Journal of Perinatology (2014), 1–6 © 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp
ORIGINAL ARTICLE
Predictors of sustained maternal milk feeds in extremely preterm infants S Omarsdottir1, A Adling2, AKE Bonamy2, L Legnevall2, MK Tessma3 and M Vanpée2 OBJECTIVE: To investigate the predictors of maternal milk feeds (MMFs) in extremely preterm (EPT) infants during neonatal stay. STUDY DESIGN: Maternal characteristics, obstetrical data and infant characteristics were correlated to MMFs in 97 EPT infants during the first 6 weeks of life and at hospital discharge. RESULT: High MMFs (490%) at second week predicted sustained MMFs the first 6 weeks of life; nonuniversity education and non-Nordic origin were unfavorable predictors. The proportion of MMFs the first 6 weeks of life and maternal age were positively associated with MMFs at discharge, whereas overweight was an unfavorable predictor. High MMFs at second week, assisted reproduction technology and employment were predictive factors for exclusive MMFs at discharge. CONCLUSION: High MMFs at week 2 promote sustained MMFs in EPT infants and exclusive MMFs at discharge. Mothers who are either young, overweight, non-Nordic or without university education may need special interventions to establish successful lactation. Journal of Perinatology advance online publication, 27 November 2014; doi:10.1038/jp.2014.212
INTRODUCTION Human milk is the most advantageous nutrition for the preterm infant. It protects against neonatal bacterial infection, necrotizing enterocolitis and retinopathy of prematurity and it precipitates full enteral feeds, promotes earlier discharge and positively affects long-term neurodevelopmental outcome and skeletal mineralization.1,2 Very preterm infants ( o32 weeks of gestation) are unable to breastfeed immediately after birth. Their mothers need to express breast milk that is subsequently given by a nasogastric tube.3 However, preterm mothers, especially mothers of extremely preterm (EPT) infants, have a limited ability to establish and maintain sufficient milk supply because of delayed onset of lactation, and the duration of breastfeeding is shorter compared with mothers of term infants.4–6 Although several studies have investigated maternal and infant factors affecting lactation in mothers of very preterm or very-low birth weight infants,7–14 only one study has investigated mothers of EPT infants ( o28 weeks of gestation).15 In this study, previous breastfeeding experience was related to higher milk volumes at 3 weeks postpartum in singleton mothers, but no associations were demonstrated for socioeconomic, maternal or infant characteristics. In Sweden, preterm infants are preferably fed maternal milk and the overall breastfeeding rates are high.16 Given that EPT infants may benefit even more from maternal milk compared with other preterm infants, because of their increased vulnerability, a better identification of predictors of maternal milk output to target support programs for mothers of EPT infants is of the utmost importance.17 This study investigated maternal and infant factors associated with maternal milk provision in EPT infants during the first 6 weeks of life and at hospital discharge. 1
METHODS Subjects and study design We performed secondary analysis of data from a cohort of singleton EPT infants and their mothers who agreed to participate in a randomized study comparing transmission rates of cytomegalovirus from maternal milk. The randomized study was conducted at the Karolinska University Hospital and South General Hospital, Stockholm, Sweden, from October 2005 to June 2009. The inclusion criteria were birth at o 28 weeks of gestation and intention of the mother to breastfeed her infant. Exclusion criteria were life-threatening congenital birth defects or diseases and congenital cytomegalovirus infection.18 Ninety-seven mothers and their 97 singleton infants from the initial randomized study were included in the cohort after exclusion of multiples to analyze maternal milk intake the first 6 weeks of life. Thereafter, 82 mother–infant pairs were followed until discharge from hospital or home care occurring within 6 months of age (Figure 1). The study was approved by the Regional Ethical Review Board in Stockholm (Dnr 2005/331-31/3, 2006/1417-32, 2007/1255-31/3 and 2008/1837-32).
Nutritional protocol Nutritional feeding practices were comparable at both participating hospitals. Mothers were encouraged to start expressing breast milk with electric breast pumps as soon as possible within 6 h after birth, consistent with hospital routines. Enteral feeds were started within 1–2 days postpartum. Infants randomized to the intervention group (Figure 1) were only fed with thawed maternal milk that had been frozen at –20 °C for a minimum of 3 days. Awaiting this procedure, enteral feeds started with donor milk. Infants of control mothers were fed according to local clinical practice with fresh maternal milk as soon as it was available and donor milk as necessary. In the control group, excess maternal milk was frozen at –20 °C and given in combination with the fresh maternal milk in a chronological order. Infants in both groups were preferably fed with maternal milk and supplemented with donor milk if available until 34 weeks and thereafter with preterm formula. All maternal milk and donor
Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden; 2Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden and Department of Learning, Informatics, Management and Ethics, Karolinska Institute, Stockholm, Sweden. Correspondence: Dr S Omarsdottir, Department of Pediatric Rheumatology, Q1:02, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm 171 76, Sweden. E-mail: [email protected] Received 2 May 2014; revised 14 September 2014; accepted 20 October 2014 3
Predictors of breast milk intake in preterm babies S Omarsdottir et al
2 Enrollment
Assessed for eligibility (n=294)
Excluded (n=154) ♦ Not meeting inclusion criteria (n=35)
Randomized (n=140)
4 congenital anomalies 22 outborn referrals 9 not breastfed ♦ Declined to participate (n=53) ♦ Other reasons (n=66) 19 early deceased 13 fed fresh breast milk before allocation 2 early transfers 32 not approached
Allocation
♦ Did not receive allocated
Allocated to only freezethawed milk (n=69)
• Allocated to fresh and freeze-thawed milk (n=71)
intervention (n=12) 3 not breastfed 1 received fresh milk 2 withdrawals 5 early deceased 1 congenital cytomegalovirus infection ♦ Excluded from analysis (n=14) 1 missing data 13 multiples
♦ Did not receive allocated
intervention (n=3) 1 not breastfed 2 congenital cytomegalovirus infection ♦ Excluded from analysis (n=14) 2 missing data 12 multiples
Received allocated intervention (n=43)
Received allocated intervention (n=54)
Neonatal Analysis n=97
Lost to follow-up (n=15) 5 deceased within 6 months 1 transfer 9 long term patients
Follow Up Analysis n=82
Figure 1. Flow diagram of subject enrollment and allocation for the randomized study and participating subjects for the neonatal and follow-up cohorts in this study.
milk was enriched with powdered protein and liquid lipid supplements when full enteral feeds were established. The enrichment was individualized according to the milk analysis for protein, fat and carbohydrates for all bank milk provided and every other week for maternal milk. The enrichment process impacted minimally on the volume of the feeds, at the most 4 ml of liquid per 100 ml milk. No mother was treated with galactogogues.
Data collection Maternal demographics, anthropometric data and history were obtained from the first maternity prenatal visit. Maternal perinatal data and infant birth data were collected from medical charts (Table 1 and Supplementary Table). Maternal overweight was defined as the body mass index 425. An estimated maternal income was made using average income data from Statistics Sweden according to a housing area in 2008.19 Assisted reproduction technology (ART) included ovarian stimulation, in vitro fertilization or intracytoplastic sperm injection. Chorioamnionitis and placental abruption were defined by placental pathology or by the clinical course. Postnatal anemia was defined both as anemia needing or not needing a blood transfusion. Perinatal infection was defined as a suspected or confirmed perinatal infection in the mother with clinical symptoms and/or laboratorial findings. The Apgar score was dichotomized into moderate asphyxia (o4 or ⩾ 4) at 5 min. Small for gestational age was defined as birth weight ⩽ 2 s.d. for gestational age. Neonatal charts were used to collect information about enteral Journal of Perinatology (2014), 1 – 6
feeds for the first 6 weeks of life and at discharge. Enteral feeds with maternal milk were designated as maternal milk feeds (MMFs) expressed either as an intake in milliliters per kilogram per day or as a proportion in the percentage of total enteral feeds. MMFs covering more than 90% of the infant’s enteral feeds during week 2 of life were defined as High MMFs w2.
Outcome measures Maternal and infant predictors of MMFs in EPT infants during the first 6 weeks of life and at hospital discharge were investigated.
Data analysis Multiple linear regression was employed to estimate relationships between the continuous outcome variable and predictor variables while controlling for other demographic and clinical variables. Predictor variables were selected on the basis of findings of earlier research and results of the simple regression. Multiple logistic regression was used to estimate associations between a categorical outcome variable and the explanatory variables. Crude association of each explanatory variable was determined to examine its relationship with the outcome variable in univariate models. Variables whose univariate test had a P-value o0.10 were entered into a multivariate model along with variables of known clinical importance. An interaction test was performed and multicollinearity problems checked. A variation inflation factor greater than 5 was considered as a cut-off © 2014 Nature America, Inc.
Predictors of breast milk intake in preterm babies S Omarsdottir et al
3 Maternal characteristics, n ¼ 97 Age, years, mean (s.d.) 31.2 (5.9) Body mass index, mean (s.d.) 24.7 (4.1) Non-Nordic origin (born in non-Nordic countries), 26 (27) n (%) Pre-pregnancy nicotine, n (%) 14 (15) Pre-pregnancy alcohol, n (%) 37 (41) Nonuniversity education (below third year of university), 53 (55) n (%) Unemployed, n (%) 27 (28) Non-cohabiting status, n (%) 9 (9) Preschool children at home, n (%) 26 (27) a Mean incomeo250 000 Swedish crowns per year , n (%) 54 (56) Maternal obstetrical history, n ¼ 97 Primipara, n (%) Assisted reproduction technology, n (%) Pre-eclampsia (with or without organ involvement), n (%) Preterm premature rupture of membranes 412 h, n (%) Premature contractions, n (%) Chorioamnionitis, n (%) Placental abruption, n (%) Prenatal steroids 424 h, n (%) Caeserian section, n (%) Placenta accrete, n (%) Postnatal anemia, n (%) Postnatal infection, n (%) Hospital stay, days, median (IQR) Infant characteristics, n ¼ 97 Gestational age, weeks, mean (s.d.) Birth weight, grams, mean (s.d.) Male gender, n (%) Small for gestational age (birth weight ⩽ 2 s.d.), n (%) Apgar scoreo4 at 5 min, n (%) Fasting days, days, median (IQR) Age at discharge, days, median (IQR)
61 (63) 13 (13) 15 (15)
Mean total enteral feeds
160 140 120 100 80 60 40 20 0
1
2
3
4
5
6
Postnatal week
Figure 2. Mean infant feeds (ml kg-1 per day) for all infants by week for the first 6 weeks of life shown as mean maternal feeds and mean total enteral feeds.
23 (24) Infants stratified by % of MMFs/total enteral feeds week 1-6
68 47 24 71 52 13 21 58 6 25.9 852 55 14 9 1 107
(70) (48) (25) (73) (54) (13) (22) (60) (8) (1.2) (192) (57) (14) (9) (2) (40)
Abbreviation: IQR, interquartile range. Values are in mean (s.d.), n (%) or median (IQR) as indicated. aMean yearly income based on age and housing area according to the Statistics Sweden (250 000 SEK per year≈100 USD per day). Missing data for variable (n): overweight (9), pre-pregnancy nicotine (2), pre-pregnancy alcohol (6), nonuniversity education (1), unemployed (2), non-cohabiting status (1), Apgar score o4 at 5 min (1) and age at discharge (6).
criterion for deciding when a given predictor variable displayed ‘too great’ a multicollinearity problem. A Durbin Watson coefficient between 1.5 and 2.5 indicated independence of observations. A Cook’s distance value D44/n-1 was taken as a criterion to indicate a possible outlier problem, where n was the sample size. The model building procedure and the guidelines for reporting regression analysis are described elsewhere.20,21 SPSS version 20.0 (IBM Corp., Armonk, NY, USA) was used for all data analyses. The level of significance was specified at 0.05.
RESULTS MMFs the first 6 weeks of life At the end of the sixth week 80 (82%) mothers were still producing breast milk. Mean enteral feeds for the infants increased from 23 to 139 ml kg-1 per day from the first to the sixth week of life, whereas mean MMFs rose from 7 to 91 ml kg-1 per day (Figure 2). The mean proportion of enteral feeds that was MMFs reached a maximum of 76% in the third week but decreased thereafter to 66% during the sixth week. The mean proportion of MMFs during the whole period was 69%. The median age of the infants at full enteral feeds was 16 days (interquartile range, 10–22 days). © 2014 Nature America, Inc.
Mean infant feeds by week, ml/kg/d
Characteristics of the mothers and infants
>80%
61-80%
41-60%
≤20%
21-40%
1 Mean maternal milk feeds/total enteral feeds
Table 1.
Mean maternal milk feeds
n=59 0.9 0.8 0.7 n=10
0.6 0.5 0.4 0.3
n=6 0.2 n=8 0.1 n=14 0 1
2
3
4
5
6
Postnatal week
Figure 3. Time trend of maternal milk feeds in all infants as a percentage (%) of the total enteral feeds. The infants are stratified by the percent of the infants’ total maternal milk feeds during all 6 weeks. n denotes number of infants in each stratum.
After stratifying infants by their mean proportional intake of maternal milk during the first 6 weeks, we found that most mothers providing 480% MMFs throughout the time period expressed enough milk to cover 490% of enteral feeds already at week 2 (Figure 3). In contrast, the mothers providing o20% MMFs the first 6 weeks had already at week 2 low milk production covering o 20% MMFs. Using univariate analysis, the maternal variables nonuniversity education, non-Nordic origin, chorioamnionitis and body mass index were negatively associated with high MMFs w2 (Po 0.05). After multivariable logistic regression analysis, only maternal body mass index prevailed as significant (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.78–0.99). Univariate analysis revealed that allocation to the control group was strongly associated with high MMFs w2 (P o 0.0001). No associations were found for infant predictors and High MMFs w2. High MMFs w2 and ART were positively associated with MMFs the first 6 weeks of life using univariate analysis, whereas negative associations were found for non-Nordic origin, pre-pregnancy nicotine use, nonuniversity education, unemployment, mean yearly income o250 000 SEK per year and prenatal steroids (Po 0.05). No associations were found for randomization groups or infant predictors. Multivariable linear regression analysis revealed that High MMFs w2, non-Nordic Journal of Perinatology (2014), 1 – 6
Predictors of breast milk intake in preterm babies S Omarsdottir et al
4 Table 2.
Results of multivariable regression analyses of predictors on MMFs in infants during the first 6 weeks of life and at discharge Outcome measures and predictors MMFs the first 6 weeks High MMFs (490%) at week 2 Nonuniversity education Non-Nordic origin
B 0.23 − 0.18 − 0.17
Any MMFs at discharge
OR
Log MMF first 6 weeks Age (years) Overweight
3.8 1.3 0.15
Exclusive MMFs at discharge
OR
High MMF at week 2 ART Unemployment
8.8 18.3 0.19
95% CI for B 0.11 − 0.30 − 0.31
0.35*** − 0.05** − 0.03*
95% CI for OR 1.9 1.1 0.04
7.7*** 1.5*** 0.67*
95% CI for OR 1.8 2.3 0.04
43** 148** 0.99*
Abbreviations: ART, assisted reproduction technology; CI, confidence interval; MMFs, maternal milk feeds; OR, odds ratio. *Po 0.05 **Po0.01 ***Po0.001.
origin and nonuniversity education remained statistically significant (Table 2). We did not observe significant interaction between nonNordic origin and nonuniversity education. In mothers who provided 480% MMF the first 6 weeks of life, positive associations were found for High MMFs w2, ART and mean yearly income4250 000 SEK per year, whereas negative associations were found for unemployment, non-Nordic origin, nonuniversity education and pre-pregnancy nicotine by univariate analysis (Po0.05). After multivariable logistic regression analysis, only High MMFs w2 (OR 5.1, 95% CI 1.7–15.2) and unemployment (OR 0.28, 95% CI 0.09–0.99) remained significant. MMFs at discharge At discharge, 54 infants (66%) were receiving maternal milk. Twenty-two infants (27%) were exclusively receiving maternal milk (11 infants exclusively breastfed), and 32 (39%) were fed a combined diet of maternal milk and formula. Using univariate analysis, the variables High MMFs w2, the proportion of MMFs during the first 6 weeks and maternal age were positively associated with the provision of MMFs at discharge, whereas negative associations were found for overweight, prepregnancy nicotine use, nonuniversity education, unemployment, non-cohabiting status and mean yearly incomeo250 000 SEK per year (Po0.05). No correlations were found between randomization groups or infant predictors and MMFs at discharge. Multivariable logistic regression analysis showed that overweight was an unfavorable predictor for MMFs at discharge, whereas the proportion of MMFs during the first 6 weeks and maternal age were favorable predictors (Table 2). For exclusive MMFs at discharge, univariate analysis revealed that High MMFs w2, the proportion of MMFs during the first 6 weeks of life and ART were all positively associated, whereas a negative association was found for unemployment (Po0.05). After multivariable logistic regression High MMFs w2, ART and unemployment remained significant (Table 2). For exclusive breastfeeding at discharge, favorable predictors by univariate analysis were ART and caesarean section, whereas a negative association was found for infant´s age at discharge (Po0.05). ART (OR 5.6, 95% CI 1.1–28.6) and caesarean section (OR 9.7, 95% CI 1.1–81.3) prevailed as statistically significant after multivariable logistic regression. No associations were found Journal of Perinatology (2014), 1 – 6
between randomization groups and exclusive MMFs or exclusive breastfeeding at discharge. DISCUSSION This is the first study in a country with high breastfeeding rates to examine predictors for maternal milk provision in EPT infants. High MMFs at 2 weeks were a favorable predictor for both maternal milk intake the first 6 weeks of life and at discharge. Unfavorable maternal predictors for provision of maternal milk were nonuniversity education, non-Nordic origin, younger age and overweight. ART was a favorable predictor for exclusive maternal milk intake at discharge. The strength of this study is a hitherto unexplored study population consisting exclusively of mothers delivering at EPT age and their infants. In addition, in Sweden we have optimal circumstances to perform research pertaining to breastfeeding, as it is socially well accepted and breastfeeding rates are high.16 A weakness in the study is that our cohort was derived from another randomized study in which subjects were initially allocated to separate feeding groups. We found that infants allocated to the intervention group were less likely to have High MMFs w2, reflecting a delay in the administration of maternal milk due to the freeze-thawing intervention procedure, but univariate analyses showed no associations between randomization groups and outcome measures in our study. Likewise, included mothers may have been more motivated to breastfeed compared with other mothers; however, the selection procedure should not have influenced the associations between the outcome measures and the maternal and infant factors investigated. Another weakness is that we did not collect information about the mothers’ milk pumping procedures or on skin-to-skin care. Studies of milk production in mothers of older preterm infants have found that milk expression techniques as well as the duration, time points and frequency of milk pumping can affect the milk volumes and the duration of lactation.9,10,22 Although mothers in our study received similar lactation support, we cannot exclude different individual pumping routines. We used the proportional intake of maternal milk as a proxy for the mother’s ability to express breast milk during the first 6 weeks of life. As maternal milk is always chosen before donor milk in our units, we believe that our results accurately reflect maternal milk production. The proportion of MMFs reached a maximum during the third week of life after which expressed volumes of maternal milk could not keep up with the infants’ increasing enteral feeds. The same temporal pattern is described among mothers of preterm very-low birth weight infants.5 Diminished milk production occurring at this time may reflect a physiological switch from central to autocrine control of milk production during which lactation becomes more dependent on the frequent and total emptying of the breast rather than on hormonal control.23 In term infants, the mechanism of breastfeeding on demand will adjust the production volume satisfying the infant’s needs. As preterm infants have small enteral intakes during the first weeks after birth, mothers need to express greater milk volumes than the infant’s needs during the first weeks of life to be able to exclusively breastfeed later on. We found that High MMFs w2 were positively associated with the proportion of MMFs the first 6 weeks of life, which in turn was correlated to maternal milk intake at discharge. These findings are consistent with the results of Hill et al22 illustrating that milk volumes at week 2 were predictive of milk volumes at week 5 in mothers of very preterm infants. A follow-up study by the same author showed that mothers with high milk volumes during week 6 (4500 ml per day) after delivery were more likely to provide maternal milk at 12 weeks postpartum.24 Likewise, Flacking et al25 found that an insufficient milk supply by the end of the first week after delivery increased the risk for weaning at 2 months and at 4 months in mothers of low birth weight infants. © 2014 Nature America, Inc.
Predictors of breast milk intake in preterm babies S Omarsdottir et al
Contrary to Bishara et al,15 we found that maternal milk supply was related to mother’s age, ethnic origin, education and body mass index, respectively. Our study included almost 4 times as many study subjects and observed MMFs for a longer period of time, which could explain our different findings. In the study of Bishara et al, previous breastfeeding experience was related to higher milk volumes at 3 weeks postpartum in EPT infants of singleton mothers. We did not include previous breastfeeding as a predictor in our study. However, the majority (63%) of the mothers in our cohort were primiparae and thus without breastfeeding experience. Maternal overweight was an unfavorable predictor of high MMFs w2 and of MMFs at discharge. High pre-pregnant maternal body mass index is an identified risk factor for the failure to initiate and sustain breastfeeding, but as far as we know this association has hitherto not been reported in mothers of EPT infants.26 Maternal overweight delays lactogenesis II, and this may render the predisposed preterm mothers at an even greater risk for lactation failure.27 However, as we did not collect any information about the volumes of milk expressed by the mothers, we were not able to document the time point of Lactogenesis II in this study. In our study, nonuniversity education and non-Nordic origin were both negatively associated with the proportion of MMFs the first 6 weeks of life, whereas employment was the only maternal predictor associated with the provision of 480% MMF the first 6 weeks of life. Hill et al7 found that income was independently predictive for milk output at week 6 in mothers of very preterm infants, and income in turn was related to both maternal education and ethnicity. By comparison, in the study of Flacking et al,13 low income was the only socioeconomic determinant of weaning at 2 months in mothers of very preterm infants o 32 gestational weeks. In another study by Morton et al,10 education did not affect milk output at 8 weeks in mothers to preterm infants o31 weeks of gestation. Although non-Nordic origin was negatively related to the proportion of MMFs the first 6 weeks of life, ethnic origin did not affect the provision of MMFs or exclusive breastfeeding at discharge. It could be speculated that the non-Nordic mothers may have received inadequate information about the importance of milk expression during the first 6 weeks, possibly because of language or cultural barriers, and that they were more receptive to lactation support during the transition to breastfeeding. In a previous study of term infants from Sweden, the maternal region of birth neither influenced the initiation of breastfeeding nor the breastfeeding rate at 6 months.28 Some previous studies have reported a positive correlation between age and lactation duration in mothers of very preterm or very-low birth weight infants, whereas others have not confirmed this relationship.8,9,12,29,30 In our study, older age was the only favorable maternal predictor for the provision of MMFs at discharge. ART was a favorable predictor for both exclusive MMFs and exclusive breastfeeding at discharge. In the study by Morton et al,10 in vitro fertilization did not affect milk output at postnatal weeks 2 and 8 in mothers of infantso31 weeks of gestation. Likewise, a recent study from Canada found no differences in breastfeeding initiation or breastfeeding at 4 months in mothers who conceived using ART; however, in that study, the ART mothers were older compared with the mothers that conceived spontaneously.31 In another Australian study, ART mothers were more likely to initiate breastfeeding compared with other mothers, but at 3 months the proportion of ART mothers that was exclusively breastfeeding was smaller. The authors suggested that the observed decrease in breastfeeding rate could be associated with a lower confidence in the ability to breastfeed among the ART mothers.32 We speculate that the ART mothers in our study may have been more motivated to breastfeed compared with the other mothers in the study. This, in combination with continuous access to counseling and support by neonatal personnel, could explain the lactation success of these mothers. © 2014 Nature America, Inc.
5 Infants’ birth characteristics were not associated with the outcome measures of our study. In a previous study from California, breast milk feedings at discharge in very-low birth weight infants were less common in infants with lower birth weight and lower gestational age.29 By comparison, in the study of Flacking et al,13 breastfeeding duration was not affected by the degree of prematurity or size at birth. Early establishment of high milk volumes in mothers of EPT infants is necessary to assure further successful lactation. A pilot study by Parker et al33 indicated that milk expression within 1 h after birth may be an effective strategy to increase milk volumes and decrease time to lactogenesis II in mothers of very-low birth weight infants. Likewise, in a recently published prospective national cohort study from Denmark, the initiation of breast milk pumping before 12 h postpartum increased the odds of adequate exclusive breastfeeding duration in preterm infants.34 In view of the proven short- and long-term benefits of maternal milk intake in preterm infants, postnatal intervention should be undertaken immediately after birth to facilitate lactation.1 Apart from early milk expression, such actions should include frequent pumping, kangaroo mother care as soon as the infant’s medical condition allows and continuous support throughout the neonatal period.10,35–37 Galactagogues may have a place for those women not responding to these interventions.38 In conclusion, this study indicates that an establishment of high MMFs at week 2 in EPT infants predicts sustained MMFs the first 6 weeks of life and the provision of exclusive MMFs at discharge. Mothers of EPT infants should aim for a high breast milk production immediately after delivery in order to promote lactation. Special support may be needed for those mothers who are either young, overweight, non-Nordic or without university education. CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We thank all participating study subjects and the neonatal personnel at the Karolinska University Hospital and Stockholm South General Hospital, especially the personnel in the milk kitchen, for their invaluable contribution to the study. This paper was funded by Mjölkdroppen Foundation, HRH Crown Princess Lovisa's Foundation, Queen Silvia Jubilee Fund, Samariten Foundation, Society Barnavård, Anna Britas and Bo Castegrens Memory Foundation, Pediatric Research Foundation of Astrid Lindgren Children’s Hospital, Allmänna BB:s Memory Foundation and KID funding of the Karolinska Institute.
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6 9 Furman L, Minich N, Hack M. Correlates of lactation in mothers of very low birth weight infants. Pediatrics 2002; 109: e57. 10 Morton J, Hall JY, Wong RJ, Thairu L, Benitz WE, Rhine WD. Combining hand techniques with electric pumping increases milk production in mothers of preterm infants. J Perinatol 2009; 29: 757–764. 11 Sisk PM, Lovelady CA, Dillard RG, Gruber KJ, O’Shea TM. Maternal and infant characteristics associated with human milk feeding in very low birth weight infants. J Hum Lact 2009; 25: 412–419. 12 Pineda RG. Predictors of breastfeeding and breastmilk feeding among very low birth weight infants. Breastfeed Med 2011; 6: 15–19. 13 Flacking R, Wallin L, Ewald U. Perinatal and socioeconomic determinants of breastfeeding duration in very preterm infants. Acta Paediatr 2007; 96: 1126–1130. 14 Murase M, Nommsen-Rivers L, Morrow AL, Hatsuno M, Mizuno K, Taki M. Predictors of low milk volume among mothers who delivered preterm. J Hum Lact. 2014; 30: 425–435. 15 Bishara R, Dunn MS, Merko SE, Darling P. Volume of foremilk, hindmilk, and total milk produced by mothers of very preterm infants born at less than 28 weeks of gestation. J Hum Lact 2009; 25: 272–279. 16 The National Board of Health and Welfare. Breast-feeding and smoking habits among parents of infants born in 2010. Published 2012. Available at http://www. socialstyrelsen.se/publikationer2012/2012-8-13. Accessed October 2012. 17 Tudehope D, Fewtrell M, Kashyap S, Udaeta E. Nutritional needs of the micropreterm infant. J Pediatr 2013; 162: S72–S80. 18 Omarsdottir S, Printz C, Gustafsson F, Legnevall L, Zweygberg-Wirgart B, Grillner L et al. 180 The transmission rate of cytomegalovirus to extremely preterm infants is not reduced by routine freezing of maternal milk [abstract]. Pediatr Res 2010; 68: 94–94. 19 Statistics Sweden. Available at http://www.scb.se/default____2154.aspx. Accessed October 2011. 20 Hosmer D, Lemeshow S. Model Building Strategies and Methods for Logistic Regression. In: Hosmer D, Lemeshow S (eds). Applied Logistic Regression, 2nd edn, John Wiley & Sons Inc: New York, 2000, pp 91–142. 21 Lang AT, Secic M. Predicting Values from One or More Variables: Reporting regression analyses. In: Lang AT, Secic M (eds). How to Report Statistics in Medicine. Annotated Guidelines for Authors, Editors and Reviewers, 2nd edn, American College of Physicians: Philadelphia, 2006, pp 85–106. 22 Hill PD, Aldag JC, Chatterton RT. Effects of pumping style on milk production in mothers of non-nursing preterm infants. J Hum Lact 1999; 15: 209–216. 23 Kent JC. How breastfeeding works. J Midwifery Womens Health 2007; 52: 564–570.
24 Hill PD, Aldag JC, Zinaman M, Chatterton RT. Predictors of preterm infant feeding methods and perceived insufficient milk supply at week 12 postpartum. J Hum Lact 2007; 23: 32–38. 25 Flacking R, Nyqvist KH, Ewald U, Wallin L. Long-term duration of breastfeeding in Swedish low birth weight infants. J Hum Lact 2003; 19: 157–165. 26 Oddy WH, Li J, Landsborough L, Kendall GE, Henderson S, Downie J. The association of maternal overweight and obesity with breastfeeding duration. J Pediatr 2006; 149: 185–191. 27 Rasmussen KM, Hilson JA, Kjolhede CL. Obesity may impair lactogenesis II. J Nutr 2001; 131: 3009S–3011SS. 28 Wallby T, Hjern A. Region of birth, income and breastfeeding in a Swedish county. Acta Paediatr 2009; 98: 1799–1804. 29 Lee HC, Gould JB. Factors influencing breast milk versus formula feeding at discharge for very low birth weight infants in California. J Pediatr 2009; 155: 657–662. 30 Zachariassen G, Faerk J, Grytter C, Esberg B, Juvonen P, Halken S. Factors associated with successful establishment of breastfeeding in very preterm infants. Acta Paediatr 2010; 99: 1000–1004. 31 O’Quinn C, Metcalfe A, McDonald SW, Raguz N, Tough SC. Exclusive breastfeeding and assisted reproductive technologies: a Calgary cohort. Reproductive Sys Sexual Disord 2012; S5: 002. 32 Hammarberg K, Fisher JRW, Wynter KH, Rowe HJ. Breastfeeding after assisted conception: a prospective cohort study. Acta Paediatr 2011; 100: 529–533. 33 Parker LA, Sullivan S, Krueger C, Kelechi T, Mueller M. Effect of early breast milk expression on milk volume and timing of lactogenesis stage II among mothers of very low birth weight infants: a pilot study. J Perinatol 2012; 32: 205–209. 34 Maastrup R, Hansen BM, Kronborg H, Bojesen SN, Hallum K, Frandsen A et al. Factors associated with exclusive breastfeeding of preterm infants. Results from a prospective national cohort study. PLoS One 2014; 9: e89077. 35 Flacking R, Ewald U, Wallin L. Positive effect of kangaroo mother care on longterm breastfeeding in very preterm infants. J Obstet Gynecol Neonatal Nurs 2011; 40: 190–197. 36 Parker LA, Sullivan S, Krueger C, Kelechi T, Mueller M. Strategies to increase milk volume in mothers of VLBW infants. MCN Am J Matern Child Nurs 2013; 38: 385–390. 37 Nyqvist KH, Häggkvist AP, Hansen MN, Kylberg E, Frandsen AL, Maastrup R et al. Baby-Friendly Hospital Initiative Expert Group. Expansion of the baby-friendly hospital initiative ten steps to successful breastfeeding into neonatal intensive care: expert group recommendations. J Hum Lact 2013; 29: 300–309. 38 Anderson PO, Valdés V. A critical review of pharmaceutical galactagogues. Breastfeed Med 2007; 2: 229–242.
Supplementary Information accompanies the paper on the Journal of Perinatology website (http://www.nature.com/jp)
Journal of Perinatology (2014), 1 – 6
© 2014 Nature America, Inc.
ORIGINAL ARTICLE
Predictors of sustained maternal milk feeds in extremely preterm infants S Omarsdottir1, A Adling2, AKE Bonamy2, L Legnevall2, MK Tessma3 and M Vanpée2 OBJECTIVE: To investigate the predictors of maternal milk feeds (MMFs) in extremely preterm (EPT) infants during neonatal stay. STUDY DESIGN: Maternal characteristics, obstetrical data and infant characteristics were correlated to MMFs in 97 EPT infants during the first 6 weeks of life and at hospital discharge. RESULT: High MMFs (490%) at second week predicted sustained MMFs the first 6 weeks of life; nonuniversity education and non-Nordic origin were unfavorable predictors. The proportion of MMFs the first 6 weeks of life and maternal age were positively associated with MMFs at discharge, whereas overweight was an unfavorable predictor. High MMFs at second week, assisted reproduction technology and employment were predictive factors for exclusive MMFs at discharge. CONCLUSION: High MMFs at week 2 promote sustained MMFs in EPT infants and exclusive MMFs at discharge. Mothers who are either young, overweight, non-Nordic or without university education may need special interventions to establish successful lactation. Journal of Perinatology advance online publication, 27 November 2014; doi:10.1038/jp.2014.212
INTRODUCTION Human milk is the most advantageous nutrition for the preterm infant. It protects against neonatal bacterial infection, necrotizing enterocolitis and retinopathy of prematurity and it precipitates full enteral feeds, promotes earlier discharge and positively affects long-term neurodevelopmental outcome and skeletal mineralization.1,2 Very preterm infants ( o32 weeks of gestation) are unable to breastfeed immediately after birth. Their mothers need to express breast milk that is subsequently given by a nasogastric tube.3 However, preterm mothers, especially mothers of extremely preterm (EPT) infants, have a limited ability to establish and maintain sufficient milk supply because of delayed onset of lactation, and the duration of breastfeeding is shorter compared with mothers of term infants.4–6 Although several studies have investigated maternal and infant factors affecting lactation in mothers of very preterm or very-low birth weight infants,7–14 only one study has investigated mothers of EPT infants ( o28 weeks of gestation).15 In this study, previous breastfeeding experience was related to higher milk volumes at 3 weeks postpartum in singleton mothers, but no associations were demonstrated for socioeconomic, maternal or infant characteristics. In Sweden, preterm infants are preferably fed maternal milk and the overall breastfeeding rates are high.16 Given that EPT infants may benefit even more from maternal milk compared with other preterm infants, because of their increased vulnerability, a better identification of predictors of maternal milk output to target support programs for mothers of EPT infants is of the utmost importance.17 This study investigated maternal and infant factors associated with maternal milk provision in EPT infants during the first 6 weeks of life and at hospital discharge. 1
METHODS Subjects and study design We performed secondary analysis of data from a cohort of singleton EPT infants and their mothers who agreed to participate in a randomized study comparing transmission rates of cytomegalovirus from maternal milk. The randomized study was conducted at the Karolinska University Hospital and South General Hospital, Stockholm, Sweden, from October 2005 to June 2009. The inclusion criteria were birth at o 28 weeks of gestation and intention of the mother to breastfeed her infant. Exclusion criteria were life-threatening congenital birth defects or diseases and congenital cytomegalovirus infection.18 Ninety-seven mothers and their 97 singleton infants from the initial randomized study were included in the cohort after exclusion of multiples to analyze maternal milk intake the first 6 weeks of life. Thereafter, 82 mother–infant pairs were followed until discharge from hospital or home care occurring within 6 months of age (Figure 1). The study was approved by the Regional Ethical Review Board in Stockholm (Dnr 2005/331-31/3, 2006/1417-32, 2007/1255-31/3 and 2008/1837-32).
Nutritional protocol Nutritional feeding practices were comparable at both participating hospitals. Mothers were encouraged to start expressing breast milk with electric breast pumps as soon as possible within 6 h after birth, consistent with hospital routines. Enteral feeds were started within 1–2 days postpartum. Infants randomized to the intervention group (Figure 1) were only fed with thawed maternal milk that had been frozen at –20 °C for a minimum of 3 days. Awaiting this procedure, enteral feeds started with donor milk. Infants of control mothers were fed according to local clinical practice with fresh maternal milk as soon as it was available and donor milk as necessary. In the control group, excess maternal milk was frozen at –20 °C and given in combination with the fresh maternal milk in a chronological order. Infants in both groups were preferably fed with maternal milk and supplemented with donor milk if available until 34 weeks and thereafter with preterm formula. All maternal milk and donor
Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden; 2Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden and Department of Learning, Informatics, Management and Ethics, Karolinska Institute, Stockholm, Sweden. Correspondence: Dr S Omarsdottir, Department of Pediatric Rheumatology, Q1:02, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm 171 76, Sweden. E-mail: [email protected] Received 2 May 2014; revised 14 September 2014; accepted 20 October 2014 3
Predictors of breast milk intake in preterm babies S Omarsdottir et al
2 Enrollment
Assessed for eligibility (n=294)
Excluded (n=154) ♦ Not meeting inclusion criteria (n=35)
Randomized (n=140)
4 congenital anomalies 22 outborn referrals 9 not breastfed ♦ Declined to participate (n=53) ♦ Other reasons (n=66) 19 early deceased 13 fed fresh breast milk before allocation 2 early transfers 32 not approached
Allocation
♦ Did not receive allocated
Allocated to only freezethawed milk (n=69)
• Allocated to fresh and freeze-thawed milk (n=71)
intervention (n=12) 3 not breastfed 1 received fresh milk 2 withdrawals 5 early deceased 1 congenital cytomegalovirus infection ♦ Excluded from analysis (n=14) 1 missing data 13 multiples
♦ Did not receive allocated
intervention (n=3) 1 not breastfed 2 congenital cytomegalovirus infection ♦ Excluded from analysis (n=14) 2 missing data 12 multiples
Received allocated intervention (n=43)
Received allocated intervention (n=54)
Neonatal Analysis n=97
Lost to follow-up (n=15) 5 deceased within 6 months 1 transfer 9 long term patients
Follow Up Analysis n=82
Figure 1. Flow diagram of subject enrollment and allocation for the randomized study and participating subjects for the neonatal and follow-up cohorts in this study.
milk was enriched with powdered protein and liquid lipid supplements when full enteral feeds were established. The enrichment was individualized according to the milk analysis for protein, fat and carbohydrates for all bank milk provided and every other week for maternal milk. The enrichment process impacted minimally on the volume of the feeds, at the most 4 ml of liquid per 100 ml milk. No mother was treated with galactogogues.
Data collection Maternal demographics, anthropometric data and history were obtained from the first maternity prenatal visit. Maternal perinatal data and infant birth data were collected from medical charts (Table 1 and Supplementary Table). Maternal overweight was defined as the body mass index 425. An estimated maternal income was made using average income data from Statistics Sweden according to a housing area in 2008.19 Assisted reproduction technology (ART) included ovarian stimulation, in vitro fertilization or intracytoplastic sperm injection. Chorioamnionitis and placental abruption were defined by placental pathology or by the clinical course. Postnatal anemia was defined both as anemia needing or not needing a blood transfusion. Perinatal infection was defined as a suspected or confirmed perinatal infection in the mother with clinical symptoms and/or laboratorial findings. The Apgar score was dichotomized into moderate asphyxia (o4 or ⩾ 4) at 5 min. Small for gestational age was defined as birth weight ⩽ 2 s.d. for gestational age. Neonatal charts were used to collect information about enteral Journal of Perinatology (2014), 1 – 6
feeds for the first 6 weeks of life and at discharge. Enteral feeds with maternal milk were designated as maternal milk feeds (MMFs) expressed either as an intake in milliliters per kilogram per day or as a proportion in the percentage of total enteral feeds. MMFs covering more than 90% of the infant’s enteral feeds during week 2 of life were defined as High MMFs w2.
Outcome measures Maternal and infant predictors of MMFs in EPT infants during the first 6 weeks of life and at hospital discharge were investigated.
Data analysis Multiple linear regression was employed to estimate relationships between the continuous outcome variable and predictor variables while controlling for other demographic and clinical variables. Predictor variables were selected on the basis of findings of earlier research and results of the simple regression. Multiple logistic regression was used to estimate associations between a categorical outcome variable and the explanatory variables. Crude association of each explanatory variable was determined to examine its relationship with the outcome variable in univariate models. Variables whose univariate test had a P-value o0.10 were entered into a multivariate model along with variables of known clinical importance. An interaction test was performed and multicollinearity problems checked. A variation inflation factor greater than 5 was considered as a cut-off © 2014 Nature America, Inc.
Predictors of breast milk intake in preterm babies S Omarsdottir et al
3 Maternal characteristics, n ¼ 97 Age, years, mean (s.d.) 31.2 (5.9) Body mass index, mean (s.d.) 24.7 (4.1) Non-Nordic origin (born in non-Nordic countries), 26 (27) n (%) Pre-pregnancy nicotine, n (%) 14 (15) Pre-pregnancy alcohol, n (%) 37 (41) Nonuniversity education (below third year of university), 53 (55) n (%) Unemployed, n (%) 27 (28) Non-cohabiting status, n (%) 9 (9) Preschool children at home, n (%) 26 (27) a Mean incomeo250 000 Swedish crowns per year , n (%) 54 (56) Maternal obstetrical history, n ¼ 97 Primipara, n (%) Assisted reproduction technology, n (%) Pre-eclampsia (with or without organ involvement), n (%) Preterm premature rupture of membranes 412 h, n (%) Premature contractions, n (%) Chorioamnionitis, n (%) Placental abruption, n (%) Prenatal steroids 424 h, n (%) Caeserian section, n (%) Placenta accrete, n (%) Postnatal anemia, n (%) Postnatal infection, n (%) Hospital stay, days, median (IQR) Infant characteristics, n ¼ 97 Gestational age, weeks, mean (s.d.) Birth weight, grams, mean (s.d.) Male gender, n (%) Small for gestational age (birth weight ⩽ 2 s.d.), n (%) Apgar scoreo4 at 5 min, n (%) Fasting days, days, median (IQR) Age at discharge, days, median (IQR)
61 (63) 13 (13) 15 (15)
Mean total enteral feeds
160 140 120 100 80 60 40 20 0
1
2
3
4
5
6
Postnatal week
Figure 2. Mean infant feeds (ml kg-1 per day) for all infants by week for the first 6 weeks of life shown as mean maternal feeds and mean total enteral feeds.
23 (24) Infants stratified by % of MMFs/total enteral feeds week 1-6
68 47 24 71 52 13 21 58 6 25.9 852 55 14 9 1 107
(70) (48) (25) (73) (54) (13) (22) (60) (8) (1.2) (192) (57) (14) (9) (2) (40)
Abbreviation: IQR, interquartile range. Values are in mean (s.d.), n (%) or median (IQR) as indicated. aMean yearly income based on age and housing area according to the Statistics Sweden (250 000 SEK per year≈100 USD per day). Missing data for variable (n): overweight (9), pre-pregnancy nicotine (2), pre-pregnancy alcohol (6), nonuniversity education (1), unemployed (2), non-cohabiting status (1), Apgar score o4 at 5 min (1) and age at discharge (6).
criterion for deciding when a given predictor variable displayed ‘too great’ a multicollinearity problem. A Durbin Watson coefficient between 1.5 and 2.5 indicated independence of observations. A Cook’s distance value D44/n-1 was taken as a criterion to indicate a possible outlier problem, where n was the sample size. The model building procedure and the guidelines for reporting regression analysis are described elsewhere.20,21 SPSS version 20.0 (IBM Corp., Armonk, NY, USA) was used for all data analyses. The level of significance was specified at 0.05.
RESULTS MMFs the first 6 weeks of life At the end of the sixth week 80 (82%) mothers were still producing breast milk. Mean enteral feeds for the infants increased from 23 to 139 ml kg-1 per day from the first to the sixth week of life, whereas mean MMFs rose from 7 to 91 ml kg-1 per day (Figure 2). The mean proportion of enteral feeds that was MMFs reached a maximum of 76% in the third week but decreased thereafter to 66% during the sixth week. The mean proportion of MMFs during the whole period was 69%. The median age of the infants at full enteral feeds was 16 days (interquartile range, 10–22 days). © 2014 Nature America, Inc.
Mean infant feeds by week, ml/kg/d
Characteristics of the mothers and infants
>80%
61-80%
41-60%
≤20%
21-40%
1 Mean maternal milk feeds/total enteral feeds
Table 1.
Mean maternal milk feeds
n=59 0.9 0.8 0.7 n=10
0.6 0.5 0.4 0.3
n=6 0.2 n=8 0.1 n=14 0 1
2
3
4
5
6
Postnatal week
Figure 3. Time trend of maternal milk feeds in all infants as a percentage (%) of the total enteral feeds. The infants are stratified by the percent of the infants’ total maternal milk feeds during all 6 weeks. n denotes number of infants in each stratum.
After stratifying infants by their mean proportional intake of maternal milk during the first 6 weeks, we found that most mothers providing 480% MMFs throughout the time period expressed enough milk to cover 490% of enteral feeds already at week 2 (Figure 3). In contrast, the mothers providing o20% MMFs the first 6 weeks had already at week 2 low milk production covering o 20% MMFs. Using univariate analysis, the maternal variables nonuniversity education, non-Nordic origin, chorioamnionitis and body mass index were negatively associated with high MMFs w2 (Po 0.05). After multivariable logistic regression analysis, only maternal body mass index prevailed as significant (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.78–0.99). Univariate analysis revealed that allocation to the control group was strongly associated with high MMFs w2 (P o 0.0001). No associations were found for infant predictors and High MMFs w2. High MMFs w2 and ART were positively associated with MMFs the first 6 weeks of life using univariate analysis, whereas negative associations were found for non-Nordic origin, pre-pregnancy nicotine use, nonuniversity education, unemployment, mean yearly income o250 000 SEK per year and prenatal steroids (Po 0.05). No associations were found for randomization groups or infant predictors. Multivariable linear regression analysis revealed that High MMFs w2, non-Nordic Journal of Perinatology (2014), 1 – 6
Predictors of breast milk intake in preterm babies S Omarsdottir et al
4 Table 2.
Results of multivariable regression analyses of predictors on MMFs in infants during the first 6 weeks of life and at discharge Outcome measures and predictors MMFs the first 6 weeks High MMFs (490%) at week 2 Nonuniversity education Non-Nordic origin
B 0.23 − 0.18 − 0.17
Any MMFs at discharge
OR
Log MMF first 6 weeks Age (years) Overweight
3.8 1.3 0.15
Exclusive MMFs at discharge
OR
High MMF at week 2 ART Unemployment
8.8 18.3 0.19
95% CI for B 0.11 − 0.30 − 0.31
0.35*** − 0.05** − 0.03*
95% CI for OR 1.9 1.1 0.04
7.7*** 1.5*** 0.67*
95% CI for OR 1.8 2.3 0.04
43** 148** 0.99*
Abbreviations: ART, assisted reproduction technology; CI, confidence interval; MMFs, maternal milk feeds; OR, odds ratio. *Po 0.05 **Po0.01 ***Po0.001.
origin and nonuniversity education remained statistically significant (Table 2). We did not observe significant interaction between nonNordic origin and nonuniversity education. In mothers who provided 480% MMF the first 6 weeks of life, positive associations were found for High MMFs w2, ART and mean yearly income4250 000 SEK per year, whereas negative associations were found for unemployment, non-Nordic origin, nonuniversity education and pre-pregnancy nicotine by univariate analysis (Po0.05). After multivariable logistic regression analysis, only High MMFs w2 (OR 5.1, 95% CI 1.7–15.2) and unemployment (OR 0.28, 95% CI 0.09–0.99) remained significant. MMFs at discharge At discharge, 54 infants (66%) were receiving maternal milk. Twenty-two infants (27%) were exclusively receiving maternal milk (11 infants exclusively breastfed), and 32 (39%) were fed a combined diet of maternal milk and formula. Using univariate analysis, the variables High MMFs w2, the proportion of MMFs during the first 6 weeks and maternal age were positively associated with the provision of MMFs at discharge, whereas negative associations were found for overweight, prepregnancy nicotine use, nonuniversity education, unemployment, non-cohabiting status and mean yearly incomeo250 000 SEK per year (Po0.05). No correlations were found between randomization groups or infant predictors and MMFs at discharge. Multivariable logistic regression analysis showed that overweight was an unfavorable predictor for MMFs at discharge, whereas the proportion of MMFs during the first 6 weeks and maternal age were favorable predictors (Table 2). For exclusive MMFs at discharge, univariate analysis revealed that High MMFs w2, the proportion of MMFs during the first 6 weeks of life and ART were all positively associated, whereas a negative association was found for unemployment (Po0.05). After multivariable logistic regression High MMFs w2, ART and unemployment remained significant (Table 2). For exclusive breastfeeding at discharge, favorable predictors by univariate analysis were ART and caesarean section, whereas a negative association was found for infant´s age at discharge (Po0.05). ART (OR 5.6, 95% CI 1.1–28.6) and caesarean section (OR 9.7, 95% CI 1.1–81.3) prevailed as statistically significant after multivariable logistic regression. No associations were found Journal of Perinatology (2014), 1 – 6
between randomization groups and exclusive MMFs or exclusive breastfeeding at discharge. DISCUSSION This is the first study in a country with high breastfeeding rates to examine predictors for maternal milk provision in EPT infants. High MMFs at 2 weeks were a favorable predictor for both maternal milk intake the first 6 weeks of life and at discharge. Unfavorable maternal predictors for provision of maternal milk were nonuniversity education, non-Nordic origin, younger age and overweight. ART was a favorable predictor for exclusive maternal milk intake at discharge. The strength of this study is a hitherto unexplored study population consisting exclusively of mothers delivering at EPT age and their infants. In addition, in Sweden we have optimal circumstances to perform research pertaining to breastfeeding, as it is socially well accepted and breastfeeding rates are high.16 A weakness in the study is that our cohort was derived from another randomized study in which subjects were initially allocated to separate feeding groups. We found that infants allocated to the intervention group were less likely to have High MMFs w2, reflecting a delay in the administration of maternal milk due to the freeze-thawing intervention procedure, but univariate analyses showed no associations between randomization groups and outcome measures in our study. Likewise, included mothers may have been more motivated to breastfeed compared with other mothers; however, the selection procedure should not have influenced the associations between the outcome measures and the maternal and infant factors investigated. Another weakness is that we did not collect information about the mothers’ milk pumping procedures or on skin-to-skin care. Studies of milk production in mothers of older preterm infants have found that milk expression techniques as well as the duration, time points and frequency of milk pumping can affect the milk volumes and the duration of lactation.9,10,22 Although mothers in our study received similar lactation support, we cannot exclude different individual pumping routines. We used the proportional intake of maternal milk as a proxy for the mother’s ability to express breast milk during the first 6 weeks of life. As maternal milk is always chosen before donor milk in our units, we believe that our results accurately reflect maternal milk production. The proportion of MMFs reached a maximum during the third week of life after which expressed volumes of maternal milk could not keep up with the infants’ increasing enteral feeds. The same temporal pattern is described among mothers of preterm very-low birth weight infants.5 Diminished milk production occurring at this time may reflect a physiological switch from central to autocrine control of milk production during which lactation becomes more dependent on the frequent and total emptying of the breast rather than on hormonal control.23 In term infants, the mechanism of breastfeeding on demand will adjust the production volume satisfying the infant’s needs. As preterm infants have small enteral intakes during the first weeks after birth, mothers need to express greater milk volumes than the infant’s needs during the first weeks of life to be able to exclusively breastfeed later on. We found that High MMFs w2 were positively associated with the proportion of MMFs the first 6 weeks of life, which in turn was correlated to maternal milk intake at discharge. These findings are consistent with the results of Hill et al22 illustrating that milk volumes at week 2 were predictive of milk volumes at week 5 in mothers of very preterm infants. A follow-up study by the same author showed that mothers with high milk volumes during week 6 (4500 ml per day) after delivery were more likely to provide maternal milk at 12 weeks postpartum.24 Likewise, Flacking et al25 found that an insufficient milk supply by the end of the first week after delivery increased the risk for weaning at 2 months and at 4 months in mothers of low birth weight infants. © 2014 Nature America, Inc.
Predictors of breast milk intake in preterm babies S Omarsdottir et al
Contrary to Bishara et al,15 we found that maternal milk supply was related to mother’s age, ethnic origin, education and body mass index, respectively. Our study included almost 4 times as many study subjects and observed MMFs for a longer period of time, which could explain our different findings. In the study of Bishara et al, previous breastfeeding experience was related to higher milk volumes at 3 weeks postpartum in EPT infants of singleton mothers. We did not include previous breastfeeding as a predictor in our study. However, the majority (63%) of the mothers in our cohort were primiparae and thus without breastfeeding experience. Maternal overweight was an unfavorable predictor of high MMFs w2 and of MMFs at discharge. High pre-pregnant maternal body mass index is an identified risk factor for the failure to initiate and sustain breastfeeding, but as far as we know this association has hitherto not been reported in mothers of EPT infants.26 Maternal overweight delays lactogenesis II, and this may render the predisposed preterm mothers at an even greater risk for lactation failure.27 However, as we did not collect any information about the volumes of milk expressed by the mothers, we were not able to document the time point of Lactogenesis II in this study. In our study, nonuniversity education and non-Nordic origin were both negatively associated with the proportion of MMFs the first 6 weeks of life, whereas employment was the only maternal predictor associated with the provision of 480% MMF the first 6 weeks of life. Hill et al7 found that income was independently predictive for milk output at week 6 in mothers of very preterm infants, and income in turn was related to both maternal education and ethnicity. By comparison, in the study of Flacking et al,13 low income was the only socioeconomic determinant of weaning at 2 months in mothers of very preterm infants o 32 gestational weeks. In another study by Morton et al,10 education did not affect milk output at 8 weeks in mothers to preterm infants o31 weeks of gestation. Although non-Nordic origin was negatively related to the proportion of MMFs the first 6 weeks of life, ethnic origin did not affect the provision of MMFs or exclusive breastfeeding at discharge. It could be speculated that the non-Nordic mothers may have received inadequate information about the importance of milk expression during the first 6 weeks, possibly because of language or cultural barriers, and that they were more receptive to lactation support during the transition to breastfeeding. In a previous study of term infants from Sweden, the maternal region of birth neither influenced the initiation of breastfeeding nor the breastfeeding rate at 6 months.28 Some previous studies have reported a positive correlation between age and lactation duration in mothers of very preterm or very-low birth weight infants, whereas others have not confirmed this relationship.8,9,12,29,30 In our study, older age was the only favorable maternal predictor for the provision of MMFs at discharge. ART was a favorable predictor for both exclusive MMFs and exclusive breastfeeding at discharge. In the study by Morton et al,10 in vitro fertilization did not affect milk output at postnatal weeks 2 and 8 in mothers of infantso31 weeks of gestation. Likewise, a recent study from Canada found no differences in breastfeeding initiation or breastfeeding at 4 months in mothers who conceived using ART; however, in that study, the ART mothers were older compared with the mothers that conceived spontaneously.31 In another Australian study, ART mothers were more likely to initiate breastfeeding compared with other mothers, but at 3 months the proportion of ART mothers that was exclusively breastfeeding was smaller. The authors suggested that the observed decrease in breastfeeding rate could be associated with a lower confidence in the ability to breastfeed among the ART mothers.32 We speculate that the ART mothers in our study may have been more motivated to breastfeed compared with the other mothers in the study. This, in combination with continuous access to counseling and support by neonatal personnel, could explain the lactation success of these mothers. © 2014 Nature America, Inc.
5 Infants’ birth characteristics were not associated with the outcome measures of our study. In a previous study from California, breast milk feedings at discharge in very-low birth weight infants were less common in infants with lower birth weight and lower gestational age.29 By comparison, in the study of Flacking et al,13 breastfeeding duration was not affected by the degree of prematurity or size at birth. Early establishment of high milk volumes in mothers of EPT infants is necessary to assure further successful lactation. A pilot study by Parker et al33 indicated that milk expression within 1 h after birth may be an effective strategy to increase milk volumes and decrease time to lactogenesis II in mothers of very-low birth weight infants. Likewise, in a recently published prospective national cohort study from Denmark, the initiation of breast milk pumping before 12 h postpartum increased the odds of adequate exclusive breastfeeding duration in preterm infants.34 In view of the proven short- and long-term benefits of maternal milk intake in preterm infants, postnatal intervention should be undertaken immediately after birth to facilitate lactation.1 Apart from early milk expression, such actions should include frequent pumping, kangaroo mother care as soon as the infant’s medical condition allows and continuous support throughout the neonatal period.10,35–37 Galactagogues may have a place for those women not responding to these interventions.38 In conclusion, this study indicates that an establishment of high MMFs at week 2 in EPT infants predicts sustained MMFs the first 6 weeks of life and the provision of exclusive MMFs at discharge. Mothers of EPT infants should aim for a high breast milk production immediately after delivery in order to promote lactation. Special support may be needed for those mothers who are either young, overweight, non-Nordic or without university education. CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We thank all participating study subjects and the neonatal personnel at the Karolinska University Hospital and Stockholm South General Hospital, especially the personnel in the milk kitchen, for their invaluable contribution to the study. This paper was funded by Mjölkdroppen Foundation, HRH Crown Princess Lovisa's Foundation, Queen Silvia Jubilee Fund, Samariten Foundation, Society Barnavård, Anna Britas and Bo Castegrens Memory Foundation, Pediatric Research Foundation of Astrid Lindgren Children’s Hospital, Allmänna BB:s Memory Foundation and KID funding of the Karolinska Institute.
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