Although preterm infants often experience desaturation or bradycardia during oral feeding, specific guidelines for its management are lacking.
This study aimed to investigate the effects of a commercial thickened formula (TF) on oxygen saturation and heart rate stabilization during oral feeding in preterm infants.
This retrospective study included 122 infants born at a median (interquartile range [IQR]) 31+6 weeks (29+4 −34+6 weeks) of gestation weighing 1,725 g (1,353–2,620 g) and fed commercial cornstarch-containing TF due to feeding-associated desaturation or bradycardia. We excluded infants fed TF to treat symptomatic regurgitation. Desaturation and bradycardia events were compared between 3 days prior to the change and 3 days after the change to TF. Desaturation and bradycardia were defined as SpO2 <85% and heart rate <100 beats/min during or immediately after oral bottle feeding, respectively.
The median (IQR) postmenstrual age and weight were 36+1 weeks (34+6–38+0 weeks) and 2,395 g (2,160–2,780 g), respectively, at the time of change to TF. The frequency of desaturation significantly decreased after TF feeding (median [IQR]: 2.3 [1.3–3.3] events/day vs. 0.3 [0–1.7] events/day,
TF feeding significantly reduces oral feeding-associated oxygen desaturation and bradycardia in preterm infants. TF may be useful for stabilizing oxygen saturation and heart rate among preterm infants with difficulties in oral feeding.
Competent oral feeding in preterm infants is essential for hospital discharge readiness. The overall prevalence of problematic neonatal feeding is 25%–40%, which increases as the infant is more premature [
A thickened formula (TF) refers to any modified formula with the addition of thickening agents to increase viscosity aiming to decrease regurgitation [
This retrospective study was conducted in the NICU of Inha University Hospital, Incheon, Korea. Among infants admitted to the NICU from October 2018 to December 2020, preterm infants born before 37 weeks of gestation and fed a commercial TF (Novalac AR, Novalac United Pharmaceuticals, Paris, France) because of desaturation or bradycardia during or immediately after oral feeding were included. We excluded infants who were fed TF due to symptomatic regurgitation without desaturation or bradycardia. Also, infants who required any medication for apnea or symptomatic heart failure were excluded. The study was approved by the Institutional Review Board of Inha University Hospital (IRB No. 2022–05–031). The requirement for informed consent was waived by the board due to the retrospective nature of this study.
Neonatal data were collected from medical records. A percutaneous pulse oximeter sensor (Nellcor N-200; Nellor Inc., Hayward, CA, USA) was used to measure oxygen saturation (SpO2) and heart rate. Flexible skin electrocardiogram electrodes (Ambu BlueSensor BRS, Ambu Inc., Ballerup, Denmark) were used to monitor heart rate. Desaturation and bradycardia were defined as SpO2 <85% and heart rate <100 beats/min during or immediately after oral bottle feeding, respectively. The number of desaturation and bradycardia events was compared between 3 days before and after the change of milk to TF. Comorbidities and the type of milk before changing to TF were investigated. Respiratory distress syndrome was diagnosed by the attending physician based on respiratory symptoms, chest radiography, and blood gas analysis. Bronchopulmonary dysplasia (BPD) was defined as oxygen dependency at a postmenstrual age of 36 weeks with oxygen treatment for at least the first 28 days of life. Subgroup analyses were performed for infants having BPD. For safety evaluation, we collected data on weight gain, stool frequency, diarrhea, and serum electrolytes during the 5 days before and after TF feeding. In addition, parental compliance with continued TF feeding at the 1-month follow-up after discharge was also investigated.
Continuous data were assessed for normality using the ShapiroWilk test, and a paired t test or Wilcoxon signed-rank test was used to compare the data before and after formula change. A statistical analysis was performed using IBM SPSS Statistics ver. 27.0 (IBM Co., Armonk, NY, USA). Variables were expressed as median (interquartile range [IQR]) or numbers (%). A
A total of 122 preterm infants were included in this study. The median (IQR) gestational age and birth weight were 31+6 weeks (29+4−34+6 weeks) and 1,725 g (1,353–2,620 g), respectively. Respiratory distress syndrome and BPD were diagnosed in 29 (23.8%) and 16 patients (13.1%), respectively. Twelve infants (9.8%) experienced intraventricular hemorrhage (grade ≥2) and 2 of them had a history of seizures. At the time of change to TF, only 1 infant was administered one anticonvulsant with a seizure-free state. Eighty-one infants (66.4%) were breastfed wholly or partially, and 41 infants (33.6%) received only formula milk (
The median (IQR) postnatal age, postmenstrual age, and body weight at the time of change to TF were 22 days (6−38 days), 36+1 weeks (34+6–38+0 weeks), and 2,395 g (2,160–2,780 g), respectively. After the change to TF, median (IQR) bradycardia decreased from 0.3 event/day (0–1 event/day) to 0 event/day (0–0.7 event/day) (
The median (IQR) weight gain for 5 days after the change to TF was 28.8 g (0.7–42.5 g) per day and did not differ from that of 5 days before TF feeding (
This study showed that the number of desaturation and bradycardia events significantly decreased with TF feeding, suggesting that TFs can be helpful for preterm infants having feeding desaturation and bradycardia. As there are no specific guidelines for infants with feeding problems, our results are meaningful for building clinical practice evidence. Although the mechanisms involved in the improvement of feeding desaturation or bradycardia were not investigated in this study, several possibilities can be assumed.
First, TFs may be effective in stabilizing SpO2 and heart rate through reducing the frequency or amount of hidden or combined gastroesophageal reflux. Gastroesophageal reflux is very common in infants, affecting 50%–85% of infants at least once a day [
Second, TFs may be effective in stabilizing SpO2 and heart rate through enhancing coordination of the suck-swallow-breathe cycle in preterm infants. Independent oral feeding requires sophisticated control of numerous phases, including sucking, swallowing, breathing, maturation of respiratory function to endure short pauses of ventilation during swallowing, and coordination of the suck-swallow-breathe cycle [
Preterm infants with BPD are at a higher risk of developing feeding problems and issues with breathing control during feeding [
Various TFs are available on the market. Among these, cornstarch-containing TFs are widely used and considered safe for infants less than 6 months of age [
This study has several limitations. There was no control group and the long-term effects of TFs were not investigated. Additionally, this was a retrospective study. However, we observed specific changes in the desaturation and bradycardia associated with oral feeding before and after TF feeding in a relatively large group of preterm infants (n=122). Despite the lack of clear guidelines for the use of TFs, a Canadian study reported that 71% of clinicians recommended TFs containing cornstarch instead of thickeners in infants with feeding difficulties [
In this study, we observed that TF decreased the frequency of desaturation and bradycardia during oral feeding in preterm infants. To our knowledge, no previous study has evaluated the effect of TFs on the improvement in feeding desaturation and bradycardia in preterm infants. TFs may help stabilize SpO2 and heart rate in newborns with hidden gastroesophageal regurgitation or difficulty in coordinating sucking, swallowing, and breathing. Constipation should be monitored in TF-fed infants and appropriate medications could be administered if necessary.
Supplementary Table 1 can be found via
Comparison before and after feeding with a thickened formula (TF) according to previous type of milk
No potential conflict of interest relevant to this article was reported.
This work was supported by a 2022 Inha University Hospital Research Grant.
Conceptualization: JL; Formal Analysis: GL, JL; Investigation: GL, JL; Methodology: GL, JL, GWJ; Project Administration: JL, YHJ; Writing – Original Draft: GL; Writing – Review & Editing: JL, GWJ, YHJ
Box plots of frequency of bradycardia and desaturation before versus after the change to a thickened formula. The median (interquartile range [IQR]) frequency of bradycardia decreased from 0.3 (0–1) events/day to 0 (0–0.7) events/day (
Representative vital sign trend showing improved bradycardia and desaturation after change to a thickened formula.
Patients’ baseline characteristics (N=122)
Variable | Value |
---|---|
Gestational age (wk) | 31+6 (29+4–34+6) |
Birth weight (g) | 1,725 (1,353–2,620) |
Respiratory distress syndrome | 29 (23.8) |
Bronchopulmonary dysplasia | 16 (13.1) |
Intraventricular hemorrhage, grade 2 or higher | 12 (9.8) |
Type of milk before thickened formula | |
Breast milk | 29 (23.8) |
Breast milk + formula | 52 (42.6) |
Formula | 41 (33.6) |
Postnatal age at change to thickened formula feeding (day) | 22 (6 38) |
Postmenstrual age at change to thickened formula feeding (wk) | 36+1 (34+6–38+0) |
Body weight at change to thickened formula feeding(day) | 2,395 (2,160–2,780) |
Values are presented as median (interquartile range) or number (%).
Comparison of variables before and after feeding of a thickened formula (TF) (N=122)
Variable | Before TF | After TF | |
---|---|---|---|
Bradycardia |
0.3 (0–1) | 0 (0–0.7) | 0.006 |
Desaturation |
2.3 (1.3–3.3) | 0.3 (0–1.7) | <0.001 |
Serum sodium (mEq/L) | 138 (137–140) | 138 (136–139) | 0.207 |
Serum potassium (mEq/L) | 4.6 (4.2–5.0) | 4.7 (4.4–5.0) | 0.195 |
Serum glucose (mg/dL) | 89 (81–103) | 89 (78–98) | 0.152 |
Weight gain (g/day) | 20.0 (7.5–34.4) | 28.8 (0.7–42.5) | 0.092 |
Defecation (stool number/day) | 3 (2–4.6) | 2.7 (2–3.5) | 0.037 |
Values are presented as median (interquartile range).
Heart rate <100 beats/min during or immediately after oral bottle feeding.
SpO2 <85% during or immediately after oral bottle feeding.
Comparison of variables before and after feeding of a thickened formula (TF) among infants with bronchopulmonary dysplasia (N=16)
Variable | Before TF | After TF | |
---|---|---|---|
Bradycardia |
0.5 (0–1.0) | 0.3 (0–0.9) | 0.637 |
Desaturation |
2.3 (1.8–3.8) | 0.5 (0–1.5) | 0.042 |
Serum sodium (mEq/L) | 138 (137–140) | 138 (136–139) | 0.300 |
Serum potassium (mEq/L) | 4.8 (4.2–5.0) | 4.7 (4.4–4.8) | 0.977 |
Serum glucose (mg/dL) | 99 (89–111) | 96 (84–105) | 0.244 |
Weight gain (g/day) | 22.5 (3.1–36.3) | 41.3 (28.1–55.1) | 0.019 |
Defecation (stool number/day) | 2.2 (1.3–4.3) | 2.3 (1.3–3.0) | 0.364 |
Values are expressed as median (interquartile range).
Heart rate <100 beats/min during or immediately after oral bottle feeding.
SpO2 <85% during or immediately after oral bottle feeding.