Inpatient Growth in Infants Requiring Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome

Abstract

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short-acting opioids (SAOs), long-acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed-effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z-score of -0.19 at birth and decreased to a median of -0.72 at discharge. Exposure to SAO was associated with an increase in Z-scores nearing discharge across all growth parameters (Z-score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z-scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z-score for weight trends. Male infants had a decrease in Z-scores for weight (male -0.96, female -0.59, interaction p = 0.06) and length (male -1.17, female -0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z-scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z-scores for length and occipital frontal circumference (OFC).

Keywords: Z-score; growth trajectories; head circumference; length; neonatal opioid withdrawal syndrome; opioids; weight.

Figure 1

NOWS infant growth trajectories. (a) SAO associated with improved weight Z-score throughout hospitalization. (b, c) Polysubstance exposure is associated with the lowest Z-scores for length and head circumference (OFC) throughout hospitalization. (d) Adjunctive clonidine treatment had improved weight Z-score trends. (e, f) Clonidine had no significant impact on length or head circumference (OFC) throughout hospitalization.

Figure 2

NOWS infant feeding volume and caloric intake. (a, b) Overall feeding volumes and caloric intake by day. (c, d) Feeding volumes and caloric intake were not different based on prenatal exposures. (e, f) Feeding volumes and caloric intake were not different based on pharmacologic treatment.

Figure 3

NOWS infant growth trajectories by sex. Graph shows male infants with lower Z-scores for (a) weight and (b) length. Both male and female infants showed similar trend in Z-score for (c) head circumference (OFC).

Figure 4

NOWS infant growth trajectories by any maternal breast milk provided. Graphs (a–c) show improved growth trajectories for infants with any breast milk exposure, with length being statistically significant (p = 0.04).