Case #1
History (including chief complaint, history of present illness and relevant past and family medical history): A 650 g female infant was born at a referring hospital at a gestational age of 23w6d via c-section with breech presentation. Apgar scores 6 and 7 at 1 and 5 minutes of life. The mother is a 32 -year-old G6P2 with normal prenatal care and screening labs. Her past prenatal course was significant for three preterm deliveries. She presented with preterm labor at 23w1d. During labor, she received magnesium sulfate, indomethacin, antenatal steroids, vancomycin, and fluconazole. The infant's initial course was remarkable for respiratory distress syndrome, left pneumothorax, pulmonary hemorrhage, disseminated intravascular coagulopathy, large patent ductus arteriosus, Grade III-IV intraventricular hemorrhage (IVH), adrenal and renal insufficiency. At 30 days of life, the infant was transferred to our facility for intraventricular reservoir placement. At the time of transfer, the infant demonstrated polyuria (12 ml/kg/hr) and a gradual increase in serum sodium levels necessitating an increase in total fluids to 240 ml/kg/day [Figure1].
Physical examination findings (including vital signs): Vitals stable. Physical exam: extreme prematurity. Intubated and supported on an oscillator ventilator.
Laboratory or Diagnostic imaging or Procedures: High serum sodium (162 mmol/l), high serum osmolality (329 mosm/kg), and low urine osmolality (155 mosm/kg) with a relatively low plasma copeptin level (<14 pmol/L) consistent with central diabetes insipidus (CDI). The infant was started on 1 mcg twice daily intravenous formulation of DDAVP via oral route [Figure 1]. The dose was titrated (range 1 to 1.2 mcg) with close monitoring of serum sodium and urine output. On DOL 135, DDAVP was weaned off as serum sodium and urine output normalized with a total duration of therapy of 101 days.
Final Diagnosis: Central DI in the setting of Grade III-IV IVH
Case #2
History (including chief complaint, history of present illness and relevant past and family medical history): A 3600g male infant born at 39w2d of gestation at a referral hospital via emergent c-section for non-reassuring fetal heart tracing. Apgar 0, 0, and 1 at 1,5 and 10 minutes of life. The mother is a 29-year-old G4P2 with normal prenatal care and screening labs. The infant's initial course was significant was moderate to severe hypoxic-ischemic encephalopathy (HIE) and meconium aspiration requiring delivery room intubation volume expansion with normal saline and packed red blood cell transfusion and epinephrine. The infant was transferred to our facility for therapeutic hypothermia.
Physical examination findings (including vital signs): Vitals stable. Physical exam: a full-term infant with neurological findings consistent with HIE. Intubated and supported on a conventional ventilator.
Laboratory or Diagnostic imaging or Procedures: Neurological evaluation confirmed profound brain damage documented by EEG, Brain MRI, and angiogram. On DOL 5, the infant had evidence of central hypothyroidism thus IV levothyroxine 20 mcg was started. On DOL 8-9, infant had polyuria (7 ml/kg/day), rising serum sodium (150-155 mmol/L) and low urine osmolality (200 mosm/kg) consistent with CDI. The infant was started on 0.1 mcg DDAVP via subcutaneous route [Figure 2]. On DOL 13, developed hyponatremia to 124 mmol/L requiring discontinuation of DDAVP. The next day, DDAVP was resumed at a smaller dose of 0.04 mcg subcutaneously once daily for increased serum sodium levels and urine output which the infant tolerated well. No further monitoring was done since parents decided to withdraw support due to poor neurological outcome.
Final Diagnosis: Central DI in the setting of severe HIE
Discussion: We report two clinical cases of CDI who were successfully managed with oral or subcutaneous DDAVP. CDI is extremely uncommon during the neonatal period. Causes of CDI are idiopathic, intraventricular hemorrhage (IVH), asphyxia, CNS infection, and congenital CNS malformations. Different preparations of desmopressin (DDAVP) are available: oral, parenteral, and intranasal. Clinical use of DDAVP especially for VLBW infants is challenging: 1. Low doses needed for low body weights. 2. High variability in dose and duration of effect in different formulations. 3. Triphasic response of antidiuretic hormone secretion after injury and fluctuations in hormonal secretion in the initial phases. 4. Increased risk of fluid overload which can cause wide fluctuation in sodium levels. The literature reports wide variation in the use of DDAVP with no specific guidelines on dose and route of administration. In 2019, Thakore et al published a case report of a VLBW infant with grade III-IV IVH who was successfully treated with subcutaneous DDAVP. Initial low dose administration and subsequent titration of DDAVP can be an effective treatment in infants with CDI. A prospective multicenter study to evaluate the management plan using different formulations of DDAVP in neonates is needed.
