Early Expressed Milk Volume and Coming to Volume for Mother’s Own Milk Feeding in Hospitalized Infants

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Abstract Objective Assess if cumulative pumping volumes during the first 5 postnatal days (CVx5) influence coming to volume (CTV: producing > 500 milliliters breast milk per day by postnatal day 14) for mothers of hospitalized infants, with a secondary aim to develop and compare a new predictive model using CVx5 with our previous model. Study Design: A retrospective cohort analysis was conducted at Duke University Hospital for singleton mother-baby dyads of neonatal intensive care infants between January 2020 and December 2023. Results Of 887 mother-baby dyads, 325 (37%) achieved CTV and were more likely to have higher CVx5 (1 058 ± 25 ml vs. 231 ± 19 ml; p < 0.0001). In generalized regression models for CTV that included birth weight, 5x5, AMx5, and CVx5, only CVx5 and 5x5 remained significant (p < 0.0001). Conclusion CTV is significantly associated with CVx5, and with 5x5, creates a stronger model than that of 5x5 and birth weight.
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Study Design: A retrospective cohort analysis was conducted at Duke University Hospital for singleton mother-baby dyads of neonatal intensive care infants between January 2020 and December 2023. Results Of 887 mother-baby dyads, 325 (37%) achieved CTV and were more likely to have higher CVx5 (1 058 ± 25 ml vs. 231 ± 19 ml; p < 0.0001). In generalized regression models for CTV that included birth weight, 5x5, AMx5, and CVx5, only CVx5 and 5x5 remained significant (p < 0.0001). Conclusion CTV is significantly associated with CVx5, and with 5x5, creates a stronger model than that of 5x5 and birth weight. Health sciences/Health care/Paediatrics Health sciences/Health care/Patient education Figures Figure 1 Introduction Feeding mother’s own milk (MOM) to infants hospitalized in neonatal intensive care units (NICUs) is strongly associated with fewer morbidities and improved neurodevelopmental and health outcomes. 1 , 2 Establishing maternal milk supply in the first postnatal days is crucial for the longer-term supply needed for a lengthy NICU hospitalization and post-discharge. 2 – 4 Mothers who can achieve a pumped MOM volume of 500 milliliters (ml) in a 24-hour period in the first 14 postnatal days, also defined as ‘coming to volume’ (CTV), are much more likely to successfully provide MOM for their infants for an extended NICU stay. 5 Mago-Shah et al. and others have reported that increased pumping frequency, specifically defined as 5 or more milk-producing pumping episodes on postnatal day 5 (5x5) by Mago-Shah et al., is strongly correlated with achieving CTV and having increased milk volume production. 6 , 7 Recently, Hoban et al. assessed details of daily pumping efforts in the first 14 postpartum days and associations with secretory activation and CTV. 8 Their results, as well as earlier reports, stress the importance of supporting mothers of premature infants to establish pumping in the first postnatal days. While the first postpartum hours offer an opportunity to focus efforts on pumping frequency to improve likelihood of success, mothers often may not be able to pump effectively in the first few hours after birth. Therefore, early pumping frequency alone may not be sufficient. However, it is possible that accumulating milk volume in the first postnatal days could aid in identifying mothers more likely to successfully CTV by postnatal day 14. 9 Our study aims were: 1) to assess strength of the association between the accumulating volume of pumped MOM over the first 5 postnatal days (CVx5) and CTV, and how demographic and clinical factors modify any associations between CVx5 and CTV; 2) to explore CVx5 for mothers who were pumping 5x5 and those who were not; and 3) assess whether the inclusion of CVx5 in a prediction model improves the accuracy of CTV outcomes compared to our previously described model using 5x5, pumping at least once between 1 AM and 5 AM by postnatal day 5 (AMx5), and birth weight regressors. 6 Methods This observational retrospective cohort review was conducted at Duke University Hospital NICU, a 74 bed, tertiary care, open-bay intensive care unit in a large academic medical center. The inborn patient population was 93.3%. As in our prior work, this study utilized Epic® (Epic®, Verona, WI) and Timeless® (Timeless Medical Systems®, Charlottetown, PE, Canada) data from mothers and their singleton infants born at Duke and admitted to the NICU within 24 hours of delivery. Characteristics of the electronic health record and the software program used to track mothers’ milk received and dispensed have been described previously. 6 Data were collected from mothers whose infants were admitted from January 2020 to December 2023. Mothers who provided no MOM, initiated pumping after postnatal day 5, gave birth to multiples, or whose infants were hospitalized in the NICU for less than 5 days or more than 120 days were excluded (Fig. 1 ). Mothers whose infants died, including those with lethal congenital anomalies, were also excluded. We compared demographics and CVx5 between mothers who did and did not achieve CTV, and whose infants were born at Duke University Hospital and admitted to the NICU. We obtained maternal demographics including self-identified race, self-identified ethnicity, insurance status, type of delivery (cesarean or vaginal), birth weight, time and date of MOM pumped, and volume of MOM pumped per session. Infant demographics included sex, birth weight, and gestational age. Our primary outcome was CTV, defined by Hoban and colleagues as pumped MOM volume ≥ 500 ml/day for at least one 24-hour period during the first 14 days. 5 In bivariate analysis, infant sex, delivery type, maternal race, maternal ethnicity, medical insurance type, intraamniotic infection (IAI), and pre-eclampsia were tested for an association with CTV. IAI and pre-eclampsia were patient diagnoses obtained from the electronic health record. We also assessed how CVx5 produced by mothers who successfully achieved CTV compared to CVx5 for the mothers who did not achieve CTV for each of the first 14 postnatal days. A separate multivariate analysis was performed on those metrics significantly associated with CTV. Analysis of nominal cohorts with non-parametric continuous data were performed using the Wilcoxon Kruskal-Wallis test. Categorical data were compared using the Chi-square test. The general regression platform was used to create a model of CTV with the following regressors: CVx5, 5x5, AMx5, maternal race, maternal ethnicity, IAI, and maternal insurance data. 10 To address multiple collinearity concerns, reduce the risk of overfitting, and improve the model’s predictive performance, we used the adaptive double Least Absolute Shrinkage and Selection Operator (LASSO) technique. 11 We validated the model using the Bayesian Information Criterion (BIC) with the intention to create a parsimonious model with robust regressors. 12 Variable importance indices were constructed using Monte Carlo sampling and a k-nearest neighbors approach to account for correlation. Competing models to predict CTV were compared with Delong’s AUC comparison test. 13 Statistical analyses were performed using JMP Pro 17.1 (SAS®, Cary, NC). A p-value less than 0.05 was considered significant. This retrospective cohort study was reviewed and approved by the Duke Institutional Review Board. Results A total of 887 mother-baby dyads met the inclusion criteria (Supplemental Figure 1). Thirty seven percent (325/887) of the mothers achieved CTV. Six mothers in the cohort had 1 or more prior liveborn infants, of which all were preterm. Mean (standard deviation) birth weight of the infants in the cohort was 2 144 grams (± 839), and mean gestational age was 33.5 weeks (± 3.56). Fifty-three percent of the infants in these mother-baby dyads were male (Table 1). CTV comparisons by maternal demographics (Table 1) When comparing demographics between mothers achieving CTV and those who do not, we found no differences regarding perinatal factors such as maternal age, maternal race classification, mode of delivery, or preeclampsia. Mothers who identified as ethnically Hispanic were less likely to CTV than non-Hispanic mothers (29% vs. 38%; p = 0.0222). Additionally, mothers with commercial health insurance were more likely to CTV than mothers who had Medicaid, other governmental insurance, or were non-insured (42% vs. 33%; p = 0.0031). Mothers who did not have IAI were also more likely to CTV than those who did (38% vs. 18%; p = 0.0091). CVx5 comparisons by delivery mode and maternal demographics (Table 2) By postnatal day 5, mothers who delivered via cesarean section had less CVx5 compared to those who had a vaginal delivery (mean ± SE: 469 ± 25 ml vs. 647 ± 33 ml; p < 0.0001). There were no significant racial differences in cumulative MOM volume between White, Black, and Asian mothers. However, mothers identifying as “Other” pumped less MOM (419 ± 54 ml; p = 0.0079) than White mothers. Significant ethnic differences (p = 0.0249) were observed, with Hispanic mothers producing less MOM than non-Hispanic mothers (416 ± 43 ml vs. 559 ± 23 ml; p = 0.0086). Health insurance plans, infant birth weight, and gestational age did not significantly affect CVx5. Pre-eclampsia had no significant effect on CVx5 (p = 0.1082), whereas presence of IAI significantly decreased CVx5 (p = 0.0233). CVx5 by CTV, 5x5, and AMx5 (Table 3a) We found that mothers achieving CTV had a higher CVx5 than those who do not CTV (1058 ± 25 ml vs. 231 ± 19 ml; p < 0.0001). Those who pumped 5x5 also had a higher CVx5 than those who did not (894 ± 27 ml vs. 270 ± 23 ml; p < 0.0001). Mothers who did not pump 5x5 but had greater CVx5 were more likely to CTV than those with lower CVx5, though they needed to pump a greater volume to achieve CTV than mothers who did pump 5x5. Mothers who pumped AMx5 had increasingly more CVx5 than those without any AMx5 (791 ± 25 ml vs. 264 ± 26 ml; p < 0.0001). CVx5, AMx5 and predictive modeling for CTV The influence of CVx5 on CTV was significant with the likelihood of CTV increasing by over 2.9 times for each increase in CVx5 by 250 ml (Table 3b). Indeed, additional AM pumping attempts improve CVx5 (Supplemental Figure 2). Given this strong relationship, we performed a multivariate analysis to predict CTV using the following variables: CVx5, 5x5, AMx5, race, ethnicity, insurance, and maternal IAI. The current model was validated by BIC, retained CVx5 and 5x5 metrics (Table 4), and achieved an AUC of 0.9090 (Figure 1). Using the same set of data, we compared our current model against the previous model described by Mago-Shah et al. 6 The current model performed significantly better utilizing CVx5 and 5x5 data than the previous model, which relied on 5x5, AMx5, and birth weight (p < 0.0001) (Figure 1). Discussion This observational retrospective cohort analysis involved 887 mother-baby dyads to explore factors associated with CTV within the first two postpartum weeks. Our findings support earlier studies linking milk production and CTV with mode of delivery, IAI, and ethnicity. Since CTV is defined as a 500 ml threshold volume, we hypothesized that accumulating volume within the first week of life would be linked to CTV. CTV was higher among some demographic groups Demographic factors such as increased maternal age have been reported to be independently correlated with decreased MOM volume, as these mothers may produce less MOM regardless of which pumping strategy they employ. 14,15 When comparing the age of mothers achieving CTV with those who did not, we found no significant difference. However, it should be noted that CTV is a relatively early measurement of MOM production and may differ from longer, longitudinal measures of MOM supply. We did find that mothers identifying as Hispanic were less likely to CTV as compared to non-Hispanic mothers. Mothers with commercial insurance were more likely to CTV than mothers with Medicaid, governmental, or self-pay health plans. Some studies showed that public health insurance, Hispanic ethnicity, and Black maternal race were correlated with lower MOM use. 16,17 As previously reported, the influence of ethnicity, race, and insurance status are social constructs that do not contribute to production of milk once frequency and timing of pumping are controlled. 6 A combination of higher rates of preterm birth, increased economic burden associated with pumping, and lack of social or work environment support when exclusively pumping could lead to these findings, and indicate a need for both social and systemic support in establishing breast milk pumping practices during the birth hospitalization. 2 Although beyond the scope of the present paper, it will be critical to address these socioeconomic disparities in the maternal and infant population as they relate to MOM success. CVx5 and CTV CVx5 was strongly associated with CTV. We found that for every 250 ml increase in CVx5, the odds of CTV increased by 2.9. This finding further emphasizes the need for establishing methods of increasing pumped MOM volumes in the first days of life, as it positively correlates with increased CTV achievement. In this connection, several studies have also found that early MOM volume predicts volume sufficiency through discharge in hospitalized infants. 18,19 Mothers delivering by cesarean section produced less CVx5 but were no different in CTV. A reasonable explanation for this finding is that CTV is a categorical achievement, in that a mother only must pump 500 ml once in a 24-hour period by postnatal day 14. However, our finding that MOM volumes were reduced within even the first 5 postnatal days suggests that other mechanisms may be responsible for reducing MOM production. A systematic review on emergency cesarean section deliveries reported reduced oxytocin and prolactin responses to breastfeeding, which can lead to delayed onset of lactation and subsequently lower MOM volumes. 20 The logistical care required in the post-operative period and pain experienced by the mother can also delay the early breast feeding or milk expression via pumping required to achieve CTV. 2 Mothers who deliver cesarean section could benefit from intentional, early intervention to help increase expressed milk volumes soon after delivery. Marginalized and minority groups may experience increased difficulties in breastfeeding due to socioeconomic barriers and systemic inequities, including decreased lactation consultant support during the hospitalization and transportation issues leading to gaps in providing adequate pumped MOM supply to the hospitalized infant. 16 In our study, we found no differences in insurance type or race when comparing CVx5, but mothers identifying as Other produced significantly less MOM than White mothers. Hispanic-identifying mothers produced less MOM compared to non-Hispanic mothers, which parallels our findings in CTV achievement. While no published studies have yet compared MOM volumes between demographic groups, a study looking at the odds ratio of no maternal MOM at discharge in the very-low-birth-weight population found that Black mothers had higher, and Hispanic mothers lower, odds of not using MOM at discharge. 21 Another study also found that Black mothers and mothers with public insurance had lower odds ratio of using MOM at discharge, but found no differences between Hispanic and non-Hispanic mothers. 16 Nevertheless, a similar need to focus on providing socio-financial resources in helping mothers successfully develop sufficient MOM volume after delivery should be addressed. Pumping 5x5 and CVx5 The frequency and quantity of pumping episodes in the first postnatal days have been reported to have a positive correlation to breast milk production. 7 Specifically, as reported in our previous paper, pumping 5x5, or at least 5 times per day on the postnatal day 5, is associated with successful CTV. 6 Our findings from this study support our previous findings, as there were significant differences in CVx5 between those who pumped 5x5 and those who did not. Mothers who followed the 5x5 schedule had higher volumes and, consequently, a greater likelihood of achieving CTV. We also found that AMx5, or having a milk-producing pumping episode between 1 and 5 AM at least once during the first 5 postnatal days, was associated with increased CVx5. This supports previous findings that AMx5 is independently associated with MOM production and improves the likelihood of CTV. 6 Overall, both pumping 5x5 and AMx5 are positive predictive factors for CTV and for CVx5. It is important to note that AMx5 is related to 5x5 in that it is difficult to pump 5x5 without AMx5. Though both influence CVx5, AMx5 did not persist in our current model due to the strength of 5x5, and that a mother pumping 5x5 is more likely to pump AMx5 as well. Comparison of competing models to predict CTV In our previous study, we found that CTV could be predicted using a model created with the following regressors: 5x5, AMx5, and birth weight. 6 In the current study, we found that a robust model created with only two regressors, CVx5 and 5x5, outperformed our earlier model. While the precise reason for loss of AMx5 is unclear, it seems likely that its collinearity with both CVx5 and 5x5 resulted in its removal from the model. Limitations This model was based on infants in a Level IV NICU and may be less applicable to infants in community hospitals. Another important limitation to overcome is the reliance on data from infants previously discharged from the NICU. It remains to be seen if data can be collected, analyzed, and turned into actionable knowledge while the infants are still within their first week of hospitalization. The selection of the study population also excluded mothers with multiple births as well as those whose infants died during their stay in the NICU. They were excluded because of likely significant differences in maternal stress, which could confound our breast milk production study. 22 The study further only included infants whose length of hospitalization was less than 14 days. This may have created a bias towards fewer infants scored as CTV since they left before their daily MOM through DOL 14 could be assessed. Additionally, MOM volumes were brought into the hospital by mothers, and it is possible that there may be some pumped volumes that were not brought into the hospital. Another limitation of the study was the presence of multiple factors with varying degrees of collinearity. To partially address this, we employed a double LASSO technique to identify covariates for inclusion in the regression model, though collinearity concerns may persist. Another potential limitation was our choice of the BIC over the AICc as the validation tool. Although we recognize that this approach might remove potential regressors, our decision was based on the future utility of the model’s outcome: to create a simple yet robust predictive model using clinical data available by postnatal day 5. Conclusions and Implications CTV is a process involving frequent and persistent maternal participation. In addition, complex hormonal and emotional factors not examined in the present paper also influence MOM production. Our study confirms prior work that has shown that CTV is a significant predictor of MOM sufficiency in a premature NICU population. 3,5 The present study provides a simplified and more robust model to predict CTV based on historical data. More specifically, these strategies utilize available cumulative milk volume data that providers are likely able to access in pump-dependent mothers of hospitalized infants, within the first 5 postnatal days, to predict whether mothers would CTV. While our study is a retrospective evaluation of hospitalized infants and thus do not include healthier mother-baby dyads who are discharged earlier, it provides the groundwork to develop strategies and delineation points for providers to help mothers struggling to achieve CTV. Our model also allows sufficient time for providers to intervene should CTV be predicted as unattainable. Future work can build upon this study by developing and testing prediction models based on CVx5, CTV, and 5x5 with data obtained from infants while still in the NICU, and by exploring other factors that are likely to influence maternal milk production following postnatal day 5. Such a predictive, near real-time CTV tool could be beneficial in helping providers identify mothers who may need assistance while their infant is still in the NICU. Declarations No conflicts of interest for all authors. No funding was received to produce this manuscript. NC, DTT, CMC, and KG designed the study and helped to compose the manuscript. LL contributed to data collection and creation of data processing methods. KA contributed to critical review and revision. Acknowledgements : The authors gratefully recognize the support and technical assistance provided by Rick Pittman, BA. References Parker MG, Stellwagen LM, Noble L, et al. Promoting Human Milk and Breastfeeding for the Very Low Birth Weight Infant. Pediatrics 2021;148(5). DOI: 10.1542/peds.2021-054272. Hoban R, Bowker RM, Gross ME, Patel AL. Maternal production of milk for infants in the neonatal intensive care unit. Seminars in Perinatology 2021;45(2):151381. DOI: https://doi.org/10.1016/j.semperi.2020.151381. Murase M, Nommsen-Rivers L, Morrow AL, et al. Predictors of low milk volume among mothers who delivered preterm. J Hum Lact 2014;30(4):425-35. (In eng). DOI: 10.1177/0890334414543951. Chen DC, Nommsen-Rivers L, Dewey KG, Lönnerdal B. Stress during labor and delivery and early lactation performance. Am J Clin Nutr 1998;68(2):335-44. (In eng). DOI: 10.1093/ajcn/68.2.335. Hoban R, Bigger H, Schoeny M, Engstrom J, Meier P, Patel AL. Milk Volume at 2 Weeks Predicts Mother's Own Milk Feeding at Neonatal Intensive Care Unit Discharge for Very Low Birthweight Infants. Breastfeed Med 2018;13(2):135-141. (In eng). DOI: 10.1089/bfm.2017.0159. Mago-Shah DD, Athavale K, Fisher K, Heyward E, Tanaka D, Cotten CM. Early pumping frequency and coming to volume for mother’s own milk feeding in hospitalized infants. Journal of Perinatology 2023;43(5):629-634. DOI: 10.1038/s41372-023-01662-z. Fewtrell MS, Kennedy K, Ahluwalia JS, Nicholl R, Lucas A, Burton P. Predictors of expressed breast milk volume in mothers expressing milk for their preterm infant. Archives of Disease in Childhood - Fetal and Neonatal Edition 2016;101(6):F502-F506. DOI: 10.1136/archdischild-2015-308321. Hoban R, Medina-Poeliniz C, Signorile M, Janes J, Fan C-PS, Meier PP. Early postpartum pumping behaviors, pumped milk volume, and achievement of secretory activation in breast pump-dependent mothers of preterm infants. Journal of Perinatology 2024. DOI: 10.1038/s41372-024-02021-2. Fleiss N, Morrison C, Nascimento A, Stone D, Myers E. Improving Early Colostrum Administration to Very Low Birth Weight Infants in a Level 3 Neonatal Intensive Care Unit: A Quality Improvement Initiative. J Pediatr 2023;260:113421. (In eng). DOI: 10.1016/j.jpeds.2023.113421. Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection. Obstet Gynecol 2017;130(2):e95-e101. (In eng). DOI: 10.1097/aog.0000000000002236. Urminsky O, Hansen C, Chernozhukov V. 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Demographics of mothers by CTV or no CTV Overall CTV No CTV P-Value Condition 887 325 562 Birth weight, grams, mean ± SD 2,144 ± 839 2,131 ± 777 2,151 ± 873 0.7290 Gestational age, weeks, mean ± SD 33.5 ± 3.56 33.4 ± 3.47 33.6 ± 3.61 0.4412 Infant sex Male, % 471, 53.1 176, 54.2 295, 52.5 0.6236 Length of stay 5-14 days >14 days 422 465 146 179 276 286 0.2289 Mother’s age*, years, mean ± SD 31.5 + 6.26 31.06 + 5.82 31.80 + 6.49 0.0896 Mother’s race classification White Black Other/Not identifying 371 343 173 146 115 63 225 227 110 Overall: 0.3075 Ref 0.1253 0.5119 Mother’s ethnicity classification Non-Hispanics Hispanics Not identifying 732 147 8 281 42 2 451 105 6 Overall: 0.0623 Ref 0.0222 0.4384 Delivery Cesarean section Vaginal 566 321 195 130 371 191 Overall: 0.0725 Mother’s insurance status Commercial Medicaid/Government/Other 366 521 155 170 211 351 Overall: 0.0031 Maternal diagnoses Pre-Eclampsia No Pre-Eclampsia IAI No IAI 236 651 44 843 78 247 8 317 158 404 36 526 Overall: 0.1816 Overall: 0.0091 *Data missing for 5 mothers. CTV: Coming to volume SD: Standard deviation IAI: Intraamniotic infection Table 2. CVx5 by delivery mode and demographics Condition Number Mean CVx5 ( + SE) (ml) P-Value Delivery <.0001 Cesarean section Vaginal 566 321 469 (25) 647 (33) Race White Black Asian Other 371 343 51 122 584 (31) 530 (32) 469 (84) 419 (54) 0.0536 Ref 0.2514 0.2062 0.0079 Ethnicity Non-Hispanic Hispanic Not identifying 732 147 8 559 (23) 416 (43) 392 (137) 0.0249 Ref 0.0086 0.4447 Insurance Commercial Medicaid/Government/Other 366 521 574 (31) 505 (26) 0.0940 BW Intercept BW vs. cumulative volume (slope) 887 525 (55) 0.0042 (0.0241) 0.8629 14 days 422 465 542 (29) 526 (28) 0.6832 Maternal diagnoses Pre-eclampsia No pre-eclampsia IAI No IAI 236 651 44 843 480 (39) 553 (24) 333 (90) 544 (21) 0.1082 0.0233 CVx5: Cumulative volume by postnatal day 5 SE: Standard error BW: Birth weight GA: Gestational age IAI: Intraamniotic infection Tables 3a and 3b. CTV by pumping strategies Table 3a. CVx5 by CTV, 5x5, and AMx5 Condition Number Mean CVx5 ( + SE) (ml) P-Value CTV <.0001 CTV Did not CTV 325 562 1058 (25) 231 (19) 5x5 5x5 Did not 5x5 375 512 894 (27) 270 (23) <.0001 AMx5 AMx5 Did not AMx5 454 433 791 (25) 264 (26) <.0001 Table 3b. Likelihood to CTV for CVx5 increasing by 250 ml Term Odds Ratio Lower 95% Upper 95% CVx5 by 250 ml 2.927 2.535 3.379 CVx5: Cumulative volume by postnatal day 5 CTV: Coming to volume 5x5: Pumping at least 5 times per day by postnatal day 5 AMx5: Pumping at least once between 1 AM and 5 AM by postnatal day 5 SE: Standard error Table 4. Multivariable analysis table Variable Wald Chi Square Probability > Chi Square Odds Ratio Lower 95% Upper 95% CVx5 per 100 ml 154.6 < .0001 1.50 1.41 1.60 5x5 8.74 0.0031 1.87 1.24 2.84 Multivariable analysis with CTV vs CVx5, 5x5, AMx5, race, ethnicity, insurance, and birth weight. Factors remaining in the model (using Bayesian Information Criterion with early stopping) are CVx5 and 5x5. CVx5: Cumulative volume by postnatal day 5 5x5: Pumping at least 5 times per day by postnatal day 5 CTV: Coming to volume AMx5: Pumping at least once between 1 AM and 5 AM by postnatal day 5 Additional Declarations There is NO conflict of interest to disclose. Supplementary Files EarlyExpressedMilkVolumeSupplementalFigures.docx Consort diagram and AM Pumping Frequency and CTV Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Gray","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYBACCTBpAOV9YIMwJYjWwjiDeC1QwMxDjBbJ9h7DzxUFdgzy0YefSduUHTbmZ2A+eJsHjxZpnjPGkmcMkhkMz6WZSeecO2wm2cCWbI1Pi5xEjoFkgwEzg2EPg5l0btthG4MDPGbSeLXIvzH+2WBQD9TC/k3aEqjF/gD/N7xapCV4gE4xOMwgzwM0nLHtsJkBAw8bXi2SPWlllg0Gx3kMeHiKLXvOpRtLHGYztpyDR4vE8cObbzb8qZaT72HfeONHmbVhf3vzwxtv8GhhYOAAxwSPwQEGFkh0MONVDgLsD8CUfAMD8weCikfBKBgFo2BEAgCJoUEsYFPfqQAAAABJRU5ErkJggg==","orcid":"","institution":"Duke University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Keyaria","middleName":"","lastName":"Gray","suffix":""},{"id":387232535,"identity":"9a494177-b96e-449a-9508-a52decb19c84","order_by":1,"name":"Nellie Chen","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Nellie","middleName":"","lastName":"Chen","suffix":""},{"id":387232536,"identity":"604f036a-c4f7-4233-8c7d-c1ad0ddb43c8","order_by":2,"name":"David Tanaka","email":"","orcid":"https://orcid.org/0000-0002-0169-6172","institution":"DUKE UNIVERSITY MEDICAL CENTER","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Tanaka","suffix":""},{"id":387232537,"identity":"669b6dd4-8807-4090-9142-4107475715fe","order_by":3,"name":"Kamlesh Athavale","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Kamlesh","middleName":"","lastName":"Athavale","suffix":""},{"id":387232538,"identity":"05dca72e-8dbc-48e5-8376-cf0028787042","order_by":4,"name":"Lusia Li","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Lusia","middleName":"","lastName":"Li","suffix":""},{"id":387232539,"identity":"cf77c456-a9c9-462e-8bf0-8f351ef1b736","order_by":5,"name":"Michael Cotten","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Cotten","suffix":""}],"badges":[],"createdAt":"2024-12-02 15:45:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5565965/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5565965/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72301334,"identity":"50f92bf5-7fad-4293-9652-461786b2b4bf","added_by":"auto","created_at":"2024-12-25 01:33:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94921,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eModel comparisons of CVx5 and 5x5 model (current model, red) versus CTV with 5x5, AMx5, and birth weight (previous model from Mago-Shah et al., 2023, blue)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5565965/v1/2c0542c53967b9be55d9c84f.png"},{"id":73491946,"identity":"be862efe-a23f-4c81-a006-40cb89b61068","added_by":"auto","created_at":"2025-01-10 13:28:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1224644,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5565965/v1/8689aa0e-bad9-4385-84e9-40cc1f5ee98f.pdf"},{"id":72300958,"identity":"21bda830-094d-43c8-ba17-2793f07751da","added_by":"auto","created_at":"2024-12-25 01:25:27","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":179422,"visible":true,"origin":"","legend":"Consort diagram and AM Pumping Frequency and CTV","description":"","filename":"EarlyExpressedMilkVolumeSupplementalFigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-5565965/v1/a24d06e6e181b08b4adc4a6b.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Early Expressed Milk Volume and Coming to Volume for Mother’s Own Milk Feeding in Hospitalized Infants","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFeeding mother\u0026rsquo;s own milk (MOM) to infants hospitalized in neonatal intensive care units (NICUs) is strongly associated with fewer morbidities and improved neurodevelopmental and health outcomes.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Establishing maternal milk supply in the first postnatal days is crucial for the longer-term supply needed for a lengthy NICU hospitalization and post-discharge.\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Mothers who can achieve a pumped MOM volume of 500 milliliters (ml) in a 24-hour period in the first 14 postnatal days, also defined as \u0026lsquo;coming to volume\u0026rsquo; (CTV), are much more likely to successfully provide MOM for their infants for an extended NICU stay.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMago-Shah et al. and others have reported that increased pumping frequency, specifically defined as 5 or more milk-producing pumping episodes on postnatal day 5 (5x5) by Mago-Shah et al., is strongly correlated with achieving CTV and having increased milk volume production.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Recently, Hoban et al. assessed details of daily pumping efforts in the first 14 postpartum days and associations with secretory activation and CTV.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Their results, as well as earlier reports, stress the importance of supporting mothers of premature infants to establish pumping in the first postnatal days. While the first postpartum hours offer an opportunity to focus efforts on pumping frequency to improve likelihood of success, mothers often may not be able to pump effectively in the first few hours after birth. Therefore, early pumping frequency alone may not be sufficient. However, it is possible that accumulating milk volume in the first postnatal days could aid in identifying mothers more likely to successfully CTV by postnatal day 14.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur study aims were: 1) to assess strength of the association between the accumulating volume of pumped MOM over the first 5 postnatal days (CVx5) and CTV, and how demographic and clinical factors modify any associations between CVx5 and CTV; 2) to explore CVx5 for mothers who were pumping 5x5 and those who were not; and 3) assess whether the inclusion of CVx5 in a prediction model improves the accuracy of CTV outcomes compared to our previously described model using 5x5, pumping at least once between 1 AM and 5 AM by postnatal day 5 (AMx5), and birth weight regressors.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis observational retrospective cohort review was conducted at Duke University Hospital NICU, a 74 bed, tertiary care, open-bay intensive care unit in a large academic medical center. The inborn patient population was 93.3%. As in our prior work, this study utilized Epic\u0026reg; (Epic\u0026reg;, Verona, WI) and Timeless\u0026reg; (Timeless Medical Systems\u0026reg;, Charlottetown, PE, Canada) data from mothers and their singleton infants born at Duke and admitted to the NICU within 24 hours of delivery. Characteristics of the electronic health record and the software program used to track mothers\u0026rsquo; milk received and dispensed have been described previously.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Data were collected from mothers whose infants were admitted from January 2020 to December 2023. Mothers who provided no MOM, initiated pumping after postnatal day 5, gave birth to multiples, or whose infants were hospitalized in the NICU for less than 5 days or more than 120 days were excluded (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Mothers whose infants died, including those with lethal congenital anomalies, were also excluded.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe compared demographics and CVx5 between mothers who did and did not achieve CTV, and whose infants were born at Duke University Hospital and admitted to the NICU. We obtained maternal demographics including self-identified race, self-identified ethnicity, insurance status, type of delivery (cesarean or vaginal), birth weight, time and date of MOM pumped, and volume of MOM pumped per session. Infant demographics included sex, birth weight, and gestational age. Our primary outcome was CTV, defined by Hoban and colleagues as pumped MOM volume\u0026thinsp;\u0026ge;\u0026thinsp;500 ml/day for at least one 24-hour period during the first 14 days.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn bivariate analysis, infant sex, delivery type, maternal race, maternal ethnicity, medical insurance type, intraamniotic infection (IAI), and pre-eclampsia were tested for an association with CTV. IAI and pre-eclampsia were patient diagnoses obtained from the electronic health record. We also assessed how CVx5 produced by mothers who successfully achieved CTV compared to CVx5 for the mothers who did not achieve CTV for each of the first 14 postnatal days. A separate multivariate analysis was performed on those metrics significantly associated with CTV.\u003c/p\u003e \u003cp\u003eAnalysis of nominal cohorts with non-parametric continuous data were performed using the Wilcoxon Kruskal-Wallis test. Categorical data were compared using the Chi-square test. The general regression platform was used to create a model of CTV with the following regressors: CVx5, 5x5, AMx5, maternal race, maternal ethnicity, IAI, and maternal insurance data.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e To address multiple collinearity concerns, reduce the risk of overfitting, and improve the model\u0026rsquo;s predictive performance, we used the adaptive double Least Absolute Shrinkage and Selection Operator (LASSO) technique.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e We validated the model using the Bayesian Information Criterion (BIC) with the intention to create a parsimonious model with robust regressors.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Variable importance indices were constructed using Monte Carlo sampling and a k-nearest neighbors approach to account for correlation. Competing models to predict CTV were compared with Delong\u0026rsquo;s AUC comparison test.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Statistical analyses were performed using JMP Pro 17.1 (SAS\u0026reg;, Cary, NC). A p-value less than 0.05 was considered significant.\u003c/p\u003e \u003cp\u003e This retrospective cohort study was reviewed and approved by the Duke Institutional Review Board.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 887 mother-baby dyads met the inclusion criteria (Supplemental Figure 1). Thirty seven percent (325/887) of the mothers achieved CTV. Six mothers in the cohort had 1 or more prior liveborn infants, of which all were preterm. Mean (standard deviation) birth weight of the infants in the cohort was 2 144 grams (\u0026plusmn; 839), and mean gestational age was 33.5 weeks (\u0026plusmn; 3.56). Fifty-three percent of the infants in these mother-baby dyads were male (Table 1). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCTV comparisons by maternal demographics (Table 1)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWhen comparing demographics between mothers achieving CTV and those who do not, we found no differences regarding perinatal factors such as maternal age, maternal race classification, mode of delivery, or preeclampsia. Mothers who identified as ethnically Hispanic were less likely to CTV than non-Hispanic mothers (29% vs. 38%; p = 0.0222). Additionally, mothers with commercial health insurance were more likely to CTV than mothers who had Medicaid, other governmental insurance, or were non-insured (42% vs. 33%; p = 0.0031). Mothers who did not have IAI were also more likely to CTV than those who did (38% vs. 18%; p = 0.0091).\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCVx5 comparisons by delivery mode and maternal demographics (Table 2)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBy postnatal day 5, mothers who delivered via cesarean section had less CVx5 compared to those who had a vaginal delivery (mean \u0026plusmn; SE: 469 \u0026plusmn; 25 ml vs. 647 \u0026plusmn; 33 ml; p \u0026lt; 0.0001). There were no significant racial differences in cumulative MOM volume between White, Black, and Asian mothers. However, mothers identifying as \u0026ldquo;Other\u0026rdquo; pumped less MOM (419 \u0026plusmn; 54 ml; p = 0.0079) than White mothers. Significant ethnic differences (p = 0.0249) were observed, with Hispanic mothers producing less MOM than non-Hispanic mothers (416 \u0026plusmn; 43 ml vs. 559 \u0026plusmn; 23 ml; p = 0.0086). Health insurance plans, infant birth weight, and gestational age did not significantly affect CVx5. Pre-eclampsia had no significant effect on CVx5 (p = 0.1082), whereas presence of IAI significantly decreased CVx5 (p = 0.0233).\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCVx5 by CTV, 5x5, and AMx5 (Table 3a)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe found that mothers achieving CTV had a higher CVx5 than those who do not CTV (1058 \u0026plusmn; 25 ml vs. 231 \u0026plusmn; 19 ml; p \u0026lt; 0.0001). Those who pumped 5x5 also had a higher CVx5 than those who did not (894 \u0026plusmn; 27 ml vs. 270 \u0026plusmn; 23 ml; p \u0026lt; 0.0001). Mothers who did not pump 5x5 but had greater CVx5 were more likely to CTV than those with lower CVx5, though they needed to pump a greater volume to achieve CTV than mothers who did pump 5x5. Mothers who pumped AMx5 had increasingly more CVx5 than those without any AMx5 (791 \u0026plusmn; 25 ml vs. 264 \u0026plusmn; 26 ml; p \u0026lt; 0.0001).\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCVx5, AMx5 and predictive modeling for CTV\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe influence of CVx5 on CTV was significant with the likelihood of CTV increasing by over 2.9 times for each increase in CVx5 by 250 ml (Table 3b). Indeed, additional AM pumping attempts improve CVx5 (Supplemental Figure 2). Given this strong relationship, we performed a multivariate analysis to predict CTV using the following variables: CVx5, 5x5, AMx5, race, ethnicity, insurance, and maternal IAI. The current model was validated by BIC, retained CVx5 and 5x5 metrics (Table 4), and achieved an AUC of 0.9090 (Figure 1). Using the same set of data, we compared our current model against the previous model described by Mago-Shah et al.\u003csup\u003e6\u003c/sup\u003e The current model performed significantly better utilizing CVx5 and 5x5 data than the previous model, which relied on 5x5, AMx5, and birth weight (p \u0026lt; 0.0001) (Figure 1).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis observational retrospective cohort analysis involved 887 mother-baby dyads to explore factors associated with CTV within the first two postpartum weeks. Our findings support earlier studies linking milk production and CTV with mode of delivery, IAI, and ethnicity. Since CTV is defined as a 500 ml threshold volume, we hypothesized that accumulating volume within the first week of life would be linked to CTV. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCTV was higher among some demographic groups\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDemographic factors such as increased maternal age have been reported to be independently correlated with decreased MOM volume, as these mothers may produce less MOM regardless of which pumping strategy they employ.\u003csup\u003e14,15\u003c/sup\u003e When comparing the age of mothers achieving CTV with those who did not, we found no significant difference. However, it should be noted that CTV is a relatively early measurement of MOM production and may differ from longer, longitudinal measures of MOM supply. We did find that mothers identifying as Hispanic were less likely to CTV as compared to non-Hispanic mothers. Mothers with commercial insurance were more likely to CTV than mothers with Medicaid, governmental, or self-pay health plans. Some studies showed that public health insurance, Hispanic ethnicity, and Black maternal race were correlated with lower MOM use.\u003csup\u003e16,17\u003c/sup\u003e As previously reported, the influence of ethnicity, race, and insurance status are social constructs that do not contribute to production of milk once frequency and timing of pumping are controlled.\u003csup\u003e6\u003c/sup\u003e A combination of higher rates of preterm birth, increased economic burden associated with pumping, and lack of social or work environment support when exclusively pumping could lead to these findings, and indicate a need for both social and systemic support in establishing breast milk pumping practices during the birth hospitalization.\u003csup\u003e2\u003c/sup\u003e Although beyond the scope of the present paper, it will be critical to address these socioeconomic disparities in the maternal and infant population as they relate to MOM success. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCVx5 and CTV\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCVx5 was strongly associated with CTV. We found that for every 250 ml increase in CVx5, the odds of CTV increased by 2.9. This finding further emphasizes the need for establishing methods of increasing pumped MOM volumes in the first days of life, as it positively correlates with increased CTV achievement. In this connection, several studies have also found that early MOM volume predicts volume sufficiency through discharge in hospitalized infants.\u003csup\u003e18,19\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMothers delivering by cesarean section produced less CVx5 but were no different in CTV. A reasonable explanation for this finding is that CTV is a categorical achievement, in that a mother only must pump 500 ml once in a 24-hour period by postnatal day 14. However, our finding that MOM volumes were reduced within even the first 5 postnatal days suggests that other mechanisms may be responsible for reducing MOM production. A systematic review on emergency cesarean section deliveries reported reduced oxytocin and prolactin responses to breastfeeding, which can lead to delayed onset of lactation and subsequently lower MOM volumes.\u003csup\u003e20\u003c/sup\u003e The logistical care required in the post-operative period and pain experienced by the mother can also delay the early breast feeding or milk expression via pumping required to achieve CTV.\u003csup\u003e2\u003c/sup\u003e Mothers who deliver cesarean section could benefit from intentional, early intervention to help increase expressed milk volumes soon after delivery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMarginalized and minority groups may experience increased difficulties in breastfeeding due to socioeconomic barriers and systemic inequities, including decreased lactation consultant support during the hospitalization and transportation issues leading to gaps in providing adequate pumped MOM supply to the hospitalized infant.\u003csup\u003e16\u003c/sup\u003e In our study, we found no differences in insurance type or race when comparing CVx5, but mothers identifying as Other produced significantly less MOM than White mothers. Hispanic-identifying mothers produced less MOM compared to non-Hispanic mothers, which parallels our findings in CTV achievement. While no published studies have yet compared MOM volumes between demographic groups, a study looking at the odds ratio of no maternal MOM at discharge in the very-low-birth-weight population found that Black mothers had higher, and Hispanic mothers lower, odds of not using MOM at discharge.\u003csup\u003e21\u003c/sup\u003e Another study also found that Black mothers and mothers with public insurance had lower odds ratio of using MOM at discharge, but found no differences between Hispanic and non-Hispanic mothers.\u003csup\u003e16\u003c/sup\u003e Nevertheless, a similar need to focus on providing socio-financial resources in helping mothers successfully develop sufficient MOM volume after delivery should be addressed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePumping 5x5 and CVx5\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe frequency and quantity of pumping episodes in the first postnatal days have been reported to have a positive correlation to breast milk production.\u003csup\u003e7\u003c/sup\u003e Specifically, as reported in our previous paper, pumping 5x5, or at least 5 times per day on the postnatal day 5, is associated with successful CTV.\u003csup\u003e6\u003c/sup\u003e Our findings from this study support our previous findings, as there were significant differences in CVx5 between those who pumped 5x5 and those who did not. Mothers who followed the 5x5 schedule had higher volumes and, consequently, a greater likelihood of achieving CTV. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe also found that AMx5, or having a milk-producing pumping episode between 1 and 5 AM at least once during the first 5 postnatal days, was associated with increased CVx5. This supports previous findings that AMx5 is independently associated with MOM production and improves the likelihood of CTV.\u003csup\u003e6\u003c/sup\u003e Overall, both pumping 5x5 and AMx5 are positive predictive factors for CTV and for CVx5. It is important to note that AMx5 is related to 5x5 in that it is difficult to pump 5x5 without AMx5. Though both influence CVx5, AMx5 did not persist in our current model due to the strength of 5x5, and that a mother pumping 5x5 is more likely to pump AMx5 as well. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eComparison of competing models to predict CTV\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn our previous study, we found that CTV could be predicted using a model created with the following regressors: 5x5, AMx5, and birth weight.\u003csup\u003e6\u003c/sup\u003e In the current study, we found that a robust model created with only two regressors, CVx5 and 5x5, outperformed our earlier model. While the precise reason for loss of AMx5 is unclear, it seems likely that its collinearity with both CVx5 and 5x5 resulted in its removal from the model. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLimitations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis model was based on infants in a Level IV NICU and may be less applicable to infants in community hospitals. Another important limitation to overcome is the reliance on data from infants previously discharged from the NICU. It remains to be seen if data can be collected, analyzed, and turned into actionable knowledge while the infants are still within their first week of hospitalization. The selection of the study population also excluded mothers with multiple births as well as those whose infants died during their stay in the NICU. They were excluded because of likely significant differences in maternal stress, which could confound our breast milk production study.\u003csup\u003e22\u003c/sup\u003e The study further only included infants whose length of hospitalization was less than 14 days. This may have created a bias towards fewer infants scored as CTV since they left before their daily MOM through DOL 14 could be assessed. Additionally, MOM volumes were brought into the hospital by mothers, and it is possible that there may be some pumped volumes that were not brought into the hospital. Another limitation of the study was the presence of multiple factors with varying degrees of collinearity. To partially address this, we employed a double LASSO technique to identify covariates for inclusion in the regression model, though collinearity concerns may persist. Another potential limitation was our choice of the BIC over the AICc as the validation tool. Although we recognize that this approach might remove potential regressors, our decision was based on the future utility of the model\u0026rsquo;s outcome: to create a simple yet robust predictive model using clinical data available by postnatal day 5.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions and Implications","content":"\u003cp\u003eCTV is a process involving frequent and persistent maternal participation. In addition, complex hormonal and emotional factors not examined in the present paper also influence MOM production. Our study confirms prior work that has shown that CTV is a significant predictor of MOM sufficiency in a premature NICU population.\u003csup\u003e3,5\u003c/sup\u003e The present study provides a simplified and more robust model to predict CTV based on historical data. More specifically, these strategies utilize available cumulative milk volume data that providers are likely able to access in pump-dependent mothers of hospitalized infants, within the first 5 postnatal days, to predict whether mothers would CTV. While our study is a retrospective evaluation of hospitalized infants and thus do not include healthier mother-baby dyads who are discharged earlier, it provides the groundwork to develop strategies and delineation points for providers to help mothers struggling to achieve CTV. Our model also allows sufficient time for providers to intervene should CTV be predicted as unattainable. Future work can build upon this study by developing and testing prediction models based on CVx5, CTV, and 5x5 with data obtained from infants while still in the NICU, and by exploring other factors that are likely to influence maternal milk production following postnatal day 5. Such a predictive, near real-time CTV tool could be beneficial in helping providers identify mothers who may need assistance while their infant is still in the NICU.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eNo conflicts of interest for all authors. No funding was received to produce this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNC, DTT, CMC, and KG designed the study and helped to compose the manuscript. LL contributed to data collection and creation of data processing methods. KA contributed to critical review and revision.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: The authors gratefully recognize the support and technical assistance provided by Rick Pittman, BA.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eParker MG, Stellwagen LM, Noble L, et al. Promoting Human Milk and Breastfeeding for the Very Low Birth Weight Infant. Pediatrics 2021;148(5). DOI: 10.1542/peds.2021-054272.\u003c/li\u003e\n\u003cli\u003eHoban R, Bowker RM, Gross ME, Patel AL. Maternal production of milk for infants in the neonatal intensive care unit. Seminars in Perinatology 2021;45(2):151381. DOI: https://doi.org/10.1016/j.semperi.2020.151381.\u003c/li\u003e\n\u003cli\u003eMurase M, Nommsen-Rivers L, Morrow AL, et al. Predictors of low milk volume among mothers who delivered preterm. J Hum Lact 2014;30(4):425-35. (In eng). DOI: 10.1177/0890334414543951.\u003c/li\u003e\n\u003cli\u003eChen DC, Nommsen-Rivers L, Dewey KG, L\u0026ouml;nnerdal B. Stress during labor and delivery and early lactation performance. Am J Clin Nutr 1998;68(2):335-44. (In eng). DOI: 10.1093/ajcn/68.2.335.\u003c/li\u003e\n\u003cli\u003eHoban R, Bigger H, Schoeny M, Engstrom J, Meier P, Patel AL. Milk Volume at 2 Weeks Predicts Mother\u0026apos;s Own Milk Feeding at Neonatal Intensive Care Unit Discharge for Very Low Birthweight Infants. Breastfeed Med 2018;13(2):135-141. (In eng). DOI: 10.1089/bfm.2017.0159.\u003c/li\u003e\n\u003cli\u003eMago-Shah DD, Athavale K, Fisher K, Heyward E, Tanaka D, Cotten CM. Early pumping frequency and coming to volume for mother\u0026rsquo;s own milk feeding in hospitalized infants. Journal of Perinatology 2023;43(5):629-634. DOI: 10.1038/s41372-023-01662-z.\u003c/li\u003e\n\u003cli\u003eFewtrell MS, Kennedy K, Ahluwalia JS, Nicholl R, Lucas A, Burton P. Predictors of expressed breast milk volume in mothers expressing milk for their preterm infant. Archives of Disease in Childhood - Fetal and Neonatal Edition 2016;101(6):F502-F506. DOI: 10.1136/archdischild-2015-308321.\u003c/li\u003e\n\u003cli\u003eHoban R, Medina-Poeliniz C, Signorile M, Janes J, Fan C-PS, Meier PP. Early postpartum pumping behaviors, pumped milk volume, and achievement of secretory activation in breast pump-dependent mothers of preterm infants. Journal of Perinatology 2024. DOI: 10.1038/s41372-024-02021-2.\u003c/li\u003e\n\u003cli\u003eFleiss N, Morrison C, Nascimento A, Stone D, Myers E. Improving Early Colostrum Administration to Very Low Birth Weight Infants in a Level 3 Neonatal Intensive Care Unit: A Quality Improvement Initiative. J Pediatr 2023;260:113421. (In eng). DOI: 10.1016/j.jpeds.2023.113421.\u003c/li\u003e\n\u003cli\u003eCommittee Opinion No. 712: Intrapartum Management of Intraamniotic Infection. Obstet Gynecol 2017;130(2):e95-e101. (In eng). DOI: 10.1097/aog.0000000000002236.\u003c/li\u003e\n\u003cli\u003eUrminsky O, Hansen C, Chernozhukov V. Using double-lasso regression for principled variable selection. Available at SSRN 2733374 2016.\u003c/li\u003e\n\u003cli\u003eSchwarz G. Estimating the Dimension of a Model. The Annals of Statistics 1978;6(2):461-464, 4. (https://doi.org/10.1214/aos/1176344136).\u003c/li\u003e\n\u003cli\u003eDeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44(3):837-45. (In eng).\u003c/li\u003e\n\u003cli\u003eHytten FE. Clinical and chemical studies in human lactation. VIII. Relationship of the age, physique, and nutritional status of the mother to the yield and composition of her milk. Br Med J 1954;2(4892):844-5. (In eng). DOI: 10.1136/bmj.2.4892.844.\u003c/li\u003e\n\u003cli\u003eStone J, Warren RML, Pinney E, Warwick J, Cuzick J. Determinants of Percentage and Area Measures of Mammographic Density. American Journal of Epidemiology 2009;170(12):1571-1578. DOI: 10.1093/aje/kwp313.\u003c/li\u003e\n\u003cli\u003eSankar MN, Weiner Ye, Chopra N, Kan P, Williams Z, Lee HC. Barriers to optimal breast milk provision in the neonatal intensive care unit. Journal of Perinatology 2022;42(8):1076-1082. DOI: 10.1038/s41372-021-01275-4.\u003c/li\u003e\n\u003cli\u003eParker MG, Gupta M, Melvin P, et al. Racial and ethnic disparities in the use of mother\u0026apos;s milk feeding for very low birth weight infants in Massachusetts. The Journal of Pediatrics 2019;204:134-141. e1.\u003c/li\u003e\n\u003cli\u003eParker LA, Sullivan S, Krueger C, Mueller M. Association of timing of initiation of breastmilk expression on milk volume and timing of lactogenesis stage II among mothers of very low-birth-weight infants. Breastfeeding medicine 2015;10(2):84-91.\u003c/li\u003e\n\u003cli\u003eParker MG, Melvin P, Graham DA, et al. Timing of First Milk Expression to Maximize Breastfeeding Continuation Among Mothers of Very Low-Birth-Weight Infants. Obstetrics \u0026amp; Gynecology 2019;133(6):1208-1215. DOI: 10.1097/aog.0000000000003258.\u003c/li\u003e\n\u003cli\u003eMoberg KU, Ekstr\u0026ouml;m-Bergstr\u0026ouml;m A, Buckley S, et al. Maternal plasma levels of oxytocin during breastfeeding-A systematic review., 2020, 15, e0235806. DOI: https://doi org/101371/journal pone;235806.\u003c/li\u003e\n\u003cli\u003eLiu J, Parker M, Lu T, et al. Racial and Ethnic Disparities in Human Milk Intake at NICU Discharge among VLBW Infants in California. The Journal of pediatrics 2019.\u003c/li\u003e\n\u003cli\u003eDewey KG. Maternal and fetal stress are associated with impaired lactogenesis in humans. J Nutr 2001;131(11):3012s-5s. (In eng). DOI: 10.1093/jn/131.11.3012S.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Demographics of mothers by CTV or no CTV\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCTV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo CTV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCondition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e887\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e562\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight, grams, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e2,144 \u0026plusmn; 839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e2,131 \u0026plusmn; 777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e2,151 \u0026plusmn; 873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.7290\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational age, weeks, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e33.5 \u0026plusmn; 3.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e33.4 \u0026plusmn; 3.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e33.6 \u0026plusmn; 3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.4412\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfant sex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Male, %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e471, 53.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e176, 54.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e295, 52.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.6236\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength of stay\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;5-14 days\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026gt;14 days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e422\u003c/p\u003e\n \u003cp\u003e465\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003cp\u003e179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e276\u003c/p\u003e\n \u003cp\u003e286\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.2289\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMother\u0026rsquo;s age*, years, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e31.5 \u003cu\u003e+\u003c/u\u003e 6.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e31.06 \u003cu\u003e+\u003c/u\u003e 5.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e31.80 \u003cu\u003e+\u003c/u\u003e 6.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.0896\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMother\u0026rsquo;s race classification\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; White\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Black\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Other/Not\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; identifying\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003cp\u003e343\u003c/p\u003e\n \u003cp\u003e173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e225\u003c/p\u003e\n \u003cp\u003e227\u003c/p\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eOverall: 0.3075\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.1253\u003c/p\u003e\n \u003cp\u003e0.5119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMother\u0026rsquo;s ethnicity classification\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Non-Hispanics\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Hispanics\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Not identifying\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;732\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;147\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e281\u003c/p\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e451\u003c/p\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eOverall: 0.0623\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Ref\u003c/p\u003e\n \u003cp\u003e0.0222\u003c/p\u003e\n \u003cp\u003e0.4384\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelivery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Cesarean section\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Vaginal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e566\u003c/p\u003e\n \u003cp\u003e321\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e195\u003c/p\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003cp\u003e191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eOverall: 0.0725\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMother\u0026rsquo;s insurance status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Commercial\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedicaid/Government/Other\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e366\u003c/p\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e155\u003c/p\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003cp\u003e351\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eOverall: 0.0031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaternal diagnoses\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Pre-Eclampsia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;No Pre-Eclampsia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;IAI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;No IAI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003cp\u003e651\u003c/p\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003cp\u003e843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003cp\u003e247\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e158\u003c/p\u003e\n \u003cp\u003e404\u003c/p\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003cp\u003e526\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eOverall: 0.1816\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOverall: 0.0091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Data missing for 5 mothers. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCTV: Coming to volume\u003c/p\u003e\n\u003cp\u003eSD: Standard deviation\u003c/p\u003e\n\u003cp\u003eIAI: Intraamniotic infection\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. CVx5 by delivery mode and demographics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"618\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCondition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean CVx5 (\u003cu\u003e+\u003c/u\u003e SE) (ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelivery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCesarean section\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVaginal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e566\u003c/p\u003e\n \u003cp\u003e321\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e469 (25)\u003c/p\u003e\n \u003cp\u003e647 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eWhite\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBlack\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAsian\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOther\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003cp\u003e343\u003c/p\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e584 (31)\u003c/p\u003e\n \u003cp\u003e530 (32)\u003c/p\u003e\n \u003cp\u003e469 (84)\u003c/p\u003e\n \u003cp\u003e419 (54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.0536\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.2514\u003c/p\u003e\n \u003cp\u003e0.2062\u003c/p\u003e\n \u003cp\u003e0.0079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNon-Hispanic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHispanic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNot identifying\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e732\u003c/p\u003e\n \u003cp\u003e147\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e559 (23)\u003c/p\u003e\n \u003cp\u003e416 (43)\u003c/p\u003e\n \u003cp\u003e392 (137)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.0249\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.0086\u003c/p\u003e\n \u003cp\u003e0.4447\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsurance\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCommercial\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedicaid/Government/Other\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e366\u003c/p\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e574 (31)\u003c/p\u003e\n \u003cp\u003e505 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.0940\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBW\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIntercept\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBW vs. cumulative volume (slope)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e887\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e525 (55)\u003c/p\u003e\n \u003cp\u003e0.0042 (0.0241)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.8629\u003c/p\u003e\n \u003cp\u003e\u0026lt;.0001\u003c/p\u003e\n \u003cp\u003e0.8629\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIntercept\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGA vs. cumulative volume (slope)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e887\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e604 (191)\u003c/p\u003e\n \u003cp\u003e-2.1078 (5.678)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.7106\u003c/p\u003e\n \u003cp\u003e0.0016\u003c/p\u003e\n \u003cp\u003e0.7106\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength of stay\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5-14 days\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;14 days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e422\u003c/p\u003e\n \u003cp\u003e465\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e542 (29)\u003c/p\u003e\n \u003cp\u003e526 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.6832\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaternal diagnoses\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePre-eclampsia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo pre-eclampsia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIAI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo IAI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003cp\u003e651\u003c/p\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003cp\u003e843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e480 (39)\u003c/p\u003e\n \u003cp\u003e553 (24)\u003c/p\u003e\n \u003cp\u003e333 (90)\u003c/p\u003e\n \u003cp\u003e544 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.1082\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.0233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCVx5: Cumulative volume by postnatal day 5\u003c/p\u003e\n\u003cp\u003eSE: Standard error\u003c/p\u003e\n\u003cp\u003eBW: Birth weight\u003c/p\u003e\n\u003cp\u003eGA: Gestational age\u003c/p\u003e\n\u003cp\u003eIAI: Intraamniotic infection\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTables 3a and 3b. CTV by pumping strategies\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3a. CVx5 by CTV, 5x5, and AMx5\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCondition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean CVx5 (\u003cu\u003e+\u003c/u\u003e SE) (ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCTV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026lt;.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCTV\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDid not CTV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e325\u003c/p\u003e\n \u003cp\u003e562\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e1058 (25)\u003c/p\u003e\n \u003cp\u003e231 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5x5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5x5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDid not 5x5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e375\u003c/p\u003e\n \u003cp\u003e512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e894 (27)\u003c/p\u003e\n \u003cp\u003e270 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026lt;.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAMx5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAMx5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDid not AMx5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e454\u003c/p\u003e\n \u003cp\u003e433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e791 (25)\u003c/p\u003e\n \u003cp\u003e264 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026lt;.0001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3b. Likelihood to CTV for CVx5 increasing by 250 ml\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTerm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCVx5 by 250 ml\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.927\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.535\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.379\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCVx5: Cumulative volume by postnatal day 5\u003c/p\u003e\n\u003cp\u003eCTV: Coming to volume\u003c/p\u003e\n\u003cp\u003e5x5: Pumping at least 5 times per day by postnatal day 5\u003c/p\u003e\n\u003cp\u003eAMx5: Pumping at least once between 1 AM and 5 AM by postnatal day 5\u003c/p\u003e\n\u003cp\u003eSE: Standard error\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Multivariable analysis table\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWald Chi Square\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProbability\u0026thinsp;\u0026gt;\u0026thinsp;Chi Square\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCVx5 per 100 ml\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e154.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e5x5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.0031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMultivariable analysis with CTV vs CVx5, 5x5, AMx5, race, ethnicity, insurance, and birth weight. Factors remaining in the model (using Bayesian Information Criterion with early stopping) are CVx5 and 5x5.\u003c/p\u003e\n\u003cp\u003eCVx5: Cumulative volume by postnatal day 5\u003c/p\u003e\n\u003cp\u003e5x5: Pumping at least 5 times per day by postnatal day 5\u003c/p\u003e\n\u003cp\u003eCTV: Coming to volume\u003c/p\u003e\n\u003cp\u003eAMx5: Pumping at least once between 1 AM and 5 AM by postnatal day 5\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5565965/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5565965/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eAssess if cumulative pumping volumes during the first 5 postnatal days (CVx5) influence coming to volume (CTV: producing\u0026thinsp;\u0026gt;\u0026thinsp;500 milliliters breast milk per day by postnatal day 14) for mothers of hospitalized infants, with a secondary aim to develop and compare a new predictive model using CVx5 with our previous model.\u003c/p\u003e\u003ch2\u003eStudy Design:\u003c/h2\u003e \u003cp\u003e A retrospective cohort analysis was conducted at Duke University Hospital for singleton mother-baby dyads of neonatal intensive care infants between January 2020 and December 2023.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf 887 mother-baby dyads, 325 (37%) achieved CTV and were more likely to have higher CVx5 (1 058\u0026thinsp;\u0026plusmn;\u0026thinsp;25 ml vs. 231\u0026thinsp;\u0026plusmn;\u0026thinsp;19 ml; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). In generalized regression models for CTV that included birth weight, 5x5, AMx5, and CVx5, only CVx5 and 5x5 remained significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCTV is significantly associated with CVx5, and with 5x5, creates a stronger model than that of 5x5 and birth weight.\u003c/p\u003e","manuscriptTitle":"Early Expressed Milk Volume and Coming to Volume for Mother’s Own Milk Feeding in Hospitalized Infants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-25 01:25:22","doi":"10.21203/rs.3.rs-5565965/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b71a3141-7753-49c2-8bd8-0b0636b041a7","owner":[],"postedDate":"December 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":41269690,"name":"Health sciences/Health care/Paediatrics"},{"id":41269691,"name":"Health sciences/Health care/Patient education"}],"tags":[],"updatedAt":"2025-01-10T13:20:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-25 01:25:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5565965","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5565965","identity":"rs-5565965","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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