Administering Intravenous Fluid in the Immediate Postpartum Period Minimizes Ultimate Formula Feeding

Abstract

Background:

Human milk is the optimal form of nutrition for infants. Interventions associated with a decreased rate of exposure to infant formula are of benefit. We hypothesized that intravenous (IV) fluids could be associated with a reduction of infant formula when infants are separated from their mother.

Methods:

Retrospective chart review of term infants admitted to Rady Children's Neonatal Intensive Care Units (NICUs) for possible sepsis who received antibiotic treatment but did not develop sepsis. IV fluid use and formula exposure were analyzed.

Results:

Six hundred twenty-eight infants met the inclusion criteria. Around 25.6% received IV fluids and 74.4% did not. IV fluid administration was associated with a significantly reduced chance of formula exposure while in the NICU (odds ratio: 0.694, 95% confidence interval: 0.484–0.993; *p = 0.046).

Conclusion:

This retrospective chart review found that infants transferred to the NICU and separated from their mothers due to chorioamnionitis exposure who received IV fluids were significantly less likely to receive any infant formula than infants who were not administered IV fluids.

Keypoints

Infants on IV fluids were less likely to receive formula

Human milk exposure has public health benefits

Separating infants from mothers is not ideal

Introduction

The management of term neonates born to a mother with chorioamnionitis has been evolving over time.¹ It ranges from recommendation for administration of intravenous (IV) antibiotics either in the Neonatal Intensive Care Unit (NICU), or well-baby nursery, to observation without separation from the mother. At the time of data collection for this study, the standard of care of infants born to mothers with chorioamnionitis at the satellite delivery hospitals of Rady Children's Hospital was to transfer the newborns to the NICU and administer 48 hours of antibiotic coverage. The policy at the time in the delivery hospitals did not allow for antibiotic administration in the well-baby nursery. The guidelines did not include whether infants should be given maintenance IV fluids in addition to the IV antibiotics. The decision regarding administration of IV fluids upon admission varied between providers.

We hypothesized that implementation of IV fluids in the NICU is associated with a reduction of infant formula exposure. We reasoned that infant separation from the mother makes breastfeeding more difficult, therefore increasing the need for the nurses to feed the infant by bottle with formula. However, administration of IV fluids may allow for a longer duration between feeds, permitting the nurses to feel more comfortable about not giving a bottle of formula to the infant. Due to the numerous positive effects of human milk on infant health, interventions that increase human milk exposure and decrease formula supplementation should be implemented whenever possible, validating the need for this study.

Methods

This work comprises a retrospective chart review of healthy term infants admitted to Rady Children's Hospital Satellite NICUs for antibiotic administration due to exposure to maternal chorioamnionitis from January 1, 2014 to August 31, 2016. The Institutional Review Board of UCSD Human Research Protections Program reviewed and approved this study. The study population included mothers who delivered infants at Scripps Memorial Hospital La Jolla, Scripps Memorial Hospital Encinitas, Scripps Mercy Hospital Chula Vista, Scripps Mercy Hospital San Diego, Palomar Medical Center Escondido, and Rancho Springs Medical Center Murrieta, and then admitted to the Rady Children's NICUs at those locations. These hospitals cover a wide area of San Diego County and Southern Riverside County and, therefore, include a diverse patient population. Individuals from many different cultures and socioeconomic classes reside in San Diego County and subsequently receive medical care at the previously mentioned hospitals.

Infants who received treatment but did not ultimately develop sepsis were included in the study. This group incorporated infants with diagnoses of small for gestational age (SGA), intrauterine growth restriction (IUGR), or large for gestational age (LGA). However, infants that otherwise were not healthy as determined by additional diagnoses (including respiratory distress, hypoglycemia, poor feeding, and sepsis) were excluded from the study.

Maternal age, gravidity, parity, gestational age, assigned sex, delivery method type, length of stay in the NICU, birthweight, and Apgar scores were collected as baseline demographics. Analysis was done on these demographic variables to determine if an association with IV fluid exposure was evident. Two-sample t-test and chi-square tests were used for continuous and categorical variables, respectively. Additionally, data on IV fluid exposure and the types of feeds given were collected for the study population.

Infant formula exposure was the primary outcome variable. Analysis of the data was focused on determining the effect of IV fluid exposure, delivery method type, and parity on formula exposure. We created a logistic regression model with exposure to infant formula as the binary outcome variable. A univariate logistic regression model was generated to analyze the effect of the variables individually.

We performed subset analysis using a univariate logistic regression with formula exposure as the outcome and IV fluid exposure as the predictor, designed with four different subsets of the data. The subset model included groups of only infants born through C-section, only infants born through vaginal birth, excluded infants with a diagnosis of LGA or SGA, and also excluded infants with a diagnosis of LGA or SGA or IUGR or birthweight less than 2,500 g.

The statistical program “R” was used for the data analysis. Results with a p-value <0.05 were considered significant.

Results

Six hundred twenty-eight infants met the inclusion criteria. One hundred sixty-one (25.6%) infants received IV fluids while 467 (74.4%) did not. Table 1 shows demographic variables of the 628 infants in the NICU regarding exposure to IV fluids. Males received IV fluids at a significantly higher rate than females (31% of the males [n = 94 of 299] versus 20% of the females [n = 67 of 329] [**p = 0.002]). Infants born through C-section received IV fluids at a significantly higher rate than vaginal delivery (35% of C-section delivery [n = 70 of 202], compared with 21% of infants for vaginal delivery [n = 91 of 426] [***p < 0.001]). IV fluid exposure was associated with a significantly longer average length of stay in the NICU, with an average stay of 49.43 (standard deviation [SD] = 10.17) hours with IV fluid exposure, compared with 46.40 (SD = 9.45) hours for newborns that did not receive IV fluids (**p = 0.001). Infants with a higher birth weight (average 3.55 kg) were significantly more likely to receive IV fluids than those of a smaller weight (3.46 kg) (*p = 0.034).

Table 1.

Distribution of Various Demographic Variables Associated with Pregnancy and Delivery Between Two Intravenous Fluid Exposure Groups

IV fluid exposure
	No (n = 467)	Yes (n = 161)	Overall (n = 628)	p
Maternal age (SD)	28.04 (6.83)	28.64 (6.83)	28.19 (6.83)	0.336
Gravidity (%)
1	297 (63.6)	92 (57.2)	389 (61.9)	0.256
2	85 (18.2)	42 (26.1)	127 (20.2)
3	46 (9.9)	16 (9.9)	62 (9.9)
4	20 (4.3)	5 (3.1)	25 (4.0)
5	15 (3.2)	6 (3.7)	21 (3.3)
6	4 (0.9)	0 (0.0)	4 (0.6)
Parity (%)
0	347 (74.3)	120 (74.5)	467 (74.4)	0.747
1	80 (17.1)	32 (19.9)	112 (17.8)
2	23 (4.9)	6 (3.7)	29 (4.6)
3	7 (1.5)	2 (1.2)	9 (1.4)
4	7 (1.5)	1 (0.6)	8 (1.3)
5	3 (0.6)	0 (0.0)	3 (0.5)
Gestational age in weeks (SD)	39.82 (0.98)	39.84 (1.03)	39.82 (0.99)	0.783
Assigned sex
Female	262 (56.1)	67 (41.6)	329 (52.4)	0.002^**
Male	205 (43.9)	94 (58.4)	299 (47.6)
Delivery method type (SD)
C-Section	132 (28.3)	70 (43.5)	202 (32.2)	<0.001^***
Vaginal	335 (71.7)	91 (56.5)	426 (67.8)
Length of stay (hours) (SD)	46.40 (9.45)	49.43 (10.17)	47.17 (9.72)	0.001^**
Birth weight (kg) (SD)	3.46 (0.41)	3.55 (0.44)	3.49 (0.42)	0.034^*
Apgar 1 (SD)	7.33 (2.16)	7.06 (2.33)	7.26 (2.21)	0.195
Apgar 5 (SD)	8.35 (2.03)	8.31 (2.09)	8.34 (2.04)	0.839

Percentages represent the n for either no IV fluid exposure group, n for Yes IV fluid exposure, or overall, as per demographic variable.

p < 0.05.

p < 0.005.

***

p < 0.001.

IV, intravenous; SD, standard deviation.

We found that infants who received IV fluids were given formula significantly less often than infants who were not administered IV fluids (odds ratio [OR] of 0.694, 95% confidence interval [CI]: 0.484–0.993) (*p = 0.046). Delivery method type and parity were not significantly associated with formula exposure. Table 2 shows the demographics for the variables of interest; Table 3 shows the results of univariate logistic regression for these variables. Multivariable logistic regression was not performed because only one of the variables had a p-value <0.2.

Table 2.

Demographic Table of Variables of Interest Used in Univariate Logistic Regression

	Overall n = 628
IV fluid exposure (%)
No	467 (74.4)
Yes	161 (25.6)
Delivery method type (%)
C-Section	202 (32.2)
Vaginal	426 (67.8)
Parity (%)
p = 0	467 (74.4)
p > 0	161 (25.6)
Formula exposure (%)
No	289 (46.0)
Yes	339 (54.0)

Table 3.

Output of Univariate Logistic Regression Models Where Infant Formula Use is the Outcome

	Estimate	Standard error	z	p	Odds ratio	95% CI
IV fluid exposure
(Intercept)	0.254	0.093	2.723	0.006^**	—	—
IV fluid exposure: Yes	−0.366	0.183	−1.996	0.046^*	0.694	0.484–0.993
Delivery method type
(Intercept)	0.219	0.142	1.545	0.122	—	—
Delivery method type: Vaginal	−0.087	0.172	−0.507	0.612	0.917	0.654–1.283
Parity
(Intercept)	0.142	0.093	1.526	0.127	—	—
Parity: p > 0	0.070	0.184	0.383	0.701	1.073	0.749–1.540

p < 0.05.

p < 0.005.

95% CI, confidence interval.

Additionally, we found that in C-section deliveries, infants who received IV fluids received formula significantly less often than infants who did not receive IV fluids (OR of 0.5, 95% CI: 0.277–0.898) (*p = 0.021). In the subgroup, including only vaginal deliveries, infants who received IV fluids received formula less than infants who did not receive IV fluids, but this result is not statistically significant (OR of 0.822, 95% CI: 0.516–1.308) (p = 0.409). With exclusion of LGA or SGA infants, neonates who received IV fluids received formula significantly less often than infants who were not given IV fluids (OR of 0.643, 95% CI: 0.436–0.943) (*p = 0.024). Exclusion of LGA, SGA, IUGR, and birth weight less than 2,500 g similarly resulted in a significant difference in formula exposure between infants who received IV fluids compared with infants who were not administered IV fluids (OR of 0.629, 95% CI: 0.427–0.924) (*p = 0.019). Subgroup distribution with regard to formula exposure is presented in Table 4 and subgroup analysis is presented in Table 5.

Table 4.

Demographic Table of Subset Analysis Groups

Formula exposure
	No (n = 289)	Yes (n = 339)	Overall (n = 628)
Delivery method type (%)
C-section	90 (31.1)	112 (33.0)	202 (32.2)
Vaginal	199 (68.9)	227 (67.0)	426 (67.8)
LGA or SGA (%)
0	269 (93.1)	307 (90.6)	576 (91.7)
1	20 (6.9)	32 (9.4)	52 (8.3)
LGA or SGA or IUGR or BW <2,500 g (%)
0	265 (91.7)	307 (90.6)	572 (91.1)
1	24 (8.3)	32 (9.4)	56 (8.9)

BW, birth weight; IUGR, intrauterine growth restriction; LGA, large for gestational age; SGA, small for gestational age.

Table 5.

Univariate Logistic Regression Output with Subset Data (Infant Formula Use as the Outcome and Intravenous Exposure as the Predictor)

	Estimate	Standard error	z	p	Odds ratio	95% CI
Only C-section
(Intercept)	0.463	0.179	2.588	0.010^**	—	—
IV exposure: Yes	−0.692	0.300	−2.309	0.021^*	0.500	0.277–0.898
Only vaginal
(Intercept)	0.174	0.110	1.582	0.114	—	—
IV exposure: Yes	−0.196	0.237	−0.826	0.409	0.822	0.516–1.308
Exclude LGA or SGA
(Intercept)	0.239	0.096	2.479	0.013^*	—	—
IV exposure: Yes	−0.442	0.196	−2.355	0.024^*	0.643	0.436–0.943
Exclude LGA or SGA or IUGR or BW <2,500 g
(Intercept)	0.260	0.097	2.681	0.007^**	—	—
IV exposure: Yes	−0.463	0.197	−2.355	0.019^*	0.629	0.427–0.924

p < 0.05.

p < 0.005.

Discussion

In this retrospective review, IV fluid administration was associated with a significantly reduced chance of formula exposure while in the NICU (OR: 0.694, 95% CI: 0.484–0.993; *p = 0.046). Interventions that decrease formula exposure and increase the rate of exclusively breastfed infants have significant public health implications, exemplifying the importance of this association.

Not only is the duration of breastfeeding essential for generating benefits, but the establishment of exclusive breastfeeding in the first few days after birth is crucial to developing a successful breastfeeding routine.² The introduction of formula during this time can decrease the likelihood of breastfeeding continuation.^2,3 When considering infants who are separated from their mothers and admitted to the NICU, accommodations should be made to ensure exclusive breastfeeding remains a priority.

Additional interventions, including the use of IV fluids, present a promising alternative to formula supplementation. This may allow for prolonged intervals between feeds, creating more flexibility for mothers to breastfeed their infants in the NICU. There are risks to IV fluid administration, including maintenance of a peripheral IV catheter, which can be a painful procedure, electrolyte disturbances, IV leakage, and IV infiltration.⁴ However, in the study population, infants already had an IV placed for antibiotic administration, so the additional risks of providing IV fluids were minimal. The benefits of increased human milk exposure may outweigh the risks associated with IV placement in neonates who already have an IV in place for alternative reasons.

We were surprised by some of our demographic findings. In our population, males received IV fluids more commonly than females, and larger infants received more IV fluids than smaller infants. We are unable to hypothesize a reason that providers would order IV fluids differently based on assigned sex or greater weight.

Administration of IV fluids was associated with a slightly longer stay in the NICU. However, we believe the 3-hour difference in length of stay is worthwhile to decrease formula exposure, and therefore improve breastfeeding outcomes.

During the subgroup analysis, we found that, for vaginal deliveries, infants who received IV fluids received formula less than infants who did not receive IV fluids; however, this result was not statistically significant (OR of 0.822 95% CI: 0.516–1.308) (p = 0.409). We have some difficulty explaining why the findings are significant for the whole group and for the C-section subgroup but not for the vaginal delivery group. One explanation may be that the vaginal delivery subgroup did not have enough numbers for the statistical analysis to find the true effect. Another explanation may be that there is a trend; however, the trend is not significant because administration of maintenance IV fluids is less critical in vaginally delivered infants. Following vaginal deliveries, mothers may experience less pain and are able to ambulate more easily, increasing their accessibility to feed an infant in the NICU. It is established that infants delivered through C-section typically lose more weight than infants born vaginally.⁵ This effect may be due to the difficulties with feedings after C-section as a result of the factors mentioned above.

A strength of this study is that a significant effect was found through our large sample size. To our knowledge, this is the first study reporting administration of IV fluids for healthy neonates in the NICU as a supplement for mothers who are unable to breastfeed at necessary intervals.

A major limitation is that this is a retrospective study of nonmatched infants and not a case/control study and thus the limited regression analysis cannot correct for hidden biases. Other limitations of this study include that the practice of separating infants from mothers as a result of maternal chorioamnionitis is becoming less common as the standard of care changes, including the practice at the Rady Children's Hospital NICUs. However, neonates are still separated from their mothers for a variety of reasons, making this information applicable to designing future studies in cases of mother/infant separation. These data are now several years old; however, this is a population that otherwise would be hard to replicate because of the change in practice.

Conclusions

This retrospective chart review found that infants transferred to the NICU and separated from their mother due to chorioamnionitis exposure who received IV fluids were significantly less likely to receive any infant formula than infants who were not administered IV fluids (OR of 0.694, 95% CI: 0.484–0.993) (*p = 0.046). Interventions that increase human milk exposure have important implications, and further prospective studies are warranted to confirm this association.

Footnotes

Acknowledgments

The authors would like to thank Sarah Lazar and the Neonatal Clinical Research Team.

Authors' Contributions

C.S. designed the study, collected and analyzed data, and drafted and reviewed the article. E.R. analyzed data and drafted and reviewed the article. E.L. analyzed the data and reviewed the article.

Disclosure Statement

No competing financial interests exist.

Funding Information

The University of California San Diego, Division of Neonatology individual discretionary funds were used.

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