidism in baby is small, some would advocate no investigations are required.

[…]

Hypoglycaemia in infants of diabetic mothers should be anticipated and all infants should have early and regular glucose measurements until these are stable.

Hypoglycaemia may be asymptomatic or symptomatic.

Expectant management in all infants of diabetic mothers.

Early enteral feeds.

Regular (1–2 hourly) blood sugar measurements for first 12 h.

Blood glucose level.

Other investigations for hypoglycaemia are not usually required unless hypoglycaemia is persistent.

Calcium and magnesium levels are required in symptomatic babies as symptoms overlap.

Haematocrit should be assessed if the baby appears plethoric or blood sugar is difficult to control (dilutional exchange transfusion may be required if the baby is polycythaemic).

If able to tolerate enteral feeds, increase the volume and frequency of the feeds.

If unable to tolerate feeds, commence an intravenous (IV) infusion and titrate the quantity of glucose to maintain the blood glucose concentration >2.6 mmol/L. Use a higher concentration of glucose via a central line (silastic long-line or umbilical venous catheter) rather than excess volumes of 10% dextrose as the latter is likely to result in fluid overload and hyponatraemia.

If IV access is difficult, intramuscular glucagon (100–200 µg/kg/dose) or buccal hypostop (40% glucose polymer, 1 mL/kg) may restore euglycaemia and buy time to achieve vascular access.

[…]

Incidental finding on blood test.

Collapse (see Chapter 13).

Pigmented scrotum (see Chapter 11) or ambiguous genitalia (see Chapters 8 and 10) suggesting congenital adrenal hyperplasia.

Plasma potassium measurement.

Palpable kidney, or mass (renal vein thrombosis, adrenal haemorrhage).

Family history of renal problems.

Blood pressure (liable to be raised in renal rather than adrenal disorders).

Postnatal age (low glomerular filtration rate in the first few days of life).

Gestational age (renal immaturity resulting in salt loss).

latrogenic: This is the commonest cause, and may start before birth, i.e. secondary to excess maternal intravenous (IV) fluid administration.

Renal failure.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) (intracranial pathology: asphyxia, meningitis; intrathoracic pathology: pneumothorax).

Immaturity (extreme preterm infant usually from the end of first week of life).

Congenital adrenal hyperplasia (usually days 4–10).

Congenital adrenal hypoplasia.

Renal impairment, e.g. polyuric phase of acute tubular necrosis (ATN), congenital nephrotic syndrome, Bartter syndrome (hyperprostaglandin E syndrome, associated with life-threatening hypokalaemia). Congenital renal abnormality (there may be a history of polyhydramnios secondary to excessive urine output in utero).

[…]