Mother With Diabetes Mellitus and Infant With Hypertrophic Obstructive Cardiomyopathy
Milrinone Precluded Need for Extracorporeal Membrane Oxygenation
A female infant was born at 38 weeks to a mother with gestational diabetes mellitus (Hemoglobin A1c 6.7%) via an elective C-section for fetal macrosomia (birth weight 5560 g; >99.9%). The prenatal ultrasound was only significant for a large for gestational age fetus without any structural cardiac anomalies. Within the first 2 hours, the infant developed hypoglycemia and required respiratory support (nasal cannula) for respiratory distress and hypoxemia. Neonatal hyperinsulinemia (297 uIU/mL [1.9–23 uIU/mL]) confirmed maternal gestational diabetes mellitus as the cause of the hypoglycemia (growth hormone and cortisol levels were normal for age). The infant was electively intubated for worsening respiratory status. A transthoracic echocardiogram showed severe biventricular hypertrophy, especially the interventricular septum (1.2 cm at the end of systole; z score=4.55) causing left ventricular outflow tract (LVOT) obstruction with a gradient of 22 mm Hg (Figure 1; Movies I and II in the Data Supplement). The left ventricular cavity size was remarkably diminished. A color Doppler showed a bidirectional shunting across a large patent ductus arteriosus and a moderate size secundum atrial septal defect. The estimated right ventricular pressure was elevated (>69 mm Hg) based on the tricuspid jet velocity (4.1 m/s; Figure 2). The infant continued to have worsening hypoxia with increasing oxygenation indices (Figure 3) despite being on adequate ventilator support with inhaled nitric oxide and inhaled epoprostenol. Dopamine and dobutamine infusions were started on the third day of life for worsening hypotension without any significant improvement (serum lactate 3.7 mmol/L [0.31–2.0 mmol/L]) and hence were discontinued. Intravenous propranolol was also started without significant improvement in hemodynamics. Multidisciplinary teams were involved in anticipation of extracorporeal membrane oxygenation. Milrinone infusion (0.25 μg/kg per minute and titrated up to 0.75 μg/kg per minute) was then added 24 hours after the initiation of propranolol. Within a few hours, the mean arterial pressures and oxygenation indices started to improve (Figure 3). Milrinone infusion was slowly weaned off, and the infant was extubated in 10 days. The infant was discharged from the Neonatal Intensive Care Unit 2 weeks later, on oral propranolol, which was subsequently discontinued in 3 months with a normal estimated PA pressure (≈20 mm Hg).
Poor maternal glycemic control is associated with neonatal biventricular hypertrophy that may occasionally be associated with LVOT obstruction because of marked interventricular septal hypertrophy.1 Five percent to 10% of these infants may develop impaired cardiac output because of LVOT obstruction and diminished ventricular volumes.2 Spontaneous regression of hypertrophy usually occurs as plasma insulin concentrations normalize within the first few months of life (follow-up insulin level at 1 month was 5.2 uIU/mL; Figure 4; Movie III in the Data Supplement). Typical management of an infant of diabetic mother with LVOT obstruction and low cardiac output includes maintaining adequate intravascular volume and β-adrenergic blockade. β-blockade reduces the heart rate which will decrease the myocardial oxygen demand and improve coronary perfusion. They also reduce the myocardial contractility and hence LVOT obstruction, if present. Milrinone has both inotropic and vasodilatory effects. It enhances myocardial contractility with minimal chronotropic effects and contributes to an increase in cardiac output with a reduction in pulmonary capillary wedge pressure and vascular resistance. Along with these effects, milrinone has been shown to directly improve left ventricular relaxation and diastolic function (lusitropic effect).3 In the case of severe hemodynamic instability, further support such as extracorporeal membrane oxygenation may be warranted.1 Goldberg et al4 described a similar case of an infant of diabetic mother with concomitant persistent pulmonary hypertension of the newborn who ultimately needed extracorporeal membrane oxygenation. However, medical management in their case did not include the use of milrinone.
We suggest that the addition of milrinone to β-blockade may be beneficial in this subset of patients and may preclude the need for extracorporeal membrane oxygenation. This may need to be supported by further studies.
We acknowledge the contribution of Yasmine Khairandish and Margaret Galloway toward obtaining, editing, and formatting the echocardiogram movie clips included with this article.
The Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.117.006809/-/DC1.
- © 2017 American Heart Association, Inc.
- Monrad ES,
- McKay RG,
- Baim DS,
- Colucci WS,
- Fifer MA,
- Heller GV,
- Royal HD,
- Grossman W
- Goldberg JF,
- Mery CM,
- Griffiths PS,
- Parekh DR,
- Welty SE,
- Bronicki RA,
- Molossi S