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- Original article The impact of nutritional intervention by a nutrition support team on extrauterine growth restriction in very low birth weight infants in Korea: a retrospective cohort study
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Seung Yun Lee1
, Hye Su Hwang2, Waonsun Im3, Hyojoung Kim4, Mi Lim Chung1 -
Annals of Clinical Nutrition and Metabolism 2024;16(3):149-157.
DOI: https://doi.org/10.15747/ACNM.2024.16.3.149
Published online: December 1, 2024
1Department of Pediatrics, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
2Department of Pediatrics, Ewha Womans University Mokdong Hospital, Seoul, Korea
3Department of Nursing, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
4Department of Pharmacy, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
- Corresponding author: Mi Lim Chung, email: forevery52@naver.com
• Received: October 7, 2024 • Revised: November 18, 2024 • Accepted: November 25, 2024
© 2024 The Korean Society of Surgical Metabolism and Nutrition · The Korean Society for Parenteral and Enteral Nutrition
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract
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Purpose Achieving proper weight gain through adequate nutrition is critically important in very low birth weight (VLBW) infants. Despite recent active nutritional interventions, growth restriction is still common in VLBW infants. We aimed to determine whether nutritional intervention by a nutrition support team (NST) mitigated extrauterine growth restriction (EUGR) in VLBW infants.
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Methods We retrospectively reviewed the medical records of VLBW infants admitted to Haeundae Paik Hospital between March 2010 and February 2024. EUGR was defined as a decrease in the weight-for-age-z-score>1.2 from birth to the postconceptional age of 36 weeks, using Fenton growth charts.
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Results Among the 603 enrolled VLBW infants, 434 (72.0%) were diagnosed with EUGR. When comparing the control and nutritional intervention groups, the incidence of EUGR was significantly lower in infants in the intervention group (80.6% vs. 62.8%, P<0.00). Intervention group infants started enteral feeding earlier and reached half and full enteral feeding earlier (P<0.05). In addition, intravenous protein and lipid supply started sooner, increased at a faster rate, and reached peak concentrations sooner in the intervention group (P<0.05).
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Conclusion Nutritional intervention by an NST resulted in a significant decrease in the development of EUGR in VLBW infants.
Introduction
Although the survival rate of premature infants has increased sharply in recent decades due to the development of medical support, morbidities have also increased as more preterm babies survive the neonatal period. Therefore, prematurity care has begun to focus on reducing comorbidities and enhancing neurodevelopment. Nutritional support has become an important component in this field. Although, the reported incidence of extrauterine growth restriction (EUGR) in preterm infants varies depending on the definition and study populations [1,,,-7], EUGR remains a common morbidity in premature infants, especially those with very low birth weight (VLBW), despite various efforts.
Inadequate growth after birth is known to be associated with later metabolic complications such as hypertension, insulin resistance, and metabolic syndrome [8]. Moreover, many studies have reported that EUGR after preterm birth correlates with the development of adverse neurologic outcomes [9,-11]. Therefore, promoting adequate growth through active nutritional interventions is important in neonatal intensive care units (NICUs).
Although the assessment of EUGR in preterm infants has varied among studies, current EUGR definitions can be classified into two categories. The cross-sectional definition uses weight at a given time below the 10th percentile, regardless of birth weight (BW). The longitudinal definition uses weight loss between birth and a given time with various standard-deviation thresholds [5]. Zozaya et al. [12] reported that a decrease in the weight z-score from birth to 36 weeks is a more rational definition of EUGR than any of the previous definitions, and it can predict neurodevelopment. A diagnosis of EUGR based on a one-time weight has several limitations; therefore, a more reliable indicator, such as a decline in the weight-for-age z-score, is needed. The difference between the z-score at birth and a specific point in time, such as at a postconceptional age (PCA) of 36 weeks or at discharge, is a useful way to define EUGR in VLBW infants [12,13].
In this study, we defined EUGR as the change in weight-for-age z-score between birth and discharge, using the Fenton growth chart [14]. We conducted a retrospective study to investigate whether intervention by the nutritional support team (NST) could prevent EUGR in VLBW infants. We also sought risk factors for EUGR and examined the association between comorbidities and EUGR in VLBW infants.
Methods
This study was approved by the Institutional Review Board of Haeundae Paik Hospital (2024-04-029). The requirement for informed consent was waived because our study was retrospective.
This retrospective study divided patients into groups and compared them at a single institution. It was described according to the STROBE statement for a cohort study, which is available at https://www.strobe-statement.org/
We reviewed the medical records of neonates admitted to the NICU at Haeundae Paik Hospital between March 2010 and February 2024. The inclusion criteria were VLBW infants whose BW was less than 1,500 g. The exclusion criteria were infants who had severe congenital anomalies, chromosomal abnormalities, or clinically apparent congenital infections. In addition, we excluded infants who died, were discharged from the hospital, or transferred to another hospital before PCA 36 weeks. We included only infants who were born at our hospital.
We collected basic demographic information for each infant: gestational age (GA), BW, sex, Apgar score, and delivery type. To assess morbidities, we collected data on surfactant use, patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, retinopathy of prematurity (ROP), parenteral nutrition associated cholestasis (PNAC), and mortality. Significant PDA was defined as the need for surgical ligation or medical treatment. NEC was defined as Bell’s criteria stage two or greater. BPD was defined as the need for oxygen at PCA 36 weeks. Significant ROP was defined as the need for laser photocoagulation or intravitreal injections. Sepsis was diagnosed only when bacteria were identified in blood culture tests performed when there were suspicious clinical symptoms. PNAC was diagnosed when the conjugated bilirubin concentration was more than 2.0 mg/dL in VLBW infants who received parenteral nutrition (PN) support for at least 2 weeks and in whom cholestasis had no possible cause except for PN. We excluded the data when there was a temporary increase accompanying sepsis.
As the nutritional history, we analyzed the number of days until the initiation of enteral feeding, the time points at which half (60 mL/kg/d) and full (120 mL/kg/d) enteral feeding were reached, and the number of days of total PN. In addition, we reviewed and analyzed information about the start date of intravenous protein and lipid supply, rate of increase, and time to maximum concentration and the mothers’ perinatal complications. Antenatal data collected were diagnoses of maternal hypertensive disorders, diabetes mellitus, and the use of antenatal steroids. In addition, we reviewed placental pathology results. Data regarding placental biopsy–proven chorioamnionitis were also collected.
The primary outcome variable was the development of EUGR, defined as a decline in the weight-for-age z-score>1.2 from birth to PCA 36 weeks, using the Fenton growth chart.
Nutrition protocol
This hospital opened in 2010, and the NST was formed shortly after that. However, active nutritional intervention was not fully implemented until around 2015. As its active nutritional intervention for NICU patients, the NST participates in NICU rounds at least once a month and discusses updates about nutritional supply at regular NST conferences held once every two months. The pharmacist, nutritionist, and NST nurses frequently contact and exchange opinions with the NICU staff about the enteral and PN prescribed every day. To determine the effects of nutritional intervention by the NST, we divided our subjects into two groups, control and intervention, based on whether they were born before or after 2015.
1) Enteral nutrition protocol
The initial enteral feeding volume was 10–20 mL/kg/d divided into doses given every three hours and increased by 10–20 mL/kg/d according to the baby’s tolerance until full enteral feeding (120–160 mL/kg/d) was achieved. We fed premature infants either human milk or premature infant formula (Namyang or Maeil premature infant formula). After the enteral feeding volume reached 100 mL/kg/d, breast milk was fortified with a human milk fortifier (Enfamil human milk fortifier). Because enteral feeding did not begin until all procedures and initial care had been completed and the baby's vitals had stabilized, many babies were unable to feed on the first day of life. However, since nutritional intervention by the NST began, enteral feeding is started as soon as possible after birth except in rare cases in which the vital signs are extremely unstable. We now increase the feeding volume by 20 mL/kg/d for all babies, if tolerated.
2) PN protocol
(1) Protein
The infants were started at 0.5 g/kg/d just after birth. That dose was increased daily by 0.5 g/kg increments to a maximum dose of 3.0–4.0 g/kg/d, according to the baby’s tolerance. Since nutritional intervention by the NST began, we increased the protein intake starting on the day of birth to attain the maximum protein supply more rapidly. In particular, it starts at 2 g/kg/d on the first day of life for extremely low birth weight (ELBW, BW less than 1,000 g) infants.
(2) Carbohydrates
The infants were started at 7.0–8.0 g/kg/d just after birth. The dose was increased by 1.0–2.0 g/kg/d every day to a maximum dose of 15.0–18.0 g/kg/d. The amount of dextrose was adjusted daily according to the baby’s tolerance, which was determined by measuring blood and urine sugar levels.
(3) Lipids
The intravenous lipid emulsion was started at 0.5 g/kg/d on day two and increased at a dose of 0.5 g/kg/d to a maximum dose of 3.0 g/kg/d. Each neonate’s tolerance was monitored by measuring their triglyceride levels once or twice per week; the target was to maintain triglyceride levels below 200 mg/dL. Since nutritional intervention by the NST began, we start lipid supplementation on the first day after birth and increase the dose faster, reaching the maximum dose as soon as possible after birth in VLBW infants.
No selection bias was reportable.
Sample size estimation was not conducted because our study was retrospective. All participants were selected based on the inclusion and exclusion criteria.
Continuous data are expressed as the mean±standard deviation, and categorical data are expressed as frequency (%). For continuous data, an independent t-test was applied if the assumption of normality was satisfied; otherwise, the Mann–Whitney U-test was applied. For categorical data, Pearson’s chi-square or Fisher’s exact test was applied. The numbers superscripted with the p-values indicate the test method applied to each variable. All statistical analyses were carried out using SPSS 24.0 (IBM Corp.), and P-values less than 0.05 are considered statistically significant.
Results
During the study period, 727 VLBW infants were admitted to our NICU. After applying the exclusion criteria, we enrolled 603 of them for whom complete data were available (Fig. 1).
Based on the time when active nutritional intervention by the NST was introduced, the participants were divided into control and intervention groups. Table 1 summarizes the basic demographic and clinical factors of the two groups. Among the basic demographics, GA, BW, and small for gestational age (SGA), did not differ between the groups. Major morbidities, respiratory distress syndrome (RDS), BPD, significant PDA, NEC, and sepsis, also did not show any difference. Only significant ROP decreased in infants in the post-intervention group. However, body weight at PCA 36 weeks did differ significantly between the groups, and the incidence of EUGR at PCA 36 weeks was significantly lower in the post-intervention group (P<0.05).
As shown in Table 2, VLBW infants in the intervention group started enteral feeding, parenteral amino acid (AA), and lipids earlier and reached half and full enteral feeding and maximum AA and lipid concentrations earlier than the VLBW infants in the control group (P<0.05). Earlier initiation, more rapid titration, and higher doses of parenteral protein and lipid supply did not increase the incidence of PNAC.
Table 3 shows the basic demographic and clinical characteristics of the 603 VLBW infants according to whether they developed EUGR, which was diagnosed in 434 (72.0%) infants. The EUGR group showed lower GA (28.32±2.35 weeks vs. 31.26±2.84 weeks) and lower BW (1,066.81±259.38 g vs. 1,264.23±250.56 g) than the non-EUGR group infants (P<0.05). The non-EUGR infants had gained an average of 24.35±6.05 g/d by PCA 36 weeks, whereas the EUGR infants gained only 18.75±4.15 g/d (P<0.05).
The EUGR infants lost more weight over a longer period after birth. RDS, significant PDA, NEC, BPD, sepsis, significant ROP, cholestasis, and gastrointestinal (GI) surgery were more frequent in the EUGR infants than the non-EUGR infants (P<0.05).
Maternal age, overt or gestational diabetes, premature rupture of membranes, antenatal steroid use, and fetal distress did not different between the EUGR and non-EUGR groups. However, preterm labor and histological chorioamnionitis were more frequent in the EUGR group (P<0.05; Table 4).
The non-EUGR infants started enteral feeding earlier and reached half and full enteral feeding earlier than the EUGR infants (Table 5). They also received higher doses of protein earlier and reached their peak intake sooner (P<0.05). In addition, VLBW infants in the non-EUGR group received higher doses of lipids earlier, but the maximum concentration of lipid supply did not differ between the groups.
VLBW infants in the EUGR group received a longer duration of PN and had a higher incidence of PNAC than those in the non-EUGR group (P<0.05).
Discussion
This study demonstrated that EUGR remains a common and significant problem in VLBW infants, especially those with several morbidities. Moreover, we have shown the ef- fectiveness of nutritional intervention by the NST in prevent- ing the development of EUGR at PCA 36 weeks.
The incidence of EUGR reported in published studies varies widely, between 20% and 70%, depending on the population studied and the definition of EUGR, with the highest incidence reported in VLBW infants [1,,-6]. Data on the incidence of EUGR in Korea are limited. Kim et al. [7] reported that the incidence of EUGR in VLBW infants with a GA≤32 weeks was 67% (111/166) when EUGR was defined as weight below the 10th percentile at discharge. Kim et al. [6] reported an incidence of 73.8% among enrolled ELBW infants when EUGR was defined as a decreased z-score>1 using the Fenton growth chart, and Lee et al. [3] reported that 45.9% of VLBW infants showed EUGR at discharge when EUGR was defined as a change in z-score from birth to discharge>1.28 using the Fenton chart. In this study, we defined EUGR as a decline in weight-for-age z-score>1.2 from birth to PCA 36 weeks. The overall incidence of EUGR at PCA 36 weeks in the VLBW infants we analyzed was 72.0%. When we compared the incidence rate of EUGR before and after nutritional intervention by the NST, we found that it decreased from 80.6% to 62.8%.
VLBW infants with EUGR at PCA 36 weeks had a lower GA and BW than those without EUGR, along with more frequent SGA. Infants in the EUGR group were hospitalized for a longer time (88.58±40.46 days vs. 57.73±27.51 days, P<0.05) and therefore had a longer GA at discharge (41.02±4.56 weeks vs. 39.63±2.72 weeks, P<0.05, data not shown). However, body weight at discharge did not differ between the EUGR and non-EUGR groups.
The EUGR group continued to lose weight for a longer period after birth (5.86±1.80 days vs. 5.16±1.50 days, P<0.05) and had a greater percentage of final weight loss (11.20%±4.66% vs. 9.11%±4.03%, P<0.05). Among the 25 infants who did not lose body weight within the first two weeks, 19 infants (76%) were later diagnosed with EUGR. Too much or too little early postnatal weight loss is known to have a negative effect on prognosis in prematurity [15,16]. Consistent with those findings, our data also demonstrate that EUGR occurred more frequently in babies who did not lose weight or who lost weight excessively during the first 14 days after birth. These results suggest that maintaining an adequate fluid and nutritional balance in the early postnatal period is important for preventing EUGR.
Infants who developed EUGR started enteral nutrition later than those who did not (4.34±4.15 days vs. 2.34±2.21 days, P<0.05), and it took them longer to reach half and full enteral feeding. Therefore, naturally, they received PN for a longer time (41.57±33.02 days vs. 22.23±18.09 days, P<0.05), and the incidence of PNAC was accordingly higher (114/434, 26.3% vs. 13/169, 7.7%; P<0.05). It was thus confirmed that rapid and active enteral feeding can prevent the occurrence of EUGR. Moreover, NEC was more frequent in the EUGR group than in the non-EUGR group.
Our hospital opened and began NICU treatment for premature babies in 2010. Since then, the NICU nutritional protocol has been updated to stay current with the nutritional support guidelines as new versions are released [17,-19]. However, some updates were postponed or individualized methods were maintained, depending on the attending physician. Around 2015, through rounding and in discussion with the NST, we decided on the best unified guidelines and applied a uniform policy regarding nutritional support for VLBW infants. In this study, we compared basic, clinical, and nutritional factors between babies born before and after nutritional intervention by the NST began in 2015. There were no specific differences in basic demographic factors (GA, BW, sex, Apgar score, and SGA). Cesarean section delivery was more frequent in the post-intervention group because of the high incidence of multiple births. Post-intervention group infants were treated with shorter durations of invasive ventilator care and longer non-invasive ventilator care. BPD, significant PDA, NEC, sepsis, and GI surgery did not differ significantly between the groups. However, significant ROP requiring laser photocoagulation or intravitreal injection was more frequent in the control group. Maternal factors were also analyzed, and we found that in the acitive nutritional intervention group, maternal age was older and assisted reproductive techniques were more frequently used. Several morbidities, particularly pregnancy-induced hypertension and preterm labor, were more frequent in the post-intervention group, and antenatal steroid treatment was significantly higher in the post-intervention group.
Since the introduction of nutritional intervention, we start enteral feeding on the first day of life with very rare exceptions. Previously, there was a policy to start enteral feeding as early as possible after birth, but in reality, it was often not done on the first day for reasons such as waiting for the baby’s vital signs to stabilize or the completion of necessary procedures. In addition, in the control period, enteral feeding was conducted conservatively when meconium passing was confirmed or to consider the risk of NEC. However, even in the control period, we increased the feeding amount by 20 mL/kg/d to reach full feeding as quickly as possible, although this varied depending on the tolerance of each individual. Following the new guidelines, the post-intervention group babies were able to initiate feedings sooner (3.02±3.64 days vs. 4.50±3.84 days, P<0.05), increase the feeding supply faster, and reach full feeding much sooner (28.63±27.51 days vs. 30.37±20.56 days, P<0.05) than the control group babies. We confirmed that this policy did not increase the risk of NEC or GI surgery, and the occurrence of EUGR decreased after nutritional intervention by the NST. These results are similar to those found in previous studies [17,,-22] and confirm that active oral nutrition is a relatively safe method for preventing the occurrence of EUGR without increasing the risk of NEC.
Establishing sufficient enteral feeding is difficult in sick neonates, particularly VLBW infants. Therefore, PN can be the primary source of nutrition for a significant period of time. Since the introduction of nutritional intervention by the NST, we start AA at the minimum dose immediately after birth, especially 2.0 g/kg/d in ELBW infants weighing less than 1 kg. If tolerated, the dose is increased by 1 g/kg/d up to the maximum dose of 4 g/kg on the 3rd to 4th day after birth. Lipids are also started quickly, increasing the overall calorie intake as quickly as possible. Some practitioners have concerns about starting such nutrition directly after birth, increasing too quickly, or administering too much protein, but our data confirm that at the very least, it does not cause more PNAC. Even if the PN supply was started earlier with a higher dose and increased quickly, the incidence of PNAC decreased because the PN period was shortened by reaching full enteral feeding sooner according to our active nutrition supply policy [23,-25].
First, it was performed retrospectively. Therefore, the various conditions that could affect the EUGR of patients could not be applied equally. Although nutritional interventions have changed constantly over time and would have been applied differently for each individual, we compared them only by categorizing them into two periods. Due to the increasing number of multiple pregnancies, some maternal factors were applied repeatedly during the analysis. In addition, we confirmed the association with co-morbidities only during the hospitalization period and did not observe the effects of EUGR on long-term outcomes.
Despite those limitations, this study confirms that nutritional intervention from the NST effectively prevented the occurrence of EUGR in a considerable number of VLBW infants.
We found that EUGR is common in VLBW infants and is associated with various morbidities, particularly significant PDA, BPD, ROP, NEC, and sepsis. In addition, several nutritional factors have been implicated in the development of EUGR. Moreover, aggressive nutritional interventions by the NST have helped to prevent EUGR in VLBW infants.
Acknowledgments
We would like to thank Sun-gyu Choi, a doctor and statistician at Haeundae Paik Hospital Biomedical Research Institute.
Authors’ contribution
Conceptualization: SYL, MLC. Data curation: HSH, SYL. Formal analysis: WI, HK. Funding acquisition: MLC. Investigation: HSH, SYL. Methodology: HSH, SYL, HK. Project administration: HSH, SYL, WI, HK. Resources: WI, HK. Software: WI, HK. Supervision: MLC. Validation: SYL, MLC, HSH. Visualization: SYL, MLC. Writing – original draft: SYL, MLC, HSH. Writing – review & editing: all authors.
Conflict of interest
The authors of this manuscript have no conflicts of interest to disclose.
Funding
This study was supported by a 2023 grant from the Korean Society of Parenteral and Enteral Nutrition.
Data availability
Contact the corresponding author for data availability.
Supplementary materials
None.
Fig. 1
Study flow sheet. VLBW = very low birth weight; PCA = post conceptional age; EUGR = extrauterine growth restriction.
Table 1
Comparison between the control and intervention groups
| Variable |
Control group (N=310) |
Intervention group (N=293) |
P-value |
|---|---|---|---|
| Gestational age (wk) | 28.99±2.90 | 29.31±2.74 | 0.096a |
| Birth weight (g) | 1,104.81±264.25 | 1,140.48±278.52 | 0.051a |
| Sex, male | 150 (48.4) | 150 (51.2) | 0.491b |
| Delivery type, C-section | 253 (81.6) | 265 (90.4) | 0.002b |
| Multiple birth | 107 (34.5) | 133 (45.4) | 0.006b |
| SGA | 71 (22.9) | 68 (23.2) | 0.622c |
| RDS | 279 (90.0) | 263 (89.8) | 0.923b |
| BPD | 147 (47.4) | 135 (46.1) | 0.741b |
| Duration of invasive ventilator care (day) | 18.64±28.00 | 14.01±17.24 | 0.110a |
| Duration of non-invasive ventilator care (day) | 17.40±19.25 | 22.11±18.50 | <0.001a |
| Significant PDA | 187 (60.3) | 169 (57.7) | 0.357b |
| Significant ROP | 100 (32.3) | 50 (17.1) | <0.001b |
| NEC≥2 | 48 (15.5) | 59 (20.1) | 0.135b |
| Sepsis | 95 (30.6) | 97 (33.1) | 0.517b |
| Length of hospital stays (day) | 80.06±42.82 | 79.80±36.32 | 0.606a |
| Body weight at PCA 36 weeks (g) | 1,801.77±334.62 | 1,894.57±328.21 | 0.001a |
| EUGR at PCA 36 weeks | 250 (80.6) | 184 (62.8) | <0.000b |
Values are presented as mean±standard deviation or number (%).
SGA = small for gestational age; RDS = respiratory distress syndrome; BPD = bronchopulmonary dysplasia; PDA = patent ductus arteriosus; ROP = retinopathy of prematurity; NEC = necrotizing enterocolitis; PCA = postconceptional age; EUGR = extrauterine growth restriction.
aMann–Whitney U-test, bPearson’s chi square test, cFisher’s exact test.
Table 2
Nutritional parameters in the control and intervention groups
| Variable |
Control group (N=310) |
Intervention group (N=293) |
P-value |
|---|---|---|---|
| Start day of enteral feeding (day) | 4.50±3.84 | 3.02±3.64 | <0.001a |
| Days until reaching half enteral feeding | 17.86±13.98 | 16.83±17.17 | 0.002a |
| Days until reaching full enteral feeding | 30.37±20.56 | 28.63±27.51 | <0.001a |
| Initial concentration of AA supply (g/kg/d) | 0.55±0.14 | 1.70±0.33 | <0.001a |
| Start day of AA supply | 1.76±0.42 | 1.00±0.00 | <0.001a |
| Day of maximum AA supply | 6.37±0.66 | 5.06±0.79 | <0.001a |
| Maximum AA concentration (g/kg/d) | 2.87±0.33 | 3.57±0.50 | <0.001a |
| Start day of lipid supply | 2.12±0.33 | 1.42±0.50 | <0.001a |
| Day of maximum lipid supply | 6.49±0.57 | 5.38±0.94 | <0.001a |
| Maximum concentration of lipid (g/kg/d) | 2.70±0.38 | 2.98±0.13 | <0.001a |
| Duration of PN (day) | 37.83±31.14 | 34.35±30.46 | 0.001a |
| PNAC | 60 (19.4) | 67 (22.9) | 0.299b |
Table 3
Comparison between the EUGR and non-EUGR groups
| Variable |
Non-EUGR group (N=169) |
EUGR group (N=434) |
P-value |
|---|---|---|---|
| Gestational age (wk) | 31.26±2.84 | 28.32±2.35 | <0.001a |
| Birth weight (g) | 1,264.23±250.56 | 1,066.81±259.38 | <0.001a |
| Sex, male | 87 (51.5) | 213 (49.1) | 0.596b |
| Delivery type, C-section | 151 (89.3) | 367 (84.6) | 0.129b |
| Multiple birth | 60 (35.5) | 180 (41.5) | 0.178b |
| Apgar score at 1 min | 6 (5–7) | 6 (5–6) | <0.001a |
| Apgar score at 5 min | 8 (7–8) | 7 (7–8) | <0.001a |
| SGA | 69 (40.8) | 70 (16.1) | <0.001c |
| Days of maximum initial weight loss (day) | 5.16±1.50 | 5.86±1.80 | <0.001a |
| Maximum weight loss (%) (n=578) | 9.11±4.03 | 11.20±4.66 | <0.001a |
| RDS | 127 (75.1) | 415 (95.6) | <0.001b |
| BPD | 35 (20.7) | 247 (56.9) | <0.001b |
| Significant PDA | 56 (33.1) | 300 (69.1) | <0.001b |
| Significant ROP | 13 (7.7) | 137 (31.6) | <0.001b |
| NEC≥2 | 11 (6.5) | 96 (22.1) | <0.001b |
| Sepsis | 19 (11.2) | 173 (39.9) | <0.001b |
| Body weight at PCA 36 weeks | 1,919.82±409.64 | 1,818.46±295.89 | 0.020a |
| Length of hospital stay (day) | 57.73±27.51 | 88.58±40.46 | <0.001a |
| Average weight gain (g/d) | 24.35±6.05 | 18.75±4.15 | <0.001a |
Values are presented as mean±standard deviation, number (%), or median (interquartile range).
EUGR = extrauterine growth restriction; SGA = small for gestational age; RDS = respiratory distress syndrome; BPD = bronchopulmonary dysplasia; PDA = patent ductus arteriosus; ROP = retinopathy of prematurity; NEC = necrotizing enterocolitis; PCA = postconceptional age.
aMann–Whitney U-test, bPearson’s chi square test, cFisher’s exact test.
Table 4
Comparison of maternal factors between the EUGR and non-EUGR groups
| Variable |
Non-EUGR group (N=169) |
EUGR group (N=434) |
P-value |
|---|---|---|---|
| Maternal age (yr) | 33.70±3.75 | 33.60±3.90 | 0.848a |
| Gestational diabetes | 15 (8.9) | 41 (9.4) | 0.813b |
| Pregnancy-induced hypertension | 52 (30.8) | 86 (19.8) | 0.004b |
| Premature rupture of membranes | 77 (45.6) | 232 (53.5) | 0.070b |
| Preterm labor | 94 (55.6) | 284 (65.4) | 0.019b |
| Antenatal steroid | 135 (79.9) | 365 (84.1) | 0.159b |
| Fetal distress | 66 (39.1) | 140 (32.3) | 0.129b |
| Histologic chorioamnionitis | 38 (22.5) | 143 (32.9) | 0.010b |
Table 5
Nutritional parameters in the non-EUGR and EUGR groups
| Variable |
Non-EUGR group (N=169) |
EUGR group (N=434) |
P-value |
|---|---|---|---|
| Days until initiation of enteral feeding | 2.34±2.21 | 4.34±4.15 | <0.001a |
| Days until reaching half enteral feeding | 10.60±8.99 | 20.00±16.81 | <0.001a |
| Days until reaching full enteral feeding | 18.64±15.46 | 33.76±25.61 | <0.001a |
| Initial concentration of AA supply (g/kg/d) | 1.27±0.59 | 1.04±0.63 | <0.001a |
| Start day of protein supply | 1.28±0.45 | 1.44±0.50 | <0.001a |
| Day of maximum protein supply | 5.44±0.95 | 5.85±0.97 | <0.001a |
| Maximum AA concentration (g/kg/d) | 3.36±0.55 | 3.15±0.54 | <0.001a |
| Start day of lipid supply | 1.57±0.53 | 1.86±0.53 | <0.001a |
| Day of maximum lipid supply | 5.63±0.95 | 6.08±0.91 | <0.001b |
| Maximum concentration of lipid (g/kg/d) | 2.88±0.27 | 2.82±0.33 | 0.051a |
| Duration of PN (day) | 22.23±18.09 | 41.57±33.02 | <0.001a |
| PNAC | 13 (7.7) | 114 (26.3) | <0.001c |
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XML DownloadThe impact of nutritional intervention by a nutrition support team on extrauterine growth restriction in very low birth weight infants in Korea: a retrospective cohort study
Fig. 1
Study flow sheet. VLBW = very low birth weight; PCA = post conceptional age; EUGR = extrauterine growth restriction.
Fig. 1
The impact of nutritional intervention by a nutrition support team on extrauterine growth restriction in very low birth weight infants in Korea: a retrospective cohort study
Comparison between the control and intervention groups
| Variable | Control group (N=310) |
Intervention group (N=293) |
P-value |
|---|---|---|---|
| Gestational age (wk) | 28.99±2.90 | 29.31±2.74 | 0.096 |
| Birth weight (g) | 1,104.81±264.25 | 1,140.48±278.52 | 0.051 |
| Sex, male | 150 (48.4) | 150 (51.2) | 0.491 |
| Delivery type, C-section | 253 (81.6) | 265 (90.4) | 0.002 |
| Multiple birth | 107 (34.5) | 133 (45.4) | 0.006 |
| SGA | 71 (22.9) | 68 (23.2) | 0.622 |
| RDS | 279 (90.0) | 263 (89.8) | 0.923 |
| BPD | 147 (47.4) | 135 (46.1) | 0.741 |
| Duration of invasive ventilator care (day) | 18.64±28.00 | 14.01±17.24 | 0.110 |
| Duration of non-invasive ventilator care (day) | 17.40±19.25 | 22.11±18.50 | <0.001 |
| Significant PDA | 187 (60.3) | 169 (57.7) | 0.357 |
| Significant ROP | 100 (32.3) | 50 (17.1) | <0.001 |
| NEC≥2 | 48 (15.5) | 59 (20.1) | 0.135 |
| Sepsis | 95 (30.6) | 97 (33.1) | 0.517 |
| Length of hospital stays (day) | 80.06±42.82 | 79.80±36.32 | 0.606 |
| Body weight at PCA 36 weeks (g) | 1,801.77±334.62 | 1,894.57±328.21 | 0.001 |
| EUGR at PCA 36 weeks | 250 (80.6) | 184 (62.8) | <0.000 |
Values are presented as mean±standard deviation or number (%).
SGA = small for gestational age; RDS = respiratory distress syndrome; BPD = bronchopulmonary dysplasia; PDA = patent ductus arteriosus; ROP = retinopathy of prematurity; NEC = necrotizing enterocolitis; PCA = postconceptional age; EUGR = extrauterine growth restriction.
aMann–Whitney U-test, bPearson’s chi square test, cFisher’s exact test.
Nutritional parameters in the control and intervention groups
| Variable | Control group (N=310) |
Intervention group (N=293) |
P-value |
|---|---|---|---|
| Start day of enteral feeding (day) | 4.50±3.84 | 3.02±3.64 | <0.001 |
| Days until reaching half enteral feeding | 17.86±13.98 | 16.83±17.17 | 0.002 |
| Days until reaching full enteral feeding | 30.37±20.56 | 28.63±27.51 | <0.001 |
| Initial concentration of AA supply (g/kg/d) | 0.55±0.14 | 1.70±0.33 | <0.001 |
| Start day of AA supply | 1.76±0.42 | 1.00±0.00 | <0.001 |
| Day of maximum AA supply | 6.37±0.66 | 5.06±0.79 | <0.001 |
| Maximum AA concentration (g/kg/d) | 2.87±0.33 | 3.57±0.50 | <0.001 |
| Start day of lipid supply | 2.12±0.33 | 1.42±0.50 | <0.001 |
| Day of maximum lipid supply | 6.49±0.57 | 5.38±0.94 | <0.001 |
| Maximum concentration of lipid (g/kg/d) | 2.70±0.38 | 2.98±0.13 | <0.001 |
| Duration of PN (day) | 37.83±31.14 | 34.35±30.46 | 0.001 |
| PNAC | 60 (19.4) | 67 (22.9) | 0.299 |
Values are presented as mean±standard deviation or number (%).
AA = amino acid; PN = parenteral nutrition; PNAC = parenteral nutrition associated cholestasis.
aMann–Whitney U-test, bPearson’s chi square test.
Comparison between the EUGR and non-EUGR groups
| Variable | Non-EUGR group (N=169) |
EUGR group (N=434) |
P-value |
|---|---|---|---|
| Gestational age (wk) | 31.26±2.84 | 28.32±2.35 | <0.001 |
| Birth weight (g) | 1,264.23±250.56 | 1,066.81±259.38 | <0.001 |
| Sex, male | 87 (51.5) | 213 (49.1) | 0.596 |
| Delivery type, C-section | 151 (89.3) | 367 (84.6) | 0.129 |
| Multiple birth | 60 (35.5) | 180 (41.5) | 0.178 |
| Apgar score at 1 min | 6 (5–7) | 6 (5–6) | <0.001 |
| Apgar score at 5 min | 8 (7–8) | 7 (7–8) | <0.001 |
| SGA | 69 (40.8) | 70 (16.1) | <0.001 |
| Days of maximum initial weight loss (day) | 5.16±1.50 | 5.86±1.80 | <0.001 |
| Maximum weight loss (%) (n=578) | 9.11±4.03 | 11.20±4.66 | <0.001 |
| RDS | 127 (75.1) | 415 (95.6) | <0.001 |
| BPD | 35 (20.7) | 247 (56.9) | <0.001 |
| Significant PDA | 56 (33.1) | 300 (69.1) | <0.001 |
| Significant ROP | 13 (7.7) | 137 (31.6) | <0.001 |
| NEC≥2 | 11 (6.5) | 96 (22.1) | <0.001 |
| Sepsis | 19 (11.2) | 173 (39.9) | <0.001 |
| Body weight at PCA 36 weeks | 1,919.82±409.64 | 1,818.46±295.89 | 0.020 |
| Length of hospital stay (day) | 57.73±27.51 | 88.58±40.46 | <0.001 |
| Average weight gain (g/d) | 24.35±6.05 | 18.75±4.15 | <0.001 |
Values are presented as mean±standard deviation, number (%), or median (interquartile range).
EUGR = extrauterine growth restriction; SGA = small for gestational age; RDS = respiratory distress syndrome; BPD = bronchopulmonary dysplasia; PDA = patent ductus arteriosus; ROP = retinopathy of prematurity; NEC = necrotizing enterocolitis; PCA = postconceptional age.
aMann–Whitney U-test, bPearson’s chi square test, cFisher’s exact test.
Comparison of maternal factors between the EUGR and non-EUGR groups
| Variable | Non-EUGR group (N=169) |
EUGR group (N=434) |
P-value |
|---|---|---|---|
| Maternal age (yr) | 33.70±3.75 | 33.60±3.90 | 0.848 |
| Gestational diabetes | 15 (8.9) | 41 (9.4) | 0.813 |
| Pregnancy-induced hypertension | 52 (30.8) | 86 (19.8) | 0.004 |
| Premature rupture of membranes | 77 (45.6) | 232 (53.5) | 0.070 |
| Preterm labor | 94 (55.6) | 284 (65.4) | 0.019 |
| Antenatal steroid | 135 (79.9) | 365 (84.1) | 0.159 |
| Fetal distress | 66 (39.1) | 140 (32.3) | 0.129 |
| Histologic chorioamnionitis | 38 (22.5) | 143 (32.9) | 0.010 |
Values are presented as mean±standard deviation or number (%).
EUGR = extrauterine growth restriction.
aMann–Whitney U-test, bPearson’s chi square test.
Nutritional parameters in the non-EUGR and EUGR groups
| Variable | Non-EUGR group (N=169) |
EUGR group (N=434) |
P-value |
|---|---|---|---|
| Days until initiation of enteral feeding | 2.34±2.21 | 4.34±4.15 | <0.001 |
| Days until reaching half enteral feeding | 10.60±8.99 | 20.00±16.81 | <0.001 |
| Days until reaching full enteral feeding | 18.64±15.46 | 33.76±25.61 | <0.001 |
| Initial concentration of AA supply (g/kg/d) | 1.27±0.59 | 1.04±0.63 | <0.001 |
| Start day of protein supply | 1.28±0.45 | 1.44±0.50 | <0.001 |
| Day of maximum protein supply | 5.44±0.95 | 5.85±0.97 | <0.001 |
| Maximum AA concentration (g/kg/d) | 3.36±0.55 | 3.15±0.54 | <0.001 |
| Start day of lipid supply | 1.57±0.53 | 1.86±0.53 | <0.001 |
| Day of maximum lipid supply | 5.63±0.95 | 6.08±0.91 | <0.001 |
| Maximum concentration of lipid (g/kg/d) | 2.88±0.27 | 2.82±0.33 | 0.051 |
| Duration of PN (day) | 22.23±18.09 | 41.57±33.02 | <0.001 |
| PNAC | 13 (7.7) | 114 (26.3) | <0.001 |
Values are presented as mean±standard deviation or number (%).
EUGR = extrauterine growth restriction; AA = amino acid; PN = parenteral nutrition; PNAC = parenteral nutrition associated cholestasis.
aMann–Whitney U-test, bindependent t-test, cPearson’s chi square test.
Table 1
Comparison between the control and intervention groups
Values are presented as mean±standard deviation or number (%). SGA = small for gestational age; RDS = respiratory distress syndrome; BPD = bronchopulmonary dysplasia; PDA = patent ductus arteriosus; ROP = retinopathy of prematurity; NEC = necrotizing enterocolitis; PCA = postconceptional age; EUGR = extrauterine growth restriction. aMann–Whitney U-test, bPearson’s chi square test, cFisher’s exact test.
Table 2
Nutritional parameters in the control and intervention groups
Values are presented as mean±standard deviation or number (%). AA = amino acid; PN = parenteral nutrition; PNAC = parenteral nutrition associated cholestasis. aMann–Whitney U-test, bPearson’s chi square test.
Table 3
Comparison between the EUGR and non-EUGR groups
Values are presented as mean±standard deviation, number (%), or median (interquartile range). EUGR = extrauterine growth restriction; SGA = small for gestational age; RDS = respiratory distress syndrome; BPD = bronchopulmonary dysplasia; PDA = patent ductus arteriosus; ROP = retinopathy of prematurity; NEC = necrotizing enterocolitis; PCA = postconceptional age. aMann–Whitney U-test, bPearson’s chi square test, cFisher’s exact test.
Table 4
Comparison of maternal factors between the EUGR and non-EUGR groups
Values are presented as mean±standard deviation or number (%). EUGR = extrauterine growth restriction. aMann–Whitney U-test, bPearson’s chi square test.
Table 5
Nutritional parameters in the non-EUGR and EUGR groups
Values are presented as mean±standard deviation or number (%). EUGR = extrauterine growth restriction; AA = amino acid; PN = parenteral nutrition; PNAC = parenteral nutrition associated cholestasis. aMann–Whitney U-test, bindependent t-test, cPearson’s chi square test.
